Azaquinazoline inhibitors of atypical protein kinase C

This application is a continuation application and claims the benefit under 35 U.S.C. §120 of the priority date of U.S. application Ser. No. 14/038,915, filed Sep. 27, 2013, which claims the benefit under 35 U.S.C. §119(e) of the priority date of U.S. Provisional Application Nos. 61/707,340, filed Sep. 28, 2012 and 61/781,364, filed Mar. 14, 2013, the disclosures of each of which are incorporated herein by reference in their entireties.

PKCι and PKCζ (accession numbers NM_002740 and NM_002744 respectively) together define the atypical sub-class of the protein kinase C (PKC) family. The aPKCs are structurally and functionally distinct from the other PKC sub-classes, classic/conventional and novel, as their catalytic activity is not dependent on diacylglycerol and calcium (Ono, Y., Fujii, T., Ogita, K., Kikkawa, U., Igarashi, K., and Nishizuka, Y. (1989). Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties. Proc Natl Acad Sci USA 86, 3099-3103). Structurally, PKCι and PKCζ contain a C-terminal serine/threonine kinase domain (AGC class) and an N-terminal regulatory region containing a Phox Bem 1 (PB 1) domain involved in mediating protein:protein interactions critical for aPKC function. At the amino acid level the aPKCs share 72% overall homology, however, the kinase domains share 84% identity and differ in the active site by just a single amino acid. This striking homology suggests an ATP-competitive ligand would not be expected to exhibit significant aPKC isoform selectivity.

The aPKCs have been implicated in a diverse number of signalling pathways, demonstrating both redundant and distinct signalling functions. Both isoforms have emerged as central players in the mechanisms that regulate the establishment and maintenance of cellular polarity in multiple cell types (reviewed in Suzuki, A., and Ohno, S. (2006). The PAR-aPKC system: lessons in polarity. J Cell Sci 119, 979-987). Genetic dissection of their functions using knockout mice have also revealed preferential roles for PKCζ in the regulation of NF-kB signalling (Leitges, M., Sanz, L., Martin, P., Duran, A., Braun, U., Garcia, J. F., Camacho, F., Diaz-Meco, M. T., Rennert, P. D., and Moscat, J. (2001). Targeted disruption of the zetaPKC gene results in the impairment of the NF-kappaB pathway. Mol Cell 8, 771-780), and PKCι in insulin secretion and action (Farese, R. V., Sajan, M. P., Yang, H., Li, P., Mastorides, S., Gower, W. R., Jr., Nimal, S., Choi, C. S., Kim, S., Shulman, G. I., et al. (2007). Muscle-specific knockout of PKC-lambda impairs glucose transport and induces metabolic and diabetic syndromes. J Clin Invest 117, 2289-2301). In addition, both isoforms have been implicated in the pathogenesis of cancer making a strong case for the inhibition of the aPKCs as a novel therapeutic avenue.

PKCι is a known oncogene in non-small cell lung cancer (NSCLC). In one study it was shown to be overexpressed in 69% of NSCLC cases at the protein level. Consistent with this, the PKCι gene (PRKCI residing on chromosome 3q26) was shown to be amplified in 36.5% of NSCLC tumours examined, including 96% of the squamous cell carcinoma sub-type (Regala, R. P., Weems, C., Jamieson, L., Khoor, A., Edell, E. S., Lohse, C. M., and Fields, A. P. (2005b). Atypical protein kinase C iota is an oncogene in human non-small cell lung cancer. Cancer Res 65, 8905-8911). Amplification of 3q26 has also been reported in 44% of ovarian cancers, including >70% of serous epithelial ovarian cancers where 3q26 amplification is translated into increased PKCι protein expression. Moreover, increased PKCι expression is associated with poor prognosis in NSCLC and ovarian cancer where it may serve as a diagnostic biomarker of aggressive disease (Eder, A. M., Sui, X., Rosen, D. G., Nolden, L. K., Cheng, K. W., Lahad, J. P., Kango-Singh, M., Lu, K. H., Warneke, C. L., Atkinson, E. N., et al. (2005). Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer. Proc Natl Acad Sci USA 102, 12519-12524; Zhang, L., Huang, J., Yang, N., Liang, S., Barchetti, A., Giannakakis, A., Cadungog, M. G., O'Brien-Jenkins, A., Massobrio, M., Roby, K. F., et al. (2006). Integrative genomic analysis of protein kinase C (PKC) family identifies PKCiota as a biomarker and potential oncogene in ovarian carcinoma. Cancer Res 66, 4627-4635). 3q26 amplifications have been observed in many other cancers including oesophageal squamous cell carcinoma (Yang, Y. L., Chu, J. Y., Luo, M. L., Wu, Y. P., Zhang, Y., Feng, Y. B., Shi, Z. Z., Xu, X., Han, Y. L., Cai, Y., et al. (2008). Amplification of PRKCI, located in 3q26, is associated with lymph node metastasis in esophageal squamous cell carcinoma. Genes Chromosomes Cancer 47, 127-136) and breast cancer (Kojima, Y., Akimoto, K., Nagashima, Y., Ishiguro, H., Shirai, S., Chishima, T., Ichikawa, Y., Ishikawa, T., Sasaki, T., Kubota, Y., et al. (2008). The overexpression and altered localization of the atypical protein kinase C lambda/iota in breast cancer correlates with the pathologic type of these tumors. Hum Pathol 39, 824-831) suggesting that PKCι may also participate in the pathogenesis of these diseases.

In NSCLC the primary function of PKCι is to drive transformed growth via a Rac1/PAK/MEK/ERK signalling axis. However, PKCι also functions in NSCLC survival, resistance to chemotherapy, and invasion via distinct pathways (reviewed in Fields, A. P., and Regala, R. P. (2007). Protein kinase C iota: human oncogene, prognostic marker and therapeutic target. Pharmacol Res 55, 487-497). In ovarian cancer transformed growth is correlated with deregulated epithelial cell polarity and increased cycle E expression (Eder et al., 2005) suggesting that PKCι can influence the cancer phenotype through multiple mechanisms. Compelling evidence has emerged to suggest that inhibition of PKCι may be a useful therapeutic approach to combat tumours characterised by increased PKCι expression. In transgenic models, mice with elevated PKCι activity in the colon are more susceptible to carcinogen-induced colon carcinogenesis, and expression of a kinase-dead mutant of PKCι blocks the transformation of intestinal cells by oncogenic Ras (Murray, N. R., Jamieson, L., Yu, W., Zhang, J., Gokmen-Polar, Y., Sier, D., Anastasiadis, P., Gatalica, Z., Thompson, E. A., and Fields, A. P. (2004). Protein kinase Ciota is required for Ras transformation and colon carcinogenesis in vivo. J Cell Biol 164, 797-802). Finally, genetic or pharmacological inhibition of PKCι by a gold derivative—aurothiomalate (ATM)—blocks the growth of NSCLC cells in soft agar and significantly decreases tumour volume in xenograft models of NSCLC(Regala, R. P., Thompson, E. A., and Fields, A. P. (2008). Atypical protein kinase C iota expression and aurothiomalate sensitivity in human lung cancer cells. Cancer Res 68, 5888-5895; Regala, R. P., Weems, C., Jamieson, L., Copland, J. A., Thompson, E. A., and Fields, A. P. (2005a). Atypical protein kinase Ciota plays a critical role in human lung cancer cell growth and tumorigenicity. J Biol Chem 280, 31109-31115).

Despite the high degree of similarity between aPKC isoforms, the role of PKCζ in cancer is distinct from that of PKCι. PKCζ plays a role in NSCLC cell survival by phosphorylating and antagonising the pro-apoptotic effects of Bax in response to nicotine (Xin, M., Gao, F., May, W. S., Flagg, T., and Deng, X. (2007). Protein kinase Czeta abrogates the proapoptotic function of Bax through phosphorylation. J Biol Chem 282, 21268-21277). PKCζ activity has also been linked to resistance against a wide range of cytotoxic and genotoxic agents. For instance, in human leukaemia cells, overexpression of PKCζ confers resistance against 1-β-D-arabinofuranosylcytosine (ara-C), daunorubicin, etoposide, and mitoxantrone-induced apoptosis (Filomenko, R., Poirson-Bichat, F., Billerey, C., Belon, J. P., Garrido, C., Solary, E., and Bettaieb, A. (2002). Atypical protein kinase C zeta as a target for chemosensitization of tumor cells. Cancer Res 62, 1815-1821; Plo, I., Hernandez, H., Kohlhagen, G., Lautier, D., Pommier, Y., and Laurent, G. (2002). Overexpression of the atypical protein kinase C zeta reduces topoisomerase II catalytic activity, cleavable complexes formation, and drug-induced cytotoxicity in monocytic U937 leukemia cells. J Biol Chem 277, 31407-31415). Furthermore, inhibition of PKCζ activity through expression of a kinase-dead mutant sensitises leukaemia cells to the cytotoxic effects of etoposide both in vitro and in vivo (Filomenko et al., 2002). Atypical protein kinase C regulates dual pathways for degradation of the oncogenic coactivator SRC-3/AIB1. Mol Cell 29, 465-476), and both of these proteins have been postulated to play a role in tamoxifen resistance in breast cancer (Iorns, E., Lord, C. J., and Ashworth, A. (2009). Parallel RNAi and compound screens identify the PDK1 pathway as a target for tamoxifen sensitization. Biochem J 417, 361-370; Osborne, C. K., Bardou, V., Hopp, T. A., Chamness, G. C., Hilsenbeck, S. G., Fuqua, S. A., Wong, J., Allred, D. C., Clark, G. M., and Schiff, R. (2003). Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. J Natl Cancer Inst 95, 353-361). Together these studies suggest that inhibition of PKCζ activity may have beneficial therapeutic effects by acting as a chemosensitiser to a wide array of commonly used chemotoxic agents in the clinic.

Further evidence that small molecule inhibition of PKCζ could have important therapeutic benefits has recently emerged from tumour models that link PKCζ signalling to the mTOR pathway. PKCζ is constitutively activated in follicular lymphoma and has been identified as a novel target for the anti-CD20 therapeutic antibody rituximab (Leseux, L., Laurent, G., Laurent, C., Rigo, M., Blanc, A., Olive, D., and Bezombes, C. (2008). PKC zeta mTOR pathway: a new target for rituximab therapy in follicular lymphoma. Blood 111, 285-291). Rituximab inhibits follicular lymphoma proliferation by targeting a PKCζ-MAPK-mTOR pathway, suggesting that PKCζ is both a target of Rituximab, and a key regulator of its' anti-leukaemic effect. Regulation of the mTOR/p70S6K pathway by PKCζ has also been implicated in the transition of prostate cancer cells to an androgen-independent state (Inoue, T., Yoshida, T., Shimizu, Y., Kobayashi, T., Yamasaki, T., Toda, Y., Segawa, T., Kamoto, T., Nakamura, E., and Ogawa, O. (2006). Requirement of androgen-dependent activation of protein kinase Czeta for androgen-dependent cell proliferation in LNCaP Cells and its roles in transition to androgen-independent cells. Mol Endocrinol 20, 3053-3069). Finally, mice containing a homozygous deletion of Par4, a negative regulator of PKCζ, exhibit greatly enhanced PKCζ activity. These mice spontaneously develop tumours of the prostate and endometrium, and potentiate Ras-induced lung carcinogenesis consistent with a role for PKCζ in lung cancer (Garcia-Cao, I., Duran, A., Collado, M., Carrascosa, M. J., Martin-Caballero, J., Flores, J. M., Diaz-Meco, M. T., Moscat, J., and Serrano, M. (2005). Tumour-suppression activity of the proapoptotic regulator Par4. EMBO Rep 6, 577-583; Joshi, J., Fernandez-Marcos, P. J., Galvez, A., Amanchy, R., Linares, J. F., Duran, A., Pathrose, P., Leitges, M., Canamero, M., Collado, M., et al. (2008). Par-4 inhibits Akt and suppresses Ras-induced lung tumorigenesis. EMBO J 27, 2181-2193).

The application provides a compound of formula (I)

or a salt thereof, wherein R 7 , R 8 , R 9 , G, and X are as defined herein.

A compound of formula (I) and its salts have aPKC inhibitory activity, and may be used to treat aPKC-dependent disorders or conditions.

The present application further provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof together with at least one pharmaceutically acceptable carrier, diluent, or excipient therefor.

In another aspect, the present application provides a method of treating a subject suffering from an aPKC-dependent disorder or condition comprising: administering to the subject a compound of formula (I) or a pharmaceutically acceptable salt thereof.

The present application further provides a method of treating a proliferative disorder in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.

I. Definitions

“About” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass reasonable variations of the value, such as, for example, ±10% from the specified value. For example, the phrase “about 50” encompasses reasonable variations of 50, such as ±10% of the numerical value 50, or from 45 to 55.

“Alkyl” or “alkyl group” refers to a monoradical of a branched or unbranched saturated hydrocarbon chain. Examples include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, isopropyl, tert-butyl, isobutyl, etc. Alkyl groups typically contain 1-10 carbon atoms, such as 1-6 carbon atoms or 1-4 carbon atoms, and can be substituted or unsubstituted.

“Alkylene” or “alkylene group” refers to a diradical of a branched or unbranched saturated hydrocarbon chain. Examples include, but are not limited to, methylene (—CH 2 —), the ethylene isomers (—CH(CH 3 )— and —CH 2 CH 2 —), the propylene isomers (—CH(CH 3 )CH 2 —, —CH(CH 2 CH 3 )—, —C(CH 3 ) 2 —, and —CH 2 CH 2 CH 2 —), etc. Alkylene groups typically contain 1-10 carbon atoms, such as 1-6 carbon atoms, and can be substituted or unsubstituted.

“Alkenyl” or “alkenyl group” refers to a monoradical of a branched or unbranched hydrocarbon chain containing at least one double bond. Examples include, but are not limited to, ethenyl, 3-buten-1-yl, 2-ethenylbutyl, and 3-hexen-1-yl. Alkenyl groups typically contain 2-10 carbon atoms, such as 2-6 carbon atoms or 2-4 carbon atoms, and can be substituted or unsubstituted.

“Alkynyl” or “alkynyl group” refers to a monoradical of a branched or unbranched hydrocarbon chain containing at least one triple bond. Examples include, but are not limited to, ethynyl, 3-butyn-1-yl, propynyl, 2-butyn-1-yl, and 3-pentyn-1-yl. Alkynyl groups typically contain 2-10 carbon atoms, such as 2-6 carbon atoms or 2-4 carbon atoms, and can be substituted or unsubstituted.

“Aryl” or “aryl group” refers to phenyl and 7-15 membered monoradical bicyclic or tricyclic hydrocarbon ring systems, including bridged, spiro, and/or fused ring systems, in which at least one of the rings is aromatic. Aryl groups can be substituted or unsubstituted. Examples include, but are not limited to, naphthyl, indanyl, 1,2,3,4-tetrahydronaphthalenyl, 6,7,8,9-tetrahydro-5H-benzocycloheptenyl, and 6,7,8,9-tetrahydro-5H-benzocycloheptenyl. An aryl group may contain 6 (i.e., phenyl) or 9 to 15 ring atoms, such as 6 (i.e., phenyl) or 9-11 ring atoms, e.g., 6 (i.e., phenyl), 9 or 10 ring atoms.

“Arylene” or “arylene group” refers to a phenylene (—C 6 H 4 —) or a 7-15 membered diradical bicyclic or tricyclic hydrocarbon ring systems, including bridged, spiro, and/or fused ring systems, in which at least one of the rings is aromatic. Arylene groups can be substituted or unsubstituted. For example, an arylene group may contain 6 (i.e., phenylene) or 9 to 15 ring atoms; such as 6 (i.e., phenylene) or 9-11 ring atoms; e.g., 6 (i.e., phenylene), 9 or 10 ring atoms. An arylene group can also include ring systems substituted on ring carbons with one or more —OH functional groups (which may further tautomerize to give a ring C═O group).

“Arylalkyl” or “arylalkyl group” refers to an alkyl group in which a hydrogen atom is replaced by an aryl group, wherein alkyl group and aryl group are as previously defined (i.e., arylalkyl-). Arylalkyl groups can be substituted or unsubstituted. Examples include, but are not limited to, benzyl (C 6 H 5 CH 2 —).

“Cycloalkyl” or “cycloalkyl group” refers to a monoradical non-aromatic carbocyclic ring system, which may be saturated or unsaturated, substituted or unsubstituted, and may be monocyclic, bicyclic, or tricyclic, and may be bridged, spiro, and/or fused. Examples include, but are not limited to, cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, norbornyl, norbornenyl, bicyclo[2.2.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.1]heptene, bicyclo[3.1.1]heptane, bicyclo[3.2.1]octane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.1]nonane, and bicyclo[3.3.2]decane. The cycloalkyl group may contain from 3 to 10 ring atoms, such as 3 to 7 ring atoms (e.g., 3 ring atoms, 5 ring atoms, 6 ring atoms, or 7 ring atoms).

“Cycloalkylalkyl” or “cycloalkylalkyl group” refers to an alkyl group in which a hydrogen atom is replaced by a cycloalkyl group, wherein alkyl group and cycloalkyl group are as previously defined (i.e., cycloalkylalkyl-). Cycloalkylalkyl groups can be substituted or unsubstituted. Examples include, but are not limited to, cyclohexylmethyl (C 6 H 11 CH 2 —).

“Haloalkyl” or “haloalkyl group” refers to alkyl groups in which one or more hydrogen atoms are replaced by halogen atoms. Haloalkyl includes both saturated alkyl groups and unsaturated alkenyl and alkynyl groups, such as for example —CF 3 , —CHF 2 , —CH 2 F, —CF 2 CF 3 , —CHFCF 3 , —CH 2 CF 3 , —CF 2 CH 3 , —CHFCH 3 , —CF 2 CF 2 CF 3 , —CF 2 CH 2 CH 3 , —CF═CF 2 , —CCl═CH 2 , —CBr═CH 2 , —CI═CH 2 , —C≡C—CF 3 , —CHFCH 2 CH 3 and —CHFCH 2 CF 3 .

“Halogen” includes fluorine, chlorine, bromine and iodine atoms.

“Heteroaryl” or “heteroaryl group” refers to (a) 5 and 6 membered monocyclic aromatic rings, which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen or sulfur, and (b) 7-15 membered bicyclic and tricyclic rings, which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen or sulfur, and in which at least one of the rings is aromatic. Heteroaryl groups can be substituted or unsubstituted, and may be bridged, spiro, and/or fused. Examples include, but are not limited to, 2,3-dihydrobenzofuranyl, 1,2-dihydroquinolinyl, 3,4-dihydroisoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, benzoxazinyl, benzthiazinyl, chromanyl, furanyl, 2-furanyl, 3-furanyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, oxazolyl, pyridinyl, 2-, 3-, or 4-pyridinyl, pyrimidinyl, 2-, 4-, or 5-pyrimidinyl, pyrazolyl, pyrrolyl, 2- or 3-pyrrolyl, pyrazinyl, pyridazinyl, 3- or 4-pyridazinyl, 2-pyrazinyl, thienyl, 2-thienyl, 3-thienyl, tetrazolyl, thiazolyl, thiadiazolyl, triazinyl, triazolyl, pyridin-2-yl, pyridin-4-yl, pyrimidin-2-yl, pyridazin-4-yl, pyrazin-2-yl, naphthyridinyl, pteridinyl, phthalazinyl, purinyl, alloxazinyl, benzimidazolyl, benzofuranyl, benzofurazanyl, 2H-1-benzopyranyl, benzothiadiazine, benzothiazinyl, benzothiazolyl, benzothiophenyl, benzoxazolyl, cinnolinyl, furopyridinyl, indolinyl, indolizinyl, indolyl, or 2-, 3-, 4-, 5-, 6-, or 7-indolyl, 3H-indolyl, quinazolinyl, quinoxalinyl, isoindolyl, isoquinolinyl, 10-aza-tricyclo[6.3.1.0 2,7 ]dodeca-2(7),3,5-trienyl, 12-oxa-10-aza-tricyclo[6.3.1.0 2,7 ]dodeca-2(7),3,5-trienyl, 12-aza-tricyclo[7.2.1.0 2,7 ]dodeca-2(7),3,5-trienyl, 10-aza-tricyclo[6.3.2.0 2,7 ]trideca-2(7),3,5-trienyl, 2,3,4,5-tetrahydro-1H-benzo[d]azepinyl, 1,3,4,5-tetrahydro-benzo[d]azepin-2-onyl, 1,3,4,5-tetrahydro-benzo[b]azepin-2-onyl, 2,3,4,5-tetrahydro-benzo[c]azepin-1-onyl, 1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-onyl, 2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepinyl, 5,6,8,9-tetrahydro-7-oxa-benzocycloheptenyl, 2,3,4,5-tetrahydro-1H-benzo[b]azepinyl, 1,2,4,5-tetrahydro-benzo[e][1,3]diazepin-3-onyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, 3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-onyl, 6,7,8,9-tetrahydro-5-thia-8-aza-benzocycloheptenyl, 5,5-dioxo-6,7,8,9-tetrahydro-5-thia-8-aza-benzocycloheptenyl, and 2,3,4,5-tetrahydro-benzo[f][1,4]oxazepinyl. For example, a heteroaryl group may contain 5, 6, or 8-15 ring atoms. As another example, a heteroaryl group may contain 5 to 10 ring atoms, such as 5, 6, 9, or 10 ring atoms.

“Heteroarylalkyl” or “heteroarylalkyl group” refers to an alkyl group in which a hydrogen atom is replaced by a heteroaryl group, wherein alkyl group and heteroaryl group are as previously defined (i.e., heteroarylalkyl-). Heteroarylalkyl groups can be substituted or unsubstituted. Examples include, but are not limited to, the pyridinylmethyl isomers

“Heterocycloalkyl” or “heterocycloalkyl group” refers to 3-15 membered monocyclic, bicyclic, and tricyclic non-aromatic rings, which may be saturated or unsaturated, can be substituted or unsubstituted, may be bridged, spiro, and/or fused, and which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen, sulfur or phosphorus. Examples include, but are not limited to, tetrahydrofuranyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl, indolinyl, isoindolinyl, morpholinyl, thiomorpholinyl, homomorpholinyl, homopiperidyl, homopiperazinyl, thiomorpholinyl-5-oxide, thiomorpholinyl-S,S-dioxide, pyrrolidinyl, tetrahydropyranyl, piperidinyl, tetrahydrothienyl, homopiperidinyl, homothiomorpholinyl-S,S-dioxide, oxazolidinonyl, dihydropyrazolyl, dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydrofuryl, dihydropyranyl, tetrahydrothienyl-5-oxide, tetrahydrothienyl-S,S-dioxide, homothiomorpholinyl-5-oxide, quinuclidinyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 8-oxa-3-aza-bicyclo[3.2.1]octanyl, 3,8-diaza-bicyclo[3.2.1]octanyl, 2,5-diaza-bicyclo[2.2.1]heptanyl, 3,8-diaza-bicyclo[3.2.1]octanyl, 3,9-diaza-bicyclo[4.2.1]nonanyl, 2,6-diaza-bicyclo[3.2.2]nonanyl, [1,4]oxaphosphinanyl-4-oxide, [1,4]azaphosphinanyl-4-oxide, [1,2]oxaphospholanyl-2-oxide, phosphinanyl-1-oxide, [1,3]azaphospholidinynl-3-oxide, [1,3]oxaphospholanyl-3-oxide and 7-oxabicyclo[2.2.1]heptanyl. A heterocycloalkyl group may contain, in addition to carbon atom(s), at least one nitrogen, oxygen, or sulfur. For example, a heterocycloalkyl group may contain, in addition to carbon atom(s), at least one nitrogen or oxygen. A heterocycloalkyl group may contain, in addition to carbon atom(s), at least one nitrogen. A heterocycloalkyl group may contain carbon atoms and 1 or 2 nitrogen atoms. A heterocycloalkyl group may contain carbon atoms and an oxygen atom. A heterocycloalkyl group may contain carbon atoms, a nitrogen atom, and an oxygen atom. A heterocycloalkyl group may contain carbon atoms, a nitrogen atom, and a sulfur atom. A heterocycloalkyl group may contain carbon atoms and a sulfur atom. A heterocycloalkyl group may contain from 3 to 10 ring atoms. A heterocycloalkyl group may contain from 3 to 7 ring atoms. A heterocycloalkyl group may contain from 5 to 7 ring atoms, such as 5 ring atoms, 6 ring atoms, or 7 ring atoms. Unless otherwise indicated, the foregoing heterocycloalkyl groups can be C-attached or N-attached where such is possible and results in the creation of a stable structure. For example, piperidinyl can be piperidin-1-yl (N-attached) or piperidin-4-yl (C-attached).

“Heterocycloalkylene” or “heterocycloalkylene group” refers to diradical, 3-15 membered monocyclic, bicyclic, or tricyclic non-aromatic ring systems, which may be saturated or unsaturated, can be substituted or unsubstituted, may be bridged, spiro, and/or fused, and which contain, in addition to carbon atom(s), at least one heteroatom, such as nitrogen, oxygen, sulfur or phosphorus. Examples include, but are not limited to, the azridinylene isomers

The heterocycloalkylene group may contain, in addition to carbon atom(s), at least one nitrogen, oxygen, or sulfur. The heterocycloalkylene group may contain, in addition to carbon atom(s), at least one nitrogen or oxygen. The heterocycloalkylene group may contain, in addition to carbon atom(s), at least one nitrogen. For example, a heterocycloalkylene group may contain from 3 to 10 ring atoms; such as from 3 to 7 ring atoms. A heterocycloalkylene group may contain from 5 to 7 ring atoms, such as 5 ring atoms, 6 ring atoms, or 7 ring atoms. Unless otherwise indicated, the foregoing heterocycloalkylene groups can be C-attached and/or N-attached where such is possible and results in the creation of a stable structure. A heterocycloalkylene group can also include ring systems substituted on ring carbons with one or more —OH functional groups (which may further tautomerize to give a ring C═O group) and/or substituted on a ring sulfur atom by one (1) or two (2) oxygen atoms to give S═O or SO 2 groups, respectively, and/or substituted on a ring phosphorus by an oxygen atom to give P═O.

“Heterocycloalkylalkyl” or “heterocycloalkylalkyl group” refers to an alkyl group in which a hydrogen atom is replaced by a heterocycloalkyl group, wherein alkyl group and heterocycloalkyl group are as previously defined (i.e., heterocycloalkylalkyl-). Heteroycloalkylalkyl groups can be substituted or unsubstituted. Examples include, but are not limited to, pyrrolidinylmethyl (C 4 H 8 NCH 2 —). “Pharmaceutically acceptable” refers to physiologically tolerable materials, which do not typically produce an allergic or other untoward reaction, such as gastric upset, dizziness and the like, when administered to a human. “Pharmaceutical composition” refers to a composition that can be used to treat a disease, condition, or disorder in a human. “Pseudohalogen” refers to —OCN, —SCN, —CF 3 , and —CN. “Stable” or “chemically stable” refers to a compound that is sufficiently robust to be isolated to a useful degree of purity from a reaction mixture. The present application is directed solely to the preparation of stable compounds. When lists of alternative substituents include members which, owing to valency requirements, chemical stability, or other reasons, cannot be used to substitute a particular group, the list is intended to be read in context to include those members of the list that are suitable for substituting the particular group. For example, R 1 can be C 1-6 alkyl optionally substituted by 1-13 R 19 ; when R 1 is methyl, the methyl group is optionally substituted by 1-3 R 19 . “Therapeutically effective amount” refers to an amount of a compound sufficient to inhibit, halt, or cause an improvement in a disorder or condition being treated in a particular subject or subject population. For example in a human or other mammal, a therapeutically effective amount can be determined experimentally in a laboratory or clinical setting, or may be the amount required by the guidelines of the United States Food and Drug Administration, or equivalent foreign agency, for the particular disease and subject being treated. It should be appreciated that determination of proper dosage forms, dosage amounts, and routes of administration is within the level of ordinary skill in the pharmaceutical and medical arts. “Treatment” refers to the acute or prophylactic diminishment or alleviation of at least one symptom or characteristic associated or caused by a disorder being treated. For example, treatment can include diminishment of several symptoms of a disorder or complete eradication of a disorder.

II. Compounds

The compounds of the present application are defined by the following numbered Embodiments. When a higher numbered Embodiment refers back to multiple previous lower numbered Embodiments in the alternative and contains a new limitation not present in the lower numbered Embodiments, the higher numbered Embodiment is intended to be an express description of each and every one of the alternatives. For example, if Embodiment 2 refers back to Embodiment 1 and contains a limitation not present in Embodiment 1, Embodiment 3 refers back Embodiments 1 or 2 and contains a limitation(s) not present in Embodiments 1 or 2, and Embodiment 4 refers back to any of Embodiments 1-3 and contains a limitation(s) not present in Embodiments 1, 2, or 3, then Embodiment 4 is intended to be an explicit description of a genus having the limitations of Embodiments 1 and 4, an explicit description of a genus having the limitations of Embodiments 2 and 4 (i.e., 1, 2, and 4), and an explicit description of a genus having the limitations of Embodiments 3 and 4 (i.e., 1, 3, and 4, and 1, 2, 3 and 4). By way of example, if Embodiment 1 is a compound of formula (I) defining R 7 , R 8 and R 9 independently as alkyl or aryl, Embodiment 2 is a compound of Embodiment 1 defining R 7 as alkyl, Embodiment 3 is a compound of Embodiments 1 or 2 defining R 8 as alkyl, and Embodiment 4 is a compound of any of Embodiments 1-3 defining R 9 as alkyl, then Embodiment 4 is an explicit description of a genus having the limitations of Embodiments 1 and 4 (i.e., a compound of formula (I) in which R 7 and R 8 are alkyl or aryl, and R 9 is alkyl), an explicit description of a genus having the limitations of Embodiments 2 and 4 (i.e., a compound of formula (I) in which R 8 is alkyl or aryl, and R 7 and R 9 are alkyl), an explicit description of a genus having the limitations of Embodiments 3 and 4 (i.e., a compound of formula (I) in which R 7 is alkyl or aryl, and R 8 and R 9 are alkyl; and a compound of formula (I) in which R 7 , R 8 and R 9 are all alkyl). It should be noted in this regard that when a higher numbered Embodiment refers to a lower numbered Embodiment and contains limitations for a group(s) not present in the lower numbered Embodiment, the higher numbered Embodiment should be interpreted in context to ignore the missing group(s). For example, if Embodiment 1 recites a compound of formula (I) in which X is H, C 1-10 alkyl, or —C(═O)R 28 , Embodiment 2 recites a compound of Embodiment 1 in which X is H or C 1-10 alkyl, and Embodiment 3 recites a compound of Embodiments 1 or 2 in which R 28 is alkyl, then Embodiment 3 defines a genus having the limitations of Embodiments 1 and 3 and a genus having the limitation of Embodiments 2 and 3 (i.e., 1, 2, and 3). In the genus defined by the limitations of Embodiments 2 and 3, X cannot be —C(═O)R 28 ; therefore this genus should be interpreted to ignore the Embodiment 3 definition of R 28 =alkyl (i.e., the genus of Embodiments 2 and 3 has the same scope as the genus of Embodiment 2).

The compounds of the present application are defined herein using structural formulas that do not specifically recite the mass numbers or the isotope ratios of the constituent atoms. It is intended that the present application includes compounds in which the constituent atoms are present in any ratio of isotope forms. For example, carbon atoms may be present in any ratio of 12 C, 13 C, and 14 C; hydrogen atoms may be present in any ratio of 1 H, 2 H, and 3 H; etc. Preferably, the constituent atoms in the compounds of the present application are present in their naturally occurring ratios of isotope forms.

A compound of formula (I)

or a salt form thereof,

wherein

G is a group of formula

X is chosen from H, C 1-10 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —C(═O)C(═O)R 28 , —NR 24 R 28 , —NR 24 NR 24 R 28 , —N═NR 28 , —NR 24 OR 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 C(═O)NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 C(═O)OR 28 , —NR 24 C(═O)C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR 28 , —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OC(═O)OR 28 , —OS(═O)R 28 , —OS(═O) 2 R 28 , —OS(═O) 2 OR 28 , —OS(═O) 2 NR 24 R 28 , —S(═O) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 ;

R 7 , R 8 , R 9 , R 12 , R 13 , R 14 , R 15 , R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —(═O)C(═O)R 20 , —C(═NR 25 )R 20 , —C(═NR 25 )NR 22 R 23 , —C(═NOH)NR 22 R 23 , —C(═NOR 26 )R 20 , —C(═NNR 22 R 23 )R 20 , —C(═NNR 24 C(═O)R 21 )R 20 , —C(═NNR 24 C(═O)OR 21 )R 20 , —C(═S)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(OR 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 );

or any of R 7 and R 8 , R 12 and R 13 , R 14 and R 15 , R a and R b , R a and R e , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R g , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 ;

R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 39 , C 2-6 alkenyl optionally substituted by 1-11 R 39 , C 2-6 alkynyl optionally substituted by 1-9 R 39 , C 6-11 aryl optionally substituted by 1-11 R 39 , C 7-16 arylalkyl optionally substituted by 1-19 R 39 , C 3-11 cycloalkyl optionally substituted by 1-21 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 39 , 5-15 membered heteroaryl optionally substituted by 1-15 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —C(═O)C(═O)R 30 , —C(═NR 35 )R 30 , —C(═NR 35 )NR 32 R 33 , —C(═NOH)NR 32 R 33 , —C(═NOR 36 )R 30 , —C(═NNR 32 R 33 )R 30 , —C(═NNR 34 C(═O)R 31 )R 30 , —C(═NNR 34 C(═O)OR 31 )R 30 , —C(═S)NR 32 R 33 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —N═NR 34 , ═NR 30 , ═NOR 30 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 30 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 33 , —NR 34 C(═S)R 30 , —NR 34 C(═S)OR 30 , —NR 34 C(═S)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —NR 34 P(═O)R 78 R 78 , —NR 34 P(═O)(NR 32 R 33 )(NR 32 R 33 ), —NR 34 P(═O)(OR 30 )(OR 30 ), —NR 34 P(═O)(SR 30 )(SR 30 ), —OR 30 , ═O, —OCN, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —OS(═O)R 30 , —OS(═O) 2 R 30 , —OS(═O) 2 OR 30 , —OS(═O) 2 NR 32 R 33 , —OP(═O)R 78 R 78 , —OP(═O)(NR 32 R 33 )(NR 32 R 33 ), —OP(═O)(OR 30 )(OR 30 ), —OP(═O)(SR 30 )(SR 30 ), —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —SP(═O)R 78 R 78 , —SP(═O)(NR 32 R 32 )(NR 32 R 33 ), —SP(═O)(OR 30 )(OR 30 ), —SP(═O)(SR 30 )(SR 30 ), —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 );

R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 49 , C 2-6 alkenyl optionally substituted by 1-11 R 49 , C 2-6 alkynyl optionally substituted by 1-9 R 49 , C 6-11 aryl optionally substituted by 1-11 R 49 , C 7-16 arylalkyl optionally substituted by 1-19 R 49 , C 3-11 cycloalkyl optionally substituted by 1-21 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 49 , 5-15 membered heteroaryl optionally substituted by 1-15 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 49 ;

R 28 at each occurrence is independently chosen from C 1-10 alkyl optionally substituted by 1-13 R 49 , C 2-10 alkenyl optionally substituted by 1-11 R 49 , C 2-6 alkynyl optionally substituted by 1-9 R 49 , C 6-11 aryl optionally substituted by 1-11 R 49 , C 7-16 arylalkyl optionally substituted by 1-19 R 49 , C 3-11 cycloalkyl optionally substituted by 1-21 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 49 , 5-15 membered heteroaryl optionally substituted by 1-15 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 49 ;

R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 59 , C 2-6 alkenyl optionally substituted by 1-11 R 59 , C 2-6 alkynyl optionally substituted by 1-9 R 59 , C 6-11 aryl optionally substituted by 1-11 R 59 , C 7-16 arylalkyl optionally substituted by 1-19 R 59 , C 3-11 cycloalkyl optionally substituted by 1-21 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 59 , 5-15 membered heteroaryl optionally substituted by 1-15 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 59 ;

or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 69 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 69 ;

R 39 , R 49 , R 59 and R 69 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —C(═O)C(═O)R 70 , —C(═NR 75 )R 70 , —C(═NR 75 )NR 72 R 73 , —C(═NOH)NR 72 R 73 , —C(═NOR 76 )R 70 , —C(═NNR 72 R 73 )R 70 , —C(═NNR 74 C(═O)R 71 )R 70 , —C(═NNR 74 C(═O)OR 71 )R 70 , —C(═S)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , ═NR 70 , ═NOR 70 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)C(═O)R 70 , —NR 74 C(═)OR 71 , —NR 74 C(═O)C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 C(═O)NR 74 C(═O)OR 70 , —NR 74 C(═NR 75 )NR 72 R 73 , —NR 74 C(═O)C(═O)NR 72 R 73 , —NR 74 C(═S)R 70 , —NR 74 C(═S)OR 70 , —NR 74 C(═S)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═O)(OR 70 )(OR 70 ), —NR 74 P(═O)(SR 70 )(SR 70 ), —OR 70 , ═O, —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OC(═NR 75 )NR 72 R 73 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —OP(═O)(SR 70 )(SR 70 ), —Si(R 74 ) 3 , —SCN, ═S, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R, —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 )(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), —P(═O)(OR 70 )(OR 70 ), and —P(═O)(SR 70 )(SR 70 );

R 70 , R 71 , R 74 , R 7 , R 76 and R 77 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 89 , C 2-6 alkenyl optionally substituted by 1-11 R 89 , C 2-6 alkynyl optionally substituted by 1-9 R 89 , C 6-11 aryl optionally substituted by 1-11 R 89 , C 7-16 arylalkyl optionally substituted by 1-19 R 89 , C 3-11 cycloalkyl optionally substituted by 1-21 R 89 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 89 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 89 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 89 , 5-15 membered heteroaryl optionally substituted by 1-15 R 89 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 89 ;

R 72 and R 73 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 99 , C 2-6 alkenyl optionally substituted by 1-11 R 99 , C 2-6 alkynyl optionally substituted by 1-9 R 99 , C 6-11 aryl optionally substituted by 1-11 R 99 , C 7-16 arylalkyl optionally substituted by 1-19 R 99 , C 3-11 cycloalkyl optionally substituted by 1-21 R 99 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 99 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 99 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 99 , 5-15 membered heteroaryl optionally substituted by 1-15 R 99 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 99 ;

or any R 72 and R 73 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 109 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 109 ;

R 78 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 89 , C 2-6 alkenyl optionally substituted by 1-11 R 89 , C 2-6 alkynyl optionally substituted by 1-9 R 89 , C 6-11 aryl optionally substituted by 1-11 R 89 , C 7-16 arylalkyl optionally substituted by 1-19 R 89 , C 3-11 cycloalkyl optionally substituted by 1-21 R 89 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 89 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 89 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 89 , 5-15 membered heteroaryl optionally substituted by 1-15 R 89 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 89 ;

or any two R 78 attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 89 ;

R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 119 , C 2-6 alkenyl optionally substituted by 1-11 R 119 , C 2-6 alkynyl optionally substituted by 1-9 R 119 , C 6-11 aryl optionally substituted by 1-11 R 119 , C 7-16 arylalkyl optionally substituted by 1-19 R 119 , C 3-11 cycloalkyl optionally substituted by 1-21 R 119 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 119 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 119 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 119 , 5-15 membered heteroaryl optionally substituted by 1-15 R 119 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 119 , halogen, —CN, —C(═O)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —C(═O)C(═O)R 110 , —C(═NR 115 )R 110 , —C(═NR 115 )NR 112 R 113 , —C(═NOH)NR 112 R 113 , —C(═NOR 116 )R 110 , —C(═NNR 112 R 113 )R 110 , —C(═NNR 114 C(═O)R 111 )R 110 , —C(═NNR 114 C(═O)OR 111 )R 110 , —C(═S)NR 112 R 113 , —NC, —NO 2 , —NR 112 R 113 , —NR 114 NR 112 R 113 , —N═NR 114 , ═NR 110 , ═NOR 110 , —NR 114 OR 116 , —NR 114 C(═O)R 110 , —NR 114 C(═O)C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 114 C(═O)NR 114 C(═O)OR 110 , —NR 114 C(═NR 115 )NR 112 R 113 , —NR 114 C(═O)C(═O)NR 112 R 113 , —NR 114 C(═S)R 110 , —NR 114 C(═S)OR 110 , —NR 114 C(═S)NR 112 R 113 , —NR 114 S(═O) 2 R 11 , —NR 114 S(═O) 2 NR 112 R 113 , —NR 114 P(═O)R 118 R 118 , —NR 114 P(═O)(NR 112 R 113 )(NR 112 R 113 ), —NR 114 P(═O)(OR 110 )(OR 110 )—NR 114 P(═O)(SR 110 )(SR 110 ), —OR 110 , ═O, —OCN, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═O)OR 110 , —OC(═NR 115 )NR 112 R 113 , —OS(═O)R 110 , —OS(═O) 2 R 110 , —OS(═O) 2 OR 110 , —OS(═O) 2 NR 112 R 113 , —OP(═O)R 118 R 118 , —OP(═O)(NR 112 R 113 )(NR 112 R 113 ), —OP(═O)(OR 110 )(OR 110 ), —OP(═O)(SR 110 )(SR 110 ), —Si(R 114 ) 3 , —SCN, ═S, —S(═O) n R 110 , —S(═O) 2 OR 110 , —SO 3 R 1111 , —S(═O) 2 NR 112 R 113 , —S(═O)NR 112 R 113 , —SP(═O)R 118 R 118 , —SP(═O)(NR 112 R 113 )(NR 112 R 113 ), —SP(═O)(OR 110 )(OR 110 ), —SP(═O)(SR 110 )(SR 110 ), —P(═O)R 118 R 118 , —P(═O)(NR 112 R 113 )(NR 112 R 113 ), —P(═O)(OR 110 )(OR 110 ), and —P(═O)(SR 110 )(SR 110 );

R 110 , R 111 , R 114 , R 115 , R 116 and R 117 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 129 , C 2-6 alkenyl optionally substituted by 1-11 R 129 , C 2-6 alkynyl optionally substituted by 1-9 R 129 , C 6-11 aryl optionally substituted by 1-11 R 129 , C 7-16 arylalkyl optionally substituted by 1-19 R 129 , C 3-11 cycloalkyl optionally substituted by 1-21 R 129 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 129 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 129 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 129 , 5-15 membered heteroaryl optionally substituted by 1-15 R 129 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 129 ;

R 112 and R 113 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 139 , C 2-6 alkenyl optionally substituted by 1-11 R 139 , C 2-6 alkynyl optionally substituted by 1-9 R 139 , C 6-11 aryl optionally substituted by 1-11 R 139 , C 7-16 arylalkyl optionally substituted by 1-19 R 139 , C 3-11 cycloalkyl optionally substituted by 1-21 R 139 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 139 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 139 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 139 , 5-15 membered heteroaryl optionally substituted by 1-15 R 139 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 39 ;

or any R 112 and R 113 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 149 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 149

R 118 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 129 , C 2-6 alkenyl optionally substituted by 1-11 R 129 , C 2-6 alkynyl optionally substituted by 1-9 R 129 , C 6-11 aryl optionally substituted by 1-11 R 129 , C 7-16 arylalkyl optionally substituted by 1-19 R 129 , C 3-11 cycloalkyl optionally substituted by 1-21 R 129 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 129 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 129 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 129 , 5-15 membered heteroaryl optionally substituted by 1-15 R 129 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 129 ;

R 119 , R 129 , R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 159 , C 2-6 alkenyl optionally substituted by 1-11 R 159 , C 2-6 alkynyl optionally substituted by 1-9 R 159 , C 6-11 aryl optionally substituted by 1-11 R 159 , C 7-16 arylalkyl optionally substituted by 1-19 R 159 , C 3-11 cycloalkyl optionally substituted by 1-21 R 159 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 159 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 159 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 159 , 5-15 membered heteroaryl optionally substituted by 1-15 R 159 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —C(═O)C(═O)R 150 , —C(═NR 155 )R 150 , —C(═NR 155 )NR 152 R 153 , —C(═NOH)NR 152 R 153 , —C(═NOR 156 )R 150 , —C(═NNR 152 R 153 )R 150 , —C(═NNR 154 C(═O)R 151 )R 150 , —C(═NNR 154 C(═O)OR 151 )R 150 , —C(═S)NR 152 R 153 , —NC, —NO 2 , —NR 152 R 150 , —NR 154 NR 152 R 153 , —N═NR 154 , ═NR 150 , ═NOR 15 , —NR 154 OR 156 , —NR 154 C(═O)R 150 , —NR 154 C(═O)C(═O)R 150 , —NR 154 C(═)OR 151 , —NR 154 C(═O)C(═O)OR 151 , —NR 154 C(═O)NR 152 R 153 , —NR 154 C(═O)NR 154 C(═O)R 150 , —NR 154 C(═O)NR 154 C(═O)OR 150 , —NR 154 C(═NR 155 )NR 152 R 153 , —NR 154 C(═O)C(═O)NR 152 R 153 , —NR 154 C(═S)R 150 , —NR 154 C(═S)OR 150 , —NR 154 C(═S)NR 152 R 153 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O) 2 NR 152 R 153 , —NR 154 P(═O)R 158 R 158 , —NR 154 P(═O)(NR 152 R 153 )(NR 152 R 153 ), —NR 154 P(═O)(OR 150 )(OR 150 ), —NR 154 P(═O)(SR 150 )(SR 150 ), —OR 150 , ═O, —OCN, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═)OR 150 , —OC(═NR 155 )NR 152 R 153 , —OS(═O)R 150 , —OS(═O) 2 R 150 , —OS(═O) 2 OR 15 , —OS(═O) 2 NR 152 R 153 , —OP(═O)R 158 R 158 , —OP(═O)(NR 152 R 153 )(NR 152 R 153 ), —OP(═O)(OR 150 )(OR 150 ), —OP(═O)(SR 150 )(SR 150 ), —Si(R 154 ) 3 , —SCN, ═S, —S(═O) n R 150 , —S(═O) 2 OR 150 , —SO 3 R 1515 , —S(═O) 2 NR 152 R 153 , —S(═O)NR 152 R 153 , —SP(═O)R 158 R 158 , —SP(═O)(NR 152 R 153 )(NR 152 R 153 ), —SP(═O)(OR 150 )(OR 150 ), —SP(═O)(SR 150 )(SR 150 ), —P(═O)R 158 R 158 , —P(═O)(NR 152 R 153 )(NR 152 R 153 ), —P(═O)(OR 150 )(OR 150 ), and —P(═O)(SR 150 )(SR 150 );

R 150 , R 151 , R 154 , R 155 , R 156 and R 157 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 169 , C 2-6 alkenyl optionally substituted by 1-11 R 169 , C 2-6 alkynyl optionally substituted by 1-9 R 169 , C 6-11 aryl optionally substituted by 1-11 R 169 , C 7-16 arylalkyl optionally substituted by 1-19 R 169 , C 3-11 cycloalkyl optionally substituted by 1-21 R 169 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 169 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 169 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 169 , 5-15 membered heteroaryl optionally substituted by 1-15 R 169 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 169 ;

R 152 and R 153 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 179 , C 2-6 alkenyl optionally substituted by 1-11 R 179 , C 2-6 alkynyl optionally substituted by 1-9 R 179 , C 6-11 aryl optionally substituted by 1-11 R 179 , C 7-16 arylalkyl optionally substituted by 1-19 R 179 , C 3-11 cycloalkyl optionally substituted by 1-21 R 179 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 179 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 179 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 179 , 5-15 membered heteroaryl optionally substituted by 1-15 R 179 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 179 ;

or any R 152 and R 153 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 189 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 189 ;

R 158 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 169 , C 2-6 alkenyl optionally substituted by 1-11 R 169 , C 2-6 alkynyl optionally substituted by 1-9 R 169 , C 6-11 aryl optionally substituted by 1-11 R 169 , C 7-16 arylalkyl optionally substituted by 1-19 R 169 , C 3-11 cycloalkyl optionally substituted by 1-21 R 169 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 169 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 169 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 169 , 5-15 membered heteroaryl optionally substituted by 1-15 R 169 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 69 ;

R 159 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 199 , C 2-6 alkenyl optionally substituted by 1-11 R 199 , C 2-6 alkynyl optionally substituted by 1-9 R 199 , C 6-11 aryl optionally substituted by 1-11 R 199 , C 7-16 arylalkyl optionally substituted by 1-19 R 199 , C 3-11 cycloalkyl optionally substituted by 1-21 R 199 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 199 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 199 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 199 , 5-15 membered heteroaryl optionally substituted by 1-15 R 199 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —C(═O)C(═O)R 190 , —C(═NR 195 )R 190 , —C(═NR 195 )NR 192 R 193 , —C(═NOH)NR 192 R 193 , —C(═NOR 196 )R 190 , —C(═NNR 192 R 193 )R 190 , —C(═NNR 194 C(═O)R 191 )R 190 , —C(═NNR 194 C(═O)OR 191 )R 190 , —C(═S)NR 192 R 193 , —NC, —NO 2 , —NR 192 R 193 , —NR 194 NR 192 R 193 , —N═NR 194 , ═NR 190 , ═NOR 190 , —NR 194 OR 196 , —NR 194 C(═O)R 190 , —NR 194 C(═O)C(═O)R 190 , —NR 194 C(═O)OR 191 , —NR 194 C(═O)C(═O)OR 191 , —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 C(═O)NR 194 C(═)OR 190 , —NR 194 C(═NR 195 )NR 192 R 193 , —NR 194 C(═O)C(═O)NR 192 R 193 , —NR 194 C(═S)R 190 , —NR 194 C(═S)OR 190 , —NR 194 C(═S)NR 192 R 193 , —NR 194 S(═O) 2 R 191 , —NR 194 S(═O) 2 NR 192 R 192 R 193 , —NR 194 P(═O)R 198 R 198 , —NR 194 P(═O)(NR 192 R 193 )(NR 192 R 193 )—NR 194 P(═)(OR 190 )(OR 190 ), —NR 194 P(═O)(SR 190 )(SR 190 )—OR 190 , ═O, —OCN, —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —OC(═O)OR 190 , —OC(═NR 195 )NR 192 R 193 , —OS(═O)R 190 , —OS(═O) 2 R 190 , —OS(═O) 2 OR 190 , —OS(═O) 2 NR 192 R 193 , —OP(═O)R 198 R 198 , —OP(═O)(NR 192 R 193 )(NR 192 R 193 ), —OP(═O)(OR 190 )(OR 190 ), —OP(═O)(SR 190 )(SR 190 ), —Si(R 194 ) 3 , —SCN, ═S, —S(═O) n R 190 , —S(═O) 2 R 190 , —SO 3 R 1919 , —S(═O) 2 NR 192 R 193 , —S(═O)NR 192 R 193 , —SP(═O)R 198 R 198 , —SP(═O)(NR 192 R 193 )(NR 192 R 193 ), —SP(═O)(OR 190 )(OR 190 ), —SP(═O)(SR 190 )(SR 190 ), —P(═O)R 198 R 198 , —P(═O)(NR 192 R 193 )(NR 192 R 193 ), —P(═O)(OR 190 )(OR 190 ), and —P(═O)(SR 190 )(SR 190 );

R 190 , R 91 , R 94 , R 195 , R 196 and R 197 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 209 , C 2-6 alkenyl optionally substituted by 1-11 R 209 , C 2-6 alkynyl optionally substituted by 1-9 R 209 , C 6-11 aryl optionally substituted by 1-11 R 209 , C 7-16 arylalkyl optionally substituted by 1-19 R 209 , C 3-11 cycloalkyl optionally substituted by 1-21 R 209 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 209 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 209 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 209 , 5-15 membered heteroaryl optionally substituted by 1-15 R 209 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 209

R 192 and R 193 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 219 , C 2-6 alkenyl optionally substituted by 1-11 R 219 , C 2-6 alkynyl optionally substituted by 1-9 R 219 , C 6-11 aryl optionally substituted by 1-11 R 219 , C 7-16 arylalkyl optionally substituted by 1-19 R 219 , C 3-11 cycloalkyl optionally substituted by 1-21 R 219 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 219 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 219 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 219 , 5-15 membered heteroaryl optionally substituted by 1-15 R 219 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 219 ;

or any R 192 and R 193 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 229 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 229 ;

R 198 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 209 , C 2-6 alkenyl optionally substituted by 1-11 R 209 , C 2-6 alkynyl optionally substituted by 1-9 R 209 , C 6-11 aryl optionally substituted by 1-11 R 209 , C 7-16 arylalkyl optionally substituted by 1-19 R 209 , C 3-11 cycloalkyl optionally substituted by 1-21 R 209 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 209 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 209 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 209 , 5-15 membered heteroaryl optionally substituted by 1-15 R 209 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 209

R 199 , R 209 , R 219 and R 229 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 halogen, C 2-6 alkenyl, C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl, C 3-11 cycloalkyl, C 4-17 cycloalkylalkyl, 3-15 membered heterocycloalkyl, 4-21 membered heterocycloalkylalkyl, 5-15 membered heteroaryl, 6-21 membered heteroarylalkyl, halogen, —CN, —C(═O)R 230 , —C(═)OR 230 , —C(═O)NR 230 R 230 , —C(═O)C(═O)R 230 , —C(═NR 230 )R 230 , —C(═NR 230 )NR 230 R 230 , —C(═NOH)NR 230 R 230 , —C(═NOR 230 )R 230 , —C(═NNR 230 R 230 )R 230 , —C(═NNR 230 C(═O)R 230 )R 230 , —C(═NNR 230 C(═O)OR 230 )R 230 , —C(═S)NR 230 R 230 , —NC, —NO 2 , —NR 230 R 230 , —NR 230 NR 230 R 230 , —N═NR 230 , ═NR 230 , ═NOR 230 , —NR 230 OR 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)C(═O)R 230 , —NR 230 C(═O)OR 230 , —NR 230 C(═O)C(═O)OR 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 C(═O)NR 230 C(═O)R 230 , —NR 230 C(═O)NR 230 C(═O)OR 230 , —NR 230 C(═NR 230 )NR 230 R 230 , —NR 230 C(═O)C(═O)NR 230 R 230 , —NR 230 C(═S)R 230 , —NR 230 C(═S)OR 230 , —NR 230 C(═S)NR 230 R 230 , —NR 230 S(═) 2 R 230 , —NR 230 S(═O) 2 NR 230 R 230 , —NR 230 P(═O)R 231 R 231 , —NR 230 P(═O)(NR 230 R 230 )(NR 230 R 230 ), —NR 230 P(═O)(OR 230 )(OR 230 ), —NR 230 P(═O)(SR 230 )(SR 230 ), —OR 230 , ═O, —OCN, —OC(═O)R 230 , —OC(═O)NR 230 R 230 , —OC(═O)OR 230 , —OC(═NR 230 )NR 230 R 230 , —OS(═O)R 230 , —OS(═) 2 R 230 , —OS(═O) 2 OR 230 , —OS(═O) 2 NR 230 R 230 , —OP(═O)R 231 R 231 , —OP(═O)(NR 230 R 230 )(NR 230 R 230 ), —OP(═O)(OR 230 )(OR 230 ), —OP(═O)(SR 230 )(SR 230 ), —Si(R 230 ) 3 , —SCN, ═S, —S(═O) n R 230 , —S(═O) 2 R 230 , —SO 3 R 230 , —S(═O) 2 NR 230 R 230 , —S(═O)NR 230 R 230 , —SP(═O)R 231 R 231 , —SP(═O)(NR 230 R 230 )(NR 230 R 230 ), —SP(═O)(OR 230 )(OR 230 ), —SP(═)(SR 230 )(SR 230 ), —P(═O)R 231 R 231 , —P(═O)(NR 230 R 230 )(NR 230 R 230 ), —P(═O)(OR 230 )(OR 230 ), and —P(═O)(SR 230 )(SR 230 );

R 230 at each occurrence is independently chosen from H, C 1-6 alkyl and C 1-6 -haloalkyl;

R 231 at each occurrence is independently chosen from C 1-6 alkyl and C 1-6 -haloalkyl; and

n at each occurrence is independently chosen from 0, 1, and 2;

with the proviso that the compound is not

in which D is H or

or a salt form thereof;

in which D is

or a salt form thereof; or

in which D is H or —CH 3 , or a salt form thereof.

The compound of Embodiment 1, wherein G is a group of formula

The compound of Embodiment 1, wherein G is a group of formula

The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-10 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —C(═O)C(═O)R 28 , —NR 24 R 28 , —NR 24 NR 24 R 28 , —N═NR 28 , —NR 24 OR 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 C(═O)NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 C(═O)OR 28 , —NR 24 C(═O)C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR 28 , —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OC(═O)OR, —OS(═O)R 28 , —OS(═O) 2 R 28 , —OS(═O) 2 OR 28 , —OS(═O) 2 NR 24 R 28 , —S(═O) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-10 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR 28 , —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OS(═O)R 28 , —OS(═O) 2 R 28 , —OS(═O) 2 NR 24 R 28 , —S(═O) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-10 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR 28 , —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OS(═O)R 28 , —OS(═O) 2 R 28 , —OS(═O) 2 NR 24 R 28 , —S(═O) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , C 4-7 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-7 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , 6-11 membered heteroarylalkyl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR 28 , —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OS(═O)R 28 , —OS(═O) 2 R 28 , —OS(═O) 2 NR 24 R 28 , —S(═) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , C 4-7 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-7 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , 6-11 membered heteroarylalkyl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , C 4-7 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-7 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , 6-11 membered heteroarylalkyl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)OR 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —NR 24 S(═O) 2 NR 24 R 28 , —OR 28 , —OC(═O)R 28 , —OC(═O)NR 24 R 28 , —OS(═O)R 28 , —OS(═) 2 R 28 , —OS(═O) 2 NR 24 R 28 , —S(═) n R 28 , —S(═O) 2 NR 24 R 28 , and —S(═O)NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , C 4-7 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-7 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , 6-11 membered heteroarylalkyl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O) 2 NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 S(═O) 2 R 28 , and —OR 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 S(═O) 2 R 28 , and —OR 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , C 4-7 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-7 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , 6-11 membered heteroarylalkyl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from C 1-6 alkyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═)OR 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 C(═O)NR 24 R 28 , —NR 24 S(═O) 2 R 28 , —OR 28 , —OC(═O)R 28 , —S(═O) n R 28 , and —S(═O) 2 NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from C 1-6 alkyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 S(═O) 2 R 28 , and —OR 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —C(═O)R 28 , —C(═O)NR 24 R 28 , —NR 24 R 28 , —NR 24 C(═O)R 28 , —NR 24 S(═O) 2 R 28 , and —OR 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —NR 24 R 28 , and —OR 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —NR 24 R 28 , and —OR 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from C 1-6 alkyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-6 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —NR 24 R 28 , and —OR 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , —NR 24 R 28 , and —OR 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , and —NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , and —NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , —NR 24 R 28 , —OR 28 , and —SR 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , and —NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, 3-9 membered heterocycloalkyl optionally substituted by 1-6 R 19 , and —NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from 3-9 membered heterocycloalkyl optionally substituted by 1-6 R 19 , and —NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H, 3-7 membered heterocycloalkyl optionally substituted by 1-6 R 19 , and —NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from 3-7 membered heterocycloalkyl optionally substituted by 1-6 R 19 , and —NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is 3-9 membered heterocycloalkyl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is 3-7 membered heterocycloalkyl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is 5-6 membered heterocycloalkyl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is 6 membered heterocycloalkyl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is morpholinyl, piperidinyl, or piperazinyl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is piperidinyl or piperazinyl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is piperidinyl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is piperazinyl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is —NR 24 R 28 .

The compound of any of Embodiments 1-3, wherein X is chosen from H and

wherein

A is —NR 1 R 2 , —CR i R j R k , —OR 18a , or —SR 18b ; Q is —NR 11 —, —CR m R n —, —O—, or —S—; R k is H, halogen, —CN, —NO 2 , —NR 16 R 17 , —OR 18c , —SR 18d , or —CR o R p R q ; R q is H, halogen, —CN, —NO 2 , —NR 16a R 17a or —OR 18e ; R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-19 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , and —OR 70 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —C(═O)C(═O)R 70 , —C(═NR 75 )R 70 , —C(═NR 75 )NR 72 R 73 , —C(═NOH)NR 72 R 73 , —C(═NOR 76 )R 70 , —C(═NNR 72 R 73 )R 70 , —C(═NNR 74 C(═O)R 71 )R 70 , —C(═NNR 74 C(═O)OR 71 )R 70 , —C(═S)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)C(═O)R 70 , —NR 74 C(═)OR 71 , —NR 74 C(═O)C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 C(═O)NR 74 C(═O)OR 70 , —NR 74 C(═NR 75 )NR 72 R 73 , —NR 74 C(═O)C(═O)NR 72 R 73 , —NR 74 C(═S)R 70 , —NR 74 C(═S)OR 70 , —NR 74 C(═S)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═O)(OR 70 )(OR 70 ), —NR 74 P(═O)(SR 70 )(SR 70 ), —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OC(═NR 75 )NR 72 R 73 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 OR 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —OP(═O)(SR 70 )(SR 70 ), —Si(R 74 ) 3 , —SCN, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 )(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), —P(═O)(OR 70 )(OR 70 ), and —P(═O)(SR 70 )(SR 70 ); or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R n , R 18b and R n , R 18c and R i , R 18 and R 3 , R 18 and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n can, together with the atoms linking them, form a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 79 ; or R 4 and R 5 or R n and R 5 can together form a double bond; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O, ═NR 70 , ═NOR 70 , or ═S.

The compound of any of Embodiments 1-3, wherein X is

wherein

A is —NR 1 R 2 , —CR i R j R k , —OR 18a , or —SR 18b ; Q is —NR 11 —, —CR m R n —, —O—, or —S—; R k is H, halogen, —CN, —NO 2 , —NR 16 R 17 , —OR 18c , —SR 18d , or —CR o R p R q ; R q is H, halogen, —CN, —NO 2 , —NR 16a R 17a or —OR 18e R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , and —OR 70 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-19 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 79 , 5-15 membered heteroaryl optionally substituted by 1-15 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —C(═O)C(═O)R 70 , —C(═NR 75 )R 70 , —C(═NR 75 )NR 72 R 73 , —C(═NOH)NR 72 R 73 , —C(═NOR 76 )R 70 , —C(═NNR 72 R 73 )R 70 , —C(═NNR 74 C(═O)R 71 )R 70 , —C(═NNR 74 C(═O)OR 71 )R 70 , —C(═S)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)C(═)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 C(═O)NR 74 C(═O)OR 70 , —NR 74 C(═NR 75 )NR 72 R 73 , —NR 74 C(═O)C(═O)NR 72 R 73 , —NR 74 C(═S)R 70 , —NR 74 C(═S)OR 70 , —NR 74 C(═S)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═)(OR 70 )(OR 70 ), —NR 74 P(═O)(SR 70 )(SR 70 ), —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OC(═NR 75 )NR 72 R 73 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 OR 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —OP(═O)(SR 70 )(SR 70 ), —Si(R 74 ) 3 , —SCN, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 )(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), —P(═O)(OR 70 )(OR 70 ), and —P(═O)(SR 70 )(SR 70 ); or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 1 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18C and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n can, together with the atoms linking them, form a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 79 , C 3-11 cycloalkyl optionally substituted by 1-21 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 79 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 79 ; or R 4 and R 5 or R n and R 5 can together form a double bond; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O, ═NR 70 , ═NOR 70 , or ═S.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-11 cycloalkyl optionally substituted by 1-10 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-15 membered heteroaryl optionally substituted by 1-10 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-10 R 79 , and —OR 70 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-10 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-10 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-11 cycloalkyl optionally substituted by 1-10 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-15 membered heteroaryl optionally substituted by 1-10 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-10 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —(═O)C(═O)R 70 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)C(═)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 C(═O)NR 74 C(═O)OR 70 , —NR 74 C(═O)C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═O)(OR 70 )(OR 70 ), —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 OR 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —Si(R 74 ) 3 , —SCN, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 )(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), and —P(═O)(OR 70 )(OR 70 ); or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 11 , R 18e and R 11 , R 18e and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n can, together with the atoms linking them, form a 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79 or a 5-15 membered heteroaryl optionally substituted by 1-10 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-10 R 79 , C 3-11 cycloalkyl optionally substituted by 1-10 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79 or a 5-15 membered heteroaryl optionally substituted by 1-10 R 79 ; or R 4 and R 5 or R n and R 5 can together form a double bond; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O, ═NR 70 , ═NOR 70 , or ═S.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-11 cycloalkyl optionally substituted by 1-10 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-15 membered heteroaryl optionally substituted by 1-10 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-10 R 79 , and —OR 70 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-10 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-10 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-11 cycloalkyl optionally substituted by 1-10 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-15 membered heteroaryl optionally substituted by 1-10 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-10 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —C(═O)C(═O)R 70 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═)(OR 70 )(OR 70 ), —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 OR 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —SCN, —S(═O) n R 70 , —S(═O) 2 R 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), and —P(═O)(OR 70 )(OR 70 ); or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n can, together with the atoms linking them, form a 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79 or a 5-15 membered heteroaryl optionally substituted by 1-10 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-10 R 79 , C 3-11 cycloalkyl optionally substituted by 1-10 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-10 R 79 or a 5-15 membered heteroaryl optionally substituted by 1-10 R 79 ; or R 4 and R 5 or R n and R 5 can together form a double bond; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , C 4-11 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-11 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-11 membered heteroaryl optionally substituted by 1-10 R 79 , and 6-12 membered heteroarylalkyl optionally substituted by 1-10 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-10 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-10 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , C 4-11 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-11 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-11 membered heteroaryl optionally substituted by 1-10 R 79 , 6-12 membered heteroarylalkyl optionally substituted by 1-10 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OS(═O)R 70 , —OS(═) 2 R 70 , —OS(═) 2 OR 70 , —OS(═) 2 NR 72 R 73 , —SCN, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , and —S(═O)NR 72 R 73 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-10 R 79 or a 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , 3-11 membered heterocycloalkyl optionally substituted by 1-10 R 79 or a 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; or R 4 and R 5 or R n and R 5 can together form a double bond; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-11 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , C 4-11 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-11 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-11 membered heteroaryl optionally substituted by 1-10 R 79 , and 6-12 membered heteroarylalkyl optionally substituted by 1-10 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-10 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-10 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , C 4-11 cycloalkylalkyl optionally substituted by 1-10 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 4-11 membered heterocycloalkylalkyl optionally substituted by 1-10 R 79 , 5-11 membered heteroaryl optionally substituted by 1-10 R 79 , 6-12 membered heteroarylalkyl optionally substituted by 1-10 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —SCN, —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-10 R 79 or a 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , 3-11 membered heterocycloalkyl optionally substituted by 1-10 R 79 or a 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; or R 4 and R 5 or R n and R 5 can together form a double bond; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 6-11 aryl optionally substituted by 1-11 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-10 R 79 , and 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-10 R 79 , C 2-6 alkenyl optionally substituted by 1-10 R 79 , C 2-6 alkynyl optionally substituted by 1-9 R 79 , C 6-11 aryl optionally substituted by 1-10 R 79 , C 7-16 arylalkyl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-10 R 79 , 5-11 membered heteroaryl optionally substituted by 1-10 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-10 R 79 or a 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-10 R 79 , C 3-10 cycloalkyl optionally substituted by 1-10 R 79 , 3-11 membered heterocycloalkyl optionally substituted by 1-10 R 79 or a 5-11 membered heteroaryl optionally substituted by 1-10 R 79 ; or R 4 and R 5 or R n and R 5 can together form a double bond; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 6-11 aryl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , and 5-11 membered heteroaryl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkenyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 6-11 aryl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , 5-11 membered heteroaryl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 or a 5-11 membered heteroaryl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 or a 5-11 membered heteroaryl optionally substituted by 1-6 R 79 ; or R 4 and R 5 or R n and R 5 can together form a double bond; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 2R; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , or a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , and R 18c and R n can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , or a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , and R 18c and R n can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 5 and R 6 , R i and R l , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R l , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 2R; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 1 , R 16 and R n , R j and R 11 , and R 18a and R 11 can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R l , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═) n R 70 , and —S(═O) 2 NR 72 R 73 2R; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 16 and R 5 , R j and R 11 , and R 18a and R 11 can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or R 3 and R 4 can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , —CN, —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , and —OR 70 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 16 and R 5 , R j and R 11 , and R 18a and R 11 can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or R 3 and R 4 can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 3 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 18d , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18e and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 1 , and R 18d and R n can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 or a 5-11 membered heteroaryl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 or a 5-11 membered heteroaryl optionally substituted by 1-6 R 79 ; or R 4 and R 5 or R n and R 5 can together form a double bond; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 2 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 3 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , or a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 2 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 3 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , and R 18c and R n can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m can, together with the atoms linking them, form a C 3-10 -cycloalkyl optionally substituted by 1-6 R 79 , or a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 2 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , and C 7-16 arylalkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 3 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , and R 18c and R n can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of any of Embodiments 42-59, wherein 0-3 of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl or an optionally substituted heteroaryl.

The compound of any of Embodiments 42-59, wherein 0-2 of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl or an optionally substituted heteroaryl.

The compound of any of Embodiments 42-59, wherein 1-2 of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl or an optionally substituted heteroaryl.

The compound of any of Embodiments 42-59, wherein none of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R i , R 18d and R 3 , R 18d and R, R 18d and R 11 , and R 18d and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl or an optionally substituted heteroaryl.

The compound of any of Embodiments 42-59, wherein one of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl or an optionally substituted heteroaryl.

The compound of any of Embodiments 42-59, wherein two of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl or an optionally substituted heteroaryl.

The compound of any of Embodiments 42-59, wherein 0-3 of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl.

The compound of any of Embodiments 42-59, wherein 0-2 of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl.

The compound of any of Embodiments 42-59, wherein 1-2 of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl.

The compound of any of Embodiments 42-59, wherein none of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl.

The compound of any of Embodiments 42-59, wherein one of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18a and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18 , R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl.

The compound of Embodiment 70, wherein said optionally substituted heterocarbocyclyl is a 3-7 membered heterocarbocycl optionally substituted with 1-4 R 79 .

The compound of Embodiment 70, wherein said optionally substituted heterocarbocyclyl is a 5-6 membered heterocarbocycl optionally substituted with 1-4 R 79 .

The compound of any of Embodiments 42-59, wherein two of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , R 18a and R 3 , R 18a and R 5 , R 18 and R 11 , R 18a and R n , R 18b and R 3 , R 18b and R 5 , R 18b and R 11 , R 18b and R n , R 18c and R i , R 18c and R 3 , R 18c and R 5 , R 18c and R 11 , R 18c and R n , R 18d and R i , R 18d and R 3 , R 18d and R 5 , R 18d and R 11 , and R 18d and R n , together with the atoms linking them, form an optionally substituted heterocycloalkyl.

The compound of any of Embodiments 42-73, wherein 0-2 of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m , together with the atoms linking them, form an optionally substutituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl.

The compound of any of Embodiments 42-73, wherein 0-1 of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R, R i and R 4 , R i and R 5 , R 1 and R n , R m and R n , R 4 and R m , and R 6 and R m , together with the atoms linking them, form an optionally substutituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl.

The compound of any of Embodiments 42-73, wherein none of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R 1 and R, R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m , together with the atoms linking them, form an optionally substutituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl.

The compound of any of Embodiments 42-73, wherein one of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m , together with the atoms linking them, form an optionally substutituted aryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl.

The compound of any of Embodiments 42-73, wherein 0-2 of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m , together with the atoms linking them, form an optionally substutituted cycloalkyl or optionally substituted heterocycloalkyl.

The compound of any of Embodiments 42-73, wherein 0-1 of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m , together with the atoms linking them, form an optionally substutituted cycloalkyl or optionally substituted heterocycloalkyl.

The compound of any of Embodiments 42-73, wherein none of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m , together with the atoms linking them, form an optionally substutituted cycloalkyl or optionally substituted heterocycloalkyl.

The compound of any of Embodiments 42-73, wherein one of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m , together with the atoms linking them, form an optionally substutituted cycloalkyl or optionally substituted heterocycloalkyl.

The compound of any of Embodiments 42-73, wherein 0-2 of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R 1 and R, R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m , together with the atoms linking them, form an optionally substutituted heterocycloalkyl.

The compound of any of Embodiments 42-73, wherein 0-1 of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m , together with the atoms linking them, form an optionally substutituted heterocycloalkyl.

The compound of any of Embodiments 42-73, wherein none of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m , together with the atoms linking them, form an optionally substutituted heterocycloalkyl.

The compound of any of Embodiments 42-73, wherein one of R 3 and R 4 , R 3 and R 6 , R 5 and R 6 , R i and R j , R i and R 4 , R i and R 5 , R i and R n , R m and R n , R 4 and R m , and R 6 and R m , together with the atoms linking them, form an optionally substutituted heterocycloalkyl.

The compound of Embodiment 85, wherein said optionally substituted heterocarbocyclyl is a 3-7 membered heterocarbocycl optionally substituted with 1-4 R 79 .

The compound of Embodiment 85, wherein said optionally substituted heterocarbocyclyl is a 5-6 membered heterocarbocycl optionally substituted with 1-4 R 79 .

The compound of any of Embodiments 42-87, wherein neither R 4 and R 5 nor R n and R 5 together form a double bond.

The compound of any of Embodiments 42-88, wherein none of R 3 and R 4 , R 5 and R 6 , R i and R j , or R m and R n together form ═O, ═NR 70 , ═NOR 70 , or ═S.

The compound of Embodiments 42 or 43, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; R 2 is chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H; R 3 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 11 , R 6 and R 11 , R 16 and R 17 , R 16 and R i , R 16 and R 3 , R 16 and R 5 , R 16 and R 11 , R 16 and R n , R j and R 11 , and R 18a and R 11 can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or any of R 3 and R 4 , R 5 and R 6 , R i and R j , and R m and R n can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; R 2 is chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H; R 3 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 1 , R 16 and R 5 , R l and R 1 , and R 18a and R 11 can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or R 3 and R 4 can together form ═O.

The compound of Embodiments 42 or 43, wherein R 1 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; R 2 is chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 79 ; R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H; R 3 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , —CN, —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NR 72 R 73 , and —OR 70 ; or any of R 1 and R 2 , R 1 and R 3 , R 1 and R 5 , R 1 and R 11 , R 1 and R n , R 4 and R 1 , R 16 and R 5 , R j and R 11 , and R 18a and R 11 can, together with the atoms linking them, form a 3-11 membered heterocycloalkyl optionally substituted by 1-6 R 79 ; or R 3 and R 4 can together form ═O.

The compound of any of Embodiments 42-89, wherein at least five of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; and at least four of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein at least five of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; and at least five of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein at least six of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; and at least five of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein at least six of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; and at least six of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein at least seven of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; and at least six of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein at least seven of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; and at least seven of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein at least eight of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; and at least seven of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein at least eight of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; and at least eight of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein at least nine of R, R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18 , R 18d , and R 18e are H; and at least eight of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein at least nine of R, R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18 , R 18d , and R 18e are H; and at least nine of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein at least ten of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R e are H; and at least nine of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein at least eleven of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; and at least nine of R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; and at least nine of R 3 , R 4 , R 5 , R 6 , R i R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-89, wherein at least eleven of R 1 , R 2 , R 11 , R 16 , R 17 , R 16a , R 17a , R 18a , R 18b , R 18c , R 18d , and R 18e are H; and R 3 , R 4 , R 5 , R 6 , R i , R j , R m , R n , R o , and R p are H.

The compound of any of Embodiments 42-106, wherein R q is H, —NR 16a R 7a or —OR 18e .

The compound of any of Embodiments 42-106, wherein R q is —NR 16a R 7a or —OR 18e .

The compound of any of Embodiments 42-108, wherein R k is H, halogen, —CN, —NR 16 R 17 , —OR 18 , —SR 18d , or —CR o R p R q .

The compound of any of Embodiments 42-108, wherein R k is H, —CN, —NR 16 R 17 , —OR 18c , —SR 18d , or —CR o R p R q .

The compound of any of Embodiments 42-108, wherein R k is H, —CN, —NR 16 R 17 , —OR 18c , or —CR o R p R q .

The compound of any of Embodiments 42-108, wherein R k is H, —NR 16 R 17 , —OR 18c , or —CR o R p R q .

The compound of any of Embodiments 42-108, wherein R k is —NR 16 R 17 , —OR 18c , or —CR o R p R q .

The compound of any of Embodiments 42-106, wherein R k is H.

The compound of any of Embodiments 42-106, wherein R k is —NR 16 R 17 .

The compound of any of Embodiments 42-106, wherein R k is —OR 18c .

The compound of any of Embodiments 42-108, wherein R k is —CR o R p R q .

The compound of any of Embodiments 42-117, wherein A is —NR 1 R 2 , —CR i R j R k , or —OR 18a .

The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2 or —OR 18a .

The compound of any of Embodiments 42-117, wherein A is —CR i R j R k .

The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2 .

The compound of any of Embodiments 42-106, wherein A is —OR 18a .

The compound of any of Embodiments 42-122, wherein Q is —NR 11 —, —CR m R n —, or —O—.

The compound of any of Embodiments 42-122, wherein Q is —NR 11 —.

The compound of any of Embodiments 42-122, wherein Q is —CR m R n —.

The compound of any of Embodiments 42-122, wherein Q is —O—.

The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2 , —CR i R j R k , or —OR 18a ; Q is —NR 11 —, —CR m R n —, or —O—; and R k is —NR 16 R 17 , or —OR 18c .

The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2 , —CR i R j R k , or —OR 18a ; Q is —NR 11 —; and R k is —NR 16 R 17 , or —OR 18c .

The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2 , —CR i R j R k , or —OR 18a ; Q is —NR 11 —; and R k is —OR 18c .

The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2 or —OR 18a ; and Q is —NR 11 —.

The compound of any of Embodiments 42-106, wherein A is —NR 1 R 2 ; and Q is —NR 11 —.

The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28 and 3-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28 and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28 and 5-9 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28 and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28 and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-11 aryl optionally substituted by 1-3 R 39 , C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28 and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heterocycloalkyl, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28 and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heterocycloalkyl, halogen, —CN, —C(═)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28 and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NHR 28 and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, and —OH.

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-6 R 49 ), —NH(3-10 membered heterocycloalkyl optionally substituted by 1-6 R 49 ), —NH(4-11 membered heterocycloalkylalkyl optionally substituted by 1-6 R 49 ), and 3-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-6 R 49 ), —NH(3-10 membered heterocycloalkyl), —NH(4-11 membered heterocycloalkylalkyl), and 3-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-9 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-11 aryl optionally substituted by 1-3 R 39 , C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)OR 3 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-10 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heterocycloalkyl, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)OR 30 , and —OR 30 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl optionally substituted by 1-3 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heterocycloalkyl, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(5-6 membered heterocycloalkyl), —NH(6-10 membered heterocycloalkylalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(5-6 membered heterocycloalkyl), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, and —OH.

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(C 7-11 arylalkyl), —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), —NH(6-10 membered heterocycloalkylalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heterocycloalkyl, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 3 , and —OR 30 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(benzyl), —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), —NH(6-10 membered heterocycloalkylalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), —NH(6-10 membered heterocycloalkylalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , and —OR 30 .

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ), —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms), and 5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms in which the heterocycloalkyl is optionally substituted by 1 or 2 members chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, halogen, —CN, and —OH.

The compound of any of Embodiments 1-3, wherein X is chosen from —NH(C 1-6 alkyl optionally substituted by 1-6 R 49 ) and —NH(5-6 membered heterocycloalkyl consisting of carbon atoms and 1 or 2 nitrogen atoms).

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —C(═O)C(═O)R 20 , —C(═NR 25 )R 20 , —C(═NR 25 )NR 22 R 23 , —C(═NOH)NR 22 R 23 , —C(═NOR 26 )R 20 , —C(═NNR 22 R 23 )R 20 , —C(═NNR 24 C(═O)R 21 )R 20 , —C(═NNR 24 C(═O)OR 21 )R 20 , —C(═S)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 4 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(N 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 )(NR 23 ), —SP(═O)(OR 20 )(OR 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); or R and R 8 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O) 2 R 20 , —OS(═O) 20 R 20 , —OS(═O) 2 NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-4 R 19 , C 2-6 alkenyl optionally substituted by 1-4 R 19 , C 2-6 alkynyl optionally substituted by 1-4 R 19 , C 6-10 aryl optionally substituted by 1-4 R 19 , C 7-11 arylalkyl optionally substituted by 1-4 R 19 , C 3-7 cycloalkyl optionally substituted by 1-4 R 19 , C 4-8 cycloalkylalkyl optionally substituted by 1-4 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-4 R 19 , 4-8 membered heterocycloalkylalkyl optionally substituted by 1-4 R 19 , 5-6 membered heteroaryl optionally substituted by 1-4 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-4 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═)OR 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-4 R 19 , C 3-7 cycloalkyl optionally substituted by 1-4 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-4 R 19 or a 5-6 membered heteroaryl optionally substituted by 1-4 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , C 4-8 cycloalkylalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 4-8 membered heterocycloalkylalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —S(═) n R 20 and —S(═O) 2 NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , C 4-8 cycloalkylalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 4-8 membered heterocycloalkylalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OS(═O) 2 R 20 , —OS(═O) 2 NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , C 4-8 cycloalkylalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 4-8 membered heterocycloalkylalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 7-11 arylalkyl, C 3-7 cycloalkyl, C 4-8 cycloalkylalkyl, 3-7 membered heterocycloalkyl, 4-8 membered heterocycloalkylalkyl, 5-6 membered heteroaryl, 6-21 membered heteroarylalkyl, halogen, —CN, —C(═O)R 20 , —C(═)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 , R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-10 aryl, C 3-7 cycloalkyl, 3-7 membered heterocycloalkyl or a 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , C 4-8 cycloalkylalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 4-8 membered heterocycloalkylalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , or a 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl, C 2-6 alkynyl, C 6-10 aryl, C 3-7 cycloalkyl, 3-7 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 3-7 cycloalkyl, or a 3-7 membered heterocycloalkyl.

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , and —OR 20 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 9 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , and —OR 20 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NR 22 R 23 , —NR 24 C(═O)R 20 , and —OR 20 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NR 22 R, —NR 24 C(═O)R 20 , and —OR 20 ; R 8 is chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 7-16 arylalkyl optionally substituted by 1-19 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NR 22 R, —NR 24 C(═O)R 20 , and —OR 20 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)NR 22 R 23 )(NR)(NR 23 ), —NR 24 P(═)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(OR 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R)(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); or R and R 8 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , and —S(═O)NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-10 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 2 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 NR 22 R 23 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , and —S(═O)NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —Si(R 24 ) 3 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 7 and R 8 can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —Si(R 24 ) 3 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , halogen, —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 .

The compound of any of Embodiments 1-156, wherein R 7 , R 8 , and R 9 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —S(═O) n R 20 .

The compound of any of Embodiments 1-156 or 200-222, wherein R 8 is not phenyl or morpholinyl.

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , halogen, —CN, —C(═O)R 20 , —C(═)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; R 8 is chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; and R 9 is chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 19 , C 2-6 alkenyl optionally substituted by 1-11 R 19 , C 2-6 alkynyl optionally substituted by 1-9 R 19 , C 6-11 aryl optionally substituted by 1-11 R 19 , C 3-11 cycloalkyl optionally substituted by 1-21 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 19 , 5-15 membered heteroaryl optionally substituted by 1-15 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 20 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , (═)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; R 8 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; and R 9 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —(═)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; R 8 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; and R 9 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , —S(═) n R 20 , and —S(═O) 2 NR 22 R 23 ; R 8 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , and halogen; and R 9 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 20 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═) n R 20 and —S(═O) 2 NR 22 R 23 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 and —OC(═O)R 20 ; R 8 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , and halogen; and R 9 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 3-10 -cycloalkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8 is chosen from H and halogen; and R 9 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , and —S(═O) n R 20 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 3-10 -cycloalkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8 is chosen from H and halogen; and R 9 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —S(═O) n R 20 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 3-10 -cycloalkyl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8 is chosen from H and halogen; and R 9 is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —S(═O) n R 20 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 3-6 cycloalkyl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8 is chosen from H and halogen; and R 9 is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —S(═O) n R 20 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 3-6 cycloalkyl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8 is chosen from H and halogen; and R 9 is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —S(═O) n R 20 .

The compound of any of Embodiments 1-156 or 200-233, wherein R 8 is H.

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 3-10 -cycloalkyl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —OR 20 ; R 8 is chosen from H and halogen; and R 9 is chosen from H, C 1-6 alkyl, C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 1-6 alkyl, C 3-6 cycloalkyl, halogen, —NR 22 R 23 , and —OR 20 ; R 8 is chosen from H and halogen; and R 9 is chosen from H, C 2-6 alkynyl, C 6-10 aryl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halogen, —NR 22 R 23 , —OR 20 , and —SR 20 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 3-6 cycloalkyl, and —OR 20 ; R 8 is chosen from H and halogen; and R 9 is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 3-6 cycloalkyl, and —OR 20 ; R 8 is chosen from H and halogen; and R 9 is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 3-6 cycloalkyl, and —O(C 1-6 alkyl); R 8 is chosen from H and halogen; and R 9 is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 3-6 cycloalkyl, and —OR 20 ; R 8 is H; and R 9 is H.

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 3-6 cycloalkyl, and —O(C 1-6 alkyl); R 8 is H; and R 9 is H.

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, cyclopropyl, and —O(C 1-6 alkyl); R 8 is chosen from H and halogen; and R 9 is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, cyclopropyl, and —OR 20 ; R 8 is H; and R 9 is H.

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, cyclopropyl, and —O(C 1-6 alkyl); R 8 is H; and R 9 is H.

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, cyclopropyl, and —O(CH 3 ); R 8 is H; and R 9 is H.

The compound of any of Embodiments 1-156, wherein R 7 is H; R 8 is H; and R 9 is H.

The compound of any of Embodiments 1-156, wherein R 7 is cyclopropyl; R 8 is H; and R 9 is H.

The compound of any of Embodiments 1-156, wherein R 7 is —O(CH 3 ); R 8 is H; and R 9 is H.

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, cyclopropyl, and —O(C 1-6 alkyl); R 8 is chosen from H and halogen; and R 9 is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 .

The compound of any of Embodiments 1-156, wherein R 7 is chosen from H, C 3-6 cycloalkyl, and —O(CH 3 ); R 8 is chosen from H and halogen; and R 9 is chosen from H, C 2-6 alkynyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5, 6, or 9 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , —OR 20 , and —SR 20 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 2 , R 13 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —C(═O)C(═O)R 20 , —C(═NR 25 )R 20 , —C(═NR 25 )NR 22 R 23 , —C(═NOH)NR 22 R 23 , —C(═NOR 26 )R 20 , —C(═NNR 22 R 23 )R 20 , —C(═NNR 24 C(═O)R 21 )R 20 , —C(═NNR 24 C(═O)OR 21 )R 20 , —C(═S)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 2 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(R 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); or either or both of R 12 and R 13 , and/or R 14 and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), and —P(═O)(OR 20 )(OR 20 ); or either or both of R 12 and R 13 , and/or R 14 and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR, —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(N 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), and —P(═O)(OR 20 )(OR 20 ); or either or both of R 12 and R 13 , and/or R 14 and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), and —P(═O)(OR 20 )(OR 20 ); or either or both of R 12 and R 13 , and/or R 14 and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-11 aryl optionally substituted by 1-3 R 19 , C 7-16 arylalkyl optionally substituted by 1-3 R 19 , C 3-11 cycloalkyl optionally substituted by 1-3 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-15 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 20 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), and —P(═O)(OR 20 )(OR 20 ); or either or both of R 12 and R 13 , and/or R 14 and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , C 3-11 cycloalkyl optionally substituted by 1-3 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), and —P(═O)(OR 20 )(OR 20 ); or either or both of R 12 and R 13 , and/or R 14 and R 15 , can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —P(O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), and —P(═O)(OR 20 )(OR 20 ); or either or both of R 12 and R 13 , and/or R 14 and R 15 , can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)N 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or either or both of R 12 and R 13 , and/or R 14 and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , C 3-11 cycloalkyl optionally substituted by 1-3 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 13 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or either or both of R 12 and R 13 , and/or R 14 and R 15 , can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 2 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , NR 4 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═)OR 20 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , and —S(═O)NR 22 R 23 ; or either or both of R 12 and R 13 , and/or R 14 and R 15 , can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)NR 22 R 23 )(NR 22 )(NR 23 ), —NR 24 P(═)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , and —S(═O)NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —SCN, —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a C 6 10aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 2 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 and R 14 are H; R 15 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —SCN, —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a C 6 10aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 and R 14 are H; R 15 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 and R 14 are H; R 15 is chosen from H and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 2 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 2 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , C 3-7 cycloalkyl optionally substituted by 1-3 R 19 , 3-7 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , phenyl optionally substituted by 1-3 R 19 , 5-6 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —S(═O) n R 20 and —S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 2 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , halogen, —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , and —NR 24 S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , halogen, —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , and —NR 24 S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 or a 5-6 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H and halogen; R 13 is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , and —NR 24 S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 or a 5-6 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , and —NR 24 S(═O) 2 NR 22 R 23 ; or R 12 and R 13 can, together with the atoms linking them, form a 5-6 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5-6 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 and R 14 are H; R 15 is chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 and R 15 are H; R 12 is chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5-6 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 and R 14 are H; R 15 is chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 and R 15 are H; R 12 is chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-2 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 and R 14 are H; R 15 is chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-2 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 and R 15 are H; R 12 is chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-2 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 and R 14 are H; R 15 is chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 and R 15 are H; R 12 is chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 is H; R 12 and R 15 are independently chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a pyrrolyl ring optionally substituted by 1 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 and R 14 are H; R 15 is chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a pyrrolyl ring optionally substituted by 1 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 14 and R 15 are H; R 12 is chosen from H and halogen; R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a pyrrolyl ring optionally substituted by 1 R 19 .

The compound of any of Embodiments 300-340, wherein R 14 is H.

The compound of any of Embodiments 300-341, wherein R 15 is H.

The compound of any of Embodiments 300-342, wherein R 12 is H.

The compound of any of Embodiments 300-343, wherein R 13 is H.

The compound of any of Embodiments 300-340, wherein R 14 and R 15 are H.

The compound of any of Embodiments 300-340, wherein R 12 are R 15 are H.

The compound of any of Embodiments 300-340, wherein R 12 , R 14 and R 15 are H.

The compound of any of Embodiments 300-340, wherein R 12 are R 14 are H.

The compound of any of Embodiments 1, 2, 4-156, 200-250, or 300-340, wherein R 12 , R 13 , R 14 , and R 15 are H.

The compound of any of Embodiments 300-342, wherein R 12 and R 13 , together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1-2 R 19 .

The compound of any of Embodiments 300-342, wherein R 12 and R 13 , together with the atoms linking them, form a 5 membered heteroaryl optionally substituted by 1 R 19 .

The compound of any of Embodiments 300-342, wherein R 12 and R 13 , together with the atoms linking them, form a pyrrolyl ring optionally substituted by 1 R 19 .

The compound of any of Embodiments 300-342, wherein R 12 and R 13 , together with the atoms linking them, form a pyrrolyl ring.

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, C 7-16 arylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, C 7-16 arylalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, C 7-16 arylalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 in which the heterocycloalkyl contains carbon atoms and 1 or 2 nitrogen atoms, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms.

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, halogen, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 in which the heterocycloalkyl contains carbon atoms and 1 nitrogen atom, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 in which the heteroaryl contains carbon atoms and 1 nitrogen atom.

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, —NR 22 R 23 , and —NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 in which the heterocycloalkyl contains carbon atoms and 1 or 2 nitrogen atoms, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms.

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, —NR 22 R 23 , and NR 24 C(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 in which the heterocycloalkyl contains carbon atoms and 1 nitrogen atom, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 in which the heteroaryl contains carbon atoms and 1 nitrogen atom.

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 in which the heterocycloalkyl contains carbon atoms and 1 or 2 nitrogen atoms, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms.

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a phenyl optionally substituted by 1-3 R 19 , 5-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 in which the heterocycloalkyl contains carbon atoms and 1 nitrogen atom, or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 in which the heteroaryl contains carbon atoms and 1 nitrogen atom.

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms.

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H, —NHR 23 , and —NHC(═O)R 20 ; or R 12 and R 13 can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 in which the heteroaryl contains carbon atoms and 1 nitrogen atom.

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H and —NHR 23 ; or R 12 and R 13 can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H and —NHR 23 ; or R 12 and R 13 can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 in which the heteroaryl contains carbon atoms and 1 or 2 nitrogen atoms.

The compound of any of Embodiments 1, 2, 4-156, or 200-250, wherein R 12 , R 14 , and R 15 are H, and R 13 is chosen from H and —NHR 23 ; or R 12 and R 13 can, together with the atoms linking them, form a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 in which the heteroaryl contains carbon atoms and 1 nitrogen atom.

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —C(═O)C(═O)R 20 , —C(═NR 25 )R 20 , —C(═NR 25 )NR 22 R 23 , —C(═NOH)NR 22 R 23 , —C(═NOR 26 )R 20 , —C(═NNR 22 R 23 )R 20 , —C(═NNR 24 C(═O)R 21 )R 20 , —C(═NNR 24 C(═)OR 21 )R 20 , —C(═S)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 240 R 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 7 R 7 , —OP(═O)(NR 22 R 23 )(NR 22 R 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(R 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); or any of R a and R b , R a and R c , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R g , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —C(═O)C(═O)R 20 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═)OR 21 , —NR 2 C(═O)C(═)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 )(NR 2 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 2 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(OR 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); or any of R a and R b , R a and R c , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R g , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , and —S(═O) 2 NR 22 R 23 ; or any of R a and R b , R a and R e , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R f , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 NR 22 R 23 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , and —S(═O) 2 NR 22 R 23 ; or any of R a and R b , R a and R c , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R g , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or any of R a and R b , R a and R e , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R g , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or any of R a and R b , R a and R e , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R g , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R e , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═) n R 20 , and —S(═O) 2 NR 22 R 23 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , —OC(═O)OR 20 , —S(═) n R 20 , and —S(═O) 2 NR 22 R 23 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , halogen, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , and —NR 24 S(═O) 2 R 21 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , —NR 22 R 23 , —NR 24 C(═O)R 20 , and —NR 24 S(═O) 2 R 21 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , —NR 22 R 23 , and —NR 24 C(═O)R 20 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and C 7-11 arylalkyl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and benzyl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1 R 19 , and benzyl optionally substituted by 1 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, C 1-6 alkyl optionally substituted by 1 R 19 , and benzyl.

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, methyl optionally substituted by 1 R 19 , and benzyl optionally substituted by 1 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are independently chosen from H, methyl optionally substituted by 1 R 19 , and benzyl.

The compound of any of Embodiments 400-416, wherein at least three of R a , R b , R c , R d , R e , R f , R g , and R h are H.

The compound of any of Embodiments 400-416, wherein at least four of R a , R b , R c , R d , R e , R f , R g , and R h are H.

The compound of any of Embodiments 400-416, wherein at least five of R a , R b , R c , R d , R e , R f , R g , and R h are H.

The compound of any of Embodiments 400-416, wherein at least six of R a , R b , R c , R d , R e , R f , R g , and R h are H.

The compound of any of Embodiments 400-416, wherein at least seven of R a , R b , R e , R d , R e , R f , R g , and R h are H.

The compound of any of Embodiments 400-416, wherein R a , R b R c , R e , R f , R g , and R h are H.

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —C(═O)C(═O)R 20 , —C(═NR 25 )R 20 , —C(═NR 25 )NR 22 R 23 , —C(═NOH)NR 22 R 23 , —C(═NOR 26 )R 20 , —C(═NNR 22 R 23 )R 20 , —C(═NNR 24 C(═O)R 21 )R 20 , —C(═NNR 24 C(═O)OR 21 )R 20 , —C(═S)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═NR 25 )NR 22 R 23 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 C(═S)R 20 , —NR 24 C(═S)OR 20 , —NR 24 C(═S)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 R 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(R 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR 20 )(SR 20 ); or any of R a and R b , R a and R c , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R g , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —C(═O)C(═O)R 20 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —N═NR 24 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —NR 24 P(═O)R 78 R 78 , —NR 24 P(═O)(NR 22 R 23 )(NR 22 R 23 ), —NR 24 P(═O)(OR 20 )(OR 20 ), —NR 24 P(═O)(SR 20 )(SR 20 ), —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OC(═NR 25 )NR 22 R 23 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —OP(═O)R 78 R 78 , —OP(═O)(NR 22 R 23 )(NR 22 R 23 ), —OP(═O)(OR 20 )(OR 20 ), —OP(═O)(SR 20 )(SR 20 ), —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , —S(═O) 2 NR 22 R 23 , —S(═O)NR 22 R 23 , —SP(═O)R 78 R 78 , —SP(═O)(NR 22 R 23 )(NR 22 R 23 ), —SP(═O)(OR 20 )(OR 20 ), —SP(═O)(SR 20 )(SR 20 ), —P(═O)R 78 R 78 , —P(═O)(NR 22 R 23 )(NR 22 R 23 ), —P(═O)(OR 20 )(OR 20 ), and —P(═O)(SR(SR 20 ); or any of R a and R b , R a and R e , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R g , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-11 aryl optionally substituted by 1-6 R 19 , C 7-16 arylalkyl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , and —S(═O) 2 NR 22 R 23 ; or any of R a and R b , R a and R c , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R g , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-11 aryl optionally substituted by 1-6 R 19 , C 3-11 cycloalkyl optionally substituted by 1-6 R 19 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 NR 22 R 23 , —NR 24 OR 26 , —NR 24 C(═O)R 20 , —NR 24 C(═O)C(═O)R 20 , —NR 24 C(═O)OR 21 , —NR 24 C(═O)C(═O)OR 21 , —NR 24 C(═O)NR 22 R 23 , —NR 24 C(═O)NR 24 C(═O)R 20 , —NR 24 C(═O)NR 24 C(═O)OR 20 , —NR 24 C(═O)C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OCN, —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —OS(═O)R 20 , —OS(═O) 2 R 20 , —OS(═O) 2 OR 20 , —OS(═O) 2 NR 22 R 23 , —Si(R 24 ) 3 , —SCN, —S(═O) n R 20 , —S(═O) 2 OR 20 , —SO 3 R 27 , and —S(═O) 2 NR 22 R 23 ; or any of R a and R b , R a and R e , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R g , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 19 , C 2-6 alkenyl optionally substituted by 1-6 R 19 , C 2-6 alkynyl optionally substituted by 1-6 R 19 , C 6-10 aryl optionally substituted by 1-6 R 19 , C 7-11 arylalkyl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 , 5-10 membered heteroaryl optionally substituted by 1-6 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or any of R a and R b , R a and R c , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R g , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-6 R 19 , C 3-10 cycloalkyl optionally substituted by 1-6 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 2-6 alkenyl optionally substituted by 1-3 R 19 , C 2-6 alkynyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NC, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 ; or any of R a and R b , R a and R e , R a and R e , R a and R g , R b and R d , R b and R f , R b and R h , R c and R d , R c and R e , R c and R g , R d and R f , R d and R h , R e and R f , R e and R g , R f and R h , and R g and R h can, together with the atoms linking them, form a C 6-10 aryl optionally substituted by 1-3 R 19 , C 3-10 cycloalkyl optionally substituted by 1-3 R 19 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 19 or a 5-10 membered heteroaryl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 6-10 aryl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , 5-10 membered heteroaryl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 C(═O)NR 22 R 23 , —NR 24 S(═O) 2 R 21 , —NR 24 S(═O) 2 NR 22 R 23 , —OR 20 , —OC(═O)R 20 , —OC(═O)NR 22 R 23 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , halogen, —CN, —C(═O)R 20 , —C(═O)OR 20 , —C(═O)NR 22 R 23 , —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , —NR 24 S(═O) 2 R 21 , —OR 20 , —OC(═O)R 20 , —OC(═O)OR 20 , —S(═O) n R 20 , and —S(═O) 2 NR 22 R 23 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , halogen, —NO 2 , —NR 22 R 23 , —NR 24 C(═O)R 20 , and —NR 24 S(═O) 2 R 21 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , —NR 22 R 23 , —NR 24 C(═O)R 20 , and —NR 24 S(═O) 2 R 21 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , C 7-11 arylalkyl optionally substituted by 1-3 R 19 , —NR 22 R 23 , and —NR 24 C(═O)R 20 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and C 7-11 arylalkyl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 19 , and benzyl optionally substituted by 1-3 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1 R 19 , and benzyl optionally substituted by 1 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, C 1-6 alkyl optionally substituted by 1 R 19 , and benzyl.

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, methyl optionally substituted by 1 R 19 , and benzyl optionally substituted by 1 R 19 .

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R e , R f , R g , and R h are H; and R d is chosen from H, methyl optionally substituted by 1 R 19 , and benzyl.

The compound of any of Embodiments 1, 3-156, 200-250, or 300-371, wherein R a , R b , R c , R d , R e , R f , R g , and R h are H.

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 39 , C 2-6 alkenyl optionally substituted by 1-11 R 39 , C 2-6 alkynyl optionally substituted by 1-9 R 39 , C 6-11 aryl optionally substituted by 1-11 R 39 , C 7-16 arylalkyl optionally substituted by 1-19 R 39 , C 3-11 cycloalkyl optionally substituted by 1-21 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 39 , 5-15 membered heteroaryl optionally substituted by 1-15 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —C(═O)C(═O)R 30 , —C(═NR 35 )R 30 , —C(═NR 35 )NR 32 R 33 , —C(═NOH)NR 32 R 33 , —C(═NOR 36 )R 30 , —C(═NNR 32 R 33 )R 30 , —C(═NNR 34 C(═O)R 31 )R 30 , —C(═NNR 34 C(═O)OR 31 )R 30 , —C(═S)NR 32 R 33 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —N═NR 34 , ═NR 30 , ═NOR 30 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 30 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 33 , —NR 34 C(═S)R 30 , —NR 34 C(═S)OR 30 , —NR 34 C(═S)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —NR 34 P(═O)R 78 R 78 , —NR 34 P(═O)(NR 32 R 33 )(NR 32 R 33 ), —NR 34 P(═O)(OR 30 )(OR 30 ), —NR 34 P(═O)(SR 30 )(SR 3 ), —OR 30 , ═O, —OCN, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —OS(═O)R 30 , —OS(═O) 2 R 30 , —OS(═O) 2 OR 30 , —OS(═O) 2 NR 32 R 33 , —OP(═O)R 78 R 78 , —OP(═O)(NR 32 R 33 )(NR 32 R 33 ), —OP(═O)(OR 30 ), —OP(═O)(SR 30 )(SR 30 ), —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —SP(═O)R 78 R 78 , —SP(═O)(NR 32 R 33 )(NR 32 R 33 ), —SP(═O)(OR 30 )(OR 30 ), —SP(═O)(SR 30 )(SR 30 ), —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 ).

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 39 , C 2-6 alkenyl optionally substituted by 1-6 R 39 , C 2-6 alkynyl optionally substituted by 1-6 R 39 , C 6-11 aryl optionally substituted by 1-6 R 39 , C 7-16 arylalkyl optionally substituted by 1-6 R 39 , C 3-11 cycloalkyl optionally substituted by 1-6 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 39 , 5-15 membered heteroaryl optionally substituted by 1-6 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 39 , halogen, —CN, —C(═O)R 30 , —C(═)OR 30 , —C(═O)NR 32 R 33 , —C(═O)C(═O)R 30 , —C(═NR 35 )R 30 , —C(═NR 35 )NR 32 R 33 , —C(═NOH)NR 32 R 33 , —C(═NOR 36 )R 3 , —C(═NNR 32 R 33 )R 30 , —C(═NNR 34 C(═O)R 31 )R 30 , —C(═NNR 34 C(═O)OR 31 )R 30 , —C(═S)NR 32 R 33 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —N═NR 34 , ═NR 30 , ═NOR 30 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 30 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 30 , —NR 34 C(═S)R 30 , —NR 34 C(═S)OR 30 , —NR 34 C(═S)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —NR 34 P(═O)R 78 R 78 , —NR 34 P(═O)(NR 32 R 33 )(NR 32 R 33 ), —NR 34 P(═O)(OR 30 )(OR 30 ), —NR 34 P(═O)(SR 30 )(SR 3 ), —OR 30 , ═O, —OCN, —OC(═O)R 3 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —OS(═O)R 30 , —OS(═O) 2 R 30 , —OS(═O) 2 OR 30 , —OS(═O) 2 NR 32 R 33 , —OP(═O)R 78 R 78 , —OP(═O)(NR 32 R 33 )(NR 32 R 33 ), —OP(═O)(OR 30 )(OR 30 ), —OP(═O)(SR 30 )(SR 30 ), —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —SP(═O)R 78 R 78 , —SP(═O)(NR 32 R 33 )(NR 32 R 33 ), —SP(═O)(OR 30 )(OR 30 ), —SP(═O)(SR 30 )(SR 30 ), —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 )(SR).

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 39 , C 2-6 alkenyl optionally substituted by 1-6 R 39 , C 2-6 alkynyl optionally substituted by 1-6 R 39 , C 6-11 aryl optionally substituted by 1-6 R 39 , C 7-16 arylalkyl optionally substituted by 1-6 R 39 , C 3-11 cycloalkyl optionally substituted by 1-6 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 39 , 5-15 membered heteroaryl optionally substituted by 1-6 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 39 , halogen, —CN, —C(═O)R 30 , —C(═)OR 30 , —C(═O)NR 32 R 33 , —C(═)C(═)R 30 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 30 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OCN, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 ).

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-11 aryl optionally substituted by 1-3 R 39 , C 7-16 arylalkyl optionally substituted by 1-3 R 39 , C 3-11 cycloalkyl optionally substituted by 1-3 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 39 , 5-15 membered heteroaryl optionally substituted by 1-3 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═)OR 30 , —C(═O)NR 32 R 33 , —C(═O)C(═O)R 30 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 3 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OCN, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 ).

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-10 cycloalkyl optionally substituted by 1-3 R 39 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═)OR 30 , —C(═O)NR 32 R 33 , —C(═O)C(═O)R 30 , —NC, —NO 2 , —NR 32 R 33 , —NR 34 NR 32 R 33 , —NR 34 OR 36 , —NR 34 C(═O)R 30 , —NR 34 C(═O)C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 ═O)C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 C(═O)NR 34 C(═O)R 30 , —NR 34 C(═O)NR 34 C(═O)OR 30 , —NR 34 C(═NR 35 )NR 32 R 33 , —NR 34 C(═O)C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OCN, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —OC(═O)OR 30 , —OC(═NR 35 )NR 32 R 33 , —Si(R 34 ) 3 , —SCN, ═S, —S(═O) n R 30 , —S(═O) 2 OR 30 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 ).

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-10 cycloalkyl optionally substituted by 1-3 R 39 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OC(═O)R 3 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , ═S, —S(═O) n R 30 , —S(═O) 2 OR 3 , —SO 3 R 37 , —S(═O) 2 NR 32 R 33 , —S(═O)NR 32 R 33 , —P(═O)R 78 R 78 , —P(═O)(NR 32 R 33 )(NR 32 R 33 ), —P(═O)(OR 30 )(OR 30 ), and —P(═O)(SR 30 )(SR 30 ).

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 2-6 arylalkyl optionally substituted by 1-3 R 39 , C 3-10 cycloalkyl optionally substituted by 1-3 R 39 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 3 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 C(═O)OR 31 , —NR 34 C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OC(═O)R 3 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , ═S, —S(═O) n R 3 , —S(═O) 2 NR 32 R 33 , and —S(═O)NR 32 R 33 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-10 cycloalkyl optionally substituted by 1-3 R 39 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-10 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR, ═O, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , ═S, —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkenyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 3 , —C(═O)OR 3 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , ═S, —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 3 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 S(═O) 2 R 31 , —OR 30 , ═O, —OC(═O)R 30 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 S(═O) 2 R 31 , —OR 30 , ═O, —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —OR 30 , and ═O.

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl, C 6-10 aryl, C 7-11 arylalkyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —OR 30 , and ═O.

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl, C 6-10 aryl, C 7-11 arylalkyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , and OR 30 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 39 , C 2-6 alkenyl optionally substituted by 1-11 R 39 , C 2-6 alkynyl optionally substituted by 1-9 R 39 , C 6-11 aryl optionally substituted by 1-11 R 39 , C 7-16 arylalkyl optionally substituted by 1-19 R 39 , C 3-11 cycloalkyl optionally substituted by 1-21 R 39 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 39 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 39 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 39 , 5-15 membered heteroaryl optionally substituted by 1-15 R 39 , 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 39 , halogen, —CN, —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , and —OR 30 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 39 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 6-10 aryl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —C(═O)OR 30 , —NR 32 R 33 , and —OR 30 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , phenyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —C(═O)OR 30 , —NR 32 R 33 , and —OR 3 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl, phenyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl, halogen, —C(═O)OR 30 , —NR 32 R 33 , and —OR 30 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl, phenyl optionally substituted by 1 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl optionally substituted by 1 R 39 , 5-6 membered heteroaryl, halogen, —C(═O)OR 30 , —NR 32 R 33 , and —OR 30 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —C(═O)OR 30 , —NR 32 R 33 , and —OR 30 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)R 30 , —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NO 2 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 C(═O)NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —NR 34 S(═O) 2 NR 32 R 33 , —OR 30 , ═O, —OC(═O)R 3 , —OC(═O)NR 32 R 33 , —Si(R 34 ) 3 , ═S, —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , halogen, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 C(═O)R 30 , —NR 34 S(═O) 2 R 31 , —OR 30 , ═O, —OC(═O)R 3 , —S(═O) n R 30 , and —S(═O) 2 NR 32 R 33 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 30 , and ═O.

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl optionally substituted by 1-3 R 39 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5-6 membered heteroaryl optionally substituted by 1-3 R 39 , —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , and —OR 30 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , benzyl optionally substituted by 1-3 R 39 , cyclopropyl optionally substituted by 1-3 R 39 , 6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5 membered heteroaryl optionally substituted by 1-3 R 39 , —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 30 , and ═O.

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , benzyl optionally substituted by 1-3 R 39 , cyclopropyl optionally substituted by 1-3 R 39 , 6 membered heterocycloalkyl optionally substituted by 1-3 R 39 , 5 membered heteroaryl optionally substituted by 1-3 R 39 , —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , and —OR 30 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , benzyl optionally substituted by 1-3 R 39 , cyclopropyl optionally substituted by 1-3 R 39 , morpholinyl optionally substituted by 1-3 R 39 , pyrazolyl optionally substituted by 1-3 R 39 , —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 30 , and ═O.

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl optionally substituted by 1-3 R 39 , benzyl optionally substituted by 1-3 R 39 , cyclopropyl optionally substituted by 1-3 R 39 , morpholinyl optionally substituted by 1-3 R 39 , pyrazolyl optionally substituted by 1-3 R 39 , —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , and —OR 30 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 30 , and ═O.

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, C 7-11 arylalkyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , and —OR 30 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, benzyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 30 , and ═O.

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, benzyl optionally substituted by 1-3 R 39 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , and —OR 30 .

The compound of any of Embodiments 1-156, 200-250, 300-371, or 400-440, wherein R 19 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 39 , C 2-6 alkynyl, benzyl optionally substituted by 1-3 R 39 , cyclopropyl, morpholinyl, pyrazolyl, —CN, —C(═O)OR 30 , —C(═O)NR 32 R 33 , —NR 32 R 33 , —NR 34 S(═O) 2 R 31 , —OR 30 , and ═O.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 49 , C 2-6 alkenyl optionally substituted by 1-6 R 49 , C 2-6 alkynyl optionally substituted by 1-6 R 49 , C 6-11 aryl optionally substituted by 1-6 R 49 , C 7-16 arylalkyl optionally substituted by 1-6 R 49 , C 3-11 cycloalkyl optionally substituted by 1-6 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 49 , 5-15 membered heteroaryl optionally substituted by 1-6 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 49 , C 2-6 alkenyl optionally substituted by 1-6 R 49 , C 2-6 alkynyl optionally substituted by 1-6 R 49 , C 6-10 aryl optionally substituted by 1-6 R 49 , C 7-11 arylalkyl optionally substituted by 1-6 R 49 , C 3-10 cycloalkyl optionally substituted by 1-6 R 49 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 49 , and 5-10 membered heteroaryl optionally substituted by 1-6 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 2-6 alkenyl optionally substituted by 1-3 R 49 , C 2-6 alkynyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 7-11 arylalkyl optionally substituted by 1-3 R 49 , C 3-10 cycloalkyl optionally substituted by 1-3 R 49 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 7-11 arylalkyl optionally substituted by 1-3 R 49 , C 3-10 cycloalkyl optionally substituted by 1-3 R 49 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 7-11 arylalkyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and C 3-6 cycloalkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and C 3-6 cycloalkyl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 6-10 aryl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and cyclopropyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , cyclopropyl, thienyl, and pyrazinyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl optionally substituted by 1-3 R 49 , cyclopropyl, thienyl, and pyrazinyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1-3 R 49 , cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, phenyl optionally substituted by 1 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 2 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 6-10 aryl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , cyclopropyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , cyclopropyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1-3 R 49 , cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and cyclopropyl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl optionally substituted by 1 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 6-10 aryl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and C 3-6 cycloalkyl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and C 3-6 cycloalkyl; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1-3 R 49 , cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl optionally substituted by 1-3 R 49 , cyclopropyl, thienyl, and pyrazinyl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 6-10 aryl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 3 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl, benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , cyclopropyl optionally substituted by 1-3 R 49 ; R 21 , R 24 , R 25 , R 26 , R 27 , R 3 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , and cyclopropyl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl, benzyl optionally substituted by 1-3 R 49 , cyclopropyl, thienyl, and pyrazinyl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl optionally substituted by 1 R 49 , C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl optionally substituted by 1 R 49 , C 3-6 cycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl, C 3-6 cycloalkyl, and 5-6 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 at each occurrence is independently chosen from H, phenyl, cyclopropyl, 5 membered heterocycloalkyl, and 5 membered heteroaryl; R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, or 500-533, wherein R 20 , R 21 , R 24 , R 25 , R 26 , R 27 , R 30 , R 31 , R 34 , R 35 , R 36 and R 37 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 49 , C 2-6 alkenyl optionally substituted by 1-11 R 49 , C 2-6 alkynyl optionally substituted by 1-9 R 49 , C 6-11 aryl optionally substituted by 1-11 R 49 , C 7-16 arylalkyl optionally substituted by 1-19 R 49 , C 3-11 cycloalkyl optionally substituted by 1-21 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 49 , 5-15 membered heteroaryl optionally substituted by 1-15 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 , C 2-6 alkenyl optionally substituted by 1-3 R 49 , C 2-6 alkynyl optionally substituted by 1-3 R 49 , C 6-11 aryl optionally substituted by 1-3 R 49 , C 7-16 arylalkyl optionally substituted by 1-3 R 49 , C 3-11 cycloalkyl optionally substituted by 1-3 R 49 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 49 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 49 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 49 , 5-15 membered heteroaryl optionally substituted by 1-3 R 49 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 , C 2-6 alkenyl optionally substituted by 1-3 R 49 , C 2-6 alkynyl optionally substituted by 1-3 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 7-11 arylalkyl optionally substituted by 1-3 R 49 , C 3-10 cycloalkyl optionally substituted by 1-3 R 49 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 , C 6-10 aryl optionally substituted by 1-3 R 49 , C 7-11 arylalkyl optionally substituted by 1-3 R 49 , C 3-10 cycloalkyl optionally substituted by 1-3 R 49 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl optionally substituted by 1-3 R 49 , C 3-6 cycloalkyl optionally substituted by 1-3 R 49 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 , phenyl optionally substituted by 1-3 R 49 , benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 and 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 and 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 and 5-6 membered heterocycloalkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 and 5 membered heterocycloalkyl optionally substituted by 1-6 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 and 5 membered heterocycloalkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 49 and pyrrolidinyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 49 and 5 membered heterocycloalkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is C 1-6 alkyl optionally substituted by 1-6 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, or 600-668, wherein R 28 at each occurrence is C 1-6 alkyl optionally substituted by 1-3 R 49 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 59 , C 2-6 alkenyl optionally substituted by 1-11 R 59 , C 2-6 alkynyl optionally substituted by 1-9 R 59 , C 6-11 aryl optionally substituted by 1-11 R 59 , C 7-16 arylalkyl optionally substituted by 1-19 R 59 , C 3-11 cycloalkyl optionally substituted by 1-21 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 59 , 5-15 membered heteroaryl optionally substituted by 1-15 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 59 ; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 69 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 2-6 alkenyl optionally substituted by 1-3 R 59 , C 2-6 alkynyl optionally substituted by 1-3 R 59 , C 6-11 aryl optionally substituted by 1-3 R 59 , C 7-16 arylalkyl optionally substituted by 1-3 R 59 , C 3-11 cycloalkyl optionally substituted by 1-3 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 59 , 5-15 membered heteroaryl optionally substituted by 1-3 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 59 ; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 69 or a 5-15 membered heteroaryl optionally substituted by 1-3 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 2-6 alkenyl optionally substituted by 1-3 R 59 , C 2-6 alkynyl optionally substituted by 1-3 R 59 , C 6-10 aryl optionally substituted by 1-3 R 59 , C 7-11 arylalkyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 69 or a 5-10 membered heteroaryl optionally substituted by 1-3 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 2-6 alkenyl optionally substituted by 1-3 R 59 , C 2-6 alkynyl optionally substituted by 1-3 R 59 , C 6-10 aryl optionally substituted by 1-3 R 59 , C 7-11 arylalkyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 6-10 aryl optionally substituted by 1-3 R 59 , C 7-11 arylalkyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 6-10 aryl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 4-5 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-9 membered heteroaryl optionally substituted by 1-3 R 59 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 4-5 membered heterocycloalkyl, and 5-9 membered heteroaryl optionally substituted by 1-3 R 59 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 59 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , and 6 membered heteroaryl optionally substituted by 1-3 R 59 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1 R 59 , and 6 membered heteroaryl optionally substituted by 1 R 59 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 and R 32 at each occurrence are independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 59 , C 2-6 alkenyl optionally substituted by 1-11 R 59 , C 2-6 alkynyl optionally substituted by 1-9 R 59 , C 6-11 aryl optionally substituted by 1-11 R 59 , C 7-16 arylalkyl optionally substituted by 1-19 R 59 , C 3-11 cycloalkyl optionally substituted by 1-21 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 59 , 5-15 membered heteroaryl optionally substituted by 1-15 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 59 ; R 23 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 69 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 and R 32 at each occurrence are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 2-6 alkenyl optionally substituted by 1-3 R 59 , C 2-6 alkynyl optionally substituted by 1-3 R 59 , C 6-11 aryl optionally substituted by 1-3 R 59 , C 7-16 arylalkyl optionally substituted by 1-3 R 59 , C 3-11 cycloalkyl optionally substituted by 1-3 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 59 , 5-15 membered heteroaryl optionally substituted by 1-3 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 59 ; R 23 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 69 or a 5-15 membered heteroaryl optionally substituted by 1-3 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 and R 32 at each occurrence are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 6-10 aryl optionally substituted by 1-3 R 59 , bezyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 and R 32 at each occurrence are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 and R 33 at each occurrence are independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 and R 32 at each occurrence are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , benzyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 and R 33 at each occurrence are independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 4-5 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-9 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 and R 32 at each occurrence are independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; R 23 and R 33 at each occurrence are independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 59 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 and R 32 at each occurrence are independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , benzyl, C 3-10 cycloalkyl, 4-5 membered heterocycloalkyl, and 5-9 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 59 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 6-10 aryl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 59 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 and R 32 at each occurrence are independently chosen from H, phenyl optionally substituted by 1-3 R 59 , benzyl, and 6 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, phenyl optionally substituted by 1 R 59 , and 6 membered heteroaryl optionally substituted by 1 R 59 ; R 23 , R 32 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 59 , C 2-6 alkenyl optionally substituted by 1-11 R 59 , C 2-6 alkynyl optionally substituted by 1-9 R 59 , C 6-11 aryl optionally substituted by 1-11 R 59 , C 7-16 arylalkyl optionally substituted by 1-19 R 59 , C 3-11 cycloalkyl optionally substituted by 1-21 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 59 , 5-15 membered heteroaryl optionally substituted by 1-15 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 59 ; R 23 , R 32 and R 33 at each occurrence is H; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 69 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 2-6 alkenyl optionally substituted by 1-3 R 59 , C 2-6 alkynyl optionally substituted by 1-3 R 59 , C 6-11 aryl optionally substituted by 1-3 R 59 , C 7-16 arylalkyl optionally substituted by 1-3 R 59 , C 3-11 cycloalkyl optionally substituted by 1-3 R 59 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 59 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 59 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 59 , 5-15 membered heteroaryl optionally substituted by 1-3 R 59 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is H; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 69 or a 5-15 membered heteroaryl optionally substituted by 1-3 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , C 2-6 alkenyl optionally substituted by 1-3 R 59 , C 2-6 alkynyl optionally substituted by 1-3 R 59 , C 6-10 aryl optionally substituted by 1-3 R 59 , C 7-11 arylalkyl optionally substituted by 1-3 R 59 , C 3-10 -cycloalkyl optionally substituted by 1-3 R 59 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is H; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 69 or a 5-10 membered heteroaryl optionally substituted by 1-3 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl optionally substituted by 1-3 R 59 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is H; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 69 or a 5-10 membered heteroaryl optionally substituted by 1-3 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 4-5 membered heterocycloalkyl, and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 4-5 membered heterocycloalkyl optionally substituted by 1-3 R 59 , and 5-9 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 59 , phenyl optionally substituted by 1-3 R 59 , C 3-10 cycloalkyl, 4-5 membered heterocycloalkyl, and 5-9 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, C 6-10 aryl optionally substituted by 1-3 R 59 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 59 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, phenyl optionally substituted by 1-3 R 59 , and 6 membered heteroaryl optionally substituted by 1-3 R 59 ; R 23 , R 32 and R 33 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 at each occurrence is independently chosen from H, phenyl optionally substituted by 1 R 59 , and 6 membered heteroaryl optionally substituted by 1 R 59 ; R 23 , R 32 and R 33 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-13 R 59 ; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 69 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 59 ; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 69 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 59 ; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 69 or a 5-10 membered heteroaryl optionally substituted by 1-6 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-6 R 59 ; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-6 membered heterocycloalkyl optionally substituted by 1-6 R 69 or a 5-6 membered heteroaryl optionally substituted by 1-6 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, or 700-714, wherein R 22 , R 23 , R 32 and R 33 at each occurrence is independently chosen from H and C 1-6 alkyl optionally; or any R 22 and R 23 and/or R 32 and R 33 may form, together with the nitrogen atom to which they are attached, a 3-6 membered heterocycloalkyl or a 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59 and R 69 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 79 , C 2-6 alkenyl optionally substituted by 1-6 R 79 , C 2-6 alkynyl optionally substituted by 1-6 R 79 , C 6-11 aryl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-11 cycloalkyl optionally substituted by 1-6 R 79 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 79 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 79 , 5-15 membered heteroaryl optionally substituted by 1-6 R 79 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —(═O)C(═O)R 70 , —C(═NR 75 )R 70 , —C(═NR 75 )NR 72 R 73 , —C(═NOH)NR 72 R 73 , —C(═NOR 76 )R 70 , —C(═NNR 72 R 73 )R 70 , —C(═NNR 74 C(═O)R 71 )R 70 , —C(═NNR 74 C(═O)OR 71 )R 70 , —C(═S)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —N═NR 74 , ═NR 70 , ═NOR 70 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 C(═O)NR 74 C(═O)OR 70 , —NR 74 C(═NR 75 )NR 72 R 73 , —NR 74 C(═O)C(═O)NR 72 R 73 , —NR 74 C(═S)R 70 , —NR 74 C(═S)OR 70 , —NR 74 C(═S)NR 72 R 73 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —NR 74 P(═O)R 78 R 78 , —NR 74 P(═O)(NR 72 R 73 )(NR 72 R 73 ), —NR 74 P(═)(OR 70 )(OR 70 ), —NR 74 P(═O)(SR 70 )(SR 70 ), —OR 70 , ═O, —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —OC(═NR 75 )NR 72 R 73 , —OS(═O)R 70 , —OS(═O) 2 R 70 , —OS(═O) 2 OR 70 , —OS(═O) 2 NR 72 R 73 , —OP(═O)R 78 R 78 , —OP(═O)(NR 72 R 73 )(NR 72 R 73 ), —OP(═O)(OR 70 )(OR 70 ), —OP(═O)(SR 70 )(SR 70 ), —Si(R 74 ) 3 , —SCN, ═S, —S(═O) n R 70 , —S(═O) 2 OR 70 , —SO 3 R 77 , —S(═O) 2 NR 72 R 73 , —S(═O)NR 72 R 73 , —SP(═O)R 78 R 78 , —SP(═O)(NR 72 R 73 )(NR 72 R 73 ), —SP(═O)(OR 70 )(OR 70 ), —SP(═O)(SR 70 )(SR 70 ), —P(═O)R 78 R 78 , —P(═O)(NR 72 R 73 )(NR 72 R 73 ), —P(═O)(OR 70 )(OR 70 ), and —P(═O)(SR 70 )(SR 70 ).

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59 and R 69 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 79 , C 6-11 aryl optionally substituted by 1-6 R 79 , C 7-16 arylalkyl optionally substituted by 1-6 R 79 , C 3-11 cycloalkyl optionally substituted by 1-6 R 79 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 79 , 5-15 membered heteroaryl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NC, —NO 2 , —NR 72 R 73 , —NR 74 NR 72 R 73 , —NR 74 OR 76 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , ═O, —OCN, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —Si(R 74 ) 3 , —SCN, ═S, —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59 and R 69 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 79 , C 6-10 aryl optionally substituted by 1-6 R 79 , C 7-11 arylalkyl optionally substituted by 1-6 R 79 , C 3-10 cycloalkyl optionally substituted by 1-6 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 79 , 5-10 membered heteroaryl optionally substituted by 1-6 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , ═O, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —Si(R 74 ) 3 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59 and R 69 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , C 6-10 aryl optionally substituted by 1-3 R 79 , C 7-11 arylalkyl optionally substituted by 1-3 R 79 , C 3-10 cycloalkyl optionally substituted by 1-3 R 79 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 79 , 5-10 membered heteroaryl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 C(═O)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , ═O, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —Si(R 74 ) 3 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59 and R 69 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , C 3-6 cycloalkyl optionally substituted by 1-3 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , 5-6 membered heteroaryl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 C(═)OR 71 , —NR 74 C(═O)NR 72 R 73 , —NR 74 C(═O)NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —NR 74 S(═O) 2 NR 72 R 73 , —OR 70 , ═O, —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —OC(═O)OR 70 , —Si(R 74 ) 3 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59 and R 69 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , C 3-6 cycloalkyl optionally substituted by 1-3 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , 5-6 membered heteroaryl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)R 70 , —C(═O)OR 70 , —C(═O)NR 72 R 73 , —NO 2 , —NR 72 R 73 , —NR 74 C(═O)R 70 , —NR 74 S(═O) 2 R 71 , —OR 70 , —OC(═O)R 70 , —OC(═O)NR 72 R 73 , —S(═O) n R 70 , and —S(═O) 2 NR 72 R 73 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59 and R 69 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , C 3-6 cycloalkyl optionally substituted by 1-3 R 79 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 79 , 5-6 membered heteroaryl optionally substituted by 1-3 R 79 , halogen, —CN, —C(═O)NR 72 R 73 , —NR 72 R 73 , —OR 70 , and —S(═O) n R 70 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59 and R 69 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)NR 72 R 73 , —NR 72 R 73 , —OR 70 , and —S(═O) n R 70 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59 and R 69 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , cyclopropyl, 5-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)NR 72 R 73 , —NR 72 R 73 , —OR 70 , and —S(═O) n R 70 .

The compound of any of Embodiments 800-808, wherein R 39 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , and 5-6 membered heteroaryl.

The compound of any of Embodiments 800-808, wherein R 39 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , benzyl optionally substituted by 1-3 R 79 , and 6 membered heteroaryl.

The compound of any of Embodiments 800-810, wherein R 49 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , 5-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —C(═O)NR 72 R 73 , and —NR 72 R 73 .

The compound of any of Embodiments 800-810, wherein R 49 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , 5-6 membered heterocycloalkyl, 6 membered heteroaryl, halogen, —C(═O)NR 72 R 73 , and —NR 72 R 73 .

The compound of any of Embodiments 800-812, wherein R 59 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , cyclopropyl, 5-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —NR 72 R 73 , —OR 70 , and —S(═O)R 70 .

The compound of any of Embodiments 800-812, wherein R 59 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 , phenyl optionally substituted by 1-3 R 79 , cyclopropyl, 6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —NR 72 R 73 , —OR 70 , and —S(═O) n R 70 .

The compound of any of Embodiments 800-814, wherein R 69 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59 and R 69 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 79 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, or 750-795, wherein R 39 , R 49 , R 59 and R 69 at each occurrence is independently C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76 and R 77 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 89 , C 2-6 alkenyl optionally substituted by 1-11 R 89 , C 2-6 alkynyl optionally substituted by 1-9 R 89 , C 6-11 aryl optionally substituted by 1-11 R 89 , C 7-16 arylalkyl optionally substituted by 1-19 R 89 , C 3-11 cycloalkyl optionally substituted by 1-21 R 89 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 89 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 89 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 89 , 5-15 membered heteroaryl optionally substituted by 1-15 R 89 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76 and R 77 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 89 , C 2-6 alkenyl optionally substituted by 1-6 R 89 , C 2-6 alkynyl optionally substituted by 1-6 R 89 , C 6-10 aryl optionally substituted by 1-6 R 89 , C 7-11 arylalkyl optionally substituted by 1-6 R 89 , C 3-10 cycloalkyl optionally substituted by 1-6 R 89 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 89 , and 5-10 membered heteroaryl optionally substituted by 1-6 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76 and R 77 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 89 , C 2-6 alkenyl optionally substituted by 1-3 R 89 , C 2-6 alkynyl optionally substituted by 1-3 R 89 , C 6-10 aryl optionally substituted by 1-3 R 89 , C 7-11 arylalkyl optionally substituted by 1-3 R 89 , C 3-10 cycloalkyl optionally substituted by 1-3 R 89 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 89 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76 and R 77 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 89 , phenyl optionally substituted by 1-3 R 89 , benzyl optionally substituted by 1-3 R 89 , C 3-10 cycloalkyl optionally substituted by 1-3 R 89 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 89 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76 and R 77 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, and 5-10 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76 and R 77 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 89 , phenyl optionally substituted by 1-3 R 89 , benzyl optionally substituted by 1-3 R 89 , C 5-6 cycloalkyl optionally substituted by 1-3 R 89 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 89 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76 and R 77 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76 and R 77 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76 and R 77 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl optionally substituted by 1 R 89 , and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76 and R 77 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76 and R 77 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, or 800-817, wherein R 70 , R 71 , R 74 , R 75 , R 76 and R 77 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 99 , C 2-6 alkenyl optionally substituted by 1-11 R 99 , C 2-6 alkynyl optionally substituted by 1-9 R 99 , C 6-11 aryl optionally substituted by 1-11 R 99 , C 7-16 arylalkyl optionally substituted by 1-19 R 99 , C 3-11 cycloalkyl optionally substituted by 1-21 R 99 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 99 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 99 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 99 , 5-15 membered heteroaryl optionally substituted by 1-15 R 99 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 99 ; or any R 72 and R 73 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 109 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 109 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 99 , C 2-6 alkenyl optionally substituted by 1-6 R 99 , C 2-6 alkynyl optionally substituted by 1-6 R 99 , C 6-11 aryl optionally substituted by 1-6 R 99 , C 7-16 arylalkyl optionally substituted by 1-6 R 99 , C 3-11 cycloalkyl optionally substituted by 1-6 R 99 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 99 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 99 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 99 , 5-15 membered heteroaryl optionally substituted by 1-6 R 99 , and 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 99 ; or any R 72 and R 73 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 109 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 109 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 99 , phenyl optionally substituted by 1-3 R 99 , benzyl optionally substituted by 1-3 R 99 , C 3-10 cycloalkyl optionally substituted by 1-3 R 99 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 99 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 99 ; or any R 72 and R 73 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 109 or a 5-15 membered heteroaryl optionally substituted by 1-3 R 109 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 99 , phenyl optionally substituted by 1-3 R 99 , benzyl optionally substituted by 1-3 R 99 , C 3-10 cycloalkyl optionally substituted by 1-3 R 99 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 99 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 99 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 99 , phenyl optionally substituted by 1-3 R 99 , benzyl optionally substituted by 1-3 R 99 , C 3-6 cycloalkyl optionally substituted by 1-3 R 99 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 99 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 99 ; or any R 72 and R 73 may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 109 or a 5-10 membered heteroaryl optionally substituted by 1-3 R 109 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 99 , phenyl optionally substituted by 1-3 R 99 , benzyl optionally substituted by 1-3 R 99 , C 5-6 cycloalkyl optionally substituted by 1-3 R 99 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 99 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 99 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 99 , phenyl optionally substituted by 1-3 R 99 , benzyl optionally substituted by 1-3 R 99 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 99 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 99 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; or any R 72 and R 73 may form, together with the nitrogen atom to which they are attached, a 5-6 membered heterocycloalkyl or a 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 99 , phenyl optionally substituted by 1-3 R 99 , and benzyl optionally substituted by 1-3 R 99 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 99 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, and benzyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-861, wherein R 72 and R 73 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 89 , C 2-6 alkenyl optionally substituted by 1-11 R 89 , C 2-6 alkynyl optionally substituted by 1-9 R 89 , C 6-11 aryl optionally substituted by 1-11 R 89 , C 7-16 arylalkyl optionally substituted by 1-19 R 89 , C 3-11 cycloalkyl optionally substituted by 1-21 R 89 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 89 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 89 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 89 , 5-15 membered heteroaryl optionally substituted by 1-15 R 89 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 89 ; or any two R 78 attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 89 , C 2-6 alkenyl optionally substituted by 1-3 R 89 , C 2-6 alkynyl optionally substituted by 1-3 R 89 , C 6-11 aryl optionally substituted by 1-3 R 89 , C 7-16 arylalkyl optionally substituted by 1-3 R 89 , C 3-11 cycloalkyl optionally substituted by 1-3 R 89 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 89 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 89 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 89 , 5-15 membered heteroaryl optionally substituted by 1-3 R 89 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 89 ; or any two R 78 attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 89 , C 2-6 alkenyl optionally substituted by 1-3 R 89 , C 2-6 alkynyl optionally substituted by 1-3 R 89 , C 6-10 aryl optionally substituted by 1-3 R 89 , C 7-11 arylalkyl optionally substituted by 1-3 R 89 , C 3-10 cycloalkyl optionally substituted by 1-3 R 89 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 89 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 89 ; or any two R 78 attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 89 , C 6-10 aryl optionally substituted by 1-3 R 89 , C 7-11 arylalkyl optionally substituted by 1-3 R 89 , C 3-10 cycloalkyl optionally substituted by 1-3 R 89 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 89 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 89 ; or any two R 78 attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 89 , phenyl optionally substituted by 1-3 R 89 , benzyl optionally substituted by 1-3 R 89 , C 3-6 cycloalkyl optionally substituted by 1-3 R 89 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 89 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 89 ; or any two R 78 attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; or any two R 78 attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 6 membered heterocycloalkyl optionally substituted by 1-3 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 89 , phenyl, and benzyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 89 , phenyl optionally substituted by 1-3 R 89 , and benzyl optionally substituted by 1-3 R 89 ; or any two R 78 attached to the same phosphorus atom can, together with the phosphorus atom linking them, form a 6 membered heterocycloalkyl optionally substituted by 1-3 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, and benzyl; or any two R 78 attached to the same phosphorus atom can, together with the phosphorus atom linking them, form an azaphosphinane ring optionally substituted by 1-3 C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78 at each occurrence is C 1-6 alkyl optionally substituted by 1-3 R 89 ; or any two R 78 attached to the same phosphorus atom can, together with the phosphorus atom linking them, form an azaphosphinane ring optionally substituted by 1-3 R 89 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-875, wherein R 78 at each occurrence is C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 119 , C 2-6 alkenyl optionally substituted by 1-6 R 119 , C 2-6 alkynyl optionally substituted by 1-6 R 119 , C 6-11 aryl optionally substituted by 1-6 R 119 , C 7-16 arylalkyl optionally substituted by 1-6 R 119 , C 3-11 cycloalkyl optionally substituted by 1-6 R 119 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 119 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 119 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 119 , 5-15 membered heteroaryl optionally substituted by 1-6 R 19 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 119 , halogen, —CN, —C(═O)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —C(═O)C(═O)R 110 , —C(═NR 115 )R 110 , —C(═NR 115 )NR 112 R 113 , —C(═NOH)NR 112 R 113 , —C(═NOR 116 )R 110 , —C(═NNR 112 R 113 )R 110 , —C(═NNR 114 C(═O)R 111 )R 110 , —C(═NNR 114 C(═O)OR 111 )R 110 , —C(═S)NR 112 R 113 , —NC, —NO 2 , —NR 112 R 113 , —NR 114 NR 112 R 113 , —N═NR 114 , ═NR 110 , ═NOR 110 , —NR 114 OR 116 , —NR 114 C(═O)R 110 , —NR 114 C(═O)C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 14 C(═O)NR 114 C(═O)OR 110 , —NR 14 C(═NR 115 )NR 112 R 113 , —NR 114 C(═O)C(═O)NR 112 R 113 , —NR 114 C(═S)R 110 , —NR 114 C(═S)OR 110 , —NR 114 C(═S)NR 112 R 113 , —NR 114 S(═O) 2 R 11 , —NR 114 S(═O) 2 NR 112 R 113 , —NR 114 P(═O)R 118 R 118 , —NR 114 P(═O)(NR 112 R 113 )(NR 112 R 113 ), —NR 114 P(═O)(OR 110 )(OR 110 )—NR 114 P(═O)(SR 110 )(SR 110 ), —OR 110 , ═O, —OCN, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═O)OR 110 , —OC(═NR 115 )NR 112 R 113 , —OS(═O)R 110 , —OS(═O) 2 R, —OS(═O) 2 OR 110 , —OS(═O) 2 NR 112 R 113 , —OP(═O)R 118 R 118 , —OP(═O)(NR 112 R 113 )(NR 112 R 113 ), —OP(═O)(OR 110 )(OR 110 ), —OP(═O)(SR 110 )(SR 110 ), —Si(R 114 ) 3 , —SCN, ═S, —S(═O) n R 110 , —S(═O) 2 OR 110 , —SO 3 R 1111 , —S(═O) 2 NR 112 R 113 , —S(═O)NR 112 R 113 , —SP(═O)R 118 R 118 , —SP(═O)(NR 112 R 113 )(NR 112 R 113 ), —SP(═O)(OR 110 )(OR 110 ), —SP(═O)(SR 110 )(SR 110 ), —P(═O)R 118 R 118 , —P(═O)(NR 112 R 113 )(NR 112 R 113 ), —P(═O)(OR 110 )(OR 110 ), and —P(═O)(SR 110 )(SR 110 ).

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 119 , C 6-11 aryl optionally substituted by 1-6 R 119 , C 7-16 arylalkyl optionally substituted by 1-6 R 119 , C 3-11 cycloalkyl optionally substituted by 1-6 R 119 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 119 , 5-15 membered heteroaryl optionally substituted by 1-6 R 119 , halogen, —CN, —C(═O)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NC, —NO 2 , —NR 112 R 113 , —NR 114 NR 112 R 113 , —NR 114 OR 116 , —NR 114 C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 114 S(═O) 2 R 111 , —NR 114 S(═O) 2 NR 112 R 113 , —OR 110 , ═O, —OCN, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═O)OR 110 , —Si(R 114 ) 3 , —SCN, ═S, —S(═O) n R 110 , and —S(═O) 2 NR 112 R 113 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 119 , C 6-10 aryl optionally substituted by 1-6 R 119 , C 7-11 arylalkyl optionally substituted by 1-6 R 119 , C 3-10 cycloalkyl optionally substituted by 1-6 R 119 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 119 , 5-10 membered heteroaryl optionally substituted by 1-6 R 119 , halogen, —CN, —C(═O)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —NR 114 C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 114 S(═O) 2 R 111 , —NR 114 S(═O) 2 NR 112 R 113 , —OR 110 , ═O, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═O)OR 110 , —Si(R 114 ) 3 , —S(═O) n R 110 , and —S(═O) 2 NR 112 R 113 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 119 , C 6-10 aryl optionally substituted by 1-3 R 119 , C 7-11 arylalkyl optionally substituted by 1-3 R 119 , C 3-10 cycloalkyl optionally substituted by 1-3 R 119 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 119 , 5-10 membered heteroaryl optionally substituted by 1-3 R 119 , halogen, —CN, —C(═O)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —NR 114 C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 114 S(═O) 2 R 111 , —NR 114 S(═O) 2 NR 112 R 113 , —OR 110 , ═O, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═)OR 110 , —Si(R 114 ) 3 , —S(═O) n R 110 , and —S(═O) 2 NR 112 R 113 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 119 , phenyl optionally substituted by 1-3 R 119 , benzyl optionally substituted by 1-3 R 119 , C 3-6 cycloalkyl optionally substituted by 1-3 R 119 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 119 , 5-6 membered heteroaryl optionally substituted by 1-3 R 119 , halogen, —CN, —C(═O)R 11 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —NR 114 C(═O)R 110 , —NR 114 C(═O)OR 111 , —NR 114 C(═O)NR 112 R 113 , —NR 114 C(═O)NR 114 C(═O)R 110 , —NR 114 S(═O) 2 R 111 , —NR 114 S(═O) 2 NR 112 R 113 , —OR 10 , ═O, —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —OC(═O)OR 110 , —Si(R 114 ) 3 , —S(═) n R 110 , and —S(═O) 2 NR 112 R 113 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 119 , phenyl optionally substituted by 1-3 R 119 , benzyl optionally substituted by 1-3 R 119 , C 3-6 cycloalkyl optionally substituted by 1-3 R 119 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 119 , 5-6 membered heteroaryl optionally substituted by 1-3 R 119 , halogen, —CN, —C(═O)R 11 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —NR 114 C(═O)R 111 , —NR 114 S(═O) 2 R 111 , —OR 110 , —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —S(═O) n R 110 , and —S(═O) 2 NR 112 R 113 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 110 , —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —NR 114 C(═O)R 110 , —NR 114 S(═O) 2 R 111 , —OR 110 , —OC(═O)R 110 , —OC(═O)NR 112 R 113 , —S(═O) n R 110 , and —S(═O) 2 NR 112 R 113 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, halogen, —CN, —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —OR 110 , and —S(═O) n R 110 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 119 , phenyl optionally substituted by 1-3 R 119 , benzyl optionally substituted by 1-3 R 119 , halogen, —CN, —C(═O)OR 110 , —C(═O)NR 112 R 113 , —NO 2 , —NR 112 R 113 , —OR 110 , and —S(═O) n R 110 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, halogen, —NR 112 R 113 and —OR 110 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl, halogen, —NR 12 R 113 , and —OR 110 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 119 and halogen.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 119 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, or 850-886, wherein R 79 , R 89 , R 99 and R 109 at each occurrence is independently C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 114 , R 115 , R 116 and R 117 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 129 , C 2-6 alkenyl optionally substituted by 1-11 R 129 , C 2-6 alkynyl optionally substituted by 1-9 R 129 , C 6-11 aryl optionally substituted by 1-11 R 129 , C 7-16 arylalkyl optionally substituted by 1-19 R 129 , C 3-11 cycloalkyl optionally substituted by 1-21 R 129 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 129 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 129 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 129 , 5-15 membered heteroaryl optionally substituted by 1-15 R 129 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 4 , R 115 , R 116 and R 117 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 129 , C 2-6 alkenyl optionally substituted by 1-6 R 129 , C 2-6 alkynyl optionally substituted by 1-6 R 129 , C 6-10 aryl optionally substituted by 1-6 R 129 , C 7-11 arylalkyl optionally substituted by 1-6 R 129 , C 3-10 cycloalkyl optionally substituted by 1-6 R 129 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 129 , and 5-10 membered heteroaryl optionally substituted by 1-6 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 114 , R 115 , R 116 and R 117 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 129 , C 2-6 alkenyl optionally substituted by 1-3 R 129 , C 2-6 alkynyl optionally substituted by 1-3 R 129 , C 6-10 aryl optionally substituted by 1-3 R 129 , C 7-11 arylalkyl optionally substituted by 1-3 R 129 , C 3-10 cycloalkyl optionally substituted by 1-3 R 129 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 129 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 4 , R 115 , R 116 and R 117 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 129 , phenyl optionally substituted by 1-3 R 129 , benzyl optionally substituted by 1-3 R 129 , C 3-10 cycloalkyl optionally substituted by 1-3 R 129 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 129 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 114 , R 115 , R 116 and R 117 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, and 5-10 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 114 , R 115 , R 116 and R 117 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 129 , phenyl optionally substituted by 1-3 R 129 , benzyl optionally substituted by 1-3 R 129 , C 5-6 cycloalkyl optionally substituted by 1-3 R 129 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 129 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 114 , R 115 , R 116 and R 117 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 4 , R 115 , R 116 and R 117 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 4 , R 115 , R 116 and R 117 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl optionally substituted by 1 R 129 , and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 4 , R 115 , R 116 and R 117 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 114 , R 115 , R 116 and R 117 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-913, wherein R 110 , R 111 , R 4 , R 115 , R 116 and R 117 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12 and R 113 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 139 , C 2-6 alkenyl optionally substituted by 1-11 R 139 , C 2-6 alkynyl optionally substituted by 1-9 R 139 , C 6-11 aryl optionally substituted by 1-11 R 139 , C 7-16 arylalkyl optionally substituted by 1-19 R 139 , C 3-11 optionally substituted by 1-21 R 139 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 139 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 139 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 139 , 5-15 membered heteroaryl optionally substituted by 1-15 R 139 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 139 ; or any R 112 and R 113 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 149 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 149 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12 and R 113 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 139 , C 2-6 alkenyl optionally substituted by 1-6 R 139 , C 2-6 alkynyl optionally substituted by 1-6 R 39 , C 6-11 aryl optionally substituted by 1-6 R 139 , C 7-16 arylalkyl optionally substituted by 1-6 R 139 , C 3-11 cycloalkyl optionally substituted by 1-6 R 139 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 139 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 139 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 139 , 5-15 membered heteroaryl optionally substituted by 1-6 R 139 , and 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 139 ; or any R 2 and R 113 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 149 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 149 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12 and R 113 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 139 , phenyl optionally substituted by 1-3 R 139 , benzyl optionally substituted by 1-3 R 139 , C 3-10 cycloalkyl optionally substituted by 1-3 R 139 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 139 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 139 ; or any R 112 and R 113 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 149 or a 5-15 membered heteroaryl optionally substituted by 1-3 R 149 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12 and R 113 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 139 , phenyl optionally substituted by 1-3 R 139 , benzyl optionally substituted by 1-3 R 139 , C 3-10 cycloalkyl optionally substituted by 1-3 R 139 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 139 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 139 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12 and R 113 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 139 , phenyl optionally substituted by 1-3 R 139 , benzyl optionally substituted by 1-3 R 139 , C 3-6 cycloalkyl optionally substituted by 1-3 R 139 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 139 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 139 ; or any R 112 and R 113 may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 149 or a 5-10 membered heteroaryl optionally substituted by 1-3 R 149 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12 and R 113 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 139 , phenyl optionally substituted by 1-3 R 139 , benzyl optionally substituted by 1-3 R 139 , C 5-6 cycloalkyl optionally substituted by 1-3 R 139 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 139 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 139 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12 and R 113 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 139 , phenyl optionally substituted by 1-3 R 139 , benzyl optionally substituted by 1-3 R 139 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 139 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 139 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 112 and R 113 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; or any R 112 and R 113 may form, together with the nitrogen atom to which they are attached, a 5-6 membered heterocycloalkyl or a 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12 and R 113 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12 and R 113 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 139 , phenyl optionally substituted by 1-3 R 139 , and benzyl optionally substituted by 1-3 R 139 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12 and R 113 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 139 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 112 and R 113 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, and benzyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 12 and R 113 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-925, wherein R 112 and R 113 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 129 , C 2-6 alkenyl optionally substituted by 1-11 R 129 , C 2-6 alkynyl optionally substituted by 1-9 R 129 , C 6-11 aryl optionally substituted by 1-11 R 129 , C 7-16 arylalkyl optionally substituted by 1-19 R 129 , C 3-11 cycloalkyl optionally substituted by 1-21 R 129 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 129 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 129 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 129 , 5-15 membered heteroaryl optionally substituted by 1-15 R 129 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 129 , C 2-6 alkenyl optionally substituted by 1-3 R 129 , C 2-6 alkynyl optionally substituted by 1-3 R 129 , C 6-11 aryl optionally substituted by 1-3 R 129 , C 7-16 arylalkyl optionally substituted by 1-3 R 129 , C 3-11 cycloalkyl optionally substituted by 1-3 R 129 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 129 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 129 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 129 , 5-15 membered heteroaryl optionally substituted by 1-3 R 129 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 129 , C 2-6 alkenyl optionally substituted by 1-3 R 129 , C 2-6 alkynyl optionally substituted by 1-3 R 129 , C 6-10 aryl optionally substituted by 1-3 R 129 , C 7-11 arylalkyl optionally substituted by 1-3 R 129 , C 3-10 cycloalkyl optionally substituted by 1-3 R 129 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 129 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 129 , C 6-10 aryl optionally substituted by 1-3 R 129 , C 7-11 arylalkyl optionally substituted by 1-3 R 129 , C 3-10 cycloalkyl optionally substituted by 1-3 R 129 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 129 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 129 , phenyl optionally substituted by 1-3 R 129 , benzyl optionally substituted by 1-3 R 129 , C 3-6 cycloalkyl optionally substituted by 1-3 R 129 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 129 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 129 , phenyl, and benzyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 129 , phenyl optionally substituted by 1-3 R 129 , and benzyl optionally substituted by 1-3 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, and benzyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118 at each occurrence is C 1-6 alkyl optionally substituted by 1-3 R 129 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-939, wherein R 118 at each occurrence is C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , —R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 159 , C 2-6 alkenyl optionally substituted by 1-6 R 159 , C 2-6 alkynyl optionally substituted by 1-6 R 159 , C 6-11 aryl optionally substituted by 1-6 R 159 , C 7-16 arylalkyl optionally substituted by 1-6 R 159 , C 3-11 cycloalkyl optionally substituted by 1-6 R 159 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 159 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 159 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 159 , 5-15 membered heteroaryl optionally substituted by 1-6 R 159 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —(═O)C(═O)R 150 , —C(═NR 155 )R 150 , —C(═NR 155 )NR 152 R 153 , —C(═NOH)NR 152 R 153 , —C(═NOR 156 )R 150 , —C(═NNR 152 R 153 )R 150 , —C(═NNR 154 C(═O)R 151 )R 150 , —C(═NNR 154 C(═O)OR 151 )R 150 , —C(═S)NR 152 R 153 , —NC, —NO 2 , —NR 152 R 153 , —NR 154 NR 152 R 153 , —N═NR 154 , ═NR 150 , ═NOR 150 , —NR 154 OR 156 , —NR 154 C(═O)R 150 , —NR 154 C(═O)C(═O)R 150 , —NR 154 C(═O)OR 151 , —NR 154 C(═O)C(═O)OR 151 , —NR 154 C(═O)NR 152 R 153 , —NR 154 C(═O)NR 154 C(═O)R 150 , —NR 154 C(═O)NR 154 C(═O)OR 150 , —NR 154 C(═NR 155 )NR 152 R 153 , —NR 154 C(═O)C(═O)NR 152 R 153 , —NR 154 C(═S)R 150 , —NR 154 C(═S)OR 150 , —NR 154 C(═S)NR 152 R 153 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O) 2 NR 152 R 15 , —NR 154 P(═O)R 158 R 15 , —NR 154 P(═O)(NR 152 R 153 )(NR 152 R 153 ), —NR 154 P(═)(OR 150 )(OR 150 ), —NR 154 P(═O)(SR 150 )(SR 150 ), —OR 150 , ═O, —OCN, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═O)OR 150 , —OC(═NR 155 )NR 152 R 153 , —OS(═O)R 150 , —OS(═O) 2 R 150 , —OS(═O) 2 OR 150 , —OS(═O) 2 NR 152 R 153 , —OP(═O)R 158 R 158 , —OP(═O)(NR 152 R 153 )(NR 152 R 153 ), —OP(═O)(OR 150 )(OR 150 ), —OP(═O)(SR 150 )(SR 150 ), —Si(R 154 ) 3 , —SCN, ═S, —S(═O) n R, —S(═O) 2 OR 150 , —SO 3 R 1515 , —S(═O) 2 NR 152 R 153 , —S(═O)NR 152 R 153 , —SP(═O)R 158 R 158 , —SP(═O)(NR 152 R 153 )(NR 152 R 153 ), —SP(═O)(OR 150 )(OR 150 ), —SP(═O)(SR 150 )(SR 150 ), —P(═O)R 158 R 158 , —P(═O)(NR 152 R 153 )(NR 152 R 153 ), —P(═O)(OR 150 )(OR 150 ), and —P(═O)(SR 150 )(SR 150 ).

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , —R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 159 , C 6-11 aryl optionally substituted by 1-6 R 159 , C 7-16 arylalkyl optionally substituted by 1-6 R 159 , C 3-11 cycloalkyl optionally substituted by 1-6 R 159 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 159 , 5-15 membered heteroaryl optionally substituted by 1-6 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —NC, —NO 2 , —NR 152 R 153 , —NR 154 NR 152 R 153 , —NR 154 OR 156 , —NR 154 C(═O)R 150 , —NR 154 C(═O)OR 151 , —NR 154 C(═O)NR 152 R 153 , —NR 154 C(═O)NR 154 C(═O)R 150 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O)NR 152 R 153 , —OR 150 , ═O, —OCN, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═O)OR 150 , —Si(R 154 ) 3 , —SCN, ═S, —S(═) n R 150 , and —S(═O) 2 NR 152 R 153 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , —R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 159 , C 6-10 aryl optionally substituted by 1-6 R 159 , C 7-11 arylalkyl optionally substituted by 1-6 R 159 , C 3-10 cycloalkyl optionally substituted by 1-6 R 159 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 159 , 5-10 membered heteroaryl optionally substituted by 1-6 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 153 , —NR 154 C(═O)R 150 , —NR 154 C(═O)OR 151 , —NR 154 C(═O)NR 152 R 153 , —NR 154C (═O)NR 154 C(═O)R 150 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O) 2 NR 152 R 153 , —OR 150 , ═O, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═O)OR 150 , —Si(R 154 ) 3 , —S(═O) n R 150 , and —S(═O) 2 NR 152 R 153 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 159 , C 6-10 aryl optionally substituted by 1-3 R 159 , C 7-11 arylalkyl optionally substituted by 1-3 R 159 , C 3-10 cycloalkyl optionally substituted by 1-3 R 159 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 159 , 5-10 membered heteroaryl optionally substituted by 1-3 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 153 , —NR 154 C(═O)R 150 , —NR 154 C(═O)OR 151 , —NR 154 C(═O)NR 152 R 153 , —NR 154 C(═O)NR 154 C(═O)R 150 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O) 2 NR 152 R 153 , —OR 150 , ═O, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═O)OR, —Si(R 154 ) 3 , —S(═O) n R 150 , and —S(═O) 2 NR 152 R 153 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 159 , phenyl optionally substituted by 1-3 R 159 , benzyl optionally substituted by 1-3 R 159 , C 3-6 cycloalkyl optionally substituted by 1-3 R 159 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 159 , 5-6 membered heteroaryl optionally substituted by 1-3 R 159 , halogen, —CN, —C(═O)R 150 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 153 , —NR 154 C(═O)R 150 , —NR 154 C(═O)OR 151 , —NR 154 C(═O)NR 152 R 153 , —NR 154 C(═O)NR 154 C(═O)R 150 , —NR 154 S(═O) 2 R 151 , —NR 154 S(═O) 2 NR 152 R 153 , —OR 150 , ═O, —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —OC(═O)OR 150 , —Si(R 154 ) 3 , —S(═O) n R 150 , and —S(═O) 2 NR 152 R 153 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 159 , phenyl optionally substituted by 1-3 R 159 , benzyl optionally substituted by 1-3 R 159 , C 3-6 cycloalkyl optionally substituted by 1-3 R 159 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 159 , 5-6 membered heteroaryl optionally substituted by 1-3 R 159 , halogen, —CN, —C(═O)R 150 , —C(═)OR 150 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 153 , —NR 154 C(═O)R 150 , —NR 154 S(═O) 2 R 151 , —OR 150 , —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —S(═O) n R 150 , and —S(═O) 2 NR 152 R 153 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 50 , —C(═O)OR 150 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 15 , —NR 154 C(═O)R 150 , —NR 154 S(═O) 2 R 151 , —OR 150 , —OC(═O)R 150 , —OC(═O)NR 152 R 153 , —S(═O) n R 150 , and —S(═O) 2 NR 152 R 153 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, halogen, —CN, —C(═O)OR 5 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 153 , —OR 150 , and —S(═O) n R 15 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 159 , phenyl optionally substituted by 1-3 R 159 , benzyl optionally substituted by 1-3 R 159 , halogen, —CN, —C(═O)OR 150 , —C(═O)NR 152 R 153 , —NO 2 , —NR 152 R 153 , —OR 150 , and —S(═O) n R 150 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, halogen, —NR 152 R 153 , and —OR 150 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl, halogen, —NR 152 R 153 , and —OR 150 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 159 and halogen.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139 and R 149 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 159 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-950, wherein R 119 , R 129 , R 139 and R 149 at each occurrence is independently C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 5 , R 156 and R 157 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 169 , C 2-6 alkenyl optionally substituted by 1-11 R 169 , C 2-6 alkynyl optionally substituted by 1-9 R 169 , C 6-11 aryl optionally substituted by 1-11 R 169 , C 7-16 arylalkyl optionally substituted by 1-19 R 169 , C 3-11 cycloalkyl optionally substituted by 1-21 R 169 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 169 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 169 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 169 , 5-15 membered heteroaryl optionally substituted by 1-15 R 169 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 169 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156 and R 157 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 169 , C 2-6 alkenyl optionally substituted by 1-6 R 169 , C 2-6 alkynyl optionally substituted by 1-6 R 169 , C 6-10 aryl optionally substituted by 1-6 R 169 , C 7-11 arylalkyl optionally substituted by 1-6 R 169 , C 3-10 cycloalkyl optionally substituted by 1-6 R 169 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 169 , and 5-10 membered heteroaryl optionally substituted by 1-6 R 169 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156 and R 157 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 169 , C 2-6 alkenyl optionally substituted by 1-3 R 169 , C 2-6 alkynyl optionally substituted by 1-3 R 169 , C 6-10 aryl optionally substituted by 1-3 R 169 , C 7-11 arylalkyl optionally substituted by 1-3 R 169 , C 3-10 cycloalkyl optionally substituted by 1-3 R 169 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 169 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 169 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156 and R 157 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 169 , phenyl optionally substituted by 1-3 R 169 , benzyl optionally substituted by 1-3 R 169 , C 3-10 cycloalkyl optionally substituted by 1-3 R 169 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 169 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 69 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 R 156 and R 157 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, and 5-10 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 54 , R 15 , R 156 and R 157 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 169 , phenyl optionally substituted by 1-3 R 169 , benzyl optionally substituted by 1-3 R 169 , C 5-6 cycloalkyl optionally substituted by 1-3 R 169 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 169 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 169 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156 and R 157 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156 and R 157 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156 and R 157 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl optionally substituted by 1 R 169 , and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156 and R 157 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 169 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 R 156 and R 157 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-964, wherein R 150 , R 151 , R 154 , R 155 , R 156 and R 157 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 179 , C 2-6 alkenyl optionally substituted by 1-11 R 179 , C 2-6 alkynyl optionally substituted by 1-9 R 179 , C 6-11 aryl optionally substituted by 1-11 R 179 , C 7-16 arylalkyl optionally substituted by 1-19 R 179 , C 3-11 cycloalkyl optionally substituted by 1-21 R 179 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 179 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 179 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 179 , 5-15 membered heteroaryl optionally substituted by 1-15 R 179 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 179 ; or any R 152 and R 153 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 189 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 189 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 179 , C 2-6 alkenyl optionally substituted by 1-6 R 179 , C 2-6 alkynyl optionally substituted by 1-6 R 179 , C 6-11 aryl optionally substituted by 1-6 R 179 , C 7-16 arylalkyl optionally substituted by 1-6 R 179 , C 3-11 cycloalkyl optionally substituted by 1-6 R 179 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 179 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 179 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 179 , 5-15 membered heteroaryl optionally substituted by 1-6 R 179 , and 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 179 ; or any R 152 and R 153 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 189 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 189 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 179 , phenyl optionally substituted by 1-3 R 179 , benzyl optionally substituted by 1-3 R 179 , C 3-10 cycloalkyl optionally substituted by 1-3 R 179 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 179 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 179 ; or any R 152 and R 153 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 189 or a 5-15 membered heteroaryl optionally substituted by 1-3 R 189 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 179 , phenyl optionally substituted by 1-3 R 179 , benzyl optionally substituted by 1-3 R 179 , C 3-10 cycloalkyl optionally substituted by 1-3 R 179 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 179 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 179 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 179 , phenyl optionally substituted by 1-3 R 179 , benzyl optionally substituted by 1-3 R 179 , C 3-6 cycloalkyl optionally substituted by 1-3 R 179 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 179 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 179 ; or any R 152 and R 153 may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 189 or a 5-10 membered heteroaryl optionally substituted by 1-3 R 189 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 179 , phenyl optionally substituted by 1-3 R 179 , benzyl optionally substituted by 1-3 R 179 , C 5-6 cycloalkyl optionally substituted by 1-3 R 179 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 179 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 179 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 179 , phenyl optionally substituted by 1-3 R 179 , benzyl optionally substituted by 1-3 R 179 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 179 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 179 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; or any R 152 and R 153 may form, together with the nitrogen atom to which they are attached, a 5-6 membered heterocycloalkyl or a 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 179 , phenyl optionally substituted by 1-3 R 179 , and benzyl optionally substituted by 1-3 R 179 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 179 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, and benzyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-976, wherein R 152 and R 153 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 169 , C 2-6 alkenyl optionally substituted by 1-11 R 169 , C 2-6 alkynyl optionally substituted by 1-9 R 169 , C 6-11 aryl optionally substituted by 1-11 R 169 , C 7-16 arylalkyl optionally substituted by 1-19 R 169 , C 3-11 cycloalkyl optionally substituted by 1-21 R 169 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 169 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 169 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 169 , 5-15 membered heteroaryl optionally substituted by 1-15 R 169 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 169 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 169 , C 2-6 alkenyl optionally substituted by 1-3 R 169 , C 2-6 alkynyl optionally substituted by 1-3 R 169 , C 6-11 aryl optionally substituted by 1-3 R 169 , C 7-16 arylalkyl optionally substituted by 1-3 R 169 , C 3-11 cycloalkyl optionally substituted by 1-3 R 169 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 169 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 169 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 169 , 5-15 membered heteroaryl optionally substituted by 1-3 R 169 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 169 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 169 , C 2-6 alkenyl optionally substituted by 1-3 R 169 , C 2-6 alkynyl optionally substituted by 1-3 R 169 , C 6-10 aryl optionally substituted by 1-3 R 169 , C 7-11 arylalkyl optionally substituted by 1-3 R 169 , C 3-10 cycloalkyl optionally substituted by 1-3 R 169 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 169 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 169 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 169 , C 6-10 aryl optionally substituted by 1-3 R 169 , C 7-11 arylalkyl optionally substituted by 1-3 R 169 , C 3-10 cycloalkyl optionally substituted by 1-3 R 169 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 169 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 169 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 169 , phenyl optionally substituted by 1-3 R 169 , benzyl optionally substituted by 1-3 R 169 , C 3-6 cycloalkyl optionally substituted by 1-3 R 169 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 169 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 169 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 169 , phenyl, and benzyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 169 , phenyl optionally substituted by 1-3 R 169 , and benzyl optionally substituted by 1-3 R 169 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, and benzyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158 at each occurrence is C 1-6 alkyl optionally substituted by 1-3 R 169 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-990, wherein R 158 at each occurrence is C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 199 , C 2-6 alkenyl optionally substituted by 1-6 R 199 , C 2-6 alkynyl optionally substituted by 1-6 R 199 , C 6-11 aryl optionally substituted by 1-6 R 199 , C 7-16 arylalkyl optionally substituted by 1-6 R 199 , C 3-11 cycloalkyl optionally substituted by 1-6 R 199 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 199 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 199 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 199 , 5-15 membered heteroaryl optionally substituted by 1-6 R 199 , 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 199 , halogen, —CN, —C(═O)R 190 , —C(═)OR 190 , —C(═O)NR 192 R 193 , —(═O)C(═O)R 190 , —C(═NR 195 )R 190 , —C(═NR 195 )NR 192 R 193 , —C(═NOH)NR 192 R 193 , —C(═NOR 196 )R 190 , —C(═NNR 192 R 193 )R 190 , —C(═NNR 194 C(═O)R 191 )R 190 , —C(═NNR 194 C(═O)OR 191 )R 190 , —C(═S)NR 192 R 193 , —NC, —NO 2 , —NR 192 R 193 , —NR 194 NR 192 R 193 , —N═NR 194 , ═NR 190 , ═NOR 190 , —NR 194 OR 196 , —NR 194 C(═O)R 190 , —NR 194 C(═O)C(═O)R 190 , —NR 194 C(═O)OR, —NR 194 C(═O)C(═O)OR 191 , —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 C(═O)NR 194 C(═O)OR 190 , —NR 194 C(═NR 195 )NR 192 R 193 , —NR 194 C(═O)C(═O)NR 192 R 193 , —NR 194 C(═S)R 190 , —NR 194 C(═S)OR 190 , —NR 194 C(═S)NR 192 R 193 , —NR 194 S(═O) 2 R 19 , —NR 194 S(═O) 2 NR 192 R 193 , —NR 194 P(═O)R 198 R 198 , —NR 194 P(═O)(NR 192 R 193 )(NR 192 R 193 ), —NR 194 P(═)(OR 190 )(OR 190 ), —NR 194 P(═O)(SR 190 )(SR 190 ), —OR 190 , ═O, —OCN, —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —OC(═O)OR 190 , —OC(═NR 195 )NR 192 R 193 , —OS(═O)R 190 , —OS(═O) 2 R 190 , —OS(═O) 2 OR 190 , —OS(═O) 2 NR 192 R 193 , —OP(═O)R 198 R 198 , —OP(═O)(NR 192 R 193 )(NR 192 R 193 ), —OP(═O)(OR 190 )(OR 190 ), —OP(═O)(SR 190 )(SR 190 ), —Si(R 194 ) 3 , —SCN, ═S, —S(═O) n R 190 , —S(═O) 2 OR 190 , —SO 3 R, —S(═O) 2 NR 192 R 193 , —S(═O)NR 192 R 193 , —SP(═O)R 198 R 198 , —SP(═O)(NR 192 R 193 )(NR 192 R 193 ), —SP(═O)(OR 190 )(OR 190 ), —SP(═O)(SR 190 )(SR 190 ), —P(═O)R 198 R 198 , —P(═O)(NR 192 R 193 )(NR 192 R 193 ), —P(═O)(OR 190 )(OR 190 ), and —P(═O)(SR 190 )(SR 190 ).

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 199 , C 6-11 aryl optionally substituted by 1-6 R 199 , C 7-16 arylalkyl optionally substituted by 1-6 R 199 , C 3-11 cycloalkyl optionally substituted by 1-6 R 199 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 199 , 5-15 membered heteroaryl optionally substituted by 1-6 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NC, —NO 2 , —NR 192 R 193 , —NR 194 NR 192 R 193 , —NR 194 OR 196 , —NR 194 C(═O)R 190 , —NR 194 C(═O)OR 191 , —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 S(═O) 2 R 191 , —NR 194 S(═O) 2 NR 192 R 193 , —OR 190 , ═O, —OCN, —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —OC(═O)OR 190 , —Si(R 194 ) 3 , —SCN, ═S, —S(═O) n R 190 , and —S(═O) 2 NR 192 R 193 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 159 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 R 199 , C 6-10 aryl optionally substituted by 1-6 R 199 , C 7-11 arylalkyl optionally substituted by 1-6 R 199 , C 3-10 cycloalkyl optionally substituted by 1-6 R 199 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 199 , 5-10 membered heteroaryl optionally substituted by 1-6 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NO 2 , —NR 192 R 193 , —NR 194 C(═O)R 190 , —NR 194 C(═O)OR, —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 S(═O) 2 R 191 , —NR 194 S(═O) 2 NR 192 R 193 , —OR 190 , ═O, —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —OC(═O)OR 190 , —Si(R 194 ) 3 , —S(═O) n R 190 , and —S(═O) 2 NR 192 R 193 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 199 , C 6-10 aryl optionally substituted by 1-3 R 199 , C 7-11 arylalkyl optionally substituted by 1-3 R 199 , C 3-10 cycloalkyl optionally substituted by 1-3 R 199 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 199 , 5-10 membered heteroaryl optionally substituted by 1-3 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NO 2 , —NR 192 R 193 , —NR 194 C(═O)R 190 , —NR 194 C(═O)OR 191 , —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 S(═O) 2 R 191 , —NR 194 S(═O) 2 NR 192 R 193 , —OR 190 , ═O, —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —OC(═O)OR 190 , —Si(R 194 ) 3 , —S(═O) n R 190 , and —S(═O) 2 NR 192 R 193 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 199 , phenyl optionally substituted by 1-3 R 199 , benzyl optionally substituted by 1-3 R 199 , C 3-6 cycloalkyl optionally substituted by 1-3 R 199 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 199 , 5-6 membered heteroaryl optionally substituted by 1-3 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NO 2 , —NR 192 R 193 , —NR 194 C(═O)R 190 , —NR 194 C(═O)OR 191 , —NR 194 C(═O)NR 192 R 193 , —NR 194 C(═O)NR 194 C(═O)R 190 , —NR 194 S(═O) 2 R 191 , —NR 194 S(═O) 2 NR 192 R 193 , —OR 190 , ═O, —OC(═O)R 190 , —OC(═O)NR 192 R, —OC(═O)OR 190 , —Si(R 194 ) 3 , —S(═O) n R 190 , and —S(═O) 2 NR 192 R 193 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 199 , phenyl optionally substituted by 1-3 R 199 , benzyl optionally substituted by 1-3 R 199 , C 3-6 cycloalkyl optionally substituted by 1-3 R 199 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 199 , 5-6 membered heteroaryl optionally substituted by 1-3 R 199 , halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NO 2 , —NR 192 R 193 , —NR 194 C(═O)R 190 , —NR 194 S(═O) 2 R 191 , —OR 190 , —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —S(═O) n R 190 , and —S(═O) 2 NR 192 R 193 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 190 , —C(═O)OR 190 , —C(═O)NR 192 R 9 , —NO 2 , —NR 192 R 193 , —NR 194 C(═O)R 190 , —NR 194 S(═O) 2 R 191 , —OR 190 , —OC(═O)R 190 , —OC(═O)NR 192 R 193 , —S(═O) n R 190 , and —S(═O) 2 NR 192 R 193 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, halogen, —CN, —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NO 2 , —NR 192 R 193 , —OR 190 , and —S(═O) n R 190 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 199 , phenyl optionally substituted by 1-3 R 199 , benzyl optionally substituted by 1-3 R 199 , halogen, —CN, —C(═O)OR 190 , —C(═O)NR 192 R 193 , —NO 2 , —NR 192 R 193 , —OR 190 , and —S(═O) n R 190 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 159 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, halogen, —NR 192 R 193 , and —OR 190 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl, halogen, —NR 192 R 193 , and —OR 190 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 199 and halogen.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179 and R 189 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 199 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1001, wherein R 59 , R 169 , R 179 and R 189 at each occurrence is independently C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196 and R 197 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 209 , C 2-6 alkenyl optionally substituted by 1-11 R 209 , C 2-6 alkynyl optionally substituted by 1-9 R 209 , C 6-11 aryl optionally substituted by 1-11 R 209 , C 7-16 arylalkyl optionally substituted by 1-19 R 209 , C 3-11 cycloalkyl optionally substituted by 1-21 R 209 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 209 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 209 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 209 , 5-15 membered heteroaryl optionally substituted by 1-15 R 209 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196 and R 197 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 209 , C 2-6 alkenyl optionally substituted by 1-6 R 209 , C 2-6 alkynyl optionally substituted by 1-6 R 209 , C 6-10 aryl optionally substituted by 1-6 R 209 , C 7-11 arylalkyl optionally substituted by 1-6 R 209 , C 3-10 cycloalkyl optionally substituted by 1-6 R 209 , 3-10 membered heterocycloalkyl optionally substituted by 1-6 R 209 , and 5-10 membered heteroaryl optionally substituted by 1-6 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196 and R 197 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 209 , C 2-6 alkenyl optionally substituted by 1-3 R 209 , C 2-6 alkynyl optionally substituted by 1-3 R 209 , C 6-10 aryl optionally substituted by 1-3 R 209 , C 7-11 -arylalkyl optionally substituted by 1-3 R 209 , C 3-10 cycloalkyl optionally substituted by 1-3 R 209 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 209 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196 and R 197 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 209 , phenyl optionally substituted by 1-3 R 209 , benzyl optionally substituted by 1-3 R 209 , C 3-10 cycloalkyl optionally substituted by 1-3 R 209 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 209 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196 and R 197 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, and 5-10 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196 and R 197 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 209 , phenyl optionally substituted by 1-3 R 209 , benzyl optionally substituted by 1-3 R 209 , C 5-6 cycloalkyl optionally substituted by 1-3 R 209 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 209 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196 and R 197 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196 and R 197 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196 and R 197 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl optionally substituted by 1 R 209 , and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196 and R 197 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196 and R 197 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1015, wherein R 190 , R 191 , R 194 , R 195 , R 196 and R 197 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-13 R 219 , C 2-6 alkenyl optionally substituted by 1-11 R 219 , C 2-6 alkynyl optionally substituted by 1-9 R 219 , C 6-11 aryl optionally substituted by 1-11 R 219 , C 7-16 arylalkyl optionally substituted by 1-19 R 219 , C 3-11 cycloalkyl optionally substituted by 1-21 R 219 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 219 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 219 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 219 , 5-15 membered heteroaryl optionally substituted by 1-15 R 219 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 219 ; or any R 192 and R 193 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 229 or a 5-15 membered heteroaryl optionally substituted by 1-15 R 229 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-6 R 219 , C 2-6 alkenyl optionally substituted by 1-6 R 219 , C 2-6 alkynyl optionally substituted by 1-6 R 219 , C 6-11 aryl optionally substituted by 1-6 R 219 , C 7-16 arylalkyl optionally substituted by 1-6 R 219 , C 3-11 cycloalkyl optionally substituted by 1-6 R 219 , C 4-17 cycloalkylalkyl optionally substituted by 1-6 R 219 , 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 219 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-6 R 219 , 5-15 membered heteroaryl optionally substituted by 1-6 R 219 , and 6-21 membered heteroarylalkyl optionally substituted by 1-6 R 219 ; or any R 192 and R 193 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-6 R 229 or a 5-15 membered heteroaryl optionally substituted by 1-6 R 229 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 219 , phenyl optionally substituted by 1-3 R 219 , benzyl optionally substituted by 1-3 R 219 , C 3-10 cycloalkyl optionally substituted by 1-3 R 219 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 219 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 219 ; or any R 192 and R 193 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 229 or a 5-15 membered heteroaryl optionally substituted by 1-3 R 229 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 219 , phenyl optionally substituted by 1-3 R 219 , benzyl optionally substituted by 1-3 R 219 , C 3-10 cycloalkyl optionally substituted by 1-3 R 219 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 219 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 219 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 219 , phenyl optionally substituted by 1-3 R 219 , benzyl optionally substituted by 1-3 R 219 , C 3-6 cycloalkyl optionally substituted by 1-3 R 219 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 219 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 219 ; or any R 192 and R 193 may form, together with the nitrogen atom to which they are attached, a 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 229 or a 5-10 membered heteroaryl optionally substituted by 1-3 R 229 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 219 , phenyl optionally substituted by 1-3 R 219 , benzyl optionally substituted by 1-3 R 219 , C 5-6 cycloalkyl optionally substituted by 1-3 R 219 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 219 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 219 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 219 , phenyl optionally substituted by 1-3 R 219 , benzyl optionally substituted by 1-3 R 219 , 5-6 membered heterocycloalkyl optionally substituted by 1-3 R 219 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 219 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl; or any R 192 and R 193 may form, together with the nitrogen atom to which they are attached, a 5-6 membered heterocycloalkyl or a 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, benzyl, C 5-6 cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H, C 1-6 alkyl optionally substituted by 1-3 R 219 , phenyl optionally substituted by 1-3 R 219 , and benzyl optionally substituted by 1-3 R 219 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H and C 1-6 alkyl optionally substituted by 1-3 R 219 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H, C 1-6 alkyl, phenyl, and benzyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1027, wherein R 192 and R 193 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 R 209 , C 2-6 alkenyl optionally substituted by 1-11 R 209 , C 2-6 alkynyl optionally substituted by 1-9 R 209 , C 6-11 aryl optionally substituted by 1-11 R 209 , C 7-16 arylalkyl optionally substituted by 1-19 R 209 , C 3-11 cycloalkyl optionally substituted by 1-21 R 209 , C 4-17 cycloalkylalkyl optionally substituted by 1-32 R 209 , 3-15 membered heterocycloalkyl optionally substituted by 1-28 R 209 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-40 R 209 , 5-15 membered heteroaryl optionally substituted by 1-15 R 209 , and 6-21 membered heteroarylalkyl optionally substituted by 1-27 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 209 , C 2-6 alkenyl optionally substituted by 1-3 R 209 , C 2-6 alkynyl optionally substituted by 1-3 R 209 , C 6-11 aryl optionally substituted by 1-3 R 209 , C 7-16 arylalkyl optionally substituted by 1-3 R 209 , C 3-11 cycloalkyl optionally substituted by 1-3 R 209 , C 4-17 cycloalkylalkyl optionally substituted by 1-3 R 209 , 3-15 membered heterocycloalkyl optionally substituted by 1-3 R 209 , 4-21 membered heterocycloalkylalkyl optionally substituted by 1-3 R 209 , 5-15 membered heteroaryl optionally substituted by 1-3 R 209 , and 6-21 membered heteroarylalkyl optionally substituted by 1-3 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 209 , C 2-6 alkenyl optionally substituted by 1-3 R 209 , C 2-6 alkynyl optionally substituted by 1-3 R 209 , C 6-10 aryl optionally substituted by 1-3 R 209 , C 7-11 arylalkyl optionally substituted by 1-3 R 209 , C 3-10 cycloalkyl optionally substituted by 1-3 R 209 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 209 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 209 , C 6-10 aryl optionally substituted by 1-3 R 209 , C 7-11 arylalkyl optionally substituted by 1-3 R 209 , C 3-10 cycloalkyl optionally substituted by 1-3 R 209 , 3-10 membered heterocycloalkyl optionally substituted by 1-3 R 209 , and 5-10 membered heteroaryl optionally substituted by 1-3 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 209 , phenyl optionally substituted by 1-3 R 209 , benzyl optionally substituted by 1-3 R 209 , C 3-6 cycloalkyl optionally substituted by 1-3 R 209 , 3-6 membered heterocycloalkyl optionally substituted by 1-3 R 209 , and 5-6 membered heteroaryl optionally substituted by 1-3 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, and 5-6 membered heteroaryl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 209 , phenyl, and benzyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 R 209 , phenyl optionally substituted by 1-3 R 209 , and benzyl optionally substituted by 1-3 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198 at each occurrence is independently chosen from C 1-6 alkyl, phenyl, and benzyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198 at each occurrence is C 1-6 alkyl optionally substituted by 1-3 R 209 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1041, wherein R 198 at each occurrence is C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219 and R 229 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-13 halogen, C 2-6 alkenyl, C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl, C 3-11 cycloalkyl, C 4-17 cycloalkylalkyl, 3-15 membered heterocycloalkyl, 4-21 membered heterocycloalkylalkyl, 5-15 membered heteroaryl, 6-21 membered heteroarylalkyl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —C(═O)C(═O)R 230 , —C(═NR 230 )R 230 , —C(═NR 230 )NR 230 R 230 , —C(═NOH)NR 230 R 230 , —C(═NOR 230 )R 230 , —C(═NNR 230 R 230 )R 230 , —C(═NNR 230 C(═O)R 230 )R 230 , —C(═NNR 230 C(═O)OR 230 )R 230 , —C(═S)NR 230 R 230 , —NC, —NO 2 , —NR 230 R 230 , —NR 230 NR 230 R 230 , —N═NR 230 , ═NR 230 , ═NOR 230 , —NR 230 OR 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)C(═O)R 230 , —NR 230 C(═O)OR 230 , —NR 230 C(═O)C(═O)OR 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 C(═O)NR 230 C(═O)R 230 , —NR 230 C(═O)NR 230 C(═O)OR 230 , —NR 230 C(═NR 230 )NR 230 R 230 , —NR 230 C(O)C(═O)NR 230 R 230 , —NR 230 C(═S)R 230 , —NR 230 C(═S)OR 230 , —NR 230 C(═S)NR 230 R 230 , —NR 230 S(═O) 2 R 230 , —NR 230 S(═O) 2 N 230 R 230 , —NR 230 P(═O)R 231 R 231 , —NR 230 P(═O)(NR 230 R 230 )(NR 230 R 230 ), —NR 230 P(═O)(OR 230 )(OR 230 ), —NR 230 P(═)(SR 230 )(SR 230 ), —OR 230 , ═O, —OCN, —OC(═O)R 230 , —OC(═O)NR 230 R 230 , —OC(═)OR 230 , —OC(═NR 230 )NR 230 R 230 , —OS(═O)R 230 , —OS(═O) 2 R 230 , —OS(═O) 2 OR 230 , —OS(═O) 2 NR 230 R 230 , —OP(═O)R 231 R 231 , —OP(═O)(NR 230 R 230 )(NR 230 R 230 ), —OP(═)(OR 230 )(OR 230 ), —OP(═O)(SR 230 )(SR 230 ), —Si(R 230 ) 3 , —SCN, ═S, —S(═O) n R 230 , —S(═O) 2 R 230 , —SO 3 R 230 , —S(═O) 2 NR 230 R 230 , —S(═O)NR 230 R 230 , —SP(═O)R 231 R 231 , —SP(═O)(NR 230 R 230 )(NR 230 R 230 ), —SP(═O)(OR 230 )(OR 230 ), —SP(═O)(SR 230 )(SR 230 ), —P(═O)R 231 R 231 , —P(═O)(NR 230 R 230 )(NR 230 R 230 ), —P(═O)(OR 230 )(OR 230 ), and —P(═O)(SR 230 )(SR 230 ).

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219 and R 229 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-6 halogen, C 2-6 alkenyl, C 2-6 alkynyl, C 6-11 aryl, C 7-16 arylalkyl, C 3-11 cycloalkyl, C 4-17 cycloalkylalkyl, 3-15 membered heterocycloalkyl, 4-15 membered heterocycloalkylalkyl, 5-15 membered heteroaryl, 6-15 membered heteroarylalkyl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —C(═O)C(═O)R 230 , —NC, —NO 2 , —NR 230 R 230 , —NR 230 NR 230 R 230 , —NR 230 OR 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)C(═O)R 230 , —NR 230 C(═O)OR 230 , —NR 230 C(═O)C(═O)OR 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 C(═O)NR 230 C(═O)R 230 , —NR 230 C(═O)NR 230 C(═O)OR 230 , —NR 230 C(═O)C(═O)NR 230 R 230 , —NR 230 S(═O) 2 R 230 , —NR 230 S(═O) 2 NR 230 R 230 , —NR 230 P(═O)R 231 R 231 , —NR 230 P(═O)(NR 230 R 230 )(NR 230 R 230 ), —NR 230 P(═O)(OR 230 )(OR 230 ), —OR 230 , ═O, —OCN, —OC(═O)R 230 , —OC(═O)NR 230 R 230 , —OC(═O)OR 230 , —OS(═O)R 230 , —OS(═O) 2 R 230 , —OS(═O) 2 R 230 , —OS(═O) 2 NR 230 R 230 , —OP(═O)R 231 R 231 , —OP(═O)(NR 230 R 230 )(NR 230 R 230 ), —OP(═O)(OR 230 )(OR 230 ), —Si(R 230 ) 3 , —SCN, ═S, —S(═O) n R 230 , —S(═O) 2 OR 230 , —SO 3 R 230 , —S(═O) 2 NR 230 R 230 , —S(═O)NR 230 R 230 , —P(═O)R 231 R 231 , —P(═O)(NR 230 R 230 )(NR 230 R 230 ), and —P(═O)(OR 230 )(OR 230 ).

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219 and R 229 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 halogen, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 7-11 arylalkyl, C 3-10 cycloalkyl, C 4-17 cycloalkylalkyl, 3-10 membered heterocycloalkyl, 4-10 membered heterocycloalkylalkyl, 5-10 membered heteroaryl, 6-10 membered heteroarylalkyl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —NC, —NO 2 , —NR 230 R 230 , —NR 230 OR 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)OR 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 C(═O)NR 230 C(═O)R 230 , —NR 230 S(═O) 2 R 230 , —NR 230 S(═O) 2 NR 230 R 230 , —NR 230 P(═O)R 231 R 231 , —NR 230 P(═O)(NR 230 R 230 )(NR 230 R 230 ), —NR 230 P(═O)(OR 230 )(OR 230 ), —OR 230 , ═O, —OCN, —OC(═O)R 230 , —OC(═O)NR 230 R 230 , —OS(═O) 2 NR 230 R 230 , —OP(═O)R 231 R 231 , —OP(═O)(NR 230 R 230 )(NR 230 R 230 ), —SCN, ═S, —S(═O) n R 230 , —S(═O) 2 NR 230230 , —S(═O)NR 230 R 230 , —P(═O)R 231 R 231 , and —P(═O)(NR 230 R 230 )(NR 230 R 230 ).

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219 and R 229 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 halogen, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 7-11 arylalkyl, C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —NO 2 , —NR 230 R 230 , —NR 230 OR 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 S(═O) 2 R 230 , —NR 230 S(═O) 2 NR 230 R 230 , —OR 230 , ═O, —OCN, —OC(═O)R 230 , —S(═O) n R 230 , —S(═O) 2 NR 230 R 230 , and —S(═O)NR 230 R 230 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219 and R 229 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 halogen, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —NO 2 , —NR 230 R 230 , —NR 230 C(═O)R 230 , —NR 230 C(═O)NR 230 R 230 , —NR 230 S(═O) 2 R 230 , —NR 230 S(═O) 2 NR 230 R 230 , —OR 230 , ═O, —S(═O) n R 230 , and —S(═O) 2 NR 230 R 230 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219 and R 229 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 halogen, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —NR 230 R 230 , —NR 230 C(═O)R 230 , —NR 230 S(═O) 2 R 230 , —OR 230 , ═O, —S(═O) n R 230 , and —S(═O) 2 NR 230 R 230 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219 and R 229 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 halogen, phenyl, benzyl, C 3-6 cycloalkyl, 3-6 membered heterocycloalkyl, 5-6 membered heteroaryl, halogen, —CN, —C(═O)R 230 , —C(═O)OR 230 , —C(═O)NR 230 R 230 , —NR 230 R 230 , —OR 230 , ═O, —S(═O) n R 230 , and —S(═O) 2 NR 230 R 230 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219 and R 229 at each occurrence is independently chosen from C 1-6 alkyl optionally substituted by 1-3 halogen, halogen, and —NR 2 30R 230 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219 and R 229 at each occurrence is independently chosen from C 1-6 alkyl, halogen, and —NR 230 R 230 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219 and R 229 at each occurrence is independently chosen from C 1-6 alkyl and —NR 230 R 230 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219 and R 229 at each occurrence is —NR 230 R 230 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 , R 209 , R 219 and R 229 at each occurrence is C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 at each occurrence is independently chosen from C 1-6 alkyl and —NR 230 R 230 ; R 209 , R 219 and R 229 at each occurrence is C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 at each occurrence is independently chosen from C 1-6 alkyl and —NR 230 R 230 ; R 209 , R 219 and R 229 at each occurrence is —NR 230 R 230 .

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1052, wherein R 199 at each occurrence is —NR 230 R 230 ; R 209 , R 219 and R 229 at each occurrence is C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1067, wherein R 230 at each occurrence is independently chosen from H, C 1-6 alkyl and C 1-6 -haloalkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1067, wherein R 230 at each occurrence is independently chosen from H and C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1067, wherein R 230 at each occurrence is C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1067, wherein R 230 at each occurrence is H.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1071, wherein R 231 at each occurrence is independently chosen from C 1-6 alkyl and C 1-6 -haloalkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1071, wherein R 231 at each occurrence is C 1-6 alkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1071, wherein R 231 at each occurrence is C 1-6 -haloalkyl.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is independently chosen from 0, 1, and 2.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is independently chosen from 0 and 2.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is independently chosen from 1 and 2.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is independently chosen from 0 and 1.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is 0.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is 1.

The compound of any of Embodiments 1-156, 200-250, 300-371, 400-440, 500-533, 600-668, 700-714, 750-795, 800-817, 850-886, or 900-1074, wherein n at each occurrence is 2.

The above Embodiments include salts of acidic and basic compounds of formula (I). Preferably, the salts are pharmaceutically acceptable. Pharmaceutically acceptable acid addition salts of basic compounds of formula (I) include, but are not limited to, salts derived from inorganic acids such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydriodic, and phosphorus, as well as the salts derived from organic acids, such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, alkanedioic acids, aromatic acids, and aliphatic and aromatic sulfonic acids. Such salts thus include, but are not limited to, sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, toluenesulfonate, phenylacetate, citrate, lactate, maleate, tartrate, and methanesulfonate. See, for example, Berge et al., “Pharmaceutical Salts,” J. of Pharmaceutical Science, 1977; 66:1-19.

Acid addition salts may be prepared by contacting a compound of formula (I) with a sufficient amount of the desired acid to produce the salt in the conventional manner. The free base form of the compound of formula (I) may be regenerated by contacting the salt form with a base and isolating the free base in the conventional manner.

Pharmaceutically acceptable base salts of acidic compounds of formula (I) are formed with metals or amines, such as alkali and alkaline earth metal hydroxides, or of organic amines. Examples of metals used as cations include, but are not limited to, sodium, potassium, magnesium, and calcium. Examples of suitable amines include, but are not limited to, N,N′-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine (ethane-1,2-diamine), N-methylglucamine, and procaine. See, for example, Berge et al., “Pharmaceutical Salts,” J. of Pharmaceutical Science, 1977; 66:1-19.

Base salts may be prepared by contacting a compound of formula (I) with a sufficient amount of the desired base to produce the salt in the conventional manner. The acid form of the compound of formula (I) may be regenerated by contacting the salt form with an acid and isolating the acid in a conventional manner.

Some compounds of the present application may exist as stereoisomers, including enantiomers, diastereomers, and geometric isomers. Geometric isomers include compounds of the present application that have alkenyl groups, which may exist as entgegen or zusammen conformations, in which case all geometric forms thereof, both entgegen and zusammen, cis and trans, and mixtures thereof, are within the scope of the present application. Some compounds of the present application have cycloalkyl groups, which may be substituted at more than one carbon atom, in which case all geometric forms thereof, both cis and trans, and mixtures thereof, are within the scope of the present application. All of these forms, including (R), (S), epimers, diastereomers, cis, trans, syn, anti, (E), (Z), tautomers, and mixtures thereof, are included in the compounds of the present application.

The compounds of the present application may be in any physical form, including amorphous or crystalline solids in any polymorphic form, in any state of purity. Crystalline polymorphic forms include unsolvated forms as well as solvated forms, such as hydrated forms.

III. Pharmaceutical Compositions

The present application further provides pharmaceutical compositions comprising a compound of any of the above Embodiments (e.g., a compound of formula (I) or a pharmaceutically acceptable salt thereof), together with a pharmaceutically acceptable excipient. For preparing a pharmaceutical composition from a compound of the present application, pharmaceutically acceptable excipients can be either solid or liquid. An excipient can be one or more substances which may act as, e.g., a carrier, diluent, flavoring agent, binder, preservative, tablet disintegrating agent, or an encapsulating material. The pharmaceutical composition may contain two or more compounds of the present application (e.g., two different salt forms of a compound of formula (I), may be used together in the same pharmaceutical composition). Preferably, the pharmaceutical composition contains a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt form thereof. In one embodiment, the composition contains an amount of a compound of formula (I) or a pharmaceutically acceptable salt form thereof effective to treat an atypical protein kinase C (aPKC)-dependent disorder or condition. Preferably, a compound of the present application will cause a decrease in symptoms or disease indicia associated with an aPKC-dependent disorder as measured quantitatively or qualitatively. The composition may also contain, in addition to a compound of formula (I) or a pharmaceutically acceptable salt form thereof and a pharmaceutically acceptable excipient, another therapeutic compound, such as a compound useful in the treatment of cancer.

A compound of the present application can be formulated as a pharmaceutical composition in any delivery form, such as a syrup, an elixir, a suspension, a powder, a granule, a tablet, a capsule, a lozenge, a troche, an aqueous solution, a cream, an ointment, a lotion, a gel, an emulsion, etc. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. Preferably, the pharmaceutical composition is a tablet or capsule. In one embodiment, the pharmaceutical composition is a tablet. In another embodiment, the pharmaceutical composition is a capsule.

In powders, the excipient may be a finely divided solid in a mixture with a finely divided active component (i.e., compound of the present application). In tablets, the active component may be mixed with an excipient having the necessary binding properties in suitable proportions and compacted in the shape and size desired. Suitable excipients include magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, low melting wax, cocoa butter, and the like.

The pharmaceutical composition preferably contains from 1% to 95% (w/w) of the active compound (i.e., compound of the present application). More preferably, the pharmaceutical composition contains from 5% to 70% (w/w) of the active compound.

For preparing suppositories, a low melting wax, such as a mixture of fatty acid glycerides or cocoa butter, may be melted and the active component dispersed homogeneously therein, as by stirring. The molten homogeneous mixture may then be poured into convenient sized molds, allowed to cool, and thereby to solidify.

Liquid form preparations include solutions, suspensions, and emulsions. Formulations suitable for parenteral administration, such as, for example, by intravenous, intramuscular, intradermal, and subcutaneous routes, include aqueous and non-aqueous, isotonic sterile injection solutions, which can contain antioxidants, buffers, bacteriostats, and solutes that render the formulation isotonic with the blood of the intended recipient, and aqueous and nonaqueous sterile suspensions that can include suspending agents, solubilizers, thickening agents, stabilizers, and preservatives. In practice, compositions can be administered, for example, by intravenous infusion, orally, topically, intraperitoneally, intravesically or intrathecally. The formulations of compounds can be presented in unit-dose or multi-dose sealed containers, such as ampoules and vials. Injection solutions and suspensions can be prepared from sterile powders, granules, and tablets of the kind previously described.

A compound of the present application, alone or in combination with other suitable components, can be made into aerosol formulations (e.g., they can be “nebulized”) to be administered via inhalation. Aerosol formulations can be placed into pressurized acceptable propellants, such as dichlorodifluoromethane, propane, nitrogen, and the like.

Pharmaceutically acceptable excipients are determined in part by the particular composition being administered, as well as by the particular method used to administer the composition. Accordingly, there is a wide variety of suitable formulations of pharmaceutical compositions of the present application (see, e.g., Remington: The Science and Practice of Pharmacy, 20th ed., Gennaro et al. Eds., Lippincott Williams and Wilkins, 2000).

The quantity of active component in a pharmaceutical composition may be varied or adjusted from, e.g., 1 mg to 1,000 mg, 5 mg to 500 mg, 10 mg to 300 mg, or 25 mg to 250 mg, according to the particular application and the desired size of the dosage form.

The dose administered to a subject is preferably sufficient to induce a beneficial therapeutic response in the subject over time. The beneficial dose can vary from subject to subject depending upon, e.g., the subject's condition, body weight, surface area, and side effect susceptibility. Administration can be accomplished via single or divided doses.

IV. Method of Treatment

In another aspect, the present application provides a method of treating an aPKC-dependent disorder or condition in a subject comprising: administering to the subject a compound of formula (I) as defined in any of the above Embodiments or a pharmaceutically acceptable salt form thereof. In another aspect, the present application provides a compound of formula (I) as defined in any of the above Embodiments or a pharmaceutically acceptable salt form thereof for use in treating an aPKC-dependent disorder or condition in a subject. In another aspect, the present application provides a compound of formula (I) as defined in any of the above Embodiments or a pharmaceutically acceptable salt form thereof for use in the preparation of a medicament for treating an aPKC-dependent disorder or condition in a subject. Preferably, the compound is administered to the subject as a pharmaceutical composition comprising a pharmaceutically acceptable excipient. Preferably, the compound is administered to the subject in a pharmaceutically acceptable amount. In one embodiment, the aPKC-dependent condition or disorder is cancer. In another embodiment, the aPKC-dependent condition is selected from non-small cell lung cancer (NSCLC), squamous cell carcinoma (e.g., oesophageal sq