Compounds and methods for modulating bruton's tyrosine kinase

This application claims the benefit of International Application No. PCT/US2017/021966 filed Mar. 10, 2017, U.S. Provisional Application No. 62/307,399, filed Mar. 11, 2016, and U.S. Provisional Application No. 62/342,004, filed May 26, 2016, which are incorporated herein by reference in their entirety and for all purposes.

Bruton's Tyrosine Kinase (BTK) plays an important role in B cell development, differentiation, signalling, and maturation. BTK was originally identified as a disease gene for human X-linked agammaglobulinemia, but has further been implicated in inflammation (e.g., inflammatory skin conditions), autoimmune, allergic disease conditions, and cancers (e.g., B-cell cancers such as B-cell lymphoma and lymphblastic B-cell leukemia). Thus, there is a need in the art for BTK modulators. Disclosed herein, inter alia, are solutions to these and other problems in the art.

Herein are provided, inter alia, compounds capable of modulating the level of activity of Bruton's Tyrosine Kinase (BTK) and methods of using the same.

In an aspect is provided a compound having the formula:

R 1 is independently halogen, —CX 3 , —CHX 1 2 , —CH 2 X 1 , —OCX 1 3 , —OCH 2 X 1 , —OCHX 1 2 , —CN, —SO n1 R 1D , —SO v1 NR 1A R 1B , —NHC(O)NR 1A R 1B , —N(O) m1 , —NR 1A R 1B , —C(O)R 1C , —C(O)—OR 1C , —C(O)NR 1A R 1B , —OR 1D , —NR 1A SO 2 R 1D , —NR 1A C(O)R 1C , —NR 1A C(O)O R 1C , —NR 1A OR 1C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. Two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. The symbol z1 is an integer from 0 to 5. R 2 is independently halogen, —CX 2 3 , —CHX 2 2 , —CH 2 X 2 , —OCX 2 3 , —OCH 2 X 2 , —OCHX 2 2 , —CN, —SO n2 R 2D , —SO v2 NR 2A R 2B , —NHC(O)NR 2A R 2B , —N(O) m2 , —NR 2A R 2B , —C(O)R 2C , —C(O)—OR 2C , —C(O)NR 2A R 2B , —OR 2D , —NR 2A SO 2 R 2D , —NR 2A C(O)R 2C , —NR 2A C(O)OR 2C , —NR 2A OR 2C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. Two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. The symbol z 2 is an integer from 0 to 4. R 3 is hydrogen or —NH 2 . The symbol Y 1 is N or C(R 4 ). R 4 is hydrogen, halogen, —CX 4 3 , —CHX 4 2 , —CH 2 X 4 , —OCX 4 3 , —OCH 2 X 4 , —OCHX 4 2 , —CN, —SO n4 R 4D , —SO v4 NR 4A R 4B , —NHC(O)NR 4A R 4B , —N(O) m4 , —NR 4A R 4B , —C(O)R 4C , —C(O)—OR 4C , —C(O)NR 4A R 4B , —OR 4D , —NR 4A SO 2 R 4D , —NR 4A C(O)R 4C , —NR 4A C(O)OR 4C , —NR 4A OR 4C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. The symbol Y 2 is N or C(R 5 ). R 5 is hydrogen, halogen, —CX 5 3 , —CHX 5 2 , —CH 2 X 5 , —OCX 5 3 , —OCH 2 X 5 , —OCHX 5 2 , —CN, —SO n5 R 5D , —SO v5 NR 5A R 5B , —NHC(O)NR 5A R 5B , —N(O) m5 , —NR 5A R 5B , —C(O)R 5C , —C(O)—OR 5C , —C(O)NR 5A R 5B , —OR 5D , —NR 5A SO 2 R 5D , —NR 5A C(O)R 5C , —NR 5A C(O)OR 5C , —NR 5A OR 5C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. L 1 is a bond, —S(O) 2 —, —S(O) 2 -Ph-, —NR 6 —, —O—, —S—, —C(O)—, —C(O)NR 6 —, —NR 6 C(O)—, —NR 6 C(O)NH—, —NHC(O)NR 6 —, —C(O)O—, —OC(O)—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene. R 6 is hydrogen, halogen, —CX 6 3 , —CHX 6 2 , —CH 2 X 6 , —OCX 6 3 , —OCH 2 X 6 , —OCHX 6 2 , —CN, —SO n6 R 6D , —SO v6 NR 6A R 6B , —NHC(O)NR 6A R 6B , —N(O) m6 , —NR 6A R 6B , —C(O)R 6C , —C(O)—OR 6C , —C(O)NR 6A R 6B , —OR 6D , —NR 6A SO 2 R 6D , —NR 6A C(O)R 6C , —NR 6A C(O)OR 6C , —NR 6A OR 6C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. L 2 is a bond, —S(O) 2 —, —S(O) 2 -Ph-, —NR 7A —, —O—, —S—, —C(O)—, —C(O)NR 7A —, —NR 7 C(O)—, —NR 7 C(O)NH—, —NHC(O)NR—, —C(O)O—, —OC(O)—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene. R 7 is hydrogen, halogen, —CX 7 3 , —CHX 7 2 , —CH 2 X 7 , —OCX 7 3 , —OCH 2 X 7 , —OCHX 7 2 , —CN, —SO n7 R 7D , —SO v7 NR 7A R 7B , —NHC(O)NR 7A R 7B , —N(O) m7 , —NR 7A R 7B , —C(O)R 7C , —C(O)—OR 7C , —C(O)NR 7A R 7B , —OR 7D , —NR 7A SO 2 R 7D , —NR 7A C(O)R 7C , —NR 7A C(O)OR 7C , —NR 7A OR 7C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. E is an electrophilic moiety. Each R 1A , R 1B , R 1C , R 1D , R 2A , R 2B , R 2C , R 2D , R 4A , R 4B , R 4C , R 4D , R 5A , R 5B , R 5C , R 5D , R 6A , R 6B , R 6C , R 6D , R 7A , R 7B , R 7C , and R 7D is independently hydrogen, —CX 3 , —CN, —COOH, —CONH 2 , —CHX 2 , —CH 2 X, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. R 1A and R 1B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. R 2A and R 2B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. R 4A and R 4B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. R 5A and R 5B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. R 6A and R 6B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. R 7A and R 7B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. Each X, X 1 , X 2 , X 4 , X 5 , X 6 , and X 7 is independently —F, —Cl, —Br, or —I. The symbols n1, n2, n4, n5, n6, and n7 are independently an integer from 0 to 4. The symbols m1, m2, m4, m5, m6, m7, v1, v2, v4, v5, v6, and v7 are independently an integer from 1 to 2.

In an aspect is provided a pharmaceutical composition including a compound described herein, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

In an aspect is provided a method of treating cancer including administering to a subject in need thereof an effective amount of a compound described herein.

In an aspect is provided a method of treating an inflammatory disease including administering to a subject in need thereof an effective amount of a compound described herein.

In an aspect is provided a method of treating a disease associated with Bruton's Tyrosine Kinase activity including administering to a subject in need thereof an effective amount of a compound described herein. In embodiments, the disease is associated with aberrant Bruton's Tyrosine Kinase activity.

In an aspect is provided a method of inhibiting Bruton's Tyrosine Kinase activity including contacting the Bruton's Tyrosine Kinase with a compound described herein.

In an aspect is provided a Bruton's tyrosine kinase protein covalently bonded to a compound described herein (e.g., Bruton's Tyrosine Kinase inhibitor, Bruton's Tyrosine Kinase antagonist, compound described herein, or a portion of a compound described herein).

In an aspect is provided a Bruton's Tyrosine Kinase protein (e.g., human BTK) covalently bonded to a Bruton's Tyrosine Kinase inhibitor (e.g., Bruton's Tyrosine Kinase antagonist, compound described herein, or a portion of a compound described herein).

I. Definitions

The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulae set forth herein are constructed according to the standard rules of chemical valency known in the chemical arts.

Where substituent groups are specified by their conventional chemical formulae, written from left to right, they equally encompass the chemically identical substituents that would result from writing the structure from right to left, e.g., —CH 2 O— is equivalent to —OCH 2 —.

The term “alkyl,” by itself or as part of another substituent, means, unless otherwise stated, a straight (i.e., unbranched) or branched carbon chain (or carbon), or combination thereof, which may be fully saturated, mono- or polyunsaturated and can include mono-, di- and multivalent radicals, having the number of carbon atoms designated (i.e., C 1 -C 10 means one to ten carbons). Alkyl is an uncyclized chain. Examples of saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. An unsaturated alkyl group is one having one or more double bonds or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl), ethynyl, 1- and 3-propynyl, 3-butynyl, and the higher homologs and isomers. An alkoxy is an alkyl attached to the remainder of the molecule via an oxygen linker (—O—).

The term “alkylene,” by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from an alkyl, as exemplified, but not limited by, —CH 2 CH 2 CH 2 CH 2 —. Typically, an alkyl (or alkylene) group will have from 1 to 24 carbon atoms, with those groups having 10 or fewer carbon atoms being preferred herein. A “lower alkyl” or “lower alkylene” is a shorter chain alkyl or alkylene group, generally having eight or fewer carbon atoms. The term “alkenylene,” by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from an alkene.

The term “heteroalkyl,” by itself or in combination with another term, means, unless otherwise stated, a stable straight or branched chain, or combinations thereof, including at least one carbon atom and at least one heteroatom (e.g., O, N, P, Si, or S), and wherein the nitrogen and sulfur atoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized. The heteroatom(s) (e.g., O, N, P, S, B, As, or Si) may be placed at any interior position of the heteroalkyl group or at the position at which the alkyl group is attached to the remainder of the molecule. Heteroalkyl is an uncyclized chain. Examples include, but are not limited to: —CH 2 —CH 2 —O—CH 3 , —CH 2 —CH 2 —NH—CH 3 , —CH 2 —CH 2 —N(CH 3 )—CH 3 , —CH 2 —S—CH 2 —CH 3 , —CH 2 —CH 2 , —S(O)—CH 3 , —CH 2 —CH 2 —S(O) 2 —CH 3 , —CH═CH—O—CH 3 , —Si(CH 3 ) 3 , —CH 2 —CH═N—OCH 3 , —CH═CH—N(CH 3 )—CH 3 , —O—CH 3 , —O—CH 2 —CH 3 , and —CN. Up to two or three heteroatoms may be consecutive, such as, for example, —CH 2 —NH—OCH 3 and —CH 2 —O—Si(CH 3 ) 3 . A heteroalkyl moiety may include one heteroatom (e.g., O, N, S, Si, or P). A heteroalkyl moiety may include two optionally different heteroatoms (e.g., O, N, S, Si, or P). A heteroalkyl moiety may include three optionally different heteroatoms (e.g., O, N, S, Si, or P). A heteroalkyl moiety may include four optionally different heteroatoms (e.g., O, N, S, Si, or P). A heteroalkyl moiety may include five optionally different heteroatoms (e.g., O, N, S, Si, or P). A heteroalkyl moiety may include up to 8 optionally different heteroatoms (e.g., O, N, S, Si, or P).

Similarly, the term “heteroalkylene,” by itself or as part of another substituent, means, unless otherwise stated, a divalent radical derived from heteroalkyl, as exemplified, but not limited by, —CH 2 —CH 2 —S—CH 2 —CH 2 — and —CH 2 —S—CH 2 —CH 2 —NH—CH 2 —. For heteroalkylene groups, heteroatoms can also occupy either or both of the chain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and the like). Still further, for alkylene and heteroalkylene linking groups, no orientation of the linking group is implied by the direction in which the formula of the linking group is written. For example, the formula —C(O) 2 R′— represents both —C(O) 2 R′— and —R′C(O) 2 —. As described above, heteroalkyl groups, as used herein, include those groups that are attached to the remainder of the molecule through a heteroatom, such as —C(O)R′, —C(O)NR′, —NR′R″, —OR′, —SR′, and/or —SO 2 R′. Where “heteroalkyl” is recited, followed by recitations of specific heteroalkyl groups, such as —NR′R″ or the like, it will be understood that the terms heteroalkyl and —NR′R″ are not redundant or mutually exclusive. Rather, the specific heteroalkyl groups are recited to add clarity. Thus, the term “heteroalkyl” should not be interpreted herein as excluding specific heteroalkyl groups, such as —NR′R″ or the like.

The terms “cycloalkyl” and “heterocycloalkyl,” by themselves or in combination with other terms, mean, unless otherwise stated, cyclic versions of “alkyl” and “heteroalkyl,” respectively. Cycloalkyl and heterocycloalkyl are not aromatic. Additionally, for heterocycloalkyl, a heteroatom can occupy the position at which the heterocycle is attached to the remainder of the molecule. In embodiments, a cycloalkyl is a spirocyclic cycloalkyl, wherein the spirocyclic rings are cycloalkyl rings. In embodiments, a cycloalkyl is a fused ring cycloalkyl, wherein the fused rings are cycloalkyl rings. In embodiments, a cycloalkyl is a bridged ring cycloalkyl, wherein the bridged rings are cycloalkyl rings. In embodiments, a cycloalkyl is monocyclic. In embodiments, a cycloalkyl is two rings. In embodiments, a cycloalkyl is three rings. In embodiments, a cycloalkyl is four rings. In embodiments, a cycloalkyl is five rings. In embodiments, a cycloalkyl is polycyclic. In embodiments, a heterocycloalkyl is a spirocyclic heterocycloalkyl, wherein the spirocyclic rings are one or more heterocycloalkyl rings and optionally one or more cycloalkyl rings. In embodiments, a heterocycloalkyl is a fused ring heterocycloalkyl, wherein the fused rings are one or more heterocycloalkyl rings and optionally one or more cycloalkyl rings. In embodiments, a heterocycloalkyl is a bridged ring heterocycloalkyl, wherein the bridged rings are one or more heterocycloalkyl rings and optionally one or more cycloalkyl rings. In embodiments, the rings of a spirocyclic, fused ring, or bridged ring heterocycloalkyl are heterocyclic rings. In embodiments, a heterocycloalkyl is monocyclic. In embodiments, a heterocycloalkyl is two rings. In embodiments, a heterocycloalkyl is three rings. In embodiments, a heterocycloalkyl is four rings. In embodiments, a heterocycloalkyl is five rings. In embodiments, a heterocycloalkyl is polycyclic. Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, and the like. Examples of heterocycloalkyl include, but are not limited to, 1-(1,2,5,6-tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1-piperazinyl, 2-piperazinyl, and the like. A “cycloalkylene” and a “heterocycloalkylene,” alone or as part of another substituent, means a divalent radical derived from a cycloalkyl and heterocycloalkyl, respectively. In embodiments, a cycloalkylene or heterocycloalkylene is polycyclic. In embodiments, a heterocycloalkylene is a spirocyclic heterocycloalkylene, wherein the spirocyclic rings are one or more heterocycloalkyl rings and optionally one or more cycloalkyl rings.

The terms “halo” or “halogen,” by themselves or as part of another substituent, mean, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom. Additionally, terms such as “haloalkyl” are meant to include monohaloalkyl and polyhaloalkyl. For example, the term “halo(C 1 -C 4 )alkyl” includes, but is not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, and the like.

The term “acyl” means, unless otherwise stated, —C(O)R where R is a substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

The term “aryl” means, unless otherwise stated, a polyunsaturated, aromatic, hydrocarbon substituent, which can be a single ring or multiple rings (preferably from 1 to 3 rings) that are fused together (i.e., a fused ring aryl) or linked covalently. A fused ring aryl refers to multiple rings fused together wherein at least one of the fused rings is an aryl ring. The term “heteroaryl” refers to aryl groups (or rings) that contain at least one heteroatom such as N, O, or S, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atom(s) are optionally quaternized. Thus, the term “heteroaryl” includes fused ring heteroaryl groups (i.e., multiple rings fused together wherein at least one of the fused rings is a heteroaromatic ring). A 5,6-fused ring heteroarylene refers to two rings fused together, wherein one ring has 5 members and the other ring has 6 members, and wherein at least one ring is a heteroaryl ring. Likewise, a 6,6-fused ring heteroarylene refers to two rings fused together, wherein one ring has 6 members and the other ring has 6 members, and wherein at least one ring is a heteroaryl ring. And a 6,5-fused ring heteroarylene refers to two rings fused together, wherein one ring has 6 members and the other ring has 5 members, and wherein at least one ring is a heteroaryl ring. A heteroaryl group can be attached to the remainder of the molecule through a carbon or heteroatom. Non-limiting examples of aryl and heteroaryl groups include phenyl, naphthyl, pyrrolyl, pyrazolyl, pyridazinyl, triazinyl, pyrimidinyl, imidazolyl, pyrazinyl, purinyl, oxazolyl, isoxazolyl, thiazolyl, furyl, thienyl, pyridyl, pyrimidyl, benzothiazolyl, benzoxazoyl benzimidazolyl, benzofuran, isobenzofuranyl, indolyl, isoindolyl, benzothiophenyl, isoquinolyl, quinoxalinyl, quinolyl, 1-naphthyl, 2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl, 2-benzimidazolyl, 5-indolyl, 1-isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3-quinolyl, and 6-quinolyl. Substituents for each of the above noted aryl and heteroaryl ring systems are selected from the group of acceptable substituents described below. An “arylene” and a “heteroarylene,” alone or as part of another substituent, mean a divalent radical derived from an aryl and heteroaryl, respectively. A heteroaryl group substituent may be —O— bonded to a ring heteroatom nitrogen.

Spirocyclic rings are two or more rings wherein adjacent rings are attached through a single atom. The individual rings within spirocyclic rings may be identical or different. Individual rings in spirocyclic rings may be substituted or unsubstituted and may have different substituents from other individual rings within a set of spirocyclic rings. Possible substituents for individual rings within spirocyclic rings are the possible substituents for the same ring when not part of spirocyclic rings (e.g. substituents for cycloalkyl or heterocycloalkyl rings). Spirocylic rings may be substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heterocycloalkylene and individual rings within a spirocyclic ring group may be any of the immediately previous list, including having all rings of one type (e.g. all rings being substituted heterocycloalkylene wherein each ring may be the same or different substituted heterocycloalkylene). When referring to a spirocyclic ring system, heterocyclic spirocyclic rings means a spirocyclic rings wherein at least one ring is a heterocyclic ring and wherein each ring may be a different ring. When referring to a spirocyclic ring system, substituted spirocyclic rings means that at least one ring is substituted and each substituent may optionally be different.

The symbol “ ” denotes the point of attachment of a chemical moiety to the remainder of a molecule or chemical formula.

The term “oxo,” as used herein, means an oxygen that is double bonded to a carbon atom.

The term “alkylarylene” as an arylene moiety covalently bonded to an alkylene moiety (also referred to herein as an alkylene linker). In embodiments, the alkylarylene group has the formula:

An alkylarylene moiety may be substituted (e.g. with a substituent group) on the alkylene moiety or the arylene linker (e.g. at carbons 2, 3, 4, or 6) with halogen, oxo, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —Cl 3 , —CN, —CHO, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 2 CH 3 —SO 3 H, —OSO 3 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , substituted or unsubstituted C 1 -C 5 alkyl or substituted or unsubstituted 2 to 5 membered heteroalkyl). In embodiments, the alkylarylene is unsubstituted.

Each of the above terms (e.g., “alkyl,” “heteroalkyl,” “cyclalkyl,” “heterocycloalkyl,” “aryl,” and “heteroaryl”) includes both substituted and unsubstituted forms of the indicated radical. Preferred substituents for each type of radical are provided below.

Substituents for the alkyl and heteroalkyl radicals (including those groups often referred to as alkylene, alkenyl, heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) can be one or more of a variety of groups selected from, but not limited to, —OR′, ═O, ═NR′, ═N—OR′, —NR′R″, —SR′, -halogen, —SiR′R″R′″, —OC(O)R′, —C(O)R′, —CO 2 R′, —CONR′R″, —OC(O)NR′R″, —NR″C(O)R′, —NR′—C(O)NR″R′″, —NR″C(O) 2 R′, —NR—C(NR′R″R′″)═NR″″, —NR—C(NR′R″)═NR′″, —S(O)R′, —S(O) 2 R′, —S(O) 2 NR′R″, —NRSO 2 R′, —NR′NR″R′″, —ONR′R″, —NR′C(O)NR″NR′″R″″, —CN, —NO 2 , —NR′SO 2 R″, —NR′C(O)R″, —NR′C(O)—OR″, —NR′OR″, in a number ranging from zero to (2m′+1), where m′ is the total number of carbon atoms in such radical. R, R′, R″, R′″, and R″″ each preferably independently refer to hydrogen, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl (e.g., aryl substituted with 1-3 halogens), substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, alkoxy, or thioalkoxy groups, or arylalkyl groups. When a compound described herein includes more than one R group, for example, each of the R groups is independently selected as are each R′, R″, R′″, and R″″ group when more than one of these groups is present. When R′ and R″ are attached to the same nitrogen atom, they can be combined with the nitrogen atom to form a 4-, 5-, 6-, or 7-membered ring. For example, —NR′R″ includes, but is not limited to, 1-pyrrolidinyl and 4-morpholinyl. From the above discussion of substituents, one of skill in the art will understand that the term “alkyl” is meant to include groups including carbon atoms bound to groups other than hydrogen groups, such as haloalkyl (e.g., —CF 3 and —CH 2 CF 3 ) and acyl (e.g., —C(O)CH 3 , —C(O)CF 3 , —C(O)CH 2 OCH 3 , and the like).

Similar to the substituents described for the alkyl radical, substituents for the aryl and heteroaryl groups are varied and are selected from, for example: —OR′, —NR′R″, —SR′, -halogen, —SiR′R″R′″, —OC(O)R′, —C(O)R′, —CO 2 R′, —CONR′R″, —OC(O)NR′R″, —NR″C(O)R′, —NR′—C(O)NR″R′″, —NR″C(O) 2 R′, —NR—C(NR′R″R′″)—NR″″, —NR—C(NR′R″)═NR′″, —S(O)R′, —S(O) 2 R′, —S(O) 2 NR′R″, —NRSO 2 R′, —NR′NR″R′″, —ONR′R″, —NR′C(O)NR″NR′″R″″, —CN, —NO 2 , —R′, —N 3 , —CH(Ph) 2 , fluoro(C 1 -C 4 )alkoxy, and fluoro(C 1 -C 4 )alkyl, —NR′SO 2 R″, —NR′C(O)R″, —NR′C(O)—OR″, —NR′OR″, in a number ranging from zero to the total number of open valences on the aromatic ring system; and where R′, R″, R′″, and R″″ are preferably independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. When a compound described herein includes more than one R group, for example, each of the R groups is independently selected as are each R′, R″, R′″, and R″″ groups when more than one of these groups is present.

Substituents for rings (e.g. cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene) may be depicted as substituents on the ring rather than on a specific atom of a ring (commonly referred to as a floating substituent). In such a case, the substituent may be attached to any of the ring atoms (obeying the rules of chemical valency) and in the case of fused rings or spirocyclic rings, a substituent depicted as associated with one member of the fused rings or spirocyclic rings (a floating substituent on a single ring), may be a substituent on any of the fused rings or spirocyclic rings (a floating substituent on multiple rings). When a substituent is attached to a ring, but not a specific atom (a floating substituent), and a subscript for the substituent is an integer greater than one, the multiple substituents may be on the same atom, same ring, different atoms, different fused rings, different spirocyclic rings, and each substituent may optionally be different. Where a point of attachment of a ring to the remainder of a molecule is not limited to a single atom (a floating substituent), the attachment point may be any atom of the ring and in the case of a fused ring or spirocyclic ring, any atom of any of the fused rings or spirocyclic rings while obeying the rules of chemical valency. Where a ring, fused rings, or spirocyclic rings contain one or more ring heteroatoms and the ring, fused rings, or spirocyclic rings are shown with one more floating substituents (including, but not limited to, points of attachment to the remainder of the molecule), the floating substituents may be bonded to the heteroatoms. Where the ring heteroatoms are shown bound to one or more hydrogens (e.g. a ring nitrogen with two bonds to ring atoms and a third bond to a hydrogen) in the structure or formula with the floating substituent, when the heteroatom is bonded to the floating substituent, the substituent will be understood to replace the hydrogen, while obeying the rules of chemical valency.

Two or more substituents may optionally be joined to form aryl, heteroaryl, cycloalkyl, or heterocycloalkyl groups. Such so-called ring-forming substituents are typically, though not necessarily, found attached to a cyclic base structure. In one embodiment, the ring-forming substituents are attached to adjacent members of the base structure. For example, two ring-forming substituents attached to adjacent members of a cyclic base structure create a fused ring structure. In another embodiment, the ring-forming substituents are attached to a single member of the base structure. For example, two ring-forming substituents attached to a single member of a cyclic base structure create a spirocyclic structure. In yet another embodiment, the ring-forming substituents are attached to non-adjacent members of the base structure.

Two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally form a ring of the formula -T-C(O)—(CRR′) q —U—, wherein T and U are independently —NR—, —O—, —CRR′—, or a single bond, and q is an integer of from 0 to 3. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -A-(CH 2 ) r —B—, wherein A and B are independently —CRR′—, —O—, —NR—, —S—, —S(O)—, —S(O) 2 —, —S(O) 2 NR′—, or a single bond, and r is an integer of from 1 to 4. One of the single bonds of the new ring so formed may optionally be replaced with a double bond. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula —(CRR′) s —X′—(C″R″R′″) d —, where s and d are independently integers of from 0 to 3, and X′ is —O—, —NR′—, —S—, —S(O)—, —S(O) 2 —, or —S(O) 2 NR′—. The substituents R, R′, R″, and R′″ are preferably independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

As used herein, the terms “heteroatom” or “ring heteroatom” are meant to include oxygen (O), nitrogen (N), sulfur (S), phosphorus (P), and silicon (Si).

A “substituent group,” as used herein, means a group selected from the following moieties:

(A) oxo, halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O) NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, and

(B) alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, substituted with at least one substituent selected from:

(i) oxo, halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O) NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, and

(ii) alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, substituted with at least one substituent selected from:

(a) oxo, halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O) NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl, and

(b) alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, substituted with at least one substituent selected from: oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O) NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, unsubstituted heteroaryl.

A “size-limited substituent” or “size-limited substituent group,” as used herein, means a group selected from all of the substituents described above for a “substituent group,” wherein each substituted or unsubstituted alkyl is a substituted or unsubstituted C 1 -C 2 alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2 to 20 membered heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C 3 -C 8 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3 to 8 membered heterocycloalkyl, each substituted or unsubstituted aryl is a substituted or unsubstituted C 6 -C 10 aryl, and each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5 to 10 membered heteroaryl.

A “lower substituent” or “lower substituent group,” as used herein, means a group selected from all of the substituents described above for a “substituent group,” wherein each substituted or unsubstituted alkyl is a substituted or unsubstituted C 1 -C 8 alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2 to 8 membered heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C 3 -C 7 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3 to 7 membered heterocycloalkyl, each substituted or unsubstituted aryl is a substituted or unsubstituted C 6 -C 10 aryl, and each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5 to 9 membered heteroaryl.

In some embodiments, each substituted group described in the compounds herein is substituted with at least one substituent group. More specifically, in some embodiments, each substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and/or substituted heteroarylene described in the compounds herein are substituted with at least one substituent group. In other embodiments, at least one or all of these groups are substituted with at least one size-limited substituent group. In other embodiments, at least one or all of these groups are substituted with at least one lower substituent group.

In other embodiments of the compounds herein, each substituted or unsubstituted alkyl may be a substituted or unsubstituted C 1 -C 20 alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2 to 20 membered heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C 3 -C 8 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3 to 8 membered heterocycloalkyl, each substituted or unsubstituted aryl is a substituted or unsubstituted C 6 -C 10 aryl, and/or each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5 to 10 membered heteroaryl. In some embodiments of the compounds herein, each substituted or unsubstituted alkylene is a substituted or unsubstituted C 1 -C 20 alkylene, each substituted or unsubstituted heteroalkylene is a substituted or unsubstituted 2 to 20 membered heteroalkylene, each substituted or unsubstituted cycloalkylene is a substituted or unsubstituted C 3 -C 8 cycloalkylene, each substituted or unsubstituted heterocycloalkylene is a substituted or unsubstituted 3 to 8 membered heterocycloalkylene, each substituted or unsubstituted arylene is a substituted or unsubstituted C 6 -C 10 arylene, and/or each substituted or unsubstituted heteroarylene is a substituted or unsubstituted 5 to 10 membered heteroarylene.

In some embodiments, each substituted or unsubstituted alkyl is a substituted or unsubstituted C 1 -C 8 alkyl, each substituted or unsubstituted heteroalkyl is a substituted or unsubstituted 2 to 8 membered heteroalkyl, each substituted or unsubstituted cycloalkyl is a substituted or unsubstituted C 3 -C 7 cycloalkyl, each substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted 3 to 7 membered heterocycloalkyl, each substituted or unsubstituted aryl is a substituted or unsubstituted C 6 -C 10 aryl, and/or each substituted or unsubstituted heteroaryl is a substituted or unsubstituted 5 to 9 membered heteroaryl. In some embodiments, each substituted or unsubstituted alkylene is a substituted or unsubstituted C 1 -C 8 alkylene, each substituted or unsubstituted heteroalkylene is a substituted or unsubstituted 2 to 8 membered heteroalkylene, each substituted or unsubstituted cycloalkylene is a substituted or unsubstituted C 3 -C 7 cycloalkylene, each substituted or unsubstituted heterocycloalkylene is a substituted or unsubstituted 3 to 7 membered heterocycloalkylene, each substituted or unsubstituted arylene is a substituted or unsubstituted C 6 -C 10 arylene, and/or each substituted or unsubstituted heteroarylene is a substituted or unsubstituted 5 to 9 membered heteroarylene. In some embodiments, the compound is a chemical species set forth in the Examples section, FIGURES, or tables below.

Certain compounds of the present invention possess asymmetric carbon atoms (optical or chiral centers) or double bonds; the enantiomers, racemates, diastereomers, tautomers, geometric isomers, stereoisometric forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)- or, as (D)- or (L)- for amino acids, and individual isomers are encompassed within the scope of the present invention. The compounds of the present invention do not include those that are known in art to be too unstable to synthesize and/or isolate. The present invention is meant to include compounds in racemic and optically pure forms. Optically active (R)- and (S)-, or (D)- and (L)-isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. When the compounds described herein contain olefinic bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that the compounds include both E and Z geometric isomers.

As used herein, the term “isomers” refers to compounds having the same number and kind of atoms, and hence the same molecular weight, but differing in respect to the structural arrangement or configuration of the atoms.

The term “tautomer,” as used herein, refers to one of two or more structural isomers which exist in equilibrium and which are readily converted from one isomeric form to another.

It will be apparent to one skilled in the art that certain compounds of this invention may exist in tautomeric forms, all such tautomeric forms of the compounds being within the scope of the invention.

Unless otherwise stated, structures depicted herein are also meant to include all stereochemical forms of the structure; i.e., the R and S configurations for each asymmetric center. Therefore, single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the present compounds are within the scope of the invention.

Unless otherwise stated, structures depicted herein are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by 13 C- or 14 C-enriched carbon are within the scope of this invention.

Unless otherwise stated, structures depicted herein are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by 13 C- or 14 C-enriched carbon are within the scope of this invention.

The compounds of the present invention may also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may be radiolabeled with radioactive isotopes, such as for example tritium ( 3 H), iodine-125 ( 125 I), or carbon-14 ( 14 C). All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention.

It should be noted that throughout the application that alternatives are written in Markush groups, for example, each amino acid position that contains more than one possible amino acid. It is specifically contemplated that each member of the Markush group should be considered separately, thereby comprising another embodiment, and the Markush group is not to be read as a single unit.

“Analog,” or “analogue” is used in accordance with its plain ordinary meaning within Chemistry and Biology and refers to a chemical compound that is structurally similar to another compound (i.e., a so-called “reference” compound) but differs in composition, e.g., in the replacement of one atom by an atom of a different element, or in the presence of a particular functional group, or the replacement of one functional group by another functional group, or the absolute stereochemistry of one or more chiral centers of the reference compound. Accordingly, an analog is a compound that is similar or comparable in function and appearance but not in structure or origin to a reference compound.

The terms “a” or “an,” as used in herein means one or more. In addition, the phrase “substituted with a[n],” as used herein, means the specified group may be substituted with one or more of any or all of the named substituents. For example, where a group, such as an alkyl or heteroaryl group, is “substituted with an unsubstituted C 1 -C 20 alkyl, or unsubstituted 2 to 20 membered heteroalkyl,” the group may contain one or more unsubstituted C 1 -C 20 alkyls, and/or one or more unsubstituted 2 to 20 membered heteroalkyls.

Moreover, where a moiety is substituted with an R substituent, the group may be referred to as “R-substituted.” Where a moiety is R-substituted, the moiety is substituted with at least one R substituent and each R substituent is optionally different. Where a particular R group is present in the description of a chemical genus (such as Formula (I)), a Roman alphabetic symbol may be used to distinguish each appearance of that particular R group. For example, where multiple R 1 substituents are present, each R 13 substituent may be distinguished as R 13A , R 13B , R 13C , R 13D , etc., wherein each of R 13A , R 13B , R 13C , R 13D , etc. is defined within the scope of the definition of R 13 and optionally differently.

A “covalent cysteine modifier moiety” as used herein refers to a substituent that is capable of reacting with the sulfhydryl functional group of a cysteine amino acid (e.g. cysteine 481 of the Bruton's Tyrosine Kinase protein (e.g., human BTK)) to form a covalent bond. Thus, the covalent cysteine modifier moiety is typically electrophilic.

A “detectable moiety” as used herein refers to a moiety that can be covalently or noncovalently attached to a compound or biomolecule that can be detected for instance, using techniques known in the art. In embodiments, the detectable moiety is covalently attached. The detectable moiety may provide for imaging of the attached compound or biomolecule. The detectable moiety may indicate the contacting between two compounds. Exemplary detectable moieties are fluorophores, antibodies, reactive dies, radio-labeled moieties, magnetic contrast agents, and quantum dots. Exemplary fluorophores include fluorescein, rhodamine, GFP, coumarin, FITC, Alexa fluor, Cy3, Cy5, BODIPY, and cyanine dyes. Exemplary radionuclides include Fluorine-18, Gallium-68, and Copper-64. Exemplary magnetic contrast agents include gadolinium, iron oxide and iron platinum, and manganese.

Description of compounds of the present invention are limited by principles of chemical bonding known to those skilled in the art. Accordingly, where a group may be substituted by one or more of a number of substituents, such substitutions are selected so as to comply with principles of chemical bonding and to give compounds which are not inherently unstable and/or would be known to one of ordinary skill in the art as likely to be unstable under ambient conditions, such as aqueous, neutral, and several known physiological conditions. For example, a heterocycloalkyl or heteroaryl is attached to the remainder of the molecule via a ring heteroatom in compliance with principles of chemical bonding known to those skilled in the art thereby avoiding inherently unstable compounds.

The term “pharmaceutically acceptable salts” is meant to include salts of the active compounds that are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds of the present invention contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt. When compounds of the present invention contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, oxalic, methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galactunoric acids and the like (see, for example, Berge et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Science, 1977, 66, 1-19). Certain specific compounds of the present invention contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts.

Thus, the compounds of the present invention may exist as salts, such as with pharmaceutically acceptable acids. The present invention includes such salts. Non-limiting examples of such salts include hydrochlorides, hydrobromides, phosphates, sulfates, methanesulfonates, nitrates, maleates, acetates, citrates, fumarates, proprionates, tartrates (e.g., (+)-tartrates, (−)-tartrates, or mixtures thereof including racemic mixtures), succinates, benzoates, and salts with amino acids such as glutamic acid, and quaternary ammonium salts (e.g. methyl iodide, ethyl iodide, and the like). These salts may be prepared by methods known to those skilled in the art.

The neutral forms of the compounds are preferably regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. The parent form of the compound may differ from the various salt forms in certain physical properties, such as solubility in polar solvents.

In addition to salt forms, the present invention provides compounds, which are in a prodrug form. Prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present invention. Prodrugs of the compounds described herein may be converted in vivo after administration. Additionally, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment, such as, for example, when contacted with a suitable enzyme or chemical reagent.

Certain compounds of the present invention can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms are equivalent to unsolvated forms and are encompassed within the scope of the present invention. Certain compounds of the present invention may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the present invention and are intended to be within the scope of the present invention.

“Pharmaceutically acceptable excipient” and “pharmaceutically acceptable carrier” refer to a substance that aids the administration of an active agent to and absorption by a subject and can be included in the compositions of the present invention without causing a significant adverse toxicological effect on the patient. Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, normal saline solutions, lactated Ringer's, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavors, salt solutions (such as Ringer's solution), alcohols, oils, gelatins, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxymethycellulose, polyvinyl pyrrolidine, and colors, and the like. Such preparations can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and/or aromatic substances and the like that do not deleteriously react with the compounds of the invention. One of skill in the art will recognize that other pharmaceutical excipients are useful in the present invention.

The term “preparation” is intended to include the formulation of the active compound with encapsulating material as a carrier providing a capsule in which the active component with or without other carriers, is surrounded by a carrier, which is thus in association with it. Similarly, cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid dosage forms suitable for oral administration.

An “Bruton's Tyrosine Kinase inhibitor” or “BTK compound” or “BTK inhibitor” refers to a compound (e.g. compounds described herein) that reduces the activity of Bruton's Tyrosine Kinase when compared to a control, such as absence of the compound or a compound with known inactivity.

The terms “polypeptide,” “peptide” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues, wherein the polymer may optionally be conjugated to a moiety that does not consist of amino acids. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymer.

A polypeptide, or a cell is “recombinant” when it is artificial or engineered, or derived from or contains an artificial or engineered protein or nucleic acid (e.g. non-natural or not wild type). For example, a polynucleotide that is inserted into a vector or any other heterologous location, e.g., in a genome of a recombinant organism, such that it is not associated with nucleotide sequences that normally flank the polynucleotide as it is found in nature is a recombinant polynucleotide. A protein expressed in vitro or in vivo from a recombinant polynucleotide is an example of a recombinant polypeptide. Likewise, a polynucleotide sequence that does not appear in nature, for example a variant of a naturally occurring gene, is recombinant.

An amino acid residue in a protein “corresponds” to a given residue when it occupies the same essential structural position within the protein as the given residue. For example, a selected residue in a selected protein corresponds to Cys481 of human Bruton's Tyrosine Kinase when the selected residue occupies the same essential spatial or other structural relationship as Cys481 in human Bruton's Tyrosine Kinase. In some embodiments, where a selected protein is aligned for maximum homology with the human Bruton's Tyrosine Kinase protein, the position in the aligned selected protein aligning with Cys481 is said to correspond to Cys481. Instead of a primary sequence alignment, a three dimensional structural alignment can also be used, e.g., where the structure of the selected protein is aligned for maximum correspondence with the human Bruton's Tyrosine Kinase protein and the overall structures compared. In this case, an amino acid that occupies the same essential position as Cys481 in the structural model is said to correspond to the Cys481 residue.

“Contacting” is used in accordance with its plain ordinary meaning and refers to the process of allowing at least two distinct species (e.g. chemical compounds including biomolecules or cells) to become sufficiently proximal to react, interact or physically touch. It should be appreciated; however, the resulting reaction product can be produced directly from a reaction between the added reagents or from an intermediate from one or more of the added reagents that can be produced in the reaction mixture.

The term “contacting” may include allowing two species to react, interact, or physically touch, wherein the two species may be a compound as described herein and a protein or enzyme. In some embodiments contacting includes allowing a compound described herein to interact with a protein or enzyme that is involved in a signaling pathway.

As defined herein, the term “activation”, “activate”, “activating” and the like in reference to a protein refers to conversion of a protein into a biologically active derivative from an initial inactive or deactivated state. The terms reference activation, or activating, sensitizing, or up-regulating signal transduction or enzymatic activity or the amount of a protein decreased in a disease.

As defined herein, the term “inhibition”, “inhibit”, “inhibiting” and the like in reference to a protein-inhibitor interaction means negatively affecting (e.g. decreasing) the activity or function of the protein relative to the activity or function of the protein in the absence of the inhibitor. In embodiments inhibition means negatively affecting (e.g. decreasing) the concentration or levels of the protein relative to the concentration or level of the protein in the absence of the inhibitor. In embodiments inhibition refers to reduction of a disease or symptoms of disease. In embodiments, inhibition refers to a reduction in the activity of a particular protein target. Thus, inhibition includes, at least in part, partially or totally blocking stimulation, decreasing, preventing, or delaying activation, or inactivating, desensitizing, or down-regulating signal transduction or enzymatic activity or the amount of a protein. In embodiments, inhibition refers to a reduction of activity of a target protein resulting from a direct interaction (e.g. an inhibitor binds to the target protein). In embodiments, inhibition refers to a reduction of activity of a target protein from an indirect interaction (e.g. an inhibitor binds to a protein that activates the target protein, thereby preventing target protein activation). A “Bruton's Tyrosine Kinase inhibitor” and “BTK inhibitor” is a compound that negatively affects (e.g. decreases) the activity or function of Bruton's Tyrosine Kinase relative to the activity or function of Bruton's Tyrosine Kinase in the absence of the inhibitor (e.g., wherein the BTK inhibitor binds BTK).

The terms “Bruton's Tyrosine Kinase” and “BTK” refer to a protein (including homologs, isoforms, and functional fragments thereof) with Bruton's Tyrosine Kinase activity. The term includes any recombinant or naturally-occurring form of Bruton's Tyrosine Kinase or variants thereof that maintain Bruton's Tyrosine Kinase activity (e.g. within at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 100% activity compared to wildtype Bruton's Tyrosine Kinase). In embodiments, the Bruton's Tyrosine Kinase protein encoded by the BTK gene has the amino acid sequence set forth in or corresponding to Entrez 695, UniProt Q06187, or RefSeq (protein) NP_000052. In embodiments, the Bruton's Tyrosine Kinase BTK gene has the nucleic acid sequence set forth in RefSeq (mRNA) NM_000061. In embodiments, the amino acid sequence or nucleic acid sequence is the sequence known at the time of filing of the present application. In embodiments, the sequence corresponds to GI:4557377. In embodiments, the sequence corresponds to NP_000052.1. In embodiments, the sequence corresponds to NM_000061.2. In embodiments, the sequence corresponds to GI: 213385292. In embodiments, the Bruton's Tyrosine Kinase is a human Bruton's Tyrosine Kinase, such as a human cancer causing Bruton's Tyrosine Kinase.

The term “expression” includes any step involved in the production of the polypeptide including, but not limited to, transcription, post-transcriptional modification, translation, post-translational modification, and secretion. Expression can be detected using conventional techniques for detecting protein (e.g., ELISA, Western blotting, flow cytometry, immunofluorescence, immunohistochemistry, etc.).

The terms “disease” or “condition” refer to a state of being or health status of a patient or subject capable of being treated with the compounds or methods provided herein. The disease may be a cancer. The disease may be stroke. The disease may be an inflammatory disease. In some further instances, “cancer” refers to human cancers and carcinomas, sarcomas, adenocarcinomas, lymphomas, leukemias, etc., including solid and lymphoid cancers, kidney, breast, lung, bladder, colon, ovarian, prostate, pancreas, stomach, brain, head and neck, skin, uterine, testicular, glioma, esophagus, and liver cancer, including hepatocarcinoma, lymphoma, including B-acute lymphoblastic lymphoma, non-Hodgkin's lymphomas (e.g., Burkitt's, Small Cell, and Large Cell lymphomas), Hodgkin's lymphoma, leukemia (including AML, ALL, and CML), or multiple myeloma.

As used herein, the term “inflammatory disease” refers to a disease or condition characterized by aberrant inflammation (e.g. an increased level of inflammation compared to a control such as a healthy person not suffering from a disease). Examples of inflammatory diseases include autoimmune diseases, arthritis, rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, multiple sclerosis, systemic lupus erythematosus (SLE), myasthenia gravis, juvenile onset diabetes, diabetes mellitus type 1, Guillain-Barre syndrome, Hashimoto's encephalitis, Hashimoto's thyroiditis, ankylosing spondylitis, psoriasis, Sjogren's syndrome, vasculitis, glomerulonephritis, auto-immune thyroiditis, Behcet's disease, Crohn's disease, ulcerative colitis, bullous pemphigoid, sarcoidosis, ichthyosis, Graves ophthalmopathy, inflammatory bowel disease, Addison's disease, Vitiligo, asthma, allergic asthma, acne vulgaris, celiac disease, chronic prostatitis, inflammatory bowel disease, pelvic inflammatory disease, reperfusion injury, ischemia reperfusion injury, stroke, sarcoidosis, transplant rejection, interstitial cystitis, atherosclerosis, scleroderma, and atopic dermatitis.

As used herein, the term “cancer” refers to all types of cancer, neoplasm or malignant tumors found in mammals (e.g. humans), including leukemia, carcinomas and sarcomas. Exemplary cancers that may be treated with a compound or method provided herein include brain cancer, glioma, glioblastoma, neuroblastoma, prostate cancer, colorectal cancer, pancreatic cancer, cervical cancer, gastric cancer, ovarian cancer, lung cancer, and cancer of the head. Exemplary cancers that may be treated with a compound or method provided herein include cancer of the thyroid, endocrine system, brain, breast, cervix, colon, head & neck, liver, kidney, lung, non-small cell lung, melanoma, mesothelioma, ovary, sarcoma, stomach, uterus, Medulloblastoma, colorectal cancer, pancreatic cancer. Additional examples include, Hodgkin's Disease, Non-Hodgkin's Lymphoma, multiple myeloma, neuroblastoma, glioma, glioblastoma multiforme, ovarian cancer, rhabdomyosarcoma, primary thrombocytosis, primary macroglobulinemia, primary brain tumors, cancer, malignant pancreatic insulanoma, malignant carcinoid, urinary bladder cancer, premalignant skin lesions, testicular cancer, lymphomas, thyroid cancer, neuroblastoma, esophageal cancer, genitourinary tract cancer, malignant hypercalcemia, endometrial cancer, adrenal cortical cancer, neoplasms of the endocrine or exocrine pancreas, medullary thyroid cancer, medullary thyroid carcinoma, melanoma, colorectal cancer, papillary thyroid cancer, hepatocellular carcinoma, or prostate cancer.

The term “leukemia” refers broadly to progressive, malignant diseases of the blood-forming organs and is generally characterized by a distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemia is generally clinically classified on the basis of (1) the duration and character of the disease-acute or chronic; (2) the type of cell involved; myeloid (myelogenous), lymphoid (lymphogenous), or monocytic; and (3) the increase or non-increase in the number abnormal cells in the blood-leukemic or aleukemic (subleukemic). Exemplary leukemias that may be treated with a compound or method provided herein include, for example, acute nonlymphocytic leukemia, chronic lymphocytic leukemia, acute granulocytic leukemia, chronic granulocytic leukemia, acute promyelocytic leukemia, adult T-cell leukemia, aleukemic leukemia, a leukocythemic leukemia, basophylic leukemia, blast cell leukemia, bovine leukemia, chronic myelocytic leukemia, leukemia cutis, embryonal leukemia, eosinophilic leukemia, Gross' leukemia, hairy-cell leukemia, hemoblastic leukemia, hemocytoblastic leukemia, histiocytic leukemia, stem cell leukemia, acute monocytic leukemia, leukopenic leukemia, lymphatic leukemia, lymphoblastic leukemia, lymphocytic leukemia, lymphogenous leukemia, lymphoid leukemia, lymphosarcoma cell leukemia, mast cell leukemia, megakaryocytic leukemia, micromyeloblastic leukemia, monocytic leukemia, myeloblastic leukemia, myelocytic leukemia, myeloid granulocytic leukemia, myelomonocytic leukemia, Naegeli leukemia, plasma cell leukemia, multiple myeloma, plasmacytic leukemia, promyelocytic leukemia, Rieder cell leukemia, Schilling's leukemia, stem cell leukemia, subleukemic leukemia, or undifferentiated cell leukemia.

The term “sarcoma” generally refers to a tumor which is made up of a substance like the embryonic connective tissue and is generally composed of closely packed cells embedded in a fibrillar or homogeneous substance. Sarcomas that may be treated with a compound or method provided herein include a chondrosarcoma, fibrosarcoma, lymphosarcoma, melanosarcoma, myxosarcoma, osteosarcoma, Abemethy's sarcoma, adipose sarcoma, liposarcoma, alveolar soft part sarcoma, ameloblastic sarcoma, botryoid sarcoma, chloroma sarcoma, chorio carcinoma, embryonal sarcoma, Wilms' tumor sarcoma, endometrial sarcoma, stromal sarcoma, Ewing's sarcoma, fascial sarcoma, fibroblastic sarcoma, giant cell sarcoma, granulocytic sarcoma, Hodgkin's sarcoma, idiopathic multiple pigmented hemorrhagic sarcoma, immunoblastic sarcoma of B cells, lymphoma, immunoblastic sarcoma of T-cells, Jensen's sarcoma, Kaposi's sarcoma, Kupffer cell sarcoma, angiosarcoma, leukosarcoma, malignant mesenchymoma sarcoma, parosteal sarcoma, reticulocytic sarcoma, Rous sarcoma, serocystic sarcoma, synovial sarcoma, or telangiectaltic sarcoma.

The term “melanoma” is taken to mean a tumor arising from the melanocytic system of the skin and other organs. Melanomas that may be treated with a compound or method provided herein include, for example, acral-lentiginous melanoma, amelanotic melanoma, benign juvenile melanoma, Cloudman's melanoma, S91 melanoma, Harding-Passey melanoma, juvenile melanoma, lentigo maligna melanoma, malignant melanoma, nodular melanoma, subungal melanoma, or superficial spreading melanoma.

The term “carcinoma” refers to a malignant new growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. Exemplary carcinomas that may be treated with a compound or method provided herein include, for example, medullary thyroid carcinoma, familial medullary thyroid carcinoma, acinar carcinoma, acinous carcinoma, adenocystic carcinoma, adenoid cystic carcinoma, carcinoma adenomatosum, carcinoma of adrenal cortex, alveolar carcinoma, alveolar cell carcinoma, basal cell carcinoma, carcinoma basocellulare, basaloid carcinoma, basosquamous cell carcinoma, bronchioalveolar carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, cerebriform carcinoma, cholangiocellular carcinoma, chorionic carcinoma, colloid carcinoma, comedo carcinoma, corpus carcinoma, cribriform carcinoma, carcinoma en cuirasse, carcinoma cutaneum, cylindrical carcinoma, cylindrical cell carcinoma, duct carcinoma, carcinoma durum, embryonal carcinoma, encephaloid carcinoma, epiermoid carcinoma, carcinoma epitheliale adenoides, exophytic carcinoma, carcinoma exulcere, carcinoma fibrosum, gelatinifomi carcinoma, gelatinous carcinoma, giant cell carcinoma, carcinoma gigantocellulare, glandular carcinoma, granulosa cell carcinoma, hair-matrix carcinoma, hematoid carcinoma, hepatocellular carcinoma, Hurthle cell carcinoma, hyaline carcinoma, hypernephroid carcinoma, infantile embryonal carcinoma, carcinoma in situ, intraepidermal carcinoma, intraepithelial carcinoma, Krompecher's carcinoma, Kulchitzky-cell carcinoma, large-cell carcinoma, lenticular carcinoma, carcinoma lenticulare, lipomatous carcinoma, lymphoepithelial carcinoma, carcinoma medullare, medullary carcinoma, melanotic carcinoma, carcinoma molle, mucinous carcinoma, carcinoma muciparum, carcinoma mucocellulare, mucoepidermoid carcinoma, carcinoma mucosum, mucous carcinoma, carcinoma myxomatodes, nasopharyngeal carcinoma, oat cell carcinoma, carcinoma ossificans, osteoid carcinoma, papillary carcinoma, periportal carcinoma, preinvasive carcinoma, prickle cell carcinoma, pultaceous carcinoma, renal cell carcinoma of kidney, reserve cell carcinoma, carcinoma sarcomatodes, schneiderian carcinoma, scirrhous carcinoma, carcinoma scroti, signet-ring cell carcinoma, carcinoma simplex, small-cell carcinoma, solanoid carcinoma, spheroidal cell carcinoma, spindle cell carcinoma, carcinoma spongiosum, squamous carcinoma, squamous cell carcinoma, string carcinoma, carcinoma telangiectaticum, carcinoma telangiectodes, transitional cell carcinoma, carcinoma tuberosum, tuberous carcinoma, verrucous carcinoma, or carcinoma villosum.

The terms “treating”, or “treatment” refers to any indicia of success in the therapy or amelioration of an injury, disease, pathology or condition, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the injury, pathology or condition more tolerable to the patient; slowing in the rate of degeneration or decline; making the final point of degeneration less debilitating; improving a patient's physical or mental well-being. The treatment or amelioration of symptoms can be based on objective or subjective parameters; including the results of a physical examination, neuropsychiatric exams, and/or a psychiatric evaluation. The term “treating” and conjugations thereof, may include prevention of an injury, pathology, condition, or disease. In embodiments, treating is preventing. In embodiments, treating does not include preventing.

“Patient” or “subject in need thereof” refers to a living organism suffering from or prone to a disease or condition that can be treated by administration of a pharmaceutical composition as provided herein. Non-limiting examples include humans, other mammals, bovines, rats, mice, dogs, monkeys, goat, sheep, cows, deer, and other non-mammalian animals. In some embodiments, a patient is human.

A “effective amount” is an amount sufficient for a compound to accomplish a stated purpose relative to the absence of the compound (e.g. achieve the effect for which it is administered, treat a disease, reduce enzyme activity, increase enzyme activity, reduce a signaling pathway, or reduce one or more symptoms of a disease or condition). An example of an “effective amount” is an amount sufficient to contribute to the treatment, prevention, or reduction of a symptom or symptoms of a disease, which could also be referred to as a “therapeutically effective amount.” A “reduction” of a symptom or symptoms (and grammatical equivalents of this phrase) means decreasing of the severity or frequency of the symptom(s), or elimination of the symptom(s). A “prophylactically effective amount” of a drug is an amount of a drug that, when administered to a subject, will have the intended prophylactic effect, e.g., preventing or delaying the onset (or reoccurrence) of an injury, disease, pathology or condition, or reducing the likelihood of the onset (or reoccurrence) of an injury, disease, pathology, or condition, or their symptoms. The full prophylactic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses. Thus, a prophylactically effective amount may be administered in one or more administrations. An “activity decreasing amount,” as used herein, refers to an amount of antagonist required to decrease the activity of an enzyme relative to the absence of the antagonist. A “function disrupting amount,” as used herein, refers to the amount of antagonist required to disrupt the function of an enzyme or protein relative to the absence of the antagonist. The exact amounts will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins).

For any compound described herein, the therapeutically effective amount can be initially determined from cell culture assays. Target concentrations will be those concentrations of active compound(s) that are capable of achieving the methods described herein, as measured using the methods described herein or known in the art.

As is well known in the art, therapeutically effective amounts for use in humans can also be determined from animal models. For example, a dose for humans can be formulated to achieve a concentration that has been found to be effective in animals. The dosage in humans can be adjusted by monitoring compounds effectiveness and adjusting the dosage upwards or downwards, as described above. Adjusting the dose to achieve maximal efficacy in humans based on the methods described above and other methods is well within the capabilities of the ordinarily skilled artisan.

Dosages may be varied depending upon the requirements of the patient and the compound being employed. The dose administered to a patient, in the context of the present invention should be sufficient to effect a beneficial therapeutic response in the patient over time. The size of the dose also will be determined by the existence, nature, and extent of any adverse side-effects. Determination of the proper dosage for a particular situation is within the skill of the practitioner. Generally, treatment is initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under circumstances is reached. Dosage amounts and intervals can be adjusted individually to provide levels of the administered compound effective for the particular clinical indication being treated. This will provide a therapeutic regimen that is commensurate with the severity of the individual's disease state.

As used herein, the term “administering” means oral administration, administration as a suppository, topical contact, intravenous, intraperitoneal, intramuscular, intralesional, intrathecal, intranasal or subcutaneous administration, or the implantation of a slow-release device, e.g., a mini-osmotic pump, to a subject. Administration is by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal) compatible with the preparation. Parenteral administration includes, e.g., intravenous, intramuscular, intra-arteriole, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, etc.

“Co-administer” it is meant that a composition described herein is administered at the same time, just prior to, or just after the administration of one or more additional therapies. The compounds of the invention can be administered alone or can be coadministered to the patient. Coadministration is meant to include simultaneous or sequential administration of the compounds individually or in combination (more than one compound). Thus, the preparations can also be combined, when desired, with other active substances (e.g. to reduce metabolic degradation). The compositions of the present invention can be delivered transdermally, by a topical route, or formulated as applicator sticks, solutions, suspensions, emulsions, gels, creams, ointments, pastes, jellies, paints, powders, and aerosols.

A “cell” as used herein, refers to a cell carrying out metabolic or other function sufficient to preserve or replicate its genomic DNA. A cell can be identified by well-known methods in the art including, for example, presence of an intact membrane, staining by a particular dye, ability to produce progeny or, in the case of a gamete, ability to combine with a second gamete to produce a viable offspring. Cells may include prokaryotic and eukaroytic cells. Prokaryotic cells include but are not limited to bacteria. Eukaryotic cells include but are not limited to yeast cells and cells derived from plants and animals, for example mammalian, insect (e.g., spodoptera) and human cells. Cells may be useful when they are naturally nonadherent or have been treated not to adhere to surfaces, for example by trypsinization.

“Control” or “control experiment” is used in accordance with its plain ordinary meaning and refers to an experiment in which the subjects or reagents of the experiment are treated as in a parallel experiment except for omission of a procedure, reagent, or variable of the experiment. In some instances, the control is used as a standard of comparison in evaluating experimental effects. In some embodiments, a control is the measurement of the activity of a protein in the absence of a compound as described herein (including embodiments and examples).

The term “modulator” refers to a composition that increases or decreases the level of a target molecule or the function of a target molecule or the physical state of the target of the molecule. In some embodiments, an Bruton's Tyrosine Kinase associated disease modulator is a compound that reduces the severity of one or more symptoms of a disease associated with Bruton's Tyrosine Kinase (e.g. cancer, inflammatory disease). A Bruton's Tyrosine Kinase modulator is a compound that increases or decreases the activity or function or level of activity or level of function of Bruton's Tyrosine Kinase.

The term “modulate” is used in accordance with its plain ordinary meaning and refers to the act of changing or varying one or more properties. “Modulation” refers to the process of changing or varying one or more properties. For example, as applied to the effects of a modulator on a target protein, to modulate means to change by increasing or decreasing a property or function of the target molecule or the amount of the target molecule.

The term “associated” or “associated with” in the context of a substance or substance activity or function associated with a disease (e.g. a protein associated disease, a cancer associated with Bruton's Tyrosine Kinase activity, Bruton's Tyrosine Kinase associated cancer, Bruton's Tyrosine Kinase associated disease) means that the disease (e.g. cancer, inflammatory disease) is caused by (in whole or in part), or a symptom of the disease is caused by (in whole or inpart) the substance or substance activity or function. For example, a cancer associated with Bruton's Tyrosine Kinase activity or function may be a cancer that results (entirely or partially) from aberrant Bruton's Tyrosine Kinase function (e.g. enzyme activity, protein-protein interaction, signaling pathway) or a cancer wherein a particular symptom of the disease is caused (entirely or partially) by aberrant Bruton's Tyrosine Kinase activity or function. As used herein, what is described as being associated with a disease, if a causative agent, could be a target for treatment of the disease. For example, a cancer associated with Bruton's Tyrosine Kinase activity or function or a Bruton's Tyrosine Kinase associated cancer, may be treated with a Bruton's Tyrosine Kinase modulator or Bruton's Tyrosine Kinase inhibitor, in the instance where increased Bruton's Tyrosine Kinase activity or function (e.g. signaling pathway activity) causes the cancer. For example, an inflammatory disease associated with Bruton's Tyrosine Kinase activity or function or an Bruton's Tyrosine Kinase associated inflammatory disease, may be treated with an Bruton's Tyrosine Kinase modulator or Bruton's Tyrosine Kinase inhibitor, in the instance where increased Bruton's Tyrosine Kinase activity or function (e.g. signaling pathway activity) causes the disease.

The term “aberrant” as used herein refers to different from normal. When used to describe enzymatic activity or protein function, aberrant refers to activity or function that is greater or less than a normal control or the average of normal non-diseased control samples. Aberrant activity may refer to an amount of activity that results in a disease, wherein returning the aberrant activity to a normal or non-disease-associated amount (e.g. by administering a compound or using a method as described herein), results in reduction of the disease or one or more disease symptoms.

The term “signaling pathway” as used herein refers to a series of interactions between cellular and optionally extra-cellular components (e.g. proteins, nucleic acids, small molecules, ions, lipids) that conveys a change in one component to one or more other components, which in turn may convey a change to additional components, which is optionally propogated to other signaling pathway components. For example, binding of a Bruton's Tyrosine Kinase with a compound as described herein may reduce the level of a product of the Bruton's Tyrosine Kinase catalyzed reaction or thr level of a downstream derivative of the product or binding may reduce the interactions between the Bruton's Tyrosine Kinase enzyme or an Bruton's Tyrosine Kinase reaction product and downstream effectors or signaling pathway components, resulting in changes in cell growth, proliferation, or survival.

The term “electrophilic chemical moiety” is used in accordance with its plain ordinary chemical meaning and refers to a monovalent chemical group that is electrophilic.

II. Compounds

In an aspect is provided a compound having the formula:

R 1 is independently halogen, —CX 1 3 , —CHX 1 2 , —CH 2 X 1 , —OCX 1 3 , —OCH 2 X 1 , —OCHX 1 2 , —CN, —SO n1 R 1D , —SO v1 NR 1A R 1B , —NHC(O)NR 1A R 1B , —N(O) m1 , —NR 1A R 1B , —C(O)R 1C , —C(O)—OR 1C , —C(O)NR 1A R 1B , —OR 1D , —NR 1A SO 2 R 1D , —NR 1A C(O)R 1C , —NR 1A C(O)O R 1C , —NR 1A OR 1C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. Two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. The symbol z1 is an integer from 0 to 5. R 2 is independently halogen, —CX 2 3 , —CHX 2 2 , —CH 2 X 2 , —OCX 2 3 , —OCH 2 X 2 , —OCHX 2 2 , —CN, —SO n2 R 2D , —SO v2 NR 2A R 2B , —NHC(O)NR 2A R 2B , —N(O) m2 , —NR 2A R 2B , —C(O)R 2C , —C(O)—OR 2C , —C(O)NR 2A R 2B , —OR 2D , —NR 2A SO 2 R 2D , —NR 2A C(O)R 2C , —NR 2A C(O)OR 2C , —NR 2A OR 2C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. Two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. The symbol z2 is an integer from 0 to 4. R 3 is hydrogen or —NH 2 . The symbol Y 1 is N or C(R 4 ). R 4 is hydrogen, halogen, —CX 43 , —CHX 42 , —CH 2 X 4 , —OCX 4 3 , —OCH 2 X 4 , —OCHX 42 , —CN, —SO n4 R 4D , —SO 4 NR 4A R 4B , —NHC(O)NR 4A R 4B , —N(O) m4 , —NR 4A R 4B , —C(O)R 4C , —C(O)—OR 4C , —C(O)NR 4A R 4B , —OR 4D , —NR 4A SO 2 R 4D , —NR 4A C(O)R 4C , —NR 4A C(O)OR 4C , —NR 4A OR 4C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. The symbol Y 2 is N or C(R 5 ). R 5 is hydrogen, halogen, —CX 5 3 , —CHX 5 2 , —CH 2 X 5 , —OCX 5 3 , —OCH 2 X 5 , —OCHX 5 2 , —CN, —SO n1 R 5D , —S v5 NR 5A R 5B , —NHC(O)NR 5A R 5B , —N(O) m5 , —NR 5A R 5B , —C(O)R 5C , —C(O)—OR 5C , —C(O)NR 5A R 5B , —OR 5D , —NR 5A SO 2 R 5D , —NR 5A C(O)R 5C , —NR 5A C(O)OR 5C , —NR 5A OR 5C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. L 1 is a bond, —S(O) 2 —, —S(O) 2 -Ph-, —NR 6 —, —O—, —S—, —C(O)—, —C(O)NR 6 —, —NR 6 C(O)—, —NRC(O)NH—, —NHC(O)NR 6 —, —C(O)O—, —OC(O)—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene. R 6 is hydrogen, halogen, —CX 6 3 , —CHX 6 2 , —CH 2 X 6 , —OCX 6 3 , —OCH 2 X 6 , —OCHX 6 2 , —CN, —SO n6 R 6D , —SO v6 NR 6A R 6B , —NHC(O)NR 6A R 6B , —N(O) m6 , —NR 6A R 6B , —C(O)R 6C , —C(O)—OR 6C , —C(O)NR 6A R 6B , —OR 6D , —NR 6A SO 2 R 6D , —NR 6A C(O)R 6C , —NR 6A C(O)O R 6C , —NR 6A OR 6C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. L 2 is a bond, —S(O) 2 —, —S(O) 2 -Ph-, —NR 7A —, —O—, —S—, —C(O)—, —C(O)NR 7A —, —NR 7 C(O)—, —NR 7 C(O)NH—, —NHC(O)NR—, —C(O)O—, —OC(O)—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene. R 7 is hydrogen, halogen, —CX 7 3 , —CHX 7 2 , —CH 2 X 7 , —OCX 7 3 , —OCH 2 X 7 , —OCHX 7 2 , —CN, —SO n7 R 7D , —SO v7 NR 7A R 7B , —NHC(O)NR 7A R 7B , —N(O) m7 , —NR 7A R 7B , —C(O)R 7C , —C(O)—OR 7C , —C(O)NR 7A R 7B , —OR 7D , —NR 7A SO 2 R 7D , —NR 7A C(O)R 7C , —NR 7A C(O)O R 7C , —NR 7A OR 7C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. E is an electrophilic moiety. Each R 1A , R 1B , R 1C , R 1D , R 2A , R 2B , R 2C , R 2D , R 4A , R 4B , R 4C , R 4D , R 5A , R 5B , R 5C , R 5D , R 6A , R 6B , R 6C , R 6D , R 7A , R 7B , R 7C , and R 7D is independently hydrogen, —CX 3 , —CN, —COOH, —CONH 2 , —CHX 2 , —CH 2 X, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. R 1A and R 1B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. R 2A and R 2B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. R 4A and R 4B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. R 5A and R 5B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. R 6A and R 6B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. R 7A and R 7B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. Each X, X 1 , X 2 , X 4 , X 5 , X 6 , and X 7 is independently —F, —Cl, —Br, or —I. The symbols n1, n2, n4, n5, n6, and n7 are independently an integer from 0 to 4. The symbols m1, m2, m4, m5, m6, m7, v1, v2, v4, v5, v6, and v7 are independently an integer from 1 to 2.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 1 , Y 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 1 , Y 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 1 , Y 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 1 , Y 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , R 4 , L 1 , L 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , R, L 1 , L 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , R 4 , R 5 , L 1 , L 2 , z1, z2, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 1 , Y 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 1 , Y 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , R 4 , L 1 , L 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , R 5 , L 1 , L 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , R 4 , R, L 1 , L 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 1 , Y 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 1 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 1 , Y 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , Y 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , L 1 , L 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , R 4 , L 1 , L 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , R 5 , L 1 , L 2 , z1, and E are as described herein.

In embodiments, the compound has the formula

R 1 , R 2 , R 3 , R 4 , R 5 , L 1 , L 2 , z1, and E are as described herein.

In embodiments, R 1 is independently

halogen, —CX 1 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —OCX 1 3 , —OCHX 1 2 , —CHX 1 2 , —CH 2 X 1 , substituted or unsubstituted C 1 -C 8 alkyl, or substituted or unsubstituted 2 to 8 membered heteroalkyl; two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted 3 to 8 membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 1 is independently halogen, —CX 1 3 , —CN, unsubstituted C 1 -C 4 alkyl, or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 1 is independently halogen, —CX 3 , —CN, unsubstituted methyl, unsubstituted ethyl, unsubstituted methoxy, or unsubstituted ethoxy. In embodiments, R 1 is independently unsubstituted methyl. In embodiments, R 1 is independently unsubstituted ethyl. In embodiments, R 1 is independently unsubstituted propyl. In embodiments, R 1 is independently unsubstituted n-propyl. In embodiments, R 1 is independently unsubstituted isopropyl. In embodiments, R 1 is independently unsubstituted butyl. In embodiments, R 1 is independently unsubstituted n-butyl. In embodiments, R 1 is independently unsubstituted isobutyl. In embodiments, R 1 is independently unsubstituted tert-butyl. In embodiments, R 1 is independently unsubstituted pentyl. In embodiments, R 1 is independently unsubstituted hexyl. In embodiments, R 1 is independently unsubstituted heptyl. In embodiments, R 1 is independently unsubstituted octyl. In embodiments, R 1 is independently —F. In embodiments, R 1 is independently —Cl. In embodiments, R 1 is independently —Br. In embodiments, R 1 is independently —I. In embodiments, R 1 is independently unsubstituted methoxy. In embodiments, R 1 is independently unsubstituted ethoxy. In embodiments, R 1 is independently —CF 3 . In embodiments, R 1 is independently halogen. In embodiments, R 1 is independently —CCl 3 .

In embodiments, R 1 is independently —CX 1 3 . In embodiments, R 1 is independently —CHX 2 . In embodiments, R 1 is independently —CH 2 X 1 . In embodiments, R 1 is independently —OCX 3 . In embodiments, R 1 is independently —OCH 2 X 1 . In embodiments, R 1 is independently —OCHX 12 . In embodiments, R 1 is independently —CN. In embodiments, R is independently —SO n1 R 1D . In embodiments, R 1 is independently —SO v1 NR 1A R 1B . In embodiments, R 1 is independently —NHC(O)NR 1A R 1B . In embodiments, R 1 is independently —N(O) m1 . In embodiments, R 1 is independently —NR 1A R 1B . In embodiments, R 1 is independently —C(O)R 1C . In embodiments, R 1 is independently —C(O)—OR 1C . In embodiments, R 1 is independently —C(O)NR 1A R 1B . In embodiments, R 1 is independently —OR 1D . In embodiments, R 1 is independently —NR 1A SO 2 R 1D . In embodiments, R 1 is independently —NR 1A C(O)R 1C . In embodiments, R 1 is independently —NR A C(O)OR 1C . In embodiments, R 1 is independently —NR 1A OR 1C . In embodiments, R 1 is independently —OH. In embodiments, R 1 is independently —NH 2 . In embodiments, R 1 is independently —COOH. In embodiments, R 1 is independently —CONH 2 . In embodiments, R 1 is independently —NO 2 . In embodiments, R 1 is independently —SH.

In embodiments, R 1 is independently substituted or unsubstituted alkyl. In embodiments, R 1 is independently substituted or unsubstituted heteroalkyl. In embodiments, R 1 is independently substituted or unsubstituted cycloalkyl. In embodiments, R 1 is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 1 is independently substituted or unsubstituted aryl. In embodiments, R 1 is independently substituted or unsubstituted heteroaryl. In embodiments, R 1 is independently substituted alkyl. In embodiments, R 1 is independently substituted heteroalkyl. In embodiments, R 1 is independently substituted cycloalkyl. In embodiments, R 1 is independently, substituted heterocycloalkyl. In embodiments, R 1 is independently substituted aryl. In embodiments, R 1 is independently substituted heteroaryl. In embodiments, R 1 is independently unsubstituted alkyl. In embodiments, R 1 is independently unsubstituted heteroalkyl. In embodiments, R 1 is independently unsubstituted cycloalkyl. In embodiments, R 1 is independently, unsubstituted heterocycloalkyl. In embodiments, R 1 is independently unsubstituted aryl. In embodiments, R 1 is independently unsubstituted heteroaryl. In embodiments, R 1 is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 1 is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 1 is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 1 is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1 is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 1 is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 1 is independently substituted C 1 -C 8 alkyl. In embodiments, R 1 is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 1 is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 1 is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1 is independently substituted C 6 -C 10 aryl. In embodiments, R 1 is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 1 is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 1 is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 1 is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 1 is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1 is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 1 is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 1 is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 1 is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 1 is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 1 is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1 is independently substituted or unsubstituted phenyl. In embodiments, R 1 is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 1 is independently substituted C 1 -C 4 alkyl. In embodiments, R 1 is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 1 is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 1 is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1 is independently substituted phenyl. In embodiments, R 1 is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 1 is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 1 is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 1 is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 1 is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1 is independently unsubstituted phenyl. In embodiments, R 1 is independently unsubstituted 5 to 6 membered heteroaryl.

In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to forma substituted or unsubstituted heterocycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted aryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted heteroaryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted cycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to forma substituted heterocycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted aryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted heteroaryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form an unsubstituted cycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form an unsubstituted heterocycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form an unsubstituted aryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form an unsubstituted heteroaryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted C 6 -C 10 aryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted C 3 -C 8 cycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to forma substituted 3 to 8 membered heterocycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted C 6 -C 10 aryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted 5 to 10 membered heteroaryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form an unsubstituted C 3 -C 8 cycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form an unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form an unsubstituted C 6 -C 10 aryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form an unsubstituted 5 to 10 membered heteroaryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted phenyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, two adjacent R 1 substituents may optionally be joined to forma substituted C 3 -C 6 cycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted 3 to 6 membered heterocycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted phenyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a substituted 5 to 6 membered heteroaryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form an unsubstituted C 3 -C 6 cycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form an unsubstituted phenyl. In embodiments, two adjacent R 1 substituents may optionally be joined to form an unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 1A is independently hydrogen. In embodiments, R 1A is independently —CX 1A 3 . In embodiments, R 1A is independently —CHX 1A 2 . In embodiments, R 1A is independently —CH 2 X 1A . In embodiments, R 1A is independently —CN. In embodiments, R 1A is independently —COOH. In embodiments, R 1A is independently —CONH 2 . In embodiments, R 1A is independently substituted or unsubstituted alkyl. In embodiments, R 1A is independently substituted or unsubstituted heteroalkyl. In embodiments, R 1A is independently substituted or unsubstituted cycloalkyl. In embodiments, R 1A is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 1A is independently substituted or unsubstituted aryl. In embodiments, R 1A is independently substituted or unsubstituted heteroaryl. In embodiments, R 1A is independently substituted alkyl. In embodiments, R 1A is independently substituted heteroalkyl. In embodiments, R 1A is independently substituted cycloalkyl. In embodiments, R 1A is independently, substituted heterocycloalkyl. In embodiments, R 1A is independently substituted aryl. In embodiments, R 1A is independently substituted heteroaryl. In embodiments, R 1A is independently unsubstituted alkyl. In embodiments, R 1A is independently unsubstituted heteroalkyl. In embodiments, R 1A is independently unsubstituted cycloalkyl. In embodiments, R 1A is independently, unsubstituted heterocycloalkyl. In embodiments, R 1A is independently unsubstituted aryl. In embodiments, R 1A is independently unsubstituted heteroaryl. In embodiments, R 1A is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 1A is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 1A is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 1A is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1A is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 1A is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 1A is independently substituted C 1 -C 8 alkyl. In embodiments, R 1A is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 1A is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 1A is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1A is independently substituted C 6 -C 10 aryl. In embodiments, R 1A is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 1A is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 1A is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 1A is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 1A is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1A is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 1A is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 1A is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 1A is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 1A is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 1A is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1A is independently substituted or unsubstituted phenyl. In embodiments, R 1A is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 1A is independently substituted C 1 -C 4 alkyl. In embodiments, R 1A is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 1A is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 1A is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1A is independently substituted phenyl. In embodiments, R 1A is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 1A is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 1A is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 1A is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 1A is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1A is independently unsubstituted phenyl. In embodiments, R 1A is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 1A is independently unsubstituted methyl. In embodiments, R 1A is independently unsubstituted ethyl. In embodiments, R 1A is independently unsubstituted propyl. In embodiments, R 1A is independently unsubstituted isopropyl. In embodiments, R 1A is independently unsubstituted tert-butyl.

In embodiments, R 1B is independently hydrogen. In embodiments, R 1B is independently —CX 1B 3 . In embodiments, R 1B is independently —CHX 1B 2 . In embodiments, R 1B is independently —CH 2 X 1B . In embodiments, R 1B is independently —CN. In embodiments, R 1B is independently —COOH. In embodiments, R 1B is independently —CONH 2 . In embodiments, R 1B is independently substituted or unsubstituted alkyl. In embodiments, R 1B is independently substituted or unsubstituted heteroalkyl. In embodiments, R 1B is independently substituted or unsubstituted cycloalkyl. In embodiments, R 1B is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 1B is independently substituted or unsubstituted aryl. In embodiments, R 1B is independently substituted or unsubstituted heteroaryl. In embodiments, R 1B is independently substituted alkyl. In embodiments, R 1B is independently substituted heteroalkyl. In embodiments, R 1B is independently substituted cycloalkyl. In embodiments, R 1B is independently, substituted heterocycloalkyl. In embodiments, R 1B is independently substituted aryl. In embodiments, R 1B is independently substituted heteroaryl. In embodiments, R 1B is independently unsubstituted alkyl. In embodiments, R 1B is independently unsubstituted heteroalkyl. In embodiments, R 1B is independently unsubstituted cycloalkyl. In embodiments, R 1B is independently, unsubstituted heterocycloalkyl. In embodiments, R 1B is independently unsubstituted aryl. In embodiments, R 1B is independently unsubstituted heteroaryl. In embodiments, R 1B is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 1B is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 1B is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 1B is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1B is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 1B is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 1B is independently substituted C 1 -C 8 alkyl. In embodiments, R 1B is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 1B is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 1B is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1B is independently substituted C 6 -C 10 aryl. In embodiments, R 1B is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 1B is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 1B is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 1B is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 1B is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1B is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 1B is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 1B is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 1B is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 1B is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 1B is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1B is independently substituted or unsubstituted phenyl. In embodiments, R 1B is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 1B is independently substituted C 1 -C 4 alkyl. In embodiments, R 1B is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 1B is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 1B is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1B is independently substituted phenyl. In embodiments, R 1B is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 1B is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 1B is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 1B is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 1B is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1B is independently unsubstituted phenyl. In embodiments, R 1B is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 1B is independently unsubstituted methyl. In embodiments, R 1B is independently unsubstituted ethyl. In embodiments, R 1B is independently unsubstituted propyl. In embodiments, R 1B is independently unsubstituted isopropyl. In embodiments, R 1B is independently unsubstituted tert-butyl.

In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heterocycloalkyl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heteroaryl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form a substituted heterocycloalkyl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form a substituted heteroaryl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heterocycloalkyl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heteroaryl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 10 membered heteroaryl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 6 membered heteroaryl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 1C is independently hydrogen. In embodiments, R 1C is independently —CX 1C 3 . In embodiments, R 1C is independently —CHX 1C 2 . In embodiments, R 1C is independently —CH 2 X 1C . In embodiments, R 1C is independently —CN. In embodiments, R 1C is independently —COOH. In embodiments, R 1C is independently —CONH 2 . In embodiments, R 1C is independently substituted or unsubstituted alkyl. In embodiments, R 1C is independently substituted or unsubstituted heteroalkyl. In embodiments, R 1C is independently substituted or unsubstituted cycloalkyl. In embodiments, R 1C is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 1C is independently substituted or unsubstituted aryl. In embodiments, R 1C is independently substituted or unsubstituted heteroaryl. In embodiments, R 1C is independently substituted alkyl. In embodiments, R 1C is independently substituted heteroalkyl. In embodiments, R 1C is independently substituted cycloalkyl. In embodiments, R 1C is independently, substituted heterocycloalkyl. In embodiments, R 1C is independently substituted aryl. In embodiments, R 1C is independently substituted heteroaryl. In embodiments, R 1C is independently unsubstituted alkyl. In embodiments, R 1C is independently unsubstituted heteroalkyl. In embodiments, R 1C is independently unsubstituted cycloalkyl. In embodiments, R 1C is independently, unsubstituted heterocycloalkyl. In embodiments, R 1C is independently unsubstituted aryl. In embodiments, R 1C is independently unsubstituted heteroaryl. In embodiments, R 1C is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 1C is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 1C is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 1C is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1C is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 1C is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 1C is independently substituted C 1 -C 8 alkyl. In embodiments, R 1C is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 1C is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 1C is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1C is independently substituted C 6 -C 10 aryl. In embodiments, R 1C is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 1C is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 1C is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 1C is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 1C is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1C is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 1C is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 1C is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 1C is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 1C is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 1C is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1C is independently substituted or unsubstituted phenyl. In embodiments, R 1C is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 1C is independently substituted C 1 -C 4 alkyl. In embodiments, R 1C is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 1C is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 1C is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1C is independently substituted phenyl. In embodiments, R 1C is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 1C is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 1C is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 1C is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 1C is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1C is independently unsubstituted phenyl. In embodiments, R 1C is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 1C is independently unsubstituted methyl. In embodiments, R 1C is independently unsubstituted ethyl. In embodiments, R 1C is independently unsubstituted propyl. In embodiments, R 1C is independently unsubstituted isopropyl. In embodiments, R 1C is independently unsubstituted tert-butyl.

In embodiments, R 1D is independently hydrogen. In embodiments, R 1D is independently —CX 1D 3 . In embodiments, R 1D is independently —CHX 1D 2 . In embodiments, R 1D is independently —CH 2 X 1D . In embodiments, R 1D is independently —CN. In embodiments, R 1D is independently —COOH. In embodiments, R 1D is independently —CONH 2 . In embodiments, R 1D is independently substituted or unsubstituted alkyl. In embodiments, R 1D is independently substituted or unsubstituted heteroalkyl. In embodiments, R 1D is independently substituted or unsubstituted cycloalkyl. In embodiments, R 1D is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 1D is independently substituted or unsubstituted aryl. In embodiments, R 1D is independently substituted or unsubstituted heteroaryl. In embodiments, R 1D is independently substituted alkyl. In embodiments, R 1D is independently substituted heteroalkyl. In embodiments, R 1D is independently substituted cycloalkyl. In embodiments, R 1D is independently, substituted heterocycloalkyl. In embodiments, R 1D is independently substituted aryl. In embodiments, R 1D is independently substituted heteroaryl. In embodiments, R 1D is independently unsubstituted alkyl. In embodiments, R 1D is independently unsubstituted heteroalkyl. In embodiments, R 1D is independently unsubstituted cycloalkyl. In embodiments, R 1D is independently, unsubstituted heterocycloalkyl. In embodiments, R 1D is independently unsubstituted aryl. In embodiments, R 1D is independently unsubstituted heteroaryl. In embodiments, R 1D is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 1D is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 1D is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 1D is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1D is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 1D is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 1D is independently substituted C 1 -C 8 alkyl. In embodiments, R 1D is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 1D is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 1D is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1D is independently substituted C 6 -C 10 aryl. In embodiments, R 1D is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 1D is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 1D is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 1D is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 1D is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 1D is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 1D is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 1D is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 1D is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 1D is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 1D is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1D is independently substituted or unsubstituted phenyl. In embodiments, R 1D is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 1D is independently substituted C 1 -C 4 alkyl. In embodiments, R 1D is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 1D is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 1D is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1D is independently substituted phenyl. In embodiments, R 1D is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 1D is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 1D is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 1D is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 1D is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 1D is independently unsubstituted phenyl. In embodiments, R 1D is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 1D is independently unsubstituted methyl. In embodiments, R 1D is independently unsubstituted ethyl. In embodiments, R 1D is independently unsubstituted propyl. In embodiments, R 1D is independently unsubstituted isopropyl. In embodiments, R 1D is independently unsubstituted tert-butyl.

In embodiments, R 1 is independently

halogen, —CX 1 3 , —CHX 1 2 , —CH 2 X 1 , —OCX 1 3 , —OCH 2 X 1 , —OCHX 1 2 , —CN, —SO 1 R 1D , —SO v1 NR 1A R 1B , —NHC(O)NR 1A R 1B , —N(O) m1 , —NR 1A R 1B , —C(O)R 1C , —C(O)OR 1C , —C(O)NR 1A R 1B , —OR 1D , —NR 1A SO 2 R 1D , —NR 1A C(O)R 1C , —NR 1A C(O)OR 1C , —NR 1A OR 1C , R 20 -substituted or unsubstituted alkyl, R 20 -substituted or unsubstituted heteroalkyl, R 20 -substituted or unsubstituted cycloalkyl, R 20 -substituted or unsubstituted heterocycloalkyl, R 20 -substituted or unsubstituted aryl, or R 20 -substituted or unsubstituted heteroaryl. In embodiments, R 1 is independently halogen, —CX 1 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 1 3 , —OCHX 1 2 , R 20 -substituted or unsubstituted alkyl, R 20 -substituted or unsubstituted heteroalkyl, R 20 -substituted or unsubstituted cycloalkyl, R 20 -substituted or unsubstituted heterocycloalkyl, R 20 -substituted or unsubstituted aryl, or R 20 -substituted or unsubstituted heteroaryl. In embodiments, R 1 is independently halogen, —CX 1 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 3 , —OCHX 2 , R 20 -substituted or unsubstituted C 1 -C 8 alkyl, R 20 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 20 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 20 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 20 -substituted or unsubstituted phenyl, or R 20 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 1 is —F, —Cl, —Br, or —I. In embodiments, R 1 is independently hydrogen. In embodiments, R 1 is independently methyl. In embodiments, R 1 is independently ethyl. In embodiments, R 1 is CX 3 . In embodiments, R 1 is CHX 2 . In embodiments, R 1 is CH 2 X. In embodiments, R 1 is CF 3 . In embodiments, R 1 is CHF 2 . In embodiments, R 1 is CH 2 F.

In embodiments, two adjacent R 1 substituents may optionally be joined to form a R 20 -substituted or unsubstituted cycloalkyl, R 20 -substituted or unsubstituted heterocycloalkyl, R 20 -substituted or unsubstituted aryl, or R 20 -substituted or unsubstituted heteroaryl. In embodiments, two adjacent R 1 substituents may optionally be joined to form a R 20 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 20 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 20 -substituted or unsubstituted phenyl, or R 20 -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 20 is independently oxo,

halogen, —CX 20 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 20 3 , —OCHX 20 2 , R 21 -substituted or unsubstituted alkyl, R 21 -substituted or unsubstituted heteroalkyl, R 21 -substituted or unsubstituted cycloalkyl, R 21 -substituted or unsubstituted heterocycloalkyl, R 21 -substituted or unsubstituted aryl, or R 21 -substituted or unsubstituted heteroaryl. In embodiments, R 20 is independently oxo,

halogen, —CX 20 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 20 3 , —OCHX 20 2 , R 21 -substituted or unsubstituted C 1 -C 8 alkyl, R 21 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 21 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 21 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 21 -substituted or unsubstituted phenyl, or R 21 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 20 is —F, —C, —Br, or —I.

R 21 is independently oxo,

halogen, —CX 21 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 21 3 , —OCHX 22 , R 22 -substituted or unsubstituted alkyl, R 22 -substituted or unsubstituted heteroalkyl, R 22 -substituted or unsubstituted cycloalkyl, R 22 -substituted or unsubstituted heterocycloalkyl, R 22 -substituted or unsubstituted aryl, or R 22 -substituted or unsubstituted heteroaryl. In embodiments, R 21 is independently oxo,

halogen, —CX 21 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 21 3 , —OCHX 21 2 , R 22 -substituted or unsubstituted C 1 -C 8 alkyl, R 22 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 22 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 22 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 22 -substituted or unsubstituted phenyl, or R 22 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 21 is —F, —Cl, —Br, or —I.

In embodiments, R 1A is independently hydrogen, —CX 1A 3 , —CN, —COOH, —CONH 2 , —CHX A2 , —CH 2 X 1A , R 20A -substituted or unsubstituted alkyl, R 20A -substituted or unsubstituted heteroalkyl, R 20A -substituted or unsubstituted cycloalkyl, R 20A -substituted or unsubstituted heterocycloalkyl, R 20A -substituted or unsubstituted aryl, or R 20A -substituted or unsubstituted heteroaryl. In embodiments, R 1A is independently hydrogen, —CX 1A 3 , —CN, —COOH, —CONH 2 , —CHX A2 , —CH 2 X 1A , R 20A -substituted or unsubstituted C 1 -C 8 alkyl, R 20A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 20A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 20A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 20A -substituted or unsubstituted phenyl, or R 20A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 1A is —F, —Cl, —Br, or —I. In embodiments, R 1A is independently hydrogen. In embodiments, R 1A is independently methyl. In embodiments, R 1A is independently ethyl.

In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may optionally be joined to form a R 20A -substituted or unsubstituted heterocycloalkyl or R 20A -substituted or unsubstituted heteroaryl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may optionally be joined to form a R 20A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 20A -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 20A is independently oxo,

halogen, —CX 20A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 20A 3 , —OCHX 20A 2 , R 21A -substituted or unsubstituted alkyl, R 21A substituted or unsubstituted heteroalkyl, R 21A -substituted or unsubstituted cycloalkyl, R 21A -substituted or unsubstituted heterocycloalkyl, R 21A -substituted or unsubstituted aryl, or R 21A -substituted or unsubstituted heteroaryl. In embodiments, R 20A is independently oxo,

halogen, —CX 20A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 20A 3 , —OCHX 20A 2 , R 21A -substituted or unsubstituted C 1 -C 8 alkyl, R 21A substituted or unsubstituted 2 to 8 membered heteroalkyl, R 21A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 21A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 21A -substituted or unsubstituted phenyl, or R 21A substituted or unsubstituted 5 to 6 membered heteroaryl. X 20A is —F, —Cl, —Br, or —I.

R 21A is independently oxo,

halogen, —CX 21A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 21A 3 , —OCHX 21A 2 , R 22A -substituted or unsubstituted alkyl, R 22A -substituted or unsubstituted heteroalkyl, R 22A -substituted or unsubstituted cycloalkyl, R 22A -substituted or unsubstituted heterocycloalkyl, R 22A -substituted or unsubstituted aryl, or R 22A -substituted or unsubstituted heteroaryl. In embodiments, R 21A is independently oxo,

halogen, —CX 21A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 21A 3 , —OCHX 21A 2 , R 22A -substituted or unsubstituted C 1 -C 8 alkyl, R 22A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 22A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 22A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 22A -substituted or unsubstituted phenyl, or R 22A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 21A is —F, —Cl, —Br, or —I.

In embodiments, R 1B is independently hydrogen, —CX 1B 3 , —CN, —COOH, —CONH 2 , —CHX 1B 2 , —CH 2 X 1B , R 20B -substituted or unsubstituted alkyl, R 20B -substituted or unsubstituted heteroalkyl, R 20B -substituted or unsubstituted cycloalkyl, R 20B -substituted or unsubstituted heterocycloalkyl, R 20B substituted or unsubstituted aryl, or R 20B -substituted or unsubstituted heteroaryl. In embodiments, R 1B is independently hydrogen, —CX 1B 3 , —CN, —COOH, —CONH 2 , —CHX 1B 2 , —CH 2 X 1B , R 2B -substituted or unsubstituted C 1 -C 8 alkyl, R 20B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 20B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 20B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 20B -substituted or unsubstituted phenyl, or R 20B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 1B is —F, —Cl, —Br, or —I. In embodiments, R 1B is independently hydrogen. In embodiments, R 1B is independently methyl. In embodiments, R 1B is independently ethyl.

In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may optionally be joined to form a R 20B -substituted or unsubstituted heterocycloalkyl or R 20B -substituted or unsubstituted heteroaryl. In embodiments, R 1A and R 1B substituents bonded to the same nitrogen atom may optionally be joined to form a R 20B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 20B -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 20B is independently oxo,

halogen, —CX 20B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 20B 3 , —OCHX 20B 2 , R 21B -substituted or unsubstituted alkyl, R 21B -substituted or unsubstituted heteroalkyl, R 21B -substituted or unsubstituted cycloalkyl, R 21B -substituted or unsubstituted heterocycloalkyl, R 21B -substituted or unsubstituted aryl, or R 21B -substituted or unsubstituted heteroaryl. In embodiments, R 20B is independently oxo,

halogen, —CX 20B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 20B 3 , —OCHX 20B 2 , R 21B -substituted or unsubstituted C 1 -C 8 alkyl, R 21B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 21B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 21B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 21B -substituted or unsubstituted phenyl, or R 21B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 20B is —F, —Cl, —Br, or —I.

R 21B is independently oxo,

halogen, —CX 21B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 21B 3 , —OCHX 21B 2 , R 22B -substituted or unsubstituted alkyl, R 22B -substituted or unsubstituted heteroalkyl, R 22B -substituted or unsubstituted cycloalkyl, R 22B -substituted or unsubstituted heterocycloalkyl, R 22B -substituted or unsubstituted aryl, or R 22B -substituted or unsubstituted heteroaryl. In embodiments, R 21B is independently oxo,

halogen, —CX 21B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 21B 3 , —OCHX 21B 2, R 22B -substituted or unsubstituted C 1 -C 8 alkyl, R 22B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 22B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 22B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 22B -substituted or unsubstituted phenyl, or R 22B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 21B is —F, —Cl, —Br, or —I.

In embodiments, R 1C is independently

hydrogen, —CX 1c 3 , —CN, —COOH, —CONH 2 , —CHX 1C 2 , —CH 2 X 1C , R 20C -substituted or unsubstituted alkyl, R 20C -substituted or unsubstituted heteroalkyl, R 20C -substituted or unsubstituted cycloalkyl, R 20C -substituted or unsubstituted heterocycloalkyl, R 20C -substituted or unsubstituted aryl, or R 20C -substituted or unsubstituted heteroaryl. In embodiments, R 1C is independently hydrogen, —CX 1C 3 , —CN, —COOH, —CONH 2 , —CHX 1C 2 , —CH 2 X 1C , R 20C -substituted or unsubstituted C 1 -C 8 alkyl, R 20C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 20C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 20C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 20C -substituted or unsubstituted phenyl, or R 20C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 1C is —F, —Cl, —Br, or —I. In embodiments, R 1C is independently hydrogen. In embodiments, R 1C is independently methyl. In embodiments, R 1C is independently ethyl.

R 20C is independently oxo,

halogen, —CX 20C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 20C 3 , —OCHX 20C 2 , R 21C -substituted or unsubstituted alkyl, R 21C -substituted or unsubstituted heteroalkyl, R 21C -substituted or unsubstituted cycloalkyl, R 21C -substituted or unsubstituted heterocycloalkyl, R 21C -substituted or unsubstituted aryl, or R 21C -substituted or unsubstituted heteroaryl. In embodiments, R 20C is independently oxo,

halogen, —CX 20C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 20C 3 , —OCHX 20C 2 , R 21C -substituted or unsubstituted C 1 -C 8 alkyl, R 21C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 21C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 21C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 21C -substituted or unsubstituted phenyl, or R 21C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 20C is —F, —Cl, —Br, or —I.

R 21C is independently oxo,

halogen, —CX 21C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 21C 3 , —OCHX 21C 2 , R 22C -substituted or unsubstituted alkyl, R 22C -substituted or unsubstituted heteroalkyl, R 22C -substituted or unsubstituted cycloalkyl, R 22C -substituted or unsubstituted heterocycloalkyl, R 22C -substituted or unsubstituted aryl, or R 22C -substituted or unsubstituted heteroaryl. In embodiments, R 21C is independently oxo,

halogen, —CX 21C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 21C 3 , —OCHX 21C 2 , R 22C -substituted or unsubstituted C 1 -C 8 alkyl, R 22C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 22C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 22C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 22C -substituted or unsubstituted phenyl, or R 22C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 21C is —F, —Cl, —Br, or —I.

In embodiments, R 1D is independently

hydrogen, —CX 1D 3 , —CN, —COOH, —CONH 2 , —CHX 1D 2 , —CH 2 X 1D , R 20D -substituted or unsubstituted alkyl, R 20D -substituted or unsubstituted heteroalkyl, R 20D -substituted or unsubstituted cycloalkyl, R 20D -substituted or unsubstituted heterocycloalkyl, R 20D substituted or unsubstituted aryl, or R 20D -substituted or unsubstituted heteroaryl. In embodiments, R 1D independently hydrogen, —CX 1D 3 , —CN, —COOH, —CONH 2 , —CHX 1D 2 , —CH 2 X 1D , R 20D -substituted or unsubstituted C 1 -C 8 alkyl, R 20D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 20D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 20D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 20D -substituted or unsubstituted phenyl, or R 20D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 1 is —F, —Cl, —Br, or —I. In embodiments, R 1D is independently hydrogen. In embodiments, R 1D is independently methyl. In embodiments, R 1D is independently ethyl.

R 20D is independently oxo,

halogen, —CX 20D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 20D 3 , —OCHX 20D 2 , R 21D -substituted or unsubstituted alkyl, R 21D -substituted or unsubstituted heteroalkyl, R 21D -substituted or unsubstituted cycloalkyl, R 21D -substituted or unsubstituted heterocycloalkyl, R 21D -substituted or unsubstituted aryl, or R 21D -substituted or unsubstituted heteroaryl. In embodiments, R 20D is independently oxo,

halogen, —CX 20D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 20D 3 , —OCHX 20D 2 , R 20D -substituted or unsubstituted C 1 -C 8 alkyl, R 21D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 21D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 21D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 21D -substituted or unsubstituted phenyl, or R 21D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 20D is —F, —Cl, —Br, or —I.

R 21D is independently oxo,

halogen, —CX 21D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 21D 3 , —OCHX 21D 2 , R 22D -substituted or unsubstituted alkyl, R 22D -substituted or unsubstituted heteroalkyl, R 22D -substituted or unsubstituted cycloalkyl, R 22D -substituted or unsubstituted heterocycloalkyl, R 22D -substituted or unsubstituted aryl, or R 22D -substituted or unsubstituted heteroaryl. In embodiments, R 21D is independently oxo,

halogen, —CX 21D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 21D 3 , —OCHX 21D 2 , R 22D -substituted or unsubstituted C 1 -C 8 alkyl, R 22D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 22D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 22D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 22D -substituted or unsubstituted phenyl, or R 22D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 21D is —F, —Cl, —Br, or —I.

R 22 , R 22A , R 22B , R 22C , and R 22D are independently hydrogen, oxo,

halogen, —CCl 3 , —CBr 3 , —CF 3 , —Cl 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCl 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 22 , R 22A , R 22B , R 22C , and R 22D are independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 22 , R 22A , R 22B , R 22C , and R 22D are independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted C 1 -C 8 alkyl, unsubstituted 2 to 8 membered heteroalkyl, unsubstituted C 3 -C 8 cycloalkyl, unsubstituted 3 to 6 membered heterocycloalkyl, unsubstituted phenyl, or unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 1 is independently halogen. In embodiments, R 1 is independently hydrogen. In embodiments, z1 is 2 and R 1 is independently hydrogen or halogen. In embodiments, z1 is 2 and one R 1 is independently hydrogen and one R 1 is halogen.

In embodiments, R 1 is independently methyl. In embodiments, R 1 is independently C 1 -C 4 alkyl. In embodiments, z1 is 2 and one R 1 is independently halogen and one R 1 is unsubstituted C 1 -C 4 alkyl. In embodiments, z1 is 2 and one R 1 is independently halogen and one R 1 is unsubstituted C 1 -C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently halogen and one R 1 is unsubstituted C 1 -C 2 alkyl. In embodiments, R 1 is independently halogen or unsubstituted C 1 -C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently halogen and one R 1 is methyl.

In embodiments, R 1 is independently substituted or unsubstituted methyl. In embodiments, R 1 is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 1 is independently halogen or substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 1 is independently halogen or substituted or unsubstituted C 1 -C 3 alkyl. In embodiments, R 1 is independently halogen or substituted or unsubstituted C 1 -C 2 alkyl. In embodiments, R 1 is independently halogen or substituted or unsubstituted methyl. In embodiments, R 1 is independently substituted methyl. In embodiments, R 1 is independently substituted C 1 -C 4 alkyl. In embodiments, z1 is 2 and one R 1 is independently halogen and one R 1 is substituted C 1 -C 4 alkyl. In embodiments, z1 is 2 and one R 1 is independently halogen and one R 1 is substituted C 1 -C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently halogen and one R 1 is substituted C 1 -C 2 alkyl. In embodiments, z1 is 2 and one R 1 is independently halogen and one R 1 is substituted methyl. In embodiments, R 1 is independently unsubstituted methyl. In embodiments, z1 is 2 and one R 1 is independently halogen and one R 1 is unsubstituted C 1 -C 4 alkyl. In embodiments, z1 is 2 and one R 1 is independently halogen and one R 1 is unsubstituted C 1 -C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently halogen and one R 1 is unsubstituted C 1 -C 2 alkyl. In embodiments, z1 is 2 and one R 1 is independently halogen and one R 1 is unsubstituted methyl.

In embodiments, z1 is 2 and one R 1 is independently substituted or unsubstituted C 1 -C 4 alkyl and one R 1 is substituted or unsubstituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently substituted or unsubstituted C 1 -C 3 alkyl and one R 1 is substituted or unsubstituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently substituted or unsubstituted C 1 -C 2 alkyl and one R 1 is substituted or unsubstituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently substituted or unsubstituted methyl and one R 1 is substituted or unsubstituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently substituted or unsubstituted methyl and one R 1 is substituted or unsubstituted isopropyl.

In embodiments, z1 is 2 and one R 1 is independently unsubstituted C 1 -C 4 alkyl and one R 1 is unsubstituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently unsubstituted C 1 -C 3 alkyl and one R 1 is unsubstituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently unsubstituted C 1 -C 2 alkyl and one R 1 is unsubstituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently unsubstituted methyl and one R 1 is unsubstituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently unsubstituted methyl and one R 1 is unsubstituted isopropyl.

In embodiments, z1 is 2 and one R 1 is independently substituted C 1 -C 4 alkyl and one R 1 substituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently substituted C 1 -C 3 alkyl and one R 1 is substituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently substituted C 1 -C 2 alkyl and one R 1 is substituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently substituted methyl and one R 1 is substituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently substituted methyl and one R 1 is substituted isopropyl.

In embodiments, z1 is 2 and one R 1 is independently substituted C 1 -C 4 alkyl and one R 1 is unsubstituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently substituted C 1 -C 3 alkyl and one R 1 is unsubstituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently substituted C 1 -C 2 alkyl and one R 1 is unsubstituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently substituted methyl and one R 1 is unsubstituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently substituted methyl and one R 1 is unsubstituted isopropyl.

In embodiments, z1 is 2 and one R 1 is independently unsubstituted C 1 -C 4 alkyl and one R 1 is substituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently unsubstituted C 1 -C 3 alkyl and one R 1 is substituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently unsubstituted C 1 -C 2 alkyl and one R 1 is substituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently unsubstituted methyl and one R 1 is substituted C 3 alkyl. In embodiments, z1 is 2 and one R 1 is independently unsubstituted methyl and one R 1 is substituted isopropyl.

In embodiments, z1 is 0. In embodiments, z1 is 1. In embodiments, z1 is 2. In embodiments, z1 is 3. In embodiments, z1 is 4. In embodiments, z1 is 5.

In embodiments, R 2 is independently halogen, —CX 2 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —OCX 2 3 , —OCHX 2 2 , —CHX 2 2 , —CH 2 X 2 , substituted or unsubstituted C 1 -C 8 alkyl, or substituted or unsubstituted 2 to 8 membered heteroalkyl; two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted 3 to 8 membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 2 is independently halogen, —CX 2 3 , —CN, unsubstituted C 1 -C 4 alkyl, or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 2 is independently halogen, —CX 2 3 , —CN, unsubstituted methyl, unsubstituted ethyl, unsubstituted methoxy, or unsubstituted ethoxy. In embodiments, R 2 is independently unsubstituted methyl. In embodiments, R 2 is independently unsubstituted ethyl. In embodiments, R 2 is independently unsubstituted propyl. In embodiments, R 2 is independently unsubstituted n-propyl. In embodiments, R 2 is independently unsubstituted isopropyl. In embodiments, R 2 is independently unsubstituted butyl. In embodiments, R 2 is independently unsubstituted n-butyl. In embodiments, R 2 is independently unsubstituted isobutyl. In embodiments, R 2 is independently unsubstituted tert-butyl. In embodiments, R 2 is independently unsubstituted pentyl. In embodiments, R 2 is independently unsubstituted hexyl. In embodiments, R 2 is independently unsubstituted heptyl. In embodiments, R 2 is independently unsubstituted octyl. In embodiments, R 2 is independently —F. In embodiments, R 2 is independently —Cl. In embodiments, R 2 is independently —Br. In embodiments, R 2 is independently —I. In embodiments, R 2 is independently unsubstituted methoxy. In embodiments, R 2 is independently unsubstituted ethoxy. In embodiments, R 2 is independently halogen. In embodiments, R 2 is independently —CF 3 . In embodiments, R 2 is independently —CCl 3 .

In embodiments, R 2 is independently halogen, —CX 2 . In embodiments, R 2 is independently —CHX 2 2 . In embodiments, R 2 is independently —CH 2 X 2 . In embodiments, R 2 is independently —OCX 2 3 . In embodiments, R 2 is independently —OCH 2 X 2 . In embodiments, R 2 is independently —OCHX 2 2 . In embodiments, R 2 is independently —CN. In embodiments, R 2 is independently —SO n2 R 2D . In embodiments, R 2 is independently —SO v2 NR 2A R 2B . In embodiments, R 2 is independently —NHC(O)NR 2A R 2B . In embodiments, R 2 is independently —N(O) m2 . In embodiments, R 2 is independently —NR 2A R 2B . In embodiments, R 2 is independently —C(O)R 2C . In embodiments, R 2 is independently —C(O)—OR 2C . In embodiments, R 2 is independently —C(O)NR 2A R 2B . In embodiments, R 2 is independently —OR 2D . In embodiments, R 2 is independently —NR 2A SO 2 R 2D . In embodiments, R 2 is independently —NR 2A C(O)R 2C . In embodiments, R 2 is independently —NR 2A C(O)OR 2C . In embodiments, R 2 is independently —NR 2A OR 2C . In embodiments, R 2 is independently —OH. In embodiments, R 2 is independently —NH 2 . In embodiments, R 2 is independently —COOH. In embodiments, R 2 is independently —CONH 2 . In embodiments, R 2 is independently —NO 2 . In embodiments, R 2 is independently —SH.

In embodiments, R 2 is independently substituted or unsubstituted alkyl. In embodiments, R 2 is independently substituted or unsubstituted heteroalkyl. In embodiments, R 2 is independently substituted or unsubstituted cycloalkyl. In embodiments, R 2 is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 2 is independently substituted or unsubstituted aryl. In embodiments, R 2 is independently substituted or unsubstituted heteroaryl. In embodiments, R 2 is independently substituted alkyl. In embodiments, R 2 is independently substituted heteroalkyl. In embodiments, R 2 is independently substituted cycloalkyl. In embodiments, R 2 is independently, substituted heterocycloalkyl. In embodiments, R 2 is independently substituted aryl. In embodiments, R 2 is independently substituted heteroaryl. In embodiments, R 2 is independently unsubstituted alkyl. In embodiments, R 2 is independently unsubstituted heteroalkyl. In embodiments, R 2 is independently unsubstituted cycloalkyl. In embodiments, R 2 is independently, unsubstituted heterocycloalkyl. In embodiments, R 2 is independently unsubstituted aryl. In embodiments, R 2 is independently unsubstituted heteroaryl. In embodiments, R 2 is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 2 is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 2 is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 2 is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2 is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 2 is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 2 is independently substituted C 1 -C 8 alkyl. In embodiments, R 2 is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 2 is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 2 is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2 is independently substituted C 6 -C 10 aryl. In embodiments, R 2 is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 2 is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 2 is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 2 is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 2 is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2 is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 2 is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 2 is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 2 is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 2 is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 2 is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2 is independently substituted or unsubstituted phenyl. In embodiments, R 2 is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 2 is independently substituted C 1 -C 4 alkyl. In embodiments, R 2 is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 2 is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 2 is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2 is independently substituted phenyl. In embodiments, R 2 is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 2 is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 2 is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 2 is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 2 is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2 is independently unsubstituted phenyl. In embodiments, R 2 is independently unsubstituted 5 to 6 membered heteroaryl.

In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to forma substituted or unsubstituted heterocycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted aryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted heteroaryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted cycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted heterocycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted aryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted heteroaryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form an unsubstituted cycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form an unsubstituted heterocycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form an unsubstituted aryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form an unsubstituted heteroaryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted C 6 -C 10 aryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, two adjacent R 2 substituents may optionally be joined to forma substituted C 3 -C 8 cycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted 3 to 8 membered heterocycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted C 6 -C 10 aryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted 5 to 10 membered heteroaryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form an unsubstituted C 3 -C 8 cycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form an unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form an unsubstituted C 6 -C 10 aryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form an unsubstituted 5 to 10 membered heteroaryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted phenyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, two adjacent R 2 substituents may optionally be joined to forma substituted C 3 -C 6 cycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a substituted 3 to 6 membered heterocycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to forma substituted phenyl. In embodiments, two adjacent R 2 substituents may optionally be joined to forma substituted 5 to 6 membered heteroaryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form an unsubstituted C 3 -C 6 cycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form an unsubstituted phenyl. In embodiments, two adjacent R 2 substituents may optionally be joined to form an unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 2A is independently hydrogen. In embodiments, R 2A is independently —CX 2A 3 . In embodiments, R 2A is independently —CHX 2A 2 . In embodiments, R 2A is independently —CH 2 X 2A . In embodiments, R 2A is independently —CN. In embodiments, R 2A is independently —COOH. In embodiments, R 2A is independently —CONH 2 . In embodiments, R 2A is independently substituted or unsubstituted alkyl. In embodiments, R 2A is independently substituted or unsubstituted heteroalkyl. In embodiments, R 2A is independently substituted or unsubstituted cycloalkyl. In embodiments, R 2A is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 2A is independently substituted or unsubstituted aryl. In embodiments, R 2A is independently substituted or unsubstituted heteroaryl. In embodiments, R 2A is independently substituted alkyl. In embodiments, R 2A is independently substituted heteroalkyl. In embodiments, R 2A is independently substituted cycloalkyl. In embodiments, R 2A is independently, substituted heterocycloalkyl. In embodiments, R 2A is independently substituted aryl. In embodiments, R 2A is independently substituted heteroaryl. In embodiments, R 2A is independently unsubstituted alkyl. In embodiments, R 2A is independently unsubstituted heteroalkyl. In embodiments, R 2A is independently unsubstituted cycloalkyl. In embodiments, R 2A is independently, unsubstituted heterocycloalkyl. In embodiments, R 2A is independently unsubstituted aryl. In embodiments, R 2A is independently unsubstituted heteroaryl. In embodiments, R 2A is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 2A is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 2A is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 2A is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2A is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 2A is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 2A is independently substituted C 1 -C 8 alkyl. In embodiments, R 2A is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 2A is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 2A is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2A is independently substituted C 6 -C 10 aryl. In embodiments, R 2A is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 2A is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 2A is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 2A is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 2A is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2A is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 2A is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 2A is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 2A is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 2A is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 2A is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2A is independently substituted or unsubstituted phenyl. In embodiments, R 2A is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 2 is independently substituted C 1 -C 4 alkyl. In embodiments, R 2A is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 2A is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 2A is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2A is independently substituted phenyl. In embodiments, R 2A is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 2A is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 2A is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 2A is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 2A is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2A is independently unsubstituted phenyl. In embodiments, R 2A is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 2A is independently unsubstituted methyl. In embodiments, R 2A is independently unsubstituted ethyl. In embodiments, R 2A is independently unsubstituted propyl. In embodiments, R 2A is independently unsubstituted isopropyl. In embodiments, R 2A is independently unsubstituted tert-butyl.

In embodiments, R 2B is independently hydrogen. In embodiments, R 2B is independently —CX 2B 3 . In embodiments, R 2B is independently —CHX 2B 2 . In embodiments, R 2B is independently —CH 2 X 2B . In embodiments, R 2B is independently —CN. In embodiments, R 2B is independently —COOH. In embodiments, R 2B is independently —CONH 2 . In embodiments, R 2B is independently substituted or unsubstituted alkyl. In embodiments, R 2B is independently substituted or unsubstituted heteroalkyl. In embodiments, R 2B is independently substituted or unsubstituted cycloalkyl. In embodiments, R 2B is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 2B is independently substituted or unsubstituted aryl. In embodiments, R 2B is independently substituted or unsubstituted heteroaryl. In embodiments, R 2B is independently substituted alkyl. In embodiments, R 2B is independently substituted heteroalkyl. In embodiments, R 2B is independently substituted cycloalkyl. In embodiments, R 2B is independently, substituted heterocycloalkyl. In embodiments, R 2B is independently substituted aryl. In embodiments, R 2B is independently substituted heteroaryl. In embodiments, R 2B is independently unsubstituted alkyl. In embodiments, R 2B is independently unsubstituted heteroalkyl. In embodiments, R 2B is independently unsubstituted cycloalkyl. In embodiments, R 2B is independently, unsubstituted heterocycloalkyl. In embodiments, R 2B is independently unsubstituted aryl. In embodiments, R 2B is independently unsubstituted heteroaryl. In embodiments, R 2B is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 2B is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 2B is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 2B is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2B is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 2B is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 2B is independently substituted C 1 -C 8 alkyl. In embodiments, R 2B is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 2B is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 2B is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2B is independently substituted C 6 -C 10 aryl. In embodiments, R 2B is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 2B is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 2B is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 2B is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 2B is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2B is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 2B is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 2B is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 2B is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 2B is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 2B is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2B is independently substituted or unsubstituted phenyl. In embodiments, R 2B is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 2B is independently substituted C 1 -C 4 alkyl. In embodiments, R 2B is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 2B is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 2B is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2B is independently substituted phenyl. In embodiments, R 2B is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 2B is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 2B is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 2B is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 2B is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2B is independently unsubstituted phenyl. In embodiments, R 2B is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 2B is independently unsubstituted methyl. In embodiments, R 2B is independently unsubstituted ethyl. In embodiments, R 2B is independently unsubstituted propyl. In embodiments, R 2B is independently unsubstituted isopropyl. In embodiments, R 2B is independently unsubstituted tert-butyl.

In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heterocycloalkyl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heteroaryl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form a substituted heterocycloalkyl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form a substituted heteroaryl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heterocycloalkyl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heteroaryl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 10 membered heteroaryl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to forma substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 6 membered heteroaryl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 2C is independently hydrogen. In embodiments, R 2C is independently —CX 2C 3 . In embodiments, R 2C is independently —CHX 2C 2 . In embodiments, R 2C is independently —CH 2 X 2C . In embodiments, R 2C is independently —CN. In embodiments, R 2C is independently —COOH. In embodiments, R 2C is independently —CONH 2 . In embodiments, R 2C is independently substituted or unsubstituted alkyl. In embodiments, R 2C is independently substituted or unsubstituted heteroalkyl. In embodiments, R 2C is independently substituted or unsubstituted cycloalkyl. In embodiments, R 2C is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 2C is independently substituted or unsubstituted aryl. In embodiments, R 2C is independently substituted or unsubstituted heteroaryl. In embodiments, R 2C is independently substituted alkyl. In embodiments, R 2C is independently substituted heteroalkyl. In embodiments, R 2C is independently substituted cycloalkyl. In embodiments, R 2C is independently, substituted heterocycloalkyl. In embodiments, R 2C is independently substituted aryl. In embodiments, R 2C is independently substituted heteroaryl. In embodiments, R 2C is independently unsubstituted alkyl. In embodiments, R 2C is independently unsubstituted heteroalkyl. In embodiments, R 2C is independently unsubstituted cycloalkyl. In embodiments, R 2C is independently, unsubstituted heterocycloalkyl. In embodiments, R 2C is independently unsubstituted aryl. In embodiments, R 2C is independently unsubstituted heteroaryl. In embodiments, R 2C is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 2C is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 2C is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 2C is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2C is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 2C is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 2C is independently substituted C 1 -C 8 alkyl. In embodiments, R 2C is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 2C is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 2C is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2C is independently substituted C 6 -C 10 aryl. In embodiments, R 2C is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 2C is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 2C is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 2C is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 2C is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2C is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 2C is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 2C is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 2C is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 2C is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 2C is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2C is independently substituted or unsubstituted phenyl. In embodiments, R 2C is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 2C is independently substituted C 1 -C 4 alkyl. In embodiments, R 2C is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 2C is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 2C is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2C is independently substituted phenyl. In embodiments, R 2C is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 2C is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 2C is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 2C is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 2C is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2C is independently unsubstituted phenyl. In embodiments, R 2C is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 2C is independently unsubstituted methyl. In embodiments, R 2C is independently unsubstituted ethyl. In embodiments, R 2C is independently unsubstituted propyl. In embodiments, R 2C is independently unsubstituted isopropyl. In embodiments, R 2C is independently unsubstituted tert-butyl.

In embodiments, R 2D is independently hydrogen. In embodiments, R 2D is independently —CX 2D 3 . In embodiments, R 2D is independently —CHX 2D 2 . In embodiments, R 2D is independently —CH 2 X 2D . In embodiments, R 2D is independently —CN. In embodiments, R 2D is independently —COOH. In embodiments, R 2D is independently —CONH 2 . In embodiments, R 2D is independently substituted or unsubstituted alkyl. In embodiments, R 2D is independently substituted or unsubstituted heteroalkyl. In embodiments, R 2D is independently substituted or unsubstituted cycloalkyl. In embodiments, R 2D is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 2D is independently substituted or unsubstituted aryl. In embodiments, R 2D is independently substituted or unsubstituted heteroaryl. In embodiments, R 2D is independently substituted alkyl. In embodiments, R 2D is independently substituted heteroalkyl. In embodiments, R 2D is independently substituted cycloalkyl. In embodiments, R 2D is independently, substituted heterocycloalkyl. In embodiments, R 2D is independently substituted aryl. In embodiments, R 2D is independently substituted heteroaryl. In embodiments, R 2D is independently unsubstituted alkyl. In embodiments, R 2D is independently unsubstituted heteroalkyl. In embodiments, R 2D is independently unsubstituted cycloalkyl. In embodiments, R 2D is independently, unsubstituted heterocycloalkyl. In embodiments, R 2D is independently unsubstituted aryl. In embodiments, R 2D is independently unsubstituted heteroaryl. In embodiments, R 2D is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 2D is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 2D is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 2D is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2D is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 2D is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 2D is independently substituted C 1 -C 8 alkyl. In embodiments, R 2D is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 2D is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 2D is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2D is independently substituted C 6 -C 10 aryl. In embodiments, R 2D is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 2D is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 2D is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 2D is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 2D is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 2D is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 2D is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 2D is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 2D is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 2D is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 2D is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2D is independently substituted or unsubstituted phenyl. In embodiments, R 2D is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 2D is independently substituted C 1 -C 4 alkyl. In embodiments, R 2D is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 2D is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 2D is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2D is independently substituted phenyl. In embodiments, R 2D is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 2D is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 2D is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 2D is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 2D is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 2D is independently unsubstituted phenyl. In embodiments, R 2D is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 2D is independently unsubstituted methyl. In embodiments, R 2D is independently unsubstituted ethyl. In embodiments, R 2D is independently unsubstituted propyl. In embodiments, R 2D is independently unsubstituted isopropyl. In embodiments, R 2D is independently unsubstituted tert-butyl.

In embodiments, R 2 is independently

halogen, —CX 2 3 , —CHX 2 2 , —CH 2 X 2 , —OCX 2 3 , —OCH 2 X 2 , —OCHX 2 2 , —CN, —SO n2 R 2D , —SO v2 NR 2A R 2B , —NHC(O)NR 2A R 2B , —N(O) m2 , —NR 2A R 2B , —C(O)R 2C , —C(O)OR 2C , —C(O)NR 2A R 2B , —OR 2D , —NR 2A SO 2 R 2D , —NR 2A C(O)R 2C , —NR 2A C(O)OR 2C , —NR 2A OR 2C , R 23 -substituted or unsubstituted alkyl, R 23 -substituted or unsubstituted heteroalkyl, R 23 -substituted or unsubstituted cycloalkyl, R 23 -substituted or unsubstituted heterocycloalkyl, R 23 -substituted or unsubstituted aryl, or R 23 -substituted or unsubstituted heteroaryl. In embodiments, R 2 is independently halogen, —CX 2 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 23 , —OCHX 22 , R 23 -substituted or unsubstituted alkyl, R 23 -substituted or unsubstituted heteroalkyl, R 23 -substituted or unsubstituted cycloalkyl, R 23 -substituted or unsubstituted heterocycloalkyl, R 23 -substituted or unsubstituted aryl, or R 23 -substituted or unsubstituted heteroaryl. In embodiments, R 2 is independently halogen, —CX 23 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 2 3 , —OCHX 2 2 , R 23 -substituted or unsubstituted C 1 -C 8 alkyl, R 23 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 23 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 23 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 23 -substituted or unsubstituted phenyl, or R 23 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 2 is —F, —Cl, —Br, or —I. In embodiments, R 2 is independently hydrogen. In embodiments, R 2 is independently methyl. In embodiments, R 2 is independently ethyl.

In embodiments, two adjacent R 2 substituents may optionally be joined to form a R 23 -substituted or unsubstituted cycloalkyl, R 23 -substituted or unsubstituted heterocycloalkyl, R 23 -substituted or unsubstituted aryl, or R 23 -substituted or unsubstituted heteroaryl. In embodiments, two adjacent R 2 substituents may optionally be joined to form a R 23 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 23 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 23 -substituted or unsubstituted phenyl, or R 23 -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 23 is independently oxo,

halogen, —CX 23 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 23 3 , —OCHX 23 2 , R 24 -substituted or unsubstituted alkyl, R 24 -substituted or unsubstituted heteroalkyl, R 24 -substituted or unsubstituted cycloalkyl, R 24 -substituted or unsubstituted heterocycloalkyl, R 24 -substituted or unsubstituted aryl, or R 24 -substituted or unsubstituted heteroaryl. In embodiments, R 23 is independently oxo,

halogen, —CX 23 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 23 3 , —OCHX 23 2 , R 24 -substituted or unsubstituted C 1 -C 8 alkyl, R 24 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 24 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 24 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 24 -substituted or unsubstituted phenyl, or R 24 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 23 is —F, —Cl, —Br, or —I.

R 24 is independently oxo,

halogen, —CX 24 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 24 3 , —OCHX 24 2 , R 25 -substituted or unsubstituted alkyl, R 25 -substituted or unsubstituted heteroalkyl, R 25 -substituted or unsubstituted cycloalkyl, R 25 -substituted or unsubstituted heterocycloalkyl, R 25 -substituted or unsubstituted aryl, or R 25 -substituted or unsubstituted heteroaryl. In embodiments, R 24 is independently oxo,

halogen, —CX 24 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 24 3 , —OCHX 24 2 , R 25 -substituted or unsubstituted C 1 -C 8 alkyl, R 25 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 25 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 25 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 25 -substituted or unsubstituted phenyl, or R 25 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 24 is —F, —Cl, —Br, or —I.

In embodiments, R 2A is independently

hydrogen, —CX 2A 3 , —CN, —COOH, —CONH 2 , —CHX 2A 2 , —CH 2 X 2A , R 23A -substituted or unsubstituted alkyl, R 23A -substituted or unsubstituted heteroalkyl, R 23A -substituted or unsubstituted cycloalkyl, R 23A -substituted or unsubstituted heterocycloalkyl, R 23A -substituted or unsubstituted aryl, or R 23A -substituted or unsubstituted heteroaryl. In embodiments, R 2A is independently hydrogen, —CX 2A3 , —CN, —COOH, —CONH 2 , —CHX 2A 2 , —CH 2 X 2A , R 23A -substituted or unsubstituted C 1 -C 8 alkyl, R 23A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 23A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 23A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 23A -substituted or unsubstituted phenyl, or R 23A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 2 is —F, —Cl, —Br, or —I. In embodiments, R 2A is independently hydrogen. In embodiments, R 2A is independently methyl. In embodiments, R 2A is independently ethyl.

In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may optionally be joined to form a R 23A -substituted or unsubstituted heterocycloalkyl or R 23A -substituted or unsubstituted heteroaryl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may optionally be joined to form a R 23A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 23A -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 23A is independently oxo,

halogen, —CX 23A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 23A 3 , —OCHX 23A 2 , R 24A -substituted or unsubstituted alkyl, R 24A -substituted or unsubstituted heteroalkyl, R 24A -substituted or unsubstituted cycloalkyl, R 24A -substituted or unsubstituted heterocycloalkyl, R 24A -substituted or unsubstituted aryl, or R 24A -substituted or unsubstituted heteroaryl. In embodiments, R 23A is independently oxo,

halogen, —CX 23A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 23A 3 , —OCHX 23A 2 , R 24A -substituted or unsubstituted C 1 -C 8 alkyl, R 24A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 24A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 24A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 24A . substituted or unsubstituted phenyl, or R 24A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 23A is —F, —Cl, —Br, or —I.

R 24A is independently oxo,

halogen, —CX 24A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 24A 3 , —OCHX 24A 2 , R 25A -substituted or unsubstituted alkyl, R 25A -substituted or unsubstituted heteroalkyl, R 25A -substituted or unsubstituted cycloalkyl, R 25A -substituted or unsubstituted heterocycloalkyl, R 25A -substituted or unsubstituted aryl, or R 25A substituted or unsubstituted heteroaryl. In embodiments, R 24A is independently oxo,

halogen, —CX 24A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 24A 3 , —OCHX 24A 2 , R 25A -substituted or unsubstituted C 1 -C 8 alkyl, R 25A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 25A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 25A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 25A -substituted or unsubstituted phenyl, or R 25A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 24A is —F, —Cl, —Br, or —I.

In embodiments, R 2B is independently

hydrogen, —CX 2B 3 , —CN, —COOH, —CONH 2 , —CHX 2B 2 , —CH 2 X 2B , R 23B -substituted or unsubstituted alkyl, R 23B -substituted or unsubstituted heteroalkyl, R 23B -substituted or unsubstituted cycloalkyl, R 23B -substituted or unsubstituted heterocycloalkyl, R 23B -substituted or unsubstituted aryl, or R 23B -substituted or unsubstituted heteroaryl. In embodiments, R 2B is independently hydrogen, —CX 2B 3 , —CN, —COOH, —CONH 2 , —CHX 2B 2 , —CH 2 X 2B , R 23B -substituted or unsubstituted C 1 -C 8 alkyl, R 23B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 23B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 23B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 23B -substituted or unsubstituted phenyl, or R 23B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 2B is —F, —Cl, —Br, or —I. In embodiments, R 2B is independently hydrogen. In embodiments, R 2B is independently methyl. In embodiments, R 2B is independently ethyl.

In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may optionally be joined to form a R 23B -substituted or unsubstituted heterocycloalkyl or R 23B -substituted or unsubstituted heteroaryl. In embodiments, R 2A and R 2B substituents bonded to the same nitrogen atom may optionally be joined to form a R 23B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 23B -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 23B is independently oxo,

halogen, —CX 23B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 23B 3 , —OCHX 23B 2 , R 24B -substituted or unsubstituted alkyl, R 24B -substituted or unsubstituted heteroalkyl, R 24B -substituted or unsubstituted cycloalkyl, R 24B -substituted or unsubstituted heterocycloalkyl, R 24B -substituted or unsubstituted aryl, or R 24B -substituted or unsubstituted heteroaryl. In embodiments, R 23B is independently oxo,

halogen, —CX 23B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 23B 3 , —OCHX 23B 2 , R 24B -substituted or unsubstituted C 1 -C 8 alkyl, R 24B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 24B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 24B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 24B -substituted or unsubstituted phenyl, or R 24B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 23B is —F, —Cl, —Br, or —I.

R 24B is independently oxo,

halogen, —CX 24B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 24B 3 , —OCHX 24B 2 , R 25B -substituted or unsubstituted alkyl, R 25B -substituted or unsubstituted heteroalkyl, R 25B -substituted or unsubstituted cycloalkyl, R 25 -substituted or unsubstituted heterocycloalkyl, R 25B -substituted or unsubstituted aryl, or R 25B -substituted or unsubstituted heteroaryl. In embodiments, R 24B is independently oxo,

halogen, —CX 24B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 24B 3 , —OCHX 24B 2 , R 25B -substituted or unsubstituted C 1 -C 8 alkyl, R 25B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 25B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 25B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 25B -substituted or unsubstituted phenyl, or R 25B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 24B is —F, —Cl, —Br, or —I.

In embodiments, R 2C is independently

hydrogen, —CX 2C 3 , —CN, —COOH, —CONH 2 , —CHX 2C 2 , —CH 2 X 2C , R 23C -substituted or unsubstituted alkyl, R 23C -substituted or unsubstituted heteroalkyl, R 23C -substituted or unsubstituted cycloalkyl, R 23C -substituted or unsubstituted heterocycloalkyl, R 23 -substituted or unsubstituted aryl, or R 23C -substituted or unsubstituted heteroaryl. In embodiments, R 2C is independently hydrogen, —CX 2C 3 , —CN, —COOH, —CONH 2 , —CHX 22 , —CH 2 X 2C , R 23 -substituted or unsubstituted C 1 -C 8 alkyl, R 23C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 23C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 23C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 23C -substituted or unsubstituted phenyl, or R 23C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 2 is —F, —Cl, —Br, or —I. In embodiments, R 2C is independently hydrogen. In embodiments, R 2C is independently methyl. In embodiments, R 2C is independently ethyl.

R 23C is independently oxo,

halogen, —CX 23C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 23C 3 , —OCHX 23C 2 , R 24C -substituted or unsubstituted alkyl, R 24C -substituted or unsubstituted heteroalkyl, R 24C -substituted or unsubstituted cycloalkyl, R 24C -substituted or unsubstituted heterocycloalkyl, R 24C -substituted or unsubstituted aryl, or R 24C -substituted or unsubstituted heteroaryl. In embodiments, R 23C is independently oxo,

halogen, —CX 23C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 23C 3 , —OCHX 23C 2 , R 24C -substituted or unsubstituted C 1 -C 8 alkyl, R 24C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 24C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 24C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 24 -substituted or unsubstituted phenyl, or R 24C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 23C is —F, —Cl, —Br, or —I.

R 24C is independently oxo,

halogen, —CX 24 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 24C 3 , —OCHX 24C 2 , R 25C -substituted or unsubstituted alkyl, R 25C -substituted or unsubstituted heteroalkyl, R 25C -substituted or unsubstituted cycloalkyl, R 25C -substituted or unsubstituted heterocycloalkyl, R 25C -substituted or unsubstituted aryl, or R 25C -substituted or unsubstituted heteroaryl. In embodiments, R 24C is independently oxo,

halogen, —CX 24 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 24C 3 , —OCHX 24C 2 , R 25C -substituted or unsubstituted C 1 -C 8 alkyl, R 25C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 25C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 25C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 25C -substituted or unsubstituted phenyl, or R 25C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 24C is —F, —Cl, —Br, or —I.

In embodiments, R 2D is independently

hydrogen, —CX 2D 3 , —CN, —COOH, —CONH 2 , —CHX 2D 2 , —CH 2 X 2D , R 23D -substituted or unsubstituted alkyl, R 23D -substituted or unsubstituted heteroalkyl, R 23D -substituted or unsubstituted cycloalkyl, R 23D -substituted or unsubstituted heterocycloalkyl, R 23D -substituted or unsubstituted aryl, or R 23D -substituted or unsubstituted heteroaryl. In embodiments, R 2D is independently hydrogen, —CX 2D 3 , —CN, —COOH, —CONH 2 , —CHX 2D 2 , —CH 2 X 2D , R 23D -substituted or unsubstituted C 1 -C 8 alkyl, R 23D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 23D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 23D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 23D -substituted or unsubstituted phenyl, or R 23D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 2D is —F, —Cl, —Br, or —I. In embodiments, R 2D is independently hydrogen. In embodiments, R 2D is independently methyl. In embodiments, R 2D is independently ethyl.

R 23D is independently oxo,

halogen, —CX 23D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 23D 3 , —OCHX 23D 2 , R 24D -substituted or unsubstituted alkyl, R 24D -substituted or unsubstituted heteroalkyl, R 24D -substituted or unsubstituted cycloalkyl, R 24D -substituted or unsubstituted heterocycloalkyl, R 24D -substituted or unsubstituted aryl, or R 24D -substituted or unsubstituted heteroaryl. In embodiments, R 23D is independently oxo,

halogen, —CX 23D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 23D 3 , —OCHX 23D 2 , R 24D -substituted or unsubstituted C 1 -C 8 alkyl, R 24D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 24D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 24D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 24D -substituted or unsubstituted phenyl, or R 24D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 23D is —F, —Cl, —Br, or —I.

R 24D is independently oxo,

halogen, —CX 24D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 24D 3 , —OCHX 24D 2 , R 25D -substituted or unsubstituted alkyl, R 25D -substituted or unsubstituted heteroalkyl, R 25D -substituted or unsubstituted cycloalkyl, R 25D -substituted or unsubstituted heterocycloalkyl, R 25D -substituted or unsubstituted aryl, or R 25D -substituted or unsubstituted heteroaryl. In embodiments, R 24D is independently oxo,

halogen, —CX 24D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 24D 3 , —OCHX 24D 2 , R 25D -substituted or unsubstituted C 1 -C 8 alkyl, R 25D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 25D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 25D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 25D -substituted or unsubstituted phenyl, or R 25D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 24D is —F, —Cl, —Br, or —I.

R 25 , R 25A , R 25B , R 25C , and R 25D are independently hydrogen, oxo,

halogen, —CCl 3 , —CBr 3 , —CF 3 , —Cl 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H,

—NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCl 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 25 , R 25A R 25B , R 25C , and R 25D are independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 25 , R 25A , R 25B , R 25C , and R 25D are independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted C 1 -C 8 alkyl, unsubstituted 2 to 8 membered heteroalkyl, unsubstituted C 3 -C 8 cycloalkyl, unsubstituted 3 to 6 membered heterocycloalkyl, unsubstituted phenyl, or unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 2 is independently halogen. In embodiments, R 2 is independently hydrogen. In embodiments, R 2 is independently hydrogen or halogen. In embodiments, R 2 is independently methyl. In embodiments, R 2 is independently C 1 -C 4 alkyl. In embodiments, R 2 is independently halogen or C 1 -C 4 alkyl. In embodiments, R 2 is independently halogen or C 1 -C 3 alkyl. In embodiments, R 2 is independently halogen or C 1 -C 2 alkyl. In embodiments, R 2 is independently halogen or methyl. In embodiments, R 2 is independently substituted or unsubstituted methyl. In embodiments, R 2 is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 2 is independently halogen or substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 2 is independently halogen or substituted or unsubstituted C 1 -C 3 alkyl. In embodiments, R 2 is independently halogen or substituted or unsubstituted C 1 -C 2 alkyl. In embodiments, R 2 is independently halogen or substituted or unsubstituted methyl. In embodiments, R 2 is independently substituted methyl. In embodiments, R 2 is independently substituted C 1 -C 4 alkyl. In embodiments, R 2 is independently halogen or substituted C 1 -C 4 alkyl. In embodiments, R 2 is independently halogen or substituted C 1 -C 3 alkyl. In embodiments, R 2 is independently halogen or substituted C 1 -C 2 alkyl. In embodiments, R 2 is independently halogen or substituted methyl. In embodiments, R 2 is independently unsubstituted methyl. In embodiments, R 2 is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 2 is independently halogen or unsubstituted C 1 -C 4 alkyl. In embodiments, R 2 is independently halogen or unsubstituted C 1 -C 3 alkyl. In embodiments, R 2 is independently halogen or unsubstituted C 1 -C 2 alkyl. In embodiments, R 2 is independently halogen or unsubstituted methyl.

In embodiments, R 2 is independently C 1 -C 4 alkyl. In embodiments, R 2 is independently C 1 -C 3 alkyl. In embodiments, R 2 is independently C 1 -C 2 alkyl. In embodiments, R 2 is independently methyl. In embodiments, R 2 is independently ispropyl. In embodiments, R 2 is independently substituted or unsubstituted methyl or substituted or unsubstituted isopropyl.

In embodiments, R 2 is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 2 is independently substituted or unsubstituted C 1 -C 3 alkyl. In embodiments, R 2 is independently substituted or unsubstituted C 1 -C 2 alkyl. In embodiments, R 2 is independently substituted or unsubstituted methyl.

In embodiments, z2 is 0. In embodiments, z2 is 1. In embodiments, z2 is 2. In embodiments, z2 is 3. In embodiments, z2 is 4.

In embodiments, R 3 is hydrogen. In embodiments, R 3 is —NH 2 .

In embodiments, the symbol Y 1 is N. In embodiments, the symbol Y 1 is C(R 4 ).

In embodiments, R 4 is hydrogen, substituted or unsubstituted C 1 -C 8 alkyl, or substituted or unsubstituted 2 to 8 membered heteroalkyl.

In embodiments, R 4 is independently hydrogen. In embodiments, R 4 is independently halogen. In embodiments, R 4 is independently —CX 43 . In embodiments, R 4 is independently —CHX 42 . In embodiments, R 4 is independently —CH 2 X 4 . In embodiments, R 4 is independently —OCX 43 . In embodiments, R 4 is independently —OCH 2 X 4 . In embodiments, R 4 is independently —OCHX 42 . In embodiments, R 4 is independently —CN. In embodiments, R 4 is independently —SO n4 R 4D . In embodiments, R 4 is independently —SO n4 NR 4A R 4B . In embodiments, R 4 is independently —NHC(O)NR 4A R 4B . In embodiments, R 4 is independently —N(O) m4 . In embodiments, R 4 is independently —NR 4A R 4B . In embodiments, R 4 is independently —C(O)R 4C . In embodiments, R 4 is independently —C(O)—OR 4C . In embodiments, R 4 is independently —C(O)NR 4A R 4B . In embodiments, R 4 is independently —OR 4D . In embodiments, R 4 is independently —NR 4A SO 2 R 4D . In embodiments, R 4 is independently —NR 4A C(O)R 4C . In embodiments, R 4 is independently —NR 4A C(O)OR 4C In embodiments, R 4 is independently —NR 4A OR 4C . In embodiments, R 4 is independently —OH. In embodiments, R 4 is independently —NH 2 . In embodiments, R 4 is independently —COOH. In embodiments, R 4 is independently —CONH 2 . In embodiments, R 4 is independently —NO 2 . In embodiments, R 4 is independently —SH.

In embodiments, R 4 is independently substituted or unsubstituted alkyl. In embodiments, R 4 is independently substituted or unsubstituted heteroalkyl. In embodiments, R 4 is independently substituted or unsubstituted cycloalkyl. In embodiments, R 4 is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 4 is independently substituted or unsubstituted aryl. In embodiments, R 4 is independently substituted or unsubstituted heteroaryl. In embodiments, R 4 is independently substituted alkyl. In embodiments, R 4 is independently substituted heteroalkyl. In embodiments, R 4 is independently substituted cycloalkyl. In embodiments, R 4 is independently, substituted heterocycloalkyl. In embodiments, R 4 is independently substituted aryl. In embodiments, R 4 is independently substituted heteroaryl. In embodiments, R 4 is independently unsubstituted alkyl. In embodiments, R 4 is independently unsubstituted heteroalkyl. In embodiments, R 4 is independently unsubstituted cycloalkyl. In embodiments, R 4 is independently, unsubstituted heterocycloalkyl. In embodiments, R 4 is independently unsubstituted aryl. In embodiments, R 4 is independently unsubstituted heteroaryl. In embodiments, R 4 is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 4 is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 4 is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 4 is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4 is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 4 is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 4 is independently substituted C 1 -C 8 alkyl. In embodiments, R 4 is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 4 is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 4 is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4 is independently substituted C 6 -C 10 aryl. In embodiments, R 4 is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 4 is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 4 is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 4 is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 4 is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4 is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 4 is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 4 is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 4 is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 4 is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 4 is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4 is independently substituted or unsubstituted phenyl. In embodiments, R 4 is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 4 is independently substituted C 1 -C 4 alkyl. In embodiments, R 4 is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 4 is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 4 is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4 is independently substituted phenyl. In embodiments, R 4 is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 4 is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 4 is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 4 is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 4 is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4 is independently unsubstituted phenyl. In embodiments, R 4 is independently unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 4A is independently hydrogen. In embodiments, R 4A is independently —CX 4A 3 . In embodiments, R 4A is independently —CHX 4A 2 . In embodiments, R 4A is independently —CH 2 X 4A . In embodiments, R 4A is independently —CN. In embodiments, R 4A is independently —COOH. In embodiments, R 4A is independently —CONH 2 . In embodiments, R 4A is independently substituted or unsubstituted alkyl. In embodiments, R 4A is independently substituted or unsubstituted heteroalkyl. In embodiments, R 4A is independently substituted or unsubstituted cycloalkyl. In embodiments, R 4A is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 4A is independently substituted or unsubstituted aryl. In embodiments, R 4A is independently substituted or unsubstituted heteroaryl. In embodiments, R 4A is independently substituted alkyl. In embodiments, R 4A is independently substituted heteroalkyl. In embodiments, R 4A is independently substituted cycloalkyl. In embodiments, R 4A is independently, substituted heterocycloalkyl. In embodiments, R 4A is independently substituted aryl. In embodiments, R 4A is independently substituted heteroaryl. In embodiments, R 4A is independently unsubstituted alkyl. In embodiments, R 4A is independently unsubstituted heteroalkyl. In embodiments, R 4A is independently unsubstituted cycloalkyl. In embodiments, R 4A is independently, unsubstituted heterocycloalkyl. In embodiments, R 4A is independently unsubstituted aryl. In embodiments, R 4A is independently unsubstituted heteroaryl. In embodiments, R 4A is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 4A is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 4A is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 4A is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4A is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 4A is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 4A is independently substituted C 1 -C 8 alkyl. In embodiments, R 4A is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 4A is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 4A is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4A is independently substituted C 6 -C 10 aryl. In embodiments, R 4A is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 4A is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 4A is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 4A is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 4A is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4A is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 4A is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 4A is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 4A is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 4A is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 4A is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4A is independently substituted or unsubstituted phenyl. In embodiments, R 4A is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 4A is independently substituted C 1 -C 4 alkyl. In embodiments, R 4A is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 4A is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 4A is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4A is independently substituted phenyl. In embodiments, R 4A is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 4A is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 4A is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 4A is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 4A is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4A is independently unsubstituted phenyl. In embodiments, R 4A is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 4A is independently unsubstituted methyl. In embodiments, R 4A is independently unsubstituted ethyl. In embodiments, R 4A is independently unsubstituted propyl. In embodiments, R 4A is independently unsubstituted isopropyl. In embodiments, R 4A is independently unsubstituted tert-butyl.

In embodiments, R 41 is independently hydrogen. In embodiments, R 4B is independently —CX 4B 3 . In embodiments, R 4B is independently —CHX 4B 2 . In embodiments, R 4B is independently —CH 2 X 4B . In embodiments, R 4B is independently —CN. In embodiments, R 4B is independently —COOH. In embodiments, R 4B is independently —CONH 2 . In embodiments, R 4B is independently substituted or unsubstituted alkyl. In embodiments, R 4B is independently substituted or unsubstituted heteroalkyl. In embodiments, R 4B is independently substituted or unsubstituted cycloalkyl. In embodiments, R 4B is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 4B is independently substituted or unsubstituted aryl. In embodiments, R 4B is independently substituted or unsubstituted heteroaryl. In embodiments, R 4B is independently substituted alkyl. In embodiments, R 4B is independently substituted heteroalkyl. In embodiments, R 4B is independently substituted cycloalkyl. In embodiments, R 4B is independently, substituted heterocycloalkyl. In embodiments, R 4B is independently substituted aryl. In embodiments, R 4B is independently substituted heteroaryl. In embodiments, R 4B is independently unsubstituted alkyl. In embodiments, R 4B is independently unsubstituted heteroalkyl. In embodiments, R 4B is independently unsubstituted cycloalkyl. In embodiments, R 4B is independently, unsubstituted heterocycloalkyl. In embodiments, R 4B is independently unsubstituted aryl. In embodiments, R 4B is independently unsubstituted heteroaryl. In embodiments, R 4B is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 4B is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 4B is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 4B is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4B is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 4B is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 4B is independently substituted C 1 -C 8 alkyl. In embodiments, R 4B is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 4B is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 4B is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4B is independently substituted C 6 -C 10 aryl. In embodiments, R 4B is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 4B is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 4B is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 4B is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 4B is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4B is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 4B is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 4B is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 4B is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 4B is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 4B is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4B is independently substituted or unsubstituted phenyl. In embodiments, R 4B is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 4B is independently substituted C 1 -C 4 alkyl. In embodiments, R 4B is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 4B is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 4B is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4B is independently substituted phenyl. In embodiments, R 4B is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 4B is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 4B is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 4B is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 4B is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4B is independently unsubstituted phenyl. In embodiments, R 4B is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 4B is independently unsubstituted methyl. In embodiments, R 4B is independently unsubstituted ethyl. In embodiments, R 4B is independently unsubstituted propyl. In embodiments, R 4B is independently unsubstituted isopropyl. In embodiments, R 4B is independently unsubstituted tert-butyl.

In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heterocycloalkyl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heteroaryl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form a substituted heterocycloalkyl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form a substituted heteroaryl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heterocycloalkyl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heteroaryl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 10 membered heteroaryl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 6 membered heteroaryl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 4C is independently hydrogen. In embodiments, R 4C is independently —CX 4C 3 . In embodiments, R 4C is independently —CHX 4C 2 . In embodiments, R 4C is independently —CH 2 X 4C . In embodiments, R 4C is independently —CN. In embodiments, R 4C is independently —COOH. In embodiments, R 4C is independently —CONH 2 . In embodiments, R 4C is independently substituted or unsubstituted alkyl. In embodiments, R 4C is independently substituted or unsubstituted heteroalkyl. In embodiments, R 4C is independently substituted or unsubstituted cycloalkyl. In embodiments, R 4C is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 4C is independently substituted or unsubstituted aryl. In embodiments, R 4C is independently substituted or unsubstituted heteroaryl. In embodiments, R 4C is independently substituted alkyl. In embodiments, R 4C is independently substituted heteroalkyl. In embodiments, R 4C is independently substituted cycloalkyl. In embodiments, R 4C is independently, substituted heterocycloalkyl. In embodiments, R 4C is independently substituted aryl. In embodiments, R 4C is independently substituted heteroaryl. In embodiments, R 4C is independently unsubstituted alkyl. In embodiments, R 4C is independently unsubstituted heteroalkyl. In embodiments, R 4C is independently unsubstituted cycloalkyl. In embodiments, R 4C is independently, unsubstituted heterocycloalkyl. In embodiments, R 4C is independently unsubstituted aryl. In embodiments, R 4C is independently unsubstituted heteroaryl. In embodiments, R 4C is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 4C is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 4C is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 4C is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4C is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 4C is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 4C is independently substituted C 1 -C 8 alkyl. In embodiments, R 4C is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 4C is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 4C is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4C is independently substituted C 6 -C 10 aryl. In embodiments, R 4C is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 4C is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 4C is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 4C is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 4C is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4C is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 4C is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 4C is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 4C is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 4C is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 4C is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4C is independently substituted or unsubstituted phenyl. In embodiments, R 4C is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 4C is independently substituted C 1 -C 4 alkyl. In embodiments, R 4C is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 4C is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 4C is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4C is independently substituted phenyl. In embodiments, R 4C is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 4C is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 4C is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 4C is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 4C is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4C is independently unsubstituted phenyl. In embodiments, R 4C is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 4C is independently unsubstituted methyl. In embodiments, R 4C is independently unsubstituted ethyl. In embodiments, R 4C is independently unsubstituted propyl. In embodiments, R 4C is independently unsubstituted isopropyl. In embodiments, R 4C is independently unsubstituted tert-butyl.

In embodiments, R 4D is independently hydrogen. In embodiments, R 4D is independently —CX 4D 3 . In embodiments, R 4D is independently —CHX 4D 2 . In embodiments, R 4D is independently —CH 2 X 4D . In embodiments, R 4D is independently —CN. In embodiments, R 4D is independently —COOH. In embodiments, R 4D is independently —CONH 2 . In embodiments, R 4D is independently substituted or unsubstituted alkyl. In embodiments, R 4D is independently substituted or unsubstituted heteroalkyl. In embodiments, R 4D is independently substituted or unsubstituted cycloalkyl. In embodiments, R 4D is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 4D is independently substituted or unsubstituted aryl. In embodiments, R 4D is independently substituted or unsubstituted heteroaryl. In embodiments, R 4D is independently substituted alkyl. In embodiments, R 4D is independently substituted heteroalkyl. In embodiments, R 4D is independently substituted cycloalkyl. In embodiments, R 4D is independently, substituted heterocycloalkyl. In embodiments, R 4D is independently substituted aryl. In embodiments, R 4D is independently substituted heteroaryl. In embodiments, R 4D is independently unsubstituted alkyl. In embodiments, R 4D is independently unsubstituted heteroalkyl. In embodiments, R 4D is independently unsubstituted cycloalkyl. In embodiments, R 4D is independently, unsubstituted heterocycloalkyl. In embodiments, R 4D is independently unsubstituted aryl. In embodiments, R 4D is independently unsubstituted heteroaryl. In embodiments, R 4D is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 4D is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 4D is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 4D is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4D is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 4D is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 4D is independently substituted C 1 -C 8 alkyl. In embodiments, R 4D is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 4D is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 4D is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4D is independently substituted C 6 -C 10 aryl. In embodiments, R 4D is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 4D is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 4D is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 4D is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 4D is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 4D is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 4D is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 4D is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 4D is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 4D is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 4D is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4D is independently substituted or unsubstituted phenyl. In embodiments, R 4D is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 4D is independently substituted C 1 -C 4 alkyl. In embodiments, R 4D is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 4D is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 4D is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4D is independently substituted phenyl. In embodiments, R 4D is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 4D is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 4D is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 4D is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 4D is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 4D is independently unsubstituted phenyl. In embodiments, R 4D is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 4D is independently unsubstituted methyl. In embodiments, R 4D is independently unsubstituted ethyl. In embodiments, R 4D is independently unsubstituted propyl. In embodiments, R 4D is independently unsubstituted isopropyl. In embodiments, R 4D is independently unsubstituted tert-butyl.

In embodiments, R 4 is independently hydrogen,

halogen, —CX 4 3 , —CHX 4 2 , —CH 2 X 4 , —OCX 4 3 , —OCH 2 X 4 , —OCHX 4 2 , —CN, —SO n4 R 4D , —SO v4 NR 4A R 4B , —NHC(O)NR 4A R 4B , —N(O) m4 , —NR 4A R 4B , —C(O)R 4C , —C(O)OR 4C , —C(O)NR 4A R 4B , —OR 4D , —NR 4A SO 2 R 4D , —NR 4A C(O)R 4C , —NR 4A C(O)OR 4C , —NR 4A OR 4C , R 29 -substituted or unsubstituted alkyl, R 29 -substituted or unsubstituted heteroalkyl, R 29 -substituted or unsubstituted cycloalkyl, R 29 -substituted or unsubstituted heterocycloalkyl, R 29 -substituted or unsubstituted aryl, or R 29 -substituted or unsubstituted heteroaryl. In embodiments, R 4 is independently halogen, —CX 4 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 4 3 , —OCHX 4 2 , R 29 -substituted or unsubstituted alkyl, R 29 -substituted or unsubstituted heteroalkyl, R 29 -substituted or unsubstituted cycloalkyl, R 29 -substituted or unsubstituted heterocycloalkyl, R 29 -substituted or unsubstituted aryl, or R 29 -substituted or unsubstituted heteroaryl. In embodiments, R 4 is independently halogen, —CX 4 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 4 3 , —OCHX 4 2 , R 29 -substituted or unsubstituted C 1 -C 8 alkyl, R 29 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 29 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 29 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 29 -substituted or unsubstituted phenyl, or R 29 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 4 is —F, —Cl, —Br, or —I. In embodiments, R 4 is independently hydrogen. In embodiments, R 4 is independently methyl. In embodiments, R 4 is independently ethyl.

R 29 is independently oxo,

halogen, —CX 29 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 29 3 , —OCHX 29 2 , R 30 -substituted or unsubstituted alkyl, R 30 -substituted or unsubstituted heteroalkyl, R 30 -substituted or unsubstituted cycloalkyl, R 30 -substituted or unsubstituted heterocycloalkyl, R 30 -substituted or unsubstituted aryl, or R 30 -substituted or unsubstituted heteroaryl. In embodiments, R 29 is independently oxo,

halogen, —CX 29 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 29 3 , —OCHX 29 2 , R 30 -substituted or unsubstituted C 1 -C 8 alkyl, R 30 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 30 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 30 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 30 -substituted or unsubstituted phenyl, or R 30 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 29 is —F, —Cl, —Br, or —I.

R 30 is independently oxo,

halogen, —CX 30 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 30 3 , —OCHX 30 2 , R 31 -substituted or unsubstituted alkyl, R 31 -substituted or unsubstituted heteroalkyl, R 31 -substituted or unsubstituted cycloalkyl, R 31 -substituted or unsubstituted heterocycloalkyl, R 31 -substituted or unsubstituted aryl, or R 31 -substituted or unsubstituted heteroaryl. In embodiments, R 30 is independently oxo,

halogen, —CX 30 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 30 3 , —OCHX 30 2 , R 31 -substituted or unsubstituted C 1 -C 8 alkyl, R 31 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 31 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 31 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 31 -substituted or unsubstituted phenyl, or R 31 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 30 is —F, —Cl, —Br, or —I.

In embodiments, R 4A is independently

hydrogen, —CX 4A 3 , —CN, —COOH, —CONH 2 , —CHX 4A 2 , —CH 2 X 4A , R 29A -substituted or unsubstituted alkyl, R 29A -substituted or unsubstituted heteroalkyl, R 29A -substituted or unsubstituted cycloalkyl, R 29A -substituted or unsubstituted heterocycloalkyl, R 29A -substituted or unsubstituted aryl, or R 29A -substituted or unsubstituted heteroaryl. In embodiments, R 4A is independently hydrogen, —CX 4A 3 , —CN, —COOH, —CONH 2 , —CHX 4A 2 , —CH 2 X 4 , R 29A -substituted or unsubstituted C 1 -C 8 alkyl, R 29A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 29A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 29A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 29A -substituted or unsubstituted phenyl, or R 29A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 4A is —F, —Cl, —Br, or —I. In embodiments, R 4A is independently hydrogen. In embodiments, R 4A is independently methyl. In embodiments, R 4A is independently ethyl.

In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may optionally be joined to form a R 29A -substituted or unsubstituted heterocycloalkyl or R 29A -substituted or unsubstituted heteroaryl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may optionally be joined to form a R 29A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 29A -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 29A is independently oxo,

halogen, —CX 29A3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 29A 3 , —OCHX 29A 2 , R 30A -substituted or unsubstituted alkyl, R 30A -substituted or unsubstituted heteroalkyl, R 30A -substituted or unsubstituted cycloalkyl, R 30A -substituted or unsubstituted heterocycloalkyl, R 30A -substituted or unsubstituted aryl, or R 30A -substituted or unsubstituted heteroaryl. In embodiments, R 29A is independently oxo,

halogen, —CX 29A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 29A 3 , —OCHX 29A 2 , R 30A -substituted or unsubstituted C 1 -C 8 alkyl, R 3A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 3A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 30A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 30A -substituted or unsubstituted phenyl, or R 30A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 29A is —F, —Cl, —Br, or —I.

R 30A is independently oxo,

halogen, —CX 30A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 30A 3 , —OCHX 30A 2 , R 31A -substituted or unsubstituted alkyl, R 31A -substituted or unsubstituted heteroalkyl, R 31A -substituted or unsubstituted cycloalkyl, R 31A -substituted or unsubstituted heterocycloalkyl, R 31A -substituted or unsubstituted aryl, or R 31A -substituted or unsubstituted heteroaryl. In embodiments, R 30A is independently oxo,

halogen, —CX 30A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 30A 3 , —OCHX 30A 2 , R 30A -substituted or unsubstituted C 1 -C 8 alkyl, R 31A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 31A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 31A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 31A -substituted or unsubstituted phenyl, or R 31A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 30A is —F, —Cl, —Br, or —I.

In embodiments, R 4B is independently hydrogen, —CX 4B 3 , —CN, —COOH, —CONH 2 , —CHX 4B 2 , —CH 2 X 4B , R 29B -substituted or unsubstituted alkyl, R 29B -substituted or unsubstituted heteroalkyl, R 29B -substituted or unsubstituted cycloalkyl, R 29B -substituted or unsubstituted heterocycloalkyl, R 29B -substituted or unsubstituted aryl, or R 29B -substituted or unsubstituted heteroaryl. In embodiments, R 4B is independently hydrogen, —CX 4B 3 , —CN, —COOH, —CONH 2 , —CHX 4B 2 , —CH 2 X 4B , R 29B -substituted or unsubstituted C 1 -C 8 alkyl, R 29B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 29B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 29B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 29B -substituted or unsubstituted phenyl, or R 29B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 4B is —F, —Cl, —Br, or —I. In embodiments, R 4B is independently hydrogen. In embodiments, R 4B is independently methyl. In embodiments, R 4B is independently ethyl.

In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may optionally be joined to form a R 29B -substituted or unsubstituted heterocycloalkyl or R 29B -substituted or unsubstituted heteroaryl. In embodiments, R 4A and R 4B substituents bonded to the same nitrogen atom may optionally be joined to form a R 29B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 29B -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 29B is independently oxo,

halogen, —CX 29B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 29B 3 , —OCHX 29B 2 , R 30B -substituted or unsubstituted alkyl, R 30B -substituted or unsubstituted heteroalkyl, R 30B -substituted or unsubstituted cycloalkyl, R 30B -substituted or unsubstituted heterocycloalkyl, R 30B -substituted or unsubstituted aryl, or R 30B -substituted or unsubstituted heteroaryl. In embodiments, R 29B is independently oxo,

halogen, —CX 29B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 29B 3 , —OCHX 29B 2 , R 30B -substituted or unsubstituted C 1 -C 8 alkyl, R 30B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 30B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 30B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 30B -substituted or unsubstituted phenyl, or R 30B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 29B is —F, —Cl, —Br, or —I.

R 30B is independently oxo,

halogen, —CX 30B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 30B 3 , —OCHX 30B 2 , R 31B -substituted or unsubstituted alkyl, R 31B -substituted or unsubstituted heteroalkyl, R 31B -substituted or unsubstituted cycloalkyl, R 31B -substituted or unsubstituted heterocycloalkyl, R 31B -substituted or unsubstituted aryl, or R 31B -substituted or unsubstituted heteroaryl. In embodiments, R 30B is independently oxo,

halogen, —CX 30B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 30B 3 , —OCHX 30B 2 , R 31B -substituted or unsubstituted C 1 -C 8 alkyl, R 31B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 31B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 31B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 31B -substituted or unsubstituted phenyl, or R 31B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 30B is —F, —Cl, —Br, or —I.

In embodiments, R 4C is independently

hydrogen, —CX 4C 3 , —CN, —COOH, —CONH 2 , —CHX 42 , —CH 2 X 4C , R 29C -substituted or unsubstituted alkyl, R 29C -substituted or unsubstituted heteroalkyl, R 29C -substituted or unsubstituted cycloalkyl, R 29C -substituted or unsubstituted heterocycloalkyl, R 29C -substituted or unsubstituted aryl, or R 29C -substituted or unsubstituted heteroaryl. In embodiments, R 4C is independently hydrogen, —CX 4C 3 , —CN, —COOH, —CONH 2 , —CHX 4C 2 , —CH 2 X 4C , R 29C -substituted or unsubstituted C 1 -C 8 alkyl, R 29C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 29C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 29C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 29C -substituted or unsubstituted phenyl, or R 29C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 4C is —F, —Cl, —Br, or —I. In embodiments, R 4C is independently hydrogen. In embodiments, R 4C is independently methyl. In embodiments, R 4C is independently ethyl.

R 29C is independently oxo,

halogen, —CX 29C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 29C 3 , —OCHX 29C 2 , R 30C -substituted or unsubstituted alkyl, R 30C -substituted or unsubstituted heteroalkyl, R 30C -substituted or unsubstituted cycloalkyl, R 30C -substituted or unsubstituted heterocycloalkyl, R 30C -substituted or unsubstituted aryl, or R 30C -substituted or unsubstituted heteroaryl. In embodiments, R 29C is independently oxo,

halogen, —CX 29C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 29C 3 , —OCHX 29C 2 , R 30C substituted or unsubstituted C 1 -C 8 alkyl, R 30C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 30C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 30C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 30C -substituted or unsubstituted phenyl, or R 30C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 29C is —F, —Cl, —Br, or —I.

R 30C is independently oxo,

halogen, —CX 30C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 30C 3 , —OCHX 30C 2 , R 31C -substituted or unsubstituted alkyl, R 31C -substituted or unsubstituted heteroalkyl, R 31C -substituted or unsubstituted cycloalkyl, R 31C -substituted or unsubstituted heterocycloalkyl, R 31C -substituted or unsubstituted aryl, or R 31C -substituted or unsubstituted heteroaryl. In embodiments, R 31C is independently oxo,

halogen, —CX 30C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 30C 3 , —OCHX 30C 2 , R 31C -substituted or unsubstituted C 1 -C 8 alkyl, R 31C substituted or unsubstituted 2 to 8 membered heteroalkyl, R 31C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 31C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 31C -substituted or unsubstituted phenyl, or R 31C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 30C is —F, —Cl, —Br, or —I.

In embodiments, R 4D is independently

hydrogen, —CX 4D 3 , —CN, —COOH, —CONH 2 , —CHX 4D 2 , —CH 2 X 4D , R 29D -substituted or unsubstituted alkyl, R 29D -substituted or unsubstituted heteroalkyl, R 29D -substituted or unsubstituted cycloalkyl, R 29D -substituted or unsubstituted heterocycloalkyl, R 29D -substituted or unsubstituted aryl, or R 29D -substituted or unsubstituted heteroaryl. In embodiments, R 4D is independently hydrogen, —CX 4D 3 , —CN, —COOH, —CONH 2 , —CHX 4D 2 , —CH 2 X 4D , R 29D -substituted or unsubstituted C 1 -C 8 alkyl, R 29D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 29D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 29D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 29D -substituted or unsubstituted phenyl, or R 29D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 4D is —F, —Cl, —Br, or —I. In embodiments, R 4D is independently hydrogen. In embodiments, R 4D is independently methyl. In embodiments, R 4D is independently ethyl.

R 29D is independently oxo,

halogen, —CX 29D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 29D 3 , —OCHX 29D 2 , R 30D -substituted or unsubstituted alkyl, R 30D -substituted or unsubstituted heteroalkyl, R 30D -substituted or unsubstituted cycloalkyl, R 30D -substituted or unsubstituted heterocycloalkyl, R 30D -substituted or unsubstituted aryl, or R 30D -substituted or unsubstituted heteroaryl. In embodiments, R 29D is independently oxo,

halogen, —CX 29D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 29D 3 , —OCHX 29D 2 , R 30D -substituted or unsubstituted C 1 -C 8 alkyl, R 30D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 30D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 30D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 30D -substituted or unsubstituted phenyl, or R 30D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 29D is —F, —Cl, —Br, or —I.

R 30D is independently oxo,

halogen, —CX 30D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 30D 3 , —OCHX 30D 2 , R 31D -substituted or unsubstituted alkyl, R 31D -substituted or unsubstituted heteroalkyl, R 31D -substituted or unsubstituted cycloalkyl, R 31D -substituted or unsubstituted heterocycloalkyl, R 31D -substituted or unsubstituted aryl, or R 31D -substituted or unsubstituted heteroaryl. In embodiments, R 30D is independently oxo,

halogen, —CX 30D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 30D 3 , —OCHX 30D 2 , R 31D -substituted or unsubstituted C 1 -C 8 alkyl, R 31D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 31D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 31D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 31D -substituted or unsubstituted phenyl, or R 31D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 30D is —F, —Cl, —Br, or —I.

R 31 , R 31A , R 31B , R 31C , and R 31D are independently hydrogen, oxo,

halogen, —CCl 3 , —CBr 3 , —CF 3 , —Cl 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H,

—NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCl 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 31 , R 31A , R 31B , R 31C , and R 31D are independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 31 , R 31A , R 31B , R 31C , and R 31D are independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted C 1 -C 8 alkyl, unsubstituted 2 to 8 membered heteroalkyl, unsubstituted C 3 -C 8 cycloalkyl, unsubstituted 3 to 6 membered heterocycloalkyl, unsubstituted phenyl, or unsubstituted 5 to 6 membered heteroaryl.

In embodiments, the symbol Y 2 is N. In embodiments, the symbol Y 2 is C(R 5 ).

In embodiments, R 5 is hydrogen, substituted or unsubstituted C 1 -C 8 alkyl, or substituted or unsubstituted 2 to 8 membered heteroalkyl.

In embodiments, R 5 is independently hydrogen. In embodiments, R 5 is independently halogen. In embodiments, R 5 is independently —CX 5 3 . In embodiments, R 5 is independently —CHX 5 2 . In embodiments, R 5 is independently —CH 2 X 5 . In embodiments, R 5 is independently —OCX 53 . In embodiments, R 5 is independently —OCH 2 X 5 . In embodiments, R 5 is independently —OCHX 5 2 . In embodiments, R 5 is independently —CN. In embodiments, R 5 is independently —SO 5 R 5D . In embodiments, R 5 is independently —SO v5 NR 5A R 5B . In embodiments, R 5 is independently —NHC(O)NR 5A R 5B . In embodiments, R 5 is independently —N(O) m5 . In embodiments, R 5 is independently —NR 5A R 5B . In embodiments, R 5 is independently —C(O)R 5C . In embodiments, R 5 is independently —C(O)—OR 5C . In embodiments, R 5 is independently —C(O)NR 5A R 5B . In embodiments, R 5 is independently —OR 5D . In embodiments, R 5 is independently —NR 5A SO 2 R 5D . In embodiments, R 5 is independently —NR 5A C(O)R 5C . In embodiments, R 5 is independently —NR 5A C(O)OR 5C In embodiments, R 5 is independently —NR 5A OR 5C . In embodiments, R 5 is independently —OH. In embodiments, R 5 is independently —NH 2 . In embodiments, R 5 is independently —COOH. In embodiments, R 5 is independently —CONH 2 . In embodiments, R 5 is independently —NO 2 . In embodiments, R 5 is independently —SH. In embodiments, R 5 is independently —F.

In embodiments, R 5 is independently substituted or unsubstituted alkyl. In embodiments, R 5 is independently substituted or unsubstituted heteroalkyl. In embodiments, R 5 is independently substituted or unsubstituted cycloalkyl. In embodiments, R 5 is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 5 is independently substituted or unsubstituted aryl. In embodiments, R 5 is independently substituted or unsubstituted heteroaryl. In embodiments, R 5 is independently substituted alkyl. In embodiments, R 5 is independently substituted heteroalkyl. In embodiments, R 5 is independently substituted cycloalkyl. In embodiments, R 5 is independently, substituted heterocycloalkyl. In embodiments, R 5 is independently substituted aryl. In embodiments, R 5 is independently substituted heteroaryl. In embodiments, R 5 is independently unsubstituted alkyl. In embodiments, R 5 is independently unsubstituted heteroalkyl. In embodiments, R 5 is independently unsubstituted cycloalkyl. In embodiments, R 5 is independently, unsubstituted heterocycloalkyl. In embodiments, R 5 is independently unsubstituted aryl. In embodiments, R 5 is independently unsubstituted heteroaryl. In embodiments, R 5 is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 5 is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 5 is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 5 is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5 is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 5 is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 5 is independently substituted C 1 -C 8 alkyl. In embodiments, R 5 is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 5 is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 5 is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5 is independently substituted C 6 -C 10 aryl. In embodiments, R 5 is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 5 is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 5 is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 5 is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 5 is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5 is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 5 is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 5 is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 5 is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 5 is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 5 is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5 is independently substituted or unsubstituted phenyl. In embodiments, R 5 is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 5 is independently substituted C 1 -C 4 alkyl. In embodiments, R 5 is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 5 is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 5 is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5 is independently substituted phenyl. In embodiments, R 5 is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 5 is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 5 is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 5 is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 5 is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5 is independently unsubstituted phenyl. In embodiments, R 5 is independently unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 5A is independently hydrogen. In embodiments, R 5A is independently —CX 5A 3 . In embodiments, R 5A is independently —CHX 5A 2 . In embodiments, R 5A is independently —CH 2 X 5A . In embodiments, R 5A is independently —CN. In embodiments, R 5A is independently —COOH. In embodiments, R 5A is independently —CONH 2 . In embodiments, R 5A is independently substituted or unsubstituted alkyl. In embodiments, R 5A is independently substituted or unsubstituted heteroalkyl. In embodiments, R 5A is independently substituted or unsubstituted cycloalkyl. In embodiments, R 5A is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 5A is independently substituted or unsubstituted aryl. In embodiments, R 5A is independently substituted or unsubstituted heteroaryl. In embodiments, R 5A is independently substituted alkyl. In embodiments, R 5A is independently substituted heteroalkyl. In embodiments, R 5A is independently substituted cycloalkyl. In embodiments, R 5A is independently, substituted heterocycloalkyl. In embodiments, R 5A is independently substituted aryl. In embodiments, R 5A is independently substituted heteroaryl. In embodiments, R 5A is independently unsubstituted alkyl. In embodiments, R 5A is independently unsubstituted heteroalkyl. In embodiments, R 5A is independently unsubstituted cycloalkyl. In embodiments, R 5A is independently, unsubstituted heterocycloalkyl. In embodiments, R 5A is independently unsubstituted aryl. In embodiments, R 5A is independently unsubstituted heteroaryl. In embodiments, R 5A is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 5A is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 5A is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 5A is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5A is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 5A is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 5A is independently substituted C 1 -C 8 alkyl. In embodiments, R 5A is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 5A is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 5A is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5A is independently substituted C 6 -C 10 aryl. In embodiments, R 5A is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 5A is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 5A is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 5A is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 5A is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5A is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 5A is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 5A is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 5A is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 5A is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 5A is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5A is independently substituted or unsubstituted phenyl. In embodiments, R 5A is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 5A is independently substituted C 1 -C 4 alkyl. In embodiments, R 5A is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 5A is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 5A is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5A is independently substituted phenyl. In embodiments, R 5A is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 5A is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 5A is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 5A is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 5A is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5A is independently unsubstituted phenyl. In embodiments, R 5A is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 5A is independently unsubstituted methyl. In embodiments, R 5A is independently unsubstituted ethyl. In embodiments, R 5A is independently unsubstituted propyl. In embodiments, R 5A is independently unsubstituted isopropyl. In embodiments, R 5A is independently unsubstituted tert-butyl.

In embodiments, R 5B is independently hydrogen. In embodiments, R 5B is independently —CX 5B 3 . In embodiments, R 5B is independently —CHX 5B2 . In embodiments, R 5B is independently —CH 2 X 5B . In embodiments, R 5B is independently —CN. In embodiments, R 5B is independently —COOH. In embodiments, R 5B is independently —CONH 2 . In embodiments, R 5B is independently substituted or unsubstituted alkyl. In embodiments, R 5B is independently substituted or unsubstituted heteroalkyl. In embodiments, R 5B is independently substituted or unsubstituted cycloalkyl. In embodiments, R 5B is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 5B is independently substituted or unsubstituted aryl. In embodiments, R 5B is independently substituted or unsubstituted heteroaryl. In embodiments, R 5B is independently substituted alkyl. In embodiments, R 5B is independently substituted heteroalkyl. In embodiments, R 5B is independently substituted cycloalkyl. In embodiments, R 5B is independently, substituted heterocycloalkyl. In embodiments, R 5B is independently substituted aryl. In embodiments, R 5B is independently substituted heteroaryl. In embodiments, R 5B is independently unsubstituted alkyl. In embodiments, R 5B is independently unsubstituted heteroalkyl. In embodiments, R 5B is independently unsubstituted cycloalkyl. In embodiments, R 5B is independently, unsubstituted heterocycloalkyl. In embodiments, R 5B is independently unsubstituted aryl. In embodiments, R 5B is independently unsubstituted heteroaryl. In embodiments, R 5B is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 5B is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 5B is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 5B is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5B is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 5B is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 5B is independently substituted C 1 -C 8 alkyl. In embodiments, R 5B is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 5B is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 5B is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5B is independently substituted C 6 -C 10 aryl. In embodiments, R 5B is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 5B is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 5B is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 5B is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 5B is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5B is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 5B is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 5B is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 5B is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 5B is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 5B is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5B is independently substituted or unsubstituted phenyl. In embodiments, R 5B is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 5B is independently substituted C 1 -C 4 alkyl. In embodiments, R 5B is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 5B is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 5B is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5B is independently substituted phenyl. In embodiments, R 5B is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 5B is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 5B is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 5B is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 5B is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5B is independently unsubstituted phenyl. In embodiments, R 5B is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 5B is independently unsubstituted methyl. In embodiments, R 5B is independently unsubstituted ethyl. In embodiments, R 5B is independently unsubstituted propyl. In embodiments, R 5B is independently unsubstituted isopropyl. In embodiments, R 5B is independently unsubstituted tert-butyl.

In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heterocycloalkyl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heteroaryl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form a substituted heterocycloalkyl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form a substituted heteroaryl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heterocycloalkyl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heteroaryl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 10 membered heteroaryl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 6 membered heteroaryl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 5C is independently hydrogen. In embodiments, R 5C is independently —CX 5C 3 . In embodiments, R 5C is independently —CHX 5C 2 . In embodiments, R 5C is independently —CH 2 X 5C . In embodiments, R 5C is independently —CN. In embodiments, R 5C is independently —COOH. In embodiments, R 5C is independently —CONH 2 . In embodiments, R 5C is independently substituted or unsubstituted alkyl. In embodiments, R 5C is independently substituted or unsubstituted heteroalkyl. In embodiments, R 5C is independently substituted or unsubstituted cycloalkyl. In embodiments, R 5C is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 5C is independently substituted or unsubstituted aryl. In embodiments, R 5C is independently substituted or unsubstituted heteroaryl. In embodiments, R 5C is independently substituted alkyl. In embodiments, R 5C is independently substituted heteroalkyl. In embodiments, R 5C is independently substituted cycloalkyl. In embodiments, R 5C is independently, substituted heterocycloalkyl. In embodiments, R 5C is independently substituted aryl. In embodiments, R 5C is independently substituted heteroaryl. In embodiments, R 5C is independently unsubstituted alkyl. In embodiments, R 5C is independently unsubstituted heteroalkyl. In embodiments, R 5C is independently unsubstituted cycloalkyl. In embodiments, R 5C is independently, unsubstituted heterocycloalkyl. In embodiments, R 5C is independently unsubstituted aryl. In embodiments, R 5C is independently unsubstituted heteroaryl. In embodiments, R 5C is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 5C is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 5C is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 5C is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5C is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 5C is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 5C is independently substituted C 1 -C 8 alkyl. In embodiments, R 5C is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 5C is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 5C is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5C is independently substituted C 6 -C 10 aryl. In embodiments, R 5C is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 5C is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 5C is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 5C is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 5C is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5C is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 5C is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 5C is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 5C is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 5C is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 5C is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5C is independently substituted or unsubstituted phenyl. In embodiments, R 5C is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 5C is independently substituted C 1 -C 4 alkyl. In embodiments, R 5C is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 5C is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 5C is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5C is independently substituted phenyl. In embodiments, R 5C is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 5C is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 5C is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 5C is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 5C is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5C is independently unsubstituted phenyl. In embodiments, R 5C is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 5C is independently unsubstituted methyl. In embodiments, R 5C is independently unsubstituted ethyl. In embodiments, R 5C is independently unsubstituted propyl. In embodiments, R 5C is independently unsubstituted isopropyl. In embodiments, R 5C is independently unsubstituted tert-butyl.

In embodiments, R 5D is independently hydrogen. In embodiments, R 5D is independently —CX 5D 3 . In embodiments, R 5D is independently —CHX 5D 2 . In embodiments, R 5D is independently —CH 2 X 5D . In embodiments, R 5D is independently —CN. In embodiments, R 5D is independently —COOH. In embodiments, R 5D is independently —CONH 2 . In embodiments, R 5D is independently substituted or unsubstituted alkyl. In embodiments, R 5D is independently substituted or unsubstituted heteroalkyl. In embodiments, R 5D is independently substituted or unsubstituted cycloalkyl. In embodiments, R 5D is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 5D is independently substituted or unsubstituted aryl. In embodiments, R 5D is independently substituted or unsubstituted heteroaryl. In embodiments, R 5D is independently substituted alkyl. In embodiments, R 5D is independently substituted heteroalkyl. In embodiments, R 5D is independently substituted cycloalkyl. In embodiments, R 5D is independently, substituted heterocycloalkyl. In embodiments, R 5D is independently substituted aryl. In embodiments, R 5D is independently substituted heteroaryl. In embodiments, R 5D is independently unsubstituted alkyl. In embodiments, R 5D is independently unsubstituted heteroalkyl. In embodiments, R 5D is independently unsubstituted cycloalkyl. In embodiments, R 5D is independently, unsubstituted heterocycloalkyl. In embodiments, R 5D is independently unsubstituted aryl. In embodiments, R 5D is independently unsubstituted heteroaryl. In embodiments, R 5D is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 5D is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 5D is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 5D is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5D is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 5D is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 5D is independently substituted C 1 -C 8 alkyl. In embodiments, R 5D is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 5D is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 5D is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5D is independently substituted C 6 -C 10 aryl. In embodiments, R 5D is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 5D is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 5D is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 5D is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 5D is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 5D is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 5D is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 5D is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 5D is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 5D is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 5D is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5D is independently substituted or unsubstituted phenyl. In embodiments, R 5D is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 5D is independently substituted C 1 -C 4 alkyl. In embodiments, R 5D is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 5D is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 5D is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5D is independently substituted phenyl. In embodiments, R 5D is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 5D is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 5D is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 5D is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 5D is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 5D is independently unsubstituted phenyl. In embodiments, R 5D is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 5D is independently unsubstituted methyl. In embodiments, R 5D is independently unsubstituted ethyl. In embodiments, R 5D is independently unsubstituted propyl. In embodiments, R 5 is independently unsubstituted isopropyl. In embodiments, R 5D is independently unsubstituted tert-butyl.

In embodiments, R 5 is independently hydrogen,

halogen, —CX 5 3 , —CHX 5 2 , —CH 2 X 5 , —OCX 5 3 , —OCH 2 X 5 , —OCHX 5 2 , —CN, —SO n5 R 5D , —SO v5 NR 5A R 5B , —NHC(O)NR 5A R 5B , —N(O) m5 , —NR 5A R 5B , —C(O)R 5C , —C(O)OR 5C , —C(O)NR 5A R 5B , —OR 5D , —NR 5A SO 2 R 5D , —NR 5A C(O)R 5C , —NR 5A C(O)OR 5C , —NR 5A OR 5C , R 32 -substituted or unsubstituted alkyl, R 32 -substituted or unsubstituted heteroalkyl, R 32 -substituted or unsubstituted cycloalkyl, R 32 -substituted or unsubstituted heterocycloalkyl, R 32 -substituted or unsubstituted aryl, or R 32 -substituted or unsubstituted heteroaryl. In embodiments, R 5 is independently halogen, —CX 5 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 5 3 , —OCHX 2 , R 32 -substituted or unsubstituted alkyl, R 32 -substituted or unsubstituted heteroalkyl, R 32 -substituted or unsubstituted cycloalkyl, R 32 -substituted or unsubstituted heterocycloalkyl, R 32 -substituted or unsubstituted aryl, or R 32 -substituted or unsubstituted heteroaryl. In embodiments, R 5 is independently

halogen, —CX 5 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 53 , —OCHX 52 , R 32 -substituted or unsubstituted C 1 -C 8 alkyl, R 32 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 32 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 32 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 32 -substituted or unsubstituted phenyl, or R 32 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 5 is —F, —Cl, —Br, or —I. In embodiments, R 5 is independently methyl. In embodiments, R 5 is independently ethyl.

R 32 is independently oxo,

halogen, —CX 32 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 32 3 , —OCHX 32 2 , R 33 -substituted or unsubstituted alkyl, R 33 -substituted or unsubstituted heteroalkyl, R 33 -substituted or unsubstituted cycloalkyl, R 33 -substituted or unsubstituted heterocycloalkyl, R 33 -substituted or unsubstituted aryl, or R 33 -substituted or unsubstituted heteroaryl. In embodiments, R 32 is independently oxo,

halogen, —CX 32 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 323 , —OCHX 322 , R 33 -substituted or unsubstituted C 1 -C 8 alkyl, R 33 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 33 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 33 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 33 -substituted or unsubstituted phenyl, or R 33 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 32 is —F, —Cl, —Br, or —I.

R 33 is independently oxo,

halogen, —CX 33 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 33 3 , —OCHX 33 2 , R 34 -substituted or unsubstituted alkyl, R 34 -substituted or unsubstituted heteroalkyl, R 34 -substituted or unsubstituted cycloalkyl, R 34 -substituted or unsubstituted heterocycloalkyl, R 34 -substituted or unsubstituted aryl, or R 34 -substituted or unsubstituted heteroaryl. In embodiments, R 33 is independently oxo,

halogen, —CX 33 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 33 3 , —OCHX 32 , R 34 -substituted or unsubstituted C 1 -C 8 alkyl, R 34 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 34 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 34 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 34 -substituted or unsubstituted phenyl, or R 34 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 33 is —F, —Cl, —Br, or —I.

In embodiments, R 5A is independently

hydrogen, —CX 5A 3 , —CN, —COOH, —CONH 2 , —CHX 5A 2 , —CH 2 X 5A , R 32A -substituted or unsubstituted alkyl, R 32A -substituted or unsubstituted heteroalkyl, R 32A -substituted or unsubstituted cycloalkyl, R 32A -substituted or unsubstituted heterocycloalkyl, R 32A -substituted or unsubstituted aryl, or R 32A -substituted or unsubstituted heteroaryl. In embodiments, R 5A is independently hydrogen, —CX 5A 3 , —CN, —COOH, —CONH 2 , —CHX 5A 2 , —CH 2 X 5A , R 32A -substituted or unsubstituted C 1 -C 8 alkyl, R 32A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 32A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 32A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 32A -substituted or unsubstituted phenyl, or R 32A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 5A is —F, —Cl, —Br, or —I. In embodiments, R 5A is independently hydrogen. In embodiments, R 5A is independently methyl. In embodiments, R 5A is independently ethyl.

In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may optionally be joined to form a R 32A -substituted or unsubstituted heterocycloalkyl or R 32A -substituted or unsubstituted heteroaryl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may optionally be joined to form a R 32A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 32A -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 32A is independently oxo,

halogen, —CX 32A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 32A 3 , —OCHX 32A 2 , R 33A -substituted or unsubstituted alkyl, R 33A -substituted or unsubstituted heteroalkyl, R 33A -substituted or unsubstituted cycloalkyl, R 33A -substituted or unsubstituted heterocycloalkyl, R 33A -substituted or unsubstituted aryl, or R 33A -substituted or unsubstituted heteroaryl. In embodiments, R 32A is independently oxo,

halogen, —CX 32A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 32A 3 , —OCHX 32A 2 , R 33A -substituted or unsubstituted C 1 -C 8 alkyl, R 33A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 33A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 33A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 33A -substituted or unsubstituted phenyl, or R 33A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 32A is —F, —Cl, —Br, or —I.

R 33A is independently oxo,

halogen, —CX 33A3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 33A 3 , —OCHX 33A 2 , R 34A -substituted or unsubstituted alkyl, R 34A -substituted or unsubstituted heteroalkyl, R 34A -substituted or unsubstituted cycloalkyl, R 34A -substituted or unsubstituted heterocycloalkyl, R 34A -substituted or unsubstituted aryl, or R 34A -substituted or unsubstituted heteroaryl. In embodiments, R 33A is independently oxo,

halogen, —CX 33A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 33A 3 , —OCHX 33A 2 , R 34A -substituted or unsubstituted C 1 -C 8 alkyl, R 34A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 34A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 34A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 34A -substituted or unsubstituted phenyl, or R 34A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 33A is —F, —Cl, —Br, or —I.

In embodiments, R 5B is independently

hydrogen, —CX 5B 3 , —CN, —COOH, —CONH 2 , —CHX 5B 2 , —CH 2 X 5B , R 32B -substituted or unsubstituted alkyl, R 32B -substituted or unsubstituted heteroalkyl, R 32B -substituted or unsubstituted cycloalkyl, R 32B -substituted or unsubstituted heterocycloalkyl, R 32B -substituted or unsubstituted aryl, or R 32B -substituted or unsubstituted heteroaryl. In embodiments, R 5B is independently hydrogen, —CX 5B 3 , —CN, —COOH, —CONH 2 , —CHX 5B 2 , —CH 2 X 5B , R 32B -substituted or unsubstituted C 1 -C 8 alkyl, R 32B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 32B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 32B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 32B -substituted or unsubstituted phenyl, or R 32B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 5B is —F, —Cl, —Br, or —I. In embodiments, R 5B is independently hydrogen. In embodiments, R 5B is independently methyl. In embodiments, R 5B is independently ethyl.

In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may optionally be joined to form a R 32B -substituted or unsubstituted heterocycloalkyl or R 32B -substituted or unsubstituted heteroaryl. In embodiments, R 5A and R 5B substituents bonded to the same nitrogen atom may optionally be joined to form a R 32B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 32B -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 32B is independently oxo,

halogen, —CX 32B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 32B3 , —OCHX 32B2 , R 33B -substituted or unsubstituted alkyl, R 33B -substituted or unsubstituted heteroalkyl, R 33B -substituted or unsubstituted cycloalkyl, R 33B -substituted or unsubstituted heterocycloalkyl, R 33B -substituted or unsubstituted aryl, or R 33B -substituted or unsubstituted heteroaryl. In embodiments, R 32B is independently oxo,

halogen, —CX 32B3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 32B 3 , —OCHX 32B 2 , R 33B -substituted or unsubstituted C 1 -C 8 alkyl, R 33B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 33B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 33B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 33B -substituted or unsubstituted phenyl, or R 33B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 32B is —F, —Cl, —Br, or —I.

R 33B is independently oxo,

halogen, —CX 33B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 33B 3 , —OCHX 33B 2 , R 34B -substituted or unsubstituted alkyl, R 34B -substituted or unsubstituted heteroalkyl, R 34B -substituted or unsubstituted cycloalkyl, R 34B -substituted or unsubstituted heterocycloalkyl, R 34B -substituted or unsubstituted aryl, or R 34B -substituted or unsubstituted heteroaryl. In embodiments, R 33B is independently oxo,

halogen, —CX 33B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 33B 3 , —OCHX 33B 2 , R 34B -substituted or unsubstituted C 1 -C 8 alkyl, R 34B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 34B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 34B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 34B -substituted or unsubstituted phenyl, or R 34B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 33B is —F, —Cl, —Br, or —I.

In embodiments, R 5C is independently

hydrogen, —CX 5C 3 , —CN, —COOH, —CONH 2 , —CHX 5C 2 , —CH 2 X 5C , R 32C -substituted or unsubstituted alkyl, R 32C -substituted or unsubstituted heteroalkyl, R 32C -substituted or unsubstituted cycloalkyl, R 32C -substituted or unsubstituted heterocycloalkyl, R 32C -substituted or unsubstituted aryl, or R 32C -substituted or unsubstituted heteroaryl. In embodiments, R 5C is independently hydrogen, —CX 5C 3 , —CN, —COOH, —CONH 2 , —CHX 5C 2 , —CH 2 X 5C , R 32C -substituted or unsubstituted C 1 -C 8 alkyl, R 32C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 32C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 32C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 32C -substituted or unsubstituted phenyl, or R 32C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 5C is —F, —Cl, —Br, or —I. In embodiments, R 5C is independently hydrogen. In embodiments, R 5C is independently methyl. In embodiments, R 5C is independently ethyl.

R 32C is independently oxo,

halogen, —CX 32C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 32 3 , —OCHX 32 2 , R 33C -substituted or unsubstituted alkyl, R 33C -substituted or unsubstituted heteroalkyl, R 33C -substituted or unsubstituted cycloalkyl, R 33C -substituted or unsubstituted heterocycloalkyl, R 33C -substituted or unsubstituted aryl, or R 33C -substituted or unsubstituted heteroaryl. In embodiments, R 32C is independently oxo,

halogen, —CX 32C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 32 3 , —OCHX 32 2 , R 33C -substituted or unsubstituted C 1 -C 8 alkyl, R 33C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 33C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 33C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 33C -substituted or unsubstituted phenyl, or R 33C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 32C is —F, —Cl, —Br, or —I.

R 33C is independently oxo,

halogen, —CX 33C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 33 3 , —OCHX 33 C 2 , R 34C -substituted or unsubstituted alkyl, R 34C -substituted or unsubstituted heteroalkyl, R 34C -substituted or unsubstituted cycloalkyl, R 34C -substituted or unsubstituted heterocycloalkyl, R 34C -substituted or unsubstituted aryl, or R 34C -substituted or unsubstituted heteroaryl. In embodiments, R 33C is independently oxo,

halogen, —CX 33 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 33 3 , —OCHX 33 2 , R 34C -substituted or unsubstituted C 1 -C 8 alkyl, R 34C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 34C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 34C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 34C -substituted or unsubstituted phenyl, or R 34C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 33C is —F, —Cl, —Br, or —I.

In embodiments, R 5D is independently

hydrogen, —CX 5D 3 , —CN, —COOH, —CONH 2 , —CHX 5 D2 , —CH 2 X 5D , R 32D -substituted or unsubstituted alkyl, R 32D -substituted or unsubstituted heteroalkyl, R 32D -substituted or unsubstituted cycloalkyl, R 32D -substituted or unsubstituted heterocycloalkyl, R 32D -substituted or unsubstituted aryl, or R 32D -substituted or unsubstituted heteroaryl. In embodiments, R 5D is independently hydrogen, —CX 5D 3 , —CN, —COOH, —CONH 2 , —CHX 5D 2 , —CH 2 X 5D , R 32D -substituted or unsubstituted C 1 -C 8 alkyl, R 32D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 32D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 32D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 32D -substituted or unsubstituted phenyl, or R 32D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 5D is —F, —Cl, —Br, or —I. In embodiments, R 5D is independently hydrogen. In embodiments, R 5D is independently methyl. In embodiments, R 5D is independently ethyl.

R 32D is independently oxo,

halogen, —CX 32D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 32D 3 , —OCHX 32D 2 , R 33D -substituted or unsubstituted alkyl, R 33D -substituted or unsubstituted heteroalkyl, R 33D -substituted or unsubstituted cycloalkyl, R 33D -substituted or unsubstituted heterocycloalkyl, R 33D -substituted or unsubstituted aryl, or R 33D -substituted or unsubstituted heteroaryl. In embodiments, R 32D is independently oxo,

halogen, —CX 32D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 32D 3 , —OCHX 32D 2 , R 33D -substituted or unsubstituted C 1 -C 8 alkyl, R 33D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 33D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 33 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 33D -substituted or unsubstituted phenyl, or R 33D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 32D is —F, —Cl, —Br, or —I.

R 33D is independently oxo,

halogen, —CX 33D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 33D 3 , —OCHX 33D 2 , R 34D -substituted or unsubstituted alkyl, R 34D -substituted or unsubstituted heteroalkyl, R 34D -substituted or unsubstituted cycloalkyl, R 34D -substituted or unsubstituted heterocycloalkyl, R 34D -substituted or unsubstituted aryl, or R 34D -substituted or unsubstituted heteroaryl. In embodiments, R 33D is independently oxo,

halogen, —CX 33D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 33D 3 , —OCHX 33D 2 , R 34D -substituted or unsubstituted C 1 -C 8 alkyl, R 34D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 34D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 34D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 34D -substituted or unsubstituted phenyl, or R 34D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 33D is —F, —Cl, —Br, or —I.

R 34 ,R 34A , R 34B , R 34C , and R 34D are independently hydrogen, oxo,

halogen, —CCl 3 , —CBr 3 , —CF 3 , —Cl 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H,

—NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCl 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 34 , R 34A R 34B , R 34C , and R 34D are independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 34 , R 34A , R 34B , R 34C , and R 34D are independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted C 1 -C 8 alkyl, unsubstituted 2 to 8 membered heteroalkyl, unsubstituted C 3 -C 8 cycloalkyl, unsubstituted 3 to 6 membered heterocycloalkyl, unsubstituted phenyl, or unsubstituted 5 to 6 membered heteroaryl.

In embodiments, L 1 is a bond, —S(O) 2 —, —S(O) 2 -Ph-, substituted or unsubstituted C 1 -C 8 alkylene, substituted or unsubstituted 2 to 8 membered heteroalkylene, substituted or unsubstituted C 3 -C 8 cycloalkylene, substituted or unsubstituted 3 to 8 membered heterocycloalkylene, substituted or unsubstituted phenylene, or substituted or unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 1 is a bond. In embodiments, L 1 is a substituted or unsubstituted C 1 -C 6 alkylene, substituted or unsubstituted 2 to 6 membered heteroalkylene, substituted or unsubstituted C 3 -C 6 cycloalkylene, substituted or unsubstituted 3 to 6 membered heterocycloalkylene, substituted or unsubstituted phenylene, or substituted or unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 1 is an unsubstituted C 1 -C 6 alkylene, unsubstituted 2 to 6 membered heteroalkylene, or unsubstituted C 3 -C 6 cycloalkylene. In embodiments, L 1 is an unsubstituted methylene.

In embodiments, L 1 is a bond. In embodiments, L 1 is —S(O) 2 —. In embodiments, L 1 is —S(O) 2 -Ph-. In embodiments, L 1 is —NR 6 —. In embodiments, L 1 is —O—. In embodiments, L 1 is —S—. In embodiments, L 1 is —C(O)—. In embodiments, L 1 is —C(O)NR 6 —. In embodiments, L 1 is —NR 6 C(O)—. In embodiments, L 1 is —NR 6 C(O)NH—. In embodiments, L 1 is —NHC(O)NR 6 —. In embodiments, L 1 is —C(O)O—. In embodiments, L 1 is —OC(O)—. In embodiments, L 1 is —NH—. In embodiments, L 1 is —C(O)NH—. In embodiments, L 1 is —NHC(O)—. In embodiments, L 1 is —NHC(O)NH—. In embodiments, L 1 is —CH 2 —. In embodiments, L 1 is —OCH 2 —. In embodiments, L 1 is —CH 2 O—. In embodiments, L 1 is —CH 2 CH 2 —. In embodiments, L 1 is —SCH 2 —. In embodiments, L 1 is —CH 2 S—. In embodiments, L 1 is —CHCH—. In embodiments, L 1 is —CC—. In embodiments, L 1 is —NHCH 2 —. In embodiments, L 1 is —CH 2 NH—.

In embodiments, L 1 is a substituted or unsubstituted alkylene. In embodiments, L 1 is a substituted or unsubstituted heteroalkylene. In embodiments, L 1 is a substituted or unsubstituted cycloalkylene. In embodiments, L 1 is a substituted or unsubstituted heterocycloalkylene. In embodiments, L 1 is a substituted or unsubstituted arylene. In embodiments, L 1 is a substituted or unsubstituted heteroarylene. In embodiments, L 1 is a substituted alkylene. In embodiments, L 1 is a substituted heteroalkylene. In embodiments, L 1 is a substituted cycloalkylene. In embodiments, L 1 is a substituted heterocycloalkylene. In embodiments, L 1 is a substituted arylene. In embodiments, L 1 is a substituted heteroarylene. In embodiments, L 1 is an unsubstituted alkylene. In embodiments, L 1 is an unsubstituted heteroalkylene. In embodiments, L 1 is an unsubstituted cycloalkylene. In embodiments, L 1 is an unsubstituted heterocycloalkylene. In embodiments, L 1 is an unsubstituted arylene. In embodiments, L 1 is an unsubstituted heteroarylene. In embodiments, L 1 is a substituted or unsubstituted C 1 -C 8 alkylene. In embodiments, L 1 is a substituted or unsubstituted 2 to 8 membered heteroalkylene. In embodiments, L 1 is a substituted or unsubstituted C 3 -C 8 cycloalkylene. In embodiments, L 1 is a substituted or unsubstituted 3 to 8 membered heterocycloalkylene. In embodiments, L 1 is a substituted or unsubstituted C 6 -C 10 arylene. In embodiments, L 1 is a substituted or unsubstituted 5 to 10 membered heteroarylene. In embodiments, L 1 is a substituted C 1 -C 8 alkylene. In embodiments, L 1 is a substituted 2 to 8 membered heteroalkylene. In embodiments, L 1 is a substituted C 3 -C 8 cycloalkylene. In embodiments, L 1 is a substituted 3 to 8 membered heterocycloalkylene. In embodiments, L 1 is a substituted C 6 -C 10 arylene. In embodiments, L 1 is a substituted 5 to 10 membered heteroarylene. In embodiments, L 1 is an unsubstituted C 1 -C 8 alkylene. In embodiments, L 1 is an unsubstituted 2 to 8 membered heteroalkylene. In embodiments, L 1 is an unsubstituted C 3 -C 8 cycloalkylene. In embodiments, L 1 is an unsubstituted 3 to 8 membered heterocycloalkylene. In embodiments, L 1 is an unsubstituted C 6 -C 10 arylene. In embodiments, L 1 is an unsubstituted 5 to 10 membered heteroarylene. In embodiments, L 1 is a substituted or unsubstituted C 1 -C 4 alkylene. In embodiments, L 1 is a substituted or unsubstituted 2 to 4 membered heteroalkylene. In embodiments, L 1 is a substituted or unsubstituted C 3 -C 6 cycloalkylene. In embodiments, L 1 is a substituted or unsubstituted 3 to 6 membered heterocycloalkylene. In embodiments, L 1 is a substituted or unsubstituted phenylene. In embodiments, L 1 is a substituted or unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 1 is a substituted C 1 -C 4 alkylene. In embodiments, L 1 is a substituted 2 to 4 membered heteroalkylene. In embodiments, L 1 is a substituted C 3 -C 6 cycloalkylene. In embodiments, L 1 is a substituted 3 to 6 membered heterocycloalkylene. In embodiments, L 1 is a substituted phenylene. In embodiments, L 1 is a substituted 5 to 6 membered heteroarylene. In embodiments, L 1 is an unsubstituted C 1 -C 4 alkylene. In embodiments, L 1 is an unsubstituted 2 to 4 membered heteroalkylene. In embodiments, L 1 is an unsubstituted C 3 -C 6 cycloalkylene. In embodiments, L 1 is an unsubstituted 3 to 6 membered heterocycloalkylene. In embodiments, L 1 is an unsubstituted phenylene. In embodiments, L 1 is an unsubstituted 5 to 6 membered heteroarylene.

In embodiments, L 1 is a

bond, —S(O) 2 —, —S(O) 2 -Ph-, —NR 6 —, —O—, —S—, —C(O)—, —C(O)NR 6 —, —NR 6 C(O)—, —NR 6 C(O)NH—, —NHC(O)NR—, —C(O)O—, —OC(O)—, R 41 -substituted or unsubstituted alkylene, R 41 -substituted or unsubstituted heteroalkylene, R 41 -substituted or unsubstituted cycloalkylene, R 41 -substituted or unsubstituted heterocycloalkylene, R 41 -substituted or unsubstituted arylene, or R 41 -substituted or unsubstituted heteroarylene. In embodiments, L 1 is a

bond, —S(O) 2 —, —S(O) 2 -Ph-, —NH—, —O—, —S—, —C(O)—, —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —C(O)O—, —OC(O)—, R 41 -substituted or unsubstituted alkylene, R 41 -substituted or unsubstituted heteroalkylene, R 41 -substituted or unsubstituted cycloalkylene, R 41 -substituted or unsubstituted heterocycloalkylene, R 41 -substituted or unsubstituted arylene, or R 41 -substituted or unsubstituted heteroarylene. In embodiments, L 1 is a

bond, —S(O) 2 —, —S(O) 2 -Ph-, —NH—, —O—, —S—, —C(O)—, —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —C(O)O—, —OC(O)—, R 41 -substituted or unsubstituted C 1 -C 8 alkylene, R 41 -substituted or unsubstituted 2 to 8 membered heteroalkylene, R 41 -substituted or unsubstituted C 3 -C 8 cycloalkylene, R 41 -substituted or unsubstituted 3 to 6 membered heterocycloalkylene, R 41 -substituted or unsubstituted phenylene, or R 41 -substituted or unsubstituted 5 to 6 membered heteroarylene.

R 41 is independently oxo,

halogen, —CX 41 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 41 3 , —OCHX 41 2 , R 42 -substituted or unsubstituted alkyl, R 42 -substituted or unsubstituted heteroalkyl, R 42 -substituted or unsubstituted cycloalkyl, R 42 -substituted or unsubstituted heterocycloalkyl, R 42 -substituted or unsubstituted aryl, or R 42 -substituted or unsubstituted heteroaryl. In embodiments, R 41 is independently oxo,

halogen, —CX 41 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 41 3 , —OCHX 41 2 , R 42 -substituted or unsubstituted C 1 -C 8 alkyl, R 42 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 42 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 42 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 42 -substituted or unsubstituted phenyl, or R 42 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 41 is —F, —Cl, —Br, or —I.

R 42 is independently oxo,

halogen, —CX 4 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 42 3 , —OCHX 42 2 , R 43 -substituted or unsubstituted alkyl, R 43 -substituted or unsubstituted heteroalkyl, R 43 -substituted or unsubstituted cycloalkyl, R 43 -substituted or unsubstituted heterocycloalkyl, R 43 -substituted or unsubstituted aryl, or R 43 -substituted or unsubstituted heteroaryl. In embodiments, R 42 is independently oxo,

halogen, —CX 42 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 42 3 , —OCHX 42 2 , R 43 -substituted or unsubstituted C 1 -C 8 alkyl, R 43 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 43 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 43 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 43 -substituted or unsubstituted phenyl, or R 43 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 42 is —F, —Cl, —Br, or —I.

R 43 is independently hydrogen, oxo,

halogen, —CCl 3 , —CBr 3 , —CF 3 , —Cl 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H,

—NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCl 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 43 is independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 43 is independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted C 1 -C 8 alkyl, unsubstituted 2 to 8 membered heteroalkyl, unsubstituted C 3 -C 8 cycloalkyl, unsubstituted 3 to 6 membered heterocycloalkyl, unsubstituted phenyl, or unsubstituted 5 to 6 membered heteroaryl.

In embodiments, L 1 is a bond. In embodiments, L 1 is R 41 -substituted or unsubstituted C 1 -C 2 alkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted C 1 -C 4 alkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted C 1 -C 6 alkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted C 1 -C 8 alkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted alkylene (e.g., C 1 -C 8 alkylene, C 1 -C 6 alkylene, C 1 -C 4 alkylene, C 1 -C 2 alkylene). In embodiments, L 1 is R 41 -substituted C 1 -C 2 alkylene. In embodiments, L 1 is R 41 -substituted C 1 -C 4 alkylene. In embodiments, L 1 is R 41 -substituted C 1 -C 6 alkylene. In embodiments, L 1 is R 41 -substituted C 1 -C 8 alkylene. In embodiments, L 1 is R 41 -substituted alkylene (e.g., C 1 -C 8 alkylene, C 1 -C 6 alkylene, C 1 -C 4 alkylene, C 1 -C 2 alkylene). In embodiments, L 1 is R 41 -substituted methylene. In embodiments, L 1 is unsubstituted C 1 -C 2 alkylene. In embodiments, L 1 is unsubstituted C 1 -C 4 alkylene. In embodiments, L 1 is unsubstituted C 1 -C 6 alkylene. In embodiments, L 1 is unsubstituted C 1 -C 8 alkylene. In embodiments, L 1 is unsubstituted alkylene (e.g., C 1 -C 8 alkylene, C 1 -C 6 alkylene, C 1 -C 4 alkylene, C 1 -C 2 alkylene). In embodiments, L 1 is R 41 -substituted or unsubstituted methylene. In embodiments, L 1 is R 41 -substituted methylene. In embodiments, L 1 is unsubstituted methylene.

In embodiments, L 1 is R 41 -substituted or unsubstituted 2 to 4 membered heteroalkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted 2 to 6 membered heteroalkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted 2 to 8 membered heteroalkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted heteroalkylene (e.g., 2 to 8 membered heteroalkylene, 2 to 6 membered heteroalkylene, 2 to 4 membered heteroalkylene). In embodiments, L 1 is R 41 -substituted 2 to 4 membered heteroalkylene. In embodiments, L 1 is R 41 -substituted 2 to 6 membered heteroalkylene. In embodiments, L 1 is R 41 -substituted 2 to 8 membered heteroalkylene. In embodiments, L 1 is R 41 -substituted heteroalkylene (e.g., 2 to 8 membered heteroalkylene, 2 to 6 membered heteroalkylene, 2 to 4 membered heteroalkylene). In embodiments, L 1 is unsubstituted 2 to 4 membered heteroalkylene. In embodiments, L 1 is unsubstituted 2 to 6 membered heteroalkylene. In embodiments, L 1 is unsubstituted 2 to 8 membered heteroalkylene. In embodiments, L 1 is unsubstituted heteroalkylene (e.g., 2 to 8 membered heteroalkylene, 2 to 6 membered heteroalkylene, 2 to 4 membered heteroalkylene).

In embodiments, L 1 is R 41 -substituted or unsubstituted ethylaminylene. In embodiments, L 1 is R 41 -substituted ethylaminylene. In embodiments, L 1 is unsubstituted ethylaminylene. In embodiments, L 1 is R 41 -substituted or unsubstituted propylaminylene. In embodiments, L 1 is R 41 -substituted propyl aminylene. In embodiments, L 1 is unsubstituted propylaminylene. In embodiments, L 1 is R 41 -substituted or unsubstituted butylaminylene. In embodiments, L 1 is R 41 -substituted butylaminylene. In embodiments, L 1 is unsubstituted butylaminylene.

In embodiments, L 1 is R 41 -substituted or unsubstituted C 3 -C 8 cycloalkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted C 4 -C 6 cycloalkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted C 5 -C 6 cycloalkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted cycloalkylene (e.g., C 3 -C 8 cycloalkylene, C 4 -C 6 cycloalkylene, or C 5 -C 6 cycloalkylene). In embodiments, L 1 is R 41 -substituted C 3 -C 8 cycloalkylene. In embodiments, L 1 is R 41 -substituted C 4 -C 6 cycloalkylene. In embodiments, L 1 is R 41 -substituted C 5 -C 6 cycloalkylene. In embodiments, L 1 is R 41 -substituted cycloalkylene (e.g., C 3 -C 8 cycloalkylene, C 4 -C 6 cycloalkylene, or C 5 -C 6 cycloalkylene). In embodiments, L 1 is unsubstituted C 3 -C 8 cycloalkylene. In embodiments, L 1 is unsubstituted C 4 -C 6 cycloalkylene. In embodiments, L 1 is unsubstituted C 5 -C 6 cycloalkylene. In embodiments, L 1 is unsubstituted cycloalkylene (e.g., C 3 -C 8 cycloalkylene, C 4 -C 6 cycloalkylene, or C 5 -C 6 cycloalkylene).

In embodiments, L 1 is R 41 -substituted or unsubstituted 4 membered heterocycloalkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted 5 membered heterocycloalkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted 6 membered heterocycloalkylene. In embodiments, L 1 is R 41 -substituted or unsubstituted heterocycloalkylene (e.g., 3 to 6 membered heterocycloalkylene, 4 to 6 membered heterocycloalkylene, or 5 to 6 membered heterocycloalkylene). In embodiments, L 1 is R 41 -substituted 4 membered heterocycloalkylene. In embodiments, L 1 is R 41 -substituted 5 membered heterocycloalkylene. In embodiments, L 1 is R 41 -substituted 6 membered heterocycloalkylene. In embodiments, L 1 is R 41 -substituted heterocycloalkylene (e.g., 3 to 6 membered heterocycloalkylene, 4 to 6 membered heterocycloalkylene, or 5 to 6 membered heterocycloalkylene). In embodiments, L 1 is unsubstituted 4 membered heterocycloalkylene. In embodiments, L 1 is unsubstituted 5 membered heterocycloalkylene. In embodiments, L unsubstituted 6 membered heterocycloalkylene. In embodiments, L 1 is unsubstituted heterocycloalkylene (e.g., 3 to 6 membered heterocycloalkylene, 4 to 6 membered heterocycloalkylene, or 5 to 6 membered heterocycloalkylene).

In embodiments, L 1 is R 41 -substituted or unsubstituted arylene (e.g. C 6 -C 10 arylene or C 6 arylene). In embodiments, L 1 is R 41 -substituted or unsubstituted C 6 -C 10 arylene. In embodiments, L 1 is R 41 -substituted or unsubstituted C 6 arylene. In embodiments, L 1 is R 41 -substituted arylene (e.g. C 6 -C 10 arylene or C 6 arylene). In embodiments, L 1 is R 41 -substituted C 6 -C 10 arylene. In embodiments, L 1 is R 41 -substituted C 6 arylene. In embodiments, L 1 is unsubstituted C 6 -C 10 arylene. In embodiments, L 1 is unsubstituted C 6 arylene.

In embodiments, L 1 is R 41 -substituted or unsubstituted heteroarylene (e.g. 5 to 10 membered heteroarylene, 5 to 9 membered heteroarylene, or 5 to 6 membered heteroarylene). In embodiments, L 1 is R 41 -substituted or unsubstituted 5 to 10 membered heteroarylene. In embodiments, L 1 is R 41 -substituted or unsubstituted 5 to 9 membered heteroarylene. In embodiments, L 1 is R 41 -substituted or unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 1 is R 41 -substituted heteroarylene (e.g. 5 to 10 membered heteroarylene, 5 to 9 membered heteroarylene, or 5 to 6 membered heteroarylene). In embodiments, L 1 is R 41 -substituted 5 to 10 membered heteroarylene. In embodiments, L 1 is R 41 -substituted 5 to 9 membered heteroarylene. In embodiments, L 1 is R 41 -substituted 5 to 6 membered heteroarylene. In embodiments, L 1 is unsubstituted heteroarylene (e.g. 5 to 10 membered heteroarylene, 5 to 9 membered heteroarylene, or 5 to 6 membered heteroarylene). In embodiments, L 1 is unsubstituted 5 to 10 membered heteroarylene. In embodiments, L 1 is unsubstituted 5 to 9 membered heteroarylene. In embodiments, L 1 is unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 1 is R 41 -substituted or unsubstituted indolinylene. In embodiments, L 1 is R 41 -substituted or unsubstituted indazolylene. In embodiments, L 1 is R 41 -substituted or unsubstituted benzimidazolylene. In embodiments, L 1 is R 41 -substituted or unsubstituted benzoxazolylene. In embodiments, L 1 is R 41 -substituted or unsubstituted azaindolylene. In embodiments, L 1 is R 41 -substituted or unsubstituted purinylene. In embodiments, L 1 is R 41 -substituted or unsubstituted indolylene. In embodiments, L 1 is R 41 -substituted or unsubstituted pyrazinylene. In embodiments, L 1 is R 41 -substituted or unsubstituted pyrrolylene. In embodiments, L 1 is R 41 -substituted or unsubstituted imidazolylene. In embodiments, L 1 is R 4 -substituted or unsubstituted pyrazolylene. In embodiments, L 1 is R 41 -substituted or unsubstituted triazolylene. In embodiments, L 1 is R 41 -substituted or unsubstituted tetrazolylene.

In embodiments, L 1 is R 41 -substituted indolinylene. In embodiments, L 1 is R 41 -substituted indazolylene. In embodiments, L 1 is R 41 -substituted benzimidazolylene. In embodiments, L 1 is R 41 -substituted benzoxazolylene. In embodiments, L 1 is R 41 -substituted azaindolylene. In embodiments, L 1 is R 41 -substituted purinylene. In embodiments, L 1 is R 41 -substituted indolylene. In embodiments, L 1 is R 41 -substituted pyrazinylene. In embodiments, L 1 is R 41 -substituted pyrrolylene. In embodiments, L 1 is R 41 -substituted imidazolylene. In embodiments, L 1 is R 41 -substituted pyrazolylene. In embodiments, L 1 is R 41 -substituted triazolylene. In embodiments, L 1 is R 41 -substituted tetrazolylene.

In embodiments, L 1 is unsubstituted indolinylene. In embodiments, L 1 is unsubstituted indazolylene. In embodiments, L 1 is unsubstituted benzimidazolylene. In embodiments, L 1 is unsubstituted benzoxazolylene. In embodiments, L 1 is unsubstituted azaindolylene. In embodiments, L 1 is unsubstituted purinylene. In embodiments, L 1 is unsubstituted indolylene. In embodiments, L 1 is unsubstituted pyrazinylene. In embodiments, L 1 is unsubstituted pyrrolylene. In embodiments, L 1 is unsubstituted imidazolylene. In embodiments, L 1 is unsubstituted pyrazolylene. In embodiments, L 1 is unsubstituted triazolylene. In embodiments, L 1 is unsubstituted tetrazolylene.

In embodiments, R 6 is independently hydrogen. In embodiments, R 6 is independently halogen. In embodiments, R 6 is independently —CX 6 3 . In embodiments, R 6 is independently —CHX 6 2 . In embodiments, R 6 is independently —CH 2 X 6 . In embodiments, R 6 is independently —OCX 6 3 . In embodiments, R 6 is independently —OCH 2 X 6 . In embodiments, R 6 is independently —OCHX 6 2 . In embodiments, R 6 is independently —CN. In embodiments, R 6 is independently —SO n6 R 6D . In embodiments, R 6 is independently —SO v6 NR 6A R 6B . In embodiments, R 6 is independently —NHC(O)NR 6A R 6B . In embodiments, R 6 is independently —N(O) m6 . In embodiments, R 6 is independently —NR 6A R 6B . In embodiments, R 6 is independently —C(O)R 6C . In embodiments, R 6 is independently —C(O)—OR 6C . In embodiments, R 6 is independently —C(O)NR 6A R 6B . In embodiments, R 6 is independently —OR 6D . In embodiments, R 6 is independently —NR 6A SO 2 R 6D . In embodiments, R 6 is independently —NR 6A C(O)R 6C . In embodiments, R 6 is independently —NR 6A C(O)OR 6C . In embodiments, R 6 is independently —NR 6A OR 6C . In embodiments, R 6 is independently —OH. In embodiments, R 6 is independently —NH 2 . In embodiments, R 6 is independently —COOH. In embodiments, R 6 is independently —CONH 2 . In embodiments, R 6 is independently —NO 2 . In embodiments, R 6 is independently —SH.

In embodiments, R 6 is independently substituted or unsubstituted alkyl. In embodiments, R 6 is independently substituted or unsubstituted heteroalkyl. In embodiments, R 6 is independently substituted or unsubstituted cycloalkyl. In embodiments, R 6 is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 6 is independently substituted or unsubstituted aryl. In embodiments, R 6 is independently substituted or unsubstituted heteroaryl. In embodiments, R 6 is independently substituted alkyl. In embodiments, R 6 is independently substituted heteroalkyl. In embodiments, R 6 is independently substituted cycloalkyl. In embodiments, R 6 is independently, substituted heterocycloalkyl. In embodiments, R 6 is independently substituted aryl. In embodiments, R 6 is independently substituted heteroaryl. In embodiments, R 6 is independently unsubstituted alkyl. In embodiments, R 6 is independently unsubstituted heteroalkyl. In embodiments, R 6 is independently unsubstituted cycloalkyl. In embodiments, R 6 is independently, unsubstituted heterocycloalkyl. In embodiments, R 6 is independently unsubstituted aryl. In embodiments, R 6 is independently unsubstituted heteroaryl. In embodiments, R 6 is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 6 is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 6 is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 6 is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6 is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 6 is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 6 is independently substituted C 1 -C 8 alkyl. In embodiments, R 6 is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 6 is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 6 is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6 is independently substituted C 6 -C 10 aryl. In embodiments, R 6 is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 6 is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 6 is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 6 is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 6 is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6 is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 6 is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 6 is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 6 is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 6 is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 6 is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6 is independently substituted or unsubstituted phenyl. In embodiments, R 6 is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 6 is independently substituted C 1 -C 4 alkyl. In embodiments, R 6 is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 6 is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 6 is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6 is independently substituted phenyl. In embodiments, R 6 is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 6 is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 6 is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 6 is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 6 is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6 is independently unsubstituted phenyl. In embodiments, R 6 is independently unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 6A is independently hydrogen. In embodiments, R 6A is independently —CX 6A 3 . In embodiments, R 6A is independently —CHX 6A2 . In embodiments, R 6A is independently —CH 2 X 6A . In embodiments, R 6A is independently —CN. In embodiments, R 6A is independently —COOH. In embodiments, R 6A is independently —CONH 2 . In embodiments, R 6A is independently substituted or unsubstituted alkyl. In embodiments, R 6A is independently substituted or unsubstituted heteroalkyl. In embodiments, R 6A is independently substituted or unsubstituted cycloalkyl. In embodiments, R 6A is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 6A is independently substituted or unsubstituted aryl. In embodiments, R 6A is independently substituted or unsubstituted heteroaryl. In embodiments, R 6A is independently substituted alkyl. In embodiments, R 6A is independently substituted heteroalkyl. In embodiments, R 6A is independently substituted cycloalkyl. In embodiments, R 6A is independently, substituted heterocycloalkyl. In embodiments, R 6A is independently substituted aryl. In embodiments, R 6A is independently substituted heteroaryl. In embodiments, R 6A is independently unsubstituted alkyl. In embodiments, R 6A is independently unsubstituted heteroalkyl. In embodiments, R 6A is independently unsubstituted cycloalkyl. In embodiments, R 6A is independently, unsubstituted heterocycloalkyl. In embodiments, R 6A is independently unsubstituted aryl. In embodiments, R 6A is independently unsubstituted heteroaryl. In embodiments, R 6A is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 6A is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 6A is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 6A is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6A is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 6A is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 6A is independently substituted C 1 -C 8 alkyl. In embodiments, R 6A is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 6A is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 6A is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6A is independently substituted C 6 -C 10 aryl. In embodiments, R 6A is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 6A is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 6A is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 6A is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 6A is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6A is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 6A is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 6A is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 6A is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 6A is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 6A is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6A is independently substituted or unsubstituted phenyl. In embodiments, R 6A is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 6A is independently substituted C 1 -C 4 alkyl. In embodiments, R 6A is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 6A is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 6A is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6A is independently substituted phenyl. In embodiments, R 6A is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 6A is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 6A is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 6A is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 6A is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6A is independently unsubstituted phenyl. In embodiments, R 6A is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 6A is independently unsubstituted methyl. In embodiments, R 6A is independently unsubstituted ethyl. In embodiments, R 6A is independently unsubstituted propyl. In embodiments, R 6A is independently unsubstituted isopropyl. In embodiments, R 6A is independently unsubstituted tert-butyl.

In embodiments, R 6B is independently hydrogen. In embodiments, R 6B is independently —CX 6B 3 . In embodiments, R 6B is independently —CHX 6B 2 . In embodiments, R 6B is independently —CH 2 X 6B . In embodiments, R 6B is independently —CN. In embodiments, R 6B is independently —COOH. In embodiments, R 6B is independently —CONH 2 . In embodiments, R 6B is independently substituted or unsubstituted alkyl. In embodiments, R 6B is independently substituted or unsubstituted heteroalkyl. In embodiments, R 6B is independently substituted or unsubstituted cycloalkyl. In embodiments, R 6B is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 6B is independently substituted or unsubstituted aryl. In embodiments, R 6B is independently substituted or unsubstituted heteroaryl. In embodiments, R 6B is independently substituted alkyl. In embodiments, R 6B is independently substituted heteroalkyl. In embodiments, R 6B is independently substituted cycloalkyl. In embodiments, R 6B is independently, substituted heterocycloalkyl. In embodiments, R 6B is independently substituted aryl. In embodiments, R 6B is independently substituted heteroaryl. In embodiments, R 6B is independently unsubstituted alkyl. In embodiments, R 6B is independently unsubstituted heteroalkyl. In embodiments, R 6B is independently unsubstituted cycloalkyl. In embodiments, R 6B is independently, unsubstituted heterocycloalkyl. In embodiments, R 6B is independently unsubstituted aryl. In embodiments, R 6B is independently unsubstituted heteroaryl. In embodiments, R 6B is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 6B is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 6B is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 6B is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6B is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 6B is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 6B is independently substituted C 1 -C 8 alkyl. In embodiments, R 6B is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 6B is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 6B is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6B is independently substituted C 6 -C 10 aryl. In embodiments, R 6B is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 6B is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 6B is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 6B is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 6B is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6B is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 6B is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 6B is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 6B is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 6B is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 6B is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6B is independently substituted or unsubstituted phenyl. In embodiments, R 6B is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 6B is independently substituted C 1 -C 4 alkyl. In embodiments, R 6B is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 6B is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 6B is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6B is independently substituted phenyl. In embodiments, R 6B is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 6B is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 6B is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 6B is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 6B is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6B is independently unsubstituted phenyl. In embodiments, R 6B is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 6B is independently unsubstituted methyl. In embodiments, R 6B is independently unsubstituted ethyl. In embodiments, R 6B is independently unsubstituted propyl. In embodiments, R 6B is independently unsubstituted isopropyl. In embodiments, R 6B is independently unsubstituted tert-butyl.

In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heterocycloalkyl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heteroaryl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form a substituted heterocycloalkyl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form a substituted heteroaryl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heterocycloalkyl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heteroaryl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to forma substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 10 membered heteroaryl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 6 membered heteroaryl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 6C is independently hydrogen. In embodiments, R 6C is independently —CX 6C 3 . In embodiments, R 6C is independently —CHX 6C 2 . In embodiments, R 6C is independently —CH 2 X 6C . In embodiments, R 6C is independently —CN. In embodiments, R 6C is independently —COOH. In embodiments, R 6C is independently —CONH 2 . In embodiments, R 6C is independently substituted or unsubstituted alkyl. In embodiments, R 6C is independently substituted or unsubstituted heteroalkyl. In embodiments, R 6C is independently substituted or unsubstituted cycloalkyl. In embodiments, R 6C is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 6C is independently substituted or unsubstituted aryl. In embodiments, R 6C is independently substituted or unsubstituted heteroaryl. In embodiments, R 6C is independently substituted alkyl. In embodiments, R 6C is independently substituted heteroalkyl. In embodiments, R 6C is independently substituted cycloalkyl. In embodiments, R 6C is independently, substituted heterocycloalkyl. In embodiments, R 6C is independently substituted aryl. In embodiments, R 6C is independently substituted heteroaryl. In embodiments, R 6C is independently unsubstituted alkyl. In embodiments, R 6C is independently unsubstituted heteroalkyl. In embodiments, R 6C is independently unsubstituted cycloalkyl. In embodiments, R 6C is independently, unsubstituted heterocycloalkyl. In embodiments, R 6C is independently unsubstituted aryl. In embodiments, R 6C is independently unsubstituted heteroaryl. In embodiments, R 6C is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 6C is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 6C is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 6C is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6C is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 6C is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 6C is independently substituted C 1 -C 8 alkyl. In embodiments, R 6C is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 6C is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 6C is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6C is independently substituted C 6 -C 10 aryl. In embodiments, R 6C is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 6C is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 6C is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 6C is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 6C is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6C is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 6C is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 6C is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 6C is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 6C is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 6C is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6C is independently substituted or unsubstituted phenyl. In embodiments, R 6C is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 6C is independently substituted C 1 -C 4 alkyl. In embodiments, R 6C is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 6C is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 6C is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6C is independently substituted phenyl. In embodiments, R 6C is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 6C is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 6C is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 6C is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 6C is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6C is independently unsubstituted phenyl. In embodiments, R 6C is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 6C is independently unsubstituted methyl. In embodiments, R 6C is independently unsubstituted ethyl. In embodiments, R 6C is independently unsubstituted propyl. In embodiments, R 6C is independently unsubstituted isopropyl. In embodiments, R 6C is independently unsubstituted tert-butyl.

In embodiments, R 6D is independently hydrogen. In embodiments, R 6D is independently —CX 6D 3 . In embodiments, R 6D is independently —CHX 6D 2 . In embodiments, R 6D is independently —CH 2 X 6D . In embodiments, R 6D is independently —CN. In embodiments, R 6D is independently —COOH. In embodiments, R 6D is independently —CONH 2 . In embodiments, R 6D is independently substituted or unsubstituted alkyl. In embodiments, R 6D is independently substituted or unsubstituted heteroalkyl. In embodiments, R 6D is independently substituted or unsubstituted cycloalkyl. In embodiments, R 6D is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 6D is independently substituted or unsubstituted aryl. In embodiments, R 6D is independently substituted or unsubstituted heteroaryl. In embodiments, R 6D is independently substituted alkyl. In embodiments, R 6D is independently substituted heteroalkyl. In embodiments, R 6D is independently substituted cycloalkyl. In embodiments, R 6D is independently, substituted heterocycloalkyl. In embodiments, R 6D is independently substituted aryl. In embodiments, R 6D is independently substituted heteroaryl. In embodiments, R 6D is independently unsubstituted alkyl. In embodiments, R 6D is independently unsubstituted heteroalkyl. In embodiments, R 6D is independently unsubstituted cycloalkyl. In embodiments, R 6D is independently, unsubstituted heterocycloalkyl. In embodiments, R 6D is independently unsubstituted aryl. In embodiments, R 6D is independently unsubstituted heteroaryl. In embodiments, R 6D is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 6D is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 6D is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 6D is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6D is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 6D is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 6D is independently substituted C 1 -C 8 alkyl. In embodiments, R 6D is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 6D is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 6D is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6D is independently substituted C 6 -C 10 aryl. In embodiments, R 6D is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 6D is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 6D is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 6D is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 6D is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 6D is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 6D is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 6D is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 6D is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 6D is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 6D is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6D is independently substituted or unsubstituted phenyl. In embodiments, R 6D is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 6D is independently substituted C 1 -C 4 alkyl. In embodiments, R 6D is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 6D is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 6D is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6D is independently substituted phenyl. In embodiments, R 6D is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 6D is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 6D is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 6D is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 6D is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 6D is independently unsubstituted phenyl. In embodiments, R 6D is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 6D is independently unsubstituted methyl. In embodiments, R 6D is independently unsubstituted ethyl. In embodiments, R 6D is independently unsubstituted propyl. In embodiments, R 6D is independently unsubstituted isopropyl. In embodiments, R 6D is independently unsubstituted tert-butyl.

In embodiments, R 6 is independently hydrogen,

halogen, —CX 6 3 , —CHX 6 2 , —CH 2 X 6 , —OCX 6 3 , —OCH 2 X 6 , —OCHX 6 2 , —CN, —SO n6 R 6D , —SO v6 NR 6A R 6B , —NHC(O)NR 6A R 6B , —N(O) m6 , —NR 6A R 6B , —C(O)R 6C , —C(O)OR 6C , —C(O)NR 6A R 6B , —OR 6D , —NR 6A SO 2 R 6D , —NR 6A C(O)R 6C , —NR 6A C(O)OR 6C , —NR 6A OR 6C , R 35 -substituted or unsubstituted alkyl, R 35 -substituted or unsubstituted heteroalkyl, R 35 -substituted or unsubstituted cycloalkyl, R 35 -substituted or unsubstituted heterocycloalkyl, R 35 -substituted or unsubstituted aryl, or R 35 -substituted or unsubstituted heteroaryl. In embodiments, R 6 is independently halogen, —CX 6 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 63 , —OCHX 62 , R 35 -substituted or unsubstituted alkyl, R 35 -substituted or unsubstituted heteroalkyl, R 35 -substituted or unsubstituted cycloalkyl, R 35 -substituted or unsubstituted heterocycloalkyl, R 35 -substituted or unsubstituted aryl, or R 35 -substituted or unsubstituted heteroaryl. In embodiments, R 6 is independently

halogen, —CX 6 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 6 3 , —OCHX 6 2 , R 35 -substituted or unsubstituted C 1 -C 8 alkyl, R 35 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 35 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 35 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 35 -substituted or unsubstituted phenyl, or R 35 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 6 is —F, —Cl, —Br, or —I. In embodiments, R 6 is independently hydrogen. In embodiments, R 6 is independently methyl. In embodiments, R 6 is independently ethyl.

R 35 is independently oxo,

halogen, —CX 35 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 35 3 , —OCHX 35 2 , R 36 -substituted or unsubstituted alkyl, R 36 -substituted or unsubstituted heteroalkyl, R 36 -substituted or unsubstituted cycloalkyl, R 36 -substituted or unsubstituted heterocycloalkyl, R 36 -substituted or unsubstituted aryl, or R 36 -substituted or unsubstituted heteroaryl. In embodiments, R 35 is independently oxo,

halogen, —CX 35 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 35 3 , —OCHX 35 2 , R 36 -substituted or unsubstituted C 1 -C 8 alkyl, R 36 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 36 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 36 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 36 -substituted or unsubstituted phenyl, or R 36 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 35 is —F, —Cl, —Br, or —I.

R 36 is independently oxo,

halogen, —CX 36 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 36 3 , —OCHX 36 2 , R 37C -substituted or unsubstituted alkyl, R 37C -substituted or unsubstituted heteroalkyl, R 37C -substituted or unsubstituted cycloalkyl, R 37C -substituted or unsubstituted heterocycloalkyl, R 37C -substituted or unsubstituted aryl, or R 37C -substituted or unsubstituted heteroaryl. In embodiments, R 36 is independently oxo,

halogen, —CX 36 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 36 3, —OCHX 36 2, R 37C -substituted or unsubstituted C 1 -C 8 alkyl, R 37C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 37C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 37C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 37C -substituted or unsubstituted phenyl, or R 37C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 36 is —F, —Cl, —Br, or —I.

In embodiments, R 6A is independently

hydrogen, —CX 6A 3 , —CN, —COOH, —CONH 2 , —CHX 6A 2 , —CH 2 X 6A , R 35A -substituted or unsubstituted alkyl, R 35A -substituted or unsubstituted heteroalkyl, R 35A -substituted or unsubstituted cycloalkyl, R 35A -substituted or unsubstituted heterocycloalkyl, R 35A -substituted or unsubstituted aryl, or R 35A -substituted or unsubstituted heteroaryl. In embodiments, R 6A is independently hydrogen, —CX 6A 3 , —CN, —COOH, —CONH 2 , —CHX 6A 2 , —CH 2 X 6A , R 35A -substituted or unsubstituted C 1 -C 8 alkyl, R 35A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 35A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 35A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 35A -substituted or unsubstituted phenyl, or R 35A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 6A is —F, —Cl, —Br, or —I. In embodiments, R 6A is independently hydrogen. In embodiments, R 6A is independently methyl. In embodiments, R 6A is independently ethyl.

In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may optionally be joined to form a R 35A -substituted or unsubstituted heterocycloalkyl or R 35A -substituted or unsubstituted heteroaryl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may optionally be joined to form a R 35A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 35A -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 35A is independently oxo,

halogen, —CX 35A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 35A 3 , —OCHX 35A 2 , R 36A -substituted or unsubstituted alkyl, R 36A -substituted or unsubstituted heteroalkyl, R 36A -substituted or unsubstituted cycloalkyl, R 36A -substituted or unsubstituted heterocycloalkyl, R 36A -substituted or unsubstituted aryl, or R 36A -substituted or unsubstituted heteroaryl. In embodiments, R 35A is independently oxo,

halogen, —CX 35A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 35A 3 , —OCHX 35A 2 , R 36A -substituted or unsubstituted C 1 -C 8 alkyl, R 36A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 36A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 36A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 36A -substituted or unsubstituted phenyl, or R 36A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 35A is —F, —Cl, —Br, or —I.

R 36A is independently oxo,

halogen, —CX 36A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 36A 3 , —OCHX 36A 2 , R 37A -substituted or unsubstituted alkyl, R 37A -substituted or unsubstituted heteroalkyl, R 37A -substituted or unsubstituted cycloalkyl, R 37A -substituted or unsubstituted heterocycloalkyl, R 37A -substituted or unsubstituted aryl, or R 37A -substituted or unsubstituted heteroaryl. In embodiments, R 36A is independently oxo,

halogen, —CX 36A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 36A 3 , —OCHX 36A 2 , R 37A -substituted or unsubstituted C 1 -C 8 alkyl, R 37A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 37A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 37A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 37A -substituted or unsubstituted phenyl, or R 37A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 36A is —F, —Cl, —Br, or —I.

In embodiments, R 6B is independently

hydrogen, —CX 6B 3 , —CN, —COOH, —CONH 2 , —CHX 6B 2 , —CH 2 X 6B , R 35B -substituted or unsubstituted alkyl, R 35B -substituted or unsubstituted heteroalkyl, R 35B -substituted or unsubstituted cycloalkyl, R 35B -substituted or unsubstituted heterocycloalkyl, R 35B -substituted or unsubstituted aryl, or R 35B -substituted or unsubstituted heteroaryl. In embodiments, R 6B is independently hydrogen, —CX 6B 3 , —CN, —COOH, —CONH 2 , —CHX 6B 2 , —CH 2 X 6B , R 35B -substituted or unsubstituted C 1 -C 8 alkyl, R 35B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 35B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 35B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 35B -substituted or unsubstituted phenyl, or R 35B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 6B is —F, —Cl, —Br, or —I. In embodiments, R 6B is independently hydrogen. In embodiments, R 6B is independently methyl. In embodiments, R 6B is independently ethyl.

In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may optionally be joined to form a R 35B -substituted or unsubstituted heterocycloalkyl or R 35B -substituted or unsubstituted heteroaryl. In embodiments, R 6A and R 6B substituents bonded to the same nitrogen atom may optionally be joined to form a R 35B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 35B -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 35B is independently oxo,

halogen, —CX 35B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 35B 3 , —OCHX 35B 2 , R 36B -substituted or unsubstituted alkyl, R 36B -substituted or unsubstituted heteroalkyl, R 36B -substituted or unsubstituted cycloalkyl, R 36B -substituted or unsubstituted heterocycloalkyl, R 36B -substituted or unsubstituted aryl, or R 36B -substituted or unsubstituted heteroaryl. In embodiments, R 35B is independently oxo,

halogen, —CX 35B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 35B 3 , —OCHX 35B 2 , R 36B -substituted or unsubstituted C 1 -C 8 alkyl, R 36B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 36B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 36B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 36B -substituted or unsubstituted phenyl, or R 36B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 35B is —F, —Cl, —Br, or —I.

R 36B is independently oxo,

halogen, —CX 36B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 36B 3 , —OCHX 36B 2 , R 37B -substituted or unsubstituted alkyl, R 37B -substituted or unsubstituted heteroalkyl, R 37B -substituted or unsubstituted cycloalkyl, R 37B -substituted or unsubstituted heterocycloalkyl, R 37B -substituted or unsubstituted aryl, or R 37B -substituted or unsubstituted heteroaryl. In embodiments, R 36B is independently oxo,

halogen, —CX 36B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 36B 3 , —OCHX 36B 2 , R 37B -substituted or unsubstituted C 1 -C 8 alkyl, R 37B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 37B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 37B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 37B -substituted or unsubstituted phenyl, or R 37B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 36B is —F, —Cl, —Br, or —I.

In embodiments, R 6C is independently

hydrogen, —CX 6C 3 , —CN, —COOH, —CONH 2 , —CHX 62 , —CH 2 X 6C , R 35C -substituted or unsubstituted alkyl, R 35C -substituted or unsubstituted heteroalkyl, R 35C -substituted or unsubstituted cycloalkyl, R 35C -substituted or unsubstituted heterocycloalkyl, R 35C -substituted or unsubstituted aryl, or R 35C -substituted or unsubstituted heteroaryl. In embodiments, R 6C is independently hydrogen, —CX 6C 3 , —CN, —COOH, —CONH 2 , —CHX 62 , —CH 2 X 6C , R 35C -substituted or unsubstituted C 1 -C 8 alkyl, R 35C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 35C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 35C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 35C -substituted or unsubstituted phenyl, or R 35C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 6C is —F, —Cl, —Br, or —I. In embodiments, R 6C is independently hydrogen. In embodiments, R 6C is independently methyl. In embodiments, R 6C is independently ethyl.

R 35C is independently oxo,

halogen, —CX 35C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 35C 3 , —OCHX 35 2 , R 36C -substituted or unsubstituted alkyl, R 36C -substituted or unsubstituted heteroalkyl, R 36C -substituted or unsubstituted cycloalkyl, R 36C -substituted or unsubstituted heterocycloalkyl, R 36C -substituted or unsubstituted aryl, or R 36C -substituted or unsubstituted heteroaryl. In embodiments, R 35C is independently oxo,

halogen, —CX 35C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 35C 3 , OCHX 35C 2 , R 36C -substituted or unsubstituted C 1 -C 8 alkyl, R 36 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 36C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 36C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 36 -substituted or unsubstituted phenyl, or R 36C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 35C is —F, —Cl, —Br, or —I.

R 36C is independently oxo,

halogen, —CX 36 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 36C 3 , —OCHX 36 2 , R 37C -substituted or unsubstituted alkyl, R 37C -substituted or unsubstituted heteroalkyl, R 37C -substituted or unsubstituted cycloalkyl, R 37C -substituted or unsubstituted heterocycloalkyl, R 37C -substituted or unsubstituted aryl, or R 37C -substituted or unsubstituted heteroaryl. In embodiments, R 36C is independently oxo,

halogen, —CX 36 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 36C 3 , —OCHX 36 2 , R 37C -substituted or unsubstituted C 1 -C 8 alkyl, R 37C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 37C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 37C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 37C -substituted or unsubstituted phenyl, or R 37C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 36C is —F, —Cl, —Br, or —I.

In embodiments, R 6D is independently

hydrogen, —CX 6D 3 , —CN, —COOH, —CONH 2 , —CHX 6D2 , —CH 2 X 6D , R 3D -substituted or unsubstituted alkyl, R 35D -substituted or unsubstituted heteroalkyl, R 35D -substituted or unsubstituted cycloalkyl, R 35D -substituted or unsubstituted heterocycloalkyl, R 35D -substituted or unsubstituted aryl, or R 35D -substituted or unsubstituted heteroaryl. In embodiments, R 6D is independently hydrogen, —CX 6D 3 , —CN, —COOH, —CONH 2 , —CHX 6D 2 , —CH 2 X 6D , R 35D -substituted or unsubstituted C 1 -C 8 alkyl, R 35D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 35D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 35D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 3D -substituted or unsubstituted phenyl, or R 35D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 6D is —F, —Cl, —Br, or —I. In embodiments, R 6D is independently hydrogen. In embodiments, R 6D is independently methyl. In embodiments, R 6D is independently ethyl.

R 35D is independently oxo,

halogen, —CX 35D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 35D 3 , —OCHX 35D 2 , R 36D -substituted or unsubstituted alkyl, R 36D -substituted or unsubstituted heteroalkyl, R 36D -substituted or unsubstituted cycloalkyl, R 36D -substituted or unsubstituted heterocycloalkyl, R 36D -substituted or unsubstituted aryl, or R 36D -substituted or unsubstituted heteroaryl. In embodiments, R 35D is independently oxo,

halogen, —CX 35D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 35D 3 , —OCHX 35D 2 , R 36D -substituted or unsubstituted C 1 -C 8 alkyl, R 36D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 36D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 36D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 36D -substituted or unsubstituted phenyl, or R 36D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 35D is —F, —Cl, —Br, or —I.

R 36D is independently oxo,

halogen, —CX 36D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 36D 3 , —OCHX 36D 2 , R 37D -substituted or unsubstituted alkyl, R 37D -substituted or unsubstituted heteroalkyl, R 37D -substituted or unsubstituted cycloalkyl, R 37D -substituted or unsubstituted heterocycloalkyl, R 37D -substituted or unsubstituted aryl, or R 37D -substituted or unsubstituted heteroaryl. In embodiments, R 36D is independently oxo,

halogen, —CX 36D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 36D 3 , —OCHX 36D 2 , R 37D -substituted or unsubstituted C 1 -C 8 alkyl, R 37D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 37D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 37D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 37D -substituted or unsubstituted phenyl, or R 37D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 36D is —F, —Cl, —Br, or —I.

R 37 , R 37A , R 37B , R 37C , and R 37D are independently hydrogen, oxo,

halogen, —CCl 3 , —CBr 3 , —CF 3 , —Cl 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H,

—NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCl 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 37 , R 37A , R 37B , R 37C , and R 37D are independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 37 , R 37A , R 37B , R 37C , and R 37D are independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted C 1 -C 8 alkyl, unsubstituted 2 to 8 membered heteroalkyl, unsubstituted C 3 -C 8 cycloalkyl, unsubstituted 3 to 6 membered heterocycloalkyl, unsubstituted phenyl, or unsubstituted 5 to 6 membered heteroaryl.

In embodiments, L 1 is given by the formula L 100 -L 108 .

L 100 is a

bond, —S(O) 2 —, —S(O) 2 -Ph-, —NR 101 —, —O—, —S—, —C(O)—, —C(O)NR 101 —, —NR 101 C(O)—, —NR 101 C(O)NH—, —NHC(O)NR 101 —, —C(O)O—, —OC(O)—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene. R 101 is hydrogen, halogen, —CX 101 3 , —CHX 101 2 , —CH 2 X 101 , —OCX 101 3 , —

OCH 2 X 101 , —OCHX 101 2 , —CN, —SO n101 R 101D , —SO v101 NR 101A R 101B , —NHC(O)NR 101A R 101B , —N(O) m101 , —NR 101A R 101B , —C(O)R 101C , —C(O)—OR 101C , —C(O)NR 101A R 101B , —OR 101D , —NR 101A SO 2 R 101D , —NR 101A C(O)R 101C , —NR 101A C(O)OR 101C , —NR 101A OR 101C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. The symbols v101 and m101 are independently an integer from 1 to 2. The symbol n101 is an integer from 0 to 4.

L 108 is a

bond, —S(O) 2 —, —S(O) 2 -Ph-, —NR 109A —, —O—, —S—, —C(O)—, —C(O)NR 109A —, —NR 109 C(O)—, —NR 109 C(O)NH—, —NHC(O)NR 109A —, —C(O)O—, —OC(O)—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene. R 109 is hydrogen, halogen, —CX 109 3 , —CHX 109 2 , —CH 2 X 109 , —OCX 109 3 , —

OCH 2 X 109 , —OCHX 109 2 , —CN, —SO n109 R 109D , —SO v109 NR 109A R 109B , —NHC(O)NR 109A R 109B , —N(O) m109 , —NR 109A R 109B , —C(O)R 109C , —C(O)—OR 109C , —C(O)NR 109A R 109B , —OR 109D , —NR 109A SO 2 R 109D , —NR 109A C(O)R 109C , —NR 109A C(O)OR 109C , —NR 109A OR 109C , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. The symbols v109 and m109 are independently an integer from 1 to 2. The symbol n109 is an integer from 0 to 4.

In embodiments, L 100 is a bond, —S(O) 2 —, —S(O) 2 -Ph-, substituted or unsubstituted C 1 -C 8 alkylene, substituted or unsubstituted 2 to 8 membered heteroalkylene, substituted or unsubstituted C 3 -C 8 cycloalkylene, substituted or unsubstituted 3 to 8 membered heterocycloalkylene, substituted or unsubstituted phenylene, or substituted or unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 100 is a bond. In embodiments, L 100 is a substituted or unsubstituted C 1 -C 6 alkylene, substituted or unsubstituted 2 to 6 membered heteroalkylene, substituted or unsubstituted C 3 -C 6 cycloalkylene, substituted or unsubstituted 3 to 6 membered heterocycloalkylene, substituted or unsubstituted phenylene, or substituted or unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 100 is an unsubstituted C 1 -C 6 alkylene, unsubstituted 2 to 6 membered heteroalkylene, or unsubstituted C 3 -C 6 cycloalkylene. In embodiments, L 100 is an unsubstituted methylene.

In embodiments, L 100 is a bond. In embodiments, L 100 is —S(O) 2 —. In embodiments, L 100 is —S(O) 2 -Ph-. In embodiments, L 100 is —NR 101 —. In embodiments, L 100 is —O—. In embodiments, L 100 is —S—. In embodiments, L 100 is —C(O)—. In embodiments, L 100 is —C(O)NR 101 —. In embodiments, L 100 is —NR 101 C(O)—. In embodiments, L 100 is —NR 10 C(O)NH—. In embodiments, L 100 is —NHC(O)NR 101 —. In embodiments, L 100 is —C(O)O—. In embodiments, L 100 is —OC(O)—. In embodiments, L 100 is —NH—. In embodiments, L 100 is —C(O)NH—. In embodiments, L 100 is —NHC(O)—. In embodiments, L 100 is —NHC(O)NH—. In embodiments, L 100 is —CH 2 —. In embodiments, L 100 is —OCH 2 —. In embodiments, L 100 is —CH 2 O—. In embodiments, L 100 is —CH 2 CH 2 —. In embodiments, L 100 is —SCH 2 —. In embodiments, L 100 is —CH 2 S—. In embodiments, L 100 is —CHCH—. In embodiments, L 100 is —CC—. In embodiments, L 100 is —NHCH 2 —. In embodiments, L 100 is —CH 2 NH—.

In embodiments, L 100 is a substituted or unsubstituted alkylene. In embodiments, L 100 is a substituted or unsubstituted heteroalkylene. In embodiments, L 100 is a substituted or unsubstituted cycloalkylene. In embodiments, L 100 is a substituted or unsubstituted heterocycloalkylene. In embodiments, L 100 is a substituted or unsubstituted arylene. In embodiments, L 100 is a substituted or unsubstituted heteroarylene. In embodiments, L 100 is a substituted alkylene. In embodiments, L 100 is a substituted heteroalkylene. In embodiments, L 100 is a substituted cycloalkylene. In embodiments, L 100 is a substituted heterocycloalkylene. In embodiments, L 100 is a substituted arylene. In embodiments, L 100 is a substituted heteroarylene. In embodiments, L 100 is an unsubstituted alkylene. In embodiments, L 100 is an unsubstituted heteroalkylene. In embodiments, L 100 is an unsubstituted cycloalkylene. In embodiments, L 100 is an unsubstituted heterocycloalkylene. In embodiments, L 100 is an unsubstituted arylene. In embodiments, L 100 is an unsubstituted heteroarylene. In embodiments, L 100 is a substituted or unsubstituted C 1 -C 8 alkylene. In embodiments, L 100 is a substituted or unsubstituted 2 to 8 membered heteroalkylene. In embodiments, L 100 is a substituted or unsubstituted C 3 -C 8 cycloalkylene. In embodiments, L 100 is a substituted or unsubstituted 3 to 8 membered heterocycloalkylene. In embodiments, L 100 is a substituted or unsubstituted C 6 -C 10 arylene. In embodiments, L 100 is a substituted or unsubstituted 5 to 10 membered heteroarylene. In embodiments, L 100 is a substituted C 1 -C 8 alkylene. In embodiments, L 100 is a substituted 2 to 8 membered heteroalkylene. In embodiments, L 100 is a substituted C 3 -C 8 cycloalkylene. In embodiments, L 100 is a substituted 3 to 8 membered heterocycloalkylene. In embodiments, L 100 is a substituted C 6 -C 10 arylene. In embodiments, L 100 is a substituted 5 to 10 membered heteroarylene. In embodiments, L 100 is an unsubstituted C 1 -C 8 alkylene. In embodiments, L 100 is an unsubstituted 2 to 8 membered heteroalkylene. In embodiments, L 100 is an unsubstituted C 3 -C 8 cycloalkylene. In embodiments, L 100 is an unsubstituted 3 to 8 membered heterocycloalkylene. In embodiments, L 100 is an unsubstituted C 6 -C 10 arylene. In embodiments, L 100 is an unsubstituted 5 to 10 membered heteroarylene. In embodiments, L 100 is a substituted or unsubstituted C 1 -C 4 alkylene. In embodiments, L 100 is a substituted or unsubstituted 2 to 4 membered heteroalkylene. In embodiments, L 100 is a substituted or unsubstituted C 3 -C 6 cycloalkylene. In embodiments, L 100 is a substituted or unsubstituted 3 to 6 membered heterocycloalkylene. In embodiments, L 100 is a substituted or unsubstituted phenylene. In embodiments, L 100 is a substituted or unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 100 is a substituted C 1 -C 4 alkylene. In embodiments, L 100 is a substituted 2 to 4 membered heteroalkylene. In embodiments, L 100 is a substituted C 3 -C 6 cycloalkylene. In embodiments, L 100 is a substituted 3 to 6 membered heterocycloalkylene. In embodiments, L 100 is a substituted phenylene. In embodiments, L 100 is a substituted 5 to 6 membered heteroarylene. In embodiments, L 100 is an unsubstituted C 1 -C 4 alkylene. In embodiments, L 100 is an unsubstituted 2 to 4 membered heteroalkylene. In embodiments, L 100 is an unsubstituted C 3 -C 6 cycloalkylene. In embodiments, L 100 is an unsubstituted 3 to 6 membered heterocycloalkylene. In embodiments, L 100 is an unsubstituted phenylene. In embodiments, L 100 is an unsubstituted 5 to 6 membered heteroarylene.

In embodiments, L 100 is a

bond, —S(O) 2 —, —S(O) 2 -Ph-, —NR 101 —, —O—, —S—, —C(O)—, —C(O)NR 101 —, —NR 101 C(O)—, —NR 101 C(O)NH—, —NHC(O)NR 101 —, —C(O)O—, —OC(O)—, R 105 -substituted or unsubstituted alkylene, R 105 -substituted or unsubstituted heteroalkylene, R 105 -substituted or unsubstituted cycloalkylene, R 105 -substituted or unsubstituted heterocycloalkylene, R 105 -substituted or unsubstituted arylene, or R 105 -substituted or unsubstituted heteroarylene. In embodiments, L 100 is a bond, —S(O) 2 —, —S(O) 2 -Ph-, —NH—, —O—, —S—, —C(O)—, —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —C(O)O—, —OC(O)—, R 105 -substituted or unsubstituted alkylene, R 105 -substituted or unsubstituted heteroalkylene, R 105 -substituted or unsubstituted cycloalkylene, R 105 -substituted or unsubstituted heterocycloalkylene, R 105 -substituted or unsubstituted arylene, or R 105 -substituted or unsubstituted heteroarylene. In embodiments, L 100 is a bond, —S(O) 2 —, —S(O) 2 -Ph-, —NH—, —O—, —S—, —C(O)—, —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —C(O)O—, —OC(O)—, R 10 -substituted or unsubstituted C 1 -C 8 alkylene, R 105 -substituted or unsubstituted 2 to 8 membered heteroalkylene, R 105 -substituted or unsubstituted C 3 -C 8 cycloalkylene, R 105 -substituted or unsubstituted 3 to 6 membered heterocycloalkylene, R 105 -substituted or unsubstituted phenylene, or R 105 -substituted or unsubstituted 5 to 6 membered heteroarylene.

R 105 is independently oxo,

halogen, —CX 105 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 105 3 , —OCHX 105 2 , R 106 -substituted or unsubstituted alkyl, R 106 -substituted or unsubstituted heteroalkyl, R 106 -substituted or unsubstituted cycloalkyl, R 106 -substituted or unsubstituted heterocycloalkyl, R 106 -substituted or unsubstituted aryl, or R 106 -substituted or unsubstituted heteroaryl. In embodiments, R 105 is independently oxo,

halogen, —CX 105 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 105 3 , —OCHX 105 2 , R 106 -substituted or unsubstituted C 1 -C 8 alkyl, R 106 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 106 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 106 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 106 -substituted or unsubstituted phenyl, or R 106 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 105 is —F, —Cl, —Br, or —I.

R 106 is independently oxo,

halogen, —CX 106 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 106 3 , —OCHX 106 2 , R 107 -substituted or unsubstituted alkyl, R 107 -substituted or unsubstituted heteroalkyl, R 107 -substituted or unsubstituted cycloalkyl, R 107 -substituted or unsubstituted heterocycloalkyl, R 107 -substituted or unsubstituted aryl, or R 107 -substituted or unsubstituted heteroaryl. In embodiments, R 106 is independently oxo,

halogen, —CX 106 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 106 3 , —OCHX 106 2 , R 107 -substituted or unsubstituted C 1 -C 8 alkyl, R 107 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 107 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 107 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 107 -substituted or unsubstituted phenyl, or R 107 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 106 is —F, —Cl, —Br, or —I.

R 107 is independently hydrogen, oxo,

halogen, —CCl 3 , —CBr 3 , —CF 3 , —Cl 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H,

—NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCl 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 107 is independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 107 is independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted C 1 -C 8 alkyl, unsubstituted 2 to 8 membered heteroalkyl, unsubstituted C 3 -C 8 cycloalkyl, unsubstituted 3 to 6 membered heterocycloalkyl, unsubstituted phenyl, or unsubstituted 5 to 6 membered heteroaryl.

In embodiments, L 100 is a bond. In embodiments, L 100 is R 105 -substituted or unsubstituted C 1 -C 2 alkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted C 1 -C 4 alkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted C 1 -C 6 alkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted C 1 -C 8 alkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted alkylene (e.g., C 1 -C 8 alkylene, C 1 -C 6 alkylene, C 1 -C 4 alkylene, C 1 -C 2 alkylene). In embodiments, L 100 is R 105 -substituted C 1 -C 2 alkylene. In embodiments, L 100 is R 105 -substituted C 1 -C 4 alkylene. In embodiments, L 100 is R 105 -substituted C 1 -C 6 alkylene. In embodiments, L 100 is R 105 -substituted C 1 -C 8 alkylene. In embodiments, L 100 is R 105 -substituted alkylene (e.g., C 1 -C 8 alkylene, C 1 -C 6 alkylene, C 1 -C 4 alkylene, C 1 -C 2 alkylene). In embodiments, L 100 is R 105 -substituted methylene. In embodiments, L 100 is unsubstituted C 1 -C 2 alkylene. In embodiments, L 100 is unsubstituted C 1 -C 4 alkylene. In embodiments, L 100 is unsubstituted C 1 -C 6 alkylene. In embodiments, L 100 is unsubstituted C 1 -C 8 alkylene. In embodiments, L 100 is unsubstituted alkylene (e.g., C 1 -C 8 alkylene, C 1 -C 6 alkylene, C 1 -C 4 alkylene, C 1 -C 2 alkylene). In embodiments, L 100 is R 105 -substituted or unsubstituted methylene. In embodiments, L 100 is R 105 -substituted methylene. In embodiments, L 100 is unsubstituted methylene.

In embodiments, L 100 is R 105 -substituted or unsubstituted 2 to 4 membered heteroalkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted 2 to 6 membered heteroalkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted 2 to 8 membered heteroalkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted heteroalkylene (e.g., 2 to 8 membered heteroalkylene, 2 to 6 membered heteroalkylene, 2 to 4 membered heteroalkylene). In embodiments, L 100 is R 105 -substituted 2 to 4 membered heteroalkylene. In embodiments, L 100 is R 105 -substituted 2 to 6 membered heteroalkylene. In embodiments, L 100 is R 105 -substituted 2 to 8 membered heteroalkylene. In embodiments, L 100 is R 105 -substituted heteroalkylene (e.g., 2 to 8 membered heteroalkylene, 2 to 6 membered heteroalkylene, 2 to 4 membered heteroalkylene). In embodiments, L 100 is unsubstituted 2 to 4 membered heteroalkylene. In embodiments, L 100 is unsubstituted 2 to 6 membered heteroalkylene. In embodiments, L 100 is unsubstituted 2 to 8 membered heteroalkylene. In embodiments, L 100 is unsubstituted heteroalkylene (e.g., 2 to 8 membered heteroalkylene, 2 to 6 membered heteroalkylene, 2 to 4 membered heteroalkylene).

In embodiments, L 100 is R 105 -substituted or unsubstituted ethylaminylene. In embodiments, L 100 is R 105 -substituted ethylaminylene. In embodiments, L 100 is unsubstituted ethylaminylene. In embodiments, L 100 is R 105 -substituted or unsubstituted propylaminylene. In embodiments, L 100 is R 105 -substituted propyl aminylene. In embodiments, L 100 is unsubstituted propylaminylene. In embodiments, L 100 is R 105 -substituted or unsubstituted butylaminylene. In embodiments, L 100 is R 105 -substituted butylaminylene. In embodiments, L 100 is unsubstituted butylaminylene.

In embodiments, L 100 is R 105 -substituted or unsubstituted C 3 -C 8 cycloalkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted C 4 -C 6 cycloalkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted C 5 -C 6 cycloalkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted cycloalkylene (e.g., C 3 -C 8 cycloalkylene, C 4 -C 6 cycloalkylene, or C 5 -C 6 cycloalkylene). In embodiments, L 100 is R 105 -substituted C 3 -C 8 cycloalkylene. In embodiments, L 100 is R 105 -substituted C 4 -C 6 cycloalkylene. In embodiments, L 100 is R 105 -substituted C 5 -C 6 cycloalkylene. In embodiments, L 100 is R 105 -substituted cycloalkylene (e.g., C 3 -C 8 cycloalkylene, C 4 -C 6 cycloalkylene, or C 5 -C 6 cycloalkylene). In embodiments, L 100 is unsubstituted C 3 -C 8 cycloalkylene. In embodiments, L 100 is unsubstituted C 4 -C 6 cycloalkylene. In embodiments, L 100 is unsubstituted C 5 -C 6 cycloalkylene. In embodiments, L 100 is unsubstituted cycloalkylene (e.g., C 3 -C 8 cycloalkylene, C 4 -C 6 cycloalkylene, or C 5 -C 6 cycloalkylene).

In embodiments, L 100 is R 105 -substituted or unsubstituted 4 membered heterocycloalkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted 5 membered heterocycloalkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted 6 membered heterocycloalkylene. In embodiments, L 100 is R 105 -substituted or unsubstituted heterocycloalkylene (e.g., 3 to 6 membered heterocycloalkylene, 4 to 6 membered heterocycloalkylene, or 5 to 6 membered heterocycloalkylene). In embodiments, L 100 is R 105 -substituted 4 membered heterocycloalkylene. In embodiments, L 100 is R 105 -substituted 5 membered heterocycloalkylene. In embodiments, L 100 is R 105 -substituted 6 membered heterocycloalkylene. In embodiments, L 100 is R 105 -substituted heterocycloalkylene (e.g., 3 to 6 membered heterocycloalkylene, 4 to 6 membered heterocycloalkylene, or 5 to 6 membered heterocycloalkylene). In embodiments, L 100 is unsubstituted 4 membered heterocycloalkylene. In embodiments, L 100 is unsubstituted 5 membered heterocycloalkylene. In embodiments, L 100 unsubstituted 6 membered heterocycloalkylene. In embodiments, L 100 is unsubstituted heterocycloalkylene (e.g., 3 to 6 membered heterocycloalkylene, 4 to 6 membered heterocycloalkylene, or 5 to 6 membered heterocycloalkylene).

In embodiments, L 100 is R 105 -substituted or unsubstituted arylene (e.g. C 6 -C 10 arylene or C 6 arylene). In embodiments, L 100 is R 105 -substituted or unsubstituted C 6 -C 10 arylene. In embodiments, L 100 is R 105 -substituted or unsubstituted C 6 arylene. In embodiments, L 100 is R 105 -substituted arylene (e.g. C 6 -C 10 arylene or C 6 arylene). In embodiments, L 100 is R 105 -substituted C 6 -C 10 arylene. In embodiments, L 100 is R 105 -substituted C 6 arylene. In embodiments, L 100 is unsubstituted C 6 -C 10 arylene. In embodiments, L 100 is unsubstituted C 6 arylene.

In embodiments, L 100 is R 105 -substituted or unsubstituted heteroarylene (e.g. 5 to 10 membered heteroarylene, 5 to 9 membered heteroarylene, or 5 to 6 membered heteroarylene). In embodiments, L 100 is R 105 -substituted or unsubstituted 5 to 10 membered heteroarylene. In embodiments, L 100 is R 105 -substituted or unsubstituted 5 to 9 membered heteroarylene. In embodiments, L 100 is R 105 -substituted or unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 100 is R 105 -substituted heteroarylene (e.g. 5 to 10 membered heteroarylene, 5 to 9 membered heteroarylene, or 5 to 6 membered heteroarylene). In embodiments, L 100 is R 105 -substituted 5 to 10 membered heteroarylene. In embodiments, L 100 is R 105 -substituted 5 to 9 membered heteroarylene. In embodiments, L 100 is R 105 -substituted 5 to 6 membered heteroarylene. In embodiments, L 100 is unsubstituted heteroarylene (e.g. 5 to 10 membered heteroarylene, 5 to 9 membered heteroarylene, or 5 to 6 membered heteroarylene). In embodiments, L 100 is unsubstituted 5 to 10 membered heteroarylene. In embodiments, L 100 is unsubstituted 5 to 9 membered heteroarylene. In embodiments, L 100 is unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 100 is R 105 -substituted or unsubstituted indolinylene. In embodiments, L 100 is R 105 -substituted or unsubstituted indazolylene. In embodiments, L 100 is R 105 -substituted or unsubstituted benzimidazolylene. In embodiments, L 100 is R 105 -substituted or unsubstituted benzoxazolylene. In embodiments, L 100 is R 105 -substituted or unsubstituted azaindolylene. In embodiments, L 100 is R 105 -substituted or unsubstituted purinylene. In embodiments, L 100 is R 105 -substituted or unsubstituted indolylene. In embodiments, L 100 is R 05 -substituted or unsubstituted pyrazinylene. In embodiments, L 100 is R 105 -substituted or unsubstituted pyrrolylene. In embodiments, L 100 is R 105 -substituted or unsubstituted imidazolylene. In embodiments, L 100 is R 105 -substituted or unsubstituted pyrazolylene. In embodiments, L 100 is R 105 -substituted or unsubstituted triazolylene. In embodiments, L 100 is R 105 -substituted or unsubstituted tetrazolylene.

In embodiments, L 100 is R 105 -substituted indolinylene. In embodiments, L 100 is R 105 -substituted indazolylene. In embodiments, L 100 is R 105 -substituted benzimidazolylene. In embodiments, L 100 is R 105 -substituted benzoxazolylene. In embodiments, L 100 is R 105 -substituted azaindolylene. In embodiments, L 100 is R 105 -substituted purinylene. In embodiments, L 100 is R 105 -substituted indolylene. In embodiments, L 100 is R 105 -substituted pyrazinylene. In embodiments, L 100 is R 105 -substituted pyrrolylene. In embodiments, L 100 is R 105 -substituted imidazolylene. In embodiments, L 100 is R 105 -substituted pyrazolylene. In embodiments, L 100 is R 105 -substituted triazolylene. In embodiments, L 100 is R 105 -substituted tetrazolylene.

In embodiments, L 100 is unsubstituted indolinylene. In embodiments, L 100 is unsubstituted indazolylene. In embodiments, L 100 is unsubstituted benzimidazolylene. In embodiments, L 100 is unsubstituted benzoxazolylene. In embodiments, L 100 is unsubstituted azaindolylene. In embodiments, L 100 is unsubstituted purinylene. In embodiments, L 100 is unsubstituted indolylene. In embodiments, L 100 is unsubstituted pyrazinylene. In embodiments, L 100 is unsubstituted pyrrolylene. In embodiments, L 100 is unsubstituted imidazolylene. In embodiments, L 100 is unsubstituted pyrazolylene. In embodiments, L 100 is unsubstituted triazolylene. In embodiments, L 100 is unsubstituted tetrazolylene.

In embodiments, R 101 is independently hydrogen. In embodiments, R 101 is independently halogen. In embodiments, R 101 is independently —CX 103 . In embodiments, R 101 is independently —CHX 101 2 . In embodiments, R 101 is independently —CH 2 X 101 . In embodiments, R 101 is independently —OCX 101 3 . In embodiments, R 101 is independently —OCH 2 X 101 . In embodiments, R 101 is independently —OCHX 101 2 . In embodiments, R 101 is independently —CN. In embodiments, R 101 is independently —SO n101 R 101D . In embodiments, R 101 is independently —SO n101 NR 101A R 101B . In embodiments, R 101 is independently —NHC(O)NR 101A R 101B . In embodiments, R 101 is independently —N(O) m101 . In embodiments, R 101 is independently —NR 101A R 101B . In embodiments, R 101 is independently —C(O)R 101C . In embodiments, R 101 is independently —C(O)—OR 101C . In embodiments, R 101 is independently —C(O)NR 101A R 101B . In embodiments, R 101 is independently —OR 101D . In embodiments, R 101 is independently —NR 101A SO 2 R 101D . In embodiments, R 101 is independently —NR 101A C(O)R 101C . In embodiments, R 101 is independently —NR 101A C(O)OR 101C . In embodiments, R 101 is independently —NR 101A OR 101C . In embodiments, R 101 is independently —OH. In embodiments, R 101 is independently —NH 2 . In embodiments, R 101 is independently —COOH. In embodiments, R 101 is independently —CONH 2 . In embodiments, R 101 is independently —NO 2 . In embodiments, R 101 is independently —SH.

In embodiments, R 101 is independently substituted or unsubstituted alkyl. In embodiments, R 101 is independently substituted or unsubstituted heteroalkyl. In embodiments, R 101 is independently substituted or unsubstituted cycloalkyl. In embodiments, R 101 is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 101 is independently substituted or unsubstituted aryl. In embodiments, R 101 is independently substituted or unsubstituted heteroaryl. In embodiments, R 101 is independently substituted alkyl. In embodiments, R 101 is independently substituted heteroalkyl. In embodiments, R 101 is independently substituted cycloalkyl. In embodiments, R 101 is independently, substituted heterocycloalkyl. In embodiments, R 101 is independently substituted aryl. In embodiments, R 101 is independently substituted heteroaryl. In embodiments, R 101 is independently unsubstituted alkyl. In embodiments, R 101 is independently unsubstituted heteroalkyl. In embodiments, R 101 is independently unsubstituted cycloalkyl. In embodiments, R 101 is independently, unsubstituted heterocycloalkyl. In embodiments, R 101 is independently unsubstituted aryl. In embodiments, R 101 is independently unsubstituted heteroaryl. In embodiments, R 101 is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 101 is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 101 is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 101 is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101 is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 101 is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 101 is independently substituted C 1 -C 8 alkyl. In embodiments, R 101 is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 101 is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 101 is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101 is independently substituted C 6 -C 10 aryl. In embodiments, R 101 is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 101 is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 101 is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 101 is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 101 is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101 is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 101 is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 101 is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 101 is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 101 is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 101 is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101 is independently substituted or unsubstituted phenyl. In embodiments, R 101 is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 101 is independently substituted C 1 -C 4 alkyl. In embodiments, R 101 is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 101 is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 101 is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101 is independently substituted phenyl. In embodiments, R 101 is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 101 is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 101 is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 101 is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 101 is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101 is independently unsubstituted phenyl. In embodiments, R 101 is independently unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 101A is independently hydrogen. In embodiments, R 101A is independently —CX 101A 3 . In embodiments, R 101A is independently —CHX 101A 2 . In embodiments, R 101A is independently —CH 2 X 101A . In embodiments, R 101A is independently —CN. In embodiments, R 101A is independently —COOH. In embodiments, R 101A is independently —CONH 2 . In embodiments, R 101A is independently substituted or unsubstituted alkyl. In embodiments, R 101A is independently substituted or unsubstituted heteroalkyl. In embodiments, R 101A is independently substituted or unsubstituted cycloalkyl. In embodiments, R 101A is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 101A is independently substituted or unsubstituted aryl. In embodiments, R 101A is independently substituted or unsubstituted heteroaryl. In embodiments, R 101A is independently substituted alkyl. In embodiments, R 101A is independently substituted heteroalkyl. In embodiments, R 101A is independently substituted cycloalkyl. In embodiments, R 101A is independently, substituted heterocycloalkyl. In embodiments, R 101A is independently substituted aryl. In embodiments, R 101A is independently substituted heteroaryl. In embodiments, R 101A is independently unsubstituted alkyl. In embodiments, R 101A is independently unsubstituted heteroalkyl. In embodiments, R 101A is independently unsubstituted cycloalkyl. In embodiments, R 101A is independently, unsubstituted heterocycloalkyl. In embodiments, R 101A is independently unsubstituted aryl. In embodiments, R 101A is independently unsubstituted heteroaryl. In embodiments, R 101A is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R A is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 101A is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 101A is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101A is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 101A is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 101A is independently substituted C 1 -C 8 alkyl. In embodiments, R 101A is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 101A is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 101A is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101A is independently substituted C 6 -C 10 aryl. In embodiments, R 101A is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 101A is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 101A is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 101A is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 101A is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101A is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 101A is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 101A is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 101A is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 101A is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 101A is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101A is independently substituted or unsubstituted phenyl. In embodiments, R 101A is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 101A is independently substituted C 1 -C 4 alkyl. In embodiments, R 101A is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 101A is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 101A is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101A is independently substituted phenyl. In embodiments, R 101A is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 101A is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 101A is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 1A is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 101A is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101A is independently unsubstituted phenyl. In embodiments, R 101A is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 101A is independently unsubstituted methyl. In embodiments, R 101A is independently unsubstituted ethyl. In embodiments, R 101A is independently unsubstituted propyl. In embodiments, R 101A is independently unsubstituted isopropyl. In embodiments, R 101A is independently unsubstituted tert-butyl.

In embodiments, R 101B is independently hydrogen. In embodiments, R 101B is independently —CX 101B 3 . In embodiments, R 101B is independently —CHX 101B 2 . In embodiments, R 101B is independently —CH 2 X 101B . In embodiments, R 101B is independently —CN. In embodiments, R 101B is independently —COOH. In embodiments, R 101B is independently —CONH 2 . In embodiments, R 101B is independently substituted or unsubstituted alkyl. In embodiments, R 101B is independently substituted or unsubstituted heteroalkyl. In embodiments, R 101B is independently substituted or unsubstituted cycloalkyl. In embodiments, R 101B is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 101B is independently substituted or unsubstituted aryl. In embodiments, R 101B is independently substituted or unsubstituted heteroaryl. In embodiments, R 101B is independently substituted alkyl. In embodiments, R 101B is independently substituted heteroalkyl. In embodiments, R 101B is independently substituted cycloalkyl. In embodiments, R 101B is independently, substituted heterocycloalkyl. In embodiments, R 101B is independently substituted aryl. In embodiments, R 101B is independently substituted heteroaryl. In embodiments, R 101B is independently unsubstituted alkyl. In embodiments, R 101B is independently unsubstituted heteroalkyl. In embodiments, R 101B is independently unsubstituted cycloalkyl. In embodiments, R 101B is independently, unsubstituted heterocycloalkyl. In embodiments, R 101B is independently unsubstituted aryl. In embodiments, R 101B is independently unsubstituted heteroaryl. In embodiments, R 101B is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 101B is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 101B is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 101B is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101B is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 101B is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 101B is independently substituted C 1 -C 8 alkyl. In embodiments, R 101B is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 101B is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 101B is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101B is independently substituted C 6 -C 10 aryl. In embodiments, R 101B is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 101B is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 101B is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 101B is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 101B is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101B is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 101B is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 101B is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 101B is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 101B is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 101B is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101B is independently substituted or unsubstituted phenyl. In embodiments, R 101B is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 101B is independently substituted C 1 -C 4 alkyl. In embodiments, R 101B is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 101B is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 101B is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101B is independently substituted phenyl. In embodiments, R 101B is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 101B is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 101B is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 101B is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 101B is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101B is independently unsubstituted phenyl. In embodiments, R 101B is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 101B is independently unsubstituted methyl. In embodiments, R 101B is independently unsubstituted ethyl. In embodiments, R 101B is independently unsubstituted propyl. In embodiments, R 101B is independently unsubstituted isopropyl. In embodiments, R 101B is independently unsubstituted tert-butyl.

In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heterocycloalkyl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heteroaryl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form a substituted heterocycloalkyl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form a substituted heteroaryl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heterocycloalkyl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heteroaryl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 10 membered heteroaryl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 6 membered heteroaryl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 101C is independently hydrogen. In embodiments, R 101C is independently —CX 101C 3 . In embodiments, R 101C is independently —CHX 101C 2 . In embodiments, R 101C is independently —CH 2 X 101C . In embodiments, R 101C is independently —CN. In embodiments, R 101C is independently —COOH. In embodiments, R 101C is independently —CONH 2 . In embodiments, R 101C is independently substituted or unsubstituted alkyl. In embodiments, R 101C is independently substituted or unsubstituted heteroalkyl. In embodiments, R 101C is independently substituted or unsubstituted cycloalkyl. In embodiments, R 101C is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 101C is independently substituted or unsubstituted aryl. In embodiments, R 101C is independently substituted or unsubstituted heteroaryl. In embodiments, R 101C is independently substituted alkyl. In embodiments, R 101C is independently substituted heteroalkyl. In embodiments, R 101C is independently substituted cycloalkyl. In embodiments, R 101C is independently, substituted heterocycloalkyl. In embodiments, R 101C is independently substituted aryl. In embodiments, R 101C is independently substituted heteroaryl. In embodiments, R 101C is independently unsubstituted alkyl. In embodiments, R 101C is independently unsubstituted heteroalkyl. In embodiments, R 101C is independently unsubstituted cycloalkyl. In embodiments, R 101C is independently, unsubstituted heterocycloalkyl. In embodiments, R 101C is independently unsubstituted aryl. In embodiments, R 101C is independently unsubstituted heteroaryl. In embodiments, R 101C is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 101C is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 101C is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 101C is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101C is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 101C is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 101C is independently substituted C 1 -C 8 alkyl. In embodiments, R 101C is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 101C is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 101C is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101C is independently substituted C 6 -C 10 aryl. In embodiments, R 101C is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 101C is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 101C is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 101C is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 101C is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101C is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 101C is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 101C is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 101C is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 101C is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 101C is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101C is independently substituted or unsubstituted phenyl. In embodiments, R 101C is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 101C is independently substituted C 1 -C 4 alkyl. In embodiments, R 101C is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 101C is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 101C is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101C is independently substituted phenyl. In embodiments, R 101C is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 101C is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 101C is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 101C is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 101C is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101C is independently unsubstituted phenyl. In embodiments, R 101C is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 101C is independently unsubstituted methyl. In embodiments, R 101C is independently unsubstituted ethyl. In embodiments, R 101C is independently unsubstituted propyl. In embodiments, R 101C is independently unsubstituted isopropyl. In embodiments, R 101C is independently unsubstituted tert-butyl.

In embodiments, R 101D is independently hydrogen. In embodiments, R 101D is independently —CX 101D 3 . In embodiments, R 101D is independently —CHX 101D 2 . In embodiments, R 101D is independently —CH 2 X 101D . In embodiments, R 101D is independently —CN. In embodiments, R 101D is independently —COOH. In embodiments, R 101D is independently —CONH 2 . In embodiments, R 101D is independently substituted or unsubstituted alkyl. In embodiments, R 101D is independently substituted or unsubstituted heteroalkyl. In embodiments, R 101D is independently substituted or unsubstituted cycloalkyl. In embodiments, R 101D is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 101D is independently substituted or unsubstituted aryl. In embodiments, R 101D is independently substituted or unsubstituted heteroaryl. In embodiments, R 101D is independently substituted alkyl. In embodiments, R 101D is independently substituted heteroalkyl. In embodiments, R 101D is independently substituted cycloalkyl. In embodiments, R 101D is independently, substituted heterocycloalkyl. In embodiments, R 101D is independently substituted aryl. In embodiments, R 101D is independently substituted heteroaryl. In embodiments, R 101D is independently unsubstituted alkyl. In embodiments, R 101D is independently unsubstituted heteroalkyl. In embodiments, R 101D is independently unsubstituted cycloalkyl. In embodiments, R 101D is independently, unsubstituted heterocycloalkyl. In embodiments, R 101D is independently unsubstituted aryl. In embodiments, R 101D is independently unsubstituted heteroaryl. In embodiments, R 101D is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 101D is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 101D is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 101D is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101D is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 101D is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 101D is independently substituted C 1 -C 8 alkyl. In embodiments, R 101D is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 101D is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 101D is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101D is independently substituted C 6 -C 10 aryl. In embodiments, R 101D is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 101D is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 101D is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 101D is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 101D is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 101D is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 101D is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 101D is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 101D is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 101D is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 101D is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101D is independently substituted or unsubstituted phenyl. In embodiments, R 101D is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 101D is independently substituted C 1 -C 4 alkyl. In embodiments, R 101D is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 101D is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 101D is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101D is independently substituted phenyl. In embodiments, R 101D is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 101D is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 101D is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 101D is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 101D is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 101D is independently unsubstituted phenyl. In embodiments, R 101D is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 101D is independently unsubstituted methyl. In embodiments, R 101D is independently unsubstituted ethyl. In embodiments, R 101D is independently unsubstituted propyl. In embodiments, R 101D is independently unsubstituted isopropyl. In embodiments, R 101D is independently unsubstituted tert-butyl.

In embodiments, R 101 is independently hydrogen,

halogen, —CX 101 3 , —CHX 101 2 , —CH 2 X 101 , —OCX 101 3 , —OCH 2 X 101 , —OCHX 101 2 , —CN, —SO n101 R 101D , —SO v101 NR 101A R 101B , —NHC(O)NR 101A R 101B , —N(O) m101 , —NR 101A R 101B , —C(O)R 101C , —C(O)OR 101C , —C(O)NR 101A R 101B , —OR 101D , —NR 101A SO 2 R 101D , —NR 101A C(O)R 101C , —NR 101A C(O)OR 101C , —NR 101A OR 101C , R 102 -substituted or unsubstituted alkyl, R 102 -substituted or unsubstituted heteroalkyl, R 102 -substituted or unsubstituted cycloalkyl, R 102 -substituted or unsubstituted heterocycloalkyl, R 102 -substituted or unsubstituted aryl, or R 102 -substituted or unsubstituted heteroaryl. In embodiments, R 101 is independently

halogen, —CX 101 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 101 3 , —OCHX 101 2 , R 102 -substituted or unsubstituted alkyl, R 102 -substituted or unsubstituted heteroalkyl, R 102 -substituted or unsubstituted cycloalkyl, R 102 -substituted or unsubstituted heterocycloalkyl, R 102 -substituted or unsubstituted aryl, or R 102 -substituted or unsubstituted heteroaryl. In embodiments, R 102 is independently halogen, —CX 101 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 101 3 , —OCHX 102 , R 102 -substituted or unsubstituted C 1 -C 8 alkyl, R 102 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 102 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 102 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 102 -substituted or unsubstituted phenyl, or R 102 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 101 is —F, —Cl, —Br, or —I. In embodiments, R 101 is independently hydrogen. In embodiments, R 101 is independently methyl. In embodiments, R 101 is independently ethyl.

In embodiments, R 101 is independently

halogen, —CX 101 3 , —CN, —OH, —COOH, —CONH 2 , —OCX 101 3 , —OCHX 101 2 , R 102 -substituted or unsubstituted C 1 -C 8 alkyl, R 102 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 102 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 102 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 102 -substituted or unsubstituted phenyl, or R 102 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 101 is —F, —Cl, —Br, or —I. In embodiments, R 101 is independently hydrogen. In embodiments, R 101 is independently methyl. In embodiments, R 101 is independently ethyl.

R 102 is independently oxo,

halogen, —CX 102 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 102 3 , —OCHX 102 2 , R 103 -substituted or unsubstituted alkyl, R 103 -substituted or unsubstituted heteroalkyl, R 103 -substituted or unsubstituted cycloalkyl, R 103 -substituted or unsubstituted heterocycloalkyl, R 103 -substituted or unsubstituted aryl, or R 103 -substituted or unsubstituted heteroaryl. In embodiments, R 102 is independently oxo,

halogen, —CX 102 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 102 3 , —OCHX 102 2 , R 103 -substituted or unsubstituted C 1 -C 8 alkyl, R 103 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 103 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 103 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 103 -substituted or unsubstituted phenyl, or R 103 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 102 is —F, —Cl, —Br, or —I.

R 103 is independently oxo,

halogen, —CX 103 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 103 3 , —OCHX 103 2 , R 104 -substituted or unsubstituted alkyl, R 104 -substituted or unsubstituted heteroalkyl, R 104 -substituted or unsubstituted cycloalkyl, R 104 -substituted or unsubstituted heterocycloalkyl, R 104 -substituted or unsubstituted aryl, or R 104 -substituted or unsubstituted heteroaryl. In embodiments, R 103 is independently oxo,

halogen, —CX 103 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 103 3 , —OCHX 103 2 , R 104 -substituted or unsubstituted C 1 -C 8 alkyl, R 104 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 104 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 104 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 104 -substituted or unsubstituted phenyl, or R 104 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 103 is —F, —Cl, —Br, or —I.

In embodiments, R 101A is independently

hydrogen, —CX 101A 3 , —CN, —COOH, —CONH 2 , —CHX 101A 2 , —CH 2 X 101A , R 102A -substituted or unsubstituted alkyl, R 102A -substituted or unsubstituted heteroalkyl, R 102A -substituted or unsubstituted cycloalkyl, R 102A -substituted or unsubstituted heterocycloalkyl, R 102A -substituted or unsubstituted aryl, or R 102A -substituted or unsubstituted heteroaryl. In embodiments, R 101A is independently hydrogen, —CX 101A 3 , —CN, —COOH, —CONH 2 , —CHX 101A 2 , —CH 2 X 101A , R 102A -substituted or unsubstituted C 1 -C 8 alkyl, R 102A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 102A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 102A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 102A -substituted or unsubstituted phenyl, or R 102A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 101A is —F, —Cl, —Br, or —I. In embodiments, R 101A is independently hydrogen. In embodiments, R 101A is independently methyl. In embodiments, R 101A is independently ethyl.

In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may optionally be joined to form a R 102A -substituted or unsubstituted heterocycloalkyl or R 102A -substituted or unsubstituted heteroaryl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may optionally be joined to form a R 102A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 102A -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 102A is independently oxo,

halogen, —CX 102A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 102A 3 , —OCHX 102A 2 , R 103A -substituted or unsubstituted alkyl, R 103A -substituted or unsubstituted heteroalkyl, R 103A -substituted or unsubstituted cycloalkyl, R 103A -substituted or unsubstituted heterocycloalkyl, R 13A -substituted or unsubstituted aryl, or R 103A -substituted or unsubstituted heteroaryl. In embodiments, R 102A is independently oxo,

halogen, —CX 102A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 102A 3 , —OCHX 102A 2 , R 103A -substituted or unsubstituted C 1 -C 8 alkyl, R 103A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 103A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 103A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 103A -substituted or unsubstituted phenyl, or R 103A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 102A is —F, —Cl, —Br, or —I.

R 103A is independently oxo,

halogen, —CX 103A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 103A 3 , —OCHX 103A 2 , R 104A -substituted or unsubstituted alkyl, R 104A -substituted or unsubstituted heteroalkyl, R 104A -substituted or unsubstituted cycloalkyl, R 104A -substituted or unsubstituted heterocycloalkyl, R 104A -substituted or unsubstituted aryl, or R 104A -substituted or unsubstituted heteroaryl. In embodiments, R 103A is independently oxo,

halogen, —CX 103A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 103A 3 , —OCHX 103A 2 , R 104A -substituted or unsubstituted C 1 -C 8 alkyl, R 104A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 104A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 104A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 104A -substituted or unsubstituted phenyl, or R 104A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 103A is —F, —Cl, —Br, or —I.

In embodiments, R 101B is independently

hydrogen, —CX 101B 3 , —CN, —COOH, —CONH 2 , —CHX 101B 2 , —CH 2 X 101B , R 102B -substituted or unsubstituted alkyl, R 102B -substituted or unsubstituted heteroalkyl, R 102B -substituted or unsubstituted cycloalkyl, R 102B -substituted or unsubstituted heterocycloalkyl, R 102B -substituted or unsubstituted aryl, or R 102B -substituted or unsubstituted heteroaryl. In embodiments, R 101B is independently

hydrogen, —CX 101B 3 , —CN, —COOH, —CONH 2 , —CHX 101B 2 , —CH 2 X 101B , R 102B -substituted or unsubstituted C 1 -C 8 alkyl, R 102B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 102B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 102B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 102B -substituted or unsubstituted phenyl, or R 102B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 101B is —F, —Cl, —Br, or —I. In embodiments, R 101B is independently hydrogen. In embodiments, R 101B is independently methyl. In embodiments, R 101B is independently ethyl.

In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may optionally be joined to form a R 102B -substituted or unsubstituted heterocycloalkyl or R 102B -substituted or unsubstituted heteroaryl. In embodiments, R 101A and R 101B substituents bonded to the same nitrogen atom may optionally be joined to form a R 102B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 102B -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 102B is independently oxo,

halogen, —CX 102B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 102B 3 , —OCHX 102B 2 , R 103B -substituted or unsubstituted alkyl, R 103B -substituted or unsubstituted heteroalkyl, R 103B -substituted or unsubstituted cycloalkyl, R 103B -substituted or unsubstituted heterocycloalkyl, R 103B -substituted or unsubstituted aryl, or R 103B -substituted or unsubstituted heteroaryl. In embodiments, R 102B is independently oxo,

halogen, —CX 102B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 102B 3 , —OCHX 102B 2 , R 103B -substituted or unsubstituted C 1 -C 8 alkyl, R 103B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 103B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 103B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 103B -substituted or unsubstituted phenyl, or R 103B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 102B is —F, —Cl, —Br, or —I.

R 103B is independently oxo,

halogen, —CX 103B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 103B 3 , —OCHX 103B 2 , R 104B -substituted or unsubstituted alkyl, R 104B -substituted or unsubstituted heteroalkyl, R 104B -substituted or unsubstituted cycloalkyl, R 104B -substituted or unsubstituted heterocycloalkyl, R 104B -substituted or unsubstituted aryl, or R 104B -substituted or unsubstituted heteroaryl. In embodiments, R 103B is independently oxo,

halogen, —CX 103B 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 103B 3 , —OCHX 103B 2 , R 104B -substituted or unsubstituted C 1 -C 8 alkyl, R 104B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 104B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 104B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 104B -substituted or unsubstituted phenyl, or R 104B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 103B is —F, —Cl, —Br, or —I.

In embodiments, R 101C is independently

hydrogen, —CX 101C 3 , —CN, —COOH, —CONH 2 , —CHX 101C 2 , —CH 2 X 101C , R 102C -substituted or unsubstituted alkyl, R 102C -substituted or unsubstituted heteroalkyl, R 102C -substituted or unsubstituted cycloalkyl, R 102C -substituted or unsubstituted heterocycloalkyl, R 102C -substituted or unsubstituted aryl, or R 102C -substituted or unsubstituted heteroaryl. In embodiments, R 101C is independently hydrogen, —CX 101C 3 , —CN, —COOH, —CONH 2 , —CHX 101C 2 , —CH 2 X 101C , R 102C -substituted or unsubstituted C 1 -C 8 alkyl, R 102C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 102C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 102C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 102C -substituted or unsubstituted phenyl, or R 102C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 101C is —F, —Cl, —Br, or —I. In embodiments, R 101C is independently hydrogen. In embodiments, R 101C is independently methyl. In embodiments, R 101C is independently ethyl.

R 102C is independently oxo,

halogen, —CX 102C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 102C 3 , —OCHX 102C 2 , R 103C -substituted or unsubstituted alkyl, R 103C -substituted or unsubstituted heteroalkyl, R 103C -substituted or unsubstituted cycloalkyl, R 103C -substituted or unsubstituted heterocycloalkyl, R 103C -substituted or unsubstituted aryl, or R 103C -substituted or unsubstituted heteroaryl. In embodiments, R 102C is independently oxo,

halogen, —CX 102C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 102C 3 , —OCHX 102C 2 , R 103C -substituted or unsubstituted C 1 -C 8 alkyl, R 103C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 103C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 103C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 103C -substituted or unsubstituted phenyl, or R 103C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 102C is —F, —Cl, —Br, or —I.

R 103C is independently oxo,

halogen, —CX 103C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 103C 3 , —OCHX 103C 2 R 104C -substituted or unsubstituted alkyl, R 104C -substituted or unsubstituted heteroalkyl, R 104C -substituted or unsubstituted cycloalkyl, R 104C -substituted or unsubstituted heterocycloalkyl, R 104C -substituted or unsubstituted aryl, or R 104C -substituted or unsubstituted heteroaryl. In embodiments, R 103C is independently oxo,

halogen, —CX 103C 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 103C 3 , —OCHX 103C 2 , R 104C -substituted or unsubstituted C 1 -C 8 alkyl, R 104C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 104C -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 104C -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 104C -substituted or unsubstituted phenyl, or R 104C -substituted or unsubstituted 5 to 6 membered heteroaryl. X 103C is —F, —Cl, —Br, or —I.

In embodiments, R 101D is independently

hydrogen, —CX 101D 3 , —CN, —COOH, —CONH 2 , —CHX 101D 2 , —CH 2 X 101D , R 102D -substituted or unsubstituted alkyl, R 102D -substituted or unsubstituted heteroalkyl, R 102D -substituted or unsubstituted cycloalkyl, R 102D -substituted or unsubstituted heterocycloalkyl, R 102D -substituted or unsubstituted aryl, or R 102D -substituted or unsubstituted heteroaryl. In embodiments, R 101D is independently

hydrogen, —CX 101D 3 , —CN, —COOH, —CONH 2 , —CHX 101D 2 , —CH 2 X 101D , R 102D -substituted or unsubstituted C 1 -C 8 alkyl, R 102D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 102D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 102D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 102D -substituted or unsubstituted phenyl, or R 102D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 101D is —F, —Cl, —Br, or —I. In embodiments, R 101D is independently hydrogen. In embodiments, R 101D is independently methyl. In embodiments, R 101D is independently ethyl.

R 102D is independently oxo,

halogen, —CX 102D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 102D 3 , —OCHX 102D 2 , R 103D -substituted or unsubstituted alkyl, R 103D -substituted or unsubstituted heteroalkyl, R 103D -substituted or unsubstituted cycloalkyl, R 103D -substituted or unsubstituted heterocycloalkyl, R 103D -substituted or unsubstituted aryl, or R 103D -substituted or unsubstituted heteroaryl. In embodiments, R 102D is independently oxo,

halogen, —CX 102D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 102D 3 , —OCHX 102D 2 , R 103D -substituted or unsubstituted C 1 -C 8 alkyl, R 103D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 103D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 103D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 103D -substituted or unsubstituted phenyl, or R 103D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 102D is —F, —Cl, —Br, or —I.

R 103D is independently oxo,

halogen, —CX 103D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 103D 3 , —OCHX 103D 2 , R 104D -substituted or unsubstituted alkyl, R 104D -substituted or unsubstituted heteroalkyl, R 104D -substituted or unsubstituted cyclalkyl, R 104D -substituted or unsubstituted heterocycloalkyl, R 104D -substituted or unsubstituted aryl, or R 104D -substituted or unsubstituted heteroaryl. In embodiments, R 103D is independently oxo,

halogen, —CX 103D 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 103D 3 , —OCHX 103D 2 , R 104D -substituted or unsubstituted C 1 -C 8 alkyl, R 104D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 104D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 104D -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 104D -substituted or unsubstituted phenyl, or R 104D -substituted or unsubstituted 5 to 6 membered heteroaryl. X 103D is —F, —Cl, —Br, or —I.

R 104 , R 104A , R 104B , R 104C , and R 104D are hydrogen, oxo,

halogen, —CCl 3 , —CBr 3 , —CF 3 , —Cl 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H,

—NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCl 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 104 , R 104A , R 104B , R 104C , and R 104D are independently oxo,

halogen, —CCl 3 , —CBr 3 , —CF 3 , —Cl 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H,

—NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCl 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 104 , R 104A , R 104B , R 104C , and R 104D are independently hydrogen, oxo,

halogen, —CCl 3 , —CBr 3 , —CF 3 , —Cl 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H,

—NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCl 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , unsubstituted C 1 -C 8 alkyl, unsubstituted 2 to 8 membered heteroalkyl, unsubstituted C 3 -C 8 cycloalkyl, unsubstituted 3 to 6 membered heterocycloalkyl, unsubstituted phenyl, or unsubstituted 5 to 6 membered heteroaryl.

In embodiments, L 108 is a bond, —S(O) 2 —, —S(O) 2 -Ph-, substituted or unsubstituted C 1 -C 8 alkylene, substituted or unsubstituted 2 to 8 membered heteroalkylene, substituted or unsubstituted C 3 -C 8 cycloalkylene, substituted or unsubstituted 3 to 8 membered heterocycloalkylene, substituted or unsubstituted phenylene, or substituted or unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 108 is a bond. In embodiments, L 108 is a substituted or unsubstituted C 1 -C 6 alkylene, substituted or unsubstituted 2 to 6 membered heteroalkylene, substituted or unsubstituted C 3 -C 6 cycloalkylene, substituted or unsubstituted 3 to 6 membered heterocycloalkylene, substituted or unsubstituted phenylene, or substituted or unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 108 is an unsubstituted C 1 -C 6 alkylene, unsubstituted 2 to 6 membered heteroalkylene, or unsubstituted C 3 -C 6 cycloalkylene. In embodiments, L 108 is an unsubstituted methylene.

In embodiments, L 108 is a bond. In embodiments, L 108 is —S(O) 2 —. In embodiments, L 108 is —S(O) 2 -Ph-. In embodiments, L 108 is —NR 109A —. In embodiments, L 108 is —O—. In embodiments, L 108 is —S—. In embodiments, L 108 is —C(O)—. In embodiments, L 108 is —C(O)NR 109A —. In embodiments, L 108 is —NR 109 C(O)—. In embodiments, L 108 is —NR 109 C(O)NH—. In embodiments, L 108 is —NHC(O)NR 109A —. In embodiments, L 108 is —C(O)O—. In embodiments, L 108 is —OC(O)—. In embodiments, L 108 is —NH—. In embodiments, L 108 is —C(O)NH—. In embodiments, L 108 is —NHC(O)—. In embodiments, L 108 is —NHC(O)NH—. In embodiments, L 108 is —CH 2 —. In embodiments, L 108 is —OCH 2 —. In embodiments, L 108 is —CH 2 O—. In embodiments, L 108 is —CH 2 CH 2 —. In embodiments, L 108 is —SCH 2 —. In embodiments, L 108 is —CH 2 S—. In embodiments, L 108 is —CHCH—. In embodiments, L 108 is —CC—. In embodiments, L 108 is —NHCH 2 —. In embodiments, L 108 is —CH 2 NH—.

In embodiments, L 108 is a substituted or unsubstituted alkylene. In embodiments, L 108 is a substituted or unsubstituted heteroalkylene. In embodiments, L 108 is a substituted or unsubstituted cycloalkylene. In embodiments, L 108 is a substituted or unsubstituted heterocycloalkylene. In embodiments, L 108 is a substituted or unsubstituted arylene. In embodiments, L 108 is a substituted or unsubstituted heteroarylene. In embodiments, L 108 is a substituted alkylene. In embodiments, L 108 is a substituted heteroalkylene. In embodiments, L 108 is a substituted cycloalkylene. In embodiments, L 108 is a substituted heterocycloalkylene. In embodiments, L 108 is a substituted arylene. In embodiments, L 108 is a substituted heteroarylene. In embodiments, L 108 is an unsubstituted alkylene. In embodiments, L 108 is an unsubstituted heteroalkylene. In embodiments, L 108 is an unsubstituted cycloalkylene. In embodiments, L 108 is an unsubstituted heterocycloalkylene. In embodiments, L 108 is an unsubstituted arylene. In embodiments, L 108 is an unsubstituted heteroarylene. In embodiments, L 108 is a substituted or unsubstituted C 1 -C 8 alkylene. In embodiments, L 108 is a substituted or unsubstituted 2 to 8 membered heteroalkylene. In embodiments, L 108 is a substituted or unsubstituted C 3 -C 8 cycloalkylene. In embodiments, L 108 is a substituted or unsubstituted 3 to 8 membered heterocycloalkylene. In embodiments, L 108 is a substituted or unsubstituted C 6 -C 10 arylene. In embodiments, L 108 is a substituted or unsubstituted 5 to 10 membered heteroarylene. In embodiments, L 108 is a substituted C 1 -C 8 alkylene. In embodiments, L 108 is a substituted 2 to 8 membered heteroalkylene. In embodiments, L 108 is a substituted C 3 -C 8 cycloalkylene. In embodiments, L 108 is a substituted 3 to 8 membered heterocycloalkylene. In embodiments, L 108 is a substituted C 6 -C 10 arylene. In embodiments, L 108 is a substituted 5 to 10 membered heteroarylene. In embodiments, L 108 is an unsubstituted C 1 -C 8 alkylene. In embodiments, L 108 is an unsubstituted 2 to 8 membered heteroalkylene. In embodiments, L 108 is an unsubstituted C 3 -C 8 cycloalkylene. In embodiments, L 108 is an unsubstituted 3 to 8 membered heterocycloalkylene. In embodiments, L 108 is an unsubstituted C 6 -C 10 arylene. In embodiments, L 108 is an unsubstituted 5 to 10 membered heteroarylene. In embodiments, L 108 is a substituted or unsubstituted C 1 -C 4 alkylene. In embodiments, L 108 is a substituted or unsubstituted 2 to 4 membered heteroalkylene. In embodiments, L 108 is a substituted or unsubstituted C 3 -C 6 cycloalkylene. In embodiments, L 108 is a substituted or unsubstituted 3 to 6 membered heterocycloalkylene. In embodiments, L 108 is a substituted or unsubstituted phenylene. In embodiments, L 108 is a substituted or unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 108 is a substituted C 1 -C 4 alkylene. In embodiments, L 108 is a substituted 2 to 4 membered heteroalkylene. In embodiments, L 108 is a substituted C 3 -C 6 cycloalkylene. In embodiments, L 108 is a substituted 3 to 6 membered heterocycloalkylene. In embodiments, L 108 is a substituted phenylene. In embodiments, L 108 is a substituted 5 to 6 membered heteroarylene. In embodiments, L 108 is an unsubstituted C 1 -C 4 alkylene. In embodiments, L 108 is an unsubstituted 2 to 4 membered heteroalkylene. In embodiments, L 108 is an unsubstituted C 3 -C 6 cycloalkylene. In embodiments, L 108 is an unsubstituted 3 to 6 membered heterocycloalkylene. In embodiments, L 108 is an unsubstituted phenylene. In embodiments, L 108 is an unsubstituted 5 to 6 membered heteroarylene.

In embodiments, L 108 is a

bond, —S(O) 2 —, —S(O) 2 -Ph-, —NR 109A —, —O—, —S—, —C(O)—, —C(O)NR 109A —, —NR 109 C(O)—, —NR 109 C(O)NH—, —NHC(O)NR 109A —, —C(O)O—, —OC(O)—, R 113 -substituted or unsubstituted alkylene, R 113 -substituted or unsubstituted heteroalkylene, R 113 -substituted or unsubstituted cycloalkylene, R 113 -substituted or unsubstituted heterocycloalkylene, R 113 -substituted or unsubstituted arylene, or R 113 -substituted or unsubstituted heteroarylene. In embodiments, L 108 is a bond, —S(O) 2 —, —S(O) 2 -Ph-, —NH—, —O—, —S—, —C(O)—, —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —C(O)O—, —OC(O)—, R 113 -substituted or unsubstituted alkylene, R 113 -substituted or unsubstituted heteroalkylene, R 113 -substituted or unsubstituted cycloalkylene, R 113 -substituted or unsubstituted heterocycloalkylene, R 113 -substituted or unsubstituted arylene, or R 113 -substituted or unsubstituted heteroarylene. In embodiments, L 108 is a

bond, —S(O) 2 —, —S(O) 2 -Ph-, —NH—, —O—, —S—, —C(O)—, —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —C(O)O—, —OC(O)—, R 113 -substituted or unsubstituted C 1 -C 8 alkylene, R 113 -substituted or unsubstituted 2 to 8 membered heteroalkylene, R 113 -substituted or unsubstituted C 3 -C 8 cycloalkylene, R 113 -substituted or unsubstituted 3 to 6 membered heterocycloalkylene, R 113 -substituted or unsubstituted phenylene, or R 113 -substituted or unsubstituted 5 to 6 membered heteroarylene.

In embodiments, L 108 has the formula

R 113 is independently oxo,

halogen, —CX 113 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 113 3 , —OCHX 113 2 , R 114 -substituted or unsubstituted alkyl, R 114 -substituted or unsubstituted heteroalkyl, R 114 -substituted or unsubstituted cycloalkyl, R 114 -substituted or unsubstituted heterocycloalkyl, R 114 -substituted or unsubstituted aryl, or R 114 -substituted or unsubstituted heteroaryl. In embodiments, R 113 is independently oxo,

halogen, —CX 113 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH,

—SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 113 3 , —OCHX 113 2 , R 114 -substituted or unsubstituted C 1 -C 8 alkyl, R 114 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 114 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 114 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 114 -substituted or unsubstituted phenyl, or R 114 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 113 is —F, —Cl, —Br, or —I.

R 114 is independently oxo,

halogen, —CX 114 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 114 3 , —OCHX 114 2 , R 115 -substituted or unsubstituted alkyl, R 15 -substituted or unsubstituted heteroalkyl, R 115 -substituted or unsubstituted cycloalkyl, R 115 -substituted or unsubstituted heterocycloalkyl, R 115 -substituted or unsubstituted aryl, or R 115 -substituted or unsubstituted heteroaryl. In embodiments, R 114 is independently oxo,

halogen, —CX 114 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 114 3 , —OCHX 114 2 , R 115 -substituted or unsubstituted C 1 -C 8 alkyl, R 115 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 115 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 115 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 115 -substituted or unsubstituted phenyl, or R 115 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 114 is —F, —Cl, —Br, or —I.

R 115 is independently hydrogen, oxo,

halogen, —CCl 3 , —CBr 3 , —CF 3 , —Cl 3 ,—CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 ,

—NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H,

—NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCl 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 5 is independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl. In embodiments, R 115 is independently oxo,

halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , unsubstituted C 1 -C 8 alkyl, unsubstituted 2 to 8 membered heteroalkyl, unsubstituted C 3 -C 8 cycloalkyl, unsubstituted 3 to 6 membered heterocycloalkyl, unsubstituted phenyl, or unsubstituted 5 to 6 membered heteroaryl.

In embodiments, L 108 is a bond. In embodiments, L 108 is R 113 -substituted or unsubstituted C 1 -C 2 alkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted C 1 -C 4 alkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted C 1 -C 6 alkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted C 1 -C 8 alkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted alkylene (e.g., C 1 -C 8 alkylene, C 1 -C 6 alkylene, C 1 -C 4 alkylene, C 1 -C 2 alkylene). In embodiments, L 108 is R 113 -substituted C 1 -C 2 alkylene. In embodiments, L 108 is R 113 -substituted C 1 -C 4 alkylene. In embodiments, L 108 is R 113 -substituted C 1 -C 6 alkylene. In embodiments, L 108 is R 113 -substituted C 1 -C 8 alkylene. In embodiments, L 108 is R 113 -substituted alkylene (e.g., C 1 -C 8 alkylene, C 1 -C 6 alkylene, C 1 -C 4 alkylene, C 1 -C 2 alkylene). In embodiments, L 108 is R 113 -substituted methylene. In embodiments, L 108 is unsubstituted C 1 -C 2 alkylene. In embodiments, L 108 is unsubstituted C 1 -C 4 alkylene. In embodiments, L 108 is unsubstituted C 1 -C 6 alkylene. In embodiments, L 108 is unsubstituted C 1 -C 8 alkylene. In embodiments, L 108 is unsubstituted alkylene (e.g., C 1 -C 8 alkylene, C 1 -C 6 alkylene, C 1 -C 4 alkylene, C 1 -C 2 alkylene). In embodiments, L 108 is R 113 -substituted or unsubstituted methylene. In embodiments, L 108 is R 113 -substituted methylene. In embodiments, L 108 is unsubstituted methylene.

In embodiments, L 108 is R 113 -substituted or unsubstituted 2 to 4 membered heteroalkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted 2 to 6 membered heteroalkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted 2 to 8 membered heteroalkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted heteroalkylene (e.g., 2 to 8 membered heteroalkylene, 2 to 6 membered heteroalkylene, 2 to 4 membered heteroalkylene). In embodiments, L 108 is R 113 -substituted 2 to 4 membered heteroalkylene. In embodiments, L 108 is R 113 -substituted 2 to 6 membered heteroalkylene. In embodiments, L 108 is R 113 -substituted 2 to 8 membered heteroalkylene. In embodiments, L 108 is R 113 -substituted heteroalkylene (e.g., 2 to 8 membered heteroalkylene, 2 to 6 membered heteroalkylene, 2 to 4 membered heteroalkylene). In embodiments, L 108 is unsubstituted 2 to 4 membered heteroalkylene. In embodiments, L 108 is unsubstituted 2 to 6 membered heteroalkylene. In embodiments, L 108 is unsubstituted 2 to 8 membered heteroalkylene. In embodiments, L 108 is unsubstituted heteroalkylene (e.g., 2 to 8 membered heteroalkylene, 2 to 6 membered heteroalkylene, 2 to 4 membered heteroalkylene).

In embodiments, L 108 is R 113 -substituted or unsubstituted ethylaminylene. In embodiments, L 108 is R 113 -substituted ethylaminylene. In embodiments, L 108 is unsubstituted ethylaminylene. In embodiments, L 108 is R 113 -substituted or unsubstituted propylaminylene. In embodiments, L 108 is R 113 -substituted propyl aminylene. In embodiments, L 108 is unsubstituted propylaminylene. In embodiments, L 108 is R 113 -substituted or unsubstituted butylaminylene. In embodiments, L 108 is R 113 -substituted butylaminylene. In embodiments, L 108 is unsubstituted butylaminylene.

In embodiments, L 108 is R 113 -substituted or unsubstituted C 3 -C 8 cycloalkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted C 4 -C 6 cycloalkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted C 5 -C 6 cycloalkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted cycloalkylene (e.g., C 3 -C 8 cycloalkylene, C 4 -C 6 cycloalkylene, or C 5 -C 6 cycloalkylene). In embodiments, L 108 is R 113 -substituted C 3 -C 8 cycloalkylene. In embodiments, L 108 is R 113 -substituted C 4 -C 6 cycloalkylene. In embodiments, L 108 is R 113 -substituted C 5 -C 6 cycloalkylene. In embodiments, L 108 is R 113 -substituted cycloalkylene (e.g., C 3 -C 8 cycloalkylene, C 4 -C 6 cycloalkylene, or C 5 -C 6 cycloalkylene). In embodiments, L 108 is unsubstituted C 3 -C 8 cycloalkylene. In embodiments, L 108 is unsubstituted C 4 -C 6 cycloalkylene. In embodiments, L 108 is unsubstituted C 5 -C 6 cycloalkylene. In embodiments, L 108 is unsubstituted cycloalkylene (e.g., C 3 -C 8 cycloalkylene, C 4 -C 6 cycloalkylene, or C 5 -C 6 cycloalkylene).

In embodiments, L 108 is R 113 -substituted or unsubstituted 4 membered heterocycloalkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted 5 membered heterocycloalkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted 6 membered heterocycloalkylene. In embodiments, L 108 is R 113 -substituted or unsubstituted heterocycloalkylene (e.g., 3 to 6 membered heterocycloalkylene, 4 to 6 membered heterocycloalkylene, or 5 to 6 membered heterocycloalkylene). In embodiments, L 108 is R 113 -substituted 4 membered heterocycloalkylene. In embodiments, L 108 is R 113 -substituted 5 membered heterocycloalkylene. In embodiments, L 108 is R 113 -substituted 6 membered heterocycloalkylene. In embodiments, L 108 is R 113 -substituted heterocycloalkylene (e.g., 3 to 6 membered heterocycloalkylene, 4 to 6 membered heterocycloalkylene, or 5 to 6 membered heterocycloalkylene). In embodiments, L 108 is unsubstituted 4 membered heterocycloalkylene. In embodiments, L 108 is unsubstituted 5 membered heterocycloalkylene. In embodiments, L 108 unsubstituted 6 membered heterocycloalkylene. In embodiments, L 108 is unsubstituted heterocycloalkylene (e.g., 3 to 6 membered heterocycloalkylene, 4 to 6 membered heterocycloalkylene, or 5 to 6 membered heterocycloalkylene).

In embodiments, L 108 is R 113 -substituted or unsubstituted arylene (e.g. C 6 -C 10 arylene or C 6 arylene). In embodiments, L 108 is R 113 -substituted or unsubstituted C 6 -C 10 arylene. In embodiments, L 108 is R 113 -substituted or unsubstituted C 6 arylene. In embodiments, L 108 is R 113 -substituted arylene (e.g. C 6 -C 10 arylene or C 6 arylene). In embodiments, L 108 is R 113 -substituted C 6 -C 10 arylene. In embodiments, L 108 is R 113 -substituted C 6 arylene. In embodiments, L 108 is unsubstituted C 6 -C 10 arylene. In embodiments, L 108 is unsubstituted C 6 arylene.

In embodiments, L 108 is R 113 -substituted or unsubstituted heteroarylene (e.g. 5 to 10 membered heteroarylene, 5 to 9 membered heteroarylene, or 5 to 6 membered heteroarylene). In embodiments, L 108 is R 113 -substituted or unsubstituted 5 to 10 membered heteroarylene. In embodiments, L 108 is R 113 -substituted or unsubstituted 5 to 9 membered heteroarylene. In embodiments, L 108 is R 113 -substituted or unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 108 is R 113 -substituted heteroarylene (e.g. 5 to 10 membered heteroarylene, 5 to 9 membered heteroarylene, or 5 to 6 membered heteroarylene). In embodiments, L 108 is R 113 -substituted 5 to 10 membered heteroarylene. In embodiments, L 108 is R 113 -substituted 5 to 9 membered heteroarylene. In embodiments, L 108 is R 113 -substituted 5 to 6 membered heteroarylene. In embodiments, L 108 is unsubstituted heteroarylene (e.g. 5 to 10 membered heteroarylene, 5 to 9 membered heteroarylene, or 5 to 6 membered heteroarylene). In embodiments, L 108 is unsubstituted 5 to 10 membered heteroarylene. In embodiments, L 108 is unsubstituted 5 to 9 membered heteroarylene. In embodiments, L 108 is unsubstituted 5 to 6 membered heteroarylene. In embodiments, L 108 is R 113 -substituted or unsubstituted indolinylene. In embodiments, L 108 is R 13 -substituted or unsubstituted indazolylene. In embodiments, L 108 is R 113 -substituted or unsubstituted benzimidazolylene. In embodiments, L 108 is R 113 -substituted or unsubstituted benzoxazolylene. In embodiments, L 108 is R 113 -substituted or unsubstituted azaindolylene. In embodiments, L 108 is R 113 -substituted or unsubstituted purinylene. In embodiments, L 108 is R 113 -substituted or unsubstituted indolylene. In embodiments, L 108 is R 113 -substituted or unsubstituted pyrazinylene. In embodiments, L 108 is R 113 -substituted or unsubstituted pyrrolylene. In embodiments, L 108 is R 113 -substituted or unsubstituted imidazolylene. In embodiments, L 108 is R 113 -substituted or unsubstituted pyrazolylene. In embodiments, L 108 is R 113 -substituted or unsubstituted triazolylene. In embodiments, L 108 is R 113 -substituted or unsubstituted tetrazolylene.

In embodiments, L 108 is R 113 -substituted indolinylene. In embodiments, L 108 is R 113 substituted indazolylene. In embodiments, L 108 is R 113 -substituted benzimidazolylene. In embodiments, L 108 is R 113 -substituted benzoxazolylene. In embodiments, L 108 is R 113 -substituted azaindolylene. In embodiments, L 108 is R 113 -substituted purinylene. In embodiments, L 108 is R 113 -substituted indolylene. In embodiments, L 108 is R 113 -substituted pyrazinylene. In embodiments, L 108 is R 113 -substituted pyrrolylene. In embodiments, L 108 is R 113 -substituted imidazolylene. In embodiments, L 108 is R 113 -substituted pyrazolylene. In embodiments, L 108 is R 113 -substituted triazolylene. In embodiments, L 108 is R 113 -substituted tetrazolylene.

In embodiments, L 108 is unsubstituted indolinylene. In embodiments, L 108 is unsubstituted indazolylene. In embodiments, L 108 is unsubstituted benzimidazolylene. In embodiments, L 108 is unsubstituted benzoxazolylene. In embodiments, L 108 is unsubstituted azaindolylene. In embodiments, L 108 is unsubstituted purinylene. In embodiments, L 108 is unsubstituted indolylene. In embodiments, L 108 is unsubstituted pyrazinylene. In embodiments, L 108 is unsubstituted pyrrolylene. In embodiments, L 108 is unsubstituted imidazolylene. In embodiments, L 108 is unsubstituted pyrazolylene. In embodiments, L 108 is unsubstituted triazolylene. In embodiments, L 108 is unsubstituted tetrazolylene.

In embodiments, R 109 is independently hydrogen. In embodiments, R 109 is independently halogen. In embodiments, R 109 is independently —CX 109 3 . In embodiments, R 109 is independently —CHX 109 2 . In embodiments, R 109 is independently —CH 2 X 109 . In embodiments, R 109 is independently —OCX 109 3 . In embodiments, R 109 is independently —OCH 2 X 109 . In embodiments, R 109 is independently —OCHX 109 2 . In embodiments, R 109 is independently —CN. In embodiments, R 109 is independently —SO n109 R 109D . In embodiments, R 109 is independently —SO v109 NR 109A R 109B . In embodiments, R 109 is independently —NHC(O)NR 109A R 109B . In embodiments, R 109 is independently —N(O) m109 . In embodiments, R 109 is independently —NR 109A R 109B . In embodiments, R 109 is independently —C(O)R 109C . In embodiments, R 109 is independently —C(O)—OR 109C . In embodiments, R 109 is independently —C(O)NR 109A R 109B . In embodiments, R 109 is independently —OR 109D . In embodiments, R 109 is independently —NR 109A SO 2 R 109D . In embodiments, R 109 is independently —NR 109A C(O)R 109C . In embodiments, R 109 is independently —NR 109A C(O)OR 109C . In embodiments, R 109 is independently —NR 109A OR 109C . In embodiments, R 109 is independently —OH. In embodiments, R 109 is independently —NH 2 . In embodiments, R 109 is independently —COOH. In embodiments, R 109 is independently —CONH 2 . In embodiments, R 109 is independently —NO 2 . In embodiments, R 109 is independently —SH.

In embodiments, R 109 is independently substituted or unsubstituted alkyl. In embodiments, R 109 is independently substituted or unsubstituted heteroalkyl. In embodiments, R 109 is independently substituted or unsubstituted cycloalkyl. In embodiments, R 109 is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 109 is independently substituted or unsubstituted aryl. In embodiments, R 109 is independently substituted or unsubstituted heteroaryl. In embodiments, R 109 is independently substituted alkyl. In embodiments, R 109 is independently substituted heteroalkyl. In embodiments, R 109 is independently substituted cycloalkyl. In embodiments, R 109 is independently, substituted heterocycloalkyl. In embodiments, R 109 is independently substituted aryl. In embodiments, R 109 is independently substituted heteroaryl. In embodiments, R 109 is independently unsubstituted alkyl. In embodiments, R 109 is independently unsubstituted heteroalkyl. In embodiments, R 109 is independently unsubstituted cycloalkyl. In embodiments, R 109 is independently, unsubstituted heterocycloalkyl. In embodiments, R 109 is independently unsubstituted aryl. In embodiments, R 109 is independently unsubstituted heteroaryl. In embodiments, R 109 is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 109 is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 109 is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 109 is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109 is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 109 is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 109 is independently substituted C 1 -C 8 alkyl. In embodiments, R 109 is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 109 is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 109 is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109 is independently substituted C 6 -C 10 aryl. In embodiments, R 109 is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 109 is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 109 is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 109 is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 109 is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109 is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 109 is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 109 is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 109 is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 109 is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 109 is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109 is independently substituted or unsubstituted phenyl. In embodiments, R 109 is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 109 is independently substituted C 1 -C 4 alkyl. In embodiments, R 109 is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 109 is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 109 is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109 is independently substituted phenyl. In embodiments, R 109 is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 109 is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 109 is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 109 is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 109 is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109 is independently unsubstituted phenyl. In embodiments, R 109 is independently unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 109A is independently hydrogen. In embodiments, R 109A is independently —CX 109A 3 . In embodiments, R 109A is independently —CHX 109A 2 . In embodiments, R 109A is independently —CH 2 X 109A . In embodiments, R 109A is independently —CN. In embodiments, R 109A is independently —COOH. In embodiments, R 109A is independently —CONH 2 . In embodiments, R 109A is independently substituted or unsubstituted alkyl. In embodiments, R 109A is independently substituted or unsubstituted heteroalkyl. In embodiments, R 109A is independently substituted or unsubstituted cycloalkyl. In embodiments, R 109A is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 109A is independently substituted or unsubstituted aryl. In embodiments, R 109A is independently substituted or unsubstituted heteroaryl. In embodiments, R 109A is independently substituted alkyl. In embodiments, R 109A is independently substituted heteroalkyl. In embodiments, R 109A is independently substituted cycloalkyl. In embodiments, R 109A is independently, substituted heterocycloalkyl. In embodiments, R 109A is independently substituted aryl. In embodiments, R 109A is independently substituted heteroaryl. In embodiments, R 109A is independently unsubstituted alkyl. In embodiments, R 109A is independently unsubstituted heteroalkyl. In embodiments, R 109A is independently unsubstituted cycloalkyl. In embodiments, R 109A is independently, unsubstituted heterocycloalkyl. In embodiments, R 109A is independently unsubstituted aryl. In embodiments, R 109A is independently unsubstituted heteroaryl. In embodiments, R 109A is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 109A is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 109A is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 109A is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109A is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 109A is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 109A is independently substituted C 1 -C 8 alkyl. In embodiments, R 109A is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 109A is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 109A is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109A is independently substituted C 6 -C 10 aryl. In embodiments, R 109A is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 109A is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 109A is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 109A is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 109A is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109A is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 109A is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 109A is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 109A is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 109A is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 109A is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109A is independently substituted or unsubstituted phenyl. In embodiments, R 109A is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 109A is independently substituted C 1 -C 4 alkyl. In embodiments, R 109A is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 109A is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 109A is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109A is independently substituted phenyl. In embodiments, R 109A is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 109A is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 109A is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 109A is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 109A is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109A is independently unsubstituted phenyl. In embodiments, R 9A is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 109A is independently unsubstituted methyl. In embodiments, R 109A is independently unsubstituted ethyl. In embodiments, R 19A is independently unsubstituted propyl. In embodiments, R 109A is independently unsubstituted isopropyl. In embodiments, R 109A is independently unsubstituted tert-butyl.

In embodiments, R 109B is independently hydrogen. In embodiments, R 109B is independently —CX 109B 3 . In embodiments, R 109B is independently —CHX 109B 2 . In embodiments, R 109B is independently —CH 2 X 109B . In embodiments, R 109B is independently —CN. In embodiments, R 109B is independently —COOH. In embodiments, R 109B is independently —CONH 2 . In embodiments, R 109B is independently substituted or unsubstituted alkyl. In embodiments, R 109B is independently substituted or unsubstituted heteroalkyl. In embodiments, R 109B is independently substituted or unsubstituted cycloalkyl. In embodiments, R 109B is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 109B is independently substituted or unsubstituted aryl. In embodiments, R 109B is independently substituted or unsubstituted heteroaryl. In embodiments, R 109B is independently substituted alkyl. In embodiments, R 109B is independently substituted heteroalkyl. In embodiments, R 109B is independently substituted cycloalkyl. In embodiments, R 109B is independently, substituted heterocycloalkyl. In embodiments, R 109B is independently substituted aryl. In embodiments, R 109B is independently substituted heteroaryl. In embodiments, R 109B is independently unsubstituted alkyl. In embodiments, R 109B is independently unsubstituted heteroalkyl. In embodiments, R 109B is independently unsubstituted cycloalkyl. In embodiments, R 109B is independently, unsubstituted heterocycloalkyl. In embodiments, R 109B is independently unsubstituted aryl. In embodiments, R 109B is independently unsubstituted heteroaryl. In embodiments, R 109B is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 109B is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 109B is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 109B is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109B is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 109B is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 109B is independently substituted C 1 -C 8 alkyl. In embodiments, R 109B is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 109B is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 109B is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109B is independently substituted C 6 -C 10 aryl. In embodiments, R 109B is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 109B is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 109B is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 109B is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 109B is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109B is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 109B is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 109B is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 109B is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 109B is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 109B is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109B is independently substituted or unsubstituted phenyl. In embodiments, R 109 is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 109B is independently substituted C 1 -C 4 alkyl. In embodiments, R 109B is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 109B is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 109B is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109B is independently substituted phenyl. In embodiments, R 109B is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 109B is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 109B is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 109B is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 109B is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109B is independently unsubstituted phenyl. In embodiments, R 109B is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 109B is independently unsubstituted methyl. In embodiments, R 109B is independently unsubstituted ethyl. In embodiments, R 109B is independently unsubstituted propyl. In embodiments, R 109B is independently unsubstituted isopropyl. In embodiments, R 109B is independently unsubstituted tert-butyl.

In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heterocycloalkyl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted heteroaryl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to forma substituted heterocycloalkyl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form a substituted heteroaryl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heterocycloalkyl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted heteroaryl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 10 membered heteroaryl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form a substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form a substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form a substituted 5 to 6 membered heteroaryl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may be joined to form an unsubstituted 5 to 6 membered heteroaryl.

In embodiments, R 109C is independently hydrogen. In embodiments, R 109C is independently —CX 109C 3 . In embodiments, R 109C is independently —CHX 109C 2 . In embodiments, R 109C is independently —CH 2 X 109C . In embodiments, R 109C is independently —CN. In embodiments, R 109C is independently —COOH. In embodiments, R 109C is independently —CONH 2 . In embodiments, R 109C is independently substituted or unsubstituted alkyl. In embodiments, R 109C is independently substituted or unsubstituted heteroalkyl. In embodiments, R 109C is independently substituted or unsubstituted cycloalkyl. In embodiments, R 109C is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 109C is independently substituted or unsubstituted aryl. In embodiments, R 109C is independently substituted or unsubstituted heteroaryl. In embodiments, R 109C is independently substituted alkyl. In embodiments, R 109C is independently substituted heteroalkyl. In embodiments, R 109C is independently substituted cycloalkyl. In embodiments, R 109C is independently, substituted heterocycloalkyl. In embodiments, R 109C is independently substituted aryl. In embodiments, R 109C is independently substituted heteroaryl. In embodiments, R 109C is independently unsubstituted alkyl. In embodiments, R 109C is independently unsubstituted heteroalkyl. In embodiments, R 109C is independently unsubstituted cycloalkyl. In embodiments, R 109C is independently, unsubstituted heterocycloalkyl. In embodiments, R 109C is independently unsubstituted aryl. In embodiments, R 109C is independently unsubstituted heteroaryl. In embodiments, R 109C is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 109C is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 109C is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 109C is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109C is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 109C is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 109C is independently substituted C 1 -C 8 alkyl. In embodiments, R 109C is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 109C is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 109C is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109C is independently substituted C 6 -C 10 aryl. In embodiments, R 109C is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 109C is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 109C is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 109C is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 109C is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109C is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 109C is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 109C is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 109C is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 109C is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 109C is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109C is independently substituted or unsubstituted phenyl. In embodiments, R 109C is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 109C is independently substituted C 1 -C 4 alkyl. In embodiments, R 109C is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 109C is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 109C is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109C is independently substituted phenyl. In embodiments, R 109C is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 109C is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 109C is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 109C is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 109C is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109C is independently unsubstituted phenyl. In embodiments, R 109C is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 109C is independently unsubstituted methyl. In embodiments, R 109C is independently unsubstituted ethyl. In embodiments, R 109C is independently unsubstituted propyl. In embodiments, R 109C is independently unsubstituted isopropyl. In embodiments, R 109C is independently unsubstituted tert-butyl.

In embodiments, R 109D is independently hydrogen. In embodiments, R 109D is independently —CX 109D 3 . In embodiments, R 109D is independently —CHX 109D 2 . In embodiments, R 109D is independently —CH 2 X 109D . In embodiments, R 109D is independently —CN. In embodiments, R 109D is independently —COOH. In embodiments, R 109D is independently —CONH 2 . In embodiments, R 109D is independently substituted or unsubstituted alkyl. In embodiments, R 109D is independently substituted or unsubstituted heteroalkyl. In embodiments, R 109D is independently substituted or unsubstituted cycloalkyl. In embodiments, R 109D is independently, substituted or unsubstituted heterocycloalkyl. In embodiments, R 109D is independently substituted or unsubstituted aryl. In embodiments, R 109D is independently substituted or unsubstituted heteroaryl. In embodiments, R 109D is independently substituted alkyl. In embodiments, R 109D is independently substituted heteroalkyl. In embodiments, R 109D is independently substituted cycloalkyl. In embodiments, R 109D is independently, substituted heterocycloalkyl. In embodiments, R 109D is independently substituted aryl. In embodiments, R 109D is independently substituted heteroaryl. In embodiments, R 109D is independently unsubstituted alkyl. In embodiments, R 109D is independently unsubstituted heteroalkyl. In embodiments, R 109D is independently unsubstituted cycloalkyl. In embodiments, R 109D is independently, unsubstituted heterocycloalkyl. In embodiments, R 109D is independently unsubstituted aryl. In embodiments, R 109D is independently unsubstituted heteroaryl. In embodiments, R 109D is independently substituted or unsubstituted C 1 -C 8 alkyl. In embodiments, R 109D is independently substituted or unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 109D is independently substituted or unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 109D is independently, substituted or unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109D is independently substituted or unsubstituted C 6 -C 10 aryl. In embodiments, R 109D is independently substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 109D is independently substituted C 1 -C 8 alkyl. In embodiments, R 109D is independently substituted 2 to 8 membered heteroalkyl. In embodiments, R 109D is independently substituted C 3 -C 8 cycloalkyl. In embodiments, R 109D is independently, substituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109D is independently substituted C 6 -C 10 aryl. In embodiments, R 109D is independently substituted 5 to 10 membered heteroaryl. In embodiments, R 109D is independently unsubstituted C 1 -C 8 alkyl. In embodiments, R 109D is independently unsubstituted 2 to 8 membered heteroalkyl. In embodiments, R 109D is independently unsubstituted C 3 -C 8 cycloalkyl. In embodiments, R 109D is independently, unsubstituted 3 to 8 membered heterocycloalkyl. In embodiments, R 109D is independently unsubstituted C 6 -C 10 aryl. In embodiments, R 109D is independently unsubstituted 5 to 10 membered heteroaryl. In embodiments, R 109D is independently substituted or unsubstituted C 1 -C 4 alkyl. In embodiments, R 109D is independently substituted or unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 109D is independently substituted or unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 109D is independently, substituted or unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109D is independently substituted or unsubstituted phenyl. In embodiments, R 109D is independently substituted or unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 109D is independently substituted C 1 -C 4 alkyl. In embodiments, R 109D is independently substituted 2 to 4 membered heteroalkyl. In embodiments, R 109D is independently substituted C 3 -C 6 cycloalkyl. In embodiments, R 109D is independently, substituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109D is independently substituted phenyl. In embodiments, R 109D is independently substituted 5 to 6 membered heteroaryl. In embodiments, R 109D is independently unsubstituted C 1 -C 4 alkyl. In embodiments, R 109D is independently unsubstituted 2 to 4 membered heteroalkyl. In embodiments, R 109D is independently unsubstituted C 3 -C 6 cycloalkyl. In embodiments, R 109D is independently unsubstituted 3 to 6 membered heterocycloalkyl. In embodiments, R 109D is independently unsubstituted phenyl. In embodiments, R 109D is independently unsubstituted 5 to 6 membered heteroaryl. In embodiments, R 109D is independently unsubstituted methyl. In embodiments, R 109D is independently unsubstituted ethyl. In embodiments, R 109D is independently unsubstituted propyl. In embodiments, R 109D is independently unsubstituted isopropyl. In embodiments, R 109D is independently unsubstituted tert-butyl.

In embodiments, R 109 is independently hydrogen,

halogen, —CX 109 3 , —CHX 109 2 , —CH 2 X 109 , —OCX 109 3 , —OCH 2 X 109 , —OCHX 109 2 , —CN, —SO n109 R 109D , —SO v109 NR 109A R 109B , —NHC(O)NR 109A R 109B , —N(O) m109 , —NR 109A R 109B , —C(O)R 109C , —C(O)OR 109C , —C(O)NR 109A R 109B , —OR 109D , —NR 109A SO 2 R 109D , —NR 109A C(O)R 109C , —NR 109A C(O)OR 109C , —NR 109A OR 109C , R 110 -substituted or unsubstituted alkyl, R 110 -substituted or unsubstituted heteroalkyl, R 110 -substituted or unsubstituted cycloalkyl, R 110 -substituted or unsubstituted heterocycloalkyl, R 110 -substituted or unsubstituted aryl, or R 110 -substituted or unsubstituted heteroaryl. In embodiments, R 109 is independently

halogen, —CX 109 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 109 3 , —OCHX 109 2 , R-substituted or unsubstituted alkyl, R 110 -substituted or unsubstituted heteroalkyl, R 110 -substituted or unsubstituted cycloalkyl, R 110 -substituted or unsubstituted heterocycloalkyl, R 110 -substituted or unsubstituted aryl, or R 110 -substituted or unsubstituted heteroaryl. In embodiments, R 109 is independently

halogen, —CX 109 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —S 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 109 3 , —OCHX 109 2 , R 110 -substituted or unsubstituted C 1 -C 8 alkyl, R 110 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 110 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 110 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 110 -substituted or unsubstituted phenyl, or R 110 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 109 is —F, —Cl, —Br, or —I. In embodiments, R 109 is independently hydrogen. In embodiments, R 109 is independently methyl. In embodiments, R 109 is independently ethyl.

In embodiments, R 109 is independently

halogen, —CX 109 3 , —CN, —OH, —COOH, —CONH 2 , —OCX 109 3 , —OCHX 109 2 , R 109 -substituted or unsubstituted C 1 -C 8 alkyl, R 109 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 109 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 109 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 109 -substituted or unsubstituted phenyl, or R 109 -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 110 is independently oxo,

halogen, —CX 110 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 110 3 , —OCHX 110 2 , R 111 -substituted or unsubstituted alkyl, R 111 -substituted or unsubstituted heteroalkyl, R 111 -substituted or unsubstituted cycloalkyl, R 111 -substituted or unsubstituted heterocycloalkyl, R 111 -substituted or unsubstituted aryl, or R 111 -substituted or unsubstituted heteroaryl. In embodiments, R 110 is independently oxo,

halogen, —CX 110 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 110 3 , —OCHX 110 2 , R 111 -substituted or unsubstituted C 1 -C 8 alkyl, R 111 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 111 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 111 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 111 -substituted or unsubstituted phenyl, or R 111 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 110 is —F, —Cl, —Br, or —I.

R 111 is independently oxo,

halogen, —CX 111 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 111 3 , —OCHX 111 2 , R 112 -substituted or unsubstituted alkyl, R 112 -substituted or unsubstituted heteroalkyl, R 112 -substituted or unsubstituted cycloalkyl, R 112 -substituted or unsubstituted heterocycloalkyl, R 112 -substituted or unsubstituted aryl, or R 112 -substituted or unsubstituted heteroaryl. In embodiments, R 111 is independently oxo,

halogen, —CX 111 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —S 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 111 3 , —OCHX 111 2 , R 112 -substituted or unsubstituted C 1 -C 8 alkyl, R 112 -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 112 -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 112 -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 112 -substituted or unsubstituted phenyl, or R 112 -substituted or unsubstituted 5 to 6 membered heteroaryl. X 111 is —F, —Cl, —Br, or —I.

In embodiments, R 109A is independently

hydrogen, —CX 109A 3 , —CN, —COOH, —CONH 2 , —CHX 109A 2 , —CH 2 X 109A , R 110A -substituted or unsubstituted alkyl, R 110A -substituted or unsubstituted heteroalkyl, R 110A -substituted or unsubstituted cycloalkyl, R 110A -substituted or unsubstituted heterocycloalkyl, R 110A -substituted or unsubstituted aryl, or R 110A -substituted or unsubstituted heteroaryl. In embodiments, R 109A is independently hydrogen, —CX 109A 3 , —CN, —COOH, —CONH 2 , —CHX 109A 2 , —CH 2 X 109A , R 110A -substituted or unsubstituted C 1 -C 8 alkyl, R 110A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 110A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 110A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 110A -substituted or unsubstituted phenyl, or R 110A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 109A is —F, —Cl, —Br, or —I. In embodiments, R 109A is independently hydrogen. In embodiments, R 109A is independently methyl. In embodiments, R 109A is independently ethyl.

In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may optionally be joined to form a R 110A -substituted or unsubstituted heterocycloalkyl or R 110A -substituted or unsubstituted heteroaryl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may optionally be joined to form a R 110A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl or R 110A -substituted or unsubstituted 5 to 6 membered heteroaryl.

R 110A is independently oxo,

halogen, —CX 110A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 110A 3 , —OCHX 110A 2 , R 111A -substituted or unsubstituted alkyl, R 111A -substituted or unsubstituted heteroalkyl, R 111A -substituted or unsubstituted cycloalkyl, R 111A -substituted or unsubstituted heterocycloalkyl, R 111A -substituted or unsubstituted aryl, or R 111A -substituted or unsubstituted heteroaryl. In embodiments, R 111A is independently oxo,

halogen, —CX 110A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 110A 3 , —OCHX 110A 2 , R 111A -substituted or unsubstituted C 1 -C 8 alkyl, R 111A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 111A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 111A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 111A -substituted or unsubstituted phenyl, or R 111A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 110A is —F, —Cl, —Br, or —I.

R 111A is independently oxo,

halogen, —CX 111A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 111A 3 , —OCHX 111A 2 , R 112A -substituted or unsubstituted alkyl, R 112A -substituted or unsubstituted heteroalkyl, R 112A -substituted or unsubstituted cycloalkyl, R 112A -substituted or unsubstituted heterocycloalkyl, R 112A -substituted or unsubstituted aryl, or R 112A -substituted or unsubstituted heteroaryl. In embodiments, R 111A is independently oxo,

halogen, —CX 111A 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCX 111A3 , —OCHX 111A 2 , R 112A -substituted or unsubstituted C 1 -C 8 alkyl, R 112A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 112A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 112A -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 112A -substituted or unsubstituted phenyl, or R 112A -substituted or unsubstituted 5 to 6 membered heteroaryl. X 111A is —F, —Cl, —Br, or —I.

In embodiments, R 109B is independently

hydrogen, —CX 109B 3 , —CN, —COOH, —CONH 2 , —CHX 109B 2 , —CH 2 X 109B , R 110B -substituted or unsubstituted alkyl, R 110B -substituted or unsubstituted heteroalkyl, R 110B -substituted or unsubstituted cycloalkyl, R 110B -substituted or unsubstituted heterocycloalkyl, R 110B -substituted or unsubstituted aryl, or R 110B -substituted or unsubstituted heteroaryl. In embodiments, R 109B is independently hydrogen, —CX 109B 3 , —CN, —COOH, —CONH 2 , —CHX 109B 2 , —CH 2 X 109B , R 110B -substituted or unsubstituted C 1 -C 8 alkyl, R 110B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 110B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 110B -substituted or unsubstituted 3 to 6 membered heterocycloalkyl, R 110B -substituted or unsubstituted phenyl, or R 110B -substituted or unsubstituted 5 to 6 membered heteroaryl. X 109B is —F, —Cl, —Br, or —I. In embodiments, R 109B is independently hydrogen. In embodiments, R 109B is independently methyl. In embodiments, R 109B is independently ethyl.

In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may optionally be joined to form a R 110B -substituted or unsubstituted heterocycloalkyl or R 110B -substituted or unsubstituted heteroaryl. In embodiments, R 109A and R 109B substituents bonded to the same nitrogen atom may optionally be joined to form a R 110B -substituted or unsubstituted 3 to 6 membered h