The present disclosure compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the TEAD transcription factor, and are useful in the treatment of diseases related to the activity of TEAD transcription factor including, e.g., cancer and other diseases.

Description

36 parts

›CLAIM OF PRIORITY

This application is a national stage application under 35 USC § 371 of International Application No. PCT/US2020/022757, filed on Mar. 13, 2020, which claims priority to U.S. Patent Application Ser. No. 62/819,347, filed on Mar. 15, 2019, the entire contents of which are hereby incorporated by reference.

›GOVERNMENT SUPPORT

This invention was made with government support under Grant Nos. 1R01CA181537 and R01DK107651 awarded by the National Institutes of Health. The government has certain rights in the invention.

›TECHNICAL FIELD

The present application is concerned with pharmaceutically useful compounds. The disclosure provides new compounds as well as their compositions and methods of use. The compounds inhibit the autopalmitoylation of TEAD-transcription factors and are therefore useful in the treatment of diseases related to the activity of TEAD-transcription factors including, e.g., cancers and other diseases.

›BACKGROUND

Hippo signaling plays key roles in organ size control and tumor suppression. The signal transduction involves a core kinase cascade, including MST1/2 and Lats1/2 kinases, leading to YAP/TAZ phosphorylation, cytoplasmic retention and inhibition 3 . Physiological or pathological inactivation of these kinases leads to YAP/TAZ dephosphorylation and nuclear accumulation. Subsequently, nuclear YAP/TAZ binds to the TEA domain transcription factors (TEAD1-4 in mammals, and Scalloped in Drosophila ) to mediate the target genes expression. The TEAD-YAP complex regulates normal development of skin, muscle, lung and liver, and are also oncogenic factor amplified in many human cancers. TEADs can also bind to Vgll4, which has been implicated as a tumor suppressor by competing with YAP/TAZ for TEADs binding. Therefore, TEADs are essential in regulating the transcriptional output of Hippo pathway. Although targeting TEAD-YAP could be a promising therapeutic approach for diseases with deregulated Hippo pathway, it remains challenging to directly inhibit transcription factors with small molecules. Therefore, understanding the regulation of TEADs might reveal new therapeutic opportunities for drug discovery.

Post-translational S-palmitoylation attaches a 16-carbon palmitate to the cysteine residue through a reversible thioester bond. A large number of palmitoylated proteins have been identified through proteomic studies. Dynamic S-palmitoylation plays critical roles regulating the trafficking, membrane localization and functions of many proteins, including Src-family kinases, GTPases, and synaptic adhesion molecules. Asp-His-His-Cys (DHHC) family proteins are evolutionarily conserved protein palmitoyl acyltransferases (PATs), mediating enzymatic S-palmitoylation. In addition, some proteins could bind to palmitoyl-Coenzyme A (CoA) directly, and undergo PAT-independent autopalmitoylation. However, autopalmitoylation is poorly characterized. Most of the reported examples of autopalmitoylation are observed under non-physiological, high concentration of palmitoyl-CoA (>100 μM). To date, only a few proteins, including yeast transporter protein Bet3, are autopalmitoylated under physiological concentrations of palmitoyl-CoA (1-10 μM). Therefore, it is important to reveal additional autopalmitoylated proteins and to understand their regulations and functions.

›SUMMARY

The present disclosure provides, inter alia, a compound of Formula (I):

or a pharmaceutically acceptable salt thereof; wherein the variables are as defined below.

The present disclosure also provides a composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

The present disclosure also provides methods of treating cancer and other diseases comprising administering to a patient a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

The details of one or more embodiments are set forth in the description below. Other features, objects and advantages will be apparent from the description and from the claims.

›BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 scheme showing the structures of examples of compounds within the scope of the invention.

FIG. 2 is a scheme showing the structures of some reference compounds.

FIG. 3 is a picture showing the result of streptavidin and histidine blots showing the results of assays of the inhibition of TEAD2 in vitro autopalmitoylation by the compounds CP-1, flufenamic acid, CP-41, CP-42, CP-51, CP-52, CP-53, CP-54, CP-55, CP-56, CP-57, and CP-58.

FIG. 4 is a picture showing the result of streptavidin and histidine blots showing the results of assays of the inhibition of TEAD2 in vitro autopalmitoylation by the compound CP-55 at various concentrations.

FIG. 5 is a collection of plots showing inhibition of cell proliferation in the 92.1 uveal melanoma cell line, cellosaurus OCM1 cell line, human hepatoma huh7 cell line, SNU398 human liver hepatocellular carcinoma cell line, and the MDA-MB-453 human mammary gland metastatic carcinoma cell line by the compound CP-55 at various concentrations.

FIG. 6 is collection of plots showing inhibition of gene expression for the CYR61, CTGF and ANKRD1 genes in the huh7 human hepatoma cell line by the compound CP-55 at various time points and concentrations.

FIG. 7 is a picture showing the result of streptavidin and histidine blots showing the results of assays of the inhibition of TEAD2 in vitro autopalmitoylation by the compound CP-58 at various concentrations.

FIG. 8 is a plot showing inhibition of cell proliferation in the 92.1 uveal melanoma cell line by the compounds CP-1, CP-52, CP-55 and CP-58 at various concentrations.

FIG. 9 is a plot showing inhibition of cell proliferation in the huh7 human hepatoma cell line by the compound CP-57 at various concentrations.

FIG. 10 is a plot showing inhibition of cell proliferation in the huh7 human hepatoma cell line by the compound CP-58 at various concentrations.

FIG. 11 is a pair of plots showing inhibition of gene expression for the genes CYR61 and CTGF and ANKRD1 genes in the huh7 human hepatoma cell line by the compound CP-58 after 24 h compared to control.

FIG. 12 is a picture showing the result of streptavidin and histidine blots showing the results of assays of the inhibition of TEAD2 in vitro autopalmitoylation by the compounds CP-1, CP-55, CP-58, CP-59, CP-60, CP-61 and CP-62.

FIG. 13 is a plot inhibition of cell proliferation in the huh7 human hepatoma cell line by the compounds CP-58, CP-59, CP-60, CP-61 and CP-62 at various concentrations.

›DETAILED DESCRIPTION · 1 of 16

For the terms “e.g.” and “such as,” and grammatical equivalents thereof, the phrase “and without limitation” is understood to follow unless explicitly stated otherwise.

The singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise.

The term “about” means “approximately” (e.g., plus or minus approximately 10% of the indicated value).

The expressions, “ambient temperature” and “room temperature” (abbreviated “r.t.”) refer generally to a temperature, e.g., a reaction temperature, that is about the temperature of the room in which the reaction is carried out, e.g., a temperature from about 20° C. to about 30° C., typically about 25° C.

Through proteomic and biochemical studies, it has been identified that the TEAD transcription factors are palmitoylated at evolutionarily conserved cysteine residues. It has been found that TEADs undergo PAT-independent autopalmitoylation, under physiological concentrations of palmitoyl-CoA. The crystal structures of the lipid-bound TEADs, and revealed a new ligand-binding site in TEADs. Furthermore, autopalmitoylation plays critical roles in regulating TEAD-YAP association and their physiological functions in vitro and in vivo. Therefore, palmitoylation of TEADs plays important roles in regulating Hippo pathway transcriptional complexes.

The discovery of a new ligand-binding site in TEADs has allowed the discovery of small molecule inhibitors of TEAD autopalmitoylation. While not being bound by any theory, it is understood that the ligands bind to the palmitate-binding pocket, and inhibit TEAD-YAP interaction, cancer cell proliferation and migration. Therefore, direct inhibition of TEAD autopalmitoylation activities is useful to inhibit these oncogenic transcription factors.

I. Compounds

The present disclosure provides, inter alia, a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

L 1 is absent, or a group of formula N(R N ) or C(O); D is a group of formula (D1), (D2), (D3), (D4), (D5), (D6) or (D7):

m is 1, 2 or 3;

A 1 is C(O)R 1 , S(O) 2 R 1 , NHC(O)R 1 , (C 1-3 alkylene)-C(O)R 1 , NH(C 1-3 alkylene)-C(O)R 1 , CN, NO 2 , 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (C 1-3 alkylene)-5-10 membered heteroaryl, or (C 1-3 alkylene)-4-10 membered heterocycloalkyl, wherein the (C 1-3 alkylene) group of the (C 1-3 alkylene)-C(O)R 1 group forming A 1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR a1 , NR c1 R d1 , NR a1 (CO)(C 1-6 alkyl), and NR a1 (CO)O(C 1-6 alkyl); and wherein the 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (C 1-3 alkylene)-5-10 membered heteroaryl, or (C 1-3 alkylene)-4-10 membered heterocycloalkyl forming A 1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR a1 , SR a1 , C(O)OR a1 , NR c1 R d1 , and C(O)NR c1 R d1 ;

L 2 is absent, or a group of formula N(R N ), O, or C(O);

L 3 is absent or a group of formula CH 2 , C≡C, N(R N ) or C(O);

each R N is independently H, C 1-6 alkyl, C(O)C 1-6 alkyl, or C(O)OC 1-6 alkyl;

R 1 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Cy 1A , OH, OC 1-6 alkyl, OCy 1A O(C 1-3 alkylenyl)Cy 1A , NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl) 2 , NHCy 1A , NH(C 1-3 alkylenyl)Cy 1A , N(C 1-6 alkyl)Cy 1A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1A , wherein each of the C 1-6 alkyl forming R 1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR a1 , SR a1 , and NR c1 R d1 ;

Cy 1A is C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy 1A is unsubstituted or substituted by 0, 1 or 2 Cy 1B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

each Cy 1B is C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy 1B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 SR a1 , and NR c1 R d1 ; and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

A 2 is CR 2 or N;

A 3 is CR 3 or N;

A 4 is CR 4 or N;

A 5 is CR 5 or N;

A 6 is CR 6 or N;

A 7 is CR 7 or N;

A 8 is CR 8 or N;

A 9 is CR 9 or N;

A 10 is CR 10 or N;

A D41 is CH, C(C 1-6 alkyl) or N;

A D42 is CH 2 , NH or NC 1-6 alkyl;

R 2 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 3 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 4 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 5 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

›DETAILED DESCRIPTION · 2 of 16

R 6 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , S(O) 2 R b1 , S(O) 2 NR c1 R d1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , Cy 7A , OCy 7A , O(C 1-3 alkylenyl)Cy 7A , C(O)OCy 7A , C(O)O(C 1-3 alkylenyl)Cy 7A , NHCy 7A NH(C 1-3 alkylenyl)Cy 7A , N(C 1-6 alkyl)Cy 7A , N(C(O)C 1-6 alkyl)Cy 7A , N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A , C(O)NHCy 7A , C(O)NH(C 1-3 alkylenyl)Cy 7A , C(O)N(C 1-6 alkyl)Cy 7A , C(O)N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 7 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , S(O) 2 NR c1 R d1 , C(O)NR c1 R d1 , Cy 7A , OCy 7A , O(C 1-3 alkylenyl)Cy 7A , C(O)OCy 7A , C(O)O(C 1-3 alkylenyl)Cy 7A , NHCy 7A , NH(C 1-3 alkylenyl)Cy 7A , N(C 1-6 alkyl)Cy 7A , N(C(O)C 1-6 alkyl)Cy 7A , N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A , C(O)NHCy 7A , C(O)NH(C 1-3 alkylenyl)Cy 7A , C(O)N(C 1-6 alkyl)Cy 7A , C(O)N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

Cy 7A is C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy 7A is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy 7B , OCy 7B , NHCy 7B , and C(O)NHCy 7B , and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

each Cy 7B is C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy 7B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 ;

R 8 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , S(O) 2 NR c1 R d1 , SR a1 , NR c1 R d1 , NR c1 S(O) 2 R b1 , C(O)OR a1 , C(O)NR c1 R d1 , Cy 8A , OH, OCy 8A , O(C 1-3 alkylenyl)Cy 8A , C(O)OCy 8A , C(O)O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , N(Cy 8A ) 2 , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , N(C(O)C 1-6 alkyl)Cy 8A , SO 2 NHCy 8A , N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , C(O)NHCy 8A , C 1-3 alkylene-C(O)NHCy 8A , C(O)NH(C 1-3 alkylenyl)Cy 8A , C(O)N(C 1-6 alkyl)Cy 8A , C(O)N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

Cy 8A is C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy 8A is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy 8B , OCy 8B , NHCy 8B , and C(O)NHCy 8B , and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

each Cy 8B is C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy 8B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 9 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , NR c1 C(O)R b1 , C(O)OR a1 , C(O)NR c1 R d1 , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 10 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

Cy D71 is C 6-10 aryl, C 3-15 cycloalkyl, 5-14 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy D71 is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy D72 , CH 2 Cy D72 , OCy D72 , NHCy D72 , O—C 1-6 alkylene-Cy D72 , N(C 1-6 alkyl)Cy D72 , N(C(O)C 1-6 alkyl)Cy D72 , and C(O)NHCy D72 , and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , S(hal) 5 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , and C 1-6 alkyl or C 2-6 alkenyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , C(O)OR a1 , and NR c1 R d1 ;

›DETAILED DESCRIPTION · 3 of 16

each Cy D72 is C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy D72 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-15 cycloalkyl, 4-10 membered heterocycloalkyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from C 6-10 aryl, C 3-15 cycloalkyl, 4-10 membered heterocycloalkyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , C(O)OR a1 , and NR c1 R d1 , wherein said C 6-10 aryl, C 3-15 cycloalkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , and C(O)NR c1 R d1 ; and

R a1 , R b1 , R c1 and R d1 are each independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, HO—C 1-6 alkylene, amino-C 1-6 alkylene, C 1-6 alkylamino-C 1-6 alkylene, di(C 1-6 alkyl)amino-C 1-6 alkylene, C 1-6 alkoxy-C 1-6 alkylene, C 6-10 aryl, C 2-6 alkenyl and C 2-6 alkynyl; or

R c1 and R d1 together with the nitrogen atom to which they are both attached together form a 4-10 membered unsubstituted heterocycloalkyl ring or a heterocyclic ring that is substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , and C(O)NR c1 R d1 ;

provided:

L 1 is a group of formula N(R N ) when L 2 is C(O);

L 1 is a group of formula C(O) when L 2 is N(R N );

L 2 is absent, or a group of formula N(R N ) when L 1 is C(O);

L 2 is absent, or a group of formula C(O) when L 1 is N(R N );

A D41 is CH, C(C 1-6 alkyl) when A D42 is NH or NC 1-6 alkyl;

A D42 is CH 2 when A D41 is NH or NC 1-6 alkyl;

no more than two of A 2 , A 3 , A 4 and A 5 is N;

no more than two of A 6 , A 7 , A 8 , A 9 and A 10 is N; and

either R 1 is present and is Cy 1A , OCy 1A , O(C 1-3 alkylenyl)Cy 1A , NHCy 1A NH(C 1-3 alkylenyl)Cy 1A , N(C 1-6 alkyl)Cy 1A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1A ; or

R 7 is Cy 7A , OCy 7A , O(C 1-3 alkylenyl)Cy 7A , C(O)OCy 7A , C(O)O(C 1-3 alkylenyl)Cy 7A , NHCy 7A , NH(C 1-3 alkylenyl)Cy 7A , N(C 1-6 alkyl)Cy 7A , N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A ; C(O)NHCy 7A , C(O)NH(C 1-3 alkylenyl)Cy 7A , C(O)N(C 1-6 alkyl)Cy 7A , or C(O)N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A , or

R 8 is Cy 8A , OCy 8A , O(C 1-3 alkylenyl)Cy 8A , C(O)OCy 8A , C(O)O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , C(O)NHCy 8A , C(O)NH(C 1-3 alkylenyl)Cy 8A , C(O)N(C 1-6 alkyl)Cy 8A , or C(O)N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A .

The present disclosure provides, inter alia, a compound of Formula (I):

In some embodiments:

L 1 is a group of formula N(R N ) when L 2 is C(O); L 1 is a group of formula C(O) when L 2 is N(R N ); L 2 is absent, or a group of formula N(R N ) when L 1 is C(O); L 2 is absent, or a group of formula C(O) when L 1 is N(R N ); A D41 is CH, C(C 1-6 alkyl) when A D42 is NH or NC 1-6 alkyl; A D42 is CH 2 when A D41 is NH or NC 1-6 alkyl; no more than two of A 2 , A 3 , A 4 and A 5 is N; no more than two of A 6 , A 7 , A 8 , A 9 and A 10 is N; and either R 1 is present and is Cy 1A , OCy 1A , O(C 1-3 alkylenyl)Cy 1A , NHCy 1A NH(C 1-3 alkylenyl)Cy 1A , N(C 1-6 alkyl)Cy 1A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1A ; or R 7 is Cy 7A , OCy 7A , O(C 1-3 alkylenyl)Cy 7A C(O)OCy 7A , C(O)O(C 1-3 alkylenyl)Cy 7A , NHCy 7A , NH(C 1-3 alkylenyl)Cy 7A , N(C 1-6 alkyl)Cy 7A , N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A ; C(O)NHCy 7A , C(O)NH(C 1-3 alkylenyl)Cy 7A , C(O)N(C 1-6 alkyl)Cy 7A , or C(O)N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A , or R 8 is Cy 8A , OCy 8A , O(C 1-3 alkylenyl)Cy 8A , C(O)OCy 8A , C(O)O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , C(O)NHCy 8A , C(O)NH(C 1-3 alkylenyl)Cy 8A , C(O)N(C 1-6 alkyl)Cy 8A , or C(O)N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A .

In some embodiments, L 1 is absent.

In some embodiments, L 1 is N(R N ), e.g., NH or NMe.

In some embodiments, L 1 is C(O).

In some embodiments, D is a group of formula (D1).

In some embodiments, D is a group of formula (D2).

In some embodiments, D is a group of formula (D3).

In some embodiments, D is a group of formula (D4).

In some embodiments, D is a group of formula (D5).

In some embodiments, D is a group of formula (D6).

In some embodiments, D is a group of formula (D7).

In some embodiments, A 1 is C(O)R 1 , e.g., C(O)OH.

In some embodiments, A 1 is S(O) 2 R 1 .

In some embodiments, A 1 is NHC(O)R 1 .

In some embodiments, A 1 is NH(C 1-3 alkylene)-C(O)R 1 .

In some embodiments, wherein A 1 is (C 1-3 alkylene)-C(O)R 1 , wherein the (C 1-3 alkylene) group of the (C 1-3 alkylene)-C(O)R 1 group forming A 1 is unsubstituted or substituted by 0, 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR a1 , NR c1 R d1 , NR a1 (CO)(C 1-6 alkyl), and NR a1 (CO)O(C 1-6 alkyl).

In some embodiments, A 1 is (C 1-3 alkylene)-C(O)R 1 , wherein the (C 1-3 alkylene) group of the (C 1-3 alkylene)-C(O)R 1 group forming A 1 is substituted by NR c1 R d1 , NR a1 (CO)(C 1-6 alkyl), or NR a1 (CO)O(C 1-6 alkyl), e.g., CH 2 CH(NH 2 )C(O)OH.

In some embodiments, A 1 is CN.

In some embodiments, A 1 is NO 2 .

In some embodiments, A 1 is 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (C 1-3 alkylene)-5-10 membered heteroaryl, or (C 1-3 alkylene)-4-10 membered heterocycloalkyl that is unsubstituted or substituted by 0, 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR a1 , SR a1 , C(O)OR a1 , NR c1 R d1 and C(O)NR c1 R d1 .

In some embodiments, A 1 is 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CH 2 (5-10 membered heteroaryl), or CH 2 (4-10 membered heterocycloalkyl) that is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR a1 , SR a1 , C(O)OR a1 , NR c1 R d1 and C(O)NR c1 R d1 .

›DETAILED DESCRIPTION · 4 of 16

In some embodiments, A 2 is CR 2 .

In some embodiments, R 2 is H.

In some embodiments, A 2 is N.

In some embodiments, A 3 is CR 3 .

In some embodiments, R 3 is H, C 1-6 alkyl or C 1-6 haloalkyl.

In some embodiments, R 3 is H, methyl or trifluoroethyl.

In some embodiments, R 3 is H.

In some embodiments, A 3 is N.

In some embodiments, A 4 is CR 4 .

In some embodiments, R 4 is H.

In some embodiments, A 4 is N.

In some embodiments, A 5 is CR 5 .

In some embodiments, R 5 is H.

In some embodiments, A 5 is N.

In some embodiments, A 2 is CR 2 , A 3 is CR 3 , A 4 is CR 4 , and A 5 is CR 5 .

In some embodiments, A 2 is CR 2 , A 3 is CR 3 , A 4 is CR 4 , and A 5 is N.

In some embodiments, D is a group of formula (D4).

In some embodiments, A D41 is CH

In some embodiments, A D41 is C(C 1-6 alkyl).

In some embodiments, A D41 is N.

In some embodiments, A D42 is NH.

In some embodiments, A D42 is NC 1-6 alkyl, e.g., NMe.

In some embodiments, A D42 is CH 2 .

In some embodiments, D is a group of formula (D4) and m is 1.

In some embodiments, D is a group of formula (D4) and m is 2.

In some embodiments, D is a group of formula (D4) and m is 3.

In some embodiments, D is a group of formula (D5).

In some embodiments, D is a group of formula (D5) and m is 1.

In some embodiments, D is a group of formula (D5) and m is 2.

In some embodiments, D is a group of formula (D5) and m is 3.

In some embodiments, D is a group of formula (D6).

In some embodiments, D is a group of formula (D6) and m is 1.

In some embodiments, D is a group of formula (D6) and m is 2.

In some embodiments, D is a group of formula (D6) and m is 3.

In some embodiments, D is a group of formula (D7).

In some embodiments, L 2 is absent.

In some embodiments, L 2 is a group of formula O.

In some embodiments, L 2 is a group of formula N(R N ).

In some embodiments, L 2 is a group of formula C(O).

In some embodiments, L 3 is absent.

In some embodiments, L 3 is a group of formula CH 2 .

In some embodiments, L 3 is a group of formula N(R N ).

In some embodiments, L 3 is a group of formula C(O).

In some embodiments, L 3 is a group of formula C≡C.

In some embodiments, Cy D71 is C 6-10 aryl (e.g., phenyl).

In some embodiments, Cy D71 is C 3-15 cycloalkyl (e.g., cyclopropyl).

In some embodiments, Cy D71 is 5-10 membered heteroaryl (e.g., triazol, pyridine, dihydropyrido[2,1-b]pyrimidin-2-one, 3,4-dihydroquinolin-2-one, benzo[d]isothiazole-1,1-dioxide, 2H-indazole, pyrazole, dioxolane, pyrrole, indole, imidazole, benzimidazole).

In some embodiments, Cy D71 is 4-10 membered heterocycloalkyl (e.g., piperidine, 1,3-dioxolane, indoline, pyrrolidine).

In some embodiments, the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy D71 is unsubstituted.

In some embodiments, the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy D71 is substituted.

In some embodiments, the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy D71 is substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , and C 1-6 alkyl or C 2-6 alkenyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , C(O)OR a1 , and NR c1 R d1 .

In some embodiments, the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy D71 is substituted by 0, 1 or 2 substituents selected from Cy D72 , CH 2 Cy D72 , OCy D72 , NHCy D72 , O—C 1-6 alkylene-Cy D72 , N(C 1-6 alkyl)Cy D72 , N(C(O)C 1-6 alkyl)Cy D72 , and C(O)NHCy D72 .

In some embodiments, Cy D72 is C 6-10 aryl (e.g., phenyl).

In some embodiments, Cy D72 is C 3-15 cycloalkyl (e.g., cyclopropyl).

In some embodiments, Cy D72 is 5-10 membered heteroaryl (e.g., triazol, pyridine, dihydropyrido[2,1-b]pyrimidin-2-one, 3,4-dihydroquinolin-2-one, benzo[d]isothiazole-1,1-dioxide, 2H-indazole, pyrazole, dioxolane, pyrrole, indole, imidazole, benzimidazole).

In some embodiments, Cy D72 is 4-10 membered heterocycloalkyl (e.g., piperidine, 1,3-dioxolane, indoline, pyrrolidine).

In some embodiments, the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy D72 is unsubstituted.

In some embodiments, the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy D72 is substituted.

In some embodiments, the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy D72 is substituted by 0, 1 or 2 substituents selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-15 cycloalkyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , C(O)OR a1 , and NR c1 R d1 .

In some embodiments, R 1 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Cy 1A , OH, OC 1-6 alkyl, OCy 1A , O(C 1-3 alkylenyl)Cy 1A , NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl) 2 , NHCy 1A , NH(C 1-3 alkylenyl)Cy 1A , N(C 1-6 alkyl)Cy 1A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1A .

In some embodiments, R 1 is Cy 1A , OCy 1A , O(C 1-3 alkylenyl)Cy 1A , NHCy 1A NH(C 1-3 alkylenyl)Cy 1A , N(C 1-6 alkyl)Cy 1A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1A .

In some embodiments, R 1 is NHCy 1A .

In some embodiments, R 1 is C 1-6 alkyl (e.g., methyl), C 2-6 alkenyl, C 2-6 alkynyl, Cy 1A OH, or OC 1-6 alkyl (e.g., OMe).

In some embodiments, R 1 is OH.

In some embodiments, R 1 is a group of one of the following formulae:

wherein:

R 11 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 1B , OH, OCy 1B , O(C 1-3 alkylenyl)Cy 1B , NHCy 1B , NH(C 1-3 alkylenyl)Cy 1B , N(C 1-6 alkyl)Cy 1B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

›DETAILED DESCRIPTION · 5 of 16

R 12 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 1B , OH, OCy 1B , O(C 1-3 alkylenyl)Cy 1B , NHCy 1B , NH(C 1-3 alkylenyl)Cy 1B , N(C 1-6 alkyl)Cy 1B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 13 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 1B , OH, OCy 1B , O(C 1-3 alkylenyl)Cy 1B , NHCy 1B , NH(C 1-3 alkylenyl)Cy 1B , N(C 1-6 alkyl)Cy 1B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 14 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 1B , OH, OCy 1B , O(C 1-3 alkylenyl)Cy 1B , NHCy 1B , NH(C 1-3 alkylenyl)Cy 1B , N(C 1-6 alkyl)Cy 1B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 15 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 1B , OH, OCy 1B , O(C 1-3 alkylenyl)Cy 1B , NHCy 1B , NH(C 1-3 alkylenyl)Cy 1B , N(C 1-6 alkyl)Cy 1B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 16 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 1B , OH, OCy 1B , O(C 1-3 alkylenyl)Cy 1B , NHCy 1B , NH(C 1-3 alkylenyl)Cy 1B , N(C 1-6 alkyl)Cy 1B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 17 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 1B , OH, OCy 1B , O(C 1-3 alkylenyl)Cy 1B , NHCy 1B , NH(C 1-3 alkylenyl)Cy 1B , N(C 1-6 alkyl)Cy 1B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ; and

R 18 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 1B , OH, OCy 1B , O(C 1-3 alkylenyl)Cy 1B , NHCy 1B , NH(C 1-3 alkylenyl)Cy 1B , N(C 1-6 alkyl)Cy 1B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, R 1 is a group of one of the following formulae:

In some embodiments, Cy 1A is C 6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 0, 1 or 2 Cy 1B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, Cy 1A is C 6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 1 Cy 1B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, Cy 1A is C 6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 1 Cy 1B .

In some embodiments, each Cy 1B is C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, each Cy 1B is unsubstituted C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl).

In some embodiments, Cy 1A is a group of one of the following formulae:

wherein

›DETAILED DESCRIPTION · 6 of 16

In some embodiments, Cy 1A is a group of one of the following formulae:

In some embodiments, Cy 1A is C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 0, 1 or 2 Cy 1B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 . In some embodiments, Cy 1A is C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 In some embodiments, Cy 1A is unsubstituted C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). In some embodiments, Cy 1A is adamantyl, e.g., adamant-1-yl that is unsubstituted or substituted. In some embodiments, Cy 1A is unsubstituted adamantyl, e.g., adamant-1-yl.

In some embodiments:

R 7 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ; and R 8 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, R 7 is H and R 8 is H.

In some embodiments, L 2 is absent.

In some embodiments, L 2 is N(R N ).

In some embodiments, L 2 is C(O).

In some embodiments, R N is H.

In some embodiments, A 6 is CR 6 .

In some embodiments, R 6 is H.

In some embodiments, A 6 is N.

In some embodiments, A 7 is CR 7 .

In some embodiments, R 7 is H.

In some embodiments, R 7 is Cy 7A , OCy 7A , O(C 1-3 alkylenyl)Cy 7A , C(O)OCy 7A , C(O)O(C 1-3 alkylenyl)Cy 7A , NHCy 7A , NH(C 1-3 alkylenyl)Cy 7A , N(C 1-6 alkyl)Cy 7A , N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A ; C(O)NHCy 7A , C(O)NH(C 1-3 alkylenyl)Cy 7A , C(O)N(C 1-6 alkyl)Cy 7A , or C(O)N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A .

In some embodiments, R 7 is Cy 7A , OCy 7A , O(C 1-3 alkylenyl)Cy 7A , NHCy 7A , NH(C 1-3 alkylenyl)Cy 7A , N(C 1-6 alkyl)Cy 7A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A .

In some embodiments, R 7 is N(C(O)C 1-6 alkyl)Cy 7A .

In some embodiments, R 7 is NHCy 7A .

In some embodiments, R 7 is a group of one of the following formulae:

wherein:

R 71 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 7B , OH, OCy 7B , O(C 1-3 alkylenyl)Cy 7B , NHCy 7B , NH(C 1-3 alkylenyl)Cy 7B , N(C 1-6 alkyl)Cy 7B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 72 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 7B , OH, OCy 7B , O(C 1-3 alkylenyl)Cy 7B , NHCy 7B , NH(C 1-3 alkylenyl)Cy 7B , N(C 1-6 alkyl)Cy 7B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 73 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 7B , OH, OCy 7B , O(C 1-3 alkylenyl)Cy 7B , NHCy 7B , NH(C 1-3 alkylenyl)Cy 7B , N(C 1-6 alkyl)Cy 7B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

›DETAILED DESCRIPTION · 7 of 16

R 74 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 7B , OH, OCy 7B , O(C 1-3 alkylenyl)Cy 7B , NHCy 7B , NH(C 1-3 alkylenyl)Cy 7B , N(C 1-6 alkyl)Cy 7B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 75 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 7B , OH, OCy 7B , O(C 1-3 alkylenyl)Cy 7B , NHCy 7B , NH(C 1-3 alkylenyl)Cy 7B , N(C 1-6 alkyl)Cy 7B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 76 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 7B , OH, OCy 7B , O(C 1-3 alkylenyl)Cy 7B , NHCy 7B , NH(C 1-3 alkylenyl)Cy 7B , N(C 1-6 alkyl)Cy 7B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 77 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 7B , OH, OCy 7B , O(C 1-3 alkylenyl)Cy 7B , NHCy 7B , NH(C 1-3 alkylenyl)Cy 7B , N(C 1-6 alkyl)Cy 7B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ; and

R 78 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 7B , OH, OCy 7B , O(C 1-3 alkylenyl)Cy 7B , NHCy 7B , NH(C 1-3 alkylenyl)Cy 7B , N(C 1-6 alkyl)Cy 7B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, R 7 is a group of one of the following formulae:

In some embodiments, Cy 7A is C 6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 0, 1 or 2 Cy 7B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, Cy 7A is C 6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 1 Cy 7B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, Cy 7A is C 6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 1 Cy 7B .

In some embodiments, each Cy 7B is C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, each Cy 7B is unsubstituted C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl).

In some embodiments, Cy 7A is a group of one of the following formulae:

wherein:

R 71 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 72 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 73 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 74 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 75 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

›DETAILED DESCRIPTION · 8 of 16

R 76 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 77 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ; and

R 78 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, Cy 7A is a group of one of the following formulae:

In some embodiments, Cy 7A is C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 0, 1 or 2 Cy 7B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 . In some embodiments, Cy 7A is C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 01, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 In some embodiments, Cy 7A is unsubstituted C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). In some embodiments, Cy 7A is adamantyl, e.g., adamant-1-yl that is unsubstituted or substituted. In some embodiments, Cy 7A is unsubstituted adamantyl, e.g., adamant-1-yl.

In some embodiments:

R 1 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ; and R 8 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, A 1 is CR 1 , A 2 is CR 2 , A 3 is CR 3 , A 4 is CR 4 , A 5 is CR 5 , A 6 is CR 6 , A 8 is CR 8 , A 9 is CR 9 , and A 10 is CR 10 .

In some embodiments, A 1 is CR 1 , A 3 is CR 3 , A 4 is CR 4 , A 5 is N, A 6 is CR 6 , A 8 is CR 8 , A 9 is CR 9 , and A 10 is CR 10 .

In some embodiments, A 7 is N.

In some embodiments, A 8 is CR 8 .

In some embodiments, R 8 is H.

In some embodiments, R 8 is Cy 8A , OCy 8A , O(C 1-3 alkylenyl)Cy 8A , C(O)OCy 8A , C(O)O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , C(O)NHCy 8A , C(O)NH(C 1-3 alkylenyl)Cy 8A , C(O)N(C 1-6 alkyl)Cy 8A , or C(O)N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A .

In some embodiments, R 8 is Cy 8A , OCy 8A , O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A .

In some embodiments, R 8 is N(Cy 8A ) 2 .

In some embodiments, R 8 is N(C(O)C 1-6 alkyl)Cy 8A .

In some embodiments, R 8 is SO 2 NHCy 8A .

In some embodiments, R 8 is C 1-3 alkylene-C(O)NHCy 8A .

In some embodiments, R 8 is NHCy 8A .

In some embodiments, R 8 is a group of one of the following formulae:

wherein:

R 81 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8A , OH, OCy 8A , O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 82 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8A , OH, OCy 8A , O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 83 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8A , OH, OCy 8A , O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 84 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8A , OH, OCy 8A , O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

›DETAILED DESCRIPTION · 9 of 16

R 85 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8A , OH, OCy 8A , O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 86 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8A , OH, OCy 8A , O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 87 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8A , OH, OCy 8A , O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ; and

R 88 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8A , OH, OCy 8A , O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, R 8 is a group of one of the following formulae:

In some embodiments, Cy 8A is C 6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 0, 1 or 2 Cy 8B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, Cy 8A is C 6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 1 Cy 8B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, Cy 8A is C 6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 1 Cy 8B .

In some embodiments, each Cy 8B is C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, each Cy 8B is unsubstituted C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl).

In some embodiments, Cy 8A is a group of one of the following formulae:

wherein:

›DETAILED DESCRIPTION · 10 of 16

In some embodiments, Cy 8A is a group of one of the following formulae:

In some embodiments, Cy 8A is C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 0, 1 or 2 Cy 8B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 . In some embodiments, Cy 8A is C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 01, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 In some embodiments, Cy 8A is unsubstituted C 3-15 cycloalkyl (e.g., C 3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). In some embodiments, Cy 8A is adamantyl, e.g., adamant-1-yl that is unsubstituted or substituted. In some embodiments, Cy 8A is unsubstituted adamantyl, e.g., adamant-1-yl.

In some embodiments:

R 1 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ; and R 7 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, A 1 is CR 1 , A 2 is CR 2 , A 3 is CR 3 , A 4 is CR 4 , A 5 is CR 5 , A 6 is CR 6 , A 7 is CR 7 , A 8 is CR 8 , A 9 is CR 9 , and A 10 is CR 10 .

In some embodiments, A 1 is CR 1 , A 3 is CR 3 , A 4 is CR 4 , A 5 is N, A 6 is CR 6 , A 7 is CR 7 , A 8 is CR 8 , A 9 is CR 9 , and A 10 is CR 10 .

In some embodiments, A 8 is N.

In some embodiments, A 9 is CR 9 .

In some embodiments, R 9 is H, C 1-6 alkyl or C 1-6 haloalkyl.

In some embodiments, R 9 is H, methyl or trifluoroethyl.

In some embodiments, R 9 is H.

In some embodiments, A 9 is N.

In some embodiments, A 10 is CR 10 .

In some embodiments, R 10 is H.

In some embodiments, A 10 is N.

In some embodiments, the compound is a compound of one of the following formulae (I-1) to (I-60):

wherein:

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R N , A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , A 7 , A 8 , A 9 , A 10 , Cy 1A , Cy 1B , Cy 7A , Cy 7B , Cy 8A , Cy 8B , L 1 and L 2 , are as defined above for the compounds of formula (I), or any of the embodiments thereof;

L 7 is absent, O, NH or N(C 1-6 alkyl);

L 8 is absent, O, NH or N(C 1-6 alkyl);

›DETAILED DESCRIPTION · 11 of 16

R 81 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 82 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 83 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

›DETAILED DESCRIPTION · 12 of 16

R 84 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 85 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 86 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 87 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ; and

R 88 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1-3 alkylenyl)Cy 8B , NHCy 8B , NH(C 1-3 alkylenyl)Cy 8B , N(C 1-6 alkyl)Cy 8B , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8B , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 .

In some embodiments, R 1 is OH.

In some embodiments, R 1 is OC 1-6 alkyl (e.g., OMe).

In some embodiments, R 1 is C 2-6 alkenyl (e.g., vinyl).

In some embodiments, L 7 is NH.

In some embodiments, L 8 is NH.

In some embodiments, R a1 , R b1 , R c1 and R d1 are each independently selected from H, C 1-6 alkyl, HO—C 1-6 alkylene, C 1-6 alkoxy-C 1-6 alkylene, C 6-10 aryl, C 2-6 alkenyl and C 2-6 alkynyl.

In some embodiments, the compound is a compound of one of the following formulae, or a pharmaceutically acceptable salt thereof:

The compounds, or any of the embodiments thereof, can be provided in the form of a composition such as a pharmaceutical composition that includes the compound, or a salt such as a pharmaceutically acceptable salt thereof, and at least one additional agent such as a pharmaceutically acceptable carrier.

It is further appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment (while the embodiments are intended to be combined as if written in multiply dependent form). Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination. Thus, it is contemplated that features described as embodiments of the compounds of Formula (I) can be combined in any suitable combination.

At various places in the present specification, certain features of the compounds are disclosed in groups or in ranges. It is specifically intended that such a disclosure include each and every individual subcombination of the members of such groups and ranges. For example, the term “C 1-6 alkyl” is specifically intended to individually disclose (without limitation) methyl, ethyl, C 3 alkyl, C 4 alkyl, C 5 alkyl and C 6 alkyl.

The term “n-membered,” where n is an integer, typically describes the number of ring-forming atoms in a moiety where the number of ring-forming atoms is n. For example, piperidinyl is an example of a 6-membered heterocycloalkyl ring, pyrazolyl is an example of a 5-membered heteroaryl ring, pyridyl is an example of a 6-membered heteroaryl ring and 1,2,3,4-tetrahydro-naphthalene is an example of a 10-membered cycloalkyl group. When the term is used to refer to a carbocyclic ring (e.g., aryl or cycloalkyl), all of the ring atoms are carbon atoms. When the term is used to refer to a heterocyclic ring (e.g., heteroaryl or heterocycloalkyl), one or more of the ring atoms (e.g., 1, 2, 3, or 4) are heteroatoms (e.g., nitrogen, oxygen or sulfur) and the remainder (e.g., n−1, n−2, n−3, or n−4) are carbon atoms.

At various places in the present specification, variables defining divalent linking groups are described. It is specifically intended that each linking substituent include both the forward and backward forms of the linking substituent. For example, —NR(CR′R″) n — includes both —NR(CR′R″) n — and —(CR′R″) n NR— and is intended to disclose each of the forms individually. Where the structure requires a linking group, the Markush variables listed for that group are understood to be linking groups. For example, if the structure requires a linking group and the Markush group definition for that variable lists “alkyl” or “aryl” then it is understood that the “alkyl” or “aryl” represents a linking alkylene group or arylene group, respectively.

The term “substituted” means that an atom or group of atoms formally replaces hydrogen as a “substituent” attached to another group. The term “substituted”, unless otherwise indicated, refers to any level of substitution, e.g., mono-, di-, tri-, tetra- or penta-substitution, where such substitution is permitted. The substituents are independently selected, and substitution may be at any chemically accessible position. It is to be understood that substitution at a given atom is limited by valency. The term “optionally substituted” means unsubstituted or substituted. The term “substituted” means that a hydrogen atom is removed and replaced by a substituent. A single divalent substituent, e.g., oxo, can replace two hydrogen atoms.

›DETAILED DESCRIPTION · 13 of 16

The term “Cn-m” indicates a range which includes the endpoints, wherein n and m are integers and indicate the number of carbons. Examples include C 1-4 , C 1-6 and the like. Whenever the term is used intended to describe each member included in the group, C n through C m as if each had been explicitly set forth. For example, the term C 1-6 is intended to describe each of the members C 1 , C 2 , C 3 , C 4 , C 5 and C 6 .

The term “alkyl” employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chain or branched. The term “Cn-m alkyl”, refers to an alkyl group having n to m carbon atoms. An alkyl group formally corresponds to an alkane with one C—H bond replaced by the point of attachment of the alkyl group to the remainder of the compound. In some embodiments, the alkyl group contains from 1 to 6 carbon atoms, from 1 to 4 carbon atoms, from 1 to 3 carbon atoms, or 1 to 2 carbon atoms. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl; higher homologs such as 2-methyl-1-butyl, n-pentyl, 3-pentyl, n-hexyl, 1,2,2-trimethylpropyl and the like.

The term “alkenyl” employed alone or in combination with other terms, refers to a straight-chain or branched hydrocarbon group corresponding to an alkyl group having one or more double carbon-carbon bonds. An alkenyl group formally corresponds to an alkene with one C—H bond replaced by the point of attachment of the alkenyl group to the remainder of the compound. The term “Cn-m alkenyl” refers to an alkenyl group having n to m carbons. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. Example alkenyl groups include, but are not limited to, ethenyl, n-propenyl, isopropenyl, n-butenyl, sec-butenyl and the like.

The term “alkynyl” employed alone or in combination with other terms, refers to a straight-chain or branched hydrocarbon group corresponding to an alkyl group having one or more triple carbon-carbon bonds. An alkynyl group formally corresponds to an alkyne with one C—H bond replaced by the point of attachment of the alkyl group to the remainder of the compound. The term “Cn-m alkynyl” refers to an alkynyl group having n to m carbons. Example alkynyl groups include, but are not limited to, ethynyl, propyn-1-yl, propyn-2-yl and the like. In some embodiments, the alkynyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

The term “alkylene”, employed alone or in combination with other terms, refers to a divalent alkyl linking group. An alkylene group formally corresponds to an alkane with two C—H bond replaced by points of attachment of the alkylene group to the remainder of the compound.

The term “Cn-m alkylene” refers to an alkylene group having n to m carbon atoms. Examples of alkylene groups include, but are not limited to, ethan-1,2-diyl, propan-1,3-diyl, propan-1,2-diyl, butan-1,4-diyl, butan-1,3-diyl, butan-1,2-diyl, 2-methyl-propan-1,3-diyl and the like.

The term “alkoxy”, employed alone or in combination with other terms, refers to a group of formula —O-alkyl, wherein the alkyl group is as defined above. The term “Cn-m alkoxy” refers to an alkoxy group, the alkyl group of which has n to m carbons. Example alkoxy groups include methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), t-butoxy and the like. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

The terms “halo” or “halogen”, used alone or in combination with other terms, refers to fluoro, chloro, bromo and iodo.

The term “haloalkyl” refers to an alkyl group in which one or more of the hydrogen atoms has been replaced by a halogen atom. The term “C n-m haloalkyl” refers to a C n-m alkyl group having n to m carbon atoms and from at least one up to {2(n to m)+1} halogen atoms, which may either be the same or different. In some embodiments, the halogen atoms are fluoro atoms. In some embodiments, the haloalkyl group has 1 to 6 or 1 to 4 carbon atoms. Example haloalkyl groups include CF 3 , C 2 F 5 , CHF 2 , CCl 3 , CHCl 2 , C 2 Cl 5 and the like. In some embodiments, the haloalkyl group is a fluoroalkyl group.

The term “haloalkoxy”, employed alone or in combination with other terms, refers to a group of formula —O-haloalkyl, wherein the haloalkyl group is as defined above. The term “C n-m haloalkoxy” refers to a haloalkoxy group, the haloalkyl group of which has n to m carbons. Example haloalkoxy groups include trifluoromethoxy and the like. In some embodiments, the haloalkoxy group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

The term “amino” refers to a group of formula —NH 2 .

The term “carbamyl” refers to a group of formula —C(═O)NH 2 .

The term “carbonyl”, employed alone or in combination with other terms, refers to a —C(═O)— group, which also may be written as C(O).

The term “carbonyl”, employed alone or in combination with other terms, refers to a —C(═O)— group.

The term “carboxy” refers to a group of formula —C(═O)OH.

The term “oxo” refers to oxygen as a divalent substituent, forming a carbonyl group, or attached to a heteroatom forming a sulfoxide or sulfone group, or an N-oxide group.

The term “aromatic” refers to a carbocycle or heterocycle having one or more polyunsaturated rings having aromatic character (i.e., having (4n+2) delocalized 7r (pi) electrons where n is an integer).

The term “aryl,” employed alone or in combination with other terms, refers to an aromatic hydrocarbon group, which may be monocyclic or polycyclic (e.g., having 2, 3 or 4 fused rings). The term “Cn-m aryl” refers to an aryl group having from n to m ring carbon atoms. Aryl groups include, e.g., phenyl, naphthyl, indenyl and the like. In some embodiments, aryl groups have from 6 to 10 carbon atoms. In some embodiments, the aryl group is phenyl.

The term “arylalkylenyl,” employed alone or in combination with other terms, refers to an aryl group, as defined herein, attached to an alkylene group, as defined herein. The term “C n-m aryl C o-p alkylenyl” refers to an arylalkylenyl group with an aryl group having from n to m ring carbon atoms attached to an alkylene group having from o to p carbon atoms. Arylalkylenyl groups include, e.g., benzyl, phenethyl and the like.

›DETAILED DESCRIPTION · 14 of 16

The term “heteroaryl” or “heteroaromatic” employed alone or in combination with other terms, refers to a monocyclic or polycyclic aromatic heterocycle having at least one heteroatom ring member selected from sulfur, oxygen and nitrogen. In some embodiments, the heteroaryl is a 5- or 6-membered monocyclic heteroaryl ring. In some embodiments, the heteroaryl is 5- to 10-membered C 1-9 heteroaryl, which is monocyclic or bicyclic and which has 1, 2, 3 or 4 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. In some embodiments, any ring-forming N in a heteroaryl moiety can be an N-oxide. In some embodiments, the heteroaryl has 5-10 ring atoms including carbon atoms and 1, 2, 3 or 4 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. In some embodiments, the heteroaryl has 5-6 ring atoms and 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. In some embodiments, the heteroaryl has 5-6 ring atoms and 1 or 2 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. In some embodiments, the heteroaryl is a five-membered or six-membered heteroaryl ring. Example heteroaryl groups include, but are not limited to, pyridine, pyrimidine, pyrazine, pyridazine, pyrrole, pyrazole, azolyl, oxazole, thiazole, imidazole, furan, thiophene, quinoline, isoquinoline, indole, benzothiophene, benzofuran, benzisoxazole, imidazo[1,2-b]thiazole, imidazo[1,2-b]pyridazine, purine, furopyridine (e.g., furo[3,2-b]pyridine), thienopyridine (e.g. thieno[3,2-b]pyridine) or the like.

A five-membered heteroaryl ring is a heteroaryl group having five ring atoms wherein one or more (e.g., 1, 2, 3 or 4) ring atoms are independently selected from N, O and S. Exemplary five-membered ring heteroaryls include thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, isoxazolyl, 1,2,3-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-triazolyl, 1,2,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-triazolyl, 1,3,4-thiadiazolyl and 1,3,4-oxadiazolyl.

A six-membered heteroaryl ring is a heteroaryl group having six ring atoms wherein one or more (e.g., 1, 2 or 3) ring atoms are independently selected from N, O and S. Exemplary six-membered ring heteroaryls are pyridyl, pyrazinyl, pyrimidinyl, triazinyl and pyridazinyl.

The term “heteroarylalkylenyl,” employed alone or in combination with other terms, refers to heteroaryl group, as defined herein, attached to an alkylene group, as defined herein. The term “n-m membered heteroaryl C o-p alkylenyl” refers to a heteroaryl group having from n to m ring atoms attached to an alkylene group having from o to p carbon atoms. Heteroarylalkylenyl groups include, e.g., pyridylmethyl, pyridylethyl and the like.

The term “cycloalkyl”, employed alone or in combination with other terms, refers to a non-aromatic, saturated, monocyclic, bicyclic or polycyclic hydrocarbon ring system, including cyclized alkyl and alkenyl groups. The term “Cn-m cycloalkyl” refers to a cycloalkyl that has n to m ring member carbon atoms. Cycloalkyl groups can include mono- or polycyclic (e.g., having 2, 3 or 4 fused rings) groups and spirocycles. Cycloalkyl groups can have, e.g., 3, 4, 5, 6, 7, 8, 9 or 10 ring-forming carbons (C 3-10 ) or 3, 4, 5, 6 or 7 ring-forming carbons (C 3-7 ). In some embodiments, the cycloalkyl group has 3 to 6 ring members, 3 to 5 ring members, or 3 to 4 ring members. In some embodiments, the cycloalkyl group is monocyclic. In some embodiments, the cycloalkyl group is monocyclic or bicyclic. In some embodiments, the cycloalkyl group is a C 3-6 monocyclic cycloalkyl group. Ring-forming carbon atoms of a cycloalkyl group can be optionally substituted by oxo or sulfido. Cycloalkyl groups also include cycloalkylidenes. Example cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, norbornyl, norpinyl, bicyclo[2.1.1]hexanyl, bicyclo[1.1.1]pentanyl, adamantyl and the like. In some embodiments, cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. Also included in the definition of cycloalkyl are moieties that have one or more aromatic rings fused (i.e., having a bond in common with) to the cycloalkyl ring, e.g., benzo or thienyl derivatives of cyclopentane, cyclohexane and the like, for example indanyl or tetrahydronaphthyl. A cycloalkyl group containing a fused aromatic ring can be attached through any ring-forming atom including a ring-forming atom of the fused aromatic ring.

The term “arylalkylenyl,” employed alone or in combination with other terms, refers to a cycloalkyl group, as defined herein, attached to an alkylene group, as defined herein. The term “Cn-m cycloalkyl C o-p alkylenyl” refers to an cycloalkylalkylenyl group with a cycloalkyl group having from n to m ring carbon atoms attached to an alkylene group having from o to p carbon atoms. Cycloalkylalkylenyl groups include, e.g., cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclohexylmethyl, and the like.

The term “heterocycloalkyl”, employed alone or in combination with other terms, refers to non-aromatic ring or ring system, which may optionally contain one or more alkenylene groups as part of the ring structure, which has at least one heteroatom ring member independently selected from nitrogen, sulfur oxygen and phosphorus, and which has 4-10 ring members, 4-7 ring members or 4-6 ring members. Included in heterocycloalkyl are monocyclic 4-, 5-, 6- and 7-membered heterocycloalkyl groups. Heterocycloalkyl groups can include mono- or bicyclic (e.g., having two fused or bridged rings) ring systems. In some embodiments, the heterocycloalkyl group is a monocyclic group having 1, 2 or 3 heteroatoms independently selected from nitrogen, sulfur and oxygen. Examples of heterocycloalkyl groups include azetidine, pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, pyran, azepane, tetrahydropyran, tetrahydrofuran, dihydropyran, dihydrofuran and the like. Ring-forming carbon atoms and heteroatoms of a heterocycloalkyl group can be optionally substituted by oxo or sulfido (e.g., C(═O), S(═O), C(S) or S(═O) 2 , etc.) or a nitrogen atom can be quaternized. The heterocycloalkyl group can be attached through a ring-forming carbon atom or a ring-forming heteroatom. In some embodiments, the heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, the heterocycloalkyl group contains 0 to 2 double bonds. Also included in the definition of heterocycloalkyl are moieties that have one or more aromatic rings fused (i.e., having a bond in common with) to the heterocycloalkyl ring, e.g., benzo or thienyl derivatives of piperidine, morpholine, azepine, etc. A heterocycloalkyl group containing a fused aromatic ring can be attached through any ring-forming atom including a ring-forming atom of the fused aromatic ring. Examples of heterocycloalkyl groups include 1, 2, 3, 4-tetrahydroquinoline, dihydrobenzofuran, azetidine, azepane, diazepan (e.g., 1,4-diazepan), pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, pyran, tetrahydrofuran and di- and tetra-hydropyran.

›DETAILED DESCRIPTION · 15 of 16

The term “heterocycloalkylalkylenyl,” employed alone or in combination with other terms, refers to heterocycloalkyl group, as defined herein, attached to an alkylene group, as defined herein. The term “n-m membered heterocycloalkyl C o-p alkylenyl” refers to a heterocycloalkyl group having from n to m ring atoms attached to an alkylene group having from o to p carbon atoms. Heteroarylalkylenyl groups include, e.g., tetrahydrofurylmethyl.

At certain places, the definitions or embodiments refer to specific rings (e.g., an azetidine ring, a pyridine ring, etc.). Unless otherwise indicated, these rings can be attached to any ring member provided that the valency of the atom is not exceeded. For example, an azetidine ring may be attached at any position of the ring, whereas an azetidin-3-yl ring is attached at the 3-position.

The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers and diastereoisomers, are intended unless otherwise indicated. Compounds of the present invention that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C═N double bonds and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms.

Resolution of racemic mixtures of compounds can be carried out by any of numerous methods known in the art. One method includes fractional recrystallization using a chiral resolving acid which is an optically active, salt-forming organic acid. Suitable resolving agents for fractional recrystallization methods are, e.g., optically active acids, such as the D and L forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid or the various optically active camphorsulfonic acids such as β-camphorsulfonic acid. Other resolving agents suitable for fractional crystallization methods include stereoisomerically pure forms of α-methylbenzylamine (e.g., S and R forms, or diastereoisomerically pure forms), 2-phenylglycinol, norephedrine, ephedrine, N-methylephedrine, cyclohexylethylamine, 1,2-diaminocyclohexane and the like.

Resolution of racemic mixtures can also be carried out by elution on a column packed with an optically active resolving agent (e.g., dinitrobenzoylphenylglycine). Suitable elution solvent composition can be determined by one skilled in the art.

In some embodiments, the compounds of the invention have the (R)-configuration. In other embodiments, the compounds have the (S)-configuration. In compounds with more than one chiral centers, each of the chiral centers in the compound may be independently (R) or (S), unless otherwise indicated.

Compounds of the invention also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone-enol pairs, amide-imidic acid pairs, lactam-lactim pairs, enamine-imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, e.g., 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H-isoindole and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution.

Compounds of the invention can also include all isotopes of atoms occurring in the intermediates or final compounds. Isotopes include those atoms having the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium.

The term, “compound,” is meant to include all stereoisomers, geometric isomers, tautomers and isotopes of the structures depicted.

All compounds, and pharmaceutically acceptable salts thereof, can be found together with other substances such as water and solvents (e.g., hydrates and solvates) or can be isolated. When in the solid state, the compounds described herein and salts thereof may occur in various forms and may, e.g., take the form of solvates, including hydrates. The compounds may be in any solid state form, such as a polymorph or solvate, so unless clearly indicated otherwise, reference in the specification to compounds and salts thereof should be understood as encompassing any solid state form of the compound.

In some embodiments, the compounds of the invention, or salts thereof, are substantially isolated. By “substantially isolated” is meant that the compound is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, e.g., a composition enriched in the compounds of the invention. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compounds of the invention, or salt thereof.

The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.

The expressions, “ambient temperature” and “room temperature” are understood in the art, and refer generally to a temperature, e.g., a reaction temperature, that is about the temperature of the room in which the reaction is carried out, e.g., a temperature from about 20° C. to about 30° C.

›DETAILED DESCRIPTION · 16 of 16

The present invention also includes salts, particularly pharmaceutically acceptable salts, of the compounds described herein. The term “pharmaceutically acceptable salts” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts of the present invention include the non-toxic salts of the parent compound formed, e.g., from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, non-aqueous media like ether, ethyl acetate, alcohols (e.g., methanol, ethanol, iso-propanol or butanol) or acetonitrile (MeCN) are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17 th Ed., (Mack Publishing Company, Easton, 1985), p. 1418, Berge et al., J. Pharm. Sci., 1977, 66(1), 1-19 and in Stahl et al., Handbook of Pharmaceutical Salts: Properties, Selection, and Use , (Wiley, 2002). In some embodiments, the compounds described herein include the N-oxide forms.

The following abbreviations may be used herein: AcOH (acetic acid); Ac 2 O (acetic anhydride); Al 2 O 3 (aluminium oxide); aq. (aqueous); atm. (atmosphere(s)); Boc (t-butoxycarbonyl); Boc 2 O (di-tert-butyldicarbonate); BOP ((benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate); br (broad); c-Pr (cyclopropyl); Cbz (carboxybenzyl); calc. (calculated); CeCl 3 .7H 2 O (cerium (III) chloride heptahydrate); Cs 2 CO 3 (cesium carbonate); CuI (copper (I) iodide); d (doublet); dd (doublet of doublets); DCM (dichloromethane); DIPEA (N,N-diisopropylethylamine); DMAP (4-dimethylaminopyridine); DMF (N,N-dimethylformamide); DMSO (dimethylsulfoxide); Et (ethyl); EtOAc (ethyl acetate); EtOH (ethanol); Fmoc (9-fluorenylmethylmethoxycarbonyl); g (gram(s)); h (hour(s)); H 2 (hydrogen gas); H 2 O 2 (hydrogen peroxide); HATU (N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate); HBr (hydrogen bromide); HCl (hydrochloric acid or hydrogen chloride); HPLC (high performance liquid chromatography); Hz (hertz); i-Pr (isopropyl); i-PrOH (isopropyl alcohol); J (coupling constant); KOAc (potassium acetate); K 3 PO 4 (potassium phosphate); K 3 PO 4 .H 2 O (tripotassium phosphate hydrate); LCMS (liquid chromatography-mass spectrometry); LiAlH 4 (lithium tetrahydroaluminate); LiBH 4 (lithium tetrahydroborate); LiOH (lithium hydroxide); LiOH.H 2 O (lithium hydroxide monohydrate); m (multiplet); M (molar); mCPBA (m-chloroperbenzoic acid); Me (methyl); MeCN (acetonitrile); MeOH (methanol); MgSO 4 (magnesium sulfate); MS (mass spectrometry); mg (milligram(s)); min. (minutes(s)); mL (milliliter(s)); mmol (millimole(s)); N (normal); N 2 (nitrogen gas); NaHCO 3 (sodium bicarbonate); NaIO 4 (sodium metaperiodate); NaN 3 (sodium azide); NaOH (sodium hydroxide); Na 2 SO 4 (sodium sulfate); n-Bu (n-butyl); n-BuLi (n-butyllithium); NH 4 Cl (ammonium chloride); NH 4 OH (ammonium hydroxide); nM (nanomolar); NMR (nuclear magnetic resonance spectroscopy); Pd (palladium); Pd(dppf)Cl 2 ([1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride); Pd(OAc) 2 (palladium acetate); Pd(tBu 3 P) 2 (bis(tri-tert-butylphosphine)palladium); pM (picomolar); Pd(PPh 3 ) 4 (tetrakis(triphenylphosphine)palladium(O)); PPh 3 (triphenylphosphine); psi (pounds per square inch); PTFE (polytetrafluoroethylene); RP-HPLC (reverse phase high performance liquid chromatography); r.t. (room temperature); s (singlet); t (triplet or tertiary); tert (tertiary); tt (triplet of triplets); TBAF (tetra-n-butylammoniumfluoride); t-Bu (tert-butyl); TEA (triethylamine); TFA (trifluoroacetic acid); THF (tetrahydrofuran); μg (microgram(s)); μL (microliter(s)); m (micromolar); wt % (weight percent).

›II. SYNTHESIS

Compounds of the invention, including salts thereof, can be prepared using known organic synthesis techniques and can be synthesized according to any of numerous possible synthetic routes, such as shown in the Scheme below.

The reactions for preparing compounds of the invention can be carried out in suitable solvents which can be readily selected by one of skill in the art of organic synthesis. Suitable solvents can be substantially non-reactive with the starting materials (reactants), the intermediates or products at the temperatures at which the reactions are carried out, e.g., temperatures which can range from the solvent's freezing temperature to the solvent's boiling temperature. A given reaction can be carried out in one solvent or a mixture of more than one solvent. Depending on the particular reaction step, suitable solvents for a particular reaction step can be selected by the skilled artisan.

Preparation of compounds of the invention can involve the protection and deprotection of various chemical groups. The need for protection and deprotection, and the selection of appropriate protecting groups, can be readily determined by one skilled in the art. The chemistry of protecting groups is described, e.g., in Kocienski, Protecting Groups , (Thieme, 2007); Robertson, Protecting Group Chemistry , (Oxford University Press, 2000); Smith et al., March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6 th Ed. (Wiley, 2007); Peturssion et al., “Protecting Groups in Carbohydrate Chemistry,” J. Chem. Educ., 1997, 74(11), 1297; and Wuts et al., Protective Groups in Organic Synthesis, 4th Ed., (Wiley, 2006).

Reactions can be monitored according to any suitable method known in the art. For example, product formation can be monitored by spectroscopic means, such as nuclear magnetic resonance spectroscopy (e.g., 1 H or 13 C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), mass spectrometry or by chromatographic methods such as high performance liquid chromatography (HPLC) or thin layer chromatography (TLC).

The Schemes below provide general guidance in connection with preparing the compounds of the invention. One skilled in the art would understand that the preparations shown in the Schemes can be modified or optimized using general knowledge of organic chemistry to prepare various compounds of the invention.

Compounds of Formula (I) can be prepared as shown in Scheme 1 by coupling an aniline of Formula (II) with a compound of formula III, wherein L is a suitable leaving group, which can include halogen, such as bromine or iodine, or a sulfonate group (alkyl or aryl sulfonate, such as methanesulfonate, trifluoromethanesulfonate, benzenesulfonate, p-toluenesulfonate, or naphthalenesulfonate). The reaction can be carried out in the presence of a base such as potassium carbonate and a copper salt such as copper (I) iodide or copper (I) oxide. The reaction can also be carried out in the presence of a suitable organometallic catalyst, e.g., using Buchwald-Hartwig cross-coupling conditions. Suitable solvents for the reaction include tetrahydrofuran, 1,4-dioxane, tolune, or 1,2-dichlorobenzene. The preferred solvent is 1,2-dichlorobenzene. The reaction can typically be performed at a temperature of 0-200° C., e.g., a temperature of 100-150° C.

The present disclosure provides, inter alia, a methods of making certain compounds of Formula (I) according to Formula (Ia) by the route shown in Scheme 1:

Compounds of Formula (II) and (III) are either commercially available, known in the literature, or may be prepared by methods known to one skilled in the art.

Certain compounds of formula (I) may be useful as intermediates in the synthesis of other compounds of formula (I). For example, compounds of formula (I) wherein R 1 is OC 1-6 alkyl, OCy 1A , O(C 1-3 alkylenyl)Cy 1A , NHCy 1A NH(C 1-3 alkylenyl)Cy 1A , N(C 1-6 alkyl)Cy 1A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1A can be used to synthesize compounds of formula (I) wherein R 1 is OH via hydrolysis of the ester or amide group.

It will be appreciated by one skilled in the art that the processes described are not the exclusive means by which compounds of the invention may be synthesized and that a broad repertoire of synthetic organic reactions is available to be potentially employed in synthesizing compounds of the invention. The person skilled in the art knows how to select and implement appropriate synthetic routes. Suitable synthetic methods of starting materials, intermediates and products may be identified by reference to the literature, including reference sources such as: Advances in Heterocyclic Chemistry , Vols. 1-107 (Elsevier, 1963-2012); Journal of Heterocyclic Chemistry Vols. 1-49 (Journal of Heterocyclic Chemistry, 1964-2012); Carreira, et al. (Ed.) Science of Synthesis , Vols. 1-48 (2001-2010) and Knowledge Updates KU2010/1-4; 2011/1-4; 2012/1-2 (Thieme, 2001-2012); Katritzky, et al. (Ed.) Comprehensive Organic Functional Group Transformations , (Pergamon Press, 1996); Katritzky et al. (Ed.); Comprehensive Organic Functional Group Transformations II (Elsevier, 2 nd Edition, 2004); Katritzky et al. (Ed.), Comprehensive Heterocyclic Chemistry (Pergamon Press, 1984); Katritzky et al., Comprehensive Heterocyclic Chemistry II , (Pergamon Press, 1996); Smith et al., March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6 th Ed. (Wiley, 2007); Trost et al. (Ed.), Comprehensive Organic Synthesis (Pergamon Press, 1991).

›III. USES OF THE COMPOUNDS · 1 of 5

Compounds of the invention can inhibit the autopalmitoylation of TEAD-transcription factors and, thus, are useful in treating diseases and disorders associated with activity of TEAD-transcription factors. For the uses described herein, any of the compounds of the invention, including any of the embodiments thereof, may be used.

Thus, the present disclosure provides methods of treating a TEAD-transcription factor-associated disease or disorder in an individual (e.g., patient) by administering to the individual in need of such treatment a therapeutically effective amount or dose of a compound of Formula (I), or any of the embodiments thereof, or a pharmaceutical composition thereof. The present disclosure also provides a compound of Formula (I), or any of the embodiments thereof, or a pharmaceutical composition thereof, for use in treating a TEAD-transcription factor associated disease or disorder. Also provided is the use of a compound of Formula (I), or any of the embodiments thereof, or a pharmaceutical composition thereof, in the manufacture of a medicament for treating a TEAD-transcription factor-associated disease or disorder. The disease or disorder can be one that is associated with TEAD1, TEAD2, TEAD3, or TEAD4.

A TEAD-transcription factor-associated disease can include any disease, disorder or condition that is directly or indirectly linked to expression or activity of TEAD-transcription factors, including over-expression and/or abnormal activity levels. Abnormal activity levels can be determined by comparing activity level in normal, healthy tissue or cells with activity level in diseased cells. A TEAD-transcription factor-associated disease can also include any disease, disorder or condition that can be prevented, ameliorated, inhibited or cured by modulating TEAD-transcription factor activity. In some embodiments, the disease is characterized by the abnormal activity or expression (e.g., overexpression) of TEAD-transcription factor. A TEAD-transcription factor-associated disease can also refer to any disease, disorder or condition wherein modulating the expression or activity TEAD-transcription factor is beneficial.

TEAD-transcription factor associated diseases that can be treated using the compounds of the invention include cancer. The cancers include solid tumors, e.g., prostate cancer, colon cancer, esophageal cancer, endometrial cancer, ovarian cancer, uterine cancer, renal cancer, hepatic cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, cancers of the head or neck, thyroid cancer, glioblastoma, sarcoma, bladder cancer, etc. Other TEAD-transcription factor associated diseases include hepatocellular carcinoma, medulloblastoma, cutaneous squamous cell carcinoma, lung cancer, pancreatic cancer, esophagus cancer, liver cancer, colon cancer, melanoma, or uveal melanoma. TEAD-transcription factor associated diseases also include hematological cancers, e.g., lymphoma, leukemia such as acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, non-Hodgkin lymphoma (including relapsed non-Hodgkin lymphoma, refractory non-Hodgkin lymphoma and recurrent follicular non-Hodgkin lymphoma), Hodgkin lymphoma and multiple myeloma.

The cancer can be a cancer in which abnormally proliferating cells of the cancer express one or more TEADs, for example, a cancer that expresses one or more of TEAD1, TEAD2, TEAD3, and/or TEAD4. The method can include testing cancer cells of the individual for expression of one or more TEADs, e.g., one or more of TEAD1, TEAD2, TEAD3, and/or TEAD4, and treating the cancer according to the methods described herein based on the determination that the cancer expresses TEAD1, TEAD2, TEAD3, and/or TEAD4.

The terms “individual” or “patient,” used interchangeably, refer to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and most preferably humans.

The phrase “therapeutically effective amount” refers to the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue, system, animal, individual or human that is being sought by a researcher, veterinarian, medical doctor or other clinician.

The term “treating” or “treatment” refers to one or more of (1) inhibiting the disease; e.g., inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., arresting further development of the pathology and/or symptomatology); and (2) ameliorating the disease; e.g., ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and/or symptomatology) such as decreasing the severity of disease. In one embodiment, treating or treatment includes preventing or reducing the risk of developing the disease; e.g., preventing or reducing the risk of developing a disease, condition or disorder in an individual who may be predisposed to the disease, condition or disorder but does not yet experience or display the pathology or symptomatology of the disease.

Combination Therapies

Cancer cell growth and survival can be impacted by multiple signaling pathways. Thus, it is useful to combine different chemotherapeutic agents treat such conditions. Use of combination therapy may reduce the likelihood of drug-resistance arising in a cell population, and/or reduce the toxicity of treatment.

The compounds can be administered in combination with one or more anti-cancer drugs, such as a chemotherapeutics. Example chemotherapeutics include any of: abarelix, aldesleukin, alemtuzumab, alitretinoin, allopurinol, altretamine, anastrozole, arsenic trioxide, asparaginase, azacitidine, bevacizumab, bexarotene, bleomycin, bortezombi, bortezomib, busulfan intravenous, busulfan oral, calusterone, capecitabine, carboplatin, carmustine, cetuximab, chlorambucil, cisplatin, cladribine, clofarabine, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, dalteparin sodium, dasatinib, daunorubicin, decitabine, denileukin, denileukin diftitox, dexrazoxane, docetaxel, doxorubicin, dromostanolone propionate, eculizumab, epirubicin, erlotinib, estramustine, etoposide phosphate, etoposide, exemestane, fentanyl citrate, filgrastim, floxuridine, fludarabine, fluorouracil, fulvestrant, gefitinib, gemcitabine, gemtuzumab ozogamicin, goserelin acetate, histrelin acetate, ibritumomab tiuxetan, idarubicin, ifosfamide, imatinib mesylate, interferon alfa 2a, irinotecan, lapatinib ditosylate, lenalidomide, letrozole, leucovorin, leuprolide acetate, levamisole, lomustine, meclorethamine, megestrol acetate, melphalan, mercaptopurine, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, nandrolone phenpropionate, nelarabine, nofetumomab, oxaliplatin, paclitaxel, pamidronate, panitumumab, pegaspargase, pegfilgrastim, pemetrexed disodium, pentostatin, pipobroman, plicamycin, procarbazine, quinacrine, rasburicase, rituximab, ruxolitinib, sorafenib, streptozocin, sunitinib, sunitinib maleate, tamoxifen, temozolomide, teniposide, testolactone, thalidomide, thioguanine, thiotepa, topotecan, toremifene, tositumomab, trastuzumab, tretinoin, uracil mustard, valrubicin, vinblastine, vincristine, vinorelbine, vorinostat and zoledronate.

›III. USES OF THE COMPOUNDS · 2 of 5

When more than one pharmaceutical agent is administered to a patient, they can be administered simultaneously, sequentially, or in combination (e.g., for more than two agents).

VI. Formulation, Dosage Forms and Administration

When employed as pharmaceuticals, the compounds of the invention can be administered in the form of pharmaceutical compositions. Thus the present disclosure provides a composition comprising a compound Formula (I), or a pharmaceutically acceptable salt thereof, or any of the embodiments thereof, and at least one pharmaceutically acceptable carrier. These compositions can be prepared in a manner well known in the pharmaceutical art, and can be administered by a variety of routes, depending upon whether local or systemic treatment is indicated and upon the area to be treated. Administration may be topical (including transdermal, epidermal, ophthalmic and to mucous membranes including intranasal, vaginal and rectal delivery), pulmonary (e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal or intranasal), oral or parenteral. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal intramuscular or injection or infusion; or intracranial, e.g., intrathecal or intraventricular, administration. Parenteral administration can be in the form of a single bolus dose, or may be, e.g., by a continuous perfusion pump. Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable.

This invention also includes pharmaceutical compositions which contain, as the active ingredient, the compound of the invention or a pharmaceutically acceptable salt thereof, in combination with one or more pharmaceutically acceptable carriers (excipients). In some embodiments, the composition is suitable for topical administration. In making the compositions of the invention, the active ingredient is typically mixed with an excipient, diluted by an excipient or enclosed within such a carrier in the form of, e.g., a capsule, sachet, paper, or other container. When the excipient serves as a diluent, it can be a solid, semi-solid, or liquid material, which acts as a vehicle, carrier or medium for the active ingredient. Thus, the compositions can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), ointments containing, e.g., up to 10% by weight of the active compound, soft and hard gelatin capsules, suppositories, sterile injectable solutions and sterile packaged powders.

In preparing a formulation, the active compound can be milled to provide the appropriate particle size prior to combining with the other ingredients. If the active compound is substantially insoluble, it can be milled to a particle size of less than 200 mesh. If the active compound is substantially water soluble, the particle size can be adjusted by milling to provide a substantially uniform distribution in the formulation, e.g., about 40 mesh.

The compounds of the invention may be milled using known milling procedures such as wet milling to obtain a particle size appropriate for tablet formation and for other formulation types. Finely divided (nanoparticulate) preparations of the compounds of the invention can be prepared by processes known in the art see, e.g., WO 2002/000196.

Some examples of suitable excipients include lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup and methyl cellulose. The formulations can additionally include: lubricating agents such as talc, magnesium stearate and mineral oil; wetting agents; emulsifying and suspending agents; preserving agents such as methyl- and propylhydroxy-benzoates; sweetening agents; and flavoring agents. The compositions of the invention can be formulated so as to provide quick, sustained or delayed release of the active ingredient after administration to the patient by employing procedures known in the art.

In some embodiments, the pharmaceutical composition comprises silicified microcrystalline cellulose (SMCC) and at least one compound described herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the silicified microcrystalline cellulose comprises about 98% microcrystalline cellulose and about 2% silicon dioxide w/w.

In some embodiments, the composition is a sustained release composition comprising at least one compound described herein, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier. In some embodiments, the composition comprises at least one compound described herein, or a pharmaceutically acceptable salt thereof, and at least one component selected from microcrystalline cellulose, lactose monohydrate, hydroxypropyl methylcellulose and polyethylene oxide. In some embodiments, the composition comprises at least one compound described herein, or a pharmaceutically acceptable salt thereof, and microcrystalline cellulose, lactose monohydrate and hydroxypropyl methylcellulose. In some embodiments, the composition comprises at least one compound described herein, or a pharmaceutically acceptable salt thereof, and microcrystalline cellulose, lactose monohydrate and polyethylene oxide. In some embodiments, the composition further comprises magnesium stearate or silicon dioxide. In some embodiments, the microcrystalline cellulose is Avicel PH102™. In some embodiments, the lactose monohydrate is Fast-flo 316™. In some embodiments, the hydroxypropyl methylcellulose is hydroxypropyl methylcellulose 2208 K4M (e.g., Methocel K4 M Premier™) and/or hydroxypropyl methylcellulose 2208 K100LV (e.g., Methocel KOOLV™). In some embodiments, the polyethylene oxide is polyethylene oxide WSR 1105 (e.g., Polyox WSR 1105™).

›III. USES OF THE COMPOUNDS · 3 of 5

In some embodiments, a wet granulation process is used to produce the composition. In some embodiments, a dry granulation process is used to produce the composition.

The compositions can be formulated in a unit dosage form, each dosage containing from about 5 to about 1,000 mg (1 g), more usually about 100 mg to about 500 mg, of the active ingredient. In some embodiments, each dosage contains about 10 mg of the active ingredient. In some embodiments, each dosage contains about 50 mg of the active ingredient. In some embodiments, each dosage contains about 25 mg of the active ingredient. The term “unit dosage forms” refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient.

The components used to formulate the pharmaceutical compositions are of high purity and are substantially free of potentially harmful contaminants (e.g., at least National Food grade, generally at least analytical grade, and more typically at least pharmaceutical grade). Particularly for human consumption, the composition is preferably manufactured or formulated under Good Manufacturing Practice standards as defined in the applicable regulations of the U.S. Food and Drug Administration. For example, suitable formulations may be sterile and/or substantially isotonic and/or in full compliance with all Good Manufacturing Practice regulations of the U.S. Food and Drug Administration.

The active compound may be effective over a wide dosage range and is generally administered in a therapeutically effective amount. It will be understood, however, that the amount of the compound actually administered will usually be determined by a physician, according to the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms and the like.

The therapeutic dosage of a compound of the present invention can vary according to, e.g., the particular use for which the treatment is made, the manner of administration of the compound, the health and condition of the patient, and the judgment of the prescribing physician. The proportion or concentration of a compound of the invention in a pharmaceutical composition can vary depending upon a number of factors including dosage, chemical characteristics (e.g., hydrophobicity), and the route of administration. For example, the compounds of the invention can be provided in an aqueous physiological buffer solution containing about 0.1 to about 10% w/v of the compound for parenteral administration. Some typical dose ranges are from about 1 μg/kg to about 1 g/kg of body weight per day. In some embodiments, the dose range is from about 0.01 mg/kg to about 100 mg/kg of body weight per day. The dosage is likely to depend on such variables as the type and extent of progression of the disease or disorder, the overall health status of the particular patient, the relative biological efficacy of the compound selected, formulation of the excipient, and its route of administration. Effective doses can be extrapolated from dose-response curves derived from in vitro or animal model test systems.

For preparing solid compositions such as tablets, the principal active ingredient is mixed with a pharmaceutical excipient to form a solid preformulation composition containing a homogeneous mixture of a compound of the present invention. When referring to these preformulation compositions as homogeneous, the active ingredient is typically dispersed evenly throughout the composition so that the composition can be readily subdivided into equally effective unit dosage forms such as tablets, pills and capsules. This solid preformulation is then subdivided into unit dosage forms of the type described above containing from, e.g., about 0.1 to about 1000 mg of the active ingredient of the present invention.

The tablets or pills of the present invention can be coated or otherwise compounded to provide a dosage form affording the advantage of prolonged action. For example, the tablet or pill can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope over the former. The two components can be separated by an enteric layer which serves to resist disintegration in the stomach and permit the inner component to pass intact into the duodenum or to be delayed in release. A variety of materials can be used for such enteric layers or coatings, such materials including a number of polymeric acids and mixtures of polymeric acids with such materials as shellac, cetyl alcohol and cellulose acetate.

The liquid forms in which the compounds and compositions of the present invention can be incorporated for administration orally or by injection include aqueous solutions, suitably flavored syrups, aqueous or oil suspensions, and flavored emulsions with edible oils such as cottonseed oil, sesame oil, coconut oil, or peanut oil, as well as elixirs and similar pharmaceutical vehicles.

Compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable, aqueous or organic solvents, or mixtures thereof, and powders. The liquid or solid compositions may contain suitable pharmaceutically acceptable excipients as described supra. In some embodiments, the compositions are administered by the oral or nasal respiratory route for local or systemic effect. Compositions can be nebulized by use of inert gases. Nebulized solutions may be breathed directly from the nebulizing device or the nebulizing device can be attached to a face mask, tent, or intermittent positive pressure breathing machine. Solution, suspension, or powder compositions can be administered orally or nasally from devices which deliver the formulation in an appropriate manner.

›III. USES OF THE COMPOUNDS · 4 of 5

Topical formulations can contain one or more conventional carriers. In some embodiments, ointments can contain water and one or more hydrophobic carriers selected from, e.g., liquid paraffin, polyoxyethylene alkyl ether, propylene glycol, white Vaseline, and the like. Carrier compositions of creams can be based on water in combination with glycerol and one or more other components, e.g., glycerinemonostearate, PEG-glycerinemonostearate and cetylstearyl alcohol. Gels can be formulated using isopropyl alcohol and water, suitably in combination with other components such as, e.g., glycerol, hydroxyethyl cellulose, and the like. In some embodiments, topical formulations contain at least about 0.1, at least about 0.25, at least about 0.5, at least about 1, at least about 2 or at least about 5 wt % of the compound of the invention. The topical formulations can be suitably packaged in tubes of, e.g., 100 g which are optionally associated with instructions for the treatment of the select indication, e.g., psoriasis or other skin condition.

The amount of compound or composition administered to a patient will vary depending upon what is being administered, the purpose of the administration, such as prophylaxis or therapy, the state of the patient, the manner of administration and the like. In therapeutic applications, compositions can be administered to a patient already suffering from a disease in an amount sufficient to cure or at least partially arrest the symptoms of the disease and its complications. Effective doses will depend on the disease condition being treated as well as by the judgment of the attending clinician depending upon factors such as the severity of the disease, the age, weight and general condition of the patient and the like.

The compositions administered to a patient can be in the form of pharmaceutical compositions described above. These compositions can be sterilized by conventional sterilization techniques, or may be sterile filtered. Aqueous solutions can be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile aqueous carrier prior to administration. The pH of the compound preparations typically will be between 3 and 11, more preferably from 5 to 9 and most preferably from 7 to 8. It will be understood that use of certain of the foregoing excipients, carriers or stabilizers will result in the formation of pharmaceutical salts.

IV. Labeled Compounds and Assay Methods

The compounds of the invention can further be useful in investigations of biological processes in normal and abnormal tissues. Thus, another aspect of the present invention relates to labeled compounds of the invention (radio-labeled, fluorescent-labeled, etc.) that would be useful not only in imaging techniques but also in assays, both in vitro and in vivo, for localizing and quantitating TEAD transcription factor in tissue samples, including human, and for identifying TEAD transcription factor ligands by inhibition binding of a labeled compound. Accordingly, the present invention includes assays that contain such labeled compounds.

The present invention further includes isotopically-labeled compounds of the invention. An “isotopically” or “radio-labeled” compound is a compound of the invention where one or more atoms are replaced or substituted by an atom having an atomic mass or mass number different from the atomic mass or mass number typically found in nature (i.e., naturally occurring). Suitable radionuclides that may be incorporated in compounds of the present invention include but are not limited to 3 H (also written as T for tritium), 11 C, 13 C, 14 C, 13 N, 15 N, 15 O, 17 O, 18 O, 18 F, 35 S, 36 Cl, 82 Br, 75 Br, 76 Br, 77 Br, 123 I, 124 I, 125 I and 131 I. The radionuclide that is incorporated in the instant radio-labeled compounds will depend on the specific application of that radio-labeled compound. For example, for in vitro labeling and competition assays, compounds that incorporate 3 H, 14 C, 82 Br, 125 I, 131 I, 35 S or will generally be most useful. For radio-imaging applications 11 C, 18 F, 125 I, 123 I, 124 I, 131 I, 75 Br, 76 Br or 77 Br will generally be most useful.

It is to be understood that a “radio-labeled” or “labeled compound” is a compound that has incorporated at least one radionuclide. In some embodiments the radionuclide is selected from the group consisting of 3 H, 14 C, 125 I, 35 S and 82 Br. In some embodiments, the compound incorporates 1, 2 or 3 deuterium atoms. Synthetic methods for incorporating radio-isotopes into organic compounds are known in the art.

Specifically, a labeled compound of the invention can be used in a screening assay to identify and/or evaluate compounds. For example, a newly synthesized or identified compound (i.e., test compound) which is labeled can be evaluated for its ability to bind a TEAD transcription factor by monitoring its concentration variation when contacting with the TEAD transcription factor, through tracking of the labeling. For example, a test compound (labeled) can be evaluated for its ability to reduce binding of another compound which is known to bind to a TEAD transcription factor (i.e., standard compound). Accordingly, the ability of a test compound to compete with the standard compound for binding to the TEAD transcription factor directly correlates to its binding affinity. Conversely, in some other screening assays, the standard compound is labeled and test compounds are unlabeled. Accordingly, the concentration of the labeled standard compound is monitored in order to evaluate the competition between the standard compound and the test compound, and the relative binding affinity of the test compound is thus ascertained.

›III. USES OF THE COMPOUNDS · 5 of 5

V. Kits

The present disclosure also includes pharmaceutical kits useful, e.g., in the treatment or prevention of TEAD transcription factor-associated diseases or disorders, such as cancer, which include one or more containers containing a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), or any of the embodiments thereof. Such kits can further include one or more of various conventional pharmaceutical kit components, such as, e.g., containers with one or more pharmaceutically acceptable carriers, additional containers, etc., as will be readily apparent to those skilled in the art. Instructions, either as inserts or as labels, indicating quantities of the components to be administered, guidelines for administration, and/or guidelines for mixing the components, can also be included in the kit.

The invention will be described in greater detail by way of specific examples. The following examples are offered for illustrative purposes, and are not intended to limit the invention in any manner. Those of skill in the art will readily recognize a variety of non-critical parameters which can be changed or modified to yield essentially the same results.

›EXAMPLES · 1 of 8

Compound Synthesis

Experimental:

The MS (Mass Spectral) data provided in the examples were obtained using the following equipment: API 2000 LC/MS/MS/Triple quad; Agilent (1260 infinity) LCMS-SQD 6120/Single quad and Shimadzu LCMS-2020/Single quad.

The NMR data provided in the examples were obtained using the equipment- 1 HNMR: 1 HNMR: Varian −400 MHz, JEOL −400 MHz.

The abbreviations used in the entire specification may be summarized herein below with their particular meaning.

° C. (degree Celsius); δ (delta); % (percentage); (BOC) 2 O (Boc anhydride); bs (Broad singlet); CDCl 3 (Deuterated chloroform); DCM (Dichloromethane); DMF (Dimethyl formamide); DIPEA (N, N-Diisopropyl ethylamine); DMAP (Dimethyl aminopyridine); (DMSO-d6 (Deuterated DMSO); d (Doublet); dd (Doublet of doublet); Fe (Iron powder); g or gm (gram); HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate); H or H 2 (Hydrogen); H 2 O (Water); HCl (Hydrochloric acid); h or hr (Hours); Hz (Hertz); HPLC (High-performance liquid chromatography); J (Coupling constant); LiOH (Lithium hydroxide); MeOH (Methanol); mmol (Millimol); M (Molar); mL (Millilitre); mg (Milligram); m (Multiplet); mm (Millimeter); MHz (Megahertz); min (Minutes); NaH (Sodium hydride); NaHCO 3 (Sodium bicarbonate); Na 2 SO 4 (Sodium sulphate); N 2 (Nitrogen); NMR (Nuclear magnetic resonance spectroscopy); Pd/C (palladium carbon); RT (Room Temperature); s (Singlet); TEA (Triethylamine); TFA (Trifluoroacetic acid); TLC (Thin Layer Chromatography); THE (Tetrahydrofuran); t (Triplet); rac.BINAP ((±)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene); Pd 2 dba 3 (Tris(dibenzylideneacetone) dipalladium(0)); XPhos (2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl); in vacuo (under vacuum); eq. (equivalents); ppt (precipitate); NA (not available).

A general procedure for the synthesis of certain exemplified compounds is shown in Scheme II below:

To a solution of iodide (1 mmol) and amine (1 mmol) in 1,2-dichlorobenzene was added potassium carbonate (1.5 mmol) under nitrogen atmosphere followed by copper iodide (0.05 mmol). Resulting mixture was stirred at r.t. for 1 h and then heated at 180° C. for 2 days. After completion of the reaction resulting mixture was diluted with dichloromethane (50 mL) and filtered through bed of diatomaceous earth. The organic solution was dried with MgSO 4 , concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 20/1 hexane/ethyl acetate) as eluent Yield 40-69%.

Compound 2a was confirmed with proton NMR and Mass spectroscopy (ESI) and (R f of 0.3 with pure hexane as eluent TLC).

For Compound 2a 1 H NMR (500 MHz, CDCl 3 ): δ 9.46 (s, 1H), 7.98-7.94 (m, 1H), 7.40 (s, 1H), 7.35 (m, 1H), 7.28 (d, 1H), 7.19-7.13 (m, 3H), 6.79 (m, 1H), 3.90 (s, 3H) ppm. Mass (M+H, 307.1) Yield 56%.

Compound 2b (M+H 306.1), 2c (M+H 375.1), 2d (M+H 325.1), 2e (M+H 443.1) were confirmed with Mass spectroscopy (LC-MS/ESI) and also consistent on TLC with retention factor (R f of 0.3 with pure hexane as eluent).

A general procedure for synthesis of starting material for compounds CP-59 and CP-65 is shown in Scheme 3 below:

The requisite amine (1 mmol) and chloro-nicotinate (1 mmol) were dissolved in ethylene glycol and then heated at 140° C. for 24 h. After completion of the reaction resulting mixture was diluted with ethyl acetate (50 mL) and washed three times with 20 mL of water. The organic solution was dried with MgSO 4 , concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 15/1 hexane/ethyl acetate) as eluent. Yield 55-59%

Compound 2f (M+H, 376.1) and 2g (M+H, 322.1) were confirmed with spectroscopy (ESI) and (R f of 0.1 with pure hexane as eluent TLC)

A cross-coupling procedure used in the preparation of several example compounds is shown in Scheme 4 below.

To an oven-dried Schlenk tube was added amine (1 mmol) and bromide (1 mmol) and toluene (3 mL). To the above homogeneous solution t-BuONa (1.5 mmol) was added. After stirring for 5 minutes, Pd 2 (dba) 3 (0.05 mmol) and Bu 3 P (0.075 mmol), were added under nitrogen atmosphere. The mixture was stirred for 24 h at 110° C. After cooling to r.t., the reaction mixture was diluted with ethyl acetate (50 mL) and filtered through bed of diatomaceous earth. The organic solution was dried with MgSO 4 , concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 10/1 hexane/ethyl acetate) as eluent to give desired product. Yield 42-55%

For Compound 3a 1 H NMR (500 MHz, CDCl 3 ): δ 9.45 (s, 1H), 8.01 (s, 1H), 7.5-7.7.30 (m, 2H), 7.2-7.1 (m, 2H), 6.98 (s, 1H), 6.8 (s, 1H) 6.78-6.26 (m, 4H), 5.99 (s, 1H) 3.90 (s, 3H), 2.23-1.97 (m, 15H) ppm

For Compound 3c 1 H NMR (500 MHz, CDCl 3 ): δ 9.45 (s, 1H), 8.01 (s, 1H), 7.45-7.23. (d, 2H), 7.23-7.01 (m, 6H), 6.98-7.01 (d, 2H), 6.94 (s, 1H), 3.93 (s, 3H), 5.99 (s, 1H) 2.21-1.98 (m, 15H) ppm

For Compound 3d 1 H NMR (500 MHz, CDCl 3 ): δ 9.45 (s, 1H), 8.01 (s, 1H), 7.45-7.01 (m, 4H), 6.94 (s, 1H), 6.63 (s, 1H) 6.65-6.20 (m, 4H), 5.98 (s, 1H) 3.92 (s, 3H), 2.21-1.98 (m, 15H) ppm

A cross-coupling procedure used in the preparation of several example compounds is shown in Scheme 5 below.

For Compound 3f 1 H NMR (500 MHz, CDCl 3 ): δ 9.45 (s, 1H), 8.01 (s, 1H), 7.49-7.33. (d, 2H), 7.23-7.01 (m, 5H), 6.91-7.04 (d, 2H), 6.94 (s, 1H), 3.93 (s, 3H), 5.99 (s, 1H) 2.21-1.98 (m, 15H) ppm

›EXAMPLES · 2 of 8

Compound 3g confirmed with LC-MS/ESI (M+H 468.57)

A cross-coupling procedure used in the preparation of several example compounds is shown in Scheme 6 below.

For Compound 3b 1 H NMR (500 MHz, CDCl 3 ): δ 9.45 (s, 1H), 8.01 (s, 1H), 7.67-7.56 (d, 2H), 7.2-7.1 (m, 2H), 6.98 (s, 1H), 6.82 (s, 1H) 6.78-6.26 (m, 2H), 5.99 (s, 1H) 3.92 (s, 3H), 2.23-1.97 (m, 15H) ppm

For Compound 3e 1 H NMR (500 MHz, CDCl 3 ): δ 9.46 (s, 1H), 8.05 (s, 1H), 7.79-7.56 (m, 4H), 7.2-6.99 (m, 4H), 6.98 (s, 1H, 5.99 (s, 1H) 3.94 (s, 3H), 2.23-1.97 (m, 15H) ppm

Carboxylic acid compounds were prepared by hydrolysis reactions as shown in Schemes 7, 8, 9 and 10, and the experimental procedures described below.

To a solution of ester (1 mmol) in ethanol (10 mL) was added 2 mmol of 2N NaOH solution and heated at 40° C. for 24-48 h. Upon completion of the reaction, reaction was cooled on ice and acidified with 2N Hydrochloride solution and extracted three times with 10 mL of ethyl acetate. The organic solution was dried with MgSO 4 , concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 5/1 hexane/ethyl acetate) as eluent to give desired product. Yield 70-79%

CP-52 was confirmed by LC-MS (ESI, M+H 439.1).

CP-57 was confirmed by LC-MS (ESI M+H 521.1).

CP-62 was confirmed by LC-MS (ESI M+H 457.1).

CP-59 was confirmed by LC-MS (ESI, M+H 509.1).

CP-65 was confirmed by LC-MS (ESI, M+H 454.1).

CP-55 was confirmed by LC-MS (ESI, M+H 439.12).

CP-64 was confirmed by LC-MS (ESI, M+H 474.1).

CP-55 was confirmed by LC-MS (ESI, M+H 521.1).

CP-64 was confirmed by LC-MS (ESI, M+H 575.1).

Carboxylic acid compounds were converted to vinyl ketone compounds as shown in Scheme 11, and the experimental procedures described below.

The acid was converted to Weinreb amide. To a solution of acid (0.1 mmol) in dichloromethane (1 mL) was added triethylamine (0.25 mmol) followed by Weinreb amine salt (0.2 mmol), HATU (0.2 mmol) and stirred at r.t. for 16 h. After completion of the reaction, water was and added and extracted three times with 10 mL of ethyl acetate. The organic solution was dried with MgSO 4 , concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 5/1 hexane/ethyl acetate) as eluent to give desired product.

An ice cooled solution of Weinreb amide (1 mmol) in anhydrous THF (10 mL) was added 4 mL of 1M solution of vinyl magnesium bromide in THF and warmed to r.t. and stirred for 4 h after completion of the reaction, quenched with 1N hydrochloride solution at 0° C. and extracted three times with 10 mL of ethyl acetate. The organic solution was dried with MgSO 4 , concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 5/1 hexane/ethyl acetate) as eluent to give desired product. Yield 42-57%.

CP-55 was confirmed by LC-MS (ESI, M+H 449.14).

CP-64 was confirmed by LC-MS (ESI, M+H 449.16).

Certain exemplified compound can be synthesized and characterized as discussed below.

Intermediate-I

Step-a: Synthesis of N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl) acetamide (Ia)

To a solution of acetanilide (50 g, 369 mmol, 1.0 eq.) in 1,1,2,2-tetrachloroethane (300 mL) was added 1-bromoadamantane (87.5 g, 406 mmol, 1.1 eq.) and stirred for 5 minutes. Zinc chloride anhydrous (25.1 g, 184 mmol, 0.5 eq.) was added and stirred at 100° C. for 36 h. Reaction mixture was cooled to RT and excess tetrachloroethane was removed by concentrating in vacuo. The residue was dissolved in ethyl acetate, washed with water and brine. The organic layer was dried over anhydrous Sodium sulfate, adsorbed over silica and purified by flash column chromatography to afford title product as a white solid (58 g, 58%).

1 H NMR (400 MHz, DMSO-d6) δ 9.81 (s, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.25 (d, J=8.8 Hz, 2H), 2.04 (bs, 2H), 2.00 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H); LC-MS: m/z 270.1 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-Ia using appropriate reactants and reagents in presence of suitable solvents and appropriate reaction conditions.

Step-b: Synthesis of N-(4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)acetamide (Ib)

A solution of N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl)acetamide (25 g, 92.8 mmol, 1.0 eq.) in DMF (500 mL) at 0° C. was added with N-chlorosuccinimide (13.6 g, 101 mmol, 1.1 eq.). The reaction mixture was allowed to RT and stirred for 16 h. Excess DMF was removed by concentrating in vacuo. The residue was dissolved in ethyl acetate, washed with water and brine. The organic layer was dried over anhydrous Sodium sulfate and concentrated in vacuo. The crude solid (22 g, 780%) obtained was used in next step without further purification.

›EXAMPLES · 3 of 8

1 H NM/R (400 MHz, DMSO-d6) δ 9.42 (s, 1H), 7.58 (d, J=8.3 Hz, 1H), 7.37 (d, J=2.5 Hz, 1H), 7.29 (dd, J 1 =2.85 Hz, J 2 =8.8 Hz, 1H), 2.06 (bs, 6H), 1.75 (s, 6H), 1.69 (s, 6H); LC-MS: m/z 304.10 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-Ib using appropriate reactants and reagents in presence of suitable solvents and appropriate reaction conditions.

Step-c: Synthesis of 4-((3r,5r,7r)-adamantan-1-yl)-2-chloroaniline (Intermediate-1)

To a solution of N-(4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)acetamide (17 g, 56 mmol, 1.0 eq.) in methanol (150 mL), conc. HCl (150 mL) was added and refluxed at 100° C. for 8 h. Excess methanol was removed in vacuo. The white ppt. obtained was filtered off. The filtered solid was washed with a solution of Sodium bicarbonate followed by water and dried under vacuum. Desired product was obtained as a white solid (13 g, 880).

1 H NMR (400 MHz, DMSO-d6) δ 7.08 (d, J 1 =2.4 Hz, 1H), 7.02 (dd, J 1 =1.9 Hz, J 2 =8.3 Hz, 1H), 6.73 (d, J=8.3 Hz, 1H), 5.09 (bs, 2H), 2.01 (s, 3H), 1.76 (s, 6H), 1.66 (s, 6H); LC-MS: m/z 262.2 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-I using appropriate reactants and reagents in presence of suitable solvents and appropriate reaction conditions.

The below intermediates were prepared by a procedure similar to the ones described in literature using appropriate reactants and reagents in presence of suitable solvents and appropriate reaction conditions.

Intermediate-II

Step-a: Synthesis of methyl 2-((4-bromophenyl)amino)benzoate (Intermediate-II)

A solution of methyl 2-iodobenzoate (30 g, 114.5 mmol, 1.0 eq.) and 4-bromoaniline (19.3 g, 114.5 mmol, 1.0 eq.) in toluene (500 mL) was added with cesium carbonate (49 g, 150 mmol, 1.3 eq.) and de-gassed with N 2 gas for 15 min. Palladium acetate (1.28 g, 5.7 mmol, 0.05 eq.) and rac. BINAP (3.56 g, 5.7 mmol, 0.05 eq.) were added and de-gassed for 5 min. Reaction mass was heated at 110° C. for 16 h. Reaction mass was filtered through celite, concentrated in vacuo and purified by combi-flash to afford the title product as pale brown liquid (33 g, 940%).

1 H NMR (400 MHz, DMSO-d6) δ 9.25 (s, 1H), 7.89 (dd, J 1 =2.0 Hz, J 2 =8.3 Hz, 1H), 7.51 (d, J=2.9 Hz, 2H), 7.48 (t, J=1.9 Hz, 1H), 7.26 (d, J=7.8 Hz, 1H), 7.21 (d, J=4.9 Hz, 2H), 6.87 (t, J=1.0 Hz, 1H), 3.84 (s, 3H); LC-MS: m/z 307.9 (M+H) 2+

The below intermediates were prepared by a procedure similar to Intermediate-II using appropriate reactants and reagents employing suitable Pd & Fe catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-II.28

Step-a: Synthesis of methyl 2-((5-bromopyrimidin-2-yl)(tert-butoxycarbonyl)amino)benzoate (II.28)

To a solution of Intermediate-II.3 (1.3 g, 4.3 mmol, 1 eq.) in THF (30 mL), DMAP (0.1 g, 0.84 mmol, 0.2 eq.), pyridine (0.67 g, 8.7 mmol, 2 eq.), Boc anhydride (1.38 g, 6.3 mmol, 1.5 eq.) were added and heated at 60° C. overnight. Reaction mass was concentrated in vacuo and purified by combi-flash to afford title product as off-white solid (1.4 g, 82%). LC-MS: m/z 408.2 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-II.28 using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

The below intermediates were prepared by a procedure similar to Intermediate-II using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

Intermediates-IIIa & IIIb

Step-a: Synthesis of ethyl 2-(5-bromo-1H-indazol-1-yl)acetate & ethyl 2-(5-bromo-2H-indazol-2-yl)acetate (IIIa & IIIb)

A solution of 5-bromo-1H-indazole (1 g, 5.1 mmol, 1.0 eq.) in acetonitrile (25 mL) was added with potassium carbonate (1.8 g, 12.8 mmol, 2.5 eq.) under stirring. Ethyl bromoacetate (0.7 mL, 6.1 mmol, 1.2 eq.) was added drop wise and reaction mass was heated at reflux overnight. Reaction mass was concentrated in vacuo, adsorbed over silica after water washings and purified by combi-flash to afford title products IIIa (400 mg, 28%, white solid) and IIIb (180 mg, 13%, yellow solid).

Intermediate-IIIa: 1 H NMR (400 MHz, DMSO-d6) δ 8.10 (s, 1H), 8.05 (s, 1H), 7.68-7.65 (m, 1H), 7.53-7.51 (m, 1H), 5.40 (s, 2H), 4.18-4.12 (m, 2H), 1.19 (t, J=6.8 Hz, 3H); LC-MS: m/z 283.0 (M+H) +

Intermediate-IIIb: 1 H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 8.02 (s, 1H), 7.60-7.58 (m, 1H), 7.35-7.32 (m, 1H), 5.42 (s, 2H), 4.20-4.15 (m, 2H), 1.18 (t, J=6.4 Hz, 3H); LC-MS: m/z 283.0 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediates-IIIa & IIIb using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-IV

Step-a: Synthesis of methyl 2-(4-bromobenzamido)benzoate (Intermediate-IV)

A solution of methyl 2-aminobenzoate (5 g, 33.1 mmol, 1.0 eq.) in DCM (50 mL) was added with triethylamine (11 g, 108 mmol, 3 eq.) followed by 4-bromobenzoyl chloride (7.2 g, 33.1 mmol, 1.0 eq.) and stirred at RT overnight. Reaction mixture was extracted with ethyl acetate from water and concentrated in vacuo. The crude was washed with n-pentane and dried to afford title product (9 g, 85%).

1 H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 8.47 (d, J=8.3 Hz, 1H), 8.04 (d, J=8.4 Hz, 1H), 7.89 (d, J=8.8 Hz, 2H), 7.83 (d, J=8.8 Hz, 2H), 7.67 (t, J=7.3 Hz, 1H), 7.24 (t, J=7.3 Hz, 1H), 3.87 (s, 3H).

The below intermediates were prepared by a procedure similar to Intermediate-IV using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-V

Step-a: Synthesis of methyl 2-((4-bromophenyl)(methyl)amino)nicotinate (Intermediate-V)

A solution of Intermediate-II.10 (0.4 g, 1.3 mmol, 1.0 eq.) in DMF (3 mL) was added with sodium hydride (50% o, 0.16 g, 3.9 mmol, 3 eq.) and stirred for 10 min. Iodomethane (0.25 mL, 3.9 mmol, 3 eq.) was added drop wise and stirred at RT overnight in a seal tube. Reaction mass was poured in to water, extracted with ethyl acetate and concentrated in vacuo. The crude was purified by combi-flash to afford title product as a colourless liquid (0.21 g, 500%).

›EXAMPLES · 4 of 8

1 H NM/R (400 MHz, DMSO-d6) δ 8.46 (dd, J 1 =2.0 Hz, J 2 =4.0 Hz, 1H), 7.85 (dd, J 1 =2.0 Hz, J 2 =7.6 Hz, 1H), 7.44-7.40 (m, 2H), 7.05 (dd, J 1 =3.6 Hz, J 2 =7.2 Hz, 1H), 6.94-6.90 (m, 2H), 3.44 (s, 3H), 3.29 (s, 3H), LC-MS: m/z 321.0 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-V using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-VI

Step-a: Synthesis of methyl 2-((4-((4-((3R,5R)-adamantan-1-yl)phenyl)amino) phenyl) amino) benzoate (Intermediate-VI)

A solution of Intermediate-II (0.5 g, 1.63 mmol, 1.0 eq.) and Intermediate-I.1 (0.37 g, 1.63 mmol, 1.0 eq.) in toluene (10 mL) was de-gassed with N 2 gas for 15 min. Pd 2 dba 3 (0.12 g, 0.13 mmol, 0.08 eq.) and XPhos (0.16 g, 0.326 mmol, 0.2 eq.) were added and de-gassed for 5 min. Reaction mass was heated at 110° C. for 16 h. Reaction mass was filtered through celite, concentrated in vacuo and purified by combi-flash to afford the title product as pale yellow solid (0.26 g, 35%).

1 H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 1H), 8.02 (s, 1H), 7.86 (dd, J 1 =1.4 Hz, J 2 =7.8 Hz, 1H), 7.35 (t, J=1.4 Hz, 1H), 7.21 (d, J=8.8 Hz, 2H), 7.12-6.96 (m, 7H), 6.69 (t, J=6.8 Hz, 1H), 3.85 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H); LC-MS: m/z 452.4 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-VI using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-VII

Step-d: Synthesis of 4-((3R,5R)-adamantan-1-yl)-2-chloro-N-(4-nitrophenyl) aniline (Intermediate-VII)

A solution of Intermediate-I (8.5 g, 32.5 mmol, 1 eq.) and 4-bromonitrobenzene (6.57 g, 32.5 mmol, 1 eq.) in toluene (100 mL) was de-gassed by bubbling Nitrogen gas for 5 minutes. Cesium carbonate (16 g, 48.9 mmol, 1.5 eq.) was added followed by Palladium acetate (0.72 g, 3.25 mmol, 0.1 eq.) and XPhos (2.32 g, 4.88 mmol, 0.15 eq.) and de-gassed again for 5 min. Reaction mixture was heated at 110° C. under stirring for 16 h. Reaction mixture was cooled to RT, diluted with ethyl acetate and filtered through celite. The organic layer was adsorbed over silica and purified by flash column chromatography. Desired product was eluted in 5 to 10% ethyl acetate in hexanes. Concentrated in vacuo to afford dark yellow oil (7 g, 57%).

1 H NMR (400 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.09-8.07 (m, 2H), 7.44 (s, 1H), 7.38 (s, 2H), 6.83-6.79 (m, 2H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H); LC-MS: m/z 383.2 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-VII using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

The below intermediates were prepared by a procedure similar to Intermediate-V using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-VII

Step-a: Synthesis of N-(4-((3R,5R)-adamantan-1-yl)phenyl)-3-nitrobenzamide (Intermediate-VIII)

The title compound (1.6 g, 960) was synthesized from intermediate-I.1 (1 g, 4.4 mmol, 1 eq.) and 3-nitrobenzoyl chloride (0.82 g, 4.4 mmol, 1 eq.) using a procedure similar to Intermediate-IV. LC-MS: m/z 377.2 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-VII using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-IX

Step-a: Synthesis of (3R,5R)-1-(3-chloro-4-(4-nitrophenoxy)phenyl)adamantane (Intermediate-IX)

A solution of 4-fluoronitrobenzene (0.6 mL, 5.7 mmol) and Intermediate-1.25 (1.5 g, 6.84 mmol, 1.2 eq.) in DMSO (10 mL) was added with potassium carbonate (1.57 g, 11.4 mmol, 2 eq.) and allowed to stir at RT overnight. Reaction mass was poured on to cold water and obtained solid was filtered and dried to afford title compound as off-white solid (2 g, 910%).

1 H NMR (400 MHz, DMSO-d6) δ 8.26 (d, J=9.3 Hz, 2H), 7.58 (s, 1H), 7.47 (d, J=2.0 Hz, 1H), 7.32 (d, J=8.8 Hz, 1H), 7.1 (d, J=8.3 Hz, 2H), 2.07 (bs, 2H), 1.89 (s, 6H), 1.7 (s, 6H). LC-MS: m/z 382.0 (M−H) −

The below intermediates were prepared by a procedure similar to Intermediate-IX using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-X

Step-a: Synthesis of (3r,5r,7r)-1-(3-chloro-4-methylphenyl)adamantane (Xa)

A solution of (3r,5r,7r)-1-(p-tolyl)adamantane (2 g, 8.8 mmol) in acetic acid was added with N-chlorosuccinimide in portions for a period of 30 minutes. Reaction mass was heated at 75° C. overnight. Reaction mass was poured on to cold water and obtained solid was filtered off and dried under vacuum. Title compound was obtained as white solid (2.2 g, 960%). 1 H NM/R (400 MHz, DMSO-d6) δ 7.31 (d, J=1.9 Hz, 1H), 7.26-7.22 (m, 2H), 2.27 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).

Step-b: Synthesis of (3r,5r,7r)-1-(4-(bromomethyl)-3-chlorophenyl)adamantane (Xb)

A solution of compound Xa (1 g, 3.8 mmol) in carbon tetrachloride (40 mL) was added with Bromine (0.61 g, 3.8 mmol) drop wise and Benzoyl peroxide (catalytic). Reaction mass was heated to reflux overnight. Concentrated in vacuo and crude was purified by column chromatography to afford title product as off-white solid (0.5 g, 380%). 1 H NMR (400 MHz, DMSO-d6) δ 7.38 (d, J=8.0 Hz, 2H), 7.24 (m, 1H), 4.58 (s, 2H), 2.10 (s, 3H), 1.81 (s, 6H), 1.72 (s, 6H).

Step-c: Synthesis of 1-(4-((3R,5R)-adamantan-1-yl)-2-chlorobenzyl)-4-nitro-1H-pyrazole Intermediate-X)

This intermediate was prepared according to a similar procedure described for Intermediate-III by using Intermediate-Xb (0.3 g, 0.88 mmol, 1 eq.) and 4-nitropyrazole (0.12 g, 1.06 mmol, 1.2 eq.) to afford title product as an off-white solid (0.3 g, 91M). 1 H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.28 (s, 1H), 7.41 (d, J=2.0 Hz, 1H), 7.35 (dd, J 1 =1.9 Hz, J 2 =8.3 Hz, 1H), 7.21 (d, J=8.3 Hz, 1H), 5.47 (s, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).

›EXAMPLES · 5 of 8

The below intermediates were prepared by a procedure similar to Intermediate-X using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-XI

Step-a: Synthesis of N1-(4-((3R,5R)-adamantan-1-yl)-2-chlorophenyl)benzene-1,4-diamine (Intermediate-XI)

To a solution of Intermediate-VII (7 g, 18.3 mmol, 1 eq.) in THF:water (50 mL+50 mL), ammonium chloride (19.42 g, 36.6 mmol, 20 eq.) followed by Zinc dust (11.91 g, 183 mmol, 10 eq.) were added and stirred at RT for 16 h. Reaction mixture was diluted with ethyl acetate and filtered through celite. The filtrate was washed with water followed by brine. The organic layer was dried over anhydrous Sodium sulfate and concentrated in vacuo. The crude was washed with n-pentane and dried in vacuo to afford desired product as yellow gum (5.9 g, 91%). This was used in next step without further purification.

1 H NM/R (400 MHz, DMSO-d6) δ 7.20 (d, J=1.9 Hz, 1H) 7.04 (dd, J 1 =2.0 Hz, J 2 =8.3 Hz, 1H), 6.84 (d, J=8.8 Hz, 2H), 6.78 (s, 1H), 6.72 (d, J=8.8 Hz, 1H), 6.54 (d, J=8.8 Hz, 2H), 4.85 (s, 2H), 2.02 (s, 3H), 1.78 (s, 6H), 1.70 (s, 6H); LC-MS: m/z 353.1 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-XI using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-XII

Step-a: Synthesis of methyl 2-((4-((4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl) amino)phenyl)amino) nicotinate (Intermediate-XII)

A solution of Intermediate-XI (8 g, 22.72 mmol, 1 eq.) and methyl 2-chloronicotinate (4.27 g, 25 mmol, 1.1 eq.) in toluene (100 mL) was de-gassed by bubbling Nitrogen gas for 5 minutes. Cesium carbonate (11.1 g, 34.1 mmol, 1.5 eq.) was added followed by Palladium acetate (0.5 g, 2.27 mmol, 0.1 eq.) and rac. BINAP (2.12 g, 3.41 mmol, 0.15 eq.) and de-gassed again for 5 min. Reaction mixture was heated at 110° C. under stirring for 16 h. Reaction mixture was cooled to RT, diluted with ethyl acetate and filtered through celite. The organic layer was adsorbed over silica and purified by flash column chromatography. Desired product was eluted in 10% ethyl acetate in hexanes. Concentrated in vacuo to afford yellow solid (5.4 g, 49%).

1 H NMR (400 MHz, DMSO-d6) δ 9.93 (s, 1H), 8.37 (dd, J 1 =2.0 Hz, J 2 =4.4 Hz, 1H), 8.22 (dd, J 1 =2.0 Hz, J 2 =7.6 Hz, 1H), 7.55 (d, J=8.8 Hz, 2H), 7.41 (s, 1H), 7.31 (d, J=1.6 Hz, 1H), 7.19-7.12 (m, 2H), 7.04 (d, J=8.8 Hz, 2H), 6.84-6.81 (m, 1H), 3.89 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H); LC-MS: m/z 488.1 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-XII using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-XIII

Step-a: Synthesis of methyl 2-((1,4-dioxaspiro[4.5]decan-8-yl)amino)benzoate (XIIIa)

A solution of methyl anthranilate (3 g, 20 mmol, 1 eq.) and 1,4-Cyclohexanedione monoethylene acetal (4.6 g, 30 mmol, 1.5 eq.) in dichloroethane (50 mL) was added with acetic acid (20 mL) and stirred at RT for 2 h. Reaction mass was cooled to 0° C. and added with sodium triacetoxyborohydride (6.3 g, 30 mmol, 1.5 eq.) and allowed to stir at RT for 36 h. Reaction mass was added with saturated bicarbonate solution and extracted with dichloromethane, purified by combi-flash to afford title product (1.01 g, 17%).

1 H NMR (400 MHz, DMSO-d6) δ 7.77 (d, J=7.6 Hz, 1H), 7.71 (d, J=7.6 Hz, 1H), 7.39-7.35 (m, 1H), 6.83 (d, J=8.8 Hz, 1H), 6.57-6.53 (m, 1H), 3.87 (s, 4H), 3.78 (s, 3H), 3.60-3.58 (m, 1H), 1.95-1.90 (m, 2H), 1.70-1.61 (m, 4H), 1.60-1.48 (m, 2H); LC-MS: m/z 292.0 (M+H) +

Step-b: Synthesis of methyl 2-((4-oxocyclohexyl)amino)benzoate (XIIIb)

A solution of compound XIIIa (1.01 g, 3.4 mmol, 1 eq.) in acetone (30 mL) was added with 2N HCl (10 mL) and allowed to stir at RT overnight. Reaction mass was extracted with ethyl acetate from water and concentrated in vacuo. The crude was used further without purification.

1 H NMR (400 MHz, DMSO-d6) δ 7.81 (dd, J 1 =0.8 Hz, J 2 =7.6 Hz, 1H), 7.75 (d, J=7.6 Hz, 1H), 6.94 (d, J=8.8 Hz, 1H), 6.59 (t, J=7.6 Hz, 1H), 3.97-3.95 (m, 1H), 3.79 (s, 3H), 2.57-2.53 (m, 2H), 2.29-2.19 (m, 4H), 1.77-1.72 (m, 2H); LC-MS: m/z 248.2 (M+H) +

Step-c: Synthesis of methyl 2-((4-((4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl) amino)cyclohexyl) amino) benzoate (Intermediate-XIII)

A solution of compound XIIIb (0.5 g, 2.02 mmol, 1 eq.) and Intermediate-I (0.53 g, 2.02 mmol, 1 eq.) in acetic acid (10 mL) was added with sodium triacetoxyborohydride (1.28 g, 6.06 mmol, 3 eq.) and heated at 8° C. for 16 h. Reaction mass was extracted with ethyl acetate from sat. bicarbonate and brine and concentrated in vacuo. Crude was purified by combi-flash to afford title compound as pale pink liquid (0.67 g, 67%). LC-MS: m/z 493.3 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-XIII using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-XIV

Step-a: Synthesis of 4-((2-(methoxycarbonyl)phenyl)amino)benzoic acid (Intermediate-XIV)

A solution of Intermediate-II.20 (3 g, 9.1 mmol, 1 eq.) in DCM (30 mL) was cooled in ice for 10 minutes. TFA (3 mL) was added drop wise and allowed to stir at RT for 16 h. Reaction mass was concentrated in vacuo. The crude was triturated with n-pentane and dried in vacuo to afford title product as pale green solid (2.0 g, 800).

1 H NMR (400 MHz, DMSO-d6) δ 12.58 (s, 1H), 9.40 (s, 1H), 7.93 (dd, J 1 =0.6 Hz, J 2 =8.0 Hz, 1H), 7.87 (dd, J 1 =2.0 Hz, J 2 =6.8 Hz, 2H), 7.52-7.46 (m, 2H), 7.26 (d, J=8.8 Hz, 2H), 7.01-6.97 (m, 1H), 3.84 (s, 3H); LC-MS: m/z 272.1 (M+H) +

Alternate or General Procedure for Synthesizing the Corresponding Carboxylic Acid Compounds which are Having Methyl & Ethyl Esters

To a solution of ester (1 mmol) in THF:MeH:H 2 O (4+4+2 mL), LiOH.H 2 O (5 mmol) was added and stirred at RT for 16 h. Reaction mass was concentrated in vacuo, diluted with water and acidified with 2 N HCl to pH 5. The precipitate obtained was filtered and dried under vacuum. This solid was washed with 10% ether in hexane mixture and dried to afford desired acid.

›EXAMPLES · 6 of 8

The below intermediates were prepared by a procedure similar to Intermediate-XIV using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-XV

Step-a: Synthesis of methyl 2-(4-(4-((3R,5S)-adamantan-1-yl)phenyl)carbamoyl) phenyl) amino)benzoate (Intermediate-XV)

A solution of compound-XIV (0.2 g, 0.74 mmol, 1 eq.) and Intermediate-I.1 (0.185 g, 0.81 mmol, 1.1 eq.) was cooled in ice. HATU (0.34 g, 0.89 mmol, 1.2 eq.) followed by DIPEA (0.39 mL, 2.22 mmol, 3 eq.) were added and allowed to stir at RT for 16 h. Reaction mass was added to ice water slowly under stirring. The obtained precipitate was filtered, washed with cold water twice followed by n-pentane twice and dried in vacuo to afford title compound as cream coloured solid (0.35 g, 98%).

1 H NM/R (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 9.43 (s, 1H), 7.96-7.91 (m, 3H), 7.69 (d, J=8.4 Hz, 2H), 7.54-7.49 (m, 1H), 7.45 (d, J=8.0 Hz, 1H), 7.34-7.31 (m, 4H), 6.95 (t, J=6.8 Hz, 1H), 3.86 (s, 3H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H); LC-MS: m/z 481.1 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-XV using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-XVI

Step-a: Synthesis of N-(4-(N-(4-((3r,5r,7r)-adamantan-1-yl) phenyl)sulfamoyl)phenyl) acetamide (Intermediate-XVI)

A solution of Intermediate-I.1 (0.5 g, 2.2 mmol) in dichloromethane (10 mL) was cooled to ° C. and added with triethylamine (0.66 g, 6.6 mmol, 3 eq.) followed by 4-acetamidobenzenesulfonyl chloride (0.51 g, 2.2 mmol) and stirred at RT for 3 h. Reaction mass was concentrated in vacuo and added with cold water. The obtained solid was filtered and dried under vacuum to afford title product (0.88 g, 94%). LC-MS: m/z 425.1 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-XVI using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-XVII

Step-a: Synthesis of N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl)-4-aminobenzenesulfonamide (Intermediate-XVII)

This compound was prepared from Intermediate-XVI (0.85 g, 2 mmol, 1 eq.) by a procedure similar to the one described for Intermediate-I from Ib to afford title product as a white solid (0.75 g, 98%).

1 H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H), 7.38 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.8 Hz, 2H), 6.98 (d, J=8.8 Hz, 2H), 6.52 (d, J=8.8 Hz, 2H), 5.93 (s, 2H), 2.01 (s, 3H), 1.77 (s, 6H), 1.69 (s, 6H); LC-MS: m/z 383.0 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-XVII using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-XVIII

Step-a: Synthesis of methyl 2-(4-(N-(4-((3R,5R)-adamantan-1-yl) phenyl)sulfamoyl) phenyl) amino) benzoate (Intermediate-XVIII)

Intermediate-XVIII was prepared from Intermediate-XVII and methyl 2-bromobenzoate by a procedure similar to the one described in Intermediate-II.

1 H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 9.31 (s, 1H), 7.89 (d, J=8.4 Hz, 1H), 7.63 (d, J=8.4 Hz, 2H), 7.50 (t, J=7.6 Hz, 1H), 7.42 (d, J=8.0 Hz, 1H), 7.24-7.19 (m, 4H), 7.03-6.99 (m, 3H), 3.77 (s, 3H), 2.00 (s, 3H), 1.76 (s, 6H), 1.69 (s, 6H); LC-MS: m/z 517.1 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-XVIII using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-XIX

Step-a: Synthesis of phenyl (4-((3r,5r,7r)-adamantan-1-yl)phenyl)carbamate (XIXa)

A solution of Intermediate-I.1 (0.5 g, 2.2 mmol, 1 eq.) and phenyl chloroformate (0.42 g, 2.64 mmol, 1.2 eq.) in DCM was added with triethylamine (0.44 g, 4.4 mmol, 2 eq.) and stirred at RT for 2 h. Reaction mixture was washed with water, concentrated in vacuo and purified by combi-flash to afford title compound as white solid (0.48 g, 630%).

1 H NMR (400 MHz, DMSO-d6) δ10.10 (s, 1H), 7.44-7.39 (m, 4H), 7.31-7.19 (m, 5H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H); LC-MS: m/z 348.1 (M+H) +

Step-b: Synthesis of methyl 2-(4-(3-(4-((3R,5R)-adamantan-1-yl) phenyl)ureido)phenyl) amino) nicotinate (Intermediate-XIX)

Intermediate-XIXa (0.285 g, 0.82 mmol, 1 eq.) and methyl 2-((4-aminophenyl)amino) nicotinate (0.2 g, 0.82 mmol, 1 eq.) were taken in THF (20 mL) and added with triethylamine (0.8 mL) and refluxed overnight. Reaction mass was concentrated in vacuo, the obtained crude was washed with n-hexane twice and dried under vacuum. The crude was taken further without purification.

1 H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.52 (d, J=14.0 Hz, 2H), 8.38-8.37 (m, 1H), 7.76 (d, J=8.4 Hz, 2H), 7.41-7.35 (m, 4H), 7.25 (d, J=8.4 Hz, 2H), 6.84 (dd, J 1 =4.4 Hz, J 2 =8.0 Hz, 1H), 3.87 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H); LC-MS: m/z 497.2 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-XIX using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-XIX.4

Step-a: Synthesis of methyl ((4-((4-((3R,5S)-adamantan-1-yl)-2-chlorophenyl) amino)phenyl) carbamoyl) prolinate (XIX.4)

A solution of Intermediate-XI (0.1 g, 0.283 mmol, 1 eq.) in DCM (10 mL) at 0° C. was added with triphosgene (0.084 g, 0.283 mmol, 1 eq.) drop wise and stirred at 0° C. for 1 h. This solution was added to a solution of methyl prolinate (0.056 g, 0.32 mmol, 1.2 eq.) in DCM (10 mL) and stirred at 0° C. for 1 h. Quenched with sat. bicarbonate solution and extracted with DCM, purified by column chromatography to afford title product as pale brown solid (0.13 g, 90%).

1 H NMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.34 (d, J=8.8 Hz, 2H), 7.28 (d, J=2.0 Hz, 1H), 7.26 (s, 1H), 7.14 (dd, J 1 =2.0 Hz, J 2 =8.0 Hz, 1H), 7.04 (d, J=8.8 Hz, 1H), 6.96 (d, J=9.6 Hz, 2H), 4.37-4.34 (m, 1H), 3.62 (s, 3H), 3.56-3.46 (m, 2H), 2.21-2.14 (m, 1H), 2.03 (s, 3H), 1.98-1.84 (m, 3H), 1.81 (d, J=2.4 Hz, 6H), 1.71 (s, 6H); LC-MS: m/z 508.4 (M+H) +

›EXAMPLES · 7 of 8

The below intermediates were prepared by a procedure similar to Intermediate-XIX.4 using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Intermediate-XX

Step-a: Synthesis of methyl 2-((4-((4-((3R,5R)-adamantan-1-yl)phenyl)(methyl) amino) phenyl) (methyl) amino) benzoate (Intermediate-XX)

A solution of intermediate-VI (4 g, 8.85 mmol, 1 eq.) in DMF (80 mL) was cooled to 0° C. and added with sodium hydride (1.06 g, 44.2 mmol, 5 eq.) portion wise and stirred for 15 minutes. Methyl iodide (6.3 g, 44.2 mmol, 5 eq.) was added drop wise and the reaction mass was heated at 80° C. for 16 h in a seal tube. Reaction mass was cooled to RT and poured in to cold water. The precipitated solid was filtered and dried. This crude was absorbed over silica and purified by combi-flash to afford title product as pale-yellow solid (3 g, 70.70%).

1 H NMR (400 MHz, DMSO-d6) δ 7.65 (dd, J 1 =2.0 Hz, J 2 =8.0 Hz, 1H), 7.60 (t, J=7.6 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H), 7.26 (t, J=7.2 Hz, 1H), 7.13 (d, J=8.8 Hz, 2H), 6.90 (d, J=8.8 Hz, 2H), 6.67 (d, J=8.8 Hz, 2H), 6.59 (d, J=8.8 Hz, 2H), 3.55 (s, 3H), 3.20 (s, 3H), 3.13 (s, 3H), 2.02 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H); LC-MS: m/z 480.25 (M+H) +

The below intermediates were prepared by a procedure similar to Intermediate-XX using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

The below compounds were prepared by a procedure similar to Intermediate-VI using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

The below compounds were prepared by a procedure similar to Intermediate-XIII using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

The below compound was prepared by a procedure similar to Intermediate-XI using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

The below compound was prepared by a procedure similar to Intermediate-XIX using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Synthesis of 2-((4-((4-((3R,5R)-adamantan-1-yl)phenyl)amino) phenyl)amino)benzoic acid (Compound-24 (CP-55))

To a solution of Intermediate-VI (8.5 g, 16.5 mmol, 1 eq.) in THF:MeOH:H 2 O (40+40+20 mL) LiOH×H 2 O (3.3 g, 82.4 mmol, 5 eq.) was added and stirred at RT for 16 h. Reaction mass was concentrated in vacuo, diluted with water and acidified with 2 N HCl to pH 5. The precipitate obtained was filtered and dried under vacuum. This solid was washed with 10% ether in hexane mixture and dried to afford title product as off-white solid (5.5 g, 670).

1 H NM/R (400 MHz, DMSO-d6) δ 12.99 (s, 1H), 9.42 (s, 1H), 8.00 (s, 1H), 7.85 (d, J=6.8 Hz, 1H), 7.32 (t, 1H), 7.21 (d, J=8.8 Hz, 2H), 7.11-6.96 (m, 7H), 6.67 (t, J=3.4 Hz, 1H), 2.08 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H); LC-MS: m/z 438.4 (M+H) +

The below compounds were prepared by a procedure similar to the one described in compound-24 by using appropriate reagents in the presence of suitable solvents at appropriate reaction conditions. The physiochemical characteristics of the compounds are also summarized.

The below compounds were prepared by a procedure similar to Intermediate-XV using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

The below compounds were prepared by a procedure similar to Intermediate-XIV using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Synthesis of 2-((4-(4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)amino)phenyl)carbamoyl) benzoic acid (Compound-293) (CP-119)

Step (i): A solution of Intermediate-XI (0.05 g, 0.16 mmol, 1 eq.) and phthalic anhydride (0.024 g, 0.16 mmol, 1 eq.) in DCM was stirred at RT for 2 h. The precipitate obtained was filtered and dried in vacuo to afford title product as pale-yellow solid (0.01 g, 12.50%).

1 H NMR (400 MHz, DMSO-d6) δ12.98 (s, 1H), 10.17 (s, 1H), 7.86 (d, J=7.8 Hz, 1H), 7.63 (d, J=7.3 Hz, 1H), 7.57-7.52 (m, 4H), 7.41 (s, 1H), 7.31 (d, J=1.6 Hz, 1H), 7.17-7.12 (m, 2H), 7.04 (d, J=8.8 Hz, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 501.1 (M+H) +2

The below compounds were prepared by a procedure similar to Compound 293 using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

Experimental procedure and physiochemical characteristics of the compound CP-453

Intermediate

The above intermediate was prepared by a procedure similar to Intermediate-XII by using Intermediate-XI.16 (0.145 g, 0.43 mmol, 1 eq.) and methyl 2-bromo-5-isobutoxybenzoate (0.125 g, 0.43 mmol, 1 eq.) to afford title product as brown solid (0.05 g, 22%). 1 H NMR (400 MHz, DMSO-d 6 ): δ 8.79 (s, 1H), 7.54-7.52 (m, 1H), 7.44-7.42 (m, 1H), 7.28-6.98 (m, 9H), 3.85 (s, 3H), 3.80 (d, J=2.4 Hz, 2H), 3.37 (s, 3H), 2.04 (s, 3H), 2.00-1.96 (m, 1H), 1.83 (s, 6H), 1.72 (s, 6H), 0.97 (d, J=6.4 Hz, 6H).

Final Compound

The above compound was prepared by a procedure similar to the one described in compound-24 by using appropriate reagents in the presence of suitable solvents at appropriate reaction conditions. The physiochemical characteristics of the compound also summarized.

1 H NMR (400 MHz, DMSO-d 6 ): δ 13.10 (s, 1H), 9.12 (s, 1H), 7.37 (d, J=2.0 Hz, 1H), 7.23 (d, J=8.4 Hz, 2H), 7.10 (d, J=9.2 Hz, 2H), 7.05 (dd, J 1 =2.8 Hz, J 2 =9.2 Hz, 2H), 6.97 (d, J=8.8 Hz, 2H), 6.89 (d, J=8.8 Hz, 2H), 3.68 (d, J=6.4 Hz, 2H), 3.21 (s, 3H), 2.04 (s, 3H), 2.01-1.98 (m, 1H), 1.83 (d, J=2.6 Hz, 6H), 1.72 (s, 6H), 0.97 (d, J=6.8 Hz, 6H). LC-MS: 525.3 (M+H) +

Biological Assays

In Vitro Palmitoylation

Recombinant GST-TEAD2 or His 6 TEAD2 (500 ng) protein was pre-incubated with the compounds at indicated concentrations for 15 min. and then incubated with 1 μM of alkyne palmitoyl-5 CoA (Cayman Chemical) for 30 min or 50 mM MES, pH 6.4, followed by Click reaction with biotin-azide as previously described (Zheng, B. et al., J. Am. Chem. Soc., 2013, 135, 7082-7085). Click reaction was performed with 100 μM biotin-azide, 1 mM tris(2-carboxyethyl) phosphine hydrochloride (TCEP), 100 μM tris[(1-benzyl-1H-1,2,3-triazol-4-yl) methyl] amine (TBTA) and 1 mM CuSO 4 for 1 h at RT.

›EXAMPLES · 8 of 8

The reactions were terminated by the addition of 12 μL of 6×SDS-sample loading buffer (50 mM Tris-HCl, pH 6.8, 6% SDS, 48% Glycerol, 0.03% Bromophenol Blue, 30 mM EDTA, 9% MeSH). Samples were analysed by SDS-PAGE and Western blot was performed by probing with streptavidin HRP and histidine HRP antibodies independently. Bands intensity obtained from streptavidin blot were quantified using BIORAD, Gel doc system and the percentage of inhibition of Tead2 auto palmitoylation is determined by comparing to the DMSO control treated samples.

These compounds were tested for activity in inhibiting TEAD2 palmitoylation in the assay described above. The data for the compounds is provided in below table as a percentage of inhibition of TEAD2 palmitoylation by the compound at a concentration of 10 PM.

Cell Proliferation

HuH7 cells (or other cells) are cultured in DMEM supplemented with 10% FBS. The cells are seeded in 96-wells with 5000 cells/well density. After cell attached to the wells, compounds in DMSO solution were added (1% DMSO concentration) to the cells with serial dilutions for the indicated final concentration. The cells were further incubated for 3 days. The cell viability is then determined using CellTiter Glo, MTT or crystal violet staining. The inhibition curve is plotted by using GraphPad.

qRT-PCR

YAP target gene expression was analyzed with a LightCycler 480 (Roche). Total RNA was isolated from cells using TRIzol (Life Technologies) and then used to produce cDNA with the Transcriptor First Strand cDNA Synthesis Kit (Roche). The resulting cDNA was then used in reactions with the LightCycler 480 SYBR Green I Master mix (Roche) with probes detecting CTGF or CYR61, and GAPDH.

CMP Assay

7-Diethylamino-3-(4′-Maleimidylphenyl)-4-Methylcoumarin (CPM), which reacts with thiol of CoA liberated in the enzymatic reaction, and gives fluorescent signal (excitation ˜350-380, emission-460-480). The assay detects the product (free CoA) which is produced from palmitoyl-CoA as a method to detect the enzymatic activity. Test compounds that inhibit TEAD activity are therefore able to block the CMP fluorescent signal.

TEAD2/4 protein (10 μL of a 50 ng/μL solution) and a solution the test compound (0.5 μL, variable concentration) were pre-incubated for 30 min at r.t. A mixture prepared from MES pH 6.4 buffer (6.5 μL of a 50 mM solution), EDTA (1 μL of a 20 mM solution), palmitoyl-CoA (1 μL of a 20 μM solution), and 7-diethylamino-3-(4′-maleimidylphenyl)-4-methylcoumarin (1 μL of a 10 μM solution) was added and the resulting mixture was mixed well using a pipette. The solution was then incubated at r.t. for 30-120 min. in the dark, and fluorescence was detected at 350 nm every 30 min. until the fluorescence signal is saturated. An IC 50 for the ability of the compound to inhibit fluorescence is calculated from the results.

Results of the biological assays are shown in FIGS. 3 - 12 and Table 1 and Table 2.

Compounds Active as TEAD Palmitoylation Inhibitors

The Example compounds were tested for activity in inhibiting TEAD2 palmitoylation in the assay and CMP assay described above. The data for the compounds provided in Table 1 as a percentage of inhibition of TEAD2 palmitoylation by the compound at a concentration of 10 μM or the IC50 in the CMP assay.

Various modifications of the invention, in addition to those described herein, will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. Each reference, including without limitation all patent, patent applications, and publications, cited in the present application is incorporated herein by reference in its entirety.

›Tables in the description — 25

or a pharmaceutically acceptable salt thereof, wherein:

L 1 is absent, or a group of formula N(R N ) or C(O);

D is a group of formula (D1), (D2), (D3), (D4), (D5), (D6), or (D7):

m is 1, 2 or 3;

L 2 is absent, or a group of formula N(R N ), O, or C(O);

L 3 is absent or a group of formula CH 2 , C≡C, N(R N ) or C(O);

each R N is independently H, C 1-6 alkyl, C(O)C 1-6 alkyl, or C(O)OC 1-6 alkyl;

R 1 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Cy 1A , OH, OC 1-6 alkyl, OCy 1A , O(C 1-3 alkylenyl)Cy 1A , NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl) 2 , NHCy 1A , NH(C 1-3 alkylenyl)Cy 1A , N(C 1-6 alkyl)Cy 1A , or N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 1A , wherein each of the C 1-6 alkyl forming R 1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR a1 , SR a1 , and NR c1 R d1 ;

Cy 1A is C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy 1A is unsubstituted or substituted by 0, 1 or 2 Cy 1B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

each Cy 1B is C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy 1B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ; and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

A 2 is CR 2 or N;

A 3 is CR 3 or N;

A 4 is CR 4 or N;

A 5 is CR 5 or N;

A 6 is CR 6 or N;

A 7 is CR 7 or N;

A 8 is CR 8 or N;

A 9 is CR 9 or N;

A 10 is CR 10 or N;

A D41 is CH, C(C 1-6 alkyl) or N;

A D42 is CH 2 , NH or NC 1-6 alkyl;

R 6 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 7 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , Cy 7A , OCy 7A , O(C 1-3 alkylenyl)Cy 7A , C(O)OCy 7A , C(O)O(C 1-3 alkylenyl)Cy 7A , NHCy 7A , NH(C 1-3 alkylenyl)Cy 7A , N(C 1-6 alkyl)Cy 7A , N(C(O)C 1-6 alkyl)Cy 7A , N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A , C(O)NHCy 7A , C(O)NH(C 1-3 alkylenyl)Cy 7A , C(O)N(C 1-6 alkyl)Cy 7A , C(O)N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 7A or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 8 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , Cy 8A , OH, OCy 8A , O(C 1-3 alkylenyl)Cy 8A , C(O)OCy 8A , C(O)O(C 1-3 alkylenyl)Cy 8A , NHCy 8A , N(Cy 8A ) 2 , NH(C 1-3 alkylenyl)Cy 8A , N(C 1-6 alkyl)Cy 8A , N(C(O)C 1-6 alkyl)Cy 8A , SO 2 NHCy 8A , N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , C(O)NHCy 8A , C 1-3 alkylene-C(O)NHCy 8A , C(O)NH(C 1-3 alkylenyl)Cy 8A , C(O)N(C 1-6 alkyl)Cy 8A , C(O)N(C 1-6 alkyl)(C 1-3 alkylenyl)Cy 8A , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

each Cy 8B is C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy 8B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , and C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

R 9 is H, unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or C 1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , and NR c1 R d1 ;

Cy D71 is C 6-10 aryl, C 3-15 cycloalkyl, 5-14 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C 6-10 aryl, C 3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy D71 is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy D72 , CH 2 Cy D72 , OCy D72 , NHCy D72 , O—C 1-6 alkylene-Cy D72 , N(C 1-6 alkyl)Cy D72 , N(C(O)C 1-6 alkyl)Cy D72 , and C(O)NHCy D72 , and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , and C 1-6 alkyl or C 2-6 alkenyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C 1-6 haloalkyl, CN, OR a1 , SR a1 , C(O)OR a1 , and NR c1 R d1 ;

R a1 , R b1 , R c1 and R d1 are each independently selected from H, C 1-6 alkyl, HO—C 1-6 alkylene, C 1-6 alkoxy-C 1-6 alkylene, C 6-10 aryl, C 2-6 alkenyl and C 2-6 alkynyl; or

R c1 and R d1 together with the nitrogen atom to which they are both attached together form a 4-10 membered unsubstituted heterocycloalkyl ring;

Intermediate 1 H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.24 (d, J = 8.8 Hz, 2H), 2.13-2.11 (m, 1H), 2.00 (s, 3H), 1.65 (s, 2H), 1.49-1.32 (m, 8H), 1.17 (s, 2H), 0.84 (s, 6H). LC-MS: m/z 298.2 (M + H) +

CP	No.	Structure	Analytical data
396	Ia.1

Intermediate 1 H NMR (400 MHz, DMSO-d6) δ 9.42 (s, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.37 (d, J = 1.6 Hz, 1H), 7.28 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 1H), 2.14-2.12 (m, 1H), 2.06 (s, 3H), 1.67 (s, 2H), 1.51-1.32 (m, 8H), 1.18 (s, 2H), 0.85 (s, 6H). LC-MS: m/z 332.2 (M + H) +

CP	No.	Structure	Analytical data
170	Ib.1
1 H NMR (400 MHz, DMSO-d6) δ 8.21-8.19 (m, 1H), 7.53-7.48 (m, 2H), 7.31-7.29 (m, 1H), 2.22 (s, 3H), 2.09 (s, 3H), 1.86 (s, 6H), 1.80-1.60 (m, 6H). LC-MS: m/z 348.0 M + H) +
396	Ib.2

Intermediate 1 H NMR (400 MHz, DMSO-d6) δ 7.39-7.38 (m, 1H), 7.12-7.09 (m, 1H), 6.74-6.72 (m, 1H), 3.94 (s, 2H), 2.09 (s, 3H), 1.86 (s, 6H), 1.80-1.69 (m, 6H).

CP	No.	Structure	Analytical data
	I.1
1 H NMR (400 MHz, DMSO-d6) δ 6.99 (d, J = 8.3 Hz, 2H), 6.50 (d, J = 8.3 Hz, 1H), 4.76 (s, 2H), 2.01 (bs, 3H), 1.77 (s, 6H), 1.70 (s, 6H). LC-MS: m/z 228.1 (M + H) +
295	I.2
1 H NMR (400 MHz, DMSO-d6) δ 7.06 (d, J = 8.4 Hz, 2H), 6.63 (d, J = 7.6 Hz, 2H), 6.10-6.00 (bs, 2H), 2.10 (s, 1H), 1.61 (s, 2H), 1.45-1.30 (m, 8H), 1.15 (s, 2H), 0.84 (s, 6H). LC-MS: m/z 256.2 (M + H) +
396	I.3
1 H NMR (400 MHz, DMSO-d6) δ 7.19 (d, J = 2.0 Hz, 1H), 7.11 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 2.11-2.10 (m, 1H), 1.61 (s, 2H), 1.46- 1.30 (m, 8H), 1.15 (s, 2H), 0.84 (s, 6H). LC-MS: m/z 290.2 (M + H) +
170	I.4

	Intermediate		Literature
CP	No.	Structure	report	Analytical data
113, 132, 133	I.5
Journal of the American Chemical Society, 2000, vol. 122, 17, p. 4020-4028	1 H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 3.5 Hz, 1H), 7.19 (t, J = 3.4 Hz, 2H), 7.13 (d, J = 1.9 Hz, 2H), 7.10 (dd, J 1 = 2.0 Hz, J 2 = 8.3 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 5.40 (s, 2H), 2.23 (s, 3H). LC-MS: m/z 218.0 (M + H) +
115	I.6
Organic Letters, 2012, vol. 14, 20, p. 5306-5309	1 H NMR (400 MHz, DMSO-d6) δ 7.73-7.69 (m, 1H), 7.50 (t, J = 7.3 Hz, 1H), 7.49 (t, J = 7.9 Hz, 1H), 7.30 (d, J = 5.3 Hz, 1H), 7.22 (d, J = 1.4 Hz, 1H), 7.03 (d, J = 1.0 Hz, 1H), 6.77 (d, J = 8.3 Hz, 1H), 4.11 (s, 2H). LC-MS: m/z 271.9 (M + H) +
116	I.7
Journal of Medicinal Chemistry, 2012, vol. 55, 8, p. 3923-3933	1 H NMR (400 MHz, DMSO-d6) δ 7.46 (dd, J 1 = 3.0 Hz, J 2 = 8.8 Hz, 1H), 7.38-7.34 (m, 1H), 7.24-7.22 (m, 1H), 7.07 (d, J = 2.0 Hz, 2H), 6.61 (d, J = 4.4 Hz, 2H), 5.25 (s, 2H). LC-MS: m/z 221.9 (M + H) +
118	I.8
Journal of Medicinal Chemistry, 2009, vol. 52, 9, p. 2683-2693	1 H NMR (400 MHz, DMSO-d6) δ 7.31 (d, J = 1.9 Hz, 1H), 7.28- 7.22 (m, 2H), 7.16 (dd, J 1 = 2.5 Hz, J 2 = 8.4 Hz, 1H), 7.05 (d, J = 8.3 Hz, 1H), 6.99-6.95 (dt, J 1 = 1.0 Hz, J 2 = 6.3 Hz, 1H), 6.81 (d, J = 8.3 Hz, 1H), 5.38 (s, 2H), 3.75 (s, 3H). LC-MS: m/z 233.9 (M + H) +
121	I.9
WO2015/14944, 2015, A1	1 H NMR (400 MHz, DMSO-d6) δ 7.10-7.05 (m, 3H), 6.93 (d, J = 2.0 Hz, 1H), 6.86 (d, J = 8.3 Hz, 1H), 6.77 (dd, J 1 = 1.4 Hz, J 2 = 7.8 Hz, 1H), 5.34 (s, 2H), 1.99 (s, 6H).
122	I.10
Journal of Medicinal Chemistry, 2009, vol. 52, 9, p. 2683-2693	1 H NMR (400 MHz, DMSO-d6) δ 7.51 (d, J = 7.3 Hz, 1H), 7.38- 7.32 (m, 3H), 7.26 (d, J = 2.0 Hz, 1H), 7.12 (dd, J 1 = 1.9 Hz, J 2 = 8.3 Hz, 1H), 6.85 (d, J = 8.4 Hz, 1H), 5.53 (s, 2H). LC- MS: m/z 238.1 (M + H) +
126	I.11
Journal of Medicinal Chemistry, 2009, vol. 52, 9, p. 2683-2693	LC-MS: m/z 232.0 (M + H) +
140	I.12
WO2012/137181, 2012, A1	1 H NMR (400 MHz, DMSO-d6) δ 7.19 (t, J = 2.0 Hz, 1H), 7.10 (dd, J1 = 2.0 Hz, J2 = 8.3 Hz, 1H), 6.72 (d, J = 8.3 Hz, 1H), 5.78 (s, 1H), 5.28 (s, 2H), 2.33 (m, 2H), 1.82-1.71 (m, 4H), 0.77- 0.74 (m, 6H).
146	I.13
Journal of Medicinal Chemistry, 2002, vol. 45, 8, p. 1697-1711	1 H NMR (400 MHz, DMSO-d6) δ 7.47-7.40 (m, 4H), 7.32 (d, J = 1.6 Hz, 1H), 7.25 (d, J = 7.2 Hz, 2H), 7.05 (d, J = 1.2 Hz, 1H), 6.94 (d, J = 8.4 Hz, 2H), 6.41 (d, J = 8.8 Hz, 2H). LC-MS: m/z 236.1 (M + H) +
178	I.14
U.S. Pat. No. 5,200,550 A1	1 H NMR (400 MHz, DMSO-d6) δ 12.91 (bs, 1H), 7.93 (t, J = 1.2 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.44 (t, J = 8.0 Hz, 1H), 2.07 (s, 3H), 1.88 (s, 6H), 1.75 (s, 6H).
177, 191, 200,	I.15
Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972- 1999), 1976, p. 662-668	1 H NMR (400 MHz, DMSO-d6) δ 7.92 (t, J = 7.8 Hz, 1H), 6.56 (t, J = 2.0 Hz, 1H), 6.49 (d, J = 7.9 Hz, 1H), 6.35 (dd, J 1 = 0.9 Hz, J 2 = 7.9 Hz, 1H), 4.86 (s, 2H), 2.03 (s, 3H), 1.75 (s, 6H), 1.71 (s, 6H).
193	I.16
Chemistry-A European Journal, 2011, vol. 17, 49, p. 13832-13846	1 H NMR (400 MHz, DMSO-d6) δ 7.34 (d, J = 7.8 Hz, 1H), 7.24 (t, J = 0.9 Hz, 1H), 7.14 (t, J = 1.0 Hz, 1H), 7.05 (d, J = 1.0 Hz, 1H), 6.91 (d, J = 9.0 Hz, 2H), 6.60 (d, J = 8.3 Hz, 2H), 5.08 (s, 2H), 3.08 (m, 1H), 1.10 (d, J = 6.9 Hz, 6H).
287	I.17
Advanced Synthesis and Catalysis, 2007, vol. 349, 10, p. 1775-1780	LC-MS: m/z 235.2 (M + H) +
288	I.18
Journal of Medicinal Chemistry, 1997, vol. 40, 16, p. 2634-2642	1 H NMR (400 MHz, CDCl3) δ 6.65-6.63 (m, 4H), 3.14 (s, 2H), 3.12 (m, 4H), 1.48 (m, 4H), 1.32 (m, 4H), 0.91 (m, 6H).
292	I.19
Antibiotics Chemotherapy, 1954, vol. 4, p. 150, 152	1 H NMR (400 MHz, DMSO-d6) δ 7.05 (t, J = 7.3 Hz, 2H), 6.81 (d, J = 6.8 Hz, 2H), 6.60- 6.52 (m, 5H), 5.02 (s, 2H), 3.48 (t, J = 7.8 Hz, 2H), 1.52-1.46 (m, 2H), 1.33-1.27 (m, 2H), 0.86 (t, J = 3.9 Hz, 3H).
291, 328	I.20
WO2008/82003, 2008, A1	LC-MS: m/z 181.10 (M + H) +
309	I.21
Organic and Biomolecular Chemistry, 2006, vol. 4, 6, p. 1091- 1096	1 H NMR (400 MHz, DMSO-d6) δ 7.42-7.35 (m, 4H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 237.1 (M + H) +
318	I.22
WO2010/125390, 2010, A1	LC-MS: m/z 284.2 (M- 113) + Azetidine fragment
338	I.23
Pharmazie, 1981, vol. 36, 6, p. 400- 402	1 H NMR (400 MHz, DMSO-d6) δ 7.50 (d, J = 8.0 Hz, 2H), 7.02 (s, 1H), 6.49 (d, J = 8.4 Hz, 2H), 5.50 (s, 2H), 2.03 (s, 9H), 1.64 (s, 6H). LC-MS: m/z 271.15 (M + H) +
203	I.24
Organic Letters, 2007, vol. 9, 26, p. 5397-5400	1 H NMR (400 MHz, DMSO-d6) δ 8.07-8.05 (m, 1H), 7.94 (s, 1H), 7.61-7.57 (m, 2H), 7.30 (d, J = 7.2 Hz, 1H), 7.28- 7.24 (m, 1H), 7.20-7.16 (m, 2H), 4.20 (s, 2H), 3.11-3.07 (m, 1H), 1.06 (d, J = 6.8 Hz, 6H).
321	I.25
Letters in Organic Chemistry, 2016, vol. 13, 3, p. 171- 176	1 H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H), 7.22-7.21 (m, 1H), 7.12-7.10 (m, 1H), 6.90- 6.88 (m, 1H), 2.03 (s, 3H), 1.79 (s, 6H), 1.71 (s, 6H).
323	I.26
WO2015/51149, 2015, A1	1 H NMR (400 MHz, DMSO-d6) δ 6.62 (d, J = 8.8 Hz, 2H), 6.48 (d, J = 8.8 Hz, 2H), 4.54 (s, 2H), 3.37 (s, 2H), 1.96 (s, 3H), 1.69-1.59 (m, 12H).
337	I.27
Letters in Organic Chemistry, 2016, vol. 13, 3, p. 171- 176	1 H NMR (400 MHz, DMSO-d6) δ 7.17 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H), 2.98- 2.96 (m, 4H), 2.92-2.88 (m, 1H), 2.81-2.80 (m, 4H), 2.03 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 297.3 (M + H) +
388	I.28
Antibiotics Chemotherapy, 1954, vol. 4, p. 150, 152	1 H NMR (400 MHz, DMSO-d6) δ 7.12-7.08 (m, 2H), 6.96 (d, J = 2.0 Hz, 1H), 6.86-6.80 (m, 2H), 6.64-6.58 (m, 3H), 5.30 (s, 2H), 3.50 (t, J = 7.2 Hz, 2H), 1.51- 1.46 (m, 2H), 1.35-1.28 (m, 2H), 0.87 (t, J = 7.2 Hz, 3H). LC-MS: m/z 275.1 (M + H) +
407, 408	I.29
Tetrahedron, 1988, vol. 44, 7, p. 1893-1904	1 H NMR (400 MHz, DMSO-d6) δ 7.26-7.24 (m, 4H), 3.66 (s, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 242.2 (M + H) +
314	I.30
Letters in Organic Chemistry, 2016, vol. 13, 3, p. 171- 176	1 H NMR (400 MHz, DMSO-d6) δ 9.07 (s, 1H), 7.13-7.11 (m, 2H), 6.68-6.66 (m, 2H), 2.03 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 228.0 (M + H) +
383	I.31
Letters in Organic Chemistry, 2016, vol. 13, 3, p. 171- 176	1 H NMR (400 MHz, DMSO-d6) δ 6.87-6.83 (m, 1H), 6.65 (dd, J 1 = 2.8 Hz, J 2 = 8.8 Hz, 1H), 6.15 (d, J = 8.4 Hz, 1H), 2.08- 2.05 (m, 1H), 1.54 (s, 2H), 1.38-1.29 (m, 8H), 1.11 (s, 2H), 0.82 (s, 6H). LC-MS: m/z 289.05 (M − H) − .
360	I.32
Chemistry-A European Journal, 2011, vol. 17, 49, p. 13832-13846	1 H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.32 (t, J = 7.4 Hz, 1H), 7.19 (t, J = 6.3 Hz, 2H), 7.09 (d, J = 7.3 Hz, 1H), 7.03 (t, J = 8.3 Hz, 2H), 2.99-2.96 (m, 1H), 1.11 (d, J = 6.9 Hz, 6H). LC-MS: m/z 245.1 (M − H) − .
93	I.33
Chemistry-A European Journal, 2011, vol. 17, 49, p. 13832-13846	LC-MS: m/z 246.0 (M + H) +

Intermediate LC-MS: m/z 310.1 (M + H) +

CP	No.	Structure	Analytical data
52	II.1
LC-MS: m/z 308 (M + H) 2+
127	II.2
1 H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 8.20 (d, J = 5.6 Hz, 1H), 7.89-7.82 (m, 2H), 7.64 (t, J = 8.4 Hz, 1H), 7.27 (t, J = 7.6 Hz, 1H), 6.84 (d, J = 6.0 Hz, 1H), 3.77 (s, 3H). LC-MS: m/z 263.9 (M + H) +
141 154	II.3
1 H NMR (400 MHz, DMSO-d6) δ 10.83 (s, 1H), 8.69 (s, 2H), 8.57 (d, J = 8.4 Hz, 1H), 7.98 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.66-7.61 (m, 1H), 7.11 (t, J = 7.6 Hz, 1H), 3.86 (s, 3H). LC-MS: m/z 309.9 (M + H) 2+
142 252	II.4
1 H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 8.35 (d, J = 1.6 Hz, 1H), 8.29-8.26 (m, 2H), 7.94 (dd, J 1 = 1.6 Hz, J 2 = 7.6 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.11 (t, J = 8.0 Hz, 1H), 3.84 (s, 3H). LC-MS: m/z 309.9 (M + H) 2+
144, 152, 155	II.5
1 H NMR (400 MHz, DMSO-d6) δ 10.18 (s, 1H), 8.39 (d, J = 8.8 Hz, 1H), 8.30 (d, J = 2.4 Hz, 1H), 7.92 (dd, J 1 = 1.2 Hz, J2 = 7.6 Hz, 1H), 7.83 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 7.56 (t, J = 7.2 Hz, 1H), 7.04-6.98 (m, 2H), 3.84 (s, 3H). LC-MS: m/z 308.9 (M + H) 2+
158	II.6
1 H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1H), 7.63 (t, J = 1.5 Hz, 1H), 7.44-7.40 (m, 4H), 7.33-7.30 (m, 1H), 7.06-7.02 (m, 2H), 3.83 (s, 3H). LC- MS: m/z 307.9 (M + H) 2+
175	II.7
1 H NMR (400 MHz, DMSO-d6) δ 10.72 (s, 1H), 8.52 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 8.49 (d, J = 9.0 Hz, 1H), 8.39 (d, J =0 2.4 Hz, 1H), 8.34 (dd, J 1 = 2.0 Hz, J 2 = 8.0 Hz, 1H), 8.0 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 7.06 (dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, 1H), 3.91 (s, 3H). LC-MS: m/z 310 (M + H) 2+
194	II.8
1 H NMR (400 MHz, DMSO-d6) δ 8.29 (dd, J 1 = 1.6 Hz, J 2 = 4.4 Hz, 1H), 7.95 (dd, J 1 = 2.0 Hz, J 2 = 7.2 Hz, 1H), 6.86 (dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, 1H), 3.82 (s, 3H), 3.42 (s, 4H), 3.29-3.25 (m, 4H).
200, 233, 241, 247	II.9
1 H NMR (400 MHz, DMSO-d6) δ 10.15 (s, 1H), 8.46 (dd, J 1 = 1.4 Hz, J 2 = 4.9 Hz, 1H), 8.28 (dd, J 1 = 1.4 Hz, J 2 = 7.8 Hz, 1H), 8.20 (s, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.27 (t, J = 8.3 Hz, 1H), 7.19 (d, J = 7.8 Hz, 1H), 6.97- 6.94 (m, 1H), 3.91 (s, 3H). LC-MS: m/z 306.9 (M + H) +
218, 385, 386, 389	II.10
1 H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H), 8.44 (dd, J 1 = 1.6 Hz, J 2 = 4.8 Hz, 1H), 8.28 (dd, J 1 = 2.0 Hz, J 2 = 8.0 Hz, 1H), 7.72 (d, J = 9.2 Hz, 2H), 7.49 (d, J = 8.8 Hz, 2H), 6.95- 6.92 (m, 1H), 3.91 (s, 3H). LC-MS: m/z 307.1 (M + H) +
223	II.11
1 H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.56 (d, J = 1.0 Hz, 2H), 8.01 (s, 1H), 7.66-7.60 (m, 1H), 7.34- 7.29 (m, 2H), 7.06-7.03 (m, 1H). LC- MS: m/z 294.0 (M + H) +
242	II.12
1 H NMR (400 MHz, DMSO-d6) δ 9.98 (s, 1H), 8.28-8.26 (m, 2H), 8.06- 8.04 (m, 1H), 7.92-7.89 (m, 1H), 7.72-7.68 (m, 1H), 7.28 (t, J = 0.8 Hz, 1H). LC-MS: m/z 295.0 (M + H) +
243	II.13
1 H NMR (400 MHz, DMSO-d6) δ 9.67 (s, 1H), 8.3 (m, 2H), 7.59 (d, J = 8.8 Hz, 2H), 7.30 (m, 3H), 7.11 (d, J =8.8 Hz, 2H), 6.72 (d, J = 8.9 Hz, 2H), 3.85 (s, 3H).
251	II.14
1 H NMR (400 MHz, DMSO-d6) δ 10.17 (s, 1H), 8.70 (d, J = 1.0 Hz, 1H), 8.38 (d, J = 2.4 Hz, 1H), 8.24 (dd, J 1 = 1.9 Hz, J 2 = 8.8 Hz, 1H), 7.73 (dd, J 1 = 2.4 Hz, J 2 = 8.3 Hz, 1H), 7.62-7.56 (m, 1H), 7.01 (t, J = 1.5 Hz, 1H), 6.88 (d, J = 8.8 Hz, 1H). LC-MS: m/z 295.9 (M + H) 2+
254	II.15
1 H NMR (400 MHz, DMSO-d6) δ 10.38 (s, 1H), 8.49 (dd, J 1 = 1.5 Hz, J 2 = 4.4 Hz, 1H), 8.31 (dd, J 1 = 1.9 Hz, J 2 = 7.8 Hz, 1H), 7.89-7.84 (m, 4H), 7.02-6.99 (m, 1H), 3.92 (s, 3H), 1.54 (s, 9H).
259, 346	II.16
1 H NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.83-7.78 (m, 3H), 7.52 (d, J = 7.3 Hz, 1H), 7.13 (d, J = 8.3 Hz, 1H), 4.37- 4.32 (m, 2H), 1.54 (s, 9H), 1.36 (t, J = 6.8 Hz, 3H).
264	II.17
1 H NMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.15 (dd, J 1 = 1.2 Hz, J 2 = 5.6 Hz, 1H), 7.69-7.66 (m, 2H), 7.59-7.55 (m, 1H), 7.42-7.39 (m, 2H), 6.82 (d, J = 8.0 Hz, 1H), 6.78-6.75 (m, 1H). LC-MS: m/z 249.0 (M + H) +
265	II.18
1 H NMR (400 MHz, DMSO-d6) δ 9.30 (s, 1H), 8.11 (dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.58 (t, J = 6.8 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.09-7.05 (m, 1H), 1.54 (s, 9H). LC-MS: m/z 313.0 (M − H) −
269	II.19
1 H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.56-8.51 (m, 2H), 7.66- 7.64 (m, 2H), 7.54-7.52 (m, 2H), 7.02 (dd J 1 = 5.2 Hz, J 2 = 8.4 Hz, 1H).
274, 285,	II.20
1 H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.83 (d, J = 8.3 Hz, 2H), 7.53-7.44 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H), 6.98 (t, J = 7.8 Hz, 1H), 3.84 (s, 3H), 1.53 (s, 9H). LC-MS: m/z 328.0 (M + H) +
302	II.21
1 H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.41 (dd, J 1 = 2.0 Hz, J 2 = 4.9 Hz, 1H), 8.26 (dd, J 1 = 1.9 Hz, J 2 = 7.8 Hz, 1H), 7.66 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 6.88 (m, 1H), 3.90 (s, 3H), 3.50 (s, 2H), 1.42 (s, 9H). LC-MS: m/z 343.0 (M + H) +
303	II.22
1 H NMR (400 MHz, DMSO-d6) δ 8.93 (s, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.73 (s, 1H), 7.55-7.50 (m, 1H), 7.44 (d, J = 4.4 Hz, 2H), 7.09 (d, J = 8.8 Hz, 2H), 3.84 (s, 3H), 1.53 (s, 9H). LC-MS: m/z 328.0 (M + H) +
327	II.23
1 H NMR (400 MHz, DMSO-d6) δ 9.48 (s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.74 (t, J = 7.6 Hz, 1H), 7.47-7.42 (m, 3H), 7.05 (d, J = 8.4 Hz, 1H), 4.35- 4.30 (m, 2H), 1.35 (t, J = 7.2 Hz, 3H). LC-MS: m/z 321.0 (M + H) +
330	II.24
LC-MS: m/z 288.0 (M − 56H) + ; t-butyl fragment
333, 408	II.25
1 H NMR (400 MHz, DMSO-d6) δ 9.31 (s, 1H), 7.96-7.90 (m, 1H), 7.72 (s, 1H), 7.59-7.57 (m, 1H), 7.50-7.44 (m, 3H), 7.25 (d, J = 8.4 Hz, 1H), 3.82 (s, 3H), 1.50 (s, 9H). LC-MS: m/z 328.2 (M + H) +
334	II.26
1 H NMR (400 MHz, DMSO-d6) δ 7.91 (d, J = 9.3 Hz, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.69 (t, J = 7.8 Hz, 1H), 7.40 (t, J = 7.8 Hz, 1H), 7.20 (d, J = 8.3 Hz, 1H), 6.93 (d, J = 8.8 Hz, 2H), 3.67 (s, 3H), 1.53 (s, 9H).
347	II.27
1 H NMR (400 MHz, DMSO-d6) δ 7.57 (s, 1H), 7.29 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 7.6 Hz, 1H), 7.15-7.12 (m, 2H), 6.97-6.94 (m, 1H), 6.77 (d, J = 8.8 Hz, 2H), 2.17 (s, 3H). LC-MS: m/z 262.0 (M + H) +
651	II.28
LC-MS: m/z 324.05 (M + H) +
638	II.29

Intermediate LC-MS: m/z 410.1 (M + H) 2+

CP	No.	Reactant	Structure	Analytical data
142	II.29	II.4
LC-MS: m/z 408.9 (M + H) +
152	II.30	II.5
LC-MS: m/z 409.9 (M + H) 2+
175	II.31	II.7

Intermediate LC-MS: m/z 362.3 (M + H) +

CP	No.	Reactant	Structure	Analytical data
357	II.32	Int-II
LC-MS: m/z 419.1 (M + H) +
363	II.33	I.1
1 H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 7.6 (s, 1H), 7.33-7.25 (m, 5H), 7.04 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 362.3 (M + H) +
394	II.34
LC-MS: m/z 329.2 (M + H) +
315, 316	II.35	I.1

Intermediate 1 H NMR (400 MHz, DMSO-d6) δ 7.51 (d, J = 8.3 Hz, 2H), 7.24 (d, J = 8.3 Hz, 2H), 3.57 (s, 3H), 3.43 (s, 2H), 2.75-2.67 (m, 1H), 2.60-2.51 (m, 1H), 2.33-2.32 (m, 1H), 2.17- 2.12 (m, 1H), 2.07-2.05 (m, 1H), 1.79-1.77 (m, 1H), 1.67-1.63 (m, 1H), 1.49-1.39 (m, 2H). LC-MS: m/z 314.0 (M + H) 2+

CP	No.	Structure	Analytical data
187	III.1
1 H NMR (400 MHz, DMSO-d6) δ 7.49 (d, J = 7.6 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 3.81 (d, J = 13.6 Hz, 1H), 3.58 (s, 3H), 3.49 (d, J = 12.4 Hz, 1H), 3.27 (dd, J 1 = 5.2 Hz, J 2 = 8.8 Hz, 1H), 2.85-2.80 (m, 1H), 2.38-2.32 (m, 1H), 2.09-2.04 (m, 1H), 1.84-1.71 (m, 3H).
192	III.2
1 H NMR (400 MHz, DMSO-d6) δ 7.62 (s, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.15 (s, 1H), 7.11 (d, J = 8.4 Hz, 2H), 5.58 (s, 2H), 4.25- 4.23 (m, 2H), 2.50 (t, J = 2.0 Hz, 3H). LC- MS: m/z 308.9 (M + H) +
195	III.3
Proceeded with crude/only TLC reference
197	III.4
1 H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 9.2 Hz, 1H), 7.88 (dd, J 1 = 1.6 Hz, J 2 = 10 Hz, 1H), 7.27-7.55 (m, 1H), 7.42-7.34 (m, 1H), 5.26 (d, J = 2.8 Hz, 2H), 4.20-4.14 (m, 2H), 1.25-1.20 (m, 3H). LC-MS: m/z 282.9 (M + H) +
201	III.5
1 H NMR (400 MHz, DMSO-d6) δ 8.65 (s, 1H), 7.98 (s, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 5.4 (s, 2H). LC-MS: m/z 238 (M + H) +
202	III.6
1 H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.29 (s, 1H), 7.43-7.42 (m, 1H), 7.37- 7.35 (m, 1H), 7.22-7.19 (m, 1H), 5.47 (s, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 372.1 (M + H) +
210	III.7
1 H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 8.03 (s, 1H), 7.74 (d, J = 8.4 Hz, 1H), 7.29 (dd, J 1 = 1.6 Hz, J 2 = 8.4 Hz, 1H), 5.38 (s, 2H), 4.14 (q, J = 14 Hz, 2H), 1.20 (t, J = 7.6 Hz, 3H). LC-MS: m/z 285.0 (M + H) 2+
213	III.8
1 H NMR (400 MHz, DMSO-d6) δ 8.47 (s, 1H), 7.87 (s, 1H), 7.56-7.54 (dd, J 1 = 0.8 Hz, J 2 = 6.4 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 5.35 (s, 2H), 4.23-4.18 (m, 2H), 1.26 (t, J = 7.6 Hz, 3H). LC-MS: m/z 309.0 (M + H) +
214	III.9
LC-MS: m/z 306.0 (M + H) +
217	III.10
1 H NMR (400 MHz, DMSO-d6) δ 7.51-7.49 (dd, J 1 = 2.0 Hz, J 2 = 6.8 Hz, 2H), 7.29 (t, J = 2.0 Hz, 1H), 7.0 (d, J = 8.0 Hz, 2H), 6.91- 6.9 (dd, J 1 = 2.0 Hz, J 2 = 4.0 Hz, 1H), 6.20- 6.18 (dd, J 1 = 1.2 Hz, J 2 = 4.0 Hz, 1H), 5.51 (s, 2H), 4.16-4.11 (m, 2H), 1.12 (t, J = 6.8 Hz, 3H). LC-MS: m/z 308.0 (M + H) +
219	III.11
1 H NMR (400 MHz, DMSO-d6) δ 7.70 (s, 1H), 7.51 (d, J = 2.0 Hz, 1H), 7.36 (s, 1H), 7.18-7.14 (m, 1H), 6.3 (s, 1H), 5.14 (s, 2H), 4.17-4.12 (m, 2H), 1.24-1.19 (m, 3H). LC- MS: m/z 282.1 (M + H) +
220	III.12
1 H NMR (400 MHz, DMSO-d6) δ 8.01 (d, J = 0.8 Hz, 1H), 7.92 (s, 1H), 7.58 (s, 1H), 7.52 (d, J = 6.0 Hz, 1H), 7.34-7.33 (m, 2H), 5.25 (s, 2H), 3.72 (s, 3H). LC-MS: m/z 295.0 (M + H) +
221	III.13
1 H NMR (400 MHz, DMSO-d6) δ 8.19 (s, 1H), 7.71 (d, J = 1.2 Hz, 1H), 7.49-7.47 (dd, J 1 = 0.8 Hz, J 2 = 7.6 Hz, 1H), 7.37 (s, 1H), 7.3 (t, J = 8.0 Hz, 1H), 7.13 (d, J = 7.6 Hz, 1H), 5.52 (s, 2H), 3.73 (s, 3H). LC-MS: m/z 295.1 (M + H) +
227	III.14
1 H NMR (400 MHz, DMSO-d6) δ 7.74 (d, J = 1.2 Hz, 1H), 7.39-7.37 (m, 2H), 7.23 (dd, J 1 = 1.6 Hz, J 2 = 8.8 Hz, 1H), 6.45 (d, J = 3.2 Hz, 1H), 5.13 (s, 2H), 4.13 (q, J = 14.4 Hz, 2H), 1.2 (t, J = 7.2 Hz, 3H). LC-MS: m/z 282.0 (M + H) +
250	III.15

Intermediate LC-MS: m/z 345.0 (M + H) 2+

CP	No.	Structure	Analytical data
178	IV.1
LC-MS: m/z 387.4 (M + H) +
239	IV.2
1 H NMR (400 MHz, DMSO-d6) δ6 13.10 (bs, 1H), 10.63 (s, 1H), 7.58 (d, J = 5.4 Hz, 2H), 7.47 (d, J = 6.8 Hz, 2H), 1.44 (s, 4H). LC-MS: m/z 284.0 (M + H) +
291	IV.3
LC-MS: m/z 345.0 (M + H) +
317	IV.4
Proceeded with crude/only TLC reference
328	IV.5

Intermediate LC-MS: m/z 367.9 (M + H) +

CP	No.	Reactant	Structure	Analytical data
241	V.1	II.9
1 H NMR (400 MHz, DMSO- d6) δ8.49-8.48 (m, 1H), 7.89- 7.87 (m, 1H), 7.21-7.14 (m, 2H), 7.11-7.07 (m, 2H), 6.94- 6.91 (m, 1H), 3.43 (s, 3H), 3.32 (s, 3H). LC-MS: m/z 321.0 (M + H) +
239	V.2	IV.2
1 H NMR (400 MHz, DMSO- d6) δ 7.6 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 6.8 Hz, 2H), 3.39 (s, 3H), 3.19 (s, 3H), 1.38 (m, 2H), 1.07 (s, 2H).
252	V.3	II.4
1 H NMR (400 MHz, DMSO- d6) δ 8.19 (d, J = 1.6 Hz, 1H), 7.92 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.72-7.63 (m, 1H), 7.57 (s, 1H), 7.52-7.47 (m, 2H), 3.62 (s, 3H), 3.30 (s, 3H). LC-MS: m/z 323.9 (M + H) 2+
255	V.4	II.20
1 H NMR (400 MHz, DMSO- d6) δ 7.90-7.80 (m, 1H), 7.80- 7.70 (m, 1H), 7.65 (d, J = 9.6 Hz, 2H), 7.50-7.40 (m, 2H), 6.48 (d, J = 9.2 Hz, 2H), 3.56 (s, 3H), 3.25 (s, 3H), 1.50 (s, 9H). LC-MS: m/z 342.1 (M + H) +
258	V.5	II.15
1 H NMR (400 MHz, DMSO- d6) δ 8.57 (dd, J 1 = 2.0 Hz, J 2 = 4.9 Hz, 1H), 8.00 (dd, J 1 = 1.9 Hz, J 2 = 7.8 Hz, 1H), 7.73 (d, J = 9.3 Hz, 2H), 7.23 (m, 1H), 6.89 (d, J = 8.8 Hz, 2H), 3.45 (s, 3H), 3.32 (s, 3H), 1.52 (s, 9H).
317	V.6	IV.4
LC-MS: m/z 344.9 (M + H) +2
353	V.7	II.25
1 H NMR (400 MHz, DMSO- d6) δ 7.79 (d, J = 7.2 Hz, 1H), 7.68 (t, J = 8.0 Hz, 1H), 7.43- 7.36 (m, 2H), 7.25-7.21 (m, 2H), 7.04 (s, 1H), 6.75 (d, J = 6.8 Hz, 1H), 3.54 (s, 3H), 3.22 (s, 3H), 1.49 (s, 9H). LC- MS: m/z 342.1 (M + H) +
340	V.8	Int-IV
1 H NMR (400 MHz, DMSO- d6) δ 7.67 (d, J = 7.6 Hz, 1H), 7.60-7.58 (m, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.38-7.36 (m, 3H), 7.08 (d, J = 8.0 Hz, 2H), 3.78 (s, 3H), 3.29 (s, 3H). LC- MS: m/z 348.0 (M + H) +
357	V.9	II.32
1 H NMR (400 MHz, DMSO- d6) δ 7.69 (d, J = 8.0 Hz, 1H), 7.65-7.60 (m, 1H), 7.39-7.30 (m, 3H), 7.15-7.07 (m, 3H), 6.94 (d, J = 8.8 Hz, 2H), 6.76 (d, J = 8.0 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 3.56 (s, 3H), 3.22 (s, 3H), 3.18 (s, 3H), 2.03 (s, 9H), 1.64 (s, 6H).
318	V.10	Int-II

Inter- medi- ate 1 H NMR (400 MHz, DMSO-d6) δ 10.16 (s, 1H), 8.41 (s, 1H), 8.34 (d, J = 8.8 Hz, 1H), 8.05 (d, J = 5.6 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.43- 7.39 (m, 2H), 7.32-07.30 (m, 1H), 7.08 (t, J = 8.0 Hz, 1H), 6.32 (d, J = 6.0 Hz, 1H), 3.83 (s, 3H), 2.07 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H).

CP	No.	Reactant	Structure	Analytical data
64	VI.1	Int-II & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 7.86 (dd, J 1 = 2.0 Hz, J 2 = 9.8 Hz, 1H), 7.54 (s, 1H), 7.36-7.34 (m, 2H), 7.20 (s, 2H), 7.13 (d, J = 8.8 Hz, 2H), 6.06 (s, 1H), 7.03 (d, J = 4.9 Hz, 1H), 7.01 (s, 1H), 6.72 (t, J = 6.8 Hz, 1H),
				3.85 (s, 3H), 2.05 (bs,
				3H), 1.84 (bs, 6H), 1.31
				(bs, 6H). LC-MS: m/z
				487.2 (M + H) +
93	VI.2	Int-II & I.33
1 H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.89-7.87 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 1H), 7.71 (s, 1H), 7.42- 7.23 (m, 6H), 7.21-7.19 (m, 4H), 7.15-7.07 (m, 3H), 6.74 (t, J = 7.3 Hz, 1H), 3.86 (s, 3H), 3.06- 3.02 (m, 1H), 1.14 (d, J = 12.8 Hz, 6H). LC-
				MS: m/z 471.1 (M + H) +
113	VI.3	Int-II & I.5
1 H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.89-7.87 (dd, J 1 = 1.5 Hz, J 2 = 7.9 Hz, 1H), 7.72 (s, 1H), 7.38- 7.37 (m, 2H), 7.29-7.17 (m, 10H), 7.08 (d, J = 8.3 Hz, 1H), 6.75 (d, J = 8.3 Hz, 1H), 3.86 (s, 3H),
				2.27 (s, 3H). LC-MS:
				m/z 442.4 (M + H) +
115	VI.4	Int-II & I.6
1 H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 7.96 (d, J = 8.3 Hz, 1H), 7.73 (d, J = 7.9 Hz, 1H), 7.54 (d, J = 7.3 Hz, 1H), 7.48-7.45 (m, 1H), 7.34-7.32 (m, 1H), 7.31 (d, J = 8.8 Hz, 1H), 7.25 (d, J = 3.9 Hz, 1H), 7.24-
				7.18 (m, 6H), 7.10 (d,
				J = 9.3 Hz, 1H), 6.72-
				6.68 (m, 1H), 6.18 (s,
				1H), 3.91 (s, 3H). LC-
				MS: m/z 497.1 (M + H) +
116	VI.5	Int-II & I.7
1 H NMR (400 MHz, DMSO-d6) δ 9.20 (s, 1H), 8.34 (s, 1H), 7.87 (d, J = 6.8 Hz, 1H), 7.51 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 7.45 (t, J = 6.4 Hz, 1H), 7.36 (t, J = 7.3 Hz, 1H), 7.30-7.25 (m, 3H), 7.17 (s, 4H), 7.11
				(d, J = 8.8 Hz, 2H), 7.04
				(d, J = 8.4 Hz, 1H), 6.73
				(t, J = 7.3 Hz, 1H), 3.85
				(s, 3H).
118	VI.6	Int-II & I.8
1 H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.89-7.87 (dd, J 1 = 1.5 Hz, J 2 = 7.9 Hz, 1H), 7.71 (s, 1H), 7.53 (d, J = 1.9 Hz, 1H), 7.41- 7.36 (m, 1H), 7.34-7.29 (dd, J 1 = 1.9 Hz, J 2 = 8.3 Hz, 3H), 6.24 (d, J = 8.3 Hz, 1H), 7.21-7.15 (m, 4H), 7.09 (t, J = 9.3 Hz,
				2H), 7.01 (t, J = 7.4 Hz,
				1H), 6.76-6.72 (dd,
				J 1 = = 1.0 Hz, J 2 = 8.3 Hz,
				1H), 3.86 (s, 3H), 3.79
				(s, 3H). LC-MS: m/z
				458.3 (M + H) +
121	VI.7	Int-II & I.9
1 H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.91-7.87 (m, 1H), 7.69 (s, 1H), 7.50 (d, J = 8.8 Hz, 1H), 7.38- 7.36 (m, 1H), 7.30-7.06 (m, 8H), 6.99-6.96 (dd, J 1 = 2.0 Hz, J 2 = 8.3 Hz, 1H), 6.88-6.80 (m, 1H),
				6.74 (t, J = 6.8 Hz, 1H),
				3.86 (s, 3H), 2.03 (s,
				6H). LC-MS: m/z 457.1
				(M + H) +
122	VI.8	Int-II & I.10
1 H NMR (400 MHz, DMSO-d6) δ 9.24 (s, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.78 (s, 1H), 7.55 (d, J = 7.3 Hz, 1H), 7.49 (s, 1H), 7.43-7.37 (m, 4H), 7.26 (s, 2H), 7.21 (s, 4H), 7.1 (d, J = 8.3 Hz, 1H), 6.75 (t, J = 7.3
				Hz, 1H), 3.86 (s, 3H).
				LC-MS: m/z 463.1
				(M + H) +
125	VI.9	Int-I
LC-MS: m/z 396.3 (M + H) +
126	VI.10	Int-II & I.11
1 H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 7.87 (d, J = 1.5 Hz, 1H), 7.62 (s, 1H), 7.35 (t, J = 6.8 Hz, 1H), 7.29- 7.06 (m, 11H), 6.73 (t, J = 7.3 Hz, 1H), 3.86 (s, 3H), 2.05 (s, 3H), 1.90 (s, 3H). LC-MS: m/z
				457.1 (M + H) +
135	VI.11	Int-II
1 H NMR (400 MHz, DMSO-d6) δ 9.39 (s, 1H), 8.26 (s, 1H), 7.99- 7.92 (m, 4H), 7.70 (d, J = 8.4 Hz, 2H), 7.55-7.46 (m, 4H), 7.38-7.33 (m, 2H), 6.89 (t, J = 8.0 Hz, 1H), 3.87 (s, 3H). LC- MS: m/z 387.0 (M + H) +
140	VI.12	Int-II & I.12
1 H NMR (400 MHz, DMSO-d6) δ 9.19 (s, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.65 (s, 1H), 7.43 (s, 1H), 7.36 (t, J = 6.8 Hz, 1H), 7.27 (d, J = 6.8 Hz, 1H), 7.19-7.03 (m, 6H), 6.74 (t, J = 7.3 Hz, 1H), 5.92 (s, 1H), 3.85 (s, 3H), 2.35 (m, 2H), 1.75 (m, 4H), 0.99 (m,
				6H). LC-MS: m/z 460.3
				(M + H) +
141	VI.13	II.28 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 2H), 8.02 (s, 1H), 7.87 (dd, J 1 = 1.2 Hz, J 2 = 4.8 Hz, 1H), 7.55-7.53 (m, 1H), 7.41-7.38 (m, 2H), 7.24-7.19 (m, 2H), 7.12- 7.10 (m, 1H), 3.74 (s, 3H), 2.05 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H),
				1.34 (s, 9H).
142	VI.14	II.29 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.28 (s, 1H), 8.05 (d, J = 1.2 Hz, 1H), 7.87- 7.85 (m, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.58- 7.54 (m, 1H), 7.41-7.38 (m, 2H), 7.32-7.28 (m, 2H), 3.77 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H),
				1.73 (s, 6H). LC-MS:
				m/z 589.1 (M + H) +
144, 152	VI.15	II.30 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 7.96 (d, J = 3.2 Hz, 1H), 7.84 (dd, J 1 = 1.2 Hz, J 2 = 7.6 Hz, 1H), 7.79 (s, 1H), 7.56 (t, J = 2.0 Hz, 1H), 7.47- 7.46 (m, 1H), 7.41-7.35 (m, 3H), 7.27 (dd, J 1 = 1.2
				Hz, J 2 = 8.0 Hz, 1H), 7.21
				(d, J = 2.8 Hz, 1H), 7.15
				(d, J = 8.0 Hz, 1H), 3.75
				(s, 3H), 2.04 (s, 3H),
				1.82 (s, 6H), 1.72 (s,
				6H), 1.32 (s, 9H). LC-
				MS: m/z 588.1 (M + H) +
158	VI.16	II.6 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 8.17 (s, 1H), 7.37-7.04 (m, 12H), 3.82 (bs, 3H), 2.04 (s, 3H), 1.85 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 487.1 (M + H) +
170	VI.17	I.4
1 H NMR (400 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.41 (dd, J 1 = 2.0 Hz, J 2 = 4.4 Hz, 1H), 8.35 (d, J = 8.8 Hz, 1H), 8.30 (dd, J 1 = 2.0 Hz, J 2 = 8.0 Hz, 1H), 7.56 (d, J = 2.0 Hz, 1H), 7.37 (dd, J 1 = 1.6 Hz, J 2 = 8.8 Hz, 1H), 6.95 (dd, J 1 = 4.4 Hz, J 2 = 8.0 Hz, 1H), 3.92 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s,
				6H).
173	VI.18	Int-I
1 H NMR (400 MHz, DMSO-d6) δ 7.43 (d, J = 10.4 Hz, 2H), 7.32 (d, J = 2.0 Hz, 1H), 7.18- 7.17 (m, 2H), 7.08 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 4.1 (m, 1H), 3.61 (d, J = 2.4 Hz,
				4H), 2.90 (m, 2H), 2.80
				(m, 1H), 2.05 (s, 3H),
				1.83 (s, 6H), 1.73 (s,
				6H), 1.34-1.30 (m, 15H).
175	VI.19	II.31 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 8.55 (d, J = 2.8 Hz, 1H), 8.28 (d, J = 6.0 Hz, 1H), 7.92 (s, 1H), 7.77 (s, 1H), 7.46- 7.42 (m, 3H), 7.36 (d, J = 1.6 Hz, 1H), 7.23 (dd, J 1 = 2.0 Hz, J 2 = 8.8 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 3.78 (s, 3H), 2.04
				(s, 3H), 1.83 (s, 6H),
				1.72 (s, 6H), 1.34 (s,
				9H). LC-MS: m/z 589.1
				(M + H) +
177	VI.20	I.15
1 H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.41 (dd, J 1 = 2.0 Hz, J 2 = 4.9 Hz, 1H), 8.26 (dd, J 1 = 1.9 Hz, J 2 = 7.8 Hz, 1H), 7.68 (d, J = 6.8 Hz, 1H), 7.50 (s, 1H), 7.26 (t, J = 7.8 Hz, 1H), 7.05 (d, J = 7.9 Hz, 1H),
				6.88-6.85 (m, 1H), 3.90
				(s, 3H), 2.06 (s, 3H),
				1.88 (s, 6H), 1.74 (s,
				6H). LC-MS: m/z 363.1
				(M + H) +
185	VI.21	IIIa & Int-I
LC-MS: m/z 464.3 (M + H) +
187	VI.22	III.1 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 7.77 (s, 1H), 7.33 (s, 1H), 7.18 (s, 2H), 7.12 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.78-3.72 (m, 1H), 3.56 (s, 3H), 3.43- 3.39 (m, 1H), 3.25-3.21 (m, 1H), 2.89-2.80 (m, 1H), 2.38-2.32 (m, 1H),
				2.09-2.01 (m, 4H), 1.89-
				1.81 (m, 7H), 1.82-1.69
				(m, 8H).
192	VI.23	III.2 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 7.61 (s, 1H), 7.57 (s, 1H), 7.34 (s, 1H), 7.19 (d, J = 0.8 Hz, 2H), 7.10-7.08 (m, 3H), 6.94 (d, J = 8.4 Hz, 2H), 5.49 (s, 2H), 4.31- 4.25 (m, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.28 (t, J = 6.8
				Hz, 3H).
197	VI.24	III.4 & Int-I
LC-MS: m/z 464.1 (M + H) +
199	VI.25	IIIb & Int-I
LC-MS: m/z 464.1 (M + H) +
200	VI.26	II.9 & I.15
1 H NMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H), 8.38 (t, J = 1.4 Hz, 1H), 8.25 (d, J = 7.8 Hz, 1H), 8.12 (s, 1H), 7.66 (s, 1H), 7.19-7.11 (m, 3H), 7.02 (d, J = 7.8 Hz, 1H), 6.95 (d, J = 7.8 Hz, 1H), 6.89-6.83 (m, 2H),
				6.70 (d, J = 7.8 Hz, 1H),
				3.89 (s, 3H), 2.04 (s,
				3H), 1.75 (s, 6H), 1.72
				(s, 6H). LC-MS: m/z
				454.3 (M + H) +
210	VI.27	III.7 & Int-I
1 H NMR (400 MHz, DMSO-d6) +67 7.91 (s, 1H), 7.77 (s, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.37 (d, J = 2.0 Hz, 1H), 7.32 (d, J = 8.8 Hz, 1H), 7.23- 7.21 (m, 1H), 6.99 (s, 1H), 6.92 (d, J = 8.0 Hz, 1H), 5.19 (s, 2H), 4.12 (q, J = 14 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H), 1.17 (t, J = 6.8 Hz, 3H). LC-MS: m/z 464.2 (M + H) +
213	VI.28	III.8 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 8.38 (s, 1H), 7.85 (s, 1H), 7.64 (s, 1H), 7.34 (s, 1H), 7.21 (s, 2H), 7.17 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 8.4 Hz, 2H), 5.24 (s, 2H), 4.23-4.17 (q, J = 3.6 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.25 (t, J = 7.2 Hz,
				3H).
214	VI.29	III.9 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 8.69-8.68 (m, 1H), 8.15-8.13 (m, 1H), 7.41-7.39 (m, 2H), 7.30 (d, J = 2.0 Hz, 1H), 7.15-7.14 (m, 2H), 7.12- 7.03 (m, 3H), 6.94-6.89 (m, 1H), 4.34 (s, 2H), 3.83 (s, 3H), 2.03 (s, 3H), 1.81 (s, 6H), 1.71
				(s, 6H). LC-MS: m/z
				487.2 (M + H) +
217	VI.30	III.10 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 7.54 (s, 1H), 7.32 (s, 1H), 7.24 (t, J = 2.0 Hz, 1H), 7.17 (s, 2H), 7.01 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.88-6.87 (m, 1H), 6.15-6.14 (m, 1H), 5.43 (s, 2H), 4.20-4.15 (q, J = 7.2 Hz, 2H), 2.04
				(s, 3H), 1.82 (s, 6H),
				1.72 (s, 6H), 1.23 (t,
				J = 6.8 Hz, 3H). LC-MS:
				m/z 489.2 (M + H) +
218	VI.31	Int-V & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 8.36-8.34 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 7.71-7.67 (m, 1H), 7.5 (s, 1H), 7.32 (d, J = 1.6 Hz, 1H), 7.22- 7.19 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 6.95- 6.80 (m, 5H), 3.37 (s,
				3H), 3.29 (s, 3H), 2.04
				(s, 3H), 1.83 (s, 6H),
				1.72 (s, 6H). LC-MS:
				m/z 502.2 (M +H) +
219	VI.32	III.11 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 7.44 (d, J = 8.0 Hz, 1H), 7.29 (s, 2H), 7.20 (d, J = 2.8 Hz, 1H), 7.09-7.06 (m, 3H), 6.87 (dd, J 1 = 1.6 Hz, J 2 = 8.4 Hz, 1H), 6.37 (d, J = 2.8 Hz, 1H), 5.11 (s, 2H), 4.16-4.12 (m, 2H), 2.03 (s, 3H), 1.81 (d,
				J = 2.8 Hz, 6H), 1.71 (s,
				6H), 1.19 (t, J = 7.2 Hz,
				3H). LC-MS: m/z 463.2
				(M + H) +
220	VI.33	III.12 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 7.93 (d, J = 0.8 Hz, 1H), 7.85 (d, J = 0.8 Hz, 1H), 7.67 (s, 1H), 7.34 (s, 1H), 7.19 (t, J = 7.2 Hz, 3H), 6.89 (d, J = 8.4 Hz, 2H), 6.74 (d, J = 8.0 Hz, 1H), 5.17 (s, 2H), 3.72 (s, 3H), 2.05 (s, 3H), 1.83 (s,
				6H), 1.73 (s, 6H). LC-
				MS: m/z 476.2 (M + H) +
221	VI.34	III.13 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 8.10 (s, 1H), 7.69 (s, 1H), 7.64 (s, 1H), 7.34 (d, J = 2.0 Hz, 1H), 7.21-7.13 (m, 3H), 6.85 (d, J = 8.4 Hz, 1H), 6.77 (s, 1H), 6.61 (d, J = 8.0 Hz, 1H), 5.45 (s, 2H), 3.73 (s, 3H),
				2.05 (s, 3H), 1.84 (s,
				6H), 1.73 (s, 6H). LC-
				MS: m/z 476.3 (M + H) +
227	VI.35	III.14 & Int-I
LC-MS: m/z 463.2 (M + H) +
233	VI.36	II.9 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.38 (dd, J 1 = 2.0 Hz, J 2 = 4.9 Hz, 1H), 8.24 (dd, J 1 = 2.0 Hz, J 2 = 7.8 Hz, 1H), 7.56 (s, 1H), 7.48 (s, 1H), 7.32 (m, 2H), 7.23 (m, 1H), 7.14 (m, 2H), 6.88 (m, 1H), 6.68 (m, 1H), 3.90 (s,
				3H), 2.08 (s, 3H), 1.85
				(s, 6H), 1.72 (s, 6H).
				LC-MS: m/z 488.2
				(M + H) +
239	VI.37	V.2 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 7.74 (s, 1H), 7.36 (s, 1H), 7.23 (m, 2H), 7.1 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.41 (s, 3H), 3.15 (s, 3H), 2.05 (bs, 3H), 1.84 (bs, 6H), 1.72 (bs, 6H), 1.3 (m, 2H), 1.05 (m, 2H). LC-MS:
				m/z 493.2 (M + H) +
241	VI.38	V.1 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 8.39 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 7.79 (dd, J 1 = 2.0 Hz, J 2 = 8.0 Hz, 1H), 7.54 (s, 1H), 7.32 (d, J = 2.0 Hz, 1H), 7.25 (d, J = 8.4 Hz, 1H), 7.18 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 1H), 7.10 (t, J = 8.0 Hz,
				1H), 6.95 (dd, J 1 = 3.2
				Hz, J 2 = 7.6 Hz, 1H), 6.66
				(dd, J 1 = 2.0 Hz, J 2 = 8.4
				Hz, 1H), 6.60 (t, J = 2.0
				Hz, 1H), 6.46 (dd,
				J 1 = 1.6 Hz, J 2 = 7.6 Hz,
				1H), 3.39 (s, 3H), 3.31
				(s, 3H), 2.04 (s, 3H),
				1.82 (s, 6H), 1.72 (s,
				6H). LC-MS: m/z 502.1
				(M + H) +
243	VI.39	II.13 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 8.29 (dd, J 1 = 2.0 Hz, J 2 = 4.9 Hz, 1H), 8.25 (dd, J 1 = 2.0 Hz, J 2 = 7.3 Hz, 1H), 7.54 (s, 1H), 7.34 (s, 1H), 7.22 (m, 3H), 7.04 (d, J = 9.3 Hz, 2H), 6.99 (d, J = 9.2 Hz, 2H), 3.86 (s, 3H), 2.05 (s, 3H), 1.84
				(s, 6H), 1.72 (s, 6H).
				LC-MS: m/z 489.0
				(M + H) +
245	VI.40	Int-V & I.1
1 H NMR (400 MHz, DMSO-d6) δ 8.33 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 7.97 (s, 1H), 7.65 (dd, J 1 = 2.0 Hz, J 2 = 7.2 Hz, 1H), 7.2 (d J = 8.8 Hz, 2H), 6.97-6.94 (m, 4H), 6.89-6.82 (m, 3H), 3.35 (s, 3H), 3.27 (s, 3H), 2.04 (s, 3H), 1.82
				(s, 6H), 1.72 (s, 6H).
				LC-MS: m/z 468.1
				(M + H) +
247	VI.41	II.9 & I.1
1 H NMR (400 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.41 (dd, J 1 = 2.0 Hz, J 2 = 4.4 Hz, 1H), 8.25 (dd, J 1 = 1.9 Hz, J 2 = 7.8 Hz, 1H), 8.05 (s, 1H), 7.56 (t, J = 2.0 Hz, 1H), 7.24 (d, J = 8.4 Hz, 2H), 7.15 (t, J = 7.8 Hz, 1H), 7.13 (d, J = 7.8 Hz, 2H), 7.06 (d, J = 8.8 Hz, 1H),
				6.88 (m, 1H), 6.71 (dd,
				J 1 = 1.5 Hz, J 2 = 7.8 Hz,
				1H), 3.89 (s, 3H), 2.04
				(bs, 3H), 1.84 (s, 6H),
				1.73 (s, 6H).
250	VI.42	III.15 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 7.48 (s, 1H), 7.33 (s, 1H), 7.19 (d, J = 1.0 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 3.57 (s, 3H), 3.37 (s, 2H), 2.80-2.78 (m, 1H), 2.64- 2.61 (m, 1H), 2.10-1.99 (m, 5H), 1.83-1.72 (m,
				14H), 1.63-1.62 (m, 1H),
				1.47-1.40 (m, 2H). LC-
				MS: m/z 493.1 (M + H) +
252	VI.43	V.3 & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 8.04 (s, 1H), 7.94 (d, J = 1.6 Hz, 1H), 7.77 (dd, J 1 = 1.2 Hz, J 2 = 7.6 Hz, 1H), 7.68-7.64 (m, 2H), 7.48 (d, J = 1.6 Hz, 1H), 7.43- 7.35 (m, 2H), 7.30 (d, J = 2.4 Hz, 1H), 7.18 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz,
				1H), 3.55 (s, 3H), 3.31
				(s, 3H), 2.04 (s, 3H),
				1.82 (s, 6H). LC-MS:
				m/z 503.1 (M + H) +
276, 293	VI.44	Int-II
1 H NMR (400 MHz, DMSO-d6) δ 9.23 (s, 1H), 8.69 (s, 1H), 7.88 (dd, J 1 = 1.4 Hz, J 2 = 7.8 Hz, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.41-7.37 (m, 1H), 7.23-7.17 (m, 4H), 7.10 (d, J = 7.9 Hz, 1H), 7.02 (d, J = 8.8 Hz, 2H),
				6.77-6.73 (m, 1H), 3.75
				(s, 3H), 1.51 (s, 9H).
277	VI.45	Int-II & I.16
1 H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.24 (s, 1H), 7.87 (dd, J 1 = 1.2 Hz, J 2 = 7.6 Hz, 1H), 7.40-7.28 (m, 3H), 7.20-7.10 (m, 10H), 7.02 (d, J = 8.4 Hz, 1H), 6.71 (t, J = 7.6 Hz, 1H), 3.85 (s, 3H), 3.11-3.07 (m, 1H), 1.13 (d, J = 2.8 Hz, 6H). LC-MS: m/z
				437.1 (M + H) +
287	VI.46	Int-II & I.17
1 H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.07 (s, 1H), 7.86 (dd, J 1 = 1.2 Hz, J 2 = 7.6 Hz, 1H), 7.37-7.33 (m, 1H), 7.15-7.06 (m, 3H), 7.04-6.98 (m, 2H), 6.72- 6.68 (m, 1H), 3.85 (s, 3H), 3.40 (s, 3H), 2.36-
				2.32 (m, 5H), 1.43-1.30
				(m, 5H), 1.29-1.21 (m,
				5H), 0.84 (t, J = 7.2 Hz,
				6H). LC-MS: m/z 460.1
				(M + H) +
291	VI.47	IV.3 & I.1
1 H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H), 7.87 (d, J = 7.2 Hz, 1H), 7.7-7.65 (m, 3H), 7.32-7.28 (m, 3H), 7.17- 7.13 (m, 4H), 3.94 (s, 3H), 3.8 (s, 3H), 2.06 (s, 3H), 1.83 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 492.1 (M + H) +
292	VI.48	Int-II & I.19
1 H NMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.11 (s, 1H), 7.86 (dd, J 1 = 1.5 Hz, J 2 = 7.8 Hz, 1H), 7.33 (t, J = 1.5 Hz, 1H), 7.15-7.07 (m, 8H), 7.02-6.98 (m, 3H), 6.72-6.65 (m, 4H), 3.85 (s, 3H), 3.57 (t, J = 7.3
				Hz, 2H), 1.58-1.51 (m,
				2H), 1.36-1.30 (m, 2H),
				0.88 (t, J = 7.3 Hz, 3H).
				LC-MS: m/z 466.1
				(M + H) +
295	VI.49	Int-II & I.2
1 H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 1H), 8.02 (s, 1H), 7.86 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.35 (t, J = 8.4 Hz, 1H), 7.21 (d, J = 8.8 Hz, 2H), 7.12-7.04 (m, 4H), 7.01-7.69 (m, 3H), 6.69 (t, J = 7.2 Hz, 1H), 3.85 (s, 3H), 2.13-2.12
				(m, 1H), 1.66 (s, 2H),
				1.50-1.32 (m, 8H), 1.17
				(s, 2H), 0.85 (s, 6H).
				LC-MS: m/z 481.0
				(M + H) +
309	VI.50	V.10 & I.21
1 H NMR (400 MHz, DMSO-d6) δ 7.8 (d, J = 7.6 Hz, 1H), 7.71- 7.61 (m, 1H), 7.44-7.35 (m, 6H), 7.28 (d, J = 8.4 Hz, 2H), 6.50 (d, J = 8.4 Hz, 2H), 3.56 (s, 3H), 3.23 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 476.1 (M + H) +
317	VI.51	V.6 & I.1
1 H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H), 7.84 (d, J = 7.6 Hz, 1H), 7.78-7.71 (m, 3H), 7.35-7.29 (m, 3H), 7.19- 7.13 (m, 4H), 3.91 (s, 3H), 3.89 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 492.3 (M + H) +
318	VI.52	V.10 & I.22
1 H NMR (400 MHz, DMSO-d6) δ 7.50-7.46 (m, 2H), 7.27 (d, J = 8.8 Hz, 2H), 7.19-7.17 (m, 1H), 7.08 (t, J = 7.6 Hz, 1H), 6.80 (d, J = 8.8 Hz, 2H), 6.64 (d, J = 8.8 Hz, 2H), 6.37 (d, J = 8.8 Hz,
				2H), 5.09-5.06 (m, 1H),
				4.23-4.20 (m, 2H), 3.64-
				3.61 (m, 2H), 3.45 (s,
				3H), 3.15 (s, 3H), 2.04
				(s, 3H), 1.83 (s, 6H),
				1.72 (s, 6H). LC-MS:
				m/z 523.3 (M + H) +
323	VI.53	Int-II & I.26
1 H NMR (400 MHz, DMSO-d6) δ 9.11 (s, 1H), 7.86-7.83 (m, 2H), 7.34 (t, J = 7.6 Hz, 1H), 7.07 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 6.96-6.92 (m, 3H), 6.85 (d, J = 8.8 Hz, 2H), 6.68 (t, J = 7.2 Hz, 1H), 3.85
				(s, 3H), 3.48 (s, 2H),
				1.99 (s, 3H), 1.74-1.63
				(m, 13H). LC-MS: m/z
				483.3 (M + H) +
327	VI.54	II.23 & I.16
1 H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.04 (s, 1H), 7.72- 7.67 (m, 3H), 7.37 (t, J = 6.4 Hz, 2H), 7.29 (t, J = 6.4 Hz, 1H), 7.18 (t, J = 6.8 Hz, 1H), 7.11- 6.97 (m, 8H), 4.34-4.29 (m, 2H), 3.13-3.08 (m, 1H), 1.34 (t, J = 7.2 Hz, 3H), 1.12 (d, J = 6.8 Hz,
				6H). LC-MS: m/z 452.3
				(M + H) +
328	VI.55	IV.5 & I.1
1 H NMR (400 MHz, DMSO-d6) δ 6 8.44 (s, 1H), 7.93-7.91 (m, 1H), 7.72-7.67 (m, 1H), 7.45 (t, J = 2.0 Hz, 1H), 7.4 (t, J = 7.6 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.28- 7.27 (m, 2H), 7.23-7.17 (m, 2H), 7.12-7.1 (m, 2H), 3.94 (s, 3H), 3.78 (s, 3H), 2.08 (s, 3H), 1.84 (s, 6H), 1.72 (s,
				6H). LC-MS: m/z 492.3
				(M + H) +
337	VI.56	V.10 & I.27
LC-MS: m/z 536.3 (M + H) +
340	VI.57	V.8 & I.1
1 H NMR (400 MHz, DMSO-d6) δ 8.23 (bs, 1H), 7.70-7.59 (m, 2H), 7.47 (d, J = 7.2 Hz, 1H), 7.4-7.3 (m, 1H), 7.23 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.0 Hz, 4H), 6.72 (bs, 2H), 3.73 (s, 3H), 3.28 (s, 3H), 2.04 (s, 3H),
				1.83 (s, 6H), 1.72 (s,
				6H). LC-MS: m/z 495.3
				(M + H) +
349	VI.58	Int-IV & I.4
1 H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 8.64 (d, J = 8.3 Hz, 1H), 8.24 (s, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.64- 7.62 (m, 1H), 7.60 (s, 1H), 7.38-7.37 (m, 2H), 7.21-7.19 (m, 1H), 6.95 (d, J = 8.3 Hz, 2H), 3.91
				(s, 3H), 2.07 (s, 3H),
				1.88 (s, 6H), 1.74 (s,
				6H). LC-MS: m/z 561.2
				(M + H) 2+
350	VI.59	Int-IV & Int-I
1 H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 8.65-8.63 (dd, J 1 = 1.2 Hz, J 2 = 8.4 Hz, 1H), 8.35 (s, 1H), 8.01 (d, J = 1.6 Hz, 1H), 7.81 (d, J = 8.8 Hz, 2H), 7.69- 7.64 (m, 1H), 7.45 (d, J = 2.0 Hz, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.34 (d,
				J = 2.0 Hz, 1H), 7.22-
				7.18 (dd, J 1 = 1.2 Hz,
				J 2 = 8.4 Hz, 1H), 6.99 (d,
				J = 8.8 Hz, 2H), 3.91 (s,
				3H), 2.07 (s, 3H), 1.99
				(s, 6H), 1.74 (s, 6H).
				LC-MS: m/z 515.1
				(M + H) 2+
361	VI.60	Int-IV & I.30
1 H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 8.56 (d, J = 8.3 Hz, 1H), 8.02 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.68 (t, J = 7.0 Hz, 1H), 7.44 (d, J = 8.8 Hz, 2H), 7.24 (t, J = 7.0 Hz, 1H), 7.13 (d, J = 8.3 Hz,
				2H), 7.07 (d, J = 8.8 Hz,
				2H), 3.89 (s, 3H), 2.07
				(s, 3H), 1.89 (s, 6H),
				1.75 (s, 6H). LC-MS:
				m/z 482.3 (M + H) 1+
385	VI.61	Int-II.10 & I.19
LC-MS: m/z 467.3 (M + H) +
386	VI.62	II.10
1 H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 8.63 (s, 1H), 8.39 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 8.24 (dd, J 1 = 2.0 Hz, J 2 = 27.6 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.8 Hz, 2H), 7.16 (d, J = 8.8 Hz,
				2H), 6.98 (d, J = 8.8 Hz,
				2H), 6.86 (dd, J 1 = 4.8
				Hz, J 2 = 7.6 Hz, 1H), 3.91
				(s, 3H), 1.52 (s, 9H).
				LC-MS: m/z 420.1
				(M + H) +
388	VI.63	Int-II & I.28
1 H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 7.86 (dd, J 1 = 1.2 Hz, J 2 = 7.6 Hz, 1H), 7.55 (s, 1H), 7.37-7.26 (m, 1H), 7.25-7.19 (m, 3H), 7.11 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 2.8 Hz, 1H), 7.0-6.96 (m, 3H), 6.91-
				6.85 (m, 4H), 6.70 (t,
				J = 6.8 Hz, 1H), 3.63 (t,
				J = 7.2 Hz, 3H), 1.56-1.5
				(m, 2H), 1.36-1.3 (m,
				2H), 0.88 (t, J = 7.2 Hz,
				3H). LC-MS: m/z 500.2
				(M + H) +
389	VI.64	II.10 & I.28
1 H NMR (400 MHz, DMSO-d6) δ 9.91 (s, 1H), 8.35 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 8.22 (dd, J 1 = 2.0 Hz, J 2 = 7.6 Hz, 1H), 7.53 (d, J = 8.8 Hz, 2H), 7.44 (s, 1H), 7.24-7.20 (m, 2H), 7.16 (d, J = 8.8 Hz, 1H), 7.05
				(d, J = 2.4 Hz, 1H), 6.99
				(d, J = 8.8 Hz, 2H), 3.89
				(s, 3H), 3.61 (t, J = 7.2
				Hz, 2H), 1.56-1.52 (m,
				2H), 1.36-1.30 (m, 2H),
				0.88 (t, J = 7.2 Hz, 3H).
				LC-MS: m/z 501.2
				(M + H) +
127	VI. 65	II.2 & Int-I

Intermediate LC-MS: m/z 359.1 (M + H) +

CP	No.	Structure	Analytical data
366, 367	VIII.1
1 H NMR (400 MHz, DMSO-d6) δ 10.43 (s, 1H), 8.80 (s, 1H), 8.47-8.40 (m, 2H), 7.85 (t, J = 7.6 Hz, 1H), 7.51-7.49 (m, 2H), 7.41-7.39 (m, 1H), 2.08 (s, 3H), 1.89 (s, 6H), 1.75 (s, 6H). LC-MS: m/z 411.1 (M + H) +
373	VIII.2
LC-MS: m/z 411.05 (M + H) +
395	VIII.3
1 H NMR (400 MHz, DMSO-d6) δ 10.53 (s, 1H), 8.79 (t, J = 2.0 Hz, 1H), 8.45-8.39 (m, 2H), 7.84 (t, J = 8.0 Hz, 1H), 7.72-7.69 (m, 2H), 7.25-7.21 (m, 2H), 7.06-7.03 (m, 2H), 6.91- 6.90 (m, 2H), 6.88-6.84 (m, 1H), 3.67 (t, J = 7.2 Hz, 2H), 1.59-1.53 (m, 2H), 1.36-1.29 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H). LC-MS: m/z 390.2 (M + H) +
339	VIII.4
LC-MS: m/z 405.1 (M + H) +
586	VIII.5
LC-MS: m/z 309.1 (M − H)−
642	VIII.6
LC-MS: m/z 339.05 (M + H)+
649	VIII.7
1H NMR (400 MHz, DMSO-d6) δ 10.57 (s, 1H), 8.45 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.71-7.68 (m, 1H), 7.58 (s, 1H), 7.54-7.44 (m, 3H), 3.86 (s, 3H), 2.38 (s, 3H).
665, 666, 669, 672	VIII.8

Intermediate LC-MS: m/z 388.0 (M + H) +

CP	No.	Reactant	Structure	Analytical data
270, 314	IX.1	I.30
1 H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.8 Hz, 2H), 7.11 (m, 4H), 2.07 (s, 3H), 1.88 (s, 6H), 1.71 (s, 6H).
360	IX.2	I.32
1 H NMR (400 MHz, DMSO-d6) δ 8.31 (d, J = 8.8 Hz, 2H), 7.57 1H), 7.44-7.36 (m, 4H), 7.26 (t, J = 7.3 Hz, 1H), 7.19 (t, J = 8.8 Hz, 3H), 2.99-2.95 (m, 1H), 1.17 (d, J = 6.8 Hz, 6H).
383, 384 529, 531,	IX.3	I.31
1 H NMR (400 MHz, DMSO-d6) δ 8.27-8.23 (m, 2H), 7.58 (d, J = 2.0 Hz, 1H), 7.45 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 7.31 (d, J = 8.4 Hz, 1H), 7.09-7.03 (m, 2H), 2.17-2.14 (m, 1H), 1.72 (s, 2H), 1.55-1.36 (m, 8H), 1.20 (s, 2H), 0.87 (s, 6H).
534	IX.4
LC-MS: m/z 419.0 (M + H) +
540	IX.5
LC-MS: m/z 576.2 (M + H) + .
543, 544	IX-6
1 H NMR (400 MHz, DMSO-d6) δ 8.35-8.27 (m, 2H), 8.15 (s, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 9.2 Hz, 2H).
546, 550	IX.7
Proceeded with crude/TLC reference
561, 564	IX.8
1 H NMR (400 MHz, DMSO- d 6 ): δ 8.06 (d, J = 9.2 Hz, 1H), 7.56 (d, J = 1.6 Hz, 1H), 7.44-7.42 (m, 1H), 7.26 (d, J = 8.4 Hz, 1H), 7.04 (d, J = 2 Hz, 1H), 6.81- 6.78 (m, 1H), 2.52 (s, 3H), 2.15 (s, 1H), 1.72-1.19 (m, 12H), 0.86-0.84 (m, 6H).
566, 591	IX.9
LC-MS: m/z 368.0 (M + 2H) +
569, 570	IX.10
Proceeded with crude/TLC reference
575	IX.11
1 H NMR (400 MHz, DMSO- d 6 ): δ 8.29-8.26 (m, 2H), 7.93 (s, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.24- 6.96 (m, 3H).
587	IX.12
LC-MS: m/z 338.85 (M + H) +
599	IX.13
LC-MS: m/z 361.3 (M + H) +
600	IX.14
LC-MS: m/z 334.05 (M+) +
601	IX.15
LC-MS: m/z 319.0 (M + H) +
615	IX.16
LC-MS: m/z 377.0 (M + H) +
616	IX.17

Inter- mediate 1 H NMR (400 MHz, DMSO-d6) δ 10.4 (s, 1H), 7.84 (d, J = 8.3 Hz, 1H), 7.78 (d, J = 8.3 Hz, 2H), 7.7 (d, J = 8.3 Hz, 2H), 7.56 (t, J = 7.6 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 3.8 (s, 3H). LC-MS: m/z 371.95 (M + H) +2 .

CP	No.	Reactant	Structure	Analytical data
372	XVI.1	Int-I.1
LC-MS: m/z 411.1 (M − H) −
393, 392	XVI.2	Int-I
1 H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H), 8.80 (dd, J = 1.6 Hz, J 2 = 6.4 Hz, 1H), 8.31- 8.30 (m, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.63 (d, J = 9.2 Hz, 2H), 7.29 (d, J = 2.8 Hz, 1H), 7.26-7.24
				(m, 1H), 7.13 (d, J = 8.8
				Hz, 1H), 2.08 (s, 3H),
				2.04 (s, 3H), 1.78 (s,
				6H), 1.66 (s, 6H).
				LC-MS: m/z 459.1
				(M + H) +
396 & 397	XVI.3	Int-I
1 H NMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H), 9.76 (s, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 2.0 Hz, 1H), 7.24 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 2.11-2.09 (m, 1H),
				2.07 (s, 3H), 1.62 (s, 2H),
				1.45-1.29 (m, 8H), 1.15
				(s, 1H), 0.83 (s, 6H). LC-
				MS: m/z 485.1 (M + H) +
342	XVI.4

Inter- mediate LC-MS: m/z 511.1 (M + H) +

CP	No.	Reactant	Structure	Analytical data
300	XIX.1	VII.14 & Int-I.1
1 H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.45 (d, J = 13.2 Hz, 2H), 7.73-7.66 (m, 3H), 7.39-7.34 (m, 5H), 7.25 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.4 Hz, 1H), 4.35-4.30 (m, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H), 1.35 (t, J = 7.2 Hz, 3H). LC-MS: m/z
				511.1 (M + H) +
307	XIX.2	XI.13 & Int-I.1
1 H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 8.61 (s, 1H), 8.52 (s, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.47 (d, J = 8.3 Hz, 2H), 7.38-7.36 (m, 3H), 7.26 (d, J = 8.8 Hz, 2H), 7.18 (d, J = 8.3
				Hz, 2H), 7.05 (d, J =
				8.3 Hz, 1H), 6.75-
				6.73 (m, 1H), 3.85
				(s, 3H), 2.05 (s, 3H),
				1.84 (s, 6H), 1.73 (s,
				6H). LC-MS: m/z
				496.1 (M + H) +
299	XIX.3	XI.17 & Int-I.1

Inter- mediate

CP	No.	Reactant	Structure	Analytical data
114	XIX.5	Int-XI
1 H NMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.34 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 2.0 Hz, 1H), 7.26 (s, 1H), 7.14 (dd, J 1 = 2.0 Hz, J 2 = 8.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.96 (d, J = 9.6 Hz, 2H), 4.37- 4.34 (m, 1H), 3.62
				(s, 3H), 3.56-3.46
				(m, 2H), 2.21-2.14
				(m, 1H), 2.03 (s,
				3H), 1.98-1.84 (m,
				3H), 1.81 (d, J = 2.4
				Hz, 6H), 1.71 (s,
				6H). LC-MS: m/z
				508.2 (M + H) +
134	XIX.6	XI.2
1 H NMR (400 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.47 (s, 1H), 7.41 (d, J = 6.8 Hz, 2H), 7.33 (d, J = 1.6 Hz, 1H), 7.28-7.17 (m, 4H), 7.13-7.06 (m, 4H), 4.38-4.35 (m, 1H), 3.76 (s, 3H), 3.63-3.48 (m, 2H), 2.27 (s, 3H),
				2.25-2.17 (m, 1H),
				1.96-1.84 (m, 3H).
				LC-MS: m/z 464.1
				(M + H) +

Compound 1H-NMR (400 MHz, DMSO-d6): 7.14- 7.02 (m, 5H), 6.91 (d, J = 8.8 Hz, 2H), 6.79-6.76 (m, 1H), 6.71-6.50 (m, 4H), 5.21-5.17 (m, 1H), 4.46 (d, J = 7 Hz, 2H), 3.74 (s, 3H), 3.13 (s, 3H), 2.03 (s, 3H), 1.81-1.79 (m, 6H), 1.72-1.70 (m, 6H). LC-MS: m/z 469.3 (M + H)+.

CP	No	Reactant	Structure	Analytical data
86	29	Int-XI
1 H NMR (400 MHz, DMSO-d6) δ 7.20 (d, J = 2.0 Hz, 1H), 7.03 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.71 (d, J = 8.8 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 5.28 (d, J = 8.4 Hz, 1H), 4.03-4.00 (m, 1H), 3.89-3.81 (m, 2H), 3.11-3.06 (m, 1H), 2.02-1.90 (m, 5H), 1.88-1.78 (m, 8H), 1.73-1.61 (m, 7H), 1.56-1.49 (m, 1H), 0.96 (t, J = 7.2 Hz, 3H). LC-MS: m/z (M + H)+
87	30	Int-XI
1 H NMR (400 MHz, DMSO-d6) δ (d, J = 2.0 Hz, 1H), 7.03 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.83 (s, 1H), 6.71 (d, J = 8.8 Hz, 1H), 6.53 (d, J = 8.8 Hz, 2H), 5.55-5.50 (m, 1H), 4.05-4.03 (m, 2H), 3.97-3.91 (m, 1H), 2.69-2.61 (m, 1H), 2.02-1.95 (m, 5H), 1.79 (s, 6H), 1.78-1.68 (m, 9H), 1.54-1.45 (m, 1H), 1.15 (t, J = 7.2 Hz, 3H). LC-MS: m/z 493.2 (M + H) +
516	31	Compound 257

Compound 1 H NMR (400 MHz, DMSO-d6) δ 7.60 (s, 1H), 7.55 (d, J = 8.8 Hz, 2H), 7.46 (dd, J 1 = 1.2 Hz, J 2 = 4.8 Hz, 1H), 7.27 (d, J = 2.0 Hz, 1H), 7.15-7.11 (m, 2H), 7.02-7.00 (m, 3H), 6.87-6.85 (m, 1H), 6.58- 6.56 (m, 1H), 5.00 (s, 2H), 2.03 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 445.2 (M + H) +

CP	No	Reactant	Structure	Analytical data
231	32	XII.69

Compound 1 H NMR (400 MHz, DMSO-d6) δ 8.20 (s, 1H), 7.38 (d, J = 8.8 Hz, 2H), 7.20 (d, J = 8.8 Hz, 2H), 4.37-4.34 (m, 1H), 3.60 (s, 3H), 3.56-3.45 (m, 2H), 2.20-2.16 (m, 1H), 2.03 (s, 3H), 1.96-1.92 (m, 3H), 1.83 (d, J = 2.0 Hz, 6H), 1.72 (s, 6H). LC-MS: m/z 383.1 (M + H) +

CP	No	Reactant	Structure	Analytical data
82	33	I.1

Com- 1H NMR (400 MHz, DMSO-d6) δ 10.4 (s, 1H), 7.62-7.55 (m, 2H), 7.32-7.26 (m, 4H), 7.16- 6.95 (m, 5H), 6.61 (d, J = 7.6 Hz, 1H), 2.44-2.32 (m, 1H), 1.84-1.67 (m, 5H), 1.38-1.19 (m, 5H). LC-MS: m/z 422.0 (M + H)+

	pound	Reac-
CP	No	tant	Structure	Analytical data
52	25
LC-MS: m/z 439.1 (M + H) +
58	26
LC-MS: m/z 507.2 (M + H) +
59	27
LC-MS: m/z 506.2 (M − H) −
60	28
LC-MS: m/z 521.2 (M + H) +
61	29
LC-MS: m/z 575.2 (M + H) +
62	30
LC-MS: m/z 457.2 (M + H) +
64	31	VI.1
1 H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 9.48 (s, 1H), 7.86 (d, J = 7.3 Hz, 1H), 7.52 (s, 1H), 7.33 (t, J = 7.4 Hz, 2H), 7.20 (s, 2H), 7.13 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 7.01 (s, 1H), 6.68 (t, J = 7.4 Hz, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS:
				m/z 472.1 (M + H) +
65	32
LC-MS: m/z 454.1 (M + H) +
66	33
LC-MS: m/z 539.1 (M − H) −
67	34
MLC-MS: m/z 440.2 (M + H) +
69	35	Int-XV
1 H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 10.02 (s, 1H), 9.81 (s, 1H), 7.97-7.94 (m, 3H), 7.69 (d, J = 8.8 Hz, 2H), 7.51-7.43 (m, 2H), 7.35-7.31 (m, 4H), 6.93- 6.89 (m, 1H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s,
				6H). LC-MS: m/z 467.1
				(M + H) +
71	36
LC-MS: m/z 545.1 (M) +
80	37
LC-MS: m/z 501.1 (M − H) +
83	38	Com- pound 23
1 H NMR (400 MHz, DMSO-d6) δ 12.36 (s, 1H), 8.16 (s, 1H), 7.38 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 4.31- 4.28 (m, 1H), 3.54-3.50 (m, 1H), 3.46-3.40 (m,
				1H), 2.16-2.14 (m, 1H),
				2.03 (s, 3H), 1.95-1.85
				(m, 3H), 1.82 (s, 6H),
				1.72 (s, 6H). LC-MS:
				m/z 369.1 (M + H) +
88	39	Com- pound 20
1 H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 2.4 Hz, 1H), 7.03 (d, J = 1.6 Hz, 1H), 6.87 (d, J = 8.4 Hz, 2H), 6.83 (s, 1H), 6.75 (d, J = 8.8 Hz, 1H), 6.61 (d, J = 8.8 Hz, 2H), 3.96-3.90 (m, 1H), 2.99- 2.93 (m, 1H), 2.02-1.79 (m, 6H), 1.78-1.69 (m,
				7H), 1.70-1.62 (m, 7H),
				1.59-1.51 (m, 1H).
				LC-MS: m/z 465.2
				(M + H) +
89	40	Com- pound 21
1 H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 2.4 Hz, 1H), 7.06 (dd, J 1 = 2.0 Hz, J 2 = 8.8 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.76 (d, J = 8.0 Hz, 1H), 6.56 (d, J = 8.8 Hz, 2H), 3.93-3.91 (m, 1H), 2.61-2.59 (m, 1H), 2.02- 1.97 (m, 5H), 1.78 (s,
				6H), 1.75-1.66 (m, 9H),
				1.52-1.44 (m, 1H).
				LC-MS: m/z 465.1
				(M + H) +
93	41	VI.2
1 H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.52 (s, 1H), 7.88 (dd, J 1 = 1.5 Hz, J 2 = 8.3 Hz, 1H), 7.69 (s, 1H), 7.42-7.30 (m, 4H), 7.25 (dd, J 1 = 8.3 Hz, J 2 = 12.7 Hz, 1H), 7.21-7.07 (m, 8H), 6.71 (t, J = 7.3 Hz, 1H), 3.06-3.02 (m, 1H),
				1.14 (d, J = 6.8 Hz, 6H).
				LC-MS: m/z 457.1
				(M + H) +
98	42	Isomer- 1 of com- pound 41
1 H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 4.0 Hz, 1H), 7.04 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.74 (d, J = 8.8 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 3.93- 3.89 (m, 1H), 2.95-2.92 (m, 1H), 2.02 (s, 3H),
				1.99-1.93 (m, 1H), 1.88-
				1.78 (m, 8H), 1.74-1.63
				(m, 7H), 1.57-1.50 (m,
				1H), 1.35-1.33 (m, 1H).
				LC-MS: m/z 465.2
				(M + H) +
99	43	Isomer- 2 of com- pound 41
1 H NMR (400 MHz, DMSO-d6) δ 7.20 (d, J = 2.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.75 (d, J = 8.8 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 3.93-3.89 (m, 1H), 2.95-2.92 (m, 1H), 2.02 (s, 3H), 1.99-1.92 (m,
				1H), 1.88-1.78 (m, 8H),
				1.74-1.63 (m, 7H), 1.57-
				1.50 (m, 1H), 1.35-1.33
				(m, 1H). LC-MS: m/z
				465.2 (M + H) +
100	44	Isomer- 1 of com- pound 42
1 H NMR (400 MHz, DMSO-d6) δ 12.15 (bs, 1H), 7.21 (d, J = 2.4 Hz, 1H), 7.04 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.83 (s, 1H), 6.74 (d, J = 8.8 Hz, 1H), 6.55 (d, J = 8.8 Hz, 2H), 5.50 (bs, 1H), 3.92 (m, 1H), 2.67-2.57 (m,
				1H), 2.02 (s, 3H), 1.99-
				1.93 (m, 2H), 1.79 (s,
				6H), 1.75-1.68 (m, 9H),
				1.50-1.44 (m, 1H). LC-
				MS: m/z 46.52 (M + H) +
101	45	Isomer- 2 of com- pound 42
1 H NMR (400 MHz, DMSO-d6) δ 12.18 (bs, 1H), 7.21 (d, J = 2.0 Hz, 1H), 7.04 (dd, J 1 = 1.6 Hz, J 2 = 8.8 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.83 (s, 1H), 6.74 (d, J = 8.8 Hz, 1H), 6.55 (d, J = 8.8 Hz, 2H), 5.50 (bs, 1H), 3.93- 3.91 (m, 1H), 2.67-2.57
				(m, 1H), 2.02-1.94 (m,
				5H), 1.78 (s, 6H), 1.77-
				1.68 (m, 8H), 1.49-1.46
				(m, 1H). LC-MS: m/z
				465.2 (M + H) +
102	46	XIII.1
1 H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 2.0 Hz, 1H), 7.04 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 6.89 (s, 1H), 6.87 (s, 2H), 6.77 (d, J = 8.0 Hz, 1H), 6.66 (d, J = 8.8 Hz, 2H), 3.87 (s, 1H), 2.62 (m, 1H), 2.02 (s, 3H), 1.91-1.78 (m, 8H), 1.70 (s, 6H), 1.68- 1.42 (m, 4H), 1.41-1.25
				(m, 2H). LC-MS: m/z
				479.2 (M + H) +
103	47	XIII.1
1 H NMR (400 MHz, DMSO-d6) δ 12.00 (bs, 1H), 7.20 (d, J = 2.0 Hz, 1H), 7.03 (d, J = 6.8 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.75 (d, J = 8.8 Hz, 1H), 6.57 (d, J = 8.0 Hz, 2H), 5.20 (bs, 1H), 3.40-3.36 (m, 1H), 2.22-2.01 (m, 1H), 2.02 (s, 3H), 1.82-1.78 (m, 2H), 1.78 (s, 6H),
				1.70-1.65 (m, 9H), 1.51-
				1.42 (m, 1H), 1.38-1.29
				(m, 1H), 1.09-1.02 (m,
				1H), LC-MS: m/z 479.2
				(M + H) +
106	48	XV.2
1 H NMR (400 MHz, DMSO-d6) δ 12.4 (bs, 1H), 8.01 (bs, 1H), 7.44- 7.40 (m, 3H), 7.33-7.27 (m, 2H), 6.91 (d, J = 8.3 Hz, 2H), 4.37 (m, 1H), 3.58 (bs, 2H), 2.25-2.22 (m, 1H), 2.05 (s, 3H), 1.85 (s, 9H), 1.73 (s, 6H). LC-MS: m/z 479.2
				(M + H) +
107	49	XV.3
1 H NMR (400 MHz, DMSO-d6) δ 12.4 (bs, 1H), 7.99 (bs, 1H), 7.42- 7.38 (m, 3H), 7.31-7.25 (m, 2H), 6.89 (d, J = 8.3 Hz, 2H), 4.35 (m, 1H), 3.56 (m, 2H), 2.23-2.20 (m, 1H), 2.03 (s, 3H), 1.83 (s, 9H), 1.71 (s, 6H). LC-MS: m/z 479.2
				(M + H) +
108	50	XIX.4
1 H NMR (400 MHz, DMSO-d6) δ 12.36 (s, 1H), 8.13 (s, 1H), 7.35 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 2.4 Hz, 1H), 7.25 (s, 1H), 7.14 (dd, J 1 = 2.0 Hz, J 2 = 8.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.96 (d, J = 8.8 Hz, 2H), 4.31- 4.29 (m, 1H), 3.56-3.42 (m, 2H), 2.18-2.12 (m,
				1H), 2.03 (s, 3H), 1.95-
				1.84 (m, 3H), 1.81 (s,
				6H), 1.71 (s, 6H). LC-
				MS: m/z 494.2 (M + H) +
113	51	VI.3
1 H NMR (400 MHz, DMSO-d6) δ 12.96 (s, 1H), 9.52 (s, 1H), 7.88 (dd, J 1 = 1.5 Hz, J 2 = 7.8 Hz, 1H), 7.7 (s, 1H), 7.38-7.34 (m, 2H), 7.30- 7.16 (m, 10H), 7.08 (d, J = 8.3 Hz, 1H), 6.71 (t, J = 7.3 Hz, 1H), 2.27 (s,
				3H). LC-MS: m/z 429.1
				(M + H) +
114	52	XIX.5
1 H NMR (400 MHz, DMSO-d6) δ 12.36 (s, 1H), 8.13 (s, 1H), 7.35 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 2.4 Hz, 1H), 7.25 (s, 1H), 7.14 (dd, J 1 = 2.0 Hz, J 2 = 8.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.96 (d, J = 8.8 Hz, 2H), 4.31- 4.29 (m, 1H), 3.56-3.42 (m, 2H), 2.18-2.12 (m,
				1H), 2.03 (s, 3H), 1.95-
				1.84 (m, 3H), 1.81 (s,
				6H), 1.71 (s, 6H). LC-
				MS: m/z 492.4 (M + H) −
115	53	VI.4
1 H NMR (400 MHz, DMSO-d6) δ 13.00 (s, 1H), 9.52 (s, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.82 (d, J = 7.8 Hz, 1H), 7.75- 7.69 (m, 2H), 7.60 (t, J = 7.8 Hz, 1H), 7.44 (d, J = 7.2 Hz, 1H), 7.38-7.25 (m, 2H), 7.23-7.18 (m, 5H), 7.14-7.09 (m, 2H), 6.72 (t, J = 8.0 Hz, 1H). LC-MS: m/z 483.1
				(M + H) +
116	54	VI.5
1 H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.49 (s, 1H), 8.32 (s, 1H), 8.87 (dd, J 1 = 7.8 Hz, J 2 = 7.8 Hz, 1H), 7.88 (d, J = 1.4 Hz, 1H), 7.51 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 7.43 (dd, J 1 = 6.4 Hz, J2 = 8.8 Hz, 4H), 7.19-
				7.14 (m, 4H), 7.10 (d,
				J = 8.3 Hz, 2H), 7.04 (d,
				J = 8.3 Hz, 1H), 6.70 (t,
				J = 7.9 Hz, 1H). LC-MS:
				m/z 433.1 (M + H) +
117	55	VI.5
1 H NMR (400 MHz, DMSO- d6) δ 12.93 (s, 1H), 9.47 (s, 1H), 8.28 (s, 1H), 7.87 (d, J = 9.3 Hz, 1H), 7.64 (dd, J 1 = 5.4 Hz, J 2 = 8.3 Hz, 2H), 7.52 (d, J = 8.3 Hz, 2H), 7.33 (t, J = 7.4 Hz, 1H), 7.24 (t, J = 8.8 Hz, 2H), 7.14 (m, 6H), 7.03 (d, J = 8.3 Hz, 1H),
				6.70 (t, J = 7.3 Hz, 1H).
				LC-MS: m/z (M + H) +
118	56	VI.6
1 H NMR (400 MHz, DMSO-d6) δ 12.96 (s, 1H), 9.51 (s, 1H), 7.88 (d, J1 = 1.5 Hz, J2 = 8.3 Hz, 1H), 7.69 (s, 1H), 7.53 (d, J = 2.0 Hz, 1H), 7.38-7.29 (m, 4H), 7.24- 7.15 (m, 5H), 7.09 (t, J = 8.4 Hz, 2H), 7.01 (t,
				J = 7.4 Hz, 1H), 6.71 (t,
				J = 7.8 Hz, 1H), 3.79 (s,
				3H). LC-MS: m/z 445.1
				(M + H) +
121	57	VI.7
1 H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 9.53 (s, 1H), 7.89 (d, J = 1.0 Hz, 1H), 7.66 (s, 1H), 7.37-7.23 (m, 2H), 7.21-7.14 (m, 5H), 7.13-7.06 (m, 4H), 6.97 (dd, J 1 = 1.4 Hz, J 2 = 8.3 Hz, 1H), 6.71 (t, J = 7.3 Hz, 1H), 2.03 (s, 6H). LC-MS: m/z 442.4 (M + H) +
122	58	VI.8
1 H NMR (400 MHz, DMSO-d6) δ 12.98 (s, 1H), 9.54 (s, 1H), 7.88 (dd, J 1 = 0.9 Hz, J 2 = 7.8 Hz, 1H), 7.77 (s, 1H), 7.55 (dd, J 1 = 6.8 Hz, J 2 = 8.3 Hz, 1H), 7.48 (d, J = 1.5 Hz, 1H), 7.44-7.35 (m, 4H), 7.28-7.25 (m,
				2H), 7.23-7.19 (m, 4H),
				7.10 (d, J = 8.3 Hz, 1H),
				6.72 (t, J = 7.3 Hz, 1H).
				LC-MS: m/z 449 (M + H) +
124	59	Int-XII
1 H NMR (400 MHz, DMSO-d6) δ 12.18 (bs, 1H), 8.16-8.13 (m, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 2.0 Hz, 1H), 1 H NMR (400 MHz, DMSO-d6) δ 7.22 (s, 1H), 7.13 (dd, J 1 = 2.4 Hz, J 2 = 8.4 Hz, 1H), 7.04-
				7.02 (m, 3H), 6.66 (dd,
				J 1 = 4.8 Hz, J 2 = 7.2 Hz,
				1H), 2.03 (s, 3H), 1.82 (s,
				6H), 1.71 (s, 6H). LC-MS:
				m/z 474 (M + H) +
125	60	VI.9
1 H NMR (400 MHz, DMSO-d6) δ 13.61 (s, 1H), 10.6 (s, 1H), 8.5 (d, J = 8.8 Hz, 1H), 8.4 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 8.28 (dd, J 1 = 2.0 Hz, J 2 = 8.0 Hz, 1H), 7.4 (d, J = 2.0 Hz, 1H), 7.32 (dd, J 1 = 2.0 Hz, J 2 = 8.8 Hz, 1H), 6.92 (dd, J 1 = 4.4 Hz J 2 = 7.2 Hz, 1H), 2.06 (s,
				3H), 1.86 (d, J = 2.8 Hz,
				6H), 1.7 (s, 6H). LC-MS:
				m/z 383.0 (M + H) +
126	611	VI.10
1 H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.52 (bs, 1H), 7.87 (dd, J 1 = 1.5 Hz, J 2 = 7.8 Hz, 1H), 7.59 (s, 1H), 7.35- 7.05 (m, 12H), 6.71 (t, J = 6.9 Hz, 1H), 2.05 (s, 3H), 1.90 (s, 3H). LC-MS: m/z 443.1(M + H) +
127	62	VI.65
1 H NMR (400 MHz, DMSO-d6) δ 13.45 (s, 1H), 10.79 (s, 1H), 8.55 (s, 1H), 8.49 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 6.0 Hz, 1H), 7.94 (d, J = 7.2 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.37-7.32 (m, 2H), 7.02 (t, J = 7.2 Hz, 1H), 6.29 (d, J = 5.2 Hz,
				1H), 2.08 (s, 3H), 1.89 (s,
				6H), 1.75 (s, 6H). LC-MS:
				m/z 475.1 (M + H) +
128	63	XIII.2
1 H NMR (400 MHz, DMSO-d6) δ 11.9 (bs, 1H), 7.64 (s, 1H), 7.36 (s, 1H), 7.26-7.23 (m, 2H), 6.47 (bs, 1H), 6.40 (d, J = 9.3 Hz, 2H), 6.10 (bs, 1H), 3.91 (m, 1H), 2.94 (m, 1H), 2.05 (bs, 3H), 1.94 (m, 2H), 1.84 (s, 6H), 1.80-1.63 (m, 8H), 1.55-1.50 (m, 2H). LC-MS: m/z 533.2 (M + H) +
129	64	XIII.2
1 H NMR (400 MHz, DMSO-d6) δ 12.18 (s, 1H), 7.69 (s, 1H), 7.37 (s, 1H), 7.26 (s, 2H), 7.41- 7.38 (m, 2H), 6.30 (s, 1H), 6.08 (d, J = 6.8 Hz, 1H), 3.92-3.89 (m, 1H), 2.05 (s, 3H), 2.02-1.91 (m, 2H), 1.85 (s, 6H), 1.73 (s, 6H), 1.70-1.60 (m, 2H), 1.52-1.38 (m, 3H). LC-MS: m/z 533.2 (M + H) +
130	65	XIII.3
1 H NMR (400 MHz, DMSO-d6) δ 7.0 (d, J = 8.0 Hz, 2H), 6.53 (d, J = 8.4 Hz, 2H), 3.93-3.88 (m, 1H), 2.94-2.64 (m, 1H), 1.99 (bs, 5H), 1.95- 1.77 (m, 2H), 1.75 (bs, 7H), 1.72-1.54 (bs, 7H). LC-MS: m/z 340.1 (M + H) +
131	66	XIII.4
1 H NMR (400 MHz, DMSO-d6) δ 7.02 (d, J = 8.8 Hz, 2H), 6.55 (d, J = 8.4 Hz, 2H), 3.74 (bs, 1H), 2.08 (bs, 3H), 2.01- 1.88 (m, 1H), 1.77-1.73 (bs, 6H), 1.70 (bs, 8H), 1.53-1.47 (m, 4H), 1.37- 1.27 (m, 2H). LC-MS: m/z 354.1 (M + H) +
134	67	XIX.6
1 H NMR (400 MHz, DMSO-d6) δ 12.37 (bs, 1H), 8.21 (bs, 1H), 7.46- 7.41 (m, 3H), 7.39 (s, 1H), 7.33-7.17 (m, 4H), 7.13-7.06 (m, 4H), 4.3 (d, J = 6.4 Hz, 1H), 3.55-3.47 (m, 2H), 2.25 (s, 3H), 2.19-2.13 (m, 1H), 1.96- 1.88 (m, 3H). LC-MS: m/z 450.1 (M + H) +
135	68	VI.11
1 H NMR (400 MHz, DMSO-d6) δ 12.30- 10.99 (bs, 1H), 8.20 (s, 1H), 8.00-7.91 (m, 4H), 7.63 (d, J = 8.8 Hz, 2H), 7.55-7.48 (m, 4H), 7.33- 7.23 (m, 3H), 6.75 (t, J = 7.6 Hz, 1H). LC-MS: m/z 373.3 (M + H) +
136	69	XIII.5
1 H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 2.0 Hz, 1H), 7.05 (dd, J 1 = 2.0 Hz, J 2 = 10.8 Hz, 1H), 6.88 (d, J = 8.4 Hz, 2H), 6.83 (s, 1H), 6.76 (d, J = 8.8 Hz, 1H), 6.58 (d, J = 8.4 Hz, 2H), 3.8 (s, 1H), 2.03 (s, 3H), 1.90-
				1.83 (m, 1H), 1.80-1.65
				(m, 17H), 1.64-1.56 (m,
				3H), 1.52-1.41 (m, 3H).
				LC-MS: m/z 507.3 (M + H) +
138	70	Int-XIII
1 H NMR (400 MHz, DMSO-d6) δ 12.53 (bs, 1H), 8.81 (s, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.36- 7.32 (m, 1H), 7.18 (d, J = 2.0 Hz, 1H), 7.12 (d, J = 8.8 Hz, 1H), 6.79-6.74 (m, 2H), 6.52 (d, J = 7.2 Hz, 1H), 4.51 (d, J = 7.2
				Hz, 1H), 3.7 (s, 1H), 3.48
				(s, 1H), 2.02 (s, 3H), 1.78-
				1.7 (m, 18H), 1.58-1.55 (m,
				2H). LC-MS: m/z 479.3
				(M + H) +
139	71	Int-XIII
1 H NMR (400 MHz, DMSO-d6) δ 12.53 (s, 1H), 7.78-7.76 (m, 2H), 7.34 (t, J = 8.0 Hz, 1H), 7.17 (d, J = 2.0 Hz, 1H), 7.11 (dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, 1H), 6.78-6.73 (m, 2H), 6.54-6.50 (m, 1H), 4.5 (d, J = 8.4 Hz, 1H), 3.4-
				3.35 (m, 2H), 2.08-1.98 (m,
				7H), 1.78 (s, 6H), 1.7 (s,
				6H), 1.47-1.23 (m, 4H). LC-
				MS: m/z 479.4 (M + H) +
140	72	VI.12
1 H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.49 (bs, 1H), 7.86 (dd, J 1 = 1.5 Hz, J 2 = 7.9 Hz, 1H), 7.42 (s, 1H), 7.37 (s, 1H), 7.34 (m, 1H), 7.28-7.25 (m, 1H), 7.18-7.04 (m, 6H), 6.70 (t, J = 7.4 Hz, 1H), 5.91 (s, 1H), 2.38-2.32 (m, 2H),
				1.91-1.89 (m, 2H), 1.77-
				1.74 (m, 2H), 1.05 (m,
				6H). LC-MS: m/z 446.3
				(M + H) +
141	73	VI.13
1 H NMR (400 MHz, DMSO-d6) δ 13.00-12.8 (bs, 1H), 8.34 (s, 2H), 7.90-7.82 (m, 2H), 7.32 (d, J = 10.0 Hz, 2H), 7.26- 7.13 (m, 3H), 6.96 (bs, 1H), 1.98 (s, 3H), 1.83 (d, J = 2.4 Hz, 6H), 1.72
				(s, 6H), 1.33 (s, 9H). LC-
				MS: m/z 575.1 (M + H) +
142	74	VI.14
1 H NMR (400 MHz, DMSO-d6) δ 12.91 (bs, 1H), 8.77 (s, 1H), 8.30 (s, 1H), 8.05 (s, 1H), 7.89- 7.86 (m, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.55-7.51 (m, 1H), 7.38-7.37 (m, 2H), 7.27 (t, J = 2.0 Hz,
				2H), 2.05 (s, 3H), 1.85 (s,
				6H), 1.73 (s, 6H), 1.33 (s,
				9H). LC-MS: m/z 575.1
				(M + H) +
143	75	Int-XI
1 H NMR (400 MHz, DMSO-d6) δ 13.40- 13.00 (bs, 1H), 8.66 (s, 1H), 8.09 (d, J = 2.0 Hz, 1H), 7.76 (s, 1H), 7.37 (d, J = 1.2 Hz, 1H), 7.28- 7.22 (m, 2H), 7.17 (d, J = 7.6 Hz, 2H), 7.06 (d,
				J = 8.0 Hz, 2H), 6.89 (d,
				J = 6.8 Hz, 1H), 2.05 (s,
				3H), 1.89-1.84 9bs, 6H),
				1.73 (s, 6H). LC-MS:
				m/z 474.1 (M + H) +
144	76	VI.15
1 H NMR (400 MHz, DMSO-d6) δ 12.86 (bs, 1H), 7.97 (d, J = 2.8 Hz, 1H), 7.86 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.77 (s, 1H), 7.54-7.48 (m, 2H), 7.41-7.33 (m, 3H), 7.21 (d, J = 8.4 Hz, 2H), 7.14
				(d, J = 8.4 Hz, 1H), 2.04
				(s, 3H), 1.83 (s, 6H), 1.72
				(s, 6H), 1.32 (s, 9H). LC-
				MS: m/z 574.1 (M + H) +
145	77	XV.5
1 H NMR (400 MHz, DMSO-d6) δ 11.93 (bs, 1H), 7.99 (s, 1H), 7.83 (bs, 1H), 7.66 (d, J = 8.8 Hz, 2H), 7.40 (s, 1H), 7.29-7.26 (m, 2H), 6.90 (d, J = 8.8 Hz, 2H), 4.54- 4.50 (m, 1H), 2.92-2.90 (m, 1H), 2.08 (bs, 3H), 2.05 (m, 2H), 1.85 (s, 6H), 1.83-1.80 (m, 2H),
				1.73 (s, 6H), 1.52-1.49
				(m, 2H). LC-MS: m/z
				(M + H) +
146	78	XII.9
1 H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 9.7 (s, 1H), 7.9 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.52-7.39 (m, 5H), 7.34-7.24 (m, 5H), 7.16- 7.13 (m, 3H), 6.82 (t, J = 8.0 Hz, 1H). LC-MS: m/z 356.0 (M + H) +
148	79
LC-MS: m/z 467.3 (M + H) +
149	80
LC-MS: m/z 507.2 (M + H) +
151	81
LC-MS: m/z 438.2 (M) +
156	82	XII.10
1 H NMR (400 MHz, DMSO-d6) δ 11.2 (s, 1H), 7.74 (s, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.4 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.19-7.03 (m, 7H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 474.1 (M + H) +
157	83	XII.11
1 H NMR (400 MHz, DMSO-d6) δ 13.80-13.2 (bs, 1H), 9.50-9.0 (bs, 1H), 8.39 (s, 1H), 7.92 (d, J = 5.2 Hz, 1H), 7.64 (d, J = 4.8 Hz, 1H), 7.55 (s, 1H), 7.34 (s, 1H), 7.21 (s, 2H), 7.14 (d, J = 9.2 Hz, 2H), 7.05 (d, J = 8.8
				Hz, 2H), 2.05 (s, 3H),
				1.83 (s, 6H), 1.72 (s, 6H).
				LC-MS: m/z 474.1 (M + H) +
158	84	VI.16
1 H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 8.13 (s, 1H), 7.53 (s, 1H), 7.28 (s, 4H), 7.15- 7.14 (m, 2H), 7.08-7.04 (m, 5H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 472.1 (M + H) +
159	85	XII.12
1 H NMR (400 MHz, DMSO-d6) δ 13.82 (bs, 1H), 10.41 (bs, 1H), 8.83 (bs, 1H), 8.68 (s, 1H), 7.55 (s, 1H), 7.52 (d, J = 8.8 Hz, 2H), 7.33 (d, J = 0.8 Hz, 1H), 7.22-7.17 (m, 2H), 7.04 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H),
				1.83 (s, 6H), 1.72 (s, 6H).
				LC-MS: m/z 475.2 (M + H) +
160	86	XII.13
1 H NMR (400 MHz, DMSO-d6) δ 10.17 (s, 1H), 8.37 (d, J = 2.4 Hz, 1H), 8.04 (d, J = 2.0 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.47 (s, 1H), 7.32 (d, J = 1.6 Hz, 1H), 7.18- 7.14 (m, 2H), 7.04 (d, J = 8.8 Hz, 2H), 2.04 (s,
				3H), 1.83 (s, 6H), 1.72 (s,
				6H). LC-MS: m/z 475.2
				(M + H) +
161	87	XV.6
1 H NMR (400 MHz, DMSO-d6) δ 10.11 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.41-7.39 (m, 1H), 7.35-7.31 (m, 1H), 7.23- 7.18 (m, 3H), 7.11-7.09 (m, 1H), 3.93 (t, J = 8.8 Hz, 2H), 3.79 (t, J = 7.2 Hz, 2H), 3.62-3.54 (m, 2H), 3.52-3.49 (m, 2H),
				3.02-2.95 (m, 1H), 1.10
				(d, J = 6.8 Hz, 6H). LC-
				MS: m/z 353.1 (M + H) +
162	88	XIII.6
1 H NMR (400 MHz, DMSO-d6) δ 7.21-7.20 (m, 1H), 7.05-7.02 (m, 1H), 6.89-6.85 (m, 3H), 6.82-6.74 (m, 2H), 6.65- 6.58 (m, 5H), 3.79 (bs, 1H), 3.14-3.11 (m, 1H), 2.92-2.81 (m, 3H), 2.60- 2.56 (m, 1H), 2.34-2.32
				(m, 1H), 2.02 (s, 3H),
				1.78 (s, 7H), 1.70 (s, 8H).
				LC-MS: m/z 480.2
				(M + H) +
163	89	XII.14
1 H NMR (400 MHz, DMSO-d6) δ 13.80 (bs, 1H), 9.12 (s, 1H), 8.23 (d, J = 4.8 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.28- 7.27 (m, 3H), 7.13 (d, J = 1.2 Hz, 1H), 7.06-7.03 (m, 4H), 2.04 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H).
				LC-MS: m/z 474.3 (M + H) +
168	90	XII.15
1 H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 9.12 (s, 1H), 7.70- 7.64 (m, 3H), 7.36 (d, J = 7.2 Hz, 1H), 7.29 (d, J = 1.6 Hz, 1H), 7.25 (s, 1H), 7.15 (dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, 1H), 7.07- 7.02 (m, 3H), 6.96 (d,
				J = 8.4 Hz, 1H), 2.04 (s,
				3H), 1.82 (s, 6H), 1.72 (s,
				6H). LC-MS: m/z 474.3
				(M + H) +
169	91	XII.16
1 H NMR (400 MHz, DMSO-d6) δ 13.95 (bs, 1H), 13.2 (bs, 1H), 8.35 (d, J = 2.4 Hz, 1H), 8.30 (dd, J 1 = 2.0 Hz, J 2 = 5.2 Hz, 1H), 8.20 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 8.12 (s, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.87 (dd, J 1 = 2.8
				Hz, J 2 = 8.8 Hz, 1H), 7.34
				(d, J = 2.4 Hz, 1H), 7.26
				(dd, J 1 = 2.0 Hz, J 2 = 8.8
				Hz, 1H), 6.98 (d, J = 8.8
				Hz, 1H), 6.80 (dd, J 1 = 4.8
				Hz, J 2 = 8.0 Hz, 1H), 2.06
				(s, 3H), 1.86 (s, 6H), 1.74
				(s, 6H). LC-MS: m/z
				475.2 (M + H) +
170	92	VI.17
1 H NMR (400 MHz, DMSO-d6) δ 13.59 (bs, 1H), 10.58 (bs, 1H), 8.38-8.37 (m, 1H), 8.36 (s, 1H), 8.27 (dd, J 1 = 1.6 Hz, J 2 = 7.6 Hz, 1H), 7.55 (d, J = 2.4 Hz, 1H), 7.35 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 6.91 (dd, J 1 = 4.8 Hz, J 2 = 7.6 Hz, 1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z
				428.9 (M + H) +
172	93	XIII.7
1 H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 1.2 Hz, 1H), 7.04 (d, J = 6.8 Hz, 1H), 6.93-6.88 (m, 3H), 6.77 (d, J = 8.4 Hz, 1H), 6.61 (d, J = 8.4 Hz, 2H), 5.70 (bs, 1H), 4.09 (bs, 1H), 3.30-3.27 (m, 3H), 3.21-3.17 (m,
				1H), 2.87-2.84 (m, 1H),
				2.67 (m, 1H), 2.02 (s,
				3H), 1.78 (s, 6H), 1.70 (s,
				6H). LC-MS: m/z 466.3
				(M + H) +
173	94	VI.18
1 H NMR (400 MHz, DMSO-d6) δ 12.6 (bs, 1H), 7.42 (s, 1H), 7.32 (s, 1H), 7.16 (s, 2H), 7.09 (d, J = 7.6 Hz, 2H), 7.08- 7.00 (m, 1H), 6.93 (d, J = 8.4 Hz, 2H), 4.1 (m, 1H), 2.90 (m, 1H), 2.80
				(m, 1H), 2.05 (s, 3H),
				1.83 (s, 6H), 1.72 (s, 6H),
				1.33 (s, 9H). LC-MS:
				m/z 523.2 (M − H) +
174	95	VI.18 & Com- pound 82
1 H NMR (400 MHz, DMSO-d6) δ 7.49 (s, 1H), 7.33 (s, 1H), 7.19 (s, 1H), 7.11 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 3.65 (m, 1H), 3.12- 3.10 (m, 1H), 2.90-2.80 (m, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).
				LC-MS: m/z 425.3 (M + H) +
177	96	VI.20
1 H NMR (400 MHz, DMSO-d6) δ 13.50 (bs, 1H), 10.41 (bs, 1H), 8.37 (dd, J 1 = 1.9 Hz, J 2 = 4.9 Hz, 1H), 8.24 (dd, J 1 = 2.0 Hz, J 2 = 7.8 Hz, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.50 (s, 1H), 7.25 (t, J = 7.8 Hz,
				1H), 7.03 (d, J = 7.8 Hz,
				1H), 6.85-6.82 (m, 1H),
				2.06 (s, 3H), 1.88 (s, 6H),
				1.74 (s, 6H). LC-MS: m/z
				349.2 (M + H) +
178	97	IV.1
1 H NMR (400 MHz, DMSO-d6) δ 12.5 (bs, 1H), 8.24 (s, 1H), 8.07 (d, J = 6.8 Hz, 1H), 8.01 (s, 0.3 H), 7.84 (m, 0.6H), 7.78-7.73 (m, 2H), 7.51-7.46 (m, 2H), 7.25- 7.19 (m, 1.5H), 2.09 (s, 3H), 1.98 (s, 6H), 1.77 (s, 6H), 1.49 (s, 2H). LC- MS: m/z 373.1 (M + H) +
182 294	98	XV.20
1 H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 9.5 (s, 1H), 8.45 (s, 1H), 7.88 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.35 (t, J = 1.6 Hz, 1H), 7.23 (s, 1H), 7.20-7.14 (m, 4H), 7.07 (d, J = 8.4 Hz, 1H),
				6.99 (d, J = 8.8 Hz, 2H),
				6.73-6.69 (m, 1H), 2.06
				(s, 9H), 1.65 (s, 6H). LC-
				MS: m/z 482.1 (M + H) +
183	99
LC-MS: m/z 453.3 (M + H) +
184	100	Int-XX
1 H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 7.75 (dd, J 1 = 0.8 Hz, J 2 = 7.2 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.31 (t, J = 7.6 Hz, 2H), 7.12 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 9.2 Hz, 2H), 6.67 (d, J = 8.8 Hz, 2H), 6.56 (d, J = 8.8 Hz, 2H), 3.18 (s,
				3H), 3.13 (s, 3H), 2.02 (s,
				3H), 1.80 (s, 6H), 1.71 (s,
				6H). LC-MS: m/z 467.3
				(M + H) +
185	101	VI.21
1 H NMR (400 MHz, DMSO-d6) δ 7.81 (s, 1H), 7.38 (d, J = 8.8 Hz, 1H), 7.32-7.28 (m, 3H), 7.15-7.12 (m, 2H), 6.97 (d, J = 8.8 Hz, 1H), 4.72 (s, 2H), 2.02 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC- MS: m/z 436.0 (M + H) +
186	102	XV.7
1 H NMR (400 MHz, DMSO-d6) δ 11.59-11.3 (bs, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.39 (s, 1H), 7.30 (d, J = 2.4 Hz, 1H), 7.16 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 7.00 (d, J = 8.8 Hz, 2H), 4.47 (d, J = 8.0 Hz, 1H), 4.33 (d, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s,
				6H), 1.38 (s, 3H), 1.35 (s,
				3H), 1.25-1.22 (m, 1H).
				LC-MS: m/z 525.1 (M + H)+
187	103	VI.22
1 H NMR (400 MHz, DMSO-d6) δ 7.66 (s, 1H), 7.36 (s, 1H), 7.26- 7.23 (m, 4H), 6.96 (d, J = 8.4 Hz, 2H), 4.03 (d, J = 13.2 Hz, 1H), 3.83 (d, J = 12.8 Hz, 1H), 3.21- 3.18 (m, 2H), 2.78-2.71 (m, 1H), 2.33-2.32 (m,
				1H), 2.15-2.02 (m, 4H),
				1.95-1.79 (m, 4H), 1.74-
				1.63 (m, 8H). LC-MS:
				m/z 465.3 (M + H) +
191	104	XII.17
1 H NMR (400 MHz, DMSO-d6) δ 13.40 (bs, 1H), 10.20 (s, 1H), 8.34 (dd, J 1 = 1.9 Hz, J 2 = 4.9 Hz, 1H), 8.22 (dd, J 1 = 1.9 Hz, J 2 = 7.8 Hz, 1H), 7.95 9bs, 1H0, 7.55 (d, J = 8.8 Hz, 2H), 7.13 (t, J = 7.8 Hz, 1H), 7.05-7.00 (m, 3H), 6.85 (d, J = 7.8 Hz, 1H), 6.83-6.77 (m, 2H), 2.05 (s, 3H), 1.76 (s, 6H),
				1.69 (s, 6H). LC-MS:
				m/z 440.1 (M + H) +
192	105	VI.23
1 H NMR (400 MHz, DMSO-d6) δ 7.72 (s, 1H), 7.61 (s, 1H), 7.34 (s, 1H), 7.20 (s, 2H), 7.16- 7.13 (m, 3H), 6.95 (d, J = 8.4 Hz, 2H), 6.89 (s, 1H), 5.07 (s, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 350.2
				(M + H) +
194	106	X.4
1 H NMR (400 MHz, DMSO-d6) δ 13.0 (s, 1H), 8.26-8.25 (m, 1H), 7.92 (d, J = 7.2 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.34-7.31 (m, 2H), 6.84 (dd, J 1 = 4.4 Hz, J 2 = 7.2 Hz, 1H), 3.57 (s, 2H), 3.33 (m, 8H), 2.05 (s, 2H), 1.85 (s, 6H), 1.73 (s,
				6H). LC-MS: m/z 466.1
				(M + H) +
195	107	X.5
1 H NMR (400 MHz, DMSO-d6) δ 8.56 (dd, J 1 = 1.6 Hz, J 2 = 4.8 Hz, 1H), 8.18 (d, J = 7.6 Hz, 1H), 7.46 (dd, J 1 = 4.8 Hz, J 2 = 7.6 Hz, 1H), 7.42- 7.40 (m, 1H), 7.38-7.30 (m, 2H), 4.18 (s, 2H), 3.56 (s, 2H), 2.8 (s, 4H),
				2.55-2.54 (m, 4H), 2.04
				(s, 3H), 1.84 (s, 6H), 1.72
				(s, 6H). LC-MS: m/z 480.1
				(M + H) +
197	108	VI.24
1 H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1.5H), 8.10 (s, 0.4H), 8.03 (s, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.45-7.40 (m, 2H), 7.31 (m, 2H), 7.17 (s, 1H), 7.14 (s, 2.5 H), 7.04-6.98 (m, 2H), 5.05 (s, 1H), 4.99 (s, 2H), 2.04 (s, 5H), 1.90 (s, 9H),
				1.72 (s, 9H). LC-MS:
				m/z 436.2 (M + H) +
198	109	XX.1
1 H NMR (400 MHz, DMSO-d6) δ 12.35 (s, 1H), 8.28 (d, J = 3.2 Hz, 1H), 7.70 (d, J = 5.6 Hz, 1H), 7.47 (d, J = 1.6 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.24 (d, J = 8.4 Hz, 1H), 6.84-6.81 (m, 3H), 6.43 (d, J = 8.8 Hz, 2H), 3.3 (s, 3H), 3.13 (s, 3H), 2.06 (s, 3H), 1.88 (s, 6H),
				1.74 (s, 6H).
				LC-MS: m/z 502.2 (M + H) +
199	110	VI.25
1 H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 8.15 (s, 1H), 7.52 (d, J = 9.2 Hz, 1H), 7.37- 7.31 (m, 2H), 7.19-7.08 (m, 4H), 5.21 (s, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 1H). LC-MS: m/z 436.3 (M + H) +
200	111	VI.26
1 H NMR (400 MHz, DMSO-d6) δ 13.50 (bs, 1H), 10.40 (s, 1H), 8.36 (dd, J 1 = 2.0 Hz, J 2 = 4.9 Hz, 1H), 8.23 (dd, J 1 = 1.9 Hz, J 2 = 7.3 Hz, 1H), 8.11 (s, 1H), 7.66 (s, 1H), 7.19-7.11 (m, 3H), 7.02
				(d, J = 8.3 Hz, 1H), 6.95
				(d, J = 7.8 Hz, 1H), 6.86-
				6.83 (m, 2H), 6.70 (d,
				J = 7.8 Hz, 1H), 1.98 (s,
				3H), 1.85 (s, 6H), 1.68 (s,
				6H). LC-MS: m/z 440.3
				(M + H) +
202	112	XII.18
1 H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 10.2 (bs, 1H), 8.33 (d, J = 2.8 Hz, 1H), 8.22 (s, 1H), 8.16 (dd, J 1 = 1.2 Hz, J 2 = 7.2 Hz, 1H), 7.67 (s, 1H), 7.39 (d, J = 2.0 Hz, 1H), 7.31=7.29 (m, 1H), 6.94 (d, J = 8.4 Hz, 1H), 6.74 (dd, J 1 = 5.2 Hz, J 2 = 7.6 Hz, 1H), 5.36 (bs,
				2H), 2.04 (s, 3H), 1.83 (s,
				6H), 1.72 (s, 6H).
				LC-MS: m/z 463.2 (M + H) +
203	113	XII.19
1 H NMR (400 MHz, DMSO-d6) δ 13.54 (s, 1H), 10.40 (s, 1H), 8.32 (dd, J 1 = 1.9 Hz, J 2 = 4.8 Hz, 1H), 8.23 (dd, J 1 = 2.0 Hz, J 2 = 7.8 Hz, 1H), 7.61 (d, J = 8.3 Hz, 1H), 7.39 (s, 1H), 7.30 (d, J = 8.3
				Hz, 1H), 7.23-7.10 (m,
				4H), 6.84 (m, 1H), 6.75
				(d, J = 8.0 Hz, 1H), 4.02
				(s, 2H), 3.16 (m, 1H),
				1.10 (d, J = 6.8 Hz, 6H).
				LC-MS: m/z 347.2 (M + H) +
204	114	XII.20
1 H NMR (400 MHz, DMSO-d6) δ 8.13 (d, J = 7.6 Hz, 2H), 7.48 (s, 1H), 7.42 (s, 1H), 7.33 (d, J = 2.0 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 7.26- 7.21 (m, 3H), 7.09 (t, J = 7.6 Hz, 1H), 6.67 (s, 1H), 6.55 (d, J = 7.6 Hz, 1H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS:
				m/z 474.2 (M + H) +
205	115	XII.21
1 H NMR (400 MHz, DMSO-d6) δ 13.3 (bs, 1H), 9.63 (s, 1H), 8.41 (s, 1H), 8.33 (s, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.36 (s, 1H), 7.30 (d, J = 2.4 Hz, 1H), 7.18-7.16 (m, 1H), 7.11 (d, J = 8.4 Hz, 1H), 7.05 (d, J = 9.2 Hz,
				2H), 2.05 (s, 3H), 1.83 (s,
				6H), 1.72 (s, 6H). LC-MS:
				m/z 475.2 (M + H) +
206	116	XII.22
1 H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 8.40 (t, J = 1.9 Hz, 2H), 8.33 (s, 1H), 7.71 (m, 1H), 7.39 (s, 1H), 7.31 (s, 1H), 7.17-7.06 (m, 6H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 474.2 (M + H) +
207	117	XII.23
1 H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 7.99 (d, J = 6.8 Hz, 1H), 7.77 (s, 1H), 7.37 (s, 1H), 7.32 (s, 1H), 7.29- 7.23 (m, 2H), 7.15 (d, J = 8.8 Hz, 2H), 7.06 (d, J = 8.8 Hz, 2H), 6.9 (dd, J 1 = 2.5 Hz, J 2 = 6.9 Hz,
				1H), 2.05 (bs, 3H), 1.84
				(s, 6H), 1.73 (s, 6H).
				LC-MS: m/z 474.2 (M + H) +
210	118	VI.27
1 H NMR (400 MHz, DMSO-d6) δ 12.88 (bs, 1H), 7.88 (s, 1H), 7.75 (s, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.37 (d, J = 1.6 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.21 (dd, J 1 = 2.0 Hz, J 2 = 8.8 Hz, 1H), 7.02 (s, 1H), 6.91 (dd, J 1 = 1.6 Hz, J 2 = 8.8 Hz, 1H), 5.05 (s, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS
				m/z 436.2 (M + H) +
211	119	XII.24
1 H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 9.5 (bs, 1H), 8.2 (bs, 1H), 7.9 9bs, 1H), 7.7 (bs, 1H), 7.46 (bs, 1H), 7.40 (bs, 2H), 7.30 (bs, 1H), 7.20 (bs, 1H), 7.00 (bs, 1H), 6.82 (bs, 1H), 2.05 (s, 3H), 1.90 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 542.2 (M + H) +
212	120	XV.8
1 H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 10.16 (bs, 1H), 8.15 (s, 1H), 7.53 (s, 1H), 7.42 (d, J = 6.0 Hz, 2H), 7.32 (s, 2H), 6.92 (s, 1H), 4.71 (d, J = 6.0 Hz, 1H), 4.67 (d, J = 6.0 Hz, 1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H), 1.4 (s, 6H). LC-MS: m/z 593.2 (M + H) +
213	121	VI.28
1 H NMR (400 MHz, DMSO-d6) δ 12.25 (bs, 1H), 8.29 (s, 1H), 7.79 (s, 1H), 7.63 (s, 1H), 7.40 (s, 1H), 7.22 (s, 2H), 7.19- 7.15 (m, 2H), 6.97-6.92 (m, 2H), 5.23 (s, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 350.2 (M + H) +
214	122	VI.29
1 H NMR (400 MHz, DMSO-d6) δ 13.45 (bs, 1H), 8.59 (d, J = 3.6 Hz, 1H), 8.09 (d, J = 6.8 Hz, 1H), 7.36-7.30 (m, 3H), 7.16-7.11 (m, 2H), 7.07 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 7.6 Hz, 2H), 4.39 (s, 2H), 2.03 (s, 3H), 1.81
				(s, 6H), 1.71 (s, 6H). LC-
				MS: m/z 473.2 (M + H) +
215	123	XV.9
1 H NMR (400 MHz, DMSO-d6) δ 12.39 (s, 1H), 7.94 (s, 1H), 7.39 (d, J = 2.0 Hz, 1H), 7.33- 7.24 (m, 4H), 6.92 (d, J = 8.8 Hz, 2H), 4.20-3.99 (m, 1H), 3.98-3.62 (m, 1H), 3.10-2.92 (m, 2H), 2.45-2.37 (m, 1H), 2.06
				(s, 3H), 2.01-1.97 (m,
				1H), 1.85 (s, 6H), 1.73 (s,
				6H), 1.69-1.55 (m, 2H),
				1.44-1.39 (m, 1H). LC-
				MS: m/z 493.2 (M + H) +
217	124	VI.30
1 H NMR (400 MHz, DMSO-d6) δ 12.15 (bs, 1H), 7.52 (s, 1H), 7.32 (s, 1H), 7.18 (s, 3H), 7.02 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 6.84- 6.82 (m, 1H), 6.12-6.10 (m, 1H), 5.44 (s, 2H), 2.04 (s, 3H), 1.82 (s, 6H),
				1.72 (s, 6H). LC-MS: m/z
				461.2 (M + H) +
218	125	VI.31
1 H NMR (400 MHz, DMSO-d6) δ 12.41 (s, 1H), 8.33 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 7.75 (dd, J 1 = 2.0 Hz, J 2 = 7.2 Hz, 1H), 7.42 (s, 1H), 7.31 (s, 1H), 7.17 (s, 2H), 6.94 (d, J = 8.8 Hz, 2H), 6.89- 6.86 (m, 3H), 3.32 (s,
				3H), 2.04 (s, 3H), 1.82 (s,
				6H), 1.72 (s, 6H). LC-MS:
				m/z 488.1 (M + H) +
219	126	VI.32
1 H NMR (400 MHz, DMSO-d6) δ 12.89 (s, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.28 (s, 2H), 7.20 (d, J = 3.2 Hz, 1H), 7.09 (S, 3H), 6.86 (dd, J 1 = 1.6 Hz, J 2 = 8.4 Hz, 1H), 6.36 (d, J = 2.8 Hz, 1H), 4.9 (s, 2H), 2.04 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 435.2 (M + H) +
220	127	VI.33
1 H NMR (400 MHz, DMSO-d6) δ 12.00 (bs, 1H), 7.82 (d, J = 6.4 Hz, 2H), 7.67 (s, 1H), 7.34 (s, 1H), 7.21-7.17 (m, 3H), 6.89 (d, J = 5.6 Hz, 2H), 6.74 (d, J = 7.6 Hz, 1H), 5.16 (s, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 462.3 (M + H) +
221	128	VI.34
1 H NMR (400 MHz, DMSO-d6) δ 12.75 (bs, 1H), 8.03 (s, 1H), 7.62 (d, J = 2.8 Hz, 2H), 7.33 (d, J = 1.2 Hz, 1H), 7.19- 7.15 (m, 3H), 6.88-6.86 (m, 1H), 6.78 (s, 1H), 6.61-6.56 (m, 1H), 5.46 (s, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 462.2 (M + H) +
226	129	XII.25
1 H NMR (400 MHz, DMSO-d6) δ 12.5 (bs, 1H), 8.38 (s, 1H), 8.18 (d, J = 7.6 Hz, 1H), 8.11 (d, J = 3.6 Hz, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.34 (dd, J 1 = 1.6 Hz, J 2 = 7.6 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 6.74 (dd, J 1 = 4.8 Hz, J 2 = 7.2 Hz, 1H), 5.38 (s, 2H), 2.04 (s, 3H), 1.84
				(d, J = 2.4 Hz, 6H), 1.69
				(s, 6H). LC-MS: m/z
				464.2 (M + H) +
227	130	VI.35
1 H NMR (400 MHz, DMSO-d6) δ 12.9 (s, 1H), 7.32-7.26 (m, 3H), 7.09- 7.07 (m, 2H), 6.95 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 1H), 6.93 (d, J = 7.2 Hz, 1H), 6.35 (d, J = 2.4 Hz, 1H), 4.97 (s, 2H), 2.03 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 435.2 (M + H) +
228	131	XII.26
1 H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 10.2 (s, 1H), 8.40- 8.30 (m, 2H), 7.40-7.39 (m, 2H), 7.38-7.30 (m, 1H), 699-6.90 (m, 2H), 6.90-6.80 (m, 1H), 6.80- 6.70 (m, 1H), 4.30 (s, 2H), 3.36 (m, 2H), 2.9 (m, 2H), 2.05 (s, 3H), 1.85 (d, J = 2.4
				Hz, 6H), 1.73 (s, 6H). LC-
				MS: m/z 514.2 (M + H)
233	132	XX.2
1 H NMR (400 MHz, DMSO-d6) δ 12.53 (bs, 1H), 8.35 (dd, J 1 = 1.9 Hz, J 2 = 4.4 Hz, 1H), 7.83 (dd, J 1 = 2.0 Hz, J 2 = 7.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.34 (dd, J 1 = 1.9 Hz, J 2 = 8.8 Hz, 1H), 7.23 (d, J = 8.4 Hz, 1H), 7.0-6.92 (m, 2H), 6.3 (dd, J 1 = 1.9 Hz, J 2 = 8.3 Hz, 1H), 6.1 (dd,
				J 1 = 1.9 Hz, J 2 = 8.3 Hz,
				1H), 6.04 (d, J = 2.5 Hz,
				1H), 3.34 (s, 3H), 3.07 (s,
				3H), 2.06 (s, 3H), 1.86 (s,
				6H), 1.74 (s, 6H). LC-MS:
				m/z 502.3 (M + H) +
236	133	XX.3
1 H NMR (400 MHz, DMSO-d6) δ 12.60 (bs, 1H), 8.30 (dd, J 1 = 2.0 Hz, J 2 = 4.9 Hz, 1H), 7.82 (dd, J 1 = 1.5 Hz, J 2 = 7.4 Hz, 1H), 7.71 (s, 1H), 7.38 (d, J = 2.9 Hz, 2H), 7.32 (dd, J 1 = 1.9 Hz, J 2 = 8.3 Hz, 1H), 6.88 (m, 2H), 5.27 (s, 2H), 3.25 (s, 2H), 2.08 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS:
				m/z 477.2 (M + H) +
240	134	XII.27
1 H NMR (400 MHz, DMSO-d6) δ 13.82-13.2 (bs, 1H), 10.44 (s, 1H), 8.37 (dd, J 1 = 1.6 Hz, J 2 = 4.4 Hz, 1H), 8.19 (dd, J 1 = 1.6 Hz, J 2 = 7.6 Hz, 1H), 7.60 (d, J = 1.6 Hz, 1H), 7.42 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 2H), 7.34 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 1H), 7.11 (d, J = 8.4 Hz,
				1H), 6.78 (dd, J 1 = 4.8 Hz,
				J 2 = 8.0 Hz, 1H), 5.26 (s,
				2H), 2.04 (s, 3H), 1.82
				(d, J = 6.8 Hz, 6H), 1.71
				(s, 6H). LC-MS: m/z
				463.2 (M + H) +
241	135	VI.38
1 H NMR (400 MHz, DMSO-d6) δ 12.61 (s, 1H), 8.39 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 7.89 (dd, J 1 = 2.0 Hz, J 2 = 7.6 Hz, 1H), 7.46 (s, 1H), 7.29 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 2H), 7.16 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 1H), 7.07- 6.98 (m, 2H), 6.61 (t, J = 8.4 Hz, 2H), 6.41 (t,
				J = 1.6 Hz, 1H), 3.36 (s,
				3H), 2.04 (s, 3H), 1.82 (s,
				6H), 1.72 (s, 6H). LC-MS:
				m/z 488.1 (M + H) +
243	136	VI.39
1 H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 8.23 (s, 1H), 8.13 (d, J = 6.9 Hz, 1H), 7.52 (s, 1H), 7.33 (s, 1H), 7.19 (m, 3H), 7.04 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).
				LC-MS: m/z 475.1
244	137	XIII.10
1 H NMR (400 MHz, DMSO-d6) δ 8.59 (dd, J 1 = 1.6 Hz, J 2 = 4.4 Hz, 1H), 8.22 (dd, J 1 = 2.0 Hz, J 2 = 8.0 Hz, 1H), 7.49 (dd, J 1 = 4.8 Hz, J 2 = 8.0 Hz, 1H), 7.20 (d, J = 2.0 Hz, 1H), 7.12 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 6.69 (d,
				J = 8.8 Hz, 1H), 5.26 (d,
				J = 7.2 Hz, 1H), 4.45 (s,
				2H), 4.24-4.20 (m, 1H),
				3.36-3.20 (m 2H), 3.10-
				3.02 (m, 2H), 2.36-2.32
				(m, 1H), 2.02 (s, 3H),
				1.78 (s, 6H), 1.67 (s, 6H).
				LC-MS: m/z 466.20
				(M + H) +
245	138	VI.40
1 H NMR (400 MHz, DMSO-d6) δ 12.8-12.0 (bs, 1H), 8.2 (s, 1H), 7.87 (s, 1H), 7.67 (d, J = 5.6 Hz, 1H), 7.17 (d, J = 8.8 Hz, 2H), 6.95-6.89 (m, 4H), 6.85-6.82 (m, 3H), 3.3 (s, 3H), 2.03 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H).
				LC-MS: m/z 454.1
				(M + H) +
246	139	XX.4
1 H NMR (400 MHz, DMSO-d6) δ 12.49 (s, 1H), 8.34 (s, 1H), 7.77- 7.76 (m, 1H), 7.24-7.22 (m, 2H), 6.93-6.87 (m, 7H), 3.19 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 468.1 (M + H) +
247	140	XX.5
1 H NMR (400 MHz, DMSO-d6) δ 12.57 (s, 1H), 8.36 (dd, J 1 = 2.0 Hz, J 2 = 4.9 Hz, 1H), 7.86 (dd, J 1 = 1.4 Hz, J 2 = 7.3 Hz, 1H), 7.23 (d, J = 8.3 Hz, 2H), 7.09 (d, J = 8.4 Hz, 1H), 6.95 (m, 3H), 6.5 (m, 2H), 6.39 (t, J = 2.4 Hz, 1H), 3.35 (s, 3H), 3.16 (s, 3H), 2.04 (bs,
				3H), 1.82 (s, 6H), 1.69 (s,
				6H). LC-MS: m/z 468.1
				(M + H) +
248	141	XIII.11
1 H NMR (400 MHz, DMSO-d6) δ 10.80- 12.80 (bs, 1H), 8.54 (d, J = 3.4 Hz, 1H), 8.14 (d, J = 6.8 Hz, 1H), 7.42 (m, 1H), 7.16 (d, J = 2.4 Hz, 1H), 7.09 (dd, J1 = 1.9 Hz, J2 = 8.3 Hz, 1H), 6.67 (d, J = 8.8 Hz, 1H), 4.87 (d, J = 8.0 Hz, 1H), 4.16 (m, 2H), 3.57 (bs, 1H), 2.98
				(d, J = 9.2 Hz, 1H), 2.7
				(m, 1H), 2.57 (m, 3H),
				2.08 (s, 3H), 1.82-1.77
				(m, 9H), 1.73 (m, 7H),
				1.58-1.49 (m, 3H). LC-
				MS: m/z 480.1 (M + H) +
249	142	XII.28
1 H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 10.6 (bs, 1H), 8.22- 8.21 (m, 1H), 8.16 (dd, J 1 = 1.6 Hz, J 2 = 7.2 Hz, 1H), 7.47-7.38 (m, 4H), 7.27 (d, J = 8.4 Hz, 1H), 6.72 (dd, J 1 = 4.4 Hz, J 2 = 7.6 Hz, 1H), 6.52 (d, J = 8.8 Hz, 2H), 3.17 (s,
				3H), 2.07 (s, 3H), 1.89 (s,
				6H), 1.74 (s, 6H). LC-MS:
				m/z 487.2 (M + H) +
250	143	VI.42
1 H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 9.80 (s, 1H), 7.88 (s, 1H), 7.39 (d, J = 1.4 Hz, 1H), 7.33-7.27 (m, 4H), 6.98 (d, J = 8.3 Hz, 2H), 4.20-4.17 (bs, 2H), 3.49- 3.42 (m, 1H), 2.85-2.70 (m, 3H), 2.06 (s, 3H),
				1.91-1.85 (m, 7H), 1.84-
				1.72 (m, 8H), 1.57-1.40
				(m, 1H). LC-MS: m/z
				479.1 (M + H) +2
252	144	VI.43
1 H NMR (400 MHz, DMSO-d6) δ 12.72 (s, 1H), 7.99 (s, 1H), 7.96 (d, J = 1.6 Hz, 1H), 7.80 (dd, J 1 = 1.6 Hz, J 2 = 7.6 Hz, 1H), 7.68-7.61 (m, 2H), 7.42-7.35 (m, 3H), 7.29 (d, J = 2.0 Hz, 1H), 7.17 (dd, J 1 = 2.4 Hz,
				J 2 = 8.8 Hz, 1H), 3.30 (s,
				3H), 2.08 (s, 3H), 1.82 (s,
				6H), 1.71 (s, 6H). LC-MS:
				m/z 487.1 (M − H) +
254	145	XV.11
1 H NMR (400 MHz, DMSO-d6) δ 13.72 (bs, 1H), 10.74 (bs, 1H), 10.02 (s, 1H), 8.46 (dd, J 1 = 1.9 Hz, J 2 = 5.0 Hz, 1H), 8.30 (dd, J 1 = 2.0 Hz, J 2 = 7.8 Hz, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.88 (d,
				J = 8.8 Hz, 2H), 7.69 (d,
				J = 8.8 Hz, 2H), 7.32 (d,
				J = 8.8 Hz, 2H), 6.96 (m,
				1H), 2.06 (s, 3H), 1.87 (s,
				6H), 1.74 (s, 6H). LC-MS:
				m/z 468.1 (M + H) +
255	146	XV.12
1 H NMR (400 MHz, DMSO-d6) δ 13.00-12.8 (bs, 1H), 9.77 (s, 1H), 7.85 (d, J = 6.4 Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.66-7.64 (m, 3H), 7.50- 7.42 (m, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.28 (d,
				J = 8.8 Hz, 2H), 6.52 (d,
				J = 8.8 Hz, 2H), 3.26 (s,
				3H), 2.05 (s, 3H), 1.85 (s,
				6H), 1.73 (s, 6H). LC-MS:
				m/z 481.1 (M + H) +
258	147	XV.13
1 H NMR (400 MHz, DMSO-d6) δ 9.87 (s, 1H), 8.43 (bs, 1H), 7.95 (d, J = 6.9 Hz, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 8.3 Hz, 2H), 7.19 (m, 1H), 6.82 (d, J = 8.3
				Hz, 2H), 3.38 (s, 3H),
				2.05 (s, 3H), 1.86 (s, 6H),
				1.73 (s, 6H). LC-MS:
				m/z 482.25 (M + H) +
259	148	XV.14
1 H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.93 (s, 1H), 9.71 (s, 1H), 8.03 (d, J = 8.8 Hz, 2H), 7.94 (d, J = 8.8 Hz, 2H), 7.79 (m, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.51
				(d, J = 7.3 Hz, 1H), 7.31
				(d, J = 8.8 Hz, 2H), 7.12
				(d, J = 8.3 Hz, 1H), 2.06
				(s, 3H), 1.83 (s, 6H), 1.74
				(s, 6H). LC-MS: m/z 468.20
				(M + H) +
260	149	XX.6
1 H NMR (400 MHz, DMSO-d6) δ 12.00-11.8 (bs, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.5 (d, J = 8.4 Hz, 1H), 7.4-7.35 (m, 1H), 7.32-7.2 (m, 1H), 7.25-7.15 (m, 3H), 6.86 (d, J = 8.4 Hz, 2H), 6.42
				(bs, 2H), 3.16 (s, 3H),
				3.07 (s, 3H), 2.02 (s, 3H),
				1.78 (s, 6H), 1.72 (s, 6H).
				LC-MS: m/z 495.2 (M + H) +
261	150	XII.29
1 H NMR (400 MHz, DMSO-d6) δ 10.4 (bs, 1H), 7.62 (t, J = 8.0 Hz, 1H), 7.54 (s, 1H), 7.34-7.31 (m, 3H), 7.24 (dd, J 1 = 1.2 Hz, J 2 = 8.4 Hz, 1H), 7.17- 7.09 (m, 2H), 7.04 (s, 1H), 6.97 (d, J = 7.2 Hz, 1H), 6.63 (d, J = 8.4 Hz, 1H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 474.1 (M + H) +
263	151	XII.31
1 H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 11.67 (s, 1H), 9.07 (s, 1H), 8.52 (d, J = 2.0 Hz, 1H), 8.28 (d, J = 2.4 Hz, 1H), 7.60 (s, 1H), 7.51-7.45 (m, 3H), 7.34 (s, 1H), 7.22 (s, 1H), 1.91 (s, 2H), 1.72-1.64 (m, 13H). LC-MS: m/z 506.0 (M + H) +
266	152	XX.7
1 H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 8.43 (dd, J 1 = 2.0 Hz, J 2 = 4.4 Hz, 1H), 7.96 (dd, J 1 = 2.0 Hz, J 2 = 7.6 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.08-7.04 (m, 3H), 6.59-6.58 (m, 2H), 6.37 (s, 1H), 3.37 (s, 3H), 3.2 (s, 3H), 2.06 (s, 3H), 1.83 (d, J = 2.4 Hz, 6H), 1.73 (s, 6H). LC-MS: m/z 536.1 (M + H) +
267	153	XII.32
1 H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 8.83 (s, 1H), 8.54 (dd, J 1 = 0.8 Hz, J 2 = 12.0 Hz, 2H), 8.14 (s, 1H), 7.91 (s, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.35-7.28 (m, 2H), 6.84 (s, 1H), 6.73 (d, J = 13.6 Hz, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 542.2 (M + H) +
268	154	XII.24
1 H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 11.58 (s, 1H), 9.5 (s, 1H), 7.6 (t, J = 7.2 Hz, 2H), 7.49-7.43 (m, 5H), 6.63 (d, J = 8.4 Hz, 1H), 1.99 (s, 3H), 1.72-1.60 (m, 12H). LC-MS: m/z 506.2 (M + H) +
270	155	XX.8
1 H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 7.80 (m, 1H), 7.60 (m, 1H), 7.29 (m, 4H), 6.83 (t, J = 9.3 Hz, 4H), 6.57 (d, J = 8.8 Hz, 2H), 3.19 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H).
				LC-MS: m/z (M + H) +
				LC-MS: m/z 454.1 (M + H) +
271	156	XX.9
1 H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 8.52 (dd, J 1 = 1.6 Hz, J 2 = 4.4 Hz, 1H), 8.03 (dd, J 1 = 1.6 Hz, J 2 = 7.2 Hz, 1H), 7.21-7.16 (m, 4H), 7.12 (d, J = 8.8 Hz, 2H), 6.44 (d, J = 8.8 Hz, 2H), 3.44 (s, 3H), 3.06 (s, 3H), 2.02 (s, 3H), 1.79 (s, 6H), 1.67 (s, 6H). LC-MS: m/z
				536.1 (M + H) +
272	157	XV.15
1 H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 10.16 (s, 1H), 9.6 (bs, 1H), 7.89 (m, 3H), 7.77 (d, J = 9.3 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.38 (m, 1H), 7.23 (d, J = 8.8 Hz, 2H), 7.14 (d,
				J = 8.8 Hz, 1H), 6.74 (m,
				1H), 2.08 (s, 3H), 1.90 (s,
				6H), 1.76 (s, 6H). LC-MS:
				m/z 467.1 (M + H) +
273	158	XX.10
1 H NMR (400 MHz, DMSO-d6) δ 12.9 (bs, 1H), 7.85 (dd, J 1 = 1.2 Hz, J 2 = 8.8 Hz, 1H), 7.70- 7.66 (m, 1H), 7.46-7.39 (m, 2H), 7.10-7.04 (m, 3H), 6.78-6.73 (m, 2H), 6.39 (d, J = 8.8 Hz, 2H), 3.31 (s, 3H), 3.02 (s, 3H), 2.02 (s, 3H), 1.74 (s, 6H), 1.67 (s, 6H). LC-MS:
				m/z 535.1 (M + H) +
274	159	XV.16
1 H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 9.71 (s, 1H), 7.94- 7.91 (m, 1H), 7.46-7.42 (m, 1H), 7.34-7.25 (m, 5H), 6.85 (t, J = 7.2 Hz, 1H), 1.56-1.48 (m, 5H), 1.33-1.12 (m, 6H), 0.92- 0.74 (m, 7H). LC-MS: m/z 369.1 (M + H) +
275	160	XX.11
1 H NMR (400 MHz, DMSO-d6) δ 12.72 (s, 1H), 7.68-7.65 (m, 2H), 7.53 (t, J = 8.4 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.26-7.19 (m, 2H), 7.09 (d, J = 8.8 Hz, 2H), 6.88 (dd, J 1 = 3.2 Hz, J 2 = 8.8 Hz, 1H), 6.55 (d, J = 9.6 Hz, 1H), 3.29 (s, 3H),
				3.18 (s, 3H), 2.05 (s, 3H),
				1.85 (s, 6H), 1.73 (s, 6H).
				LC-MS: m/z 468.1 (M + H) +
276	161	XX.12
1 H NMR (400 MHz, DMSO-d6) δ 12.79 (s, 1H), 7.79 (dd, J 1 = 1.5 Hz, J 2 = 7.3 Hz, 1H), 7.62 (t, J = 1.5 Hz, 1H), 7.35 (m, 2H), 7.14 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 6.63 (d, J = 8.8 Hz, 2H), 6.57 (d, J = 9.3 Hz, 2H), 3.26 (m, 1H), 3.20
				(s, 3H), 3.18 (s, 3H), 1.48
				(m, 4H), 1.23 (m, 4H),
				0.83 (m, 6H). LC-MS:
				m/z 488.7 (M + H) +
277	162	XX.13
1 H NMR (400 MHz, DMSO-d6) δ 12.79 (s, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.60-7.59 (m, 1H), 7.37-7.25 (m, 4H), 7.17- 7.14 (m, 1H), 7.08-7.00 (m, 5H), 6.72 (d, J = 8.8 Hz, 2H), 6.59 (d, J = 8.8 Hz, 2H), 3.2 (s, 6H), 3.08-3.04 (m, 1H), 1.1 (d, J = 6.8 Hz, 6H). LC-MS: m/z 451.1 (M + H) +
278	163
LC-MS: m/z 495.2 (M + H) +
279	164
LC-MS: m/z 523.6 (M + H) +
282	165
LC-MS: m/z 453.1 (M + H) +
284	166	XII.36
1 H NMR (400 MHz, DMSO-d6) δ 11.90 (bs, 1H), 7.88 (d, J = 7.4 Hz, 1H), 7.46 (s, 1H), 7.30 (d, J = 2.4 Hz, 1H), 7.11 (m, 4H), 6.91 (m, 4H), 6.63 (m, 1H), 2.05 (s, 3H), 1.85 (s, 6H), 1.72 (s,
				6H). LC-MS: 474.0
				(M + H) +
285	167	XV.17
1 H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 9.90 (bs, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.45- 7.43 (m, 2H), 7.36 (d, J = 7.6 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 6.86 (t, J = 7.2 Hz, 1H), 2.07 (s,
				9H), 1.66 (s, 6H). LC-
				MS: m/z 391.0 (M + H) +
286	168	XX.14
1 H NMR (400 MHz, DMSO-d6) δ 12.7 (bs, 1H), 7.75 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.61- 7.57 (m, 1H), 7.43 (d, J = 2.0 Hz, 1H), 7.43-7.23 (m, 3H), 6.81 (t, J = 9.2 Hz, 3H), 6.57 (d, J = 8.8
				Hz, 2H), 3.19 (s, 3H),
				2.04 (s, 3H), 1.83 (s, 6H),
				1.72 (s, 6H). LC-MS: m/z
				488.0 (M + H) +
287	169	VI.46
1 H NMR (400 MHz, DMSO-d6) δ 13.60- 12.00 (bs, 1H), 9.50 (s, 1H), 8.34 (s, 1H), 7.87 (dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, 1H), 7.36-7.03 (m, 10H), 6.70 (t, J = 7.2 Hz, 1H), 4.06-4.02 (m, 2H), 2.88-2.83 (m, 3H), 1.68-
				1.55 (m, 4H), 1.33-1.10
				(m, 5H), 0.89 (t, J = 7.2
				Hz, 6H). LC-MS: m/z
				444.1 (M + H) +
288	170	XV.18
1 H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 11.9 (bs, 1H), 10.38 (bs, 1H), 9.8 (s, 1H), 7.96 (m, 4H), 7.7 (bs, 1H), 7.47 (m, 2H), 7.36 (m, 2H), 6.92 (m, 1H), 6.6 (bs, 1H), 3.44 (m, 4H),
				1.53 (m, 4H), 1.27 (m,
				4H), 0.84 (m, 6H). LC-MS:
				m/z 460.1 (M + H) +
289	71	XII.37
1 H NMR (400 MHz, DMSO-d6) δ 12.85 (bs, 1H), 7.77 (dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, 1H), 7.61- 7.57 (m, 1H), 7.35-7.32 (m, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 9.6 Hz, 2H), 6.67 (d, J = 8.8 Hz, 2H), 6.55 (d, J = 6.8
				Hz, 2H), 3.66-3.61 (m,
				2H), 3.13 (s, 3H), 2.03 (s,
				3H), 1.79 (s, 6H), 1.71 (s,
				6H), 1.13 (t, J = 7.6 Hz,
				3H). LC-MS: m/z 481.1
				(M + H) +
290	172	XII.38
1 H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 9.48 (s, 1H), 7.87 (dd, J 1 = 1.2 Hz, J 2 = 7.6 Hz, 1H), 7.35 (t, J = 6.8 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 7.15 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.8 Hz, 1H), 6.99-6.94 (m, 4H), 6.70 (t, J = 7.2 Hz,
				1H), 3.23 (s, 3H), 2.05 (s,
				3H), 1.84 (s, 6H), 1.78 (s,
				6H). LC-MS: m/z 453.1
				(M + H) +
291	173	VI.47
1 H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 8.48 (s, 1H), 7.83 (d, J = 7.2 Hz, 1H), 7.70- 7.65 (m, 3H), 7.31-7.25 (m, 3H), 7.16-7.13 (m, 4H), 3.84 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 478.1 (M + H) +
292	174	VI.48
1 H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 9.40 (s, 1H), 8.09 (s, 1H), 7.87 (d, J = 1.4 Hz, 1H), 7.33 (t, J = 6.8 Hz, 1H), 7.15-7.08 (m, 8H), 7.01-6.98 (m, 3H), 6.70- 6.65 (m, 4H), 3.58 (t, J = 7.8 Hz, 2H), 1.58-1.51 (m, 2H), 1.38-1.28 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H), LC-MS: m/z 452.1
				(M + H) +
293	175	XV.19
1 H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 9.50 (bs, 1H), 8.36 (s, 1H), 7.88 (dd, J 1 = 1.4 Hz, J 2 = 7.8 Hz, 1H), 7.36 (t, 1H), 7.21-7.13 (m, 6H), 7.06-7.01 (m, 3H), 6.70 (t, J = 7.8 Hz, 1H), 3.30 (m, 4H), 1.52-1.49
				(m, 4H), 1.23 (m, 4H),
				0.86-0.84 (m, 6H). LC-
				MS: m/z 460.1 (M + H) +
294	176	XV.20
1 H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 9.5 (s, 1H), 8.45 (s, 1H), 7.88 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.35 (t, J = 1.6 Hz, 1H), 7.23 (s, 1H), 7.20-7.14 (m, 4H), 7.07 (d, J = 8.4 Hz, 1H),
				6.99 (d, J = 8.8 Hz, 2H),
				6.73-6.69 (m, 1H), 2.06
				(s, 9H), 1.65 (s, 6H). LC-
				MS: m/z 482.1 (M + H) +
295	177	VI.49
1 H NMR (400 MHz, DMSO-d6) δ 12.83 (bs, 1H), 9.42 (s, 1H), 7.99 (s, 1H), 7.85 (dd, J 1 = 1.6 Hz, J 2 = 7.6 Hz, 1H), 7.32 (t, J = 8.8 Hz, 1H), 7.20 (d, J = 8.8 Hz, 2H), 7.11-7.04 (m, 4H), 7.01-6.96 (m, 3H), 6.67 (t, J = 7.6 Hz, 1H), 2.13-2.12 (m, 1H), 1.66 (s, 2H), 1.50-1.32
				(m, 8H), 1.17 (s, 2H),
				0.85 (s, 6H). LC-MS:
				m/z 467.1 (M + H) +
296	178	XX.15
1 H NMR (400 MHz, DMSO-d6) δ 12.79 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.58 (t, J = 6.8 Hz, 1H), 7.33-7.29 (m, 2H), 7.11 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 3.18 (s, 3H), 3.12 (s, 3H), 2.10 (m, 1H), 1.62 (s, 2H), 1.46-1.30 (m, 8H), 1.16 (s,
				2H), 0.83 (s, 6H). LC-MS:
				m/z 495.1 (M + H) +
297	179	XV.21
1 H NMR (400 MHz, DMSO-d6) δ 12.84 (bs, 1H), 10.04 (s, 1H), 9.23 (s, 1H), 7.89 (d, J = 8.3 Hz, 2H), 7.78 (d, J = 8.3 Hz, 2H), 7.67 (m, 3H), 7.51 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 6.8 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H),
				2.08 (s, 3H), 1.91 (s, 6H),
				1.76 (s, 6H). LC-MS: m/z
				468.0 (M + H) +
298	180	XI.17
1 H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 10.27 (s, 1H), 8.51 (d, J = 13.6 Hz, 2H), 8.34 (s, 1H), 8.21 (d, J = 6.8 Hz, 1H), 7.58 (d, J = 7.2 Hz, 2H), 7.40-7.35 (m, 4H), 7.25 (d, J = 7.2 Hz, 2H), 6.81 (bs, 1H), 2.04
				(s, 3H), 1.84 (s, 6H), 1.73
				(s, 6H). LC-MS: m/z 483.1
				(M + H) +
299	181	XIX.3
1 H NMR (400 MHz, DMSO-d6) δ 13.80- 12.80 (bs, 1H), 10.05 (bs, 1H), 9.86 (s, 1H), 8.25 (d, J = 2.8 Hz, 1H), 8.15 (d, J = 7.2 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.8 Hz, 2H), 7.27
				(d, J = 8.0 Hz, 2H), 6.71
				(dd, J 1 = 4.8 Hz, J 2 = 8.0
				Hz, 1H), 6.58 (d, J = 8.8
				Hz, 2H), 5.85 (bs, 1H),
				3.82 (bs, 2H), 2.04 (s,
				3H), 1.82 (s, 6H), 1.72 (s,
				6H). LC-MS: m/z 497.1
				(M + H) +
300	182	XIX.1
1 H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.13 (s, 1H), 8.50 (s, 1H), 8.43 (s, 1H), 7.68 (m, 3H), 7.37 (m, 5H), 7.25 (d, J = 8.3 Hz, 2H), 6.98 (d, J = 8.3 Hz, 1H), 2.05 (s, 3H), 1.76 (s, 6H), 1.73 (s, 6H). LC-MS: m/z
				483.1 (M + H) +
301	183	XV.22
1 H NMR (400 MHz, DMSO-d6) δ 9.76 (bs, 1H), 8.32 (bs, 1H), 8.25 (m, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.89 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.3 Hz, 1H), 7.45 (s, 1H), 7.37 (m, 1H), 6.86 (m, 1H), 2.07 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H). LC-MS:
				m/z 502.0 (M + H) +
302	184	XV.23
1 H NMR (400 MHz, DMSO-d6) δ 14.00- 13.00 (bs, 1H), 10.36 (s, 1H), 10.02 (s, 1H), 8.36 (m, 1H), 8.24 (d, J = 7.8 Hz, 1H), 7.65 (d, J = 8.3 Hz, 2H), 7.52 (d, J = 8.8 Hz, 2H), 7.28-7.25 (m, 4H), 6.86-6.83 (m, 1H),
				3.56 (s, 2H), 2.03 (s, 3H),
				1.82 (s, 6H), 1.71 (s, 6H).
				LC-MS: m/z 482.1 (M + H) +
303	185	XV.24
1 H NMR (400 MHz, DMSO-d6) δ 12.93 (bs, 1H), 9.91 (s, 1H), 8.81 (s, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.75 (s, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.48- 7.39 (m, 3H), 7.30 (d,
				J = 8.8 Hz, 2H), 7.14 (d,
				J = 8.0 Hz, 2H), 2.05 (s,
				3H), 1.86 (s, 6H), 1.73 (s,
				6H). LC-MS: m/z 467.1
				(M + H) +
304	186	Int-VI
1 H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 9.66 (s, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.40- 7.38 (m, 3H), 7.26-7.24 (m, 5H), 7.20 (d, J = 8.4 Hz, 2H), 6.82 (t, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 507.1 (M + H) +
305	187	XX.16
1 H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 7.75 (m, 1H), 7.59 (t, 1H), 7.32-7.30 (m, 2H), 7.12-7.08 (m, 2H), 6.93 (t, J = 8.3 Hz, 4H), 6.74 (d, J = 8.3 Hz, 2H), 6.64 (d, J = 7.3 Hz, 2H), 6.58 (d, J = 7.8 Hz, 3H), 3.56-3.54 (m, 2H), 3.19 (s, 3H), 3.16 (s, 3H), 1.51-1.49 (m, 2H), 1.33- 1.28 (m, 2H), 0.87 (t,
				J = 7.3 Hz, 3H), LC-MS:
				m/z 480.1 (M + H) +
306	188	XVIII.1
1 H NMR (400 MHz, DMSO-d6) δ 13.79 (bs, 1H), 10.77 (s, 1H), 10.03 (s, 1H), 8.44-8.43 (m, 1H), 8.28 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.89 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.8 Hz, 2H), 7.19 (d,
				J = 8.8 Hz, 2H), 7.03-6.96
				(m, 3H), 1.99 (s, 3H),
				1.76 (s, 6H), 1.68 (s, 6H).
				LC-MS: m/z 504.0 (M + H) +
307	189	XIX.2
1 H NMR (400 MHz, DMSO-d6) δ 12.95 (bs, 1H), 9.50 (bs, 1H), 8.60 (s, 1H), 8.52 (s, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.46 (d, J = 8.3 Hz, 2H), 7.36 (m, 3H), 7.26 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.3
				Hz, 1H), 6.70 (t, J = 7.4
				Hz, 1H), 2.05 (s, 3H),
				1.84 (s, 6H), 1.73 (s, 6H).
				LC-MS: m/z 482.0 (M + H) +
308	190	Int- XVIII
1 H NMR (400 MHz, DMSO-d6) δ 13.25 (bs, 1H), 10.02 (s, 1H), 9.75 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.49-7.41 (m, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz,
				2H), 6.96 (t, J = 7.2 Hz,
				1H), 2.00 (s, 3H), 1.77 (s,
				6H), 1.69 (s, 6H). LC-MS:
				m/z 503.0 (M + H) +
309	191	VI.50
1 H NMR (400 MHz, DMSO-d6) δ 12.8 (s, 1H), 7.81 (d, J = 7.2 Hz, 1H), 7.66-7.62 (m, 1H), 7.41-7.32 (m, 6H), 7.27 (d, J = 8.8 Hz, 2H), 6.48 (d, J = 8.0 Hz, 2H), 3.22 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 462.1 (M + H) +
310	192	XX.17
1 H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 9.8 (bs, 1H), 7.9 (m, 1H), 7.40-7.30 (m, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.21-7.19 (m, 3H), 7.08 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 6.90-
				6.80 (m, 1H), 3.34 (s,
				3H), 2.02 (s, 3H), 1.81 (s,
				6H), 1.70 (s, 6H). LC-MS:
				m/z 481.0 (M + H) +
311	193	XII.39
1 H NMR (400 MHz, DMSO-d6) δ 10.40- 10.00 (bs, 1H), 7.57 (t, J = 8.0 Hz, 1H), 7.50-7.40 (m, 2H), 7.28 (d, J = 7.2 Hz, 1H), 7.20 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.4 Hz, 1H), 6.84 (d, J = 8.8 Hz, 2H), 3.22 (s, 3H),
				2.04 (s, 3H), 1.83 (s, 6H),
				1.72 (s, 6H). LC-MS: m/z
				m/z 454.0 (M + H) +
312	194	XVIII.2
1 H NMR (400 MHz, DMSO-d6) δ 13.10 (bs, 1H), 9.97 (s, 1H), 9.76 (s, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.77 (t, J = 7.6 Hz, 1H), 7.64 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 7.2 Hz, 1H), 7.19 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 8.0 Hz,
				1H), 7.02 (d, J = 8.4 Hz,
				2H), 1.99 (s, 3H), 1.76 (s,
				6H), 1.68 (s, 6H). LC-MS:
				m/z 504.2 (M + H) +
313	195	XV.25
1 H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 7.90 (t, J = 8.8 Hz, 3H), 7.70 (d, J = 8.8 Hz, 2H), 7.35 (m, 1H), 7.23- 7.21 (m, 1H), 7.19-7.15 (m, 4H), 7.02 (d, J = 8.8 Hz, 2H), 6.82-6.76 (m, 4H), 3.63 (t, J = 7.4 Hz,
				2H), 1.53-1.51 (m, 2H),
				1.35-1.31 (m, 2H), 0.86
				(t, J = 7.3 Hz, 3H), LC-MS:
				m/z 480.2 (M + H) +
314	196	XX.18
1 H NMR (400 MHz, DMSO-d6) δ 12.60 (bs, 1H), 8.37 (dd, J 1 = 2.0 Hz, J 2 = 4.9 Hz, 1H), 7.81 (dd, J 1 = 1.9 Hz, J 2 = 7.8 Hz, 1H), 7.35 (d, J = 3.4 Hz, 2H), 6.99-6.87 (m, 7H), 3.40 (s, 3H), 2.08 (s, 3H), 1.76 (s, 6H), 1.69 (s, 6H). LC-MS: m/z 455.3 (M + H) +
315	197	XV.26
1 H NMR (400 MHz, DMSO-d6) δ 13.6 (bs, 1H), 12.1 (s, 1H), 8.74 (d, J = 8.3 Hz, 1H), 8.64 (s, 1H), 8.05 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 7.3 Hz, 1H), 7.32 (d, J = 8.3 Hz, 2H), 7.17-7.05 (m,
				5H), 2.06 (bs, 3H), 1.86
				(s, 6H), 1.74 (s, 6H). LC-
				MS: m/z 467.3 (M + H) +
316	198	XV.27
1 H NMR (400 MHz, DMSO-d6) δ 12.90 (bs, 1H), 10.10 (s, 1H), 8.55 (s, 1H), 8.40 (s, 1H), 8.04 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 7.9 Hz, 1H), 7.44 (t, J = 7.9 Hz, 1H), 7.31 (d, J = 8.3 Hz, 2H), 7.07
				(d, J = 8.3 Hz, 2H), 7.02
				(d, J = 5.4 Hz, 2H), 2.06
				(s, 3H), 1.86 (s, 6H), 1.73
				(s, 6H). LC-MS: m/z
				467.3 (M + H) +
317	199	VI.51
1 H NMR (400 MHz, DMSO-d6) δ 13.80- 12.40 (s, 1H), 8.65 (s, 1H), 7.99 (d, J = 7.2 Hz, 1H), 7.89 (d, J = 7.2 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.48 (t, J = 7.6 Hz, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.20-7.15 (m, 4H), 3.99 (s, 3H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 478.2 (M + H) +
318	200	VI.52
1 H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 7.67 (d, J = 6.4 Hz, 1H), 7.50-7.46 (m, 1H), 7.27 (d, J = 8.8 Hz, 2H), 7.20-7.17 (m, 2H), 6.80 (d, J = 8.8 Hz, 2H), 6.63 (d, J = 8.8 Hz, 2H), 6.37 (d, J = 8.4 Hz, 2H), 5.03- 5.01 (m, 1H), 4.23-4.19
				(m, 2H), 3.64-3.61 (m,
				2H), 3.14 (s, 3H), 2.04 (s,
				3H), 1.83 (s, 6H), 1.72 (s,
				6H). LC-MS: m/z 509.3
				(M + H) +
319	201	XII.41
1 H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.04 (s, 1H), 7.78 (m, 1H), 7.62 (d, J = 7.2 Hz, 3H), 7.34 (d, J = 6.4 Hz, 1H), 7.16 (d, J = 8.0 Hz, 2H), 7.00-6.92 (m, 5H), 2.12 (m, 1H), 1.65 (s, 2H), 1.49-1.32 (m,
				8H), 1.17 (s, 2H), 0.85 (s,
				6H). LC-MS: m/z 468.3
				(M + H) +
320	202	XII.42
1 H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 9.07 (s, 1H), 7.90 (s, 1H), 7.64 (m, 3H), 7.36 (d, J = 6.8 Hz, 2H), 7.11 (t, J = 7.9 Hz, 2H), 7.00 (m, 6H), 6.66 (m, 3H), 3.56 (m, 2H), 1.54 (m, 2H), 1.34 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H). LC-MS: m/z 453.3 (M + H) +
321	203	XII.43
1 H NMR (400 MHz, DMSO-d6) δ 10.4 (bs, 1H), 7.59 (m, 1H), 7.47 (m, 3H), 7.32 (d, J = 2.4 Hz, 2H), 6.96 (m, 4H), 2.05 (bs, 3H), 1.86 (s, 6H), 1.76 (s, 6H). LC-MS: m/z 475.2 (M + H) +
322	204	XII.44
1 H NMR (400 MHz, DMSO-d6) δ 13.50- 12.50 (bs, 2H), 8.72 (d, J = 2.0 Hz, 2H), 8.11 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.14-7.03 (m, 6H), 6.90 (d, J = 9.2 Hz, 2H), 3.27 (s, 3H), 2.05 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 493.4
323	205	VI.53
1 H NMR (400 MHz, DMSO-d6) δ 13.00- 12.80 (bs, 1H), 9.50-9.40 (bs, 1H), 7.84 (d, J = 7.6 Hz, 1H), 7.8 (s, 1H), 7.3 (t, J = 8.0 Hz, 1H), 7.07- 6.83 (m, 9H), 6.65 (t, J = 7.2 Hz, 1H), 3.47 (s, 2H), 1.98 (s, 3H), 1.73-1.62 (m,
				12H). LC-MS: m/z 469.2
				(M + H) +
324	206	XV.28
1 H NMR (400 MHz, DMSO-d6) δ 12.92 (s, 1H), 9.41 (s, 1H), 7.73- J = 7.6 Hz, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 7.0 (d, J = 8.4 Hz, 1H), 3.33 (s, 3H), 2.01 (s, 3H), 1.79 (s,
				6H), 1.69 (s, 6H). LC-MS:
				m/z 482.3 (M + H) +
325	207	XX.19
1 H NMR (400 MHz, DMSO-d6) δ 13.85 (bs, 1H), 11.20 (bs, 1H), 8.46 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 8.31 (dd, J 1 = 1.6 Hz, J 2 = 7.6 Hz, 1H), 7.94 (d, J = 8.8 Hz, 2H), 7.44 (dd, J = 8.8 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.05-
				6.98 (m, 3H), 3.09 (s,
				3H), 2.04 (s, 3H), 1.84 (s,
				6H), 1.72 (s, 6H). LC-MS:
				m/z 518.3 (M + H) +
326	208	XX.20
1 H NMR (400 MHz, DMSO-d6) δ 12.89 (bs, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.55-7.51 (m, 1H), 7.26 (t, J = 7.6 Hz, 2H), 6.81-6.76 (m, 6H), 6.55 (d, J = 9.2 Hz, 2H), 3.50 (s, 2H), 3.16 (s, 3H), 3.05 (s, 3H), 1.97 (s, 3H), 1.69-1.60 (m, 12H). LC-MS: m/z 497.3 (M + H) +
327	209	VI.54
1 H NMR (400 MHz, DMSO-d6) δ 7.62-7.60 (m, 3H), 7.39-7.28 (m, 4H), 7.19 (t, J = 7.2 Hz, 1H), 7.12-7.04 (m, 7H), 6.91 (d, J = 8.0 Hz, 2H), 3.11-3.08 (m, 1H), 1.12 (d, J = 6.8 Hz, 6H). LC-MS: m/z 424.2 (M + H) +
328	210	VI.55
1 H NMR (400 MHz, DMSO-d6) δ 14.00-13.20 (bs, 1H), 8.50 (s, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 7.2 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.51-7.47 (m, 2H), 7.31-7.27 (m, 4H), 7.16 (d, J = 8.4 Hz, 2H), 3.96 (s, 3H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 478.2 (M + H) +
329	211	XV.29
1 H NMR (400 MHz, DMSO- d6) δ 10.80-10.20 (bs, 1H), 10.16 (s, 1H), 7.98-7.94 (m, 3H), 7.84 (d, J = 8.4 Hz, 2H), 7.44-7.35 (m, 3H), 7.33-7.24 (m, 3H), 7.21-7.20 (m, 3H), 7.13 (d, J = 7.2 Hz, 1H), 6.90-6.86 (m, 1H), 3.07-3.01 (m, 1H), 1.13 (d, J = 7.2 Hz,
				6H). LC-MS: m/z 451.2
				(M + H) +
330	212	XV.30
1 H NMR (400 MHz, DMSO-d6) δ 13.21 (s, 1H), 10.19 (s, 1H), 8.07 (t, J = 7.8 Hz, 1H), 8.02 (d, J = 8.3 Hz, 2H), 7.85 (d, J = 7.4 Hz, 1H), 7.70 (d, J = 8.3 Hz, 2H), 7.33
				(m, 5H), 2.06 (s, 3H),
				1.87 (s, 6H), 1.74 (s, 6H).
				LC-MS: m/z 469.2 (M + H) +
331	213
LC-MS: m/z 481.2 (M + H) +
333	214	XV.31
1 H NMR (400 MHz, DMSO-d6) δ 13.17- 13.16 (bs, 1H), 10.17 (s, 1H), 9.77 (s, 1H), 6.93 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.79 (s, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.63-7.62 (m, 1H), 7.49- 7.42 (m, 3H), 7.33-7.29 (m, 3H), 6.85-6.81 (m, 1H), 2.06 (s, 3H), 1.83 (s, 6H), 1.70 (s, 6H). LC-MS:
				m/z 467.3 (M + H) +
334	215	XV.32
1 H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 10.06 (s, 1H), 7.94 (d, J = 8.3 Hz, 2H), 7.90 (d, J = 7.3 Hz, 1H), 7.68- 7.63 (m, 3H), 7.37 (t, J = 6.8 Hz, 1H), 7.32 (d, J = 8.8 Hz, 2H), 7.16 (d,
				J = 8.3 Hz, 1H), 6.96 (d,
				J = 8.3 Hz, 2H), 2.06 (s,
				3H), 1.86 (s, 6H), 1.74 (s,
				6H). LC-MS: m/z 468.1
				(M + H) +
335	216	XV.33
1 H NMR (400 MHz, DMSO-d6) δ 12.65 (bs, 1H), 9.91 (s, 1H), 7.93- 7.87 (m, 3H), 7.68 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.8 Hz, 2H), 7.22-7.16 (m, 3H), 6.74 (t, J = 7.6 Hz, 1H), 2.14-2.13 (m,
				1H), 1.69 (s, 2H), 1.53-
				1.33 (m, 8H), 0.86 (s,
				6H). LC-MS: m/z 495.3
				(M + H) +
336	217
LC-MS: m/z 468.2 (M + H) +
337	218	VI.56
1 H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.53 (t, J = 8.0 Hz, 1H), 7.26-7.19 (m, 4H), 6.92 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 6.59 (d, J = 7.2 Hz, 2H), 3.20-3.19 (m, 4H), 3.16 (s, 3H), 3.12-3.11 (m,
				4H), 2.04 (s, 3H), 1.82 (s,
				6H), 1.72 (s, 6H). LC-MS:
				m/z 522.3 (M + H) +
338	219	XII.45
1 H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.16 (s, 1H), 8.26 (s, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.68-7.63 (m, 3H), 7.37 (d, J = 6.8 Hz, 1H), 7.18 (s, 1H), 7.08 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.4 Hz, 1H), 6.91 (d,
				J = 8.4 Hz, 2H), 2.05 (s,
				9H), 1.65 (s, 6H). LC-MS:
				m/483.1z (M + H) +
339	220	XII.46
1 H NMR (400 MHz, DMSO-d6) δ 12.0 (s, 1H), 9.81 (s, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.8 Hz, 2H), 7.13- 7.01 (m, 6H), 6.58 (t, J = 6.8 Hz, 1H), 2.83 (t,
				J = 7.6 Hz, 2H), 2.56 (t,
				J = 8.0 Hz, 2H), 2.04 (s,
				3H), 1.83 (s, 6H), 1.72 (s,
				6H). LC-MS: m/z 495.3
				(M + H) +
340	221	VI.57
1 H NMR (400 MHz, DMSO-d6) δ 13.0 (bs, 1H), 8.20 (bs, 1H), 7.70- 7.60 (m, 1H), 7.60-7.50 (m, 1H), 7.35-7.31 (m, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.10-6.97 (m, 4H), 6.71 (bs, 2H), 3.26 (s, 3H), 2.04 (s, 3H), 1.82 (s,
				6H), 1.72 (s, 6H). LC-MS:
				m/z 481.2 (M + H) +
341	222	XV.35
1 H NMR (400 MHz, DMSO-d6) δ 13.10 (bs, 1H), 10.14 (s, 1H), 9.88 (bs, 1H), 7.93 (d, J = 7.6 Hz, 1H), 7.79 (s, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.61 (d, J = 7.6 Hz, 1H), 7.50-7.40 (m, 3H), 7.32- 7.29 (m, 3H), 6.82 (t, J = 7.6 Hz, 1H), 2.14-2.10 (m, 1H), 1.68 (s, 2H), 1.53-1.43 (m, 8H), 1.18 (s, 2H), 0.86 (s, 6H).
				LC-MS: m/z 495.3 (M + H) +
342	223	XVIII.3
1 H NMR (400 MHz, DMSO-d6) δ 13.8 (bs, 1H), 11.0 (bs, 1H), 8.84 (s, 1H), 7.90 (d, J = 7.2 Hz, 1H), 7.59 (d, J = 8.8 Hz, 2H), 7.55-7.48 (m, 2H), 7.43 (s, 1H), 7.33- 7.28 (m, 2H), 7.09 (t, J = 8.0 Hz, 1H), 6.82 (d, J = 8.8 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s,
				6H). LC-MS: m/z 535
				(M + H) −
343	224	XV.36
1 H NMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.84-7.80 (m, 3H), 7.62 (d, J = 7.6 Hz, 1H), 7.52-7.46 (m, 4H), 7.43- 7.31 (m, 2H), 7.27-7.19 (m, 3H), 7.13 (d, J = 8.0 Hz, 1H), 6.82 (t, J = 7.6 Hz, 1H), 3.05-3.01 (m, 1H), 1.13 (d, J = 6.8 Hz, 6H). LC-MS: m/z 451.2 (M + H) +
344	225	XV.37
1 H NMR (400 MHz, DMSO-d6) δ 14.00-13.8 (bs, 1H), 12.30 (s, 1H), 10.35 (s, 1H), 8.71 (d, J = 8.0 Hz, 1H), 8.14-8.07 (m, 5H), 7.27-7.67 (m, 3H), 7.35 (d, J = 8.0 Hz, 2H), 7.24 (t, J = 8.0 Hz, 1H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-
				MS: m/z 495.1 (M + H) +
345	226	XII.47
1 H NMR (400 MHz, DMSO-d6) δ 13.42 (s, 1H), 7.81 (d, J = 6.9 Hz, 1H), 7.61 (t, J = 7.3 Hz, 1H), 7.41 (t, J = 7.8 Hz, 1H), 7.28 (d, J = 7.9 Hz, 1H), 7.14 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 6.70 (d, J = 8.3 Hz, 2H), 6.59 (d, J = 8.8 Hz,
				2H), 4.25-4.19 (m, 1H),
				3.13 (s, 3H), 2.03 (s, 3H),
				1.80 (s, 6H), 1.71 (s, 6H),
				1.00 (d, J = 6.3 Hz, 6H).
				LC-MS: m/z 495.3 (M + H) +
346	227	XV.38
1 H NMR (400 MHz, DMSO-d6) δ 13.10 (bs, 1H), 9.94 (s, 1H), 9.69 (s, 1H), 8.01 (d, J = 8.8 Hz, 2H), 7.94 (d, J = 8.8 Hz, 2H), 7.78 (t, J = 7.6 Hz, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 7.2 Hz, 1H), 7.30 (d, J = 8.4 Hz,
				2H), 7.10 (d, J = 8.0 Hz,
				1H), 2.15-2.13 (m, 1H),
				1.69 (s, 2H), 1.53-1.33
				(m, 8H), 1.19 (s, 2H),
				0.86 (s, 6H). LC-MS: m/z
				496.2 (M + H) +
349	228	VI.58
1 H NMR (400 MHz, DMSO-d6) δ 15.33 (s, 1H), 8.63 (d, J = 8.3 Hz, 1H), 8.04 (s, 1H), 7.99 (d, J = 7.3 Hz, 1H), 7.87 (d, J = 8.3 Hz, 2H), 7.58 (s, 1H), 7.36 (s, 2H), 7.27 (t, J = 7.3 Hz, 1H), 6.96- 6.90 (m, 4H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s,
				6H). LC-MS: m/z 545.1
				(M + H) −
350	229	VI.59
1 H NMR (400 MHz, DMSO-d6) δ 13.6 (bs, 1H), 12.02 (s, 1H), 8.73 (d, J = 8.3 Hz, 1H), 8.30 (s, 1H), 8.04 (d, J = 6.8 Hz, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 7.3 Hz, 1H), 7.44 (D, J = 1.5 Hz, 1H), 7.39-7.32 (m, 2H), 7.16 (t, J = 7.8 Hz,
				1H), 6.99 (d, J = 8.3 Hz,
				2H), 2.07 (s, 3H), 1.87 (s,
				6H), 1.74 (s, 6H). LC-MS:
				m/z 501.1 (M + H) +
353	230	XV.39
1 H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 10.02 (s, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.66- 7.61 (m, 3H), 7.41-7.29 (m, 4H), 7.32-7.21 (m, 2H), 7.09 (s, 1H), 6.62 (d, J = 7.2 Hz, 1H), 3.25 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 481.2 (M + H) +
355	231	XX.21
1 H NMR (400 MHz, DMSO-d6) δ 13.01 (bs, 1H), 8.57 (d, J = 3.2 Hz, 1H), 8.13-8.11 (m, 1H), 7.34-7.26 (m, 5H), 7.03 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 3.38 (s, 3H), 3.03 (s, 3H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 532.2 (M + H) +
356	232
LC-MS: m/z 493.4 (M − H) +
357	233	XX.22
1 H NMR (400 MHz, DMSO-d6) δ 7.42-7.38 (m, 2H), 7.17-7.15 (m, 1H), 7.11 (t, J = 7.6 Hz, 2H), 7.03-7.01 (m, 3H), 6.87 (d, J = 8.8 Hz, 2H), 6.71-6.69 (m, 1H), 6.51 (d, J = 9.2 Hz, 2H), 3.16 (s, 3H), 3.15 (s, 3H), 2.04 (s, 9H), 1.64 (s, 6H). LC- MS: m/z 510.3 (M + H) +
358	234	XII.49
1 H NMR (400 MHz, DMSO-d6) δ 13.68 (s, 1H), 10.58 (s, 1H), 10.19 (s, 1H), 8.43 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 8.28 (dd, J 1 = 1.7 Hz, J 2 = 7.6 Hz, 1H), 8.14 (s, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.7 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 7.6 Hz, 1H),
				7.47 (t, J = 7.6 Hz, 1H),
				7.33 (d, J = 4.8 Hz, 2H),
				6.92 (dd, J 1 = 4.8 Hz,
				J 2 = 7.6 Hz, 1H), 2.06 (s,
				3H), 1.86 (s, 6H), 1.74 (s,
				6H). LC-MS: m/z 468.1
				(M + H) +
359	235	XII.50
1 H NMR (400 MHz, DMSO-d6) δ 12.85 (s, 1H), 10.12 (s, 1H), 8.57 (s, 1H), 7.68-7.61 (m, 4H), 7.45-7.27 (m, 8H), 2.05 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 465.1 (M − H) −
360	236	XX.23
1 H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 7.78 (d, J = 7.9 Hz, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.37-7.31 (m, 3H), 7.23-7.12 (m, 3H), 6.94 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.3 Hz, 1H), 6.61 (d, J = 8.8 Hz, 2H), 3.17
				(s, 3H), 2.97-2.91 (m,
				1H), 1.09 (d, J = 7.3 Hz,
				6H), LC-MS: m/z 472.2
				(M + H) +
361	237	VI.60
1 H NMR (400 MHz, DMSO-d6) δ 13.75 (s, 1H), 12.15 (s, 1H), 8.69 (d, J = 8.3 Hz, 1H), 8.05 (d, J = 8.3 Hz, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.65 (t, J = 7.3 Hz, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.20 (t, J = 7.8 Hz, 1H), 7.12 (d, J = 8.8 Hz, 2H), 7.07 (d, J =
				8.3 Hz, 2H), 2.07 (s, 3H),
				1.88 (s, 6H), 1.74 (s, 6H).
				LC-MS: m/z 468.1 (M + H) +
362	238	XX.24
1 H NMR (400 MHz, DMSO-d6) δ 12.76 (s, 1H), 7.41 (t, J = 8.3 Hz, 1H), 7.12 (d, J = 8.8 Hz, 2H), 7.00 (d, J = 8.3 Hz, 1H), 6.91 (d, J = 8.4 Hz, 2H), 6.76 (d, J = 7.8 Hz, 1H), 6.66 (d, J = 8.3 Hz, 2H), 6.60 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H), 3.13 (s, 3H), 3.09 (s, 3H), 2.02 (s,
				3H), 1.80 (s, 6H), 1.71 (s,
				6H). LC-MS: m/z 497.3
				(M + H) +
363	239	XV.40
1 H NMR (400 MHz, DMSO-d6) δ 8.66 (d, J = 8.4 Hz, 1H), 8.29 (s, 1H), 8.02 (dd, J 1 = 1.2 Hz, J 2 = 7.6 Hz, 2H), 7.65 (s, 1H), 7.44-7.32 (m, 3H), 7.26 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 7.6 Hz, 1H), 7.10-7.04 (m, 2H), 2.05
				(s, 3H), 1.85 (s, 6H), 1.73
				(s, 6H). LC-MS: m/z 467.3
				(M + H) +
364	240	XV.41
1 H NMR (400 MHz, DMSO-d6) δ 10.4 (s, 1H), 8.4 (s, 1H), 8.26 (s, 1H), 8.00 (d, J = 9.2 Hz, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.59 (s, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.35-7.32 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.21-7.19 (m,
				1H), 7.08 (d, J = 8.8 Hz,
				2H), 2.05 (s, 3H), 1.84 (s,
				6H), 1.73 (s, 6H). LC-MS:
				m/z 467.3 (M + H) +
366	241	XII.53
1 H NMR (400 MHz, DMSO-d6) δ 13.69 (bs, 1H), 10.61 (s, 1H), 9.99 (s, 1H), 8.42 (dd, J 1 = 1.0 Hz, J 2 = 4.8 Hz, 1H), 8.28 (dd, J 1 = 1.0 Hz, J 2 = 7.6 Hz, 1H), 8.20 (s, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.67 (m, 1H), 7.54-7.46 (m, 3H), 7.39-7.38 (m,
				1H), 6.92 (dd, J 1 = 4.8 Hz,
				J 2 = 7.6 Hz, 1H), 2.07 (s,
				3H), 1.88 (d, J = 2.4 Hz,
				6H), 1.71 (s, 6H). LC-MS:
				502.2 (M + H) +
367	242	XII.54
1 H NMR (400 MHz, DMSO-d6) δ 10.0 (s, 1H), 9.81-9.79 (bs, 1H), 7.93 (dd, J 1 = 1.2 Hz, J 2 = 7.6 Hz, 1H), 7.82 (s, 1H), 7.65-7.63 (m, 1H), 7.51-7.43 (m, 5H), 7.38- 7.36 (m, 1H), 7.32 (d, J = 8.0 Hz, 1H), 6.86-6.82 (m, 1H), 2.07 (s, 3H),
				1.86 (d, J = 2.4 Hz, 6H),
				1.74 (s, 6H). LC-MS:
				m/z 501.1 (M + H) +
369	243
LC-MS: m/z 493.4 (M − H) +
370	244	Com- pound 14
1 H NMR (400 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 3.2 Hz, 1H), 7.39 (d, J = 8.8 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.19-7.14 (m, 3H), 7.11-7.07 (m, 3H), 6.63 (d, J = 2.4 Hz, 1H), 2.06 (s, 3H), 1.85 (d, J = 2.4
				Hz, 6H), 1.73 (s, 6H).
				LC-MS: m/z 491.3 (M + H) +
371	245	Com- pound 14
1 H NMR (400 MHz, DMSO-d6) δ 7.70-7.58 (m, 4H), 7.21-7.14 (m, 3H), 7.07 (d, J = 8.0 Hz, 1H), 6.96 (d, J = 8.8 Hz, 2H), 6.89-6.84 (m, 5H), 6.35 (d, J = 15.6 Hz, 1H), 2.04 (s, 3H), 1.86 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 465.3 (M + H) +
372	246	XVIII.4
1 H NMR (400 MHz, DMSO-d6) δ 13.21 (bs, 1H), 10.11 (s, 1H), 9.71 (bs, 1H), 7.92 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.53 (s, 1H), 7.49-7.35 (m, 4H), 7.23 (d, J = 8.4 Hz, 2H), 7.07-7.01 (m, 3H),
				6.90 (t, J = 7.6 Hz, 1H),
				2.00 (s, 3H), 1.76 (s, 6H),
				1.68 (s, 6H). LC-MS:
				m/z 503.2 (M + H) +
373	247	XII.55
1 H NMR (400 MHz, DMSO-d6) δ 11.89 (s, 1H), 10.22 (s, 1H), 9.22 (s, 1H), 8.36-8.28 (m, 2H), 7.7-7.51 (m, 4H), 7.33 (d, J = 8.0 Hz, 2H), 6.93 (s, 1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 502.2 (M + H) +
376	248	XII.57
1 H NMR (400 MHz, DMSO-d6) δ 13.00-12.8 (bs, 1H), 10.07 (s, 1H), 8.03 (bs, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.56 (s, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.36-7.26 (m, 4H), 7.21 (dd, J 1 = 0.8 Hz, J 2 = 7.6 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.68 (d, J = 8.4 Hz, 1H), 3.79 (s, 3H), 2.06 (s, 3H), 1.85
				(d, J = 2.4 Hz, 6H), 1.73
				(s, 6H). LC-MS: m/z 497.3
				(M + H) +
377	249	XII.58
1 H NMR (400 MHz, DMSO-d6) δ 12.16 (s, 1H), 9.12 (s, 1H), 7.99 (s, 1H), 7.21 (d, J = 8.4 Hz, 2H), 7.08-6.98 (m, 6H), 6.07 (d, J = 2.4 Hz, 1H), 6.0 (d, J = 2.4 Hz, 1H), 3.81 (s, 3H), 3.67 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 499.2 (M + H) +
379	250	XII.59
1 H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 9.2 (bs, 1H), 7.39 (d, J = 2.9 Hz, 1H), 7.22 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 6.3 Hz, 1H), 7.09 (d, J = 5.8 Hz, 2H), 7.03 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 6.97 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 3.71 (s, 3H), 3.21 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 483.3 (M + H) +
380	251	XII.60
1 H NMR (400 MHz, DMSO-d6) δ 9.57 (s, 1H), 8.04 (s, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.8 Hz, 2H), 7.06 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 6.41 (d, J = 2.0 Hz, 1H), 6.28 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 2H), 3.69 (s, 3H), 2.06 (s, 3H), 1.83 (d, J = 2.0 Hz, 2H), 1.69 (s, 6H). LC-MS: m/z 469.3 (M + H) +
381	252	XII.61
1 H NMR (400 MHz, DMSO-d6) δ 13.62 (bs, 1H), 10.36 (s, 1H), 8.36 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 8.24 (dd, J 1 = 2.0 Hz, J 2 = 8.0 Hz, 1H), 7.71- 7.67 (m, 2H), 7.49 (d, J = 2.0 Hz, 1H), 7.35 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz,
				JH), 6.98-6.93 (m, 3H),
				6.85 (dd, J 1 = 4.8 Hz,
				H 2 = 7.6 Hz, 1H), 2.06 (s,
				3H), 1.86 (s, 6H), 1.76 (s,
				6H). LC-MS: m/z 475.2
				(M + H) +
383	253	XII.62
1 H NMR (400 MHz, DMSO-d6) δ 13.15 (bs, 1H), 9.65 (bs, 1H), 7.88 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.49 (d, J = 2.4 Hz, 1H), 7.37-7.33 (m, 2H), 7.32 (d, J = 2.0 Hz, 2H), 7.09 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 8.8 Hz, 1H),
				6.94 (d, J = 8.8 Hz,
				2H), 6.74 (t, J = 7.6 Hz,
				1H), 2.14 (m, 1H), 1.69
				(s, 2H), 1.53-1.32 (m,
				8H), 1.18 (s, 2H), 0.86 (s,
				6H). LC-MS: m/z 502.2
				(M + H) +
384	254	XII.63
1 H NMR (400 MHz, DMSO-d6) δ 11.20 (bs, 1H), 8.27-8.26 (m, 1H), 8.20 (dd, J 1 = 2.4 Hz, J 2 = 7.6 Hz, 1H), 7.72- 7.68 (m, 2H), 7.47 (d, J = 2.4 Hz, 1H), 7.30 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 6.94-6.92 (m, 3H),
				6.80-6.77 (m, 1H), 2.14-
				2.13 (m, 1H), 1.68 (s,
				2H), 1.52-1.23 (m, 8H),
				1.18 (s, 2H), 0.85 (s, 6H).
				LC-MS: m/z 503.3 (M + H) +
385	255	VI.61
1 H NMR (400 MHz, DMSO-d6) δ 13.49 (s, 1H), 10.29 (s, 1H), 8.33 (s, 1H), 8.21 (d, J = 6.4 Hz, 1H), 8.08-8.05 (bs, 1H), 7.60-7.52 (bs, 2H), 7.22-6.46 (m, 12H), 3.60- 3.58 (bs, 2H), 1.60-1.54 (bs, 2H), 1.33 (bs, 2H), 0.85 (t, J = 6.8 Hz, 3H). LC-MS: m/z 453.3 (M + H) +
386	256	XV.44
1 H NMR (400 MHz, DMSO-d6) δ 13.5 (bs, 1H), 10.42 (bs, 1H), 8.31-8.26 (m, 2H), 8.18 (d, J = 7.6 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.16- 7.06 (m, 4H), 6.94 (d, J = 8.4 Hz, 2H), 6.77 (dd, J 1 = 4.8 Hz, J 2 = 7.6 Hz, 1H), 3.27 (m, 6H), 1.84- 1.45 (m, 4H), 1.30-1.1
				(m, 4H), 0.90-0.70 (m,
				6H). LC-MS: m/z 461.3
				(M + H) +
387	257	XV.45
1 H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 8.50-8.40 (bs, 1H), 8.34-8.25 (m, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.25 (s, 1H), 7.13 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.84 (dd, J 1 = 4.8
				Hz, J 2 = 7.6 Hz, 1H), 2.06
				(s, 9H), 1.65 (s, 6H). LC-
				MS: m/z 483.1 (M + H) +
388	258	VI.63
1 H NMR (400 MHz, DMSO-d6) δ 12.9 (s, 1H), 9.46 (s, 1H), 7.85 (dd, J 1 = 1.6 Hz, J 2 = 8.4 Hz, 1H), 7.52 (s, 1H), 7.34-7.30 (m, 1H), 7.26- 7.18 (m, 3H), 7.11 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 2.4 Hz, 1H), 7.00-6.97 (m, 3H), 6.91-6.84 (m, 4H), 6.67 (t, J = 8.0 Hz,
				1H), 3.62 (t, J = 7.2 Hz,
				2H), 1.58-1.50 (m, 2H),
				1.38-1.29 (m, 2H), 0.88
				(t, J = 7.6 Hz, 3H). LC-MS:
				m/z 486.2 (M + H) +
389	259	VI.64
1 H NMR (400 MHz, DMSO-d6) δ 13.24 (s, 1H), 10.2 (s, 1H), 8.32 (s, 1H), 8.22 (d, J = 7.6 Hz, 1H), 7.53 (bs, 2H), 7.22- 6.84 (m, 12H), 3.51 (bs, 2H), 1.54 (s, 2H), 1.34- 1.23 (m, 2H), 0.88 (t, J = 6.8 Hz, 3H). LC-MS: m/z 487.2 (M + H) +
392	260	XVIII.5
1 H NMR (400 MHz, DMSO-d6) δ 13.40- 13.20 (bs, 1H), 9.79 (s, 1H), 9.70 (s, 1H), 7.95 (dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, 1H), 7.62 (d, J = 8.8 Hz, 2H), 7.52-7.43 (m, 2H), 7.32-7.25 (m, 4H), 7.25-7.20 (m, 1H), 6.99-6.95 (m, 1H), 2.02 (s, 3H), 1.79 (d, J = 2.4 Hz,
				6H), 1.67 (s, 6H). LC-MS:
				m/z 537.2 (M + H) +
393	261	XVIII.6
1 H NMR (400 MHz, DMSO-d6) δ 13.8 (bs, 1H), 10.85 (s, 1H), 9.71 (s, 1H), 8.46 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 8.31 (dd, J 1 = 1.6 Hz, J 2 = 7.6 Hz, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.66 (d, J = 8.8 Hz, 2H), 7.30 (d, J = 2.0 Hz, 1H), 7.26 (dd, J 1 = 2.0
				Hz, J 2 = 8.4 Hz, 1H), 7.17
				(d, J = 8.0 Hz, 1H), 6.99
				(dd, J 1 = 5.2 Hz, J 2 = 8.0
				Hz, 1H), 2.02 (s, 3H),
				1.79 (s, 6H), 1.66 (s, 6H).
				LC-MS: m/z 538.0 (M + H) +
394	262	XV.46
1 H NMR (400 MHz, DMSO-d6) δ 13.70 (bs, 1H), 10.80 (bs, 1H), 9.94 (s, 1H), 8.40 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 8.27 (dd, J 1 = 2.0 Hz, J 2 = 7.6 Hz, 1H), 8.20 (s, 1H), 8.07 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H),
				7.49-7.46 (m, 2H), 7.37
				(dd, J 1 = 2.0, J 2 = 8.4
				Hz, 1H), 6.90 (dd, J 1 = 4.4
				Hz, J 2 = 7.2 Hz, 1H), 2.16-
				2.15 (m, 1H), 1.71 (s,
				2H), 1.56-1.34 (m, 8H),
				1.20 (s, 2H), 0.87 (s, 6H).
				LC-MS: m/z 503.2 (M + H) +
395	263	XII.64
1 H NMR (400 MHz, DMSO-d6) δ 11.40-11.0 (bs, 1H), 10.17 (s, 1H), 7.92 (d, J = 7.2 Hz, 1H), 7.73-7.69 (m, 3H), 7.51 (d, J = 7.2 Hz, 1H), 7.45- 7.38 (m, 2H), 7.29 (d, J = 2.4 Hz, 2H), 7.22-7.18 (m, 2H), 7.03 (d, J = 8.8 Hz, 2H), 6.86-6.74 (m,
				4H), 3.65 (t, J = 7.2 Hz,
				2H), 1.56-1.53 (m, 2H),
				1.36-1.3 (m, 2H), 0.88 (t,
				J = 7.6 Hz, 3H). LC-MS:
				m/z 480.3 (M + H) +
396	264	XVIII.7
1 H NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1H), 9.80 (s, 1H), 9.73 (s, 1H), 7.94 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.60 (d, J = 8.8 Hz, 2H), 7.52-7.43 (m, 2H), 7.32-7.24 (m, 4H), 7.16 (d, J = 8.4 Hz, 1H), 6.97 (t, J = 7.6 Hz, 1H), 2.11-2.09 (m, 1H), 1.62 (s, 2H), 1.42-1.32 (m, 8H),
				1.15 (s, 2H), 0.83 (s, 6H),
				LC-MS: m/z 565.2 (M + H) +
397	265	XVIII.8
1 H NMR (400 MHz, DMSO-d6) δ 13.80 (bs, 1H), 10.80 (s, 1H), 9.69 (s, 1H), 8.46 (dd, J 1 = 1.6 Hz, J 2 = 4.4 Hz, 1H), 8.30 (dd, J 1 = 1.6 Hz, J 2 = 7.6 Hz, 1H), 7.92 (d, J = 9.2 Hz, 2H), 7.65 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 2.0 Hz, 1H), 7.25 (dd, J 1 = 2.0 Hz, J2 = 8.4 Hz, 1H), 7.16
				(d, J = 8.4 Hz, 1H), 6.99
				(dd, J 1 = 4.8 Hz, J 2 = 7.6
				Hz, 1H), 2.11-2.09 (m,
				1H), 1.62 (s, 2H), 1.46-
				1.29 (m, 8H), 1.15 (s,
				2H), 0.82 (s, 6H). LC-
				MS: m/z 566.2 (M + H) +
398	266	XII.65
1 H NMR (400 MHz, DMSO-d6) δ 13.7 (s, 1H), 10.61 (s, 1H), 10.22 (s, 1H), 8.43 (dd, J 1 = 2.0 Hz, J 2 = 4.8 Hz, 1H), 8.28 (dd, J 1 = 2.0 Hz, J 2 = 7.6 Hz, 1H), 8.14 (s, 1H), 8.05 (s, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.52 (s, 1H), 7.47 (s, 1H), 7.23-7.21 (m, 2H),
				7.04 (d, J = 8.8 Hz, 2H),
				6.92-6.80 (m, 4H), 3.66 (t,
				J = 7.2 Hz, 2H), 1.57-1.53
				(m, 2H), 1.36-1.31 (m, 2H),
				0.88 (t, J = 7.6 Hz, 3H).
				LC-MS: m/z 481.2 (M + H) +
407	267	XV.47
1 H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 9.78 (s, 1H), 8.85 (t, J = 5.8 Hz, 1H), 7.93 (dd, J 1 = 1.5 Hz, J 2 = 8.3 Hz, 1H), 7.87 (d, J = 8.3 Hz, 2H), 7.49-7.40 (m, 2H), 7.32-7.23 (m, 6H), 6.89 (t, J = 6.9 Hz, 1H), 4.43 (d, J = 5.9 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73
				(s, 6H). LC-MS: m/z 481.3
				(M + H) +
408	268	XV.48
1 H NMR (400 MHz, DMSO-d6) δ 12.00 (bs, 1H), 8.96 (t, J = 5.9 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.64 (s, 1H), 7.38- 7.16 (m, 10H), 6.68 (t, J = 7.4 Hz, 1H), 4.41 (d, J = 5.9 Hz, 2H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 481.3 (M + H) +
420	269	XII.66
1 H NMR (400 MHz, DMSO- d6) δ 13.2-13.0 (bs, 1H) 9.3- 9.0 (bs, 1H), 7.38 (d, J = 2.8 Hz, 1H), 7.24-7.22 (m, 2H), 7.11-7.05 (m, 4H), 6.98-6.96 (m, 2H), 6.89 (d, J = 9.2 Hz, 2H), 4.04-4.02 (m, 2H), 3.64-3.62 (m, 2H), 3.21 (s, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).
				LC-MS: m/z 572.3 (M + H) +
453	35	XII.70
1H NMR (400 MHz, DMSO-d6): δ 13.10 (s, 1H), 9.12 (s, 1H), 7.37 (d, J = 2.0 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 9.2 Hz, 2H), 7.05 (dd, J1 = 2.8 Hz, J2 = 9.2 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 3.68 (d, J = 6.4 Hz, 2H), 3.21 (s, 3H), 2.04 (s, 3H), 2.01-1.98 (m, 1H), 1.83 (d, J = 2.6
				Hz, 6H), 1.72 (s, 6H),
				0.97 (d, J = 6.8 Hz, 6H).
				LC-MS: m/z 525.3 (M + H)+
473	36	Com- pound 20
1H-NMR (400 MHz, DMSO-d6): 12.67 (s, 1H), 10.01 (s, 1H), 9.57 (s, 1H), 7.78 (d, J = 8.8 Hz, 1H), 7.43 (s, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 7.01-6.95 (m, 5H), 3.57 (t, J = 5.6 Hz, 2H), 3.24 (s, 3H), 3.21 (s, 3H), 2.04 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 554.3 (M + H)+
521	37	XII.71
1H NMR (400 MHz, DMSO-d6): δ 13.20 (bs, 1H), 9.22 (bs, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.41 (d, J = 2.8 Hz, 1H), 7.29 (d, J = 9.2 Hz, 1H), 7.23- 7.09 (m, 5H), 6.81 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.27 (s, 3H). LC-MS: m/z 417.2 (M + H)+.
522	38	XII.72
1H NMR (400 MHz, DMSO-d6): δ 13.09 (bs, 1H), 9.08 (s, 1H), 7.35 (d, J = 2.8 Hz, 1H), 7.10- 7.02 (m, 6H), 6.94 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 3.69 (s, 3H), 3.18 (s, 3H), 2.42- 2.39 (m, 1H), 1.76-1.65 (m, 5H), 1.38-1.20 (m, 5H).
				LC-MS: m/z 431.2
				(M + H)+.
525	39	XII.73
1H NMR (400 MHz, CDCl3) δ 7.71 (s, 1H), 7.26-7.12 (m, 5H), 6.99 (d, J = 8 Hz, 2H), 6.88- 6.83 (m, 3H), 4.41 (s, 2H), 3.49-3.22 (m, 10H), 2.10-2.07 (m, 7H), 1.89 (s, 5H), 1.79-1.75 (s, 6H). LC-MS: m/z 566.3 (M + H)+.
526	40	XII.74
1H NMR (400 MHz, DMSO-d6): δ 7.46 (d, J = 2 Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.12-7.04 (m, 4H), 6.97 (d, J = 8 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 4.13 (t, J = 5.2 Hz, 2H), 3.2 (s, 3H), 3.06 (s, 2H), 2.55 (s, 6H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 540.3 (M + H)+.
527	41	XII.75
1H NMR (400 MHz, DMSO-d6): δ 13.18 (s, 1H), 9.25 (s, 1H), 7.61 (dd, J1 = 2.4 & J2 = 7.6 Hz, 2H), 7.41 (d, J = 3.2 Hz, 1H), 7.30 (d, J = 9.2 Hz, 1H), 7.23-7.16 (m, 4H), 7.09 (dd, J1 = 3.2 Hz, & J2 = 9.2 Hz, 1H), 6.73 (d, J = 9.2 Hz, 2H), 3.74
				(s, 3H), 3.27 (s, 3H). LC-
				MS: m/z 475.1 (M + H)+.
535	42	XII.76
1H NMR (400 MHz, DMSO-d6): δ 13.15 (s, 1H), 9.10 (s, 1H), 7.39 (d, J = 3.2 Hz, 1H), 7.23- 7.16 (m, 5H), 7.11-7.07 (m, 3H), 6.81 (dd, J1 = 2.4 Hz, & J2 = 6.8 Hz, 2H), 3.73 (s, 3H), 3.21 (s, 3H). LC-MS: m/z 382.84 (M + H)+
536	43	XII.77
1H NMR (400 MHz, DMSO-d6): δ 7.39 (d, J = 2.8 Hz, 1H), 7.08 (d, J = 8.4 Hz, 5H), 7.03-7.02 (m, 1H), 6.95 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.0 Hz, 2H), 4.02 (t, J = 4.0 Hz, 2H), 3.62 (t, J = 4.8 Hz, 2H), 3.30 (s, 3H), 3.19 (s, 3H), 2.46-2.42
				(m, 1H), 1.77-1.65 (m,
				5H), 1.37-1.23 (m, 5H).
				LC-MS: m/z 474.3
				(M + H)+.
537	44	XII.78
1H NMR (400 MHz, DMSO-d6): δ 13.18 (bs, 1H), 8.95 (s, 1H), 7.37- 7.32 (m, 3H), 7.22 (t, J = 9.2 Hz, 1H), 7.08-7.03 (m, 3H), 6.83-6.75 (m, 2H), 6.66 (d, J = 8.4 Hz, 1H), 3.70 (s, 3H), 3.23 (s, 3H), 2.05 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS:
				m/z 501.3 (M + H)+.
538	45	XII.79
1H NMR (400 MHz, DMSO-d6): δ 11.6-11.2 (bs, 1H), 7.47 (s, 1H), 7.09 (d, J = 8.8 Hz, 1H), 7.04-7.01 (m, 4H), 6.94 (d, J = 8.8 Hz, 2H), 6.81- 6.78 (m, 1H), 6.74 (d, J = 8.4 Hz, 2H), 3.68 (s, 3H), 3.16 (s, 3H), 2.61- 2.59 (m, 1H), 2.29 (s,
				1H), 2.19 (s, 1H), 1.66-
				1.65 (m, 1H), 1.58-1.51
				(m, 3H), 1.44 (d, J = 10
				Hz, 1H), 1.31-1.21 (m,
				2H), 1.11-1.09 (m, 1H).
				LC-MS: m/z 443.2
				(M + H)+.
541	46	XII.80
1H NMR (400 MHz, DMSO-d6): δ 10.48 (s, 1H), 8.39 (dd, J1 = 2.0 Hz & J2 = 4.8 Hz, 1H), 8.27 (dd, J1 = 2 Hz, & J2 = 8.0 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.46 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 8.8 Hz, 2H), 6.90-6.87 (m, 1H), 6.82 (d, J = 8.8 Hz,
				2H), 3.29 (s, 3H). LC-MS:
				m/z 388.1 (M + H)+.
542	47	XII.81
1H NMR (400 MHz, DMSO-d6): δ 13.10- 12.90 (bs, 1H), 9.02 (s, 1H), 7.23 (d, J = 2.0 Hz, 1H), 7.49 (dd, J1 = 2.0 Hz & J2 = 8.0 Hz, 1H), 7.40 (d, J = 8.8 Hz, 1H), 7.35 (d, J = 2.4 Hz, 2H), 7.05- 6.94 (m, 4H), 6.60 (d, J = 8.8 Hz, 2H), 3.70 (s,
				3H), 3.19 (s, 3H). LC-MS:
				m/z 419.1 (M + H)+.
543	48	XII.82
1H NMR (400 MHz, DMSO-d6): δ 13.1 (bs, 1H), 9.63 (s, 1H), 8.03 (d, J = 2 Hz, 1H), 7.92- 7.90 (m, 1H), 7.69 (dd, J1 = 1.6 Hz, & J2 = 8.8 Hz, 1H), 7.40-7.33 (m, 3H), 7.21-7.10 (m, 4H), 6.81-
				6.77 (m, 1H). LC-MS:
				m/z 408 (M + H)+.
544	49	XII.83
1H NMR (400 MHz, DMSO-d6): δ 13.22 (bs, 1H), 9.17 (s, 1H), 8.01 (d, J = 2 Hz, 1H), 7.67 (dd, J1 = 1.6 Hz, & J2 = 8.8 Hz, 1H), 7.40 (d, J = 3.2 Hz, 1H), 7.26-7.23 (m, 3H), 7.12-7.07 (m, 4H),
				3.73 (s, 3H). LC-MS: m/z
				438.0 (M + H)+.
545	50	XII.84
1H NMR (400 MHz, DMSO-d6): δ 12.96 (bs, 1H), 8.97 (bs, 1H), 7.33 (d, J = 2.8 Hz, 1H), 7.27 (t, J = 7.8 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 7.01- 6.96 (m, 4H), 6.89 (d, J = 8.8 Hz, 1H), 6.33 (d, J = 8.8 Hz, 2H), 3.73 (s,
				3H), 3.69 (s, 3H), 3.17 (s,
				3H). LC-MS: m/z 379.2
				(M + H)+.
546	51	XII.85
1H NMR (400 MHz, DMSO-d6): δ 13.03 (s, 1H), 9.54 (s, 1H), 7.88 (d, J = 8 Hz, 1H), 7.42- 7.34 (m, 2H), 7.26-7.20 (m, 3H), 7.09 (d, J = 8.4 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 6.95 (d, J = 8 Hz,
				2H), 6.74 (t, J = 7.2 Hz,
				1H), 1.80-1.67 (m, 5H),
				1.44-1.11 (m, 6H). LC-
				MS: m/z 422.1 (M + H)+.
547	52	XII.86
1H NMR (400 MHz, DMSO-d6): δ 13.0 (s, 1H), 9.1 (s, 1H), 7.35 (d, J = 2.8 Hz, 1H), 7.04-6.91 (m, 8H), 6.79 (d, J = 8.8 Hz, 2H), 3.74-3.70 (m, 7H), 3.17 (s, 3H), 3.06- 3.04 (m, 4H). LC-MS: m/z 434.2 (M + H)+.
548	53	XII.87
1H NMR (400 MHz, DMSO-d6): δ 13.2 (s, 1H), 9.2 (s, 1H), 7.39 (d, J = 3.2 Hz, 1H), 7.24-7.09 (m, 8H), 6.84 (d, J = 8.8 Hz, 2H), 3.73 (s, 3H), 3.23 (s, 3H). LC-MS: m/z 433.1 (M + H)+.
549	54	XII.88
1H NMR (400 MHz, DMSO-d6): δ 13.15 (bs, 1H), 8.94 (s, 1H), 7.37 (d, J = 2.8 Hz, 1H), 7.24- 7.19 (m, 3H), 7.06-7.03 (m, 3H), 6.82-6.74 (m, 2H), 6.64 (dd, J1 = 2 Hz, & J2 = 8.8 Hz, 1H), 3.70 (s, 3H), 3.23 (s, 3H), 2.46- 2.42 (m, 1H), 1.80-1.68
				(m, 5H), 1.40-1.21 (m,
				5H). LC-MS: m/z 449.2
				(M + H)+.
550	55	XII.89
1H NMR (400 MHz, DMSO-d6): δ 13.1 (bs, 1H), 9.1 (bs, 1H), 7.39 (dd, J1 = 2.8 & J2 = 9.2 Hz, 2H), 7.20-7.13 (m, 4H), 7.08-7.05 (m, 1H), 6.98-6.90 (m, 3H), 3.72 (s, 3H), 1.79-1.67 (m,
				5H), 1.40-1.33 (m, 5H),
				one proton merged in
				DMSO. LC-MS: m/z
				452.1 (M + H)+.
551	56	XII.90
1H NMR (400 MHz, DMSO-d6): δ 13.07 (bs, 1H), 8.95 (s, 1H), 7.27 (d, J = 3.2 Hz, 1H), 7.23 (dd, J1 = 6.8 Hz & J2 = 8.8 Hz, 2H), 7.13 (d, J = 8.4 Hz, 1H), 7.03 (dd, J1 = 3.2 Hz & J2 = 9.2 Hz, 1H), 6.94-6.89 (m, 3H), 6.82- 6.76 (m, 2H), 3.70 (s,
				3H), 3.21 (s, 3H), 3.21 (s,
				3H), 1.98 (s, 3H), 1.84 (s,
				6H), 1.69 (s, 6H). LC-MS:
				m/z 497.3 (M + H)+.
552	57	XII.91
1H NMR (400 MHz, DMSO-d6): δ 13.1 (s, 1H), 9.11 (s, 1H), 7.38 (d, J = 2.8 Hz, 1H), 7.14- 7.05 (m, 6H), 6.98 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8 Hz, 2H), 3.71 (s, 3H), 3.20 (s, 3H), 2.67- 2.59 (m, 1H), 2.08-1.83 (m, 6H), 1.66-1.56 (m, 2H). LC-MS: m/z 467.2
				(M + H)+.
553	58	XII.92
1H NMR (400 MHz, DMSO-d6): δ 13.06 (bs, 1H), 9.07 (bs, 1H), 7.37 (s, 1H), 7.08-7.0 (m, 8H), 6.87 (d, J = 7.6 Hz, 2H), 4.70 (q, J = 8.8 Hz, 2H), 3.71 (s, 3H), 3.19 (s, 3H). LC-MS: m/z 447 (M + H)+.
554	59	XII.93
1H NMR (400 MHz, DMSO-d6): δ 13.0 (bs, 1H), 9.1 (bs, 1H), 7.37 (d, J = 2.8 Hz, 1H), 7.11- 7.06 (m, 6H), 6.95-6.85 (m, 4H), 3.71 (s, 3H), 3.19 (s, 3H), 2.23 (s, 3H). LC-MS: m/z 363.1 (M + H)+.
555	60	XII.94
1H NMR (400 MHz, DMSO-d6): δ 13.2 (s, 1H), 11.73 (s, 1H), 9.1 (s, 1H), 7.59 (brm, 2H), 7.40-7.12 (brm, 7H), 6.84 (brm, 2H), 3.73 (s, 3H), 3.41-3.25 (brm, 7H), 2.01-1.77 (brm, 5H), 1.53 (brm, 1H). LC-MS: m/z 432.4 (M + H)+.
556	61	XII.95
1H NMR (400 MHz, DMSO-d6): δ 13.1 (bs, 1H), 9.12 (bs, 1H), 7.37 (d, J = 3.2 Hz, 1H), 7.13- 7.04 (m, 6H), 6.96 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 3.71 (s, 3H), 3.45-3.41 (m, 1H), 3.20 (s, 3H), 2.25-2.22 (m, 2H), 2.07-1.91 (m,
				3H), 1.82-1.77 (m, 1H).
				LC-MS: m/z 403.2
				(M + H)+.
557	62	XII.96
1H NMR (400 MHz, DMSO-d6): δ 13.15 (bs, 1H), 9.18 (bs, 1H), 7.39 (d, J = 2.8 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.20- 7.14 (m, 3H), 7.10-7.05 (m, 3H), 6.82 (d, J = 8.8 Hz, 2H), 5.87 (bs, 1H), 3.72 (s, 3H), 3.23 (s, 3H), 2.73-2.61 (m, 4H), 2.18- 2.11 (m, 2H). LC-MS:
				m/z 465.2 (M + H)+.
558	63	XII.97
1H NMR (400 MHz, DMSO-d6): δ 10.24 (bs, 1H), 8.32 (d, J = 2.8 Hz, 1H), 8.21 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 6.85-6.78 (m, 3H), 3.21 (s, 3H), 2.40-2.32 (m, 1H), 1.78-1.67 (m, 5H),
				1.37-1.23 (m, 5H). LC-MS:
				m/z 402.3 (M + H)+.
560	64	XII.99
1H NMR (400 MHz, DMSO-d6): δ 13.04 (s, 1H), 8.94 (s, 1H), 7.37 (d, J = 2.4 Hz, 1H), 7.13- 7.10 (m, 3H), 7.04-7.01 (m, 1H), 6.92-6.88 (m, 3H), 6.81-6.75 (m, 2H), 3.70 (s, 3H), 3.21 (s, 3H), 2.42-2.40 (m, 1H), 2.12 (s, 3H), 1.78-1.67 (m,
				5H), 1.40-1.23 (m, 4H),
				1.22 (s, 1H). LC-MS:
				m/z 445.3 (M + H)+.
561	65	XII.100
1H NMR (400 MHz, DMSO-d6): δ 13.0 (s, 1H), 9.39 (s, 1H), 7.87 (dd, J1 = 2 Hz & J2 = 8.0 Hz, 1H), 7.49 (d, J = 2.4 Hz, 1H), 7.36-7.26 (m, 3H), 7.05 (d, J = 8.4 Hz, 1H), 6.97 (d, J = 2.4 Hz, 1H), 6.79-6.68 (m, 3H), 2.16 (s, 3H), 1.69-1.18
				(m, 13H), 0.85 (s, 6H).
				LC-MS: m/z 515.15
				(M + H)+.
563	66	XII.101
1H NMR (400 MHz, DMSO-d6): δ 13.21 (s, 1H), 9.13 (s, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.41 (d, J = 2.8 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H), 7.16 (d, J = 2.4 Hz, 1H), 7.11- 7.04 (m, 3H), 6.83 (d, J = 8.8 Hz, 2H), 3.73 (s, 3H), 3.28 (s, 3H), 2.21 (s,
				3H). LC-MS: m/z 431.1
				(M + H)+.
564	67	XII.102
1H NMR (400 MHz, DMSO-d6) δ 13.1 (s, 1H), 9.0 (s, 1H), 7.48 (d, J = 2.4 Hz, 1H), 7.33 (dd, J1 = 2.0 Hz, J2 = 2.4 Hz, 3H), 7.05-6.94 (m, 3H), 6.81-6.73 (m, 2H), 3.71 (s, 3H), 2.14 (s, 3H), 1.69 (s, 2H), 1.52-1.18 (m, 11H), 0.86-0.84 (m,
				6H). LC-MS: m/z 547.2
				(M + 2)+
565	68	XII.103
1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 8.91 (s, 1H), 7.36 (d, J = 2.8 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 7.05- 6.95 (m, 5H), 6.81 (s, 1H), 6.71-6.68 (m, 2H), 4.74-4.67 (m, 2H), 3.69 (s, 3H), 3.20 (s, 3H), 2.09 (s, 3H). LC-MS: m/z
				461.2 (M + H)+.
566	69	XII.104
1H NMR (400 MHz, DMSO-d6) δ 13.06 (s, 1H), 9.45 (s, 1H), 8.03 (d, J = 2.4 Hz, 1H), 7.89- 7.87 (m, 1H), 7.80 (dd, J1 = 2.4 Hz, J2 = 8.8 Hz, 1H), 7.40-7.34 (m, 2H), 7.26-7.20 (m, 2H), 7.10
				(d, J = 8.4 Hz, 1H), 6.94
				(d, J = 8.4 Hz, 1H), 6.76
				(t, J = 7.2 Hz, 1H), 2.58-
				2.52 (m, 1H), 1.80-1.68
				(m, 5H), 1.46-1.23 (m,
				5H). LC-MS: m/z 423.1
				(M + H)+.
567	70	XIII.12
1H NMR (400 MHz, CDCl3): δ 7.55 (d, J = 3.2 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.24 (s, 1H), 7.16-7.14 (m, 2H), 7.08- 7.06 (m, 2H), 7.03-7.0 (m, 1H), 6.76 (d, J = 8.4 Hz, 2H), 4.07 (s, 2H), 3.80 (s, 3H), 3.5 (s, 2H), 3.25 (s, 3H), 2.56 (s, 3H),
				2.73 (s, 2H), 1.82 (s, 4H).
				LC-MS: m/z 446.2
				(M + H)+
568	71	XII.106
1H NMR (400 MHz, DMSO-d6): δ 13.15 (s, 1H), 8.9 (s, 1H), 7.36 (d, J = 2.8 Hz, 1H), 7.22-7.02 (m, 6H), 6.76 (d, J = 8.8 Hz, 1H), 6.67 (dd, J1 = 2.4 Hz & J2 = 13.6 Hz, 1H), 6.54 (dd, J1 = 2.4 Hz & J2 = 8.8 Hz, 1H), 4.75 (q, J = 8.8 Hz, 2H), 3.70 (s,
				3H), 3.21 (s, 3H). LC-MS:
				m/z 465.1 (M + H)+.
569	72	XII.107
1H NMR (400 MHz, DMSO-d6): δ 13.13 (s, 1H), 9.22 (s, 1H), 7.49- 7.45 (m, 2H), 7.35 (d, J = 2.8 Hz, 1H), 7.27 (dd, J1 = 1.6 & J2 = 8, 1H), 7.15 (d, J = 8.8 Hz, 1H), 7.08 (dd, J1 = 2.8 Hz & J2 = 9.2, 1H), 7.01-6.96 (m, 2H), 6.68 (dd, J1 = 3.2 Hz & J2 = 10, 1H), 3.71 (s, 3H), 2.13 (s, 1H), 1.66 (s, 2H), 1.5-1.3 (m, 8H), 1.17 (s, 2H), 0.88 (s, 6H). LC-MS: m/z 550.2
				(M + H)+.
570	73	XII.107
1H NMR (400 MHz, DMSO-d6): δ 13.26 (s, 1H), 9.11 (s, 1H), 7.50 (d, J = 2 Hz, 1H), 7.42- 7.34 (m, 3H), 7.11-7.06 (m, 2H), 7.01-6.94 (m, 2H), 6.72 (d, J = 8.8 Hz, 1H), 3.72 (s, 3H), 2.14 (s, 1H), 1.69 (s, 2H), 1.53- 1.33 (m, 8H), 1.23-1.18 (m, 2H), 0.86 (s, 6H). LC-MS: m/z 550.2
				(M + H)+
571	74	XII.108
1H NMR (400 MHz, DMSO-d6): δ 13.4 (bs, 1H), 9.14 (s, 1H), 7.62 (d, J = 9.2 Hz, 2H), 7.42 (d, J = 2.4 Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 7.18 (d, J = 2 Hz, 1H), 7.12- 7.06 (m, 3H), 6.76 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.29 (s, 3H), 2.22 (s,
				3H). LC-MS: m/z 489.1
				(M + H)+.
572	75	XII.109
1H NMR (400 MHz, DMSO-d6): δ 13.35 (s, 1H), 9.25 (s, 1H), 7.51 (d, J = 8.8 Hz, 2H), 7.46- 7.41 (m, 2H), 7.23-7.11 (m, 3H), 7.03-7.01 (m, 1H), 6.93 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.30 (s, 3H). LC-MS: m/z 435.1 (M + H)+.
573	76	XII.110
1H NMR (400 MHz, DMSO-d6): δ 13.4 (bs, 1H), 9.27 (s, 1H), 7.65 (d, J = 9.2 Hz, 2H), 7.48- 7.43 (m, 2H), 7.28-7.11 (m, 3H), 7.05 (d, J = 8.4 Hz, 1H), 6.85 (d, J = 9.2 Hz, 2H), 3.75 (s, 3H), 3.30 (s, 3H). LC-MS: m/z 493.1 (M + H)+.
574	77	XII.111
1H NMR (400 MHz, DMSO-d6): δ 13.30- 12.80 (bs, 1H), 9.11 (s, 1H), 7.37 (d, J = 2.8 Hz, 1H), 7.15-7.07 (m, 6H), 6.98-6.95 (m, 2H), 6.90- 6.87 (m, 2H), 3.71 (S, 3H), 3.21 (s, 3H), 1.91- 1.88 (m, 1H), 1.80-1.30 (m, 9H), 1.0 (d, J = 6.8
				Hz, 3H). LC-MS: m/z
				445.3 (M + H)+.
575	78	XII.112
1H NMR (400 MHz, DMSO-d6): δ 13.2 (s, 1H), 9.2 (s, 1H), 7.8 (s, 1H), 7.53 (d, J = 8.8 Hz, 1H), 7.40 (d, J = 2.8 Hz, 1H), 7.24-7.20 (m, 3H), 7.16-6.88 (m, 5H), 3.73 (s, 3H). LC-MS: m/z
				420.2 (M + H)+.
576	79	XII.113
1H NMR (400 MHz, DMSO-d6) δ 13.24 (s, 1H), 9.20 (s, 1H), 8.46 (s, 1H), 7.67 (dd, J1 = 2.0 Hz, J2 = 8.8 Hz, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.34 (d, J = 8.8 Hz, 1H), 7.24 (m, 4H), 7.12 (dd, J1 = 3.6 Hz, J2 = 9.2 Hz, 1H), 6.49 (d, J = 8.8 Hz, 1H), 3.74 (s,
				3H), 3.41 (s, 3H). LC-
				MS: m/z 471.66 (M + H)+
577	80	XII.114
1H NMR (400 MHz, DMSO-d6) δ 13.1 (s, 1H), 8.90 (s, 1H), 7.37 (d, J = 3.6 Hz, 1H), 7.11 (d, J = 8.4 Hz, 3H), 7.02 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 6.92-6.88 (m, 3H), 6.81-6.75 (m, 2H), 3.70 (s, 3H), 3.21 (s, 3H), 2.67-2.65 (m, 1H), 2.32-
				2.31 (m, 1H), 2.22 (s,
				1H), 2.11 (s, 3H), 1.71-
				1.40 (m, 4H), 1.40-1.11
				(m, 4H). LC-MS: m/z
				456.15 (M + H)+
578	81	XII.115
1H NMR (400 MHz, DMSO-d6) δ 13.30 (s, 1H), 9.18 (s, 1H), 7.98 (d, J = 2.4 Hz, 1H), 7.56 (d, J = 10 Hz, 2H), 7.41 (d, J = 2.8 Hz, 1H), 7.30- 7.17 (m, 5H), 7.13-7.10 (m, 1H), 3.74 (s, 3H), 3.30 (s, 3H), 1.25-1.21 (m, 7H), 1.10 (s, 4H).
				LC-MS: m/z 432.3
				(M + H)+
579	82	XII.116
1H NMR (400 MHz, DMSO-d6) δ 13.45 (s, 1H), 9.61 (s, 1H), 8.09 (s, 1H), 7.60-7.57 (m, 1H), 7.17 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.8 Hz, 1H), 7.01 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 2.4 Hz, 1H), 6.77 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.68 (d,
				J = 9.2 Hz, 1H), 3.24 (s,
				3H), 2.46-2.42 (m, 1H),
				2.09 (s, 3H), 1.80-1.68
				(m, 5H), 1.43-1.23 (m,
				5H). LC-MS: m/z 481.10
				(M + H)+.
580	83	XII.117
1H NMR (400 MHz, DMSO-d6) δ 13.38 (bs, 1H), 9.29 (s, 1H), 7.72 (s, 1H), 7.33 (dd, J1 = 2.4 Hz, J2 = 9.6 Hz, 1H), 7.14 (t, J = 8.4 Hz, 3H), 6.98 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 1.6 Hz, 1H), 6.78 (dd, J1 = 1.6 Hz, J2 = 8.0 Hz, 1H), 6.67 (d, J = 9.2 Hz,
				1H), 3.23 (s, 3H), 2.46-
				2.42 (m, 1H), 2.10 (s,
				3H), 1.79-1.68 (m, 5H),
				1.39-1.20 (m, 5H). LC-
				MS: m/z 498.15 (M + H)+
581	84	XII.118
1H NMR (400 MHz, DMSO-d6) δ 13.28 (s, 1H), 9.20 (s, 1H), 7.85 (s, 1H), 7.67 (s, 1H), 7.42 (d, J = 3.2 Hz, 1H), 7.35- 7.23 (m, 5H), 7.14-7.11 (m, 1H), 6.70 (d, J = 6.70 Hz, 1H), 3.78 (s, 3H), 3.40 (s, 3H), 1.78-1.72 (m, 6H), 1.38-1.32 (m,
				5H). LC-MS: m/z 432.60
				(M + H)+
582	85	XII.119
1H NMR (400 MHz, DMSO-d6) δ 9.2 (s, 1H), 7.38 (d, J = 3.2 Hz, 1H), 7.15-7.07 (m, 6H), 6.99 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H 3.72 (s, 3H), 3.48 (brm, 2H), 3.21 (s, 3H), 3.08-2.99 (brm, 2H), 2.77 (s, 3H), 2.68 (brm, 1H), 2.0-1.8 (brm,
				4H). LC-MS? m/z 445.24
				(M + H)+.
583	86	Com- pound 319
1H NMR (400 MHz, DMSO-d6) δ 13.12 (s, 1H), 9.10 (d, J = 5.2 Hz, 1H), 7.37 (d, J = 3.2 Hz, 1H), 7.15-7.07 (m, 6H), 6.98-6.95 (m, 2H), 6.88 (d, J = 8.8 Hz, 2H), 3.71 (s, 3H), 3.21 (s, 3H), 2.46-2.44 (m, 1H), 1.91- 1.88 (m, 1H), 1.72-1.45
				(m, 8H), 1.00 (d, J = 7.2
				Hz, 3H). LC-MS: m/z
				445.2 (M + H)+
584	87	Com- pound 319
1H NMR (400 MHz, DMSO-d6) δ 13.20- 12.90 (bs, 1H), 9.21-8.95 (bs, 1H), 7.37 (d, J = 2.8 Hz, 1H), 7.11-7.04 (m, 6H), 6.96 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 3.71 (s, 3H), 3.20 (s, 3H), 2.40-2.32 (m, 1H), 1.80-1.74 (m, 4H), 1.42-
				1.35 (m, 3H), 1.10-0.95
				(m, 2H), 0.90 (d, J = 6.4
				Hz, 3H). LC-MS: m/z
				445.3 (M + H)+
585	88	XII.120
1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 8.95 (s, 1H), 7.37 (d, J = 3.6 Hz, 1H), 7.24- 7.18 (m, 3H), 7.06-7.03 (m, 3H), 6.82-6.74 (m, 2H), 6.64 (dd, J1 = 2.0 Hz, J2 = 8.4 Hz, 1H), 3.70 (s, 3H), 3.21 (s, 3H), 2.70- 2.67 (m, 1H), 2.33-2.26
				(m, 2H), 1.72-1.69 (m,
				1H), 1.62-1.42 (m, 4H),
				1.40-1.11 (m, 4H). LC-
				MS: m/z 461.2 (M + H)+
586	89	XII.121
1H NMR (400 MHz, DMSO-d6) δ 13.3 (s, 1H), 10.55 (s, 1H), 9.50- 9.2 (brs, 1H), 8.0 (d, J = 8.4 Hz, 2H), 7.71 (dd, J1 = 8.8 Hz, J2 = 12.8 Hz, 3H), 7.52-7.51 (m, 1H), 7.47-7.33 (m, 4H), 7.14- 7.12 (m, 1H), 3.75 (s, 3H). LC-MS: m/z 431.1 (M + H)+
587	90	XX.25
1H NMR (400 MHz, DMSO-d6) δ 12.5 (s, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.31 (d, J = 2.8 Hz, 1H), 7.19-7.06 (m, 4H), 6.88 (d, J = 8.8 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H) 3.79 (s, 3H), 3.25 (s, 3H). LC-MS: m/z 418.2 (M + H)+
588	91	XII.123
1H NMR (400 MHz, DMSO-d6) δ 13.50- 12.90 (brs, 1H), 9.60- 9.10 (brs, 1H), 7.42-7.32 (m, 5H), 7.23 (d, J = 8.8 Hz, 2H)), 7.12 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 3.75 (s, 3H), 3.42 (s, 3H). LC-MS: m/z 424.0 (M + H)+
589	92	XII.124
1H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 9.09 (brs, 1H), 7.4 (d, J = 3.2 Hz, 1H), 7.32 (m, 1H), 7.25 (d, J = 8.8 Hz, 2H), 7.12-7.00 (m, 5H), 6.86-6.82 (m, 1H), 3.70 (s, 3H), 3.26 (s, 3H). LC-MS: m/z 451.2 (M + H)+
590	93	XII.125
1H NMR (400 MHz, DMSO-d6) δ 13.18 (s, 1H), 9.05 (s, 1H), 7.39 (d, J = 3.2 Hz, 1H), 7.25- 7.19 (m, 3H), 7.08-7.05 (m, 2H), 6.98-6.86 (m, 4H), 3.72 (s, 3H), 3.24 (s, 3H), 2.17 (s, 3H). LC-MS: m/z 447.2 (M + H)+
591	94	XII.126
1H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 9.08 (bs, 1H), 7.97 (d, J = 2.8 Hz, 1H), 7.73 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 7.39-7.38 (m, 2H), 7.24-7.17 (m, 2H), 7.07-6.99 (m, 3H), 3.71
				(s, 3H), 2.57-2.52 (m,
				1H), 1.8-1.68 (m, 5H)
				1.43-1.31 (m, 5H). LC-
				MS: m/z 453.2 (M + H)+
592	95	XII.127
1H NMR (400 MHz, DMSO-d6) δ 13.55- 12.95 (brs, 1H), 9.05 (s, 1H), 8.18 (d, J = 2.4 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.54 (dd, J1 = 2.4 Hz, J2 = 8.8 Hz, 1H), 7.39 (d, J = 2.8 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.09-7.02 (m, 3H), 3.72 (s, 3H), 3.44 (s, 3H). LC-MS:
				m/z 481.2 (M + H)+
593	96	XII.128
1H NMR (400 MHz, DMSO-d6) δ 13.11 (s, 1H), 9.20 (s, 1H), 7.37 (d, J = 2.8 Hz, 1H), 7.14- 7.03 (m, 6H), 6.98-6.86 (m, 4H), 3.71 (s, 3H), 3.20 (s, 3H), 2.33-2.32 (m, 1H), 1.58-1.42 (m, 6H), 1.33-1.29 (m, 2H), 0.95-0.93 (m, 6H). LC- MS: m/z 459.3 (M + H)+
594	97	XII.129
1H NMR (400 MHz, DMSO-d6) δ 13.2-13.0 (brs, 1H), 9.0-8.7 (bs, 1H), 8.29 (s, 2H), 7.37 (d, J = 2.8 Hz, 1H), 7.23 (dd, J1 = 8.8 Hz, J2 = 11.6 Hz, 4H), 6.99 (dd, J1 = 3.2 Hz, J2 = 9.6 Hz, 1H), 6.73 (d, J = 8.8 Hz, 1H), 3.69 (s, 3H), 3.44 (s, 3H),
				1.81-1.69 (m, 6H), 1.43-
				1.35 (m, 5H) LC-MS:
				m/z 433.2 (M + H)+
595	98	XII.130
1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 9.05 (bs, 1H), 8.18 (d, J = 2.8 Hz, 1H), 7.79 (d, J = 9.2 Hz, 2H), 7.63 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 7.40 (t, J = 1.6 Hz, 1H), 7.29 (d, J = 8.8 Hz, 2H), 7.12 (d, J = 9.2 Hz, 1H), 7.09 (d, J = 1.6
				Hz, 2H). 3.37 (s, 3H),
				3.44 (s, 3H), LC-MS:
				m/z 476.1 (M + H)+.
596	99	XII.131
1H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 9.0 (s, 1H), 8.09 (d, J = 2.4 Hz, 1H), 7.44 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 7.39-7.37 (m, 5H), 7.02 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 6.88 (d, J = 8.8 Hz, 1H), 6.74 (d, J = 9.6 Hz, 1H), 3.70 (s,
				3H), 3.39 (s, 3H). LC-MS:
				m/z 434.1 (M + H)+
597	100	XII.132
1H NMR (400 MHz, DMSO-d6) δ 9.2 (s, 1H), 7.42-7.38 (m, 3H), 7.33 (d, J = 9.2 Hz, 1H) 7.22 (d, J = 8.8 Hz, 2H), 7.15- 7.12 (m, 1H), 6.39 (s, 1H), 3.84 (s, 3H), 3.48 (s, 3H), 1.98-1.95 (m, 2H), 1.96-1.66 (m, 3H), 1.35- 1.16 (m, 6H). LC-MS: m/z 438.2 (M + H)+
598	101	XII.133
1H NMR (400 MHz, DMSO-d6) δ 13.60-12.80 (brs, 1H), 8.91 (s, 1H), 7.97 (s, 1H), 7.60 (s, 1H), 7.38-7.27 (m, 5H), 7.05 (dd, J1 = 2.8 Hz, J2 = 9.2 Hz, 1H), 6.87 (d, J = 9.2 Hz, 1H), 6.69 (d, J = 8.8 Hz, 1H), 3.71 (s, 3H), 3.42 (s, 3H), 1.75-1.65
				(m, 5H), 1.50-1.10 (m,
				6H) LC-MS: m/z 432.2
				(M + H)+
599	102	XII.134
1H NMR (400 MHz, DMSO-d6) δ 13.15 (bs, 1H), 8.92 (s, 1H), 7.94 (s, 1H), 7.39-7.37 (m, 2H), 7.24-7.17 (m, 2H), 7.08 (s, 1H), 7.01 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 6.57 (d, J = 9.2 Hz, 1H), 3.69
				(s, 3H), 2.57-2.53 (m,
				1H), 2.19 (s, 3H), 1.81-
				1.68 (m, 5H), 1.43-1.33
				(m, 5H). LC-MS: m/z
				467.1 (M + H)+
600	103	XII.135
1H NMR (400 MHz, DMSO-d6) δ 13.10 (s, 1H), 9.06 (s, 1H), 8.00 (d, J = 2.0 Hz, 1H), 7.77- 7.74 (m, 2H), 7.43 (s, 2H), 7.39 (s, 1H), 7.14 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 9.2 Hz, 2H), 3.72
				(s, 3H). LC-MS: m/z
				455.0 (M + H)+.
601	104	XII.136
1H NMR (400 MHz, DMSO-d6) δ 13.3 (s, 1H), 9.1 (s, 1H), 8.04- 8.01 (m, 2H), 7.80-7.75 (m, 2H), 7.47 (d, J = 8.8 Hz, 1H), 7.40 (s, 1H), 7.10-7.05 (m, 2H), 3.72 (s, 3H). LC-MS: m/z
				439.5.1 (M + H)+
602	105	XII.137
1H NMR (400 MHz, DMSO-d6) δ 13.16 (s, 1H), 8.90 (s, 1H), 8.39 (s, 2H), 7.71 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.38 (d, J = 3.2 Hz, 1H), 7.06-7.02 (m, 1H), 6.87-6.83 (m, 1H), 3.71 (s, 3H), 3.55 (s, 3H). LC- MS: m/z 410.10 (M + H)+
603	106	XII.138
1H NMR (400 MHz, DMSO-d6) δ 7.39 (d, J = 2.8 Hz, 2H), 7.13-7.09 (m, 6H), 6.98 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.4 Hz, 2H), 3.71 (s, 3H), 3.20 (s, 3H), 2.60-2.40 (m, 1H), 1.76-1.70 (m, 10H). LC-MS: m/z 498.25 (M + H)+
609	107	XII.139
1H NMR (400 MHz, DMSO-d6) δ 13.00 (s, 1H), 8.74 (s, 1H), 7.97 (s, 1H), 7.35 (d, J = 3.2 Hz, 1H), 7.27 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 6.99 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.49 (s, 1H), 6.44 (d, J = 9.6 Hz, 1H), 3.69 (s, 3H), 3.36 (s,
				3H), 1.96 (s, 3H), 1.81-
				1.69 (m, 5H), 1.43-1.23
				(m, 6H). LC-MS: m/z
				446.3 (M + H)+.
612	108	XII.140
1H NMR (400 MHz, DMSO-d6) δ 13.22 (s, 1H), 9.20 (s, 1H), 7.40 (d, J = 2.8 Hz, 1H), 7.31 (d, J = 9.2 Hz, 1H), 7.23- 7.01 (m, 5H), 6.80 (s, 1H), 6.61 (d, J = 1.2 Hz, 2H), 3.74 (s, 3H), 3.22 (s, 3H). LC-MS: m/z 417.1 (M + H)+.
613	109	XII.141
1H NMR (400 MHz, DMSO-d6) δ 13.26 (s, 1H), 9.51 (s, 1H), 9.39 (s, 1H), 7.79 (d, J = 2.0 Hz, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.33-7.21 (m, 6H), 6.85 (d, J = 8.8 Hz, 2H), 3.30 (s, 3H), 2.91 (s, 3H). LC-MS: m/z 480.1 (M + H)+.
614	110	XII.142
1H NMR (400 MHz, DMSO-d6) δ 13.42 (s, 1H), 9.70 (s, 1H), 8.25 (d, J = 2.0 Hz, 1H), 7.62 (dd, J1 = 2.0 Hz, J2 = 8.8 Hz, 1H), 7.22-7.12 (m, 4H), 7.02 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 2.4 Hz, 1H), 6.77 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 1H), 6.69 (d,
				J = 8.8 Hz, 1H), 3.25 (s,
				3H), 2.37 (d, J = 5.2 Hz,
				3H), 2.10 (s, 3H), 1.80-
				1.68 (m, 5H), 1.40-1.23
				(m, 6H). LC-MS: 508.2
				(M + H)+.
615	111	XII.143
1H NMR (400 MHz, DMSO-d6) δ 13.24 (s, 1H), 9.08 (s, 1H), 8.24 (d, J = 2.8 Hz, 1H), 8.03 (d, J = 2.8 Hz, 1H), 7.96- 7.93 (m, 1H), 7.80-7.77 (m, 1H), 7.48 (d, J = 9.2 Hz, 1H), 7.40 (d, J = 2.0
				Hz, 1H), 7.20 (d, J = 8.4
				Hz, 1H), 7.09-7.08 (m,
				2H), 3.73 (s, 3H). LC-MS:
				m/z 497.0 (M + H)+.
616	112	XII.144
1H NMR (400 MHz, DMSO-d6) δ 11.94-11.83 (bs, 1H), 8.41 (s, 2H), 7.50 (d, J = 2.4 Hz, 1H), 7.39 (s, 1H), 7.24 (s, 2H), 7.03 (d, J = 8.8 Hz, 1H), 6.79-6.76 (m, 1H), 3.77 (s, 3H), 3.60-3.50
				(m, 1H), 1.91-1.68 (m,
				5H), 1.51-1.22 (m, 5H),
				LC-MS: m/z 454.1
				(M + H)+.
617	113	XII.145
1H NMR (400 MHz, DMSO-d6) δ 13.70- 12.80 (bs, 1H), 9.80-8.90 (bs, 1H), 7.54-7.51 (m, 1H), 7.42 (d, J = 3.2 Hz, 1H), 7.32 (d, J = 9.2 Hz, 1H), 7.25-7.09 (m, 5H), 6.81 (d, J = 2.4 Hz, 1H), 6.68-6.65 (m, 1H), 3.74 (s, 3H), 3.28 (s, 3H).
				LC-MS: m/z 451.2
				(M + H)+
618	114	XII.146
1H NMR (400 MHz, DMSO-d6) δ 13.40- 12.80 (bs, 1H), 9.30-8.80 (bs, 1H), 7.34 (d, J = 2.8 Hz, 1H), 7.08-6.95 (m, 4H), 6.60-6.58 (m, 2H), 5.89 (s, 1H), 3.69 (s, 3H), 3.43 (s, 3H), 3.16 (s, 3H), 1.91-1.89 (m, 2H), 1.75- 1.72 (m, 3H), 1.37-1.23 (m, 6H). LC-MS: m/z 435.2 (M + H)+
619	115	XII.147
1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 8.96 (s, 1H), 7.54 (d, J = 2.8 Hz, 1H), 7.12- 7.08 (m, 3H), 7.05 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.90-6.87 (m, 3H), 6.79-6.72 (m, 2H), 3.78- 3.72 (m, 1H), 3.19 (s, 3H), 2.46-2.40 (m, 1H),
				2.10 (s, 3H), 1.76-1.66
				(m, 5H), 1.39-1.28 (m,
				5H), 0.72-0.70 (m, 2H),
				0.69-0.66 (m, 2H). LC-
				MS: m/z 471.2 (M + H)+.
620	116	XII.148
1H NMR (400 MHz, DMSO-d6) δ 8.67 (s, 1H), 7.14-7.04 (m, 4H), 6.92-6.88 (m, 2H), 6.84- 6.75 (m, 5H), 3.84 (d, J = 10.4 Hz, 2H), 3.40- 3.34 (m, 3H), 3.17 (s, 3H), 2.43-2.38 (m, 1H), 2.12 (s, 3H), 1.89-1.65 (m, 6H), 1.35-1.17 (m,
				8H). LC-MS: m/z 514.3
				(M + H)+.
621	117	XII.149
1H NMR (400 MHz, DMSO-d6) δ 13.00- 12.90 (bs, 1H), 8.96 (s, 1H), 7.38 (d, J = 2.8 Hz, 1H), 7.14-7.10 (m, 4H), 6.93-6.88 (m, 3H), 6.81- 6.77 (m, 2H), 3.76-3.71 (m, 4H), 3.21 (s, 3H), 2.96-2.94 (m, 4H), 2.46- 2.39 (m, 1H), 2.12 (s, 3H), 1.78-1.76 (m, 4H),
				1.38-1.30 (m, 6H). LC-MS:
				m/z 499.2 (M + H)+.
622	118	XII.150
1H NMR (400 MHz, DMSO-d6) δ 13.20 (s, 1H), 9.20 (s, 1H), 7.46- 7.41 (m, 3H), 7.30 (d, J = 7.2 Hz, 1H), 7.23-7.10 (m, 5H), 6.77 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.27 (s, 3H), LC-MS: m/z 449.1 (M + H)+
623	119	XII.153
1H NMR (400 MHz, DMSO-d6) δ 13.00 (s, 1H), 9.30 (s, 1H), 7.33- 7.26 (m, 3H), 7.05 (dd, J1 = 2.8 Hz, J2 = 9.2 Hz, 1H), 6.94-6.87 (m, 4H), 6.48 (d, J = 8.8 Hz, 2H), 3.69 (s, 3H), 3.08 (s, 3H), 2.32-2.20 (m, 1H), 1.86- 1.60 (m, 5H), 1.40-1.10 (m, 6H), 0.90-0.82 (m, 2H), 0.60-0.56 (m, 2H). LC-MS: m/z 471.2 (M + H)+.
624	120	XII.151
1H NMR (400 MHz, DMSO-d6) δ 13.2-12.8 (bs, 1H), 9.40-8.80 (bs, 1H), 7.36 (d, J = 1.6 Hz, 1H), 7.11 (d, J = 8.8 Hz, 2H), 7.03 (s, 2H), 6.68 (d, J = 8.8 Hz, 2H), 6.63 (s, 1H), 3.70 (s, 3H), 3.59 (s, 3H), 3.22 (s, 3H). LC- MS: m/z 421.2 (M + H)+
625	121	XII.152
1H NMR (400 MHz, DMSO-d6) δ 13.26 (bs, 1H), 9.10 (s, 1H), 7.56 (dd, J1 = 3.2 Hz, J2 = 9.6 Hz, 1H), 7.23-7.22 (m, 1H), 7.14-7.11 (m, 3H), 6.96-6.91 (m, 3H), 6.79 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.69-6.65 (m, 1H), 3.32 (s, 3H), 2.49-
				2.43 (m, 1H), 2.10 (s,
				3H), 1.79-1.67 (m, 5H),
				1.38-1.22 (m, 5H). LC-
				MS: m/z 433.2 (M + H)+.
626	122	XII.153
1H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 9.30 (s, 1H), 7.38- 7.36 (m, 1H), 7.16 (d, J = 8.4 Hz, 1H), 7.09-7.02 (m, 3H), 6.95 (d, J = 9.2 Hz, 1H), 6.84 (d, J = 8.4 Hz, 2H), 6.78 (dd, J1 = 2.8 Hz, J2 = 8.4 Hz, 1H), 6.65 (d, J = 2.8 Hz, 1H), 3.71 (s, 3H), 3.19 (s, 3H),
				2.49-2.43 (m, 1H), 1.83-
				1.67 (m, 6H), 1.37-1.21
				(m, 5H), 0.86 (dd, J1 = 1.6
				Hz, J2 = 8.0 Hz, 2H),
				0.57-0.53 (m, 2H). LC-
				MS: m/z 470.2 (M+)+.
627	123	XII.154
1H NMR (400 MHz, DMSO-d6) δ 8.79 (bs, 1H), 7.10-7.08 (m, 3H), 6.92-6.79 (m, 6H), 6.64- 6.62 (m, 1H), 4.69 (s, 4H), 3.88 (s, 4H), 3.19 (s, 3H), 2.46-2.40 (m, 1H), 2.11 (s, 3H), 1.78-1.67 (m, 5H), 1.37-1.29 (m, 5H). LC-MS: m/z 511.25 (M + H)+.
628	124	XII.155
1H NMR (400 MHz, DMSO-d6) δ 13.10- 13.00 (bs, 1H), 8.90-9.10 (bs, 1H), 7.36 (d, J = 3.2 Hz, 1H), 7.14-7.10 (m, 3H), 7.02 (dd, J1 = 2.8 Hz, J2 = 9.2 Hz, 1H), 6.93- 6.88 (m, 3H), 6.81-6.74 (m, 2H), 3.89 (t, J = 6.4 Hz, 2H), 3.21 (s, 3H),
				2.45-2.30 (m, 1H), 2.12
				(s, 3H), 1.78-1.64 (m,
				6H), 1.43-1.33 (m, 8H),
				0.94 (t, J = 4.4 Hz, 3H).
				LC-MS: m/z 486.2
				(M + H)+.
630	125	XII.156
1H NMR (400 MHz, DMSO-d6) δ 12.83 (bs, 1H), 9.12 (s, 1H), 7.59 (d, J = 2.0 Hz, 1H), 7.12 (d, J = 8.8 Hz, 3H), 7.05 (dd, J1 = 2.0, J2 = 8.4 Hz, 1H), 6.93-6.91 (m, 3H), 6.79 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 1H), 6.65 (d, J = 8.0 Hz, 1H), 3.21 (s,
				3H), 2.46-2.42 (m, 1H),
				2.10 (s, 3H), 1.92-1.67
				(m, 6H), 1.41-1.33 (m,
				5H), 0.86-0.82 (m, 2H),
				0.54-0.51 (m, 2H). LC-MS:
				m/z 455.3 (M + H)+.
631	126	XII.157
1H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 9.14 (s, 1H), 7.67 (d, J = 1.6 Hz, 1H), 7.16 7.11 (m, 4H), 6.93-6.91 (m, 3H), 6.81-6.78 (m, 1H), 6.67-6.64 (m, 1H), 3.22 (s, 3H), 2.43 (s, 1H), 2.20 (s, 3H), 2.11 (s, 3H), 1.80-1.68 (m, 5H), 1.38-
				1.23 (m, 5H). LC-MS:
				m/z 429.3 (M + H)+.
632	127	XII.158
1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 9.60 (s, 1H), 8.42 (d, J = 2.4 Hz, 1H), 8.24 (d, J = 4.8 Hz, 1H), 7.76 (dd, J1 = 2.0, J2 = 8.8 Hz, 1H), 7.17-7.12 (m, 3H), 6.99 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 2.4 Hz, 1H), 6.78 (dd, J1 = 2.8 Hz,
				J2 = 8.8 Hz, 1H), 6.62 (d,
				J = 9.2 Hz, 1H), 3.24 (s,
				3H), 2.73 (d, J = 4.8 Hz,
				3H), 2.46-2.44 (m, 1H),
				2.10 (s, 3H), 1.79-1.68
				(m, 5H), 1.39-1.16 (m,
				5H). LC-MS: m/z 472.4
				(M + H)+.
633	128	XII.159
1H NMR (400 MHz, DMSO-d6) δ 13.10- 13.00 (bs, 1H), 8.96 (s, 1H), 7.36 (d, J = 3.2 Hz, 1H), 7.12 (dd, J1 = 4.4 Hz, J2 = 8.4 Hz, 3H), 7.04 (dd, J1 = 4.0 Hz, J2 = 9.2 Hz, 1H), 6.93-6.89 (m, 3H), 6.81-6.74 (m, 2H), 3.48 (s, 2H), 3.21 (s, 3H),
				2.33-2.32 (m, 1H), 2.12
				(s, 3H), 1.79-1.68 (m,
				6H), 1.41-1.17 (m, 4H),
				0.99 (s, 9H). LC-MS:
				m/z 501.4 (M+)+
634	129	XII.160
1H NMR (400 MHz, DMSO-d6) δ 13.10- 12.90 (bs, 1H), 8.95 (s, 1H), 7.38 (d, J = 3.2 Hz, 1H), 7.12 (t, J = 8.0 Hz, 3H), 7.03 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.92- 6.89 (m, 3H), 6.80 (dd, J1 = 2.4 Hz, J2 = 8.0 Hz, 1H), 6.74 (d, J = 8.8 Hz,
				1H), 4.15-4.09 (m, 1H),
				3.21 (s, 3H), 2.45-2.38
				(m, 1H), 2.12 (s, 3H),
				1.89-1.86 (m, 2H), 1.79-
				1.68 (m, 4H), 1.55-1.24
				(m, 14H). LC-MS: m/z
				512.3 (M+)+.
635	130	XII.161
1H NMR (400 MHz, DMSO-d6) δ 13.1 (s, 1H), 9.35 (s, 1H), 8.15 (s, 3H), 7.99 (d, J = 2.0 Hz, 1H), 7.41 (dd, J1 = 2.0 Hz, J2 = 8.8 Hz, 1H), 7.16- 7.09 (m, 3H), 6.97 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 2.4 Hz, 1H), 6.79 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz,
				1H), 6.65 (d, J = 8.4 Hz,
				1H), 3.92-3.87 (m, 2H),
				3.23 (s, 3H), 2.40 (s, 1H),
				2.10 (s, 3H), 1.79-1.68
				(m, 5H), 1.39-1.22 (m,
				5H). LC-MS: m/z 427.2
				(M + H)+.
636	131	XII.162
1H NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H), 7.61-7.59 (m, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H), 7.11 (d, J = 8.8 Hz, 2H), 6.91-6.88 (m, 3H), 6.80- 6.78 (m, 1H), 6.72 (d, J = 8.0 Hz, 1H), 3.21 (s, 3H), 2.49-2.45 (m, 1H),
				2.15 (s, 3H), 1.79-1.67
				(m, 5H), 1.38-1.33 (m,
				5H). LC-MS: m/z 416.3
				(M + H)+.
637	132	XII.163
1H NMR (400 MHz, DMSO-d6) δ 9.62-9.50 (bs, 1H), 8.90-8.70 (bs, 1H), 8.02 (d, J = 1.2 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.16-7.10 (m, 3H), 6.98-6.91 (m, 3H), 6.79 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.67 (d, J = 8.8 Hz, 1H), 3.98 (s, 2H),
				3.23 (s, 3H), 2.54 (s, 1H),
				2.50 (s, 3H), 2.10 (s, 3H),
				1.79-1.68 (m, 5H), 1.39-
				1.23 (m, 5H). LC-MS:
				m/z 456.3 (M − H)+.
638	133	XV.49
1H NMR (400 MHz, DMSO-d6) δ 13.00- 12.90 (bs, 1H), 10.12 (s, 1H), 8.57 (s, 1H), 8.40 (t, J = 2.0 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.63 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.17 (d, J = 8.4 Hz, 2H), 7.11-7.05 (m, 4H), 2.46-2.42 (m,
				1H), 1.81-1.78 (m, 5H),
				1.42-1.32 (m, 5H). LC-MS:
				m/z 415.2 (M + H)+.
640	134	XII.164
1H NMR (400 MHz, DMSO-d6) δ 8.09 (s, 1H), 7.18 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 2.4 Hz, 1H), 6.87 (d, J = 8.4 Hz, 2H), 6.82-6.77 (m, 2H), 3.72 (s, 2H), 3.20 (s, 3H), 2.43 (s, 3H), 2.50 (s, 3H), 2.14 (s, 3H), 1.78-1.67
				(m, 5H), 1.40-1.32 (m,
				5H). LC-MS: m/z 470.3
				(M + H)+.
641	135	XII.165
1H NMR (400 MHz, DMSO-d6) δ 8.38 (s, 1H), 7.68-7.64 (m, 1H), 7.37-7.31 (m, 3H), 7.17- 7.03 (M, 6H), 6.78 (s, 1H), 2.46 (s, 1H), 1.79- 1.68 (m, 5H), 1.39-1.16 (m, 5H). LC-MS: m/z 456.1 (M + H)+.
642	136	XII.166
1H NMR (400 MHz, DMSO-d6) δ 10.00 (s, 1H), 8.57 (s, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.82- 7.66 (m, 5H), 7.47 (d, J = 7.6 Hz, 1H), 7.21-7.17 (m, 3H), 2.36 (s, 3H), 1.79-1.69 (m, 5H), 1.44- 1.21 (m, 6H). LC-MS:
				m/z 430.2 (M + H)+.
643	137	XII.167
1H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 9.06 (s, 1H), 8.67 (d, J = 2.0 Hz, 1H), 7.84 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 7.64 (t, J = 8.0 Hz, 1H), 7.35 (d, J = 6.8 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 8.4
				Hz, 1H), 6.58 (d, J = 8.8
				Hz, 1H), 3.34 (s, 3H),
				1.90-1.69 (m, 5H), 1.42-
				1.22 (m, 6H). LC-MS:
				m/z 403.2 (M + H)+.
646	138	XII.168
1H NMR (400 MHz, DMSO-d6) δ 13.20- 12.40 (bs, 1H), 8.32 (s, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.33-7.28 (m, 2H), 7.05-7.00 (m, 4H), 6.78 (d, J = 2.4 Hz, 1H), 6.71- 6.67 (m, 2H), 4.75-4.68 (m, 2H), 3.20 (s, 3H),
				2.13 (s, 3H). LC-MS: m/z
				432.2 (M + H)+.
647	139	XII.169
1H NMR (400 MHz, DMSO-d6) δ 8.42 (s, 1H), 7.66-7.60 (m, 2H), 7.35 (d, J = 6.4 Hz, 1H), 7.19 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 2.4 Hz, 1H), 6.97-6.85 (m, 4H), 3.25 (s, 3H), 2.21 (s, 3H). LC- MS: m/z 418.05 (M + H)+
648	140	XII.170
1H NMR (400 MHz, DMSO-d6) δ 9.43 (s, 1H), 7.91 (d, J = 9.2 Hz, 2H), 7.74-7.70 (m, 1H), 7.46-7.43 (m, 3H), 7.17 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.0 Hz, 1H), 6.78 (d, J = 8.8 Hz, 2H), 3.28 (s, 3H). LC-MS: m/z
				388.05 (M + H)+.
649	141	XII.171
1H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 10.21 (s, 1H), 8.40 (s, 1H), 8.32 (s, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.45- 7.39 (m, 2H), 7.14 (d, J = 8.4 Hz, 2H), 7.05 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 7.2 Hz, 2H), 2.36 (s, 3H), 1.79-1.68 (m, 5H), 1.39-1.23 (m, 6H). LC-
				MS: m/z 429.2 (M + H)+.
650	142	XII.172
1H NMR (400 MHz, DMSO-d6) δ 12.90 (s, 1H), 8.80 (s, 1H), 7.53- 7.50 (m, 4H), 7.27 (d, J = 2.0 Hz, 1H), 7.18 (s, 1H), 7.13-7.11 (m, 1H), 7.01 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 8.8 Hz, 1H),
				3.75 (s, 3H), 2.03 (s, 3H),
				1.81-1.71 (m, 12H). LC-
				MS: m/z 506.3 (M + 2H)+.
651	143	XV.50
1H NMR (400 MHz, DMSO-d6) δ 13.0 (s, 1H), 10.1 (s, 1H), 8.39 (s, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 1.6 Hz, 1H), 7.72-7.69 (m, 1H), 6.63 (d, J = 7.6 Hz, 1H), 7.55 (s, 1H), 7.46-7.44 (m, 1H), 7.16-7.11 (m, 3H), 7.07 (d, J = 8.8 Hz, 2H), 2.52-2.46 (m, 1H), 2.29 (S, 3H), 1.80-1.68
				(m, 5H), 1.40-1.17 (m,
				5H), LC-MS: m/z 427.2
				(M + H)+.
652	144	XII.173
1H NMR (400 MHz, DMSO-d6) δ 8.62 (s, 1H), 8.49 (s, 1H), 7.73- 7.69 (m, 1H), 7.42 (d, J = 7.6 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.22-7.09 (m, 1H) 6.76 (s, 1H), 3.42 (s, 3H), 2.25 (s, 3H), 1.85-1.70 (m, 5H), 1.45-
				1.23 (m, 6H). LC-MS:
				m/z 417.2 (M + H)+.
654	145	XII.174
1H NMR (400 MHz, DMSO-d6) δ 12.90 (s, 1H), 8.76 (s, 1H), 8.52 (d, J = 2.4 Hz, 1H), 7.71- 7.68 (m, 1H), 7.51 (d, J = 9.2 Hz, 1H), 7.23-7.12 (m, 4H), 6.87 (d, J = 9.2 Hz, 1H), 6.58 (d, J = 8.8 Hz, 1H), 3.74 (s, 3H), 3.29 (s, 3H), 2.49-2.47
				(m, 1H), 1.81-1.79 (m,
				5H), 1.39-1.37 (m, 5H).
				LC-MS: m/z 431.3
				(M − H)+.
655	146	XII.175
1H NMR (400 MHz, DMSO-d6) δ 7.70 (d, J = 2.4 Hz, 1H), 7.48-7.47 (m, 2H), 7.37 (dd, J1 = 6.8 Hz, J2 = 7.6 Hz, 1H), 7.27-7.13 (m, 5H), 7.05- 7.03 (m, 1H), 6.70 (d, J = 9.2 Hz, 1H), 3.38 (s, 3H), 2.48-2.47 (m, 1H),
				1.79-1.66 (m, 5H), 1.42-
				1.10 (m, 6H). LC-MS:
				m/z 402.5 (M + H)+.
656	147	XII.176
1H NMR (400 MHz, DMSO-d6) δ 8.02-7.60 (m, 2H), 7.14 (d, J = 8.4 Hz, 4H), 6.97 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 2.4 Hz, 1H), 6.76-6.74 (m, 1H), 6.40-6.30 (m, 1H), 3.22 (d, J = 8.8 Hz, 3H), 2.40 (s, 3H), 2.14 (s, 3H), 1.89-1.72 (m, 5H), 1.42- 1.31 (m, 6H). LC-MS:
				m/z 509.2 (M + H)+.
659	148	XII.177
1H NMR (400 MHz, DMSO-d6) δ 8.37 (bs, 1H), 7.65 (bs, 1H), 7.55 (t, J = 8.0 Hz, 1H), 7.43 (d, J = 1.6 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.30- 7.25 (m, 2H), 6.75 (d, J = 7.6 Hz, 1H), 6.19 (d, J = 8.8 Hz, 1H), 3.29 (s, 3H), 2.45-2.41 (m, 1H),
				1.84-1.69 (m, 5H), 1.45-
				1.32 (m, 5H). LC-MS:
				m/z 437.2 (M + H)+.
660	149	XII.178
1H NMR (400 MHz, DMSO-d6) δ 10.75 (bs, 1H), 8.03 (s, 1H), 7.66 (t, J = 8.0 Hz, 1H), 7.38-7.32 (m, 3H), 7.23-7.17 (m, 3H), 7.09 (d, J = 7.6 Hz, 1H), 6.72 (s, 1H), 2.45- 2.41 (m, 1H), 1.79-1.67 (m, 5H), 1.43-1.30 (m, 5H). LC-MS: m/z 490.1 (M + H)+.
661	150	XII.179
1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.25 (s, 1H), 7.49 (s, 1H), 7.37-7.34 (m, 2H), 7.16 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.4 Hz, 1H), 6.65 (s, 1H), 3.69 (s, 3H), 2.46-2.39 (m, 1H), 1.79- 1.68 (m, 5H), 1.39-1.23 (m, 5H). LC-MS: m/z
				486.2 (M + H)+.
662	151	XII.180
1H NMR (400 MHz, DMSO-d6) δ 12.90 (s, 1H), 8.60 (s, 1H), 8.36 (s, 1H), 7.69 (d, J = 2.0 Hz, 1H), 7.44-7.36 (m, 3H), 7.13 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.4 Hz, 2H), 6.98 (s, 1H), 6.66 (d, J = 14.0 Hz, 2H), 1.77- 1.75 (m, 6H), 1.38-1.22 (m, 5H). LC-MS: m/z
				469.1 (M + H)+.
663	152	XII.181
1H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 7.62 (t, J = 9.6 Hz, 1H), 7.32-7.24 (m, 3H), 7.17 (d, J = 8.0 Hz, 2H), 6.62 (d, J = 7.2 Hz, 1H), 6.06 (s, 1H), 3.34 (s, 3H), 1.81-1.69 (m, 7H), 1.42- 1.23 (m, 5H), 0.84-0.82 (bs, 2H), 0.44-0.43 (m,
				2H). LC-MS: m/z 443.2
				(M + H)+.
664	153	XV.51
1H NMR (400 MHz, DMSO-d6) δ 13.20 (s, 1H), 10.14 (s, 1H), 9.90 (s, 1H), 7.93 (d, J = 6.8 Hz, 1H), 7.78 (s, 1H), 7.66-7.60 (m, 3H), 7.50- 7.40 (m, 3H), 7.30 (d, J = 4.0 Hz, 1H), 7.18 (d, J = 8.4 Hz, 2H), 6.83 (t, J = 7.2 Hz, 1H), 1.78-1.68 (m, 5H), 1.44-1.23 (m,
				6H). LC-MS: m/z 415.2
				(M + H)+.
665	154	XII.182
1H NMR (400 MHz, DMSO-d6) δ 13.72 (bs, 1H), 10.60 (s, 1H), 9.95 (s, 1H), 8.42 (d, J = 2.8 Hz, 1H), 8.29-8.27 (m, 1H), 8.20 (s, 1H), 8.07 ((d, J = 8.4 Hz, 1H), 7.62 (d, J = 7.2 Hz, 1H), 7.50- 7.46 (m, 2H), 7.38 (s, 1H), 7.24 (d, J = 8.4 Hz, 1H), 6.93-6.90 (m, 1H),
				2.49-2.47 (m, 1H), 1.81-
				1.69 (m, 5H), 1.43-1.23
				(m, 5H). LC-MS: m/z
				450.1 (M + H)+.
666	155	XII.183
1H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 9.97 (s, 1H), 9.75 (s, 1H), 7.93 (dd, J1 = 0.8 Hz, J2 = 7.6 Hz, 1H), 7.81 (s, 1H), 7.640 (d, J = 6.0 Hz, 1H), 7.52-7.38 (m, 5H), 7.31 (d, J = 8.4 Hz, 1H), 7.24-7.22 (m, 1H), 6.86- 6.82 (m, 1H), 2.49-2.43 (m, 1H), 1.81-1.68 (m,
				5H) 1.46-1.22 (m, 5H).
				LC-MS: m/z 449.05
				(M + H)+.
669	156	XII.184
1H NMR (400 MHz, DMSO-d6) δ 13.25 (bs, 1H), 9.91 (s, 1H), 9.29 (bs, 1H), 7.70 (s, 1H), 7.53 (d, J = 8 Hz, 1H), 7.47-7.32 (m, 6H), 7.23 (d, J = 8 Hz, 1H), 7.12 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 3.74 (s, 3H), 2.45-2.41 (m, 1H), 1.81- 1.68 (m, 5H), 1.46-1.31 (m, 5H). LC-MS: m/z 479.2 (M + H)+.
671	157	XII.185
1H NMR (400 MHz, DMSO-d6) δ 13.40 (s, 1H), 9.61 (s, 1H), 8.23 (d, J = 2.0 Hz, 1H), 7.60 (dd, J1 = 2.4 Hz, J2 = 9.2 Hz, 1H), 7.44 (s, 1H), 7.30 (s, 2H), 7.21 (d, J = 6.5 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.60-6.50 (m, 2H), 6.33 (dd, J1 = 2.8
				Hz, J2 = 8.2 Hz, 1H), 3.19
				(s, 3H), 2.36 (d, J = 4.8
				Hz, 3H), 2.07 (s, 3H),
				1.84-1.68 (m, 5H), 1.44-
				1.16 (m, 6H). LC-MS:
				m/z 542.2 (M + H)+.
672	158	XII.186
1H NMR (400 MHz, DMSO-d6) δ 9.88 (s, 1H), 7.63 (dd, J1 = 2.8 Hz, J2 = 6.8 Hz, 2H), 7.47 (d, J = 8 Hz, 1H), 7.41-7.33 (m, 3H), 7.29-7.21 (m, 3H), 6.97 (d, J = 7.6 Hz, 1H), 3.80-3.75 (m, 1H), 2.45-2.41 (m, 1H), 1.81- 1.68 (m, 5H), 1.46-1.32 (m, 5H), 0.74-0.73 (m,
				2H), 0.64-0.60 (m, 2H).
				LC-MS: m/z 505.2
				(M + H)+.
673	159	XII.187
1H NMR (400 MHz, DMSO-d6) δ 8.75-9.00 (bs, 1H), 7.97 (s, 1H), 7.55 (d, J = 2.4 Hz, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 7.00 (dd, J1 = 2.4 Hz, J2 = 9.2 Hz, 1H), 6.49 (s, 1H), 6.43 (d, J = 9.2 Hz, 1H), 3.78-3.71 (m, 1H),
				3.35 (s, 3H), 2.45-2.41
				(m, 1H), 1.97 (s, 3H),
				1.85-1.69 (m, 5H), 1.46-
				1.32 (m, 5H), 0.75-0.70
				(m, 2H), 0.65-0.58 (m,
				2H). LC-MS: m/z 472.25
				(M + H)+.
675	160	XII.188
1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 7.80 (s, 1H), 7.53 (s, 1H), 7.33-7.09 (m, 5H), 6.05 (s, 1H), 6.57 (d, J = 8.4 Hz, 1H), 3.63 (s, 3H), 2.49-2.47 (m, 1H), 1.80-1.67 (m, 5H), 1.40- 1.33 (m, 5H). LC-MS: m/z 518.1 (M + H)+.
676	161	XII.189
1H NMR (400 MHz, DMSO-d6) δ 12.92 (s, 1H), 8.58 (s, 1H), 8.02 (s, 1H), 7.65 (s, 1H), 7.45- 7.29 (m, 5H), 7.17-7.15 (m, 1H), 6.80 (s, 1H), 6.67 (s, 2H), 2.60-2.40 (m, 1H), 1.79-1.67 (m, 5H), 1.36-1.22 (m, 5H). LC-MS: m/z 489.2 (M + H)+.
677	162	XII.190
1H NMR (400 MHz, DMSO-d6) δ 13.60 (s, 1H), 10.48 (s, 1H), 8.34- 8.33 (m, 1H), 8.22 (dd, J1 = 2.0 Hz, J2 = 8.0 Hz, 1H), 7.54 (s, 1H), 7.47 (s, 1H), 7.29-7.20 (m, 2H), 7.15-7.09 (m, 3H), 6.83 (dd, J1 = 4.8 Hz, J2 = 7.6 Hz, 1H), 6.65-6.63 (m, 1H), 2.49-2.45 (m, 1H),
				1.77-1.67 (m, 5H), 1.42-
				1.18 (m, 5H). LC-MS:
				m/z 422.1 (M + H)+.
678	163	XII.191
1H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 9.70 (s, 1H), 8.18 (d, J = 2.4 Hz, 1H), 7.57 (dd, J1 = 2.4 Hz, J2 = 8.8 Hz, 1H), 7.17-7.12 (m, 3H), 6.99 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 2.4 Hz, 1H), 6.78 (dd, J1 = 2.8 Hz, J2 = 8.4 Hz, 1H), 6.60 (d,
				J = 8.8 Hz, 1H), 4.40 (bs,
				4H), 3.90-3.80 (m, 1H),
				3.24 (s, 3H), 2.45-2.42
				(m, 1H), 2.10 (s, 3H),
				1.79-1.77 (m, 5H), 1.39-
				1.34 (m, 5H). LC-MS:
				m/z 523.3 (M + H)+
679	164	XII.191
1H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 9.61 (s, 1H), 8.19 (s, 1H), 7.58 (dd, J1 = 1.6 Hz, J2 = 8.8 Hz, 1H), 7.47 (s, 1H), 7.17-7.12 (m, 3H), 7.03-6.98 (m, 3H), 6.91 (s, 1H), 6.78 (dd, J1 = 2.2 Hz, J2 = 8.8 Hz, 1H), 6.62 (d, J = 8.8 Hz, 1H), 4.39-
				3.98 (m, 4H), 3.23 (s,
				3H), 2.49-2.43 (m, 1H),
				2.10 (s, 3H), 1.79-1.68
				(m, 6H), 1.42-1.30 (m,
				5H). LC-MS: m/z 541.3
				(M + H)+
680	165	XII.192
1H NMR (400 MHz, DMSO-d6) δ 8.86 (s, 1H), 7.62-7.56 (m, 2H), 7.33-7.22 (m, 3H), 7.11- 7.02 (m, 2H), 6.96 (d, J = 2.0 Hz, 1H), 6.88-6.83 (m, 1H), 6.41 (d, J = 8.4 Hz, 1H), 2.47-2.42 (m, 1H), 2.09 (s, 3H), 1.81-
				1.66 (m, 5H), 1.42-1.22
				(m, 5H). LC-MS: m/z
				436.2 (M + H)+
681	166	XII.193
1H NMR (400 MHz, DMSO-d6) δ 8.25 (s, 1H), 7.56-7.54 (m, 1H), 7.41 (s, 1H), 7.28-7.23 (m, 3H), 7.15-7.12 (m, 1H), 6.57-6.47 (m, 2H), 6.30 (d, J = 5.6 Hz, 1H), 3.17 (s, 3H), 2.04 (s, 3H), 1.86-1.66 (m, 5H), 1.44- 1.15 (m, 6H). LC-MS:
				m/z 450.2 (M + H)+
682	167	XII.194

Com- pound 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.43 (d, J = 4.8 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.22-7.14 (m, 3H), 6.97 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 2.0 Hz, 1H), 6.77-6.75 (m, 2H), 6.56-6.51 (m, 1H), 3.23 (s, 3H), 2.73 (d, J = 4.8 Hz, 3H), 2.45 (d, J = 5.2 Hz, 3H), 2.14 (s, 3H), 1.79-1.68 (m, 5H), 1.44-1.34 (m, 6H). LC-MS: m/z 522.2 (M + H)+

CP	No	Reactant	Structure	Analytical data
72	277	Compound 24
LC-MS: m/z 466.1 (M + H) +
94	278	Int-XI
1 H NMR (400 MHz, DMSO-d6) δ 14.55 (bs, 1H), 10.20 (bs, 1H), 8.72 (bs, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.49 (s, 1H), 7.32 (d, J = 2.0 Hz, 1H), 7.20-7.15 (m, 2H), 7.02 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 448.1 (M + H) +
111	279	Compound 31
1 H NMR (400 MHz, DMSO-d6) δ 9.91 (s, 1H), 7.99 (s, 1H), 7.68 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.42 (s, 1H), 7.37 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.29-7.24 (m, 1H), 7.19-7.12 (m, 2H), 7.08-7.02 (m, 5H), 6.68 (t, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 472.2 (M + H) +
112	280	Compound 279
1 H NMR (400 MHz, DMSO-d6) δ 8.45 (s, 1H), 8.14-8.12 (m, 2H), 7.74-7.70 (m, 1H), 7.51 (t, J = 8.4 Hz, 1H), 7.43-7.38 (m, 4H), 7.33-7.29 (m, 1H), 7.01 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.4 Hz, 1H), 2.06 (s, 3H), 1.87 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 482.1 (M + H) +
120	281	Compound 31
1 H NMR (400 MHz, DMSO-d6) δ 9.61 (s, 1H), 8.48 (m, 1H), 7.61 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.40 (s, 1H), 7.31 (d, J = 2.4 Hz, 1H), 7.26 (t, J = 8.4 Hz, 1H), 7.19-7.01 (m, 7H), 6.74-6.70 (m, 1H), 3.29-3.24 (m, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.12 (t, J = 7.2 Hz, 3H). LC-MS: m/z 500.2 (M + H) +
123	282	Compound 31
1 H NMR (400 MHz, DMSO-d6) δ 7.41 (s, 1H), 7.29 (d, J = 2.0 Hz, 1H), 7.27 (s, 1H), 7.24-7.21 (m, 1H), 7.18-7.13 (m, 2H), 7.10-7.03 (m, 2H), 6.99 (s, 4H), 6.83 (t, J = 7.2 Hz, 1H), 2.91 (s, 6H), 2.04 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 500.4 (M + H) +
164	283	Compound 31
1 H NMR (400 MHz, DMSO-d6) δ 9.62 (s, 1H), 8.45 (s, 1H), 7.59 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.40 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.26 (t, J = 6.8 Hz, 1H), 7.20-7.02 (m, 7H), 6.72 (t, J = 7.6 Hz, 1H), 2.77 (d, J = 5.2 Hz, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC- MS: m/z 485.2 (M + H) +
208	284	Compound 92
1 H NMR (400 MHz, DMSO-d6) δ 9.0 (s, 1H), 7.6 (d, J = 7.3 Hz, 1H), 7.5 (d, J = 8.9 Hz, 2H), 7.29 (d, J = 2.9 Hz, 1H), 7.26 (s, 1H), 7.15 (m, 1H), 7.07-7.01 (m, 3H), 6.79 (t, J = 8.3 Hz, 2H), 2.98 (s, 6H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 501.3 (M + H) +
209	285	Compound 60
1 H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1H), 8.15 (dd, J 1 = 2.0 Hz, J 2 = 7.6 Hz, 1H), 7.55 (dd, J 1 = 2.0 Hz, J 2 = 7.6 Hz, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.29 (s, 2H), 7.16 (dd, J 1 = 2.8 Hz, J 2 = 8.8 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 7.01 (d, J = 8.8 Hz, 2H), 6.78 (dd, J 1 = 4.8 Hz, J 2 = 7.2 Hz, 1H), 2.97 (s, 6H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC- MS: m/z 501.3 (M + H) +
605	168	Compound 279
1H NMR (400 MHz, DMSO-d6) δ 9.35 (s, 1H), 8.08 (s, 1H), 7.51 (bs, 1H), 7.44 (d, J = 8.4 Hz, 2H), 7.30-7.27 (m, 2H), 7.12-7.00 (m, 5H), 6.77 (d, J = 8.8 Hz, 2H), 3.76 (s, 3H), 3.25 (s, 3H). LC- MS: m/z 416.10 (M + H)+.
606	169	Compound 279
1H NMR (400 MHz, DMSO-d6) δ 9.06 (s, 1H), 8.49-8.52 (m, 1H), 7.42 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 8.8 Hz, 1H), 7.17 (d, J = 2.4 Hz, 1H), 7.09-7.03 (m, 4H), 7.01-6.96 (m, 1H), 6.74 (d, J = 8.8 Hz, 2H), 3.75 (s, 3H), 3.23 (s, 3H), 2.74 (d, J = 4.8 Hz, 3H). LC-MS: m/z 430.2 (M + H)+.
607	170	Compound 279
1H NMR (400 MHz, DMSO-d6) δ 7.42 (d, J = 8.8 Hz, 3H), 7.22 (d, J = 8.8 Hz, 1H), 7.00 (d, J = 8.4 Hz, 2H), 6.97-6.94 (m, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.81 (d, J = 3.2 Hz, 1H), 6.72 (d, J = 8.8 Hz, 2H), 3.75 (s, 3H), 3.22 (s, 3H), 2.90 (s, 3H), 2.81 (s, 3H). LC-MS: m/z 444.2 (M + H)+.
653	171	XI.53

Com- pound 1H NMR (400 MHz, DMSO-d6): δ 13.38 (bs, 1H), 11.05 (bs, 1H), 8.36 (d, J = 8.8 Hz, 1H), 8.24 (s, 1H), 8.02 (s, 1H), 7.97 (d, J = 6.8 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.41 (d, J = 1.6 Hz, 1H), 7.24-7.17 (m, 2H), 6.95 (t, J = 7.2 Hz, 1H), 2.58-2.52 (m, 1H), 1.81-1.68 (m, 5H), 1.42-1.31 (m, 5H). LC-MS: m/z 424.2 (M + H)+.

CP	No	Reactant	Structure	Analytical data
109	286	XV.4
1 H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 7.50 (d, J = 8.8 Hz, 2H), 7.41 (s, 1H), 7.31 (s, 1H), 7.18 (m, 1H), 7.11 (s, 1H), 6.98 (d, J = 4.0 Hz, 2H), 3.74 (m, 1H), 2.95 (t, J = 6.9 Hz, 2H), 2.08 (m, 4H), 1.90 (m, 7H), 1.68 (m, 7H), 1.56-1.48 (m, 1H). LC- MS: m/z 450.2 (M + H) +
230	287	XV.10
1 H NMR (400 MHz, DMSO-d6) δ 9.88 (s, 1H), 7.51 (d, J = 8.8 Hz, 2H), 7.38 (s, 1H), 7.30 (d, J = 2.0 Hz, 1H), 7.16-7.14 (m, 1H), 7.1 (d, J = 8.8 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.17-1.15 (m, 2H), 0.87-0.84 (m, 2H). LC-MS: m/z 436.2 (M + H) +
152	288	Compound 77
1 H NMR (400 MHz, DMSO-d6) δ 13.21 (bs, 1H), 10.60 (bs, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 2.8 Hz, 1H), 7.94 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.51-7.44 (m, 3H), 7.31 (d, J = 2.0 Hz, 1H), 7.16 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 6.98 (t, J = 8.4 Hz, 2H), 6.87 (t, J = 8.4 Hz, 1H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 474.3 (M + H) +
155	289	Compound 288
1 H NMR (400 MHz, DMSO-d6) δ 8.36 (d, J = 2.4 Hz, 1H), 8.26 (dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, 1H), 8.07 (s, 1H), 7.88-7.84 (m, 1H), 7.75-7.70 (m, 2H), 7.56 (d, J = 10 Hz, 1H), 7.51-7.47 (m, 1H), 7.43 (d, J = 2.0 Hz, 1H), 7.32-7.26 (m, 2H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 456.3 (M + H) +
153	290	Compound 75
1 H NMR (400 MHz, DMSO-d6) δ 13.21 (bs, 1H), 10.46 (bs, 1H), 8.45 (s, 1H), 8.14 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 8.8 Hz, 1H), 8.04 (s, 1H), 7.94 (dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.47 (t, J = 8.4 Hz, 1H), 7.35 (d, J = 2.4 Hz, 1H), 7.26 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 6.87 (t, J = 7.2 Hz, 1H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 475.5 (M + H) +
154	291	Compound 74
1 H NMR (400 MHz, DMSO-d6) δ 13.43 (bs, 1H), 11.21 (bs, 1H), 8.82 (d, J = 7.6 Hz, 1H), 8.44 (s, 2H), 8.0 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 1H), 7.60-7.54 (m, 2H), 7.32 (d, J = 2.0 Hz, 1H), 7.16 (dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, 1H), 7.02-6.95 (m, 2H), 2.04 (s, 3H), 1.82-1.81 (bs, 6H), 1.72 (s, 6H). LC-MS: m/z 475.2 (M + H) +
175	292	VI.19
1 H NMR (400 MHz, DMSO-d6) δ 13.65 (bs, 1H), 10.95 (bs, 1H), 8.42 (s, 2H), 8.29 (dd, J 1 = 2.0 Hz, J 2 = 8.0 Hz, 1H), 8.10 (d, J = 3.2 Hz, 1H), 7.54 (m, 2H), 7.32 (d, J = 2.0 Hz, 1H), 7.16 (dd, J 1 = 2.0 Hz, J 2 = 8.4 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 6.92 (dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, 1H), 2.08 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 475.2 (M + H) +
540	172	IX.5
1H NMR (400 MHz, DMSO-d6): δ 13.38 (s, 1H), 10.75 (s, 1H), 8.36 (d, J = 8.4 Hz, 1H), 8.26 (d, J = 1.6 Hz, 1H), 8.05 (d, J = 1.2 Hz, 1H), 7.97 (dd, J 1 = 1.6 Hz & J 2 = 8.0 Hz, 1H), 7.55-7.51 (m, 1H), 7.49 (d, J = 2.4 Hz, 1H), 7.38-7.35 (m, 1H), 7.22 (d, J = 8.8 Hz, 1H), 6.97 (t, J = 8 Hz, 1H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H), LC-MS: m/z 476.2 (M + H)+
559	173	XII.98

Compound 1 H NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 10.19 (s, 1H), 8.06 (s, 1H), 7.85 (d, J = 7.6 Hz, 1H), 7.63 (t, J = 7.2 Hz, 1H), 7.57-7.50 (m, 3H), 7.21 (d, J = 8.4 Hz, 2H), 7.13-7.10 (m, 2H), 7.04 (d, J = 8.4 Hz, 2H), 6.71 (d, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 467.3 (M + H) +

CP	No	Reactant	Structure	Analytical data
90	294	Int-I.1
1 H NMR (400 MHz, DMSO-d6) δ 11.80 (bs, 1H), 9.75 (s, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H), 3.12-3.08 (m, 1H), 2.93-2.91 (m, 1H), 2.00-1.92 (m, 4H), 1.91-1.75 (m, 16H), 1.72-1.54 (m, 1H). LC-MS: m/z 368.1 (M + H) +
96	295	Int-XI
1 H NMR (400 MHz, DMSO-d6) δ 11.9 (bs, 1H), 9.71 (bs, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.33 (s, 1H), 7.30 (d, J = 2.5 Hz, 1H), 7.16-7.14 (m, 1H), 7.08 (m, 1H), 6.97 (d, J = 8.8 Hz, 2H), 3.12-3.08 (m, 1H), 2.94-2.90 (m, 1H), 2.04 (s, 4H), 1.99-1.82 (m, 10H), 1.71 (m, 7H). LC-MS: m/z 493.3 (M + H) +
105	296	Int-I.1
1 H NMR (400 MHz, DMSO-d6) δ 7.52 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 2.72 (t, J = 7.2 Hz, 2H), 2.67-2.63 (m, 2H), 2.05 (s, 3H), 1.79 (d, J = 7.6 Hz, 8H), 1.69 (s, 6H). LC-MS: m/z 366.1 (M + H) +
110	297	Int-XI
1 H NMR (400 MHz, DMSO-d6) δ 12.9 (bs, 1H), 10.06 (s, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.42 (s, 1H), 7.30 (d, J = 2.0 Hz, 1H), 7.17-7.10 (m, 2H), 6.98 (d, J = 8.8 Hz, 2H), 2.76 (t, J = 7.6 Hz, 2H), 2.74-2.62 (m, 2H), 2.03 (s, 3H), 1.90-1.86 (m, 2H), 1.81-1.80 (bs, 6H), 1.71 (s, 6H). LC-MS: m/z 491.1 (M + H) +
132	298	XI.2
1 H NMR (400 MHz, DMSO-d6) δ 11.83 (s, 1H), 9.74 (s, 1H), 7.54 (s, 1H), 7.5 (d, J = 8.8 Hz, 2H), 7.34 (s, 1H), 7.28-7.15 (m, 4H), 7.13 (s, 2H), 7.09 (d, J = 8.8 Hz, 2H), 3.13-3.09 (m, 1H), 2.96-2.90 (m, 1H), 2.25 (s, 3H), 2.04-1.77 (m, 4H). LC-MS: m/z 449.1 (M + H) +
133	299	XI.2
1 H NMR (400 MHz, DMSO-d6) δ 12.85 (bs, 1H), 10.15 (s, 1H), 7.62 (s, 1H), 7.55 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 2.0 Hz, 1H), 7.29-7.11 (m, 8H), 2.80-2.76 (m, 2H), 2.65-2.63 (m, 2H), 2.26 (s, 3H), 1.94-1.88 (m, 2H). LC-MS: m/z 447.1 (M + H) +
176	300	Int-XI
1 H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 10.42 (bs, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.42 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.16 (m, 1H), 7.12 (m, 1H), 6.98 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.41 (s, 4H). LC-MS: m/z 465.3 (M + H) +
216	301	XI.1
1 H NMR (400 MHz, DMSO-d6) δ 14.8 (bs, 1H), 8.04 (s, 1H), 7.46 (s, 1H), 7.41 (s, 1H), 7.30 (s, 2H), 7.19 (s, 1H), 6.82 (s, 1H), 2.06 (s, 3H), 1.86 (d, J = 2.4 Hz, 6H), 1.63 (s, 6H), 1.19 (d, J = 5.6 Hz, 2H), 1.10 (d, J = 5.6 Hz, 2H). LC-MS: m/z 533.2 (M + H) +
229	302	Compound 300
1 H NMR (400 MHz, DMSO-d6) δ 10.56 (s, 1H), 7.82 (d, J = 4.4 Hz, 1H), 7.47-7.42 (m, 3H), 7.31 (d, J = 2.0 Hz, 1H), 7.19-7.16 (m, 1H), 7.11 (d, J = 8.4 Hz, 1H), 6.98 (d, J = 8.8 Hz, 2H), 2.62 (d, J = 4.4 Hz, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.36-1.29 (m, 4H). LC-MS: m/z 478.3 (M + H) +
237	303	XI.7
1 H NMR (400 MHz, DMSO-d6) δ 7.53 (s, 1H), 7.34 (d, J = 2.0 Hz, 1H), 7.30 (s, 1H), 7.25-7.22 (m, 2H), 7.11 (t, J = 7.6 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H), 1.34-1.24 (m, 4H). LC-MS: m/z 465.2 (M + H) +
239	304	VI.37
1 H NMR (400 MHz, DMSO-d6) δ 12.4 (bs, 1H), 7.7 (s, 1H), 7.36 (s, 1H), 7.23 (s, 2H), 7.14 (d, J = 7.8 Hz, 2H), 6.95 (d, J = 8.3 Hz, 2H), 3.13 (s, 3H), 2.08 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.17 (m, 2H), 0.85 (m, 2H). LC-MS: m/z 479.2 (M + H) +
348	305	XI.30
1 H NMR (400 MHz, DMSO-d6) δ 12.85 (bs, 1H), 10.11 (bs, 1H), 7.91 (s, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.57-7.52 (m, 4H), 7.19 (d, J = 8.8 Hz, 2H), 7.02-6.96 (m, 4H), 2.04 (s, 3H), 1.83 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 465.2 (M − H) +
378	306	XI.29

TABLE 1 — Activity of Compounds as TEAD Palmitoylation Inhibitors % of inhibition of TEAD2

Compound structure	palmitoylation at 10 μM	CMP IC 50 (μM)
50
1025
70	5.09
5
5
80
20
20
20
8
80
100
100

Claims as granted

23 claims

Classifications

64 codes

IPC · International Patent Classification

Section A — Human necessities

A61K31/4965
A61K31/496
A61K31/4704
A61K31/4439
A61K31/44
A61K31/428
A61K31/4196
A61K31/4184
A61K31/416
A61K31/41
A61K31/405
A61K31/401
A61K31/397
A61K31/24
A61K31/196
A61K31/195
A61K31/18
A61K31/165
A61P35/00

Section C — Chemistry; metallurgy

C07D471/04
C07D401/12
C07D401/06
C07D317/32
C07D295/155
C07D295/135
C07D277/28
C07D275/06
C07D257/04
C07D249/10
C07D249/08
C07D241/28
C07D241/20
C07D239/88
C07D239/48
C07D239/42
C07D235/18
C07D235/08
C07D235/06
C07D233/64
C07D233/61
C07D231/56
C07D231/14
C07D215/227
C07D213/80
C07D213/79
C07D213/74
C07D211/62
C07D209/08
C07D207/34
C07D207/16
C07D205/04
C07C323/63
C07C317/28
C07C311/44
C07C255/58
C07C237/40
C07C229/58
C07C229/48
C07C229/44
C07C225/22
C07C211/60
C07C211/56
C07C211/55
C07C211/26

Claim changes

Soon

Coming soonHow the claims changed between publication and grant

See which claims were amended, added or cancelled during examination, with every added and removed word marked.

AmendedAddedCancelledUnchanged

The published claims of this application are not paired with the granted ones in what we hold.

File wrapper

⤢ drag to zoom

USPTOApplicanthover for detail · click to open

Pendency

4.8 y

1,761 days filing → grant

Office actions

after a restriction

Responses

1 RCE

Interviews

examiner interview summaries

Examiner

Sun Jae Yoo

art unit 1621 · TC 1600

Law firm

Law firm · Log in to unlock

Citations: 158 back · 0 forward

See the full prosecution history — every USPTO and applicant action on this file, in order.

Documents

Log in to open the documents of this file: the application as filed, every office action and response, the notice of allowance.

Chain of title

⤢ drag to zoom

Titlehover for detail · click to open

See the full assignment history — every owner this patent has passed through, with recordation dates and reel/frame numbers.