Novel small molecule inhibitors of TEAD transcription factors

Abstract

To provide a novel compound that is useful in the treatment of diseases associated with TEAD transcription factor activity.SOLUTION: The problem is solved by a compound of formula (I), or a pharmaceutically acceptable salt thereof. [L1 is absent or substituted / unsubstituted amino group; D is a substituted aryl group, etc.; A6 to A10 are substituted / unsubstituted C or N].SELECTED DRAWING: Figure 1-1

Description

[Technical Field]

[0001] Priority claims This application claims priority to U.S. Patent Application No. 62 / 819,347, filed March 15, 2019, the entire contents of which are incorporated herein by reference.

[0002] Government support This invention was made with government support under Grant Nos. 1R01CA181537 and R01DK107651 awarded by the National Institutes of Health. The U.S. Government has certain rights in this invention.

[0003] This application relates to pharmaceutically useful compounds. This disclosure provides new compounds, as well as compositions and methods of use thereof. The compounds inhibit the autopalmitoylation of TEAD transcription factors and are therefore useful for treating diseases associated with the activity of TEAD transcription factors, including, for example, cancer and other diseases. [Background technology]

[0004] Hippo signaling plays a key role in organ size control and tumor suppression. The signaling involves a core kinase cascade including MST1 / 2 and Lats1 / 2 kinases, leading to YAP / TAZ phosphorylation, cytoplasmic retention, and inhibition. 3Physiological or pathological inactivation of these kinases leads to YAP / TAZ dephosphorylation and nuclear accumulation. Subsequently, nuclear YAP / TAZ binds to TEA domain transcription factors (TEAD1-4 in mammals and Scalloped in Drosophila) to mediate target gene expression. The TEAD-YAP complex regulates normal development of skin, muscle, lung, and liver and is also an oncogenic factor amplified in many human cancers. TEAD can also bind to Vgll4, which has been implicated as a tumor suppressor by competing with YAP / TAZ for TEAD binding. Thus, TEAD is essential for regulating the transcriptional output of the Hippo pathway. Targeting TEAD-YAP may be a promising therapeutic approach for diseases with a dysregulated Hippo pathway, but directly inhibiting transcription factors using small molecules remains challenging. Therefore, understanding TEAD regulation may reveal new therapeutic opportunities for drug discovery.

[0005] Posttranslational S-palmitoylation attaches a 16-carbon palmitate to cysteine ​​residues via a reversible thioester bond. Numerous palmitoylated proteins have been identified through proteomic studies. Dynamic S-palmitoylation plays an important role in regulating the trafficking, membrane localization, and function of many proteins, including Src family kinases, GTPases, and synaptic adhesion molecules. The Asp-His-His-Cys (DHHC) family of proteins is an evolutionarily conserved protein palmitoyl acyltransferase (PAT) that mediates enzymatic S-palmitoylation. In addition, some proteins can directly bind palmitoyl-coenzyme A (CoA) and undergo PAT-independent autopalmitoylation. However, autopalmitoylation has not been well characterized. Most reported examples of autopalmitoylation are observed at unphysiologically high concentrations of palmitoyl-CoA (>100 μM). To date, only a few proteins, including the yeast transporter protein Bet3, are autopalmitoylated under physiological concentrations of palmitoyl-CoA (1–10 µM). Therefore, it is important to uncover additional autopalmitoylated proteins and understand their regulation and function. Summary of the Invention

[0006] The present disclosure relates, inter alia, to compounds of formula (I): [ka] or a pharmaceutically acceptable salt thereof, wherein the variables are as defined below.

[0007] The present disclosure also provides compositions comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

[0008] The present disclosure also provides a method for 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.

[0009] 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 explanation of the drawings]

[0010] [Figure 1-1] 1 is a scheme showing the structures of examples of compounds within the scope of the present invention. [Figure 1-2] 1 is a scheme showing the structures of examples of compounds within the scope of the present invention. [Figure 2] 1 is a scheme showing the structures of some reference compounds. [Figure 3] FIG. 1 shows streptavidin and histidine blot results showing the results of an assay for the inhibition of in vitro autopalmitoylation of TEAD2 by 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. [Figure 4] FIG. 1 shows streptavidin and histidine blot results showing the results of an assay for the inhibition of in vitro autopalmitoylation of TEAD2 by compound CP-55 at various concentrations. [Figure 5] 1 is a collection of plots showing the inhibition of cell proliferation in the 92.1 uveal melanoma cell line, the cellosaurus OCM1 cell line, the human hepatoma huh7 cell line, the SNU398 human liver hepatocellular carcinoma cell line, and the MDA-MB-453 human breast metastatic carcinoma cell line by compound CP-55 at various concentrations. [Figure 6] 1 is a collection of plots showing the inhibition of gene expression of CYR61, CTGF, and ANKRD1 genes in the huh7 human liver cell line by the compound CP-55 at various time points and concentrations. [Figure 7] FIG. 1 shows streptavidin and histidine blot results showing the results of an assay for the inhibition of in vitro autopalmitoylation of TEAD2 by compound CP-58 at various concentrations. [Figure 8] 1 is a plot showing inhibition of cell proliferation in the 92.1 uveal melanoma cell line by compounds CP-1, CP-52, CP-55, and CP-58 at various concentrations. [Figure 9] 1 is a plot showing inhibition of cell proliferation in the huh7 human hepatocyte cell line by compound CP-57 at various concentrations. [Figure 10] 1 is a plot showing the inhibition of cell proliferation in the huh7 human hepatocyte cell line by compound CP-58 at various concentrations. [Figure 11] 1 is a pair of plots showing the inhibition of gene expression of the genes CYR61, CTGF, and ANKRD1 in the huh7 human liver cell line by compound CP-58 after 24 hours compared to a control. [Figure 12] FIG. 1 shows streptavidin and histidine blot results showing the results of an assay for the inhibition of TEAD2 in vitro autopalmitoylation by compounds CP-1, CP-55, CP-58, CP-59, CP-60, CP-61, and CP-62. [Figure 13] 1 is a plot of the inhibition of cell proliferation in the huh7 human hepatocyte cell line by compounds CP-58, CP-59, CP-60, CP-61, and CP-62 at various concentrations. DETAILED DESCRIPTION OF THE INVENTION

[0011] The terms "for example" and "such as," as well as their grammatical equivalents, are understood to be accompanied by the phrase "without limitation," unless expressly stated otherwise.

[0012] Unless the context clearly dictates otherwise, the singular forms "a," "an," and "the" include plural referents.

[0013] The term "about" means "approximately" (eg, approximately plus or minus 10% of the indicated value).

[0014] The expressions "ambient temperature" and "room temperature" (abbreviated "rt") generally refer to a temperature near the room temperature in which a reaction is carried out, e.g., about 20°C to about 30°C, typically about 25°C, e.g., the reaction temperature.

[0015] Proteomic and biochemical studies have confirmed that TEAD transcription factors are palmitoylated at evolutionarily conserved cysteine ​​residues. TEADs have been shown to undergo PAT-independent autopalmitoylation under physiological concentrations of palmitoyl-CoA. The crystal structure of lipid-bound TEADs revealed a novel ligand-binding site in TEADs. Furthermore, autopalmitoylation plays an important role in regulating TEAD-YAP association and their physiological functions in vitro and in vivo. Therefore, TEAD palmitoylation plays an important role in regulating the Hippo pathway transcription complex.

[0016] The discovery of a new ligand-binding site in TEAD has enabled the discovery of small molecule inhibitors of TEAD autopalmitoylation. Without being bound by any theory, it is understood that ligands bind to the palmitate-binding pocket and inhibit TEAD-YAP interaction, cancer cell proliferation, and migration. Therefore, direct inhibition of TEAD autopalmitoylation activity is useful for inhibiting these oncogenic transcription factors.

[0017] I. Compound The present disclosure relates, inter alia, to compounds of formula (I) [ka] (In the formula, L 1 does not exist or does not have the formula N(R N ) or C(O) groups, D is a group of formula (D1), (D2), (D3), (D4), (D5), (D6), or (D7), [ka] m is 1, 2, or 3; A 1 But C(O)R 1 , S(O)2R 1 , NHC(O)R 1 , (C 1~3 alkylene)-C(O)R 1 , NH(C 1~3 alkylene)-C(O)R 1 , CN, NO2, 5- to 10-membered heteroaryl, 4- to 10-membered heterocycloalkyl, (C 1~3 alkylene)-5 to 10-membered heteroaryl, or (C 1~3 alkylene)-4 to 10-membered heterocycloalkyl, and A 1 Form (C 1~3 alkylene)-C(O)R 1 Group (C 1~3 alkylene) groups are unsubstituted or each independently selected from halogen, OR a1 , N.R. c1 R d1 , N.R. a1 (CO)(C 1~6 alkyl), and NR a1 (CO)O(CC 1~6 alkyl), and A 1 5- to 10-membered heteroaryl, 4- to 10-membered heterocycloalkyl, (C 1~3 alkylene)-5 to 10-membered heteroaryl, or (C 1~3 alkylene)-4 to 10-membered heterocycloalkyl are unsubstituted or independently selected from the group consisting of halogen, OR a1 , S.R. a1 , C(O)OR a1 , N.R. c1 R d1 , and C(O)NR c1 R d1 and is substituted by 1, 2, 3, 4, or 5 substituents selected from L 2 does not exist or does not have the formula N(R N ), O, or C(O), L 3does not exist or has the formula CH2, C≡C, N(R N ), or a C(O) group, Each R N However, independently, H, C 1~6 Alkyl, C(O)C 1~6 Alkyl, or C(O)OC 1~6 is alkyl, R 1 But H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, Cy 1A , OH, O.C. 1~6 Alkyl, OCy 1A , O(C 1~3 (Alkylenyl)Cy 1A , NH2, 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 and R 1 Form C 1~6 Each alkyl is unsubstituted or each independently selected from halogen, OR a1 , S.R. a1 , and N.R. c1 R d1 and is substituted by 1, 2, 3, 4, or 5 substituents selected from Cy 1A But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 1A Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or contains 0, 1, or 2 Cy 1B and each independently an unsubstituted C 1~6 Alkyl, C2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl; Each Cy 1B But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 1B Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl; A 2 But, CR 2 or N, A 3 But, CR 3 or N, A 4 But, CR 4 or N, A 5 But, CR 5 or N, A 6 But, CR 6 or N, A 7 But, CR 7 or N, A 8 But, CR 8 or N, A 9 But, CR 9 or N, A 10 But, CR 10 or N, A D41 However, CH, C(C 1~6 alkyl), or N, A D42 is CH2, NH, or NC 1~6 is alkyl, R 2 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 3 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O) c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 4 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 5 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 6 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , S(O)2R b1 , S(O)NR c1 R d1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from1~6 is alkyl, R 7 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , S(O)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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, Cy 7A But C 6~10 Aryl, C3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 7A Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or 7B ,OCy 7B , NHCy 7B , and C(O)NHCy 7B and 0, 1, or 2 substituents selected from, each independently, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl; Each Cy 7B But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 7B Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R.a1 , N.R. c1 R d1 , ,C(O)ORa1C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl; R 8 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S(O)NR c1 R d1 , S.R. a1 , N.R. c1 R d1 , N.R. c1 S(O)2R 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 , SO2NHCy 8A , N(C 1~6 Alkyl)(C 1~3 (Alkylenyl)Cy 8A , C(O)NHCy 8A , C 1~3Alkylene-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 halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, Cy 8A But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 8A Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or 8B ,OCy 8B , NHCy 8B , and C(O)NHCy 8B and 0, 1, or 2 substituents selected from, each independently, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl; Each Cy 8B But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 8B Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl; R 9 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , N.R. c1 C(O)R b1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R.c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 10 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, Cy D71 But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 14-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy D71 Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or D72 , CH2Cy D72 , O.C.y. 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, or 2 substituents selected from, each independently, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C1~6 Haloalkyl, CN, OR a1 , S(hal)5, SR a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 Alkyl or C 2~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkenyl; Each Cy D72 But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy D72 Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently is 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, ORa1, SRa1, NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently, C 6~10 Aryl, C 3~15 Cycloalkyl, 4-10 membered heterocycloalkyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R.c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl, C 6~10 Aryl, C 3~15 cycloalkyl, and 4- to 10-membered heterocycloalkyl are each optionally independently selected from C 1~6 Alkyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , and C(O)NR c1 R d1 and is substituted with 1, 2, or 3 substituents selected from R a1 , R b1 , R c1 , and R d1 However, independently, 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 form a 4- to 10-membered unsubstituted heterocycloalkyl ring, or independently, C 1~6 Alkyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , and C(O)NR c1R d1 form a heterocyclic ring substituted with 1, 2, or 3 substituents selected from however, L 1 But, L 2 is C(O), the formula N(R N ) group, L 1 But, L 2 is N(R N ), then a group of formula C(O), L 2 does not exist or L 1 is C(O), the formula N(R N ) group, L 2 does not exist or L 1 is N(R N ) is a group of formula C(O), A D41 But, A D42 is NH or NC 1~6 If it is alkyl, CH, C(C 1~6 alkyl), A D42 But, A D41 is NH or NC 1~6 When it is alkyl, it is CH2; A 2 , A 3 , A 4 , and A 5 At most two of are N, A 6 , A 7 , A 8 , A 9 , and A 10 At most two of are N, R 1 exists and Cy 1A , O.C.y. 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 1~6Alkyl)(C 1~3 (Alkylenyl)Cy 1A or R 7 But 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 But 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 1~6Alkyl)(C 1~3 (Alkylenyl)Cy 8A or a pharmaceutically acceptable salt thereof.

[0018] The present disclosure relates, inter alia, to compounds of formula (I) [ka] (In the formula, L 1 does not exist or does not have the formula N(R N ) or C(O) groups, D is a group of formula (D1), (D2), (D3), (D4), (D5), (D6), or (D7), [ka] m is 1, 2, or 3; A 1 But C(O)R 1 , S(O)2R 1 , NHC(O)R 1 , (C 1~3 alkylene)-C(O)R 1 , NH(C 1~3 alkylene)-C(O)R 1 , CN, NO2, 5- to 10-membered heteroaryl, 4- to 10-membered heterocycloalkyl, (C 1~3 alkylene)-5 to 10-membered heteroaryl, or (C 1~3 alkylene)-4 to 10-membered heterocycloalkyl, and A 1 Form (C 1~3 alkylene)-C(O)R 1 Group (C 1~3 alkylene) groups are unsubstituted or each independently selected from halogen, OR a1 , N.R. c1 R d1 , N.R. a1 (CO)(C 1~6 alkyl), and NR a1 (CO)O(C 1~6 alkyl), and A 15- to 10-membered heteroaryl, 4- to 10-membered heterocycloalkyl, (C 1~3 alkylene)-5 to 10-membered heteroaryl, or (C 1~3 alkylene)-4 to 10-membered heterocycloalkyl are unsubstituted or independently selected from the group consisting of halogen, OR a1 , S.R. a1 , C(O)OR a1 , N.R. c1 R d1 , and C(O)NR c1 R d1 and is substituted by 1, 2, 3, 4, or 5 substituents selected from L 2 does not exist or does not have the formula N(R N ), O, or C(O), L 3 does not exist or has the formula CH2, C≡C, N(R N ), or a C(O) group, Each R N However, independently, H, C 1~6 Alkyl, C(O)C 1~6 Alkyl, or C(O)OC 1~6 is alkyl, R 1 But H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, Cy 1A , OH, O.C. 1~6 Alkyl, OCy 1A , O(C 1~3 (Alkylenyl)Cy 1A , NH2, 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 and R 1 Form C 1~6Each alkyl is unsubstituted or each independently selected from halogen, OR a1 , S.R. a1 , and N.R. c1 R d1 and is substituted by 1, 2, 3, 4, or 5 substituents selected from Cy 1A But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 1A Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or contains 0, 1, or 2 Cy 1B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl; Each Cy 1B But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 1B Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl; A 2 But, CR 2 or N, A 3 But, CR 3 or N, A 4 But, CR 4 or N, A 5 But, CR 5 or N, A 6 But, CR 6 or N, A 7 But, CR 7 or N, A 8 But, CR 8 or N, A 9 But, CR 9 or N, A 10 But, CR 10 or N, A D41 However, CH, C(C 1~6 alkyl), or N, A D42 is CH2, NH, or NC 1~6 is alkyl, R 2 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 3 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 4 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1, and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 5 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 6 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 7 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, ORa1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, Cy 7A But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 7A Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or 7B,OCy 7B , NHCy 7B , and C(O)NHCy 7B and 0, 1, or 2 substituents selected from, each independently, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl; Each Cy 7B But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 7B Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 Rd1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl; R 8 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 , SO2NHCy 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R.c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, Cy 8A But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 8A Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or 8B , O.C.y. 8B , NHCy 8B , and C(O)NHCy 8B and 0, 1, or 2 substituents selected from, each independently, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl; Each Cy 8B But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 8B Form C 6~10 Aryl, C 3~15Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl; R 9 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 10 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R.c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, Cy D71 But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 14-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy D71 Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or D72 , CH2Cy D72 , O.C.y. 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, or 2 substituents selected from, each independently, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R.c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 Alkyl or C 2~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkenyl; Each Cy D72 But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy D72 Form C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently is unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~15 Cycloalkyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl; R a1 , R b1 , R c1 , and R d1 However, independently, H, C 1~6 Alkyl, HO-C 1~6 Alkylene, C 1~6 Alkoxy-C 1~6 Alkylene, C 6~10 Aryl, C 2~6Alkenyl, and C 2~6 alkynyl; or R c1 and R d1 which together with the nitrogen atom to which they are attached form a 4- to 10-membered unsubstituted heterocycloalkyl ring), or a pharmaceutically acceptable salt thereof. In some embodiments, L 1 L 2 is C(O), the formula N(R N ) group, L 1 L 2 is N(R N ), then a group of formula C(O), L 2 does not exist or L 1 is C(O), the formula N(R N ) group, L 2 does not exist or L 1 is N(R N ) is a group of formula C(O), A D41 is A D42 is NH or NC 1~6 If it is alkyl, CH, C(C 1~6 alkyl), A D42 is A D41 is NH or NC 1~6 When it is alkyl, it is CH2; A 2 , A 3 , A 4 , and A 5 At most two of are N, A 6 , A 7 , A 8 , A 9 , and A 10 At most two of are N, R 1 exists and Cy 1A , O.C.y. 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 Cy 7A , O.C.y. 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 Cy 8A , O.C.y. 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)NHCy8A , 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 or a pharmaceutically acceptable salt thereof.

[0019] In some embodiments, L 1 does not exist.

[0020] In some embodiments, L 1 is N(R N ), for example, NH or NMe.

[0021] In some embodiments, L 1 is C(O).

[0022] In some embodiments, D is a group of formula (D1).

[0023] In some embodiments, D is a group of formula (D2).

[0024] In some embodiments, D is a group of formula (D3).

[0025] In some embodiments, D is a group of formula (D4).

[0026] In some embodiments, D is a group of formula (D5).

[0027] In some embodiments, D is a group of formula (D6).

[0028] In some embodiments, D is a group of formula (D7).

[0029] In some embodiments, A 1 is C(O)R 1, for example, C(O)OH.

[0030] In some embodiments, A 1 is S(O)2R 1 is.

[0031] In some embodiments, A 1 is NHC(O)R 1 is.

[0032] In some embodiments, A 1 is NH(C 1~3 alkylene)-C(O)R 1 is.

[0033] In some embodiments, A 1 is (C 1~3 alkylene)-C(O)R 1 and A 1 Form (C 1~3 alkylene)-C(O)R 1 Group (C 1~3 alkylene) groups are unsubstituted or each independently selected from halogen, OR a1 , N.R. c1 R d1 , N.R. a1 (CO)(C 1~6 alkyl), and NR a1 (CO)O(C 1~6 and substituted by 0, 1, 2, 3, 4, or 5 substituents selected from: alkyl;

[0034] In some embodiments, A 1 is (C 1~3 alkylene)-C(O)R 1 and A 1 Form (C 1~3 alkylene)-C(O)R 1 Group (C 1~3 The alkylene group is NR c1 R d1 , N.R. a1 (CO)(C 1~6 alkyl), or NR a1 (CO)O(C 1~6alkyl), for example, CH2CH(NH2)C(O)OH.

[0035] In some embodiments, A 1 is CN.

[0036] In some embodiments, A 1 is NO2.

[0037] In some embodiments, A 1 are unsubstituted or each independently a halogen, OR a1 , S.R. a1 , C(O)OR a1 , N.R. c1 R d1 , and C(O)NR c1 R d1 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, each substituted by 0, 1, 2, 3, 4, or 5 substituents selected from 1~3 alkylene)-5 to 10-membered heteroaryl, or (C 1~3 alkylene)-4 to 10-membered heterocycloalkyl.

[0038] In some embodiments, A 1 are unsubstituted or each independently a halogen, OR a1 , S.R. a1 , C(O)OR a1 , N.R. c1 R d1 , and C(O)NR c1 R d1 and R is a 5- to 10-membered heteroaryl, a 4- to 10-membered heterocycloalkyl, CH(5- to 10-membered heteroaryl), or CH(4- to 10-membered heterocycloalkyl), each of which is substituted by 1, 2, 3, 4, or 5 substituents selected from:

[0039] In some embodiments, A 2 is CR 2 is.

[0040] In some embodiments, R2 is H.

[0041] In some embodiments, A 2 is N.

[0042] In some embodiments, A 3 is CR 3 is.

[0043] In some embodiments, R 3 is H, C 1~6 Alkyl, or C 1~6 It is haloalkyl.

[0044] In some embodiments, R 3 is H, methyl, or trifluoroethyl.

[0045] In some embodiments, R 3 is H.

[0046] In some embodiments, A 3 is N.

[0047] In some embodiments, A 4 is CR 4 is.

[0048] In some embodiments, R 4 is H.

[0049] In some embodiments, A 4 is N.

[0050] In some embodiments, A 5 is CR 5 is.

[0051] In some embodiments, R 5 is H.

[0052] In some embodiments, A 5 is N.

[0053] In some embodiments, A 2 is CR 2 and A 3 is CR 3 and A 4 is CR 4 and A 5 is CR 5 is.

[0054] In some embodiments, A 2 is CR 2 and A 3 is CR 3 and A 4 is CR 4 and A 5 is N.

[0055] In some embodiments, D is a group of formula (D4).

[0056] In some embodiments, A D41 is CH.

[0057] In some embodiments, A D41 is C(C 1~6 alkyl).

[0058] In some embodiments, A D41 is N.

[0059] In some embodiments, A D42 is NH.

[0060] In some embodiments, A D42 is NC 1~6 Alkyl, for example, NMe.

[0061] In some embodiments, A D42 is CH2.

[0062] In some embodiments, D is a group of formula (D4) and m is 1.

[0063] In some embodiments, D is a group of formula (D4) and m is 2.

[0064] In some embodiments, D is a group of formula (D4) and m is 3.

[0065] In some embodiments, D is a group of formula (D5).

[0066] In some embodiments, D is a group of formula (D5) and m is 1.

[0067] In some embodiments, D is a group of formula (D5) and m is 2.

[0068] In some embodiments, D is a group of formula (D5) and m is 3.

[0069] In some embodiments, D is a group of formula (D6).

[0070] In some embodiments, D is a group of formula (D6) and m is 1.

[0071] In some embodiments, D is a group of formula (D6) and m is 2.

[0072] In some embodiments, D is a group of formula (D6) and m is 3.

[0073] In some embodiments, D is a group of formula (D7).

[0074] In some embodiments, L 2 does not exist.

[0075] In some embodiments, L 2 is a group of formula O.

[0076] In some embodiments, L 2 is the formula N(R N ) group.

[0077] In some embodiments, L 2 is a group of formula C(O).

[0078] In some embodiments, L 3 does not exist.

[0079] In some embodiments, L 3 is a group of formula CH2.

[0080] In some embodiments, L 3 is the formula N(R N ) group.

[0081] In some embodiments, L 3 is a group of formula C(O).

[0082] In some embodiments, L 3 is a group of formula C≡C.

[0083] In some embodiments, Cy D71 is C 6~10 Aryl (eg, phenyl).

[0084] In some embodiments, Cy D71 is C 3~15 It is cycloalkyl (eg, cyclopropyl).

[0085] In some embodiments, Cy D71 is a 5- to 10-membered heteroaryl (e.g., triazole, 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).

[0086] In some embodiments, Cy D71is a 4-10 membered heterocycloalkyl (e.g., piperidine, 1,3-dioxolane, indoline, pyrrolidine).

[0087] In some embodiments, Cy D71 Form C 6~10 Aryl, C 3~15 The cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted.

[0088] In some embodiments, Cy D71 Form C 6~10 Aryl, C 3~15 The cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is substituted.

[0089] In some embodiments, Cy D71 Form C 6~10 Aryl, C 3~15 The cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl are each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 Alkyl or C 2~6 and is substituted by 1, 2, 3, 4, or 5 substituents selected from alkenyl.

[0090] In some embodiments, Cy D71 Form C 6~10 Aryl, C 3~15 Cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is Cy D72 , CH2Cy 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 is substituted by 0, 1, or 2 substituents selected from:

[0091] In some embodiments, Cy D72 is C 6~10 Aryl (eg, phenyl).

[0092] In some embodiments, Cy D72 is C 3~15 It is cycloalkyl (eg, cyclopropyl).

[0093] In some embodiments, Cy D72 is a 5- to 10-membered heteroaryl (e.g., triazole, 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).

[0094] In some embodiments, Cy D72 is a 4-10 membered heterocycloalkyl (e.g., piperidine, 1,3-dioxolane, indoline, pyrrolidine).

[0095] In some embodiments, Cy D72 Form C 6~10 Aryl, C 3~15The cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted.

[0096] In some embodiments, Cy D72 Form C 6~10 Aryl, C 3~15 The cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is substituted.

[0097] In some embodiments, Cy D72 Form C 6~10 Aryl, C 3~15 Cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~15 Cycloalkyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 and substituted by 0, 1, or 2 substituents selected from alkyl.

[0098] In some embodiments, R 1 is H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, Cy 1A , OH, O.C. 1~6 Alkyl, OCy 1A , O(C 1~3 (Alkylenyl)Cy 1A, NH2, 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 is.

[0099] In some embodiments, R 1 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 is.

[0100] In some embodiments, R 1 is NHCy 1A is.

[0101] 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 (eg, OMe).

[0102] In some embodiments, R 1 is OH.

[0103] In some embodiments, R 1 is a group of one of the following formulae: [ka] During the ceremony, R 11 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 12 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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)Cy1B , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 13 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 14 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 15 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 16 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 17 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 18 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 It is alkyl.

[0104] In some embodiments, R 1 is a group of one of the following formulae: [ka]

[0105] In some embodiments, Cy 1A is C 6~10 Aryl, e.g., unsubstituted or containing 0, 1, or 2 Cy 1B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 and phenyl substituted with 0, 1, 2, 3, 4, or 5 substituents selected from alkyl.

[0106] In some embodiments, Cy 1A is C 6~10 Aryl, e.g., unsubstituted or containing one Cy 1B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 and phenyl substituted with 0, 1, 2, 3, 4, or 5 substituents selected from alkyl.

[0107] In some embodiments, Cy 1A is C 6~10 Aryl, e.g., unsubstituted or containing one Cy 1B is phenyl substituted by

[0108] In some embodiments, each Cy 1B are unsubstituted or, each independently, an unsubstituted C 1~6Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 C substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl 3~15 Cycloalkyl (e.g., C 3~10 cycloalkyl, for example, adamantyl, for example, adamant-1-yl).

[0109] In some embodiments, each Cy 1B is the unsubstituted C 3~15 Cycloalkyl (e.g., C 3~10 cycloalkyl, for example, adamantyl, for example, adamant-1-yl).

[0110] In some embodiments, Cy 1A is a group of one of the following formulae: [ka] During the ceremony, R 11 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , Cy 1B , OH, OCy 1B , O(C 1~3 (Alkylenyl)Cy 1B , NHCy 1B , NH(C1~3 (Alkylenyl)Cy 1B , N(C 1~6 Alkyl)Cy 1B , or N(C 1~6 Alkyl)(C 1~3 (Alkylenyl)Cy 1B , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 12 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 13 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1, S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 14 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6is alkyl, R 15 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 16 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 17 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 18 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , Cy 1B , OH, OCy 1B , O(C 1~3 (Alkylenyl)Cy 1B , NHCy1B , 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 It is alkyl.

[0111] In some embodiments, Cy 1A is a group of one of the following formulae: [ka]

[0112] In some embodiments, Cy 1A is unsubstituted or contains 0, 1, or 2 Cy 1B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl, 3~15 Cycloalkyl (e.g., C 3~10In some embodiments, Cy is cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). 1A are unsubstituted or, each independently, an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 C substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl 3~15 Cycloalkyl (e.g., C 3~10 In some embodiments, Cy is cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). 1A is the unsubstituted C 3~15 Cycloalkyl (e.g., C 3~10 In some embodiments, Cy is cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). 1A is adamantyl, e.g., unsubstituted or substituted adamant-1-yl. In some embodiments, Cy 1A is unsubstituted adamantyl, for example, adamant-1-yl.

[0113] In some embodiments, R 7 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , or halogen, C 1~6Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 8 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 It is alkyl.

[0114] In some embodiments, R 7 is H and R 8 is H.

[0115] In some embodiments, L 2 does not exist.

[0116] In some embodiments, L 2 is N(R N )

[0117] In some embodiments, L 2 is C(O).

[0118] In some embodiments, R N is H.

[0119] In some embodiments, A 6 is CR 6 is.

[0120] In some embodiments, R 6 is H.

[0121] In some embodiments, A 6 is N.

[0122] In some embodiments, A 7 is CR 7 is.

[0123] In some embodiments, R 7 is H.

[0124] In some embodiments, R 7 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 7 A, 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 is.

[0125] In some embodiments, R 7 Cy 7A ,OCy 7A , O(C 1~3 (Alkylenyl)Cy 7A , NHCy 7A , NH(C 1~3 (Alkylenyl)Cy 7A , N(C1~6 Alkyl)Cy 7A , or N(C 1~6 Alkyl)(C 1~3 (Alkylenyl)Cy 7A is.

[0126] In some embodiments, R 7 is N(C(O)C 1~6 Alkyl)Cy 7A is.

[0127] In some embodiments, R 7 is NHCy 7A is.

[0128] In some embodiments, R 7 is a group of one of the following formulae: [ka] During the ceremony, R 71 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 72 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 73 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 1~6Alkyl)(C 1~3 (Alkylenyl)Cy 7B , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 74 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 75 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , Cy 7B , OH, OCy 7B , O(C1~3 (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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 76 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 77 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 78 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R.c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 It is alkyl.

[0129] In some embodiments, R 7 is a group of one of the following formulae: [ka]

[0130] In some embodiments, Cy 7A is C 6~10 Aryl, e.g., unsubstituted or containing 0, 1, or 2 Cy 7B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 and phenyl substituted with 0, 1, 2, 3, 4, or 5 substituents selected from alkyl.

[0131] In some embodiments, Cy 7A is C 6~10 Aryl, e.g., unsubstituted or containing one Cy 7B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 Rd1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 and phenyl substituted with 0, 1, 2, 3, 4, or 5 substituents selected from alkyl.

[0132] In some embodiments, Cy 7A is C 6~10 Aryl, e.g., unsubstituted or containing one Cy 7B is phenyl substituted by

[0133] In some embodiments, each Cy 7B are unsubstituted or, each independently, an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 C substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl 3~15 Cycloalkyl (e.g., C 3~10 cycloalkyl, for example, adamantyl, for example, adamant-1-yl).

[0134] In some embodiments, each Cy 7B is the unsubstituted C 3~15 Cycloalkyl (e.g., C 3~10cycloalkyl, for example, adamantyl, for example, adamant-1-yl).

[0135] In some embodiments, Cy 7A is a group of one of the following formulae: [ka] During the ceremony, R 71 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 72 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 73 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 74 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 75 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 Rd1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 76 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 77 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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(C1~6 Alkyl)(C 1~3 (Alkylenyl)Cy 8B , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 78 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 It is alkyl.

[0136] In some embodiments, Cy 7A is a group of one of the following formulae: [ka]

[0137] In some embodiments, Cy 7Ais unsubstituted or contains 0, 1, or 2 Cy 7B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl, 3~15 Cycloalkyl (e.g., C 3~10 In some embodiments, Cy is cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). 7A are unsubstituted or, each independently, an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 C is substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl 3~15 Cycloalkyl (e.g., C 3~10 In some embodiments, Cy is cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). 7A is the unsubstituted C 3~15Cycloalkyl (e.g., C 3~10 In some embodiments, Cy is cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). 7A is adamantyl, e.g., unsubstituted or substituted adamant-1-yl. In some embodiments, Cy 7A is unsubstituted adamantyl, for example, adamant-1-yl.

[0138] In some embodiments, R 1 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 8 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 It is alkyl.

[0139] In some embodiments, A 1 is CR1 and A 2 is CR 2 and A 3 is CR 3 and A 4 is CR 4 and A 5 is CR 5 and A 6 is CR 6 and A 8 is CR 8 and A 9 is CR 9 and A 10 is CR 10 is.

[0140] In some embodiments, A 1 is CR 1 and A 3 is CR 3 and A 4 is CR 4 and A 5 is N and A 6 is CR 6 and A 8 is CR 8 and A 9 is CR 9 and A 10 is CR 10 is.

[0141] In some embodiments, A 7 is N.

[0142] In some embodiments, A 8 is CR 8 is.

[0143] In some embodiments, R 8 is H.

[0144] In some embodiments, R 8 Cy 8A , O.C.y. 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 is.

[0145] In some embodiments, R 8 Cy 8A , O.C.y. 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 is.

[0146] In some embodiments, R 8 is N(Cy8 A )2.

[0147] In some embodiments, R 8 is N(C(O)C 1~6 Alkyl)Cy 8A is.

[0148] In some embodiments, R 8 is SO2NHCy 8A is.

[0149] In some embodiments, R 8 is C 1~3 Alkylene-C(O)NHCy 8A is.

[0150] In some embodiments, R 8 is NHCy 8A is.

[0151] In some embodiments, R 8 is a group of one of the following formulae: [ka] During the ceremony, R 81 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 82 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 83 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 84 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 85 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 1~6Alkyl)(C 1~3 (Alkylenyl)Cy 8A , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 86 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 87 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , Cy 8A , OH, OCy 8A , O(C1~3 (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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 88 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 It is alkyl.

[0152] In some embodiments, R 8is a group of one of the following formulae: [ka]

[0153] In some embodiments, Cy 8A is C 6~10 Aryl, e.g., unsubstituted or containing 0, 1, or 2 Cy 8B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 and phenyl substituted with 0, 1, 2, 3, 4, or 5 substituents selected from alkyl.

[0154] In some embodiments, Cy 8A is C 6~10 Aryl, e.g., unsubstituted or containing one Cy 8B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from1~6 and phenyl substituted with 0, 1, 2, 3, 4, or 5 substituents selected from alkyl.

[0155] In some embodiments, Cy 8A is C 6~10 Aryl, e.g., unsubstituted or containing one Cy 8B is phenyl substituted by

[0156] In some embodiments, each Cy 8B are unsubstituted or, each independently, an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 C substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl 3~15 Cycloalkyl (e.g., C 3~10 cycloalkyl, for example, adamantyl, for example, adamant-1-yl).

[0157] In some embodiments, each Cy 8B is the unsubstituted C 3~15 Cycloalkyl (e.g., C 3~10 cycloalkyl, for example, adamantyl, for example, adamant-1-yl).

[0158] In some embodiments, Cy 8A is a group of one of the following formulae: [ka] During the ceremony, R 81 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 82 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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)Cy8A , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 83 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 84 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 85 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 86 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 87 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 88 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 It is alkyl.

[0159] In some embodiments, Cy 8A is a group of one of the following formulae: [ka]

[0160] In some embodiments, Cy 8A is unsubstituted or contains 0, 1, or 2 Cy 8B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1, S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl, 3~15 Cycloalkyl (e.g., C 3~10 In some embodiments, Cy is cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). 8A are unsubstituted or, each independently, an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 C is substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl 3~15 Cycloalkyl (e.g., C 3~10 In some embodiments, Cy is cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). 8A is the unsubstituted C 3~15 Cycloalkyl (e.g., C 3~10 In some embodiments, Cy is cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). 8A is adamantyl, e.g., unsubstituted or substituted adamant-1-yl. In some embodiments, Cy 8Ais unsubstituted adamantyl, for example, adamant-1-yl.

[0161] In some embodiments, R 1 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 7 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 It is alkyl.

[0162] In some embodiments, A 1 is CR 1 and A 2 is CR 2 and A 3 is CR 3 and A 4 is CR 4 and A 5 is CR 5 and A 6is CR 6 and A 7 is CR 7 and A 8 is CR 8 and A 9 is CR 9 and A 10 is CR 10 is.

[0163] In some embodiments, A 1 is CR 1 and A 3 is CR 3 and A 4 is CR 4 and A 5 is N and A 6 is CR 6 and A 7 is CR 7 and A 8 is CR 8 and A 9 is CR 9 and A 10 is CR 10 is.

[0164] In some embodiments, A 8 is N.

[0165] In some embodiments, A 9 is CR 9 is.

[0166] In some embodiments, R 9 is H, C 1~6 Alkyl, or C 1~6 It is haloalkyl.

[0167] In some embodiments, R 9 is H, methyl, or trifluoroethyl.

[0168] In some embodiments, R 9 is H.

[0169] In some embodiments, A9 is N.

[0170] In some embodiments, A 10 is CR 10 is.

[0171] In some embodiments, R 10 is H.

[0172] In some embodiments, A 10 is N.

[0173] In some embodiments, the compound is a compound of one of the following formulae (I-1) to (I-60): [ka] [ka] [ka] [ka] [ka] [ka] During the ceremony, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R1 0 , R N , A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , A 7 , A 8 , A 9 , A10 , Cy 1A , Cy 1B , Cy 7A , Cy 7B , Cy 8A , Cy 8B , L 1 , and L 2 is as defined above for compounds of formula (I) or any of its embodiments, L 7 is absent or contains O, NH, or N(C 1~6 alkyl), L 8 is absent or contains O, NH, or N(C 1~6 alkyl), R 11 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 12 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 13 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 14 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 15 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 1~6Alkyl)(C 1~3 (Alkylenyl)Cy 1B , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 16 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 17 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , Cy 1B , OH, OCy 1B , O(C1~3 (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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 18 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 71 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 72 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R.c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 73 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 74 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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)Cy7B , or N(C 1~6 Alkyl)(C 1~3 (Alkylenyl)Cy 7B , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 75 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 76 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , Cy7B , 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 77 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 78 H, unsubstituted C1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 81 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, ORa1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 82 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 83 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , Cy 8B , OH, OCy 8B , O(C 1~3 (Alkylenyl)Cy 8B , NHCy 8B , NH(C 1~3 (Alkylenyl)Cy8B , N(C 1~6 Alkyl)Cy 8B , or N(C 1~6 Alkyl)(C 1~3 (Alkylenyl)Cy 8B , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 84 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 85 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R.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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 86 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 87 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 88 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 It is alkyl.

[0174] In some embodiments, R 1 is OH.

[0175] In some embodiments, R 1 is O.C. 1~6 alkyl (eg, OMe).

[0176] In some embodiments, R 1 is C 2~6 It is alkenyl (eg, vinyl).

[0177] In some embodiments, L 7 is NH.

[0178] In some embodiments, L 8 is NH.

[0179] In some embodiments, R a1 , R b1 , R c1 , and R d1 However, independently, 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.

[0180] In some embodiments, the compound is of one of the following formulas, or a pharmaceutically acceptable salt thereof: [ka]

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[0181] In some embodiments, the compound is of one of the following formulas, or a pharmaceutically acceptable salt thereof: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0182] The compound, or any of its embodiments, may be provided in the form of a composition, such as a pharmaceutical composition, comprising the compound, or a salt thereof, such as a pharmaceutically acceptable salt, and at least one additional agent, such as a pharmaceutically acceptable carrier.

[0183] It will be further understood that certain features of the invention that are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment (although it is intended that these embodiments be combined as if stated in multiple dependent forms). Conversely, various features of the invention that 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 the features described as embodiments of compounds of formula (I) can be combined in any suitable combination.

[0184] At various places in the present specification, certain characteristics of compounds are disclosed in groups or ranges. It is specifically intended that such disclosure include each member of such groups and ranges and each individual subcombination. For example, "C 1~6 The term "alkyl" is specifically intended to individually (without limitation) disclose methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl, and C6 alkyl.

[0185] The term "n-membered", where N is an integer, typically describes the number of ring-forming atoms in a moiety where n is the number of ring-forming atoms. 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 this term is used to refer to a carbocyclic ring (e.g., aryl or cycloalkyl), all of the ring atoms are carbon atoms. When this 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 remaining (e.g., n-1, n-2, n-3, or n-4) are carbon atoms.

[0186] Various places in this specification describe variables that define divalent linking groups. Specifically, each linking substituent is intended to include both the forward and backward forms of the linking substituent. For example, -NR(CR'R") n - is -NR(CR'R") n -and-(CR'R") n It is intended to include both NR- and NR-, and to disclose each form individually. If a structure requires a linking group, the Markush variable listed in that group is understood to be the linking group. For example, if a structure requires a linking group and the Markush group definition for that variable lists "alkyl" or "aryl," it is understood that "alkyl" or "aryl" represents a linking alkylene group or arylene group, respectively.

[0187] The term "substituted" means that an atom or group of atoms formally replaces hydrogen as a "substituent" attached to another group. The term "substituted" refers to any level of substitution where such substitution is permitted, e.g., mono-, di-, tri-, tetra-, or penta-substitution, unless otherwise indicated. Substituents are independently selected, and substitution may be at any chemically accessible position. It is 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 has been removed and replaced by a substituent. A single divalent substituent, e.g., oxo, can replace two hydrogen atoms.

[0188] "C n~m " denotes a range inclusive of the endpoints, where n and m are integers and indicate the number of carbons. Examples include C 1~4 , C 1~6 etc. When the term is used to describe each member of a group, C n ~C m are as if each were explicitly stated. For example, C 1~6 The term is intended to describe each of the members C1, C2, C3, C4, C5, and C6.

[0189] The term "alkyl," used alone or in combination with other terms, refers to a saturated hydrocarbon group which may be straight-chained or branched. n~mThe term "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 alkyl group's point of attachment to the remainder of the compound. In some embodiments, the alkyl group contains 1 to 6 carbon atoms, 1 to 4 carbon atoms, 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; and higher homologs such as 2-methyl-1-butyl, n-pentyl, 3-pentyl, n-hexyl, 1,2,2-trimethylpropyl, etc.

[0190] The term "alkenyl," used 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 in which one C-H bond is replaced by the point of attachment of the alkenyl group to the remainder of the compound. n~m The term "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. Examples of alkenyl groups include, but are not limited to, ethenyl, n-propenyl, isopropenyl, n-butenyl, sec-butenyl, and the like.

[0191] The term "alkynyl," used 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. n~m The term "alkynyl" refers to an alkynyl group having n to m carbons. Examples of 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.

[0192] The term "alkylene," used 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 bonds replaced by the points of attachment of the alkylene group to the remainder of the compound. n~m The term "alkylene" refers to an alkylene group having n to m carbon atoms. Examples of alkylene groups include, but are not limited to, ethane-1,2-diyl, propane-1,3-diyl, propane-1,2-diyl, butane-1,4-diyl, butane-1,3-diyl, butane-1,2-diyl, 2-methyl-propane-1,3-diyl, and the like.

[0193] The term "alkoxy", employed alone or in combination with other terms, refers to a radical of the formula -O-alkyl, wherein the alkyl radical is as defined above. n~m The term "alkoxy" refers to an alkoxy group, where the alkyl group has n to m carbons. Exemplary 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.

[0194] The terms "halo" or "halogen," employed alone or in combination with other terms, refer to fluoro, chloro, bromo, and iodo.

[0195] The term "haloalkyl" refers to an alkyl group in which one or more of the hydrogen atoms has been replaced by a halogen atom. n~m The term "haloalkyl" refers to a C alkyl group having n to m carbon atoms and at least 1 and at most {2(n to m)+1} halogen atoms. n~m"haloalkyl" refers to alkyl groups, which may be the same or different. In some embodiments, the halogen atoms are fluoro atoms. In some embodiments, haloalkyl groups have 1 to 6 or 1 to 4 carbon atoms. Examples of haloalkyl groups include CF3, C2F5, CHF2, CCl3, CHCl2, C2Cl5, etc. In some embodiments, the haloalkyl groups are fluoroalkyl groups.

[0196] The term "haloalkoxy", employed alone or in combination with other terms, refers to a radical of the formula -O-haloalkyl, wherein the haloalkyl radical is as defined above. n~m The term "haloalkoxy" refers to a haloalkoxy group where the haloalkyl group has n to m carbon atoms. Examples of 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.

[0197] The term "amino" refers to a group of formula -NH2.

[0198] The term "carbamyl" refers to a group of formula -C(=O)NH2.

[0199] The term "carbonyl," employed alone or in combination with other terms, refers to a C(=O)- group, which can also be written as C(O).

[0200] The term "carbonyl", employed alone or in combination with other terms, refers to a -C(=O)- group.

[0201] The term "carboxy" refers to a group of formula -C(=O)OH.

[0202] The term "oxo" refers to oxygen as a divalent substituent attached to a heteroatom, forming a carbonyl group, or forming a sulfoxide or sulfone group, or an N-oxide group.

[0203] The term "aromatic" refers to a carbocyclic or heterocyclic ring having one or more polyunsaturated rings with aromatic character (i.e., having (4n+2) delocalized π (pi) electrons, where n is an integer).

[0204] The term "aryl," used alone or in combination with other terms, refers to an aromatic hydrocarbon group that can be monocyclic or polycyclic (e.g., having 2, 3, or 4 fused rings). n~m The term "aryl" refers to an aryl group having n to m ring carbon atoms. Aryl groups include, for example, phenyl, naphthyl, indenyl, and the like. In some embodiments, an aryl group has 6 to 10 carbon atoms. In some embodiments, an aryl group is phenyl.

[0205] 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. n~m Aryl C o~p The term "alkylenyl" refers to an arylalkylenyl group having an aryl group having n to m ring carbon atoms attached to an alkylene group having o to p carbon atoms. Arylalkylenyl groups include, for example, benzyl, phenethyl, and the like.

[0206] The terms "heteroaryl" or "heteroaromatic," used alone or in combination with other terms, refer 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 a 5- to 10-membered C ring that is monocyclic or bicyclic and has 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur, and oxygen. 1~9Heteroaryl. In some embodiments, any ring-forming N in the heteroaryl moiety can be an N-oxide. In some embodiments, the heteroaryl has 5 to 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 to 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 to 6 ring atoms and 1 or 2 heteroatom ring members independently selected from nitrogen, sulfur, and oxygen. In some embodiments, the heteroaryl is a 5- or 6-membered heteroaryl ring. Examples of 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), and the like.

[0207] A 5-membered heteroaryl ring is a heteroaryl group having 5 ring atoms, wherein one or more (e.g., 1, 2, 3, or 4) ring atoms are independently selected from N, O, and S. Exemplary 5-membered 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.

[0208] A 6-membered heteroaryl ring is a heteroaryl group having 6 ring atoms, in which one or more (e.g., 1, 2, or 3) ring atoms are independently selected from N, O, and S. Exemplary 6-membered heteroaryl rings include pyridyl, pyrazinyl, pyrimidinyl, triazinyl, and pyridazinyl.

[0209] The term "heteroarylalkylenyl," employed alone or in combination with other terms, refers to a heteroaryl group, as defined herein, attached to an alkylene group, as defined herein. o~p The term "alkylenyl" refers to a heteroaryl group having n to m ring atoms attached to an alkylene group having o to p carbon atoms. Heteroarylalkylenyl groups include, for example, pyridylmethyl, pyridylethyl, and the like.

[0210] The term "cycloalkyl," used 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. n~m The term "cycloalkyl" refers to a cycloalkyl having n to m ring carbon atoms. Cycloalkyl groups can include monocyclic or polycyclic (e.g., having 2, 3, or 4 fused rings) groups and spirocycles. Cycloalkyl groups can have, for example, 3, 4, 5, 6, 7, 8, 9, or 10 ring carbon atoms (C 3~10 ), or 3, 4, 5, 6, or 7 ring 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 C 3~6Monocyclic cycloalkyl groups. The ring-forming carbon atoms of a cycloalkyl group can be optionally substituted with oxo or sulfido. Cycloalkyl groups also include cycloalkylidenes. Examples of 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 within the definition of cycloalkyl are moieties having one or more aromatic rings fused to the cycloalkyl ring (i.e., sharing a common bond with the cycloalkyl ring), such as benzo or thienyl derivatives of cyclopentane, cyclohexane, and the like, e.g., indanyl or tetrahydronaphthyl. Cycloalkyl groups containing fused aromatic rings can be attached through any ring-forming atom, including the ring-forming atoms of the fused aromatic ring.

[0211] 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. n~m Cycloalkyl C o~p The term "alkylenyl" refers to a cycloalkylalkylenyl group having a cycloalkyl group having n to m ring carbon atoms attached to an alkylene group having o to p carbon atoms. Cycloalkylalkylenyl groups include, for example, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclohexylmethyl, and the like.

[0212] The term "heterocycloalkyl," used alone or in combination with other terms, refers to a non-aromatic ring or ring system having 4 to 10 ring members, 4 to 7 ring members, or 4 to 6 ring members, which optionally contain one or more alkenylene groups as part of the ring structure and have at least one heteroatom ring member independently selected from nitrogen, sulfur, oxygen, and phosphorus. Heterocycloalkyl includes monocyclic 4-, 5-, 6-, and 7-membered heterocycloalkyl groups. Heterocycloalkyl groups can include monocyclic or bicyclic (e.g., having two fused or bridged rings) ring systems. In some embodiments, heterocycloalkyl groups are monocyclic groups 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. The ring-forming carbon atoms and heteroatoms of a heterocycloalkyl group can be optionally substituted with oxo or sulfido (e.g., C(=O), S(=O), C(S), or S(=O), etc.), or the nitrogen atom can be quaternized. A heterocycloalkyl group can be attached through a ring-forming carbon atom or ring-forming heteroatom. In some embodiments, a heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, a heterocycloalkyl group contains 0 to 2 double bonds. Also included within the definition of heterocycloalkyl are moieties having one or more aromatic rings fused (i.e., sharing a bond with the cycloalkyl ring) to the heterocycloalkyl ring, e.g., benzo or thienyl derivatives such as piperidine, morpholine, azepine, etc. Heterocycloalkyl groups containing fused aromatic rings 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, diazepane (e.g., 1,4-diazepane), pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, pyran, tetrahydrofuran, and di- and tetra-hydropyran.

[0213] The term "heterocycloalkylalkylenyl," employed alone or in combination with other terms, refers to a heterocycloalkyl group, as defined herein, attached to an alkylene group, as defined herein. o~p The term "alkylenyl" refers to a heterocycloalkyl group having n to m ring atoms attached to an alkylene group having o to p carbon atoms. Heteroarylalkyl groups include, for example, tetrahydrofurylmethyl.

[0214] In certain places, definitions or embodiments refer to specific rings (e.g., azetidine rings, pyridine rings, etc.). Unless otherwise specified, these rings can be attached to any ring member, provided that the valence of the atom is not exceeded. For example, an azetidine ring can be attached at any position on the ring, while an azetidin-3-yl ring is attached at the 3-position.

[0215] The compounds described herein may be asymmetric (e.g., have one or more stereocenters). Unless otherwise specified, all stereoisomers, such as enantiomers and diastereoisomers, are intended. Compounds of the present invention containing 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 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 can be isolated as a mixture of isomers or as separated isomeric forms.

[0216] Resolution of a racemic mixture of compounds can be carried out by any of a number of methods known in the art. One method involves fractional recrystallization using a chiral resolving acid, which is an optically active, salt-forming organic acid. Suitable resolving agents for fractional recrystallization include, for example, optically active acids such as tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, the D- and L-forms of lactic acid, or various optically active camphorsulfonic acids, such as β-camphorsulfonic acid. Other resolving agents suitable for fractional crystallization include stereomerically pure forms (e.g., S- and R-forms, or diastereomeric pure forms) of α-methylbenzylamine, 2-phenylglycinol, norephedrine, ephedrine, N-methylephedrine, cyclohexylethylamine, 1,2-diaminocyclohexane, and the like.

[0217] 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 compositions can be determined by one skilled in the art.

[0218] In some embodiments, the compounds of the present invention have the (R) configuration. In other embodiments, the compounds have the (S) configuration. In compounds with two or more chiral centers, unless otherwise specified, each of the chiral centers in the compound may independently be either (R) or (S).

[0219] The compounds of the present invention also include tautomeric forms. Tautomeric forms result from the exchange of a single bond with an adjacent double bond and the accompanying proton migration. Tautomeric forms include prototropic tautomers, which are isomeric protonation states with the same empirical formula and total charge. Examples of prototropic tautomers include ketone-enol pairs, amide-imidic acid pairs, lactam-lactim pairs, enamine-imine pairs, and cyclic forms in which protons can occupy more than one position in the heterocyclic ring system, such as 1H- and 3H-imidazole, 1H-, 2H-, and 4H-1,2,4-triazole, 1H- and 2H-isoindole, and 1H- and 2H-pyrazole. Tautomeric forms may be in equilibrium or sterically fixed into one form by appropriate substitution.

[0220] Compounds of the present invention may also include all isotopes of atoms occurring in the intermediates or final compounds. Isotopes include atoms having the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium.

[0221] The term "compound" is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted.

[0222] All compounds and their pharmaceutically acceptable salts can be found together with other substances such as water and solvents (for example, hydrates and solvates) or can be isolated.When in solid state, the compounds described herein and their salts can occur in various forms, for example, can be in the form of solvates, including hydrates.Since the compound may be in any solid state form, such as polymorphs or solvates, unless otherwise specified, the reference herein to compounds and their salts should be understood to include any solid state form of the compound.

[0223] In some embodiments, the compound of the present invention or a salt thereof is substantially isolated. "Substantially isolated" means that the compound is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched for the compound of the present invention. Substantial separation can include a composition containing at least about 50% by weight, at least about 60% by weight, at least about 70% by weight, at least about 80% by weight, at least about 90% by weight, at least about 95% by weight, at least about 97% by weight, or at least about 99% by weight of the compound of the present invention or a salt thereof.

[0224] The phrase "pharmaceutically acceptable" is used herein to refer to compounds, materials, compositions, and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without undue toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0225] The expressions "ambient temperature" and "room temperature" are understood in the art and generally refer to a temperature near the temperature of the room in which the reaction is carried out, e.g., from about 20°C to about 30°C, e.g., the reaction temperature.

[0226] The present invention also includes salts of the compounds described herein, particularly pharmaceutically acceptable salts. The term "pharmaceutically acceptable salts" refers to derivatives of the disclosed compounds, in which the parent compound is modified by converting an existing acid or base moiety into 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. Pharmaceutically acceptable salts of the present invention include non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. Pharmaceutically acceptable salts of the present invention can be synthesized from parent compounds containing a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base form of these compounds with a stoichiometric amount of the appropriate base or acid in water or an organic solvent, or a mixture of the two. Generally, non-aqueous media such as ether, ethyl acetate, alcohol (e.g., methanol, ethanol, isopropanol, or butanol), or acetonitrile (MeCN) are preferred. Lists of suitable salts can be found in Remington's Pharmaceutical Sciences, 17th Ed., (Mack Publishing Company, Easton, 1985), p. 1418, Berge et al., J. Pharm. Sci., 1977, 66(1), 1-19, and Stahl et al., Handbook of Pharmaceutical Salts: Properties, Selection, and Use, (Wiley, 2002). In some embodiments, the compounds described herein include N-oxide forms.

[0227] The following abbreviations may be used herein: AcOH (acetic acid), Ac2O (acetic anhydride), Al2O3 (aluminum oxide), aq. (aqueous), atm. (atmosphere), Boc (t-butoxycarbonyl), Boc2O (di-tert-butyl dicarbonate), BOP ((benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate), br (broad), c-Pr (cyclopropyl), Cbz (carboxybenzyl), calc. (calculated), CeCl3·7H2O (cerium(III) chloride) ) heptahydrate), Cs2CO3 (cesium carbonate), CuI (copper(I) iodide), d (doublet), dd (doublet of doublet), DCM (dichloromethane), DIPEA (N,N-diisopropylethylamine), DMAP (4-dimethylaminopyridine), DMF (N,N-dimethylformamide), DMSO (dimethyl sulfoxide), Et (ethyl acetate), EtOAc (ethyl acetate), EtOH (ethanol), Fmoc (9-fluorenylmethylmethoxycarbonyl), g (gram), h (hour) between), H2 (hydrogen gas), H2O2 (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), K3PO4 (potassium phosphate), K3PO4 ·H2O (tripotassium phosphate hydrate), LCMS (liquid chromatography-mass spectrometry), LiAlH4 (lithium tetrahydrogen aluminate), LiBH4 (lithium tetrahydrogen borate), LiOH (lithium hydroxide), LiOH·H2O (lithium hydroxide monohydrate), m (multiplet), M (mol), mCPBA (m-chloroperbenzoic acid), Me (methyl), MeCN (acetonitrile), MeOH (methanol), MgSO4 (magnesium sulfate), MS (mass spectrometry), mg (milligram), min.(minutes), mL (milliliters), mmol (millimoles), N (normal), N2 (nitrogen gas), NaHCO3 (sodium bicarbonate), NaIO4 (sodium metaperiodate), NaN3 (sodium azide), NaOH (sodium hydroxide), Na2SO4 (sodium sulfate), n-Bu (n-butyl), n-BuLi (n-butyllithium), NH4Cl (ammonium chloride), NH4OH (ammonium hydroxide), nM (nanomole), NMR (nuclear magnetic resonance spectroscopy), Pd (palladium), Pd(dppf)Cl2 ([1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride), Pd(OAc)2 (palladium acetate), Pd(tBu3P)2 (bis(tri-tert-butylphosphino) Pd(PPh3)4 (tetrakis(triphenylphosphine)palladium(0)), pM (picomole), Pd(PPh3)4 (tetrakis(triphenylphosphine)palladium(0)), PPh3 (triphenylphosphine), psi (pounds per square inch), PTFE (polytetrafluoroethylene), RP-HPLC (reverse-phase high-performance liquid chromatography), rt (room temperature), s (singlet), t (triplet or tertiary), tert (tertiary), tt (triplet of triplets), TBAF (tetra-n-butylammonium fluoride), t-Bu (tert-butyl), TEA (triethylamine), TFA (trifluoroacetic acid), THF (tetrahydrofuran), μg (microgram), μL (microliter), μm (micromole), wt% (weight percent).

[0228] II.Synthesis The compounds of the present invention (including salts thereof) may be prepared using known organic synthesis techniques, or may be synthesized according to any of a number of possible synthetic routes, such as those shown in the following schemes.

[0229] The reaction for preparing the compound of the present invention can be carried out in a suitable solvent that can be easily selected by those skilled in the art of organic synthesis.A suitable solvent can be substantially non-reactive with the starting material (reactant), intermediate, or product at the temperature at which the reaction is carried out, for example, a temperature that can range from the freezing temperature of the solvent to the boiling temperature of the solvent.A given reaction can be carried out in one solvent or a mixture of two or more solvents.Depending on the specific reaction step, a suitable solvent for a specific reaction step can be selected by those skilled in the art.

[0230] The preparation of the compounds of the present invention may involve the protection and deprotection of various chemical groups.The need for protection and deprotection, and the selection of appropriate protecting groups, can be easily determined by those skilled in the art.The chemistry of protecting groups is described, for example, 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, 6th 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).

[0231] The reaction can be monitored according to any suitable method known in the art. For example, product formation can be monitored by nuclear magnetic resonance spectroscopy (e.g., 1 H or 13 C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), mass spectroscopy, or by chromatographic methods such as high performance liquid chromatography (HPLC) or thin layer chromatography (TLC).

[0232] The following schemes provide general guidance regarding the preparation of compounds of the present invention. Those skilled in the art will 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 present invention.

[0233] Compounds of formula (I) can be prepared by coupling an aniline of formula (II) with a compound of formula III, as shown in Scheme 1, where L is a suitable leaving group that can contain a halogen, such as bromine or iodine, or a sulfonate group (an alkyl or aryl sulfonate, e.g., 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, for example, using Buchwald-Hartwig cross-coupling conditions. Suitable solvents for the reaction include tetrahydrofuran, 1,4-dioxane, toluene, or 1,2-dichlorobenzene. A preferred solvent is 1,2-dichlorobenzene. The reaction can typically be carried out at temperatures between 0 and 200°C, e.g., between 100 and 150°C.

[0234] The present disclosure provides, inter alia, methods for making certain compounds of formula (I) according to formula (Ia) by the route shown in Scheme 1. [ka]

[0235] Compounds of formula (II) and (III) are commercially available, known in the literature, or can be prepared by methods known to those skilled in the art.

[0236] 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 O.C. 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 to prepare a compound of formula (I), wherein R 1 is OH) can be synthesized.

[0237] It will be understood by those skilled in the art that the described processes are not exclusive means of synthesizing the compounds of the present invention, and that a wide repertoire of synthetic organic reactions is potentially available for synthesizing the compounds of the present invention. Those skilled in the art will know how to select and carry out appropriate synthetic routes. Suitable methods for synthesizing starting materials, intermediates, and products can be identified by reference to the literature, including the following cited sources: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, 2nd 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, 6th Ed. (Wiley, 2007), Trost et al. (Ed.), Comprehensive Organic Synthesis (Pergamon Press, 1991).

[0238] III. Use of Compounds The compounds of the present invention can inhibit the autopalmitoylation of TEAD transcription factors and are therefore useful for treating diseases and disorders associated with the activity of TEAD transcription factors. Any of the compounds of the present invention, including any of the embodiments thereof, can be used for the uses described herein.

[0239] Thus, the present disclosure provides a method of treating a TEAD transcription factor-associated disease or disorder in an individual (e.g., a patient) by administering a therapeutically effective amount or dose of a compound of Formula (I), or any of its embodiments, or a pharmaceutical composition thereof, to the individual (e.g., patient) in need of treatment. The present disclosure also provides a compound of Formula (I), or any of its embodiments, 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 its embodiments, 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 may be a disease or disorder associated with TEAD1, TEAD2, TEAD3, or TEAD4.

[0240] A TEAD transcription factor-associated disease can include any disease, disorder, or condition directly or indirectly related to the expression or activity of a TEAD transcription factor, including overexpression and / or abnormal activity levels. Abnormal activity levels can be determined by comparing activity levels in normal, healthy tissues or cells with activity levels 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 abnormal activity or expression (e.g., overexpression) of a TEAD transcription factor. A TEAD transcription factor-associated disease can also refer to any disease, disorder, or condition in which modulating expression or activity of a TEAD transcription factor is beneficial.

[0241] TEAD transcription factor-related diseases that can be treated using the compounds of the present invention include cancer. Cancers include solid tumors such as prostate cancer, colon cancer, esophageal cancer, endometrial cancer, ovarian cancer, uterine cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer, breast cancer, lung cancer, head and neck cancer, thyroid cancer, glioblastoma, sarcoma, bladder cancer, etc. Other TEAD transcription factor-related diseases include hepatocellular carcinoma, medulloblastoma, cutaneous squamous cell carcinoma, lung cancer, pancreatic cancer, esophageal cancer, liver cancer, colon cancer, melanoma, and bladder melanoma. TEAD transcription factor-associated diseases also include hematological cancers, such as lymphoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, non-Hodgkin's lymphoma (including relapsed non-Hodgkin's lymphoma, refractory non-Hodgkin's lymphoma, and relapsed follicular non-Hodgkin's lymphoma), Hodgkin's lymphoma, and multiple myeloma.

[0242] The cancer can be one in which abnormally proliferating cells of the cancer express one or more TEADs, e.g., one or more of TEAD1, TEAD2, TEAD3, and / or TEAD4. The method can include testing the individual's cancer cells 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 a determination that the cancer expresses TEAD1, TEAD2, TEAD3, and / or TEAD4.

[0243] The terms "individual" or "patient," used interchangeably, refer to any animal, including a mammal, preferably a mouse, rat, other rodent, rabbit, dog, cat, pig, cow, sheep, horse, or primate, most preferably a human.

[0244] The phrase "therapeutically effective amount" refers to that amount of an 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, physician, or other clinician.

[0245] The term "treating" or "treatment" refers to one or more of: (1) inhibiting a disease, e.g., inhibiting a disease, condition, or disorder in an individual experiencing or exhibiting the pathology or symptomology of the disease, condition, or disorder (i.e., halting further development of the pathology and / or symptomology), and (2) ameliorating a disease, e.g., ameliorating a disease, condition, or disorder in an individual experiencing or exhibiting the pathology or symptomology of the disease, condition, or disorder (i.e., reversing the pathology and / or symptomology), such as reducing the severity of the disease. In one embodiment, treating or treatment includes preventing or reducing the risk of developing a 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 who has not yet experienced or exhibited the pathology or symptomology of the disease.

[0246] Combination therapy The proliferation and survival of cancer cells can be influenced by multiple signal transduction pathways.Therefore, it is useful to combine different chemotherapeutic agents to treat such conditions.The use of combination therapy can reduce the possibility of drug resistance occurring in cell population and / or reduce the toxicity of treatment.

[0247] The compound may be administered in combination with one or more anti-cancer agents, such as chemotherapeutic agents, such as abarelix, aldesleukin, alemtuzumab, alitretinoin, allopurinol, altretamine, anastrozole, arsenic trioxide, asparaginase, azacitidine, bevacizumab, bexarotene, bleomycin, bortezomib, IV busulfan, oral busulfan, calsterone, capecitabine, carboplatin, cetuximab, chlorambucil, cisplatin, cladribine, clofarabine, cyclophosphamide, cytarabine, dacarbazine, and 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, histolytica acetate Tolerin, ibritumomab tiuxetan, idarubicin, ifosfamide, imatinib mesylate, interferon α2a, irinotecan, lapatinib ditosylate, lenalidomide, letrozole, leucovorin, leuprolide acetate, levamisole, lomustine, mechlorethamine, megestrol acetate, melphalan, mercaptopurine, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, nandrolone phenpropionate, nelarabine, nofetumomab, oxaliplatin, paclitaxel, paclitaxel Midronate, 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, barbican,These include vinblastine, vincristine, vinorelbine, vorinostat, and zoledronate.

[0248] When two or more pharmaceutical agents are administered to a patient, they may be administered simultaneously, sequentially, or in combination (eg, for three or more agents).

[0249] VI. Formulation, Dosage Forms, and Administration When used as a pharmaceutical, the compounds of the present invention can be administered in the form of a pharmaceutical composition. Accordingly, the present disclosure provides a composition comprising the compound of formula (I), or a pharmaceutically acceptable salt thereof, or any of its embodiments, and at least one pharmaceutically acceptable carrier. These compositions can be prepared by methods well known in the pharmaceutical arts and can be administered by various routes depending on whether local or systemic treatment is indicated and the area to be treated. Administration can be topical (including transdermal, epidermal, ophthalmic, and mucosal, including intranasal, intravaginal, and rectal delivery), pulmonary (e.g., intratracheal or intranasal, by inhalation or insufflation of powder or aerosol, including by nebulizer), 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, for example, 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.

[0250] The present invention also includes pharmaceutical compositions containing the compound of the present invention or its pharmaceutically acceptable salt as an active ingredient in combination with one or more pharmaceutically acceptable carriers (excipients). In some embodiments, the compositions are suitable for topical administration. When preparing the compositions of the present invention, the active ingredient is typically mixed with an excipient, diluted by an excipient, or enclosed in such a carrier, for example, in the form of a capsule, sachet, paper, or other container. When the excipient serves as a diluent, it can be a solid, semi-solid, or liquid substance that 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 solids or in liquid media), for example, ointments containing up to 10% by weight of the active compound, soft and hard gelatin capsules, suppositories, sterile injection solutions, and sterile packaged powders.

[0251] When preparing formulation, before being combined with other components, active compound can be pulverized to obtain suitable particle size.If active compound is substantially insoluble, it can be pulverized to the particle size of less than 200 mesh.If active compound is substantially water-soluble, it can be pulverized to adjust particle size to, for example, about 40 mesh, so as to provide substantially uniform distribution in formulation.

[0252] The compounds of the present invention can be milled using known milling procedures, such as wet milling, to obtain particle sizes suitable for tableting and other formulations.Finely divided (nanoparticulate) preparations of the compounds of the present invention can be prepared by processes known in the art, for example, see WO2002 / 000196.

[0253] Some examples of suitable excipients include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup and methylcellulose.In addition, preparation can contain lubricant such as talc, magnesium stearate and mineral oil, wetting agent, emulsifying agent and suspending agent, preservative such as methyl and propylhydroxybenzoate, sweetener and flavoring agent.The composition of the present invention can be formulated to provide rapid release, sustained release or delayed release of active ingredient after being administered to patient by using the procedure known in the art.

[0254] 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.

[0255] 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 K4M Premier™) and / or hydroxypropyl methylcellulose 2208 K100LV (e.g., Methocel K00LV™). In some embodiments, the polyethylene oxide is polyethylene oxide WSR 1105 (e.g., Polyox WSR1105™).

[0256] In some embodiments, the composition is produced using a wet granulation process. In some embodiments, the composition is produced using a dry granulation process.

[0257] Compositions may be formulated in 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 form" refers to a physically discrete unit suitable as a unitary dosage for human subjects and other mammals, each unit containing a predetermined quantity of the active material calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient.

[0258] The components used to formulate pharmaceutical compositions are of high purity and 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, compositions are preferably manufactured or formulated under standards of good manufacturing practice, as defined in applicable U.S. Food and Drug Administration regulations. For example, suitable formulations can be sterile and / or substantially isotonic and / or fully compliant with all U.S. Food and Drug Administration good manufacturing practice regulations.

[0259] The active compounds can be effective over a wide dosage range and are generally administered in a therapeutically effective amount. However, it will be understood that the amount of compound actually administered will usually be determined by the physician according to the relevant circumstances, including the condition being treated, the selected route of administration, the actual compound being administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, etc.

[0260] Therapeutic dosages of the compounds of the invention can vary according to, for example, the particular application for which the treatment is being administered, the mode 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 on several factors, including dosage, chemical characteristics (e.g., hydrophobicity), and route of administration. For example, for parenteral administration, 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. Some typical dosage ranges are about 1 μg to about 1 g per kg of body weight per day. In some embodiments, the dosage range is about 0.01 mg to about 100 mg per kg of body weight per day. The dosage can depend on variables such as the type and progression of the disease or disorder, the overall health of the particular patient, the relative biological availability of the selected compound, the excipient formulation, and its route of administration. Effective doses can be extrapolated from dose-response curves derived from in vitro or animal model test systems.

[0261] To prepare solid compositions such as tablets, the primary active ingredient is mixed with pharmaceutical excipients to form a solid preformulation composition containing a homogeneous mixture of the compound of the present invention. When these preformulation compositions are referred to as homogeneous, the active ingredient is typically dispersed evenly throughout the composition so that the composition can be easily 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, for example, containing about 0.1 to about 1000 mg of the active ingredient of the present invention.

[0262] The tablets or pills of the present invention can be coated or otherwise compounded to provide a dosage form that provides the advantage of prolonged action.For example, the tablets or pills can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope covering the former.The two components can be separated by an enteric layer that resists disintegration in the stomach and allows the inner component to pass intact into the duodenum or be delayed in release.Various materials can be used for such enteric layers or coatings, including several polymeric acids and mixtures of polymeric acids with materials such as shellac, cetyl alcohol, and cellulose acetate.

[0263] Liquid forms into which the compounds and compositions of the present invention may be incorporated for oral or injectable administration include aqueous solutions, suitably flavored syrups, aqueous or oily suspensions, and emulsions flavored with edible oils such as cottonseed oil, sesame oil, coconut oil, or peanut oil, as well as elixirs and similar pharmaceutical vehicles.

[0264] Compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable aqueous or organic solvents, or mixtures thereof, and powders. Liquid or solid compositions may contain suitable pharmaceutically acceptable excipients as described above. In some embodiments, the compositions are administered by oral or nasal respiratory route for local or systemic effect. Compositions may be nebulized by use of an inert gas. Nebulized solutions may be inhaled directly from the nebulizing device, or the nebulizing device may be attached to a face mask, obturator, or intermittent positive pressure breathing machine. Solution, suspension, or powder compositions may be administered orally or nasally from a device that delivers the formulation in an appropriate manner.

[0265] Topical formulations may contain one or more conventional carriers. In some embodiments, ointments may contain water and one or more hydrophobic carriers selected from, for example, liquid paraffin, polyoxyethylene alkyl ether, propylene glycol, white petrolatum, etc. Cream carrier compositions may be based on a combination of water with glycerol and one or more other components, such as glycerol monostearate, PEG-glycerol monostearate, and cetylstearyl alcohol. Gels may be formulated using isopropyl alcohol and water, suitably combined with other components, such as glycerol, hydroxyethylcellulose, etc. In some embodiments, topical formulations contain at least about 0.1% by weight, at least about 0.25% by weight, at least about 0.5% by weight, at least about 1% by weight, at least about 2% by weight, or at least about 5% by weight of a compound of the present invention. Optionally, topical formulations associated with indications for the treatment of a selected indication, such as psoriasis or other skin conditions, may be suitably packaged, for example, in a 100g tube.

[0266] The amount of compound or composition administered to a patient will vary depending on what is being administered, the purpose of administration, such as prophylaxis or treatment, the condition of the patient, the mode of administration, etc. In therapeutic applications, the compositions may 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. The effective dose will depend on the disease state being treated and the judgment of the attending physician based on factors such as the severity of the disease, the age, weight, and general condition of the patient.

[0267] The compositions administered to patients may be in the form of pharmaceutical compositions described above. These compositions may be sterilized by conventional sterilization techniques or may be sterile filtered. Aqueous solutions may be packaged or lyophilized for immediate use, although lyophilized preparations are combined with a sterile aqueous carrier prior to administration. The pH of the compound preparations will typically be 3-11, more preferably 5-9, and most preferably 7-8. It will be understood that the use of some of the aforementioned excipients, carriers, or stabilizers may result in the formation of pharmaceutical salts.

[0268] Therapeutic dosages of the compounds of the invention can vary according to, for example, the particular application for which the treatment is being administered, the mode 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 on several factors, including dosage, chemical characteristics (e.g., hydrophobicity), and route of administration. For example, for parenteral administration, 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. Some typical dosage ranges are about 1 μg to about 1 g per kg of body weight per day. In some embodiments, the dosage range is about 0.01 mg to about 100 mg per kg of body weight per day. The dosage can depend on variables such as the type and progression of the disease or disorder, the overall health of the particular patient, the relative biological availability of the selected compound, the excipient formulation, and its route of administration. Effective doses can be extrapolated from dose-response curves derived from in vitro or animal model test systems.

[0269] IV. Labeled Compounds and Assay Methods The compounds of the present invention may further be useful in investigating biological processes in normal and abnormal tissues. Accordingly, another aspect of the present invention relates to labeled compounds (radiolabeled, fluorescently labeled, etc.) of the present invention that may be useful not only in imaging techniques but also in assays for localizing and quantifying TEAD transcription factors in tissue samples, including humans, both in vitro and in vivo, and for identifying TEAD transcription factor ligands through inhibitory binding of the labeled compounds. Thus, the present invention includes assays containing such labeled compounds.

[0270] The present invention further includes isotopically labeled compounds of the present invention. An "isotopically" or "radiolabeled" compound is a compound of the present invention in which one or more atoms have been replaced or substituted by an atom having an atomic mass or mass number different from that typically found in nature (i.e., naturally occurring). Suitable radionuclides that can be incorporated into the compounds of the present invention include: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 The radionuclide incorporated into the radiolabeled compound will depend on the particular application of the radiolabeled compound. For example, for in vitro labeling and competitive assays, 3 H, 14 C. 82 Br, 125 I, 131 I, 35 Compounds incorporating S are generally most useful. For radioimaging applications, 11 C. 18 F, 125 I, 123 I, 124 I, 131 I, 75 Br, 76 Br, or 77 Br is most useful.

[0271] It is understood that a "radiolabel" or "labeled compound" is a compound that incorporates at least one radionuclide. In some embodiments, the radionuclide is 3 H, 14 C. 125 I, 35 S, and 82 In some embodiments, the compound incorporates 1, 2, or 3 deuterium atoms. Synthetic methods for incorporating radioisotopes into organic compounds are known in the art.

[0272] Specifically, the labeled compounds of the present invention can be used in screening assays to identify and / or evaluate compounds. For example, a labeled newly synthesized or identified compound (i.e., a test compound) can be evaluated for its ability to bind to a TEAD transcription factor by monitoring its concentration fluctuation when contacting the TEAD transcription factor through label tracking. For example, a test compound (labeled) can be evaluated for its ability to reduce the binding of another compound known to bind to a TEAD transcription factor (i.e., a standard compound). Thus, the ability of a test compound to compete with a standard compound for binding to a TEAD transcription factor is directly correlated with its binding affinity. Conversely, in some other screening assays, the standard compound is labeled, and the test compound is not. Therefore, to evaluate the competition between the standard compound and the test compound, the concentration of the labeled standard compound is monitored, thereby determining the relative binding affinity of the test compound.

[0273] V. Kit The present disclosure also includes pharmaceutical kits useful for treating or preventing TEAD transcription factor-associated diseases or disorders, such as cancer, which include one or more containers containing a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula (I), or any of its embodiments. Such kits can further include one or more of a variety of conventional pharmaceutical kit components, such as, for example, a container with one or more pharmaceutically acceptable carriers, additional containers, etc., as would be readily apparent to one of ordinary skill in the art. Instructions, either as an insert or label, indicating the amounts of components to be administered, guidelines for administration, and / or guidelines for mixing the components, can also be included in the kit.

[0274] The present invention will be described in more detail using specific examples. The following examples are provided for illustrative purposes and are not intended to limit the present invention in any way. Those skilled in the art will easily recognize various non-critical parameters that can be changed or modified to produce essentially the same results. [Example]

[0275] Compound synthesis experiment: The MS (mass spectrometry) data provided in the examples was obtained using the following instruments: API 2000 LC / MS / MS / Triple quad, Agilent (1260 infinity) LCMS-SQD 6120 / Single quad, and Shimadzu LCMS-2020 / Single quad.

[0276] The NMR data provided in the examples are instrument- 1 HNMR was used to obtain the data. 1 HNMR: Varian-400MHz, JEOL-400MHz.

[0277] Abbreviations used throughout this specification may be summarized below with their specific meanings.

[0278] °C (degrees Celsius), δ (delta), % (percentage), (BOC)2O (Boc anhydride), bs (broad singlet), CDCl3 (deuterated chloroform), DCM (dichloromethane), DMF (dimethylformamide), DIPEA (N,N-diisopropylethylamine), DMAP (dimethylaminopyridine), (DMSO-d6 (deuterated DMSO), d (doublet), dd (doublet of doublets), Fe (iron powder) , g or gm (grams), HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxodohexafluorophosphate), H or H2 (hydrogen), HO (water), HCl (hydrochloric acid), h or hr (hours), Hz (hertz), HPLC (high performance liquid chromatography), J (coupling constant), LiOH (lithium hydroxide), MeOH (methanol), mmol (millimoles), M (mole), mL (milliliters), mg (milligrams), m (multiplet), mm (millimeters), MHz (megahertz), min (minutes), NaH (sodium hydride), NaHCO3 (sodium bicarbonate), Na2SO4 (sodium sulfate), N2 (nitrogen), NMR (nuclear magnetic resonance spectroscopy), Pd / C (palladium on carbon), RT (room temperature), s (singlet), TEA (triethylamine) (Trifluoroacetic acid), TFA (trifluoroacetic acid), TLC (thin layer chromatography), THF (tetrahydrofuran), t (triplet), rac.BINAP ((±)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene), Pd2dba3 (tris(dibenzylideneacetone)dipalladium(0)), XPhos (2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl), in vacuo, eq. (equivalent), ppt (precipitate), NA (not available).

[0279] A general procedure for the synthesis of certain exemplary compounds is shown below in Scheme II. [ka]

[0280] To a solution of iodide (1 mmol) and amine (1 mmol) in 1,2-dichlorobenzene under a nitrogen atmosphere, potassium carbonate (1.5 mmol) was added, followed by copper iodide (0.05 mmol). The resulting mixture was stirred at room temperature for 1 h and then heated at 180 °C for 2 days. After completion of the reaction, the resulting mixture was diluted with dichloromethane (50 mL) and filtered through a bed of diatomaceous earth. The organic solution was dried over MgSO4, concentrated under vacuum, and purified by flash column chromatography using hexane / ethyl acetate (gradient of pure hexane to 20 / 1 hexane / ethyl acetate) as the eluent. Yields ranged from 40% to 69%.

[0281] Compound 2a was analyzed by proton NMR and mass spectrometry (ESI) and (pure hexane as eluent on TLC) with an R of 0.3. f ) was confirmed.

[0282] In the case of compound 2a, 1 H NMR (500 MHz, CDCl): 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%.

[0283] Compounds 2b (M+H 306.1), 2c (M+H 375.1), 2d (M+H 325.1), and 2e (M+H 443.1) were confirmed by mass spectrometry (LC-MS / ESI) and also by retention factor (R of 0.3 using pure hexane as eluent). f ) and matched by TLC.

[0284] The general procedure for the synthesis of the starting materials for compounds CP-59 and CP-65 is shown below in Scheme 3. [ka]

[0285] The required amine (1 mmol) and chloronicotinate (1 mmol) were dissolved in ethylene glycol and then heated at 140 °C for 24 h. After completion of the reaction, the resulting mixture was diluted with ethyl acetate (50 mL) and washed three times with 20 mL of water. The organic solution was dried over MgSO4, concentrated under vacuum, and purified by flash column chromatography using hexane / ethyl acetate (gradient from pure hexane to 15 / 1 hexane / ethyl acetate) as the eluent. Yields ranged from 55 to 59%.

[0286] Compounds 2f (M+H, 376.1) and 2g (M+H, 322.1) were analyzed by spectroscopy (ESI) and TLC (pure hexane as eluent) with an R of 0.1. f ) was confirmed.

[0287] The cross-coupling procedure used to prepare some exemplary compounds is shown below in Scheme 4. [ka]

[0288] To an oven-dried Schlenk tube, the amine (1 mmol), bromide (1 mmol), and toluene (3 mL) were added. To the above homogeneous solution, t-BuONa (1.5 mmol) was added. After stirring for 5 min, Pd2(dba)3 (0.05 mmol) and Bu3P (0.075 mmol) were added under a nitrogen atmosphere. The mixture was stirred at 110 °C for 24 h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (50 mL) and filtered through a bed of diatomaceous earth. The organic solution was dried over MgSO4, concentrated under vacuum, and purified by flash column chromatography using hexane / ethyl acetate (gradient of pure hexane to 10 / 1 hexane / ethyl acetate) as the eluent to give the desired product. Yields ranged from 42 to 55%.

[0289] In the case of compound 3a, 1H NMR (500MHz, CDCl3): δ9.45(s,1H),8.01(s,1H),7.5-7.7.30(m,2H),7.2-7.1(m,2H),6.9 8(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

[0290] In the case of compound 3c, 1 H NMR (500MHz, CDCl3): δ9.45(s,1H),8.01(s,1H),7.45-7.23(d,2H),7.23-7.01(m,6 H),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 (500MHz, CDCl3): δ9.45(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

[0291] The cross-coupling procedure used to prepare some exemplary compounds is shown below in Scheme 5. [ka]

[0292] To an oven-dried Schlenk tube, the amine (1 mmol), bromide (1 mmol), and toluene (3 mL) were added. To the above homogeneous solution, t-BuONa (1.5 mmol) was added. After stirring for 5 min, Pd2(dba)3 (0.05 mmol) and Bu3P (0.075 mmol) were added under a nitrogen atmosphere. The mixture was stirred at 110 °C for 24 h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (50 mL) and filtered through a bed of diatomaceous earth. The organic solution was dried over MgSO4, concentrated under vacuum, and purified by flash column chromatography using hexane / ethyl acetate (gradient of pure hexane to 10 / 1 hexane / ethyl acetate) as the eluent to give the desired product. Yields: 50-54%

[0293] For compound 3f, 1 H NMR (500 MHz, CDCl): 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. Compound 3g confirmed by LC-MS / ESI (M+H 468.57).

[0294] The cross-coupling procedure used to prepare some exemplary compounds is shown below in Scheme 6. [ka]

[0295] To an oven-dried Schlenk tube, the amine (1 mmol), bromide (1 mmol), and toluene (3 mL) were added. To the above homogeneous solution, t-BuONa (1.5 mmol) was added. After stirring for 5 min, Pd2(dba)3 (0.05 mmol) and Bu3P (0.075 mmol) were added under a nitrogen atmosphere. The mixture was stirred at 110 °C for 24 h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (50 mL) and filtered through a bed of diatomaceous earth. The organic solution was dried over MgSO4, concentrated in vacuo, and purified by flash column chromatography using hexane / ethyl acetate (gradient from pure hexane to 10 / 1 hexane / ethyl acetate) as the eluent to give the desired product (39–55% yield).

[0296] In the case of compound 3b, 1 H NMR (500MHz, CDCl3): δ9.45(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.

[0297] For compound 3e, 1 H NMR (500MHz, CDCl3): δ9.46(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.

[0298] The carboxylic acid compounds were prepared by hydrolysis reactions as shown in Schemes 7, 8, 9, and 10 and the experimental procedures described below. [ka]

[0299] To a solution of the ester (1 mmol) in ethanol (10 mL), 2 mmol of 2N NaOH solution was added and heated at 40 °C for 24-48 h. Upon completion, the reaction was cooled on ice, acidified with 2N hydrochloride solution, and extracted three times with 10 mL of ethyl acetate. The organic solution was dried over MgSO4, concentrated under vacuum, and purified by flash column chromatography using hexane / ethyl acetate (gradient of pure hexane to 5 / 1 hexane / ethyl acetate) as eluent to give the desired product. Yields ranged from 70-79%.

[0300] CP-52 was confirmed by LC-MS (ESI, M+H 439.1).

[0301] CP-57 was confirmed by LC-MS (ESI M+H 521.1).

[0302] CP-62 was confirmed by LC-MS (ESI M+H 457.1). [ka]

[0303] To a solution of the ester (1 mmol) in ethanol (10 mL), 2 mmol of 2N NaOH solution was added and heated at 40 °C for 24–48 h. Upon completion, the reaction was cooled on ice, acidified with 2N hydrochloride solution, and extracted three times with 10 mL of ethyl acetate. The organic solution was dried over MgSO4, concentrated in vacuo, and purified by flash column chromatography using hexane / ethyl acetate (gradient of pure hexane to 5 / 1 hexane / ethyl acetate) as the eluent to give the desired product. Yields ranged from 80–83%.

[0304] CP-59 was confirmed by LC-MS (ESI, M+H 509.1).

[0305] CP-65 was confirmed by LC-MS (ESI, M+H 454.1). [ka]

[0306] CP-55 was confirmed by LC-MS (ESI, M+H 439.12).

[0307] CP-64 was confirmed by LC-MS (ESI, M+H 474.1). [ka]

[0308] To a solution of the ester (1 mmol) in ethanol (10 mL), 2 mmol of 2N NaOH solution was added and heated at 40 °C for 24-48 h. Upon completion, the reaction was cooled on ice, acidified with 2N hydrochloride solution, and extracted three times with 10 mL of ethyl acetate. The organic solution was dried over MgSO4, concentrated under vacuum, and purified by flash column chromatography using hexane / ethyl acetate (gradient of pure hexane to 5 / 1 hexane / ethyl acetate) as eluent to give the desired product. Yields ranged from 73-87%.

[0309] CP-55 was confirmed by LC-MS (ESI, M+H 521.1).

[0310] CP-64 was confirmed by LC-MS (ESI, M+H 575.1).

[0311] Carboxylic acid compounds were converted to vinyl ketone compounds as shown in Scheme 11, and the following experimental procedures were carried out. [ka]

[0312] The acid was converted to the Weinreb amide. To a solution of the acid (0.1 mmol) in dichloromethane (1 mL), triethylamine (0.25 mmol) was added, followed by Weinreb amine salt (0.2 mmol), and HATU (0.2 mmol) and stirred at room temperature for 16 hours. After completion of the reaction, water was added and extracted three times with 10 mL of ethyl acetate. The organic solution was dried over MgSO4, concentrated in vacuo, and purified by flash column chromatography using hexane / ethyl acetate (gradient from pure hexane to 5 / 1 hexane / ethyl acetate) as the eluent to give the desired product.

[0313] An ice-cold solution of Weinreb amide (1 mmol) in anhydrous THF (10 mL) was added with 4 mL of 1 M vinylmagnesium bromide solution in THF, warmed to room temperature, and stirred for 4 h. After completion of the reaction, it was quenched with 1 N hydrochloride solution at 0 °C and extracted three times with 10 mL of ethyl acetate. The organic solution was dried over MgSO4, concentrated under vacuum, and purified by flash column chromatography using hexane / ethyl acetate (gradient from pure hexane to 5 / 1 hexane / ethyl acetate) as eluent to give the desired product. Yields ranged from 42% to 57%.

[0314] CP-55 was confirmed by LC-MS (ESI, M+H 449.14).

[0315] CP-64 was confirmed by LC-MS (ESI, M+H 449.16).

[0316] Certain exemplary compounds can be synthesized and characterized as described below. [ka] Intermediate-I

[0317] 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 equiv.) in 1,1,2,2-tetrachloroethane (300 mL), 1-bromoadamantane (87.5 g, 406 mmol, 1.1 equiv.) was added and stirred for 5 minutes. Anhydrous zinc chloride (25.1 g, 184 mmol, 0.5 equiv.) was added and stirred at 100° C. for 36 hours. The reaction mixture was cooled to room temperature, and excess tetrachloroethane was removed by concentration under vacuum. The residue was dissolved in ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, adsorbed onto silica, and purified by flash column chromatography to give the title product as a white solid (58 g, 58%). 1 H NMR(400MHz,DMSO-d6)δ9.81(s,1H),7.47(d,J=8.8Hz,2H),7.25(d,J=8.8Hz,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) +

[0318] The following intermediates were prepared by similar procedures to Intermediate-Ia using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 1]

[0319] Step b: Synthesis of N-(4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)acetamide (Ib) To a solution of N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl)acetamide (25 g, 92.8 mmol, 1.0 equiv) in DMF (500 mL) at 0° C. was added N-chlorosuccinimide (13.6 g, 101 mmol, 1.1 equiv). The reaction mixture was allowed to reach room temperature and stirred for 16 h. Excess DMF was removed by concentration in vacuo. The residue was dissolved in ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting crude solid (22 g, 78%) was used in the next step without further purification. 1 H NMR(400MHz,DMSO-d6)δ9.42(s,1H),7.58(d,J=8.3Hz,1H),7.37(d,J=2.5Hz,1H),7. 29(dd,J1=2.85Hz,J2=8.8Hz,1H),2.06(bs,6H),1.75(s,6H),1.69(s,6H);LC-MS:m / z 304.10(M+H) +

[0320] The following intermediates were prepared by similar procedures to Intermediate-Ib using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 2]

[0321] Step c: Synthesis of 4-((3r,5r,7r)-adamantan-1-yl)-2-chloroaniline (Intermediate-I) To a solution of N-(4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)acetamide (17 g, 56 mmol, 1.0 equiv.) in methanol (150 mL) was added concentrated HCl (150 mL) and refluxed at 100° C. for 8 hours. Excess methanol was removed under vacuum. The resulting white ppt. was filtered off. The filtered solid was washed with a solution of sodium bicarbonate followed by water and dried under vacuum. The desired product was obtained as a white solid (13 g, 88%). 1H NMR(400MHz,DMSO-d6)δ7.08(d,J=2.4Hz,1H),7.02(dd,J1=1.9Hz,J2=8.3Hz,1H),6. 73(d,J=8.3Hz,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) +

[0322] The following intermediates were prepared by similar procedures to Intermediate-I using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 3]

[0323] The following intermediates were prepared by procedures similar to those described in the literature using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 4-1] [Table 4-2] [Table 4-3] [Table 4-4] [Table 4-5] [Table 4-6] [Table 4-7]

[0324] Intermediate-II: [ka]

[0325] Step-a: Synthesis of methyl 2-((4-bromophenyl)amino)benzoate (Intermediate-II) To a solution of methyl 2-iodobenzoate (30 g, 114.5 mmol, 1.0 equiv.) and 4-bromoaniline (19.3 g, 114.5 mmol, 1.0 equiv.) in toluene (500 mL), cesium carbonate (49 g, 150 mmol, 1.3 equiv.) was added and degassed with N gas for 15 minutes. Palladium acetate (1.28 g, 5.7 mmol, 0.05 equiv.) and rac.BINAP (3.56 g, 5.7 mmol, 0.05 equiv.) were added and degassed for 5 minutes. The reaction mass was heated at 110 °C for 16 hours. The reaction mass was filtered through Celite, concentrated under vacuum, and purified by Combiflash to give the title product as a light brown liquid (33 g, 94%). 1 H NMR(400MHz,DMSO-d6)δ9.25(s,1H),7.89(dd,J1=2.0Hz,J2=8.3Hz,1H),7.51(d,J=2.9Hz,2H),7.48(t,J LC-MS:m / z 307.9(M+H) 2+

[0326] The following intermediates were prepared by similar procedures as Intermediate-II using appropriate reactants and reagents with suitable Pd and Fe catalysts and ligands in the presence of suitable solvents and under suitable reaction conditions. [Table 5-1] [Table 5-2] [Table 5-3] [Table 5-4] [Table 5-5]

[0327] Intermediate-II.28: [ka]

[0328] 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 equiv) in THF (30 mL) was added DMAP (0.1 g, 0.84 mmol, 0.2 equiv), pyridine (0.67 g, 8.7 mmol, 2 equiv), Boc anhydride (1.38 g, 6.3 mmol, 1.5 equiv) and heated at 60° C. overnight. The reaction mass was concentrated under vacuum and purified by Combiflash to give the title product as an off-white solid (1.4 g, 82%). LC-MS: m / z 408.2 (M+H). + The following intermediates were prepared by similar procedures to Intermediate-II.28 using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 6]

[0329] The following intermediates were prepared by similar procedures as Intermediate-II using appropriate reactants and reagents with suitable Pd catalyst and ligand in the presence of suitable solvent and under suitable reaction conditions. [Table 7]

[0330] Intermediates-IIIa and IIIb: [ka]

[0331] Step-a: Synthesis of ethyl 2-(5-bromo-1H-indazol-1-yl)acetate and ethyl 2-(5-bromo-2H-indazol-2-yl)acetate (IIIa and IIIb) To a solution of 5-bromo-1H-indazole (1 g, 5.1 mmol, 1.0 equiv.) in acetonitrile (25 mL), potassium carbonate (1.8 g, 12.8 mmol, 2.5 equiv.) was added under stirring. Ethyl bromoacetate (0.7 mL, 6.1 mmol, 1.2 equiv.) was added dropwise, and the reaction mass was heated at reflux overnight. The reaction mass was concentrated under vacuum, washed with water, adsorbed onto silica, and purified by Combiflash to give the title products IIIa (400 mg, 28%, white solid) and IIIb (180 mg, 13%, yellow solid).

[0332] Intermediate-IIIa: 1 H NMR(400MHz,DMSO-d6)δ8.10(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=6.8Hz,3H);LC-MS:m / z 283.0(M+H) +

[0333] Intermediate-IIIb: 1 H NMR(400MHz,DMSO-d6)δ8.41(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=6.4Hz,3H);LC-MS:m / z 283.0(M+H) +

[0334] The following intermediates were prepared by similar procedures to Intermediates-IIIa and IIIb using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 8-1] [Table 8-2] [Table 8-3]

[0335] Intermediate-IV: [ka]

[0336] Step-a: Synthesis of methyl 2-(4-bromobenzamido)benzoate (Intermediate-IV) To a solution of methyl 2-aminobenzoate (5 g, 33.1 mmol, 1.0 equiv.) in DCM (50 mL) was added triethylamine (11 g, 108 mmol, 3 equiv.) followed by 4-bromobenzoyl chloride (7.2 g, 33.1 mmol, 1.0 equiv.) and stirred at room temperature overnight. The reaction mixture was extracted with ethyl acetate from water and concentrated in vacuo. The crude product was washed with n-pentane and dried to give the title product (9 g, 85%). 1 H NMR(400MHz,DMSO-d6)δ11.52(s,1H),8.47(d,J=8.3Hz,1H),8.04(d,J=8.4Hz,1H),7.89(d,J =8.8Hz,2H),7.83(d,J=8.8Hz,2H),7.67(t,J=7.3Hz,1H),7.24(t,J=7.3Hz,1H),3.87(s,3H).

[0337] The following intermediates were prepared by similar procedures to Intermediate-IV using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 9]

[0338] Intermediate-V: [ka]

[0339] Step-a: Synthesis of methyl 2-((4-bromophenyl)(methyl)amino)nicotinate (Intermediate-V): To a solution of Intermediate-II.10 (0.4 g, 1.3 mmol, 1.0 equiv) in DMF (3 mL) was added sodium hydride (50%, 0.16 g, 3.9 mmol, 3 equiv) and stirred for 10 min. Iodomethane (0.25 mL, 3.9 mmol, 3 equiv) was added dropwise and stirred overnight at room temperature in a sealed tube. The reaction mass was poured into water, extracted with ethyl acetate, and concentrated under vacuum. The crude product was purified by Combiflash to give the title product as a colorless liquid (0.21 g, 50%). 1 H NMR(400MHz,DMSO-d6)δ8.46(dd,J1=2.0Hz,J2=4.0Hz,1H),7.85(dd,J1=2.0Hz,J2=7.6Hz,1H),7.44-7 .40(m,2H),7.05(dd,J1=3.6Hz,J2=7.2Hz,1H),6.94-6.90(m,2H),3.44(s,3H),3.29(s,3H);LC-MS:m / z 321.0(M+H)

[0340] The following intermediates were prepared by similar procedures to Intermediate-V using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 10-1] [Table 10-2]

[0341] Intermediate-VI: [ka]

[0342] 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 equiv) and Intermediate-I.1 (0.37 g, 1.63 mmol, 1.0 equiv) in toluene (10 mL) was degassed with N gas for 15 minutes. Pd2dba3 (0.12 g, 0.13 mmol, 0.08 equiv) and XPhos (0.16 g, 0.326 mmol, 0.2 equiv) were added and degassed for 5 minutes. The reaction mass was heated at 110 °C for 16 hours. The reaction mass was filtered through Celite, concentrated under vacuum, and purified by Combiflash to give the title product as a pale yellow solid (0.26 g, 35%). 1 H NMR(400MHz,DMSO-d6)δ9.14(s,1H),8.02(s,1H),7.86(dd,J1=1.4Hz,J2=7.8Hz,1H),7.35(t,J=1.4Hz,1H),7.21(d,J LC-MS:m / z 452.4(M+H) +

[0343] The following intermediates were prepared by similar procedures to Intermediate-VI using appropriate reactants and reagents with suitable Pd catalyst and ligand in the presence of suitable solvent and under suitable reaction conditions. [Table 11-1] [Table 11-2] [Table 11-3] [Table 11-4] [Table 11-5] [Table 11-6] [Table 11-7] [Table 11-8] [Table 11-9] [Table 11-10] [Table 11-11] [Table 11-12] [Table 11-13] [Table 11-14] [Table 11-15] [Table 11-16] [Table 11-17] [Table 11-18]

[0344] Intermediate-VII: [ka]

[0345] 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 equiv.) and 4-bromonitrobenzene (6.57 g, 32.5 mmol, 1 equiv.) in toluene (100 mL) was degassed by bubbling nitrogen gas through it for 5 minutes. Cesium carbonate (16 g, 48.9 mmol, 1.5 equiv.) was added, followed by palladium acetate (0.72 g, 3.25 mmol, 0.1 equiv.) and XPhos (2.32 g, 4.88 mmol, 0.15 equiv.), and the mixture was degassed again for 5 minutes. The reaction mixture was heated at 110 °C with stirring for 16 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through Celite. The organic layer was adsorbed onto silica and purified by flash column chromatography. The desired product was eluted with 5–10% ethyl acetate in hexane. Concentration in vacuo afforded a dark yellow oil (7 g, 57%). 1 H NMR(400MHz,DMSO-d6)δ8.98(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) +

[0346] The following intermediates were prepared by similar procedures to Intermediate-VII using appropriate reactants and reagents with suitable Pd catalyst and ligand in the presence of suitable solvent and under suitable reaction conditions. [Table 12-1] [Table 12-2] [Table 12-3] [Table 12-4] [Table 12-5] [Table 12-6] [Table 12-7] [Table 12-8] [Table 12-9] [Table 12-10] [Table 12-11] [Table 12-12]

[0347] The following intermediates were prepared by similar procedures to Intermediate-V using appropriate reactants and reagents with suitable Pd catalyst and ligand in the presence of suitable solvent and under suitable reaction conditions. [Table 13-1] [Table 13-2] [Table 13-3] [Table 13-4] [Table 13-5] [Table 13-6] [Table 13-7] [Table 13-8] [Table 13-9]

[0348] Intermediate-VIII: [ka]

[0349] Step-a: Synthesis of N-(4-((3R,5R)-adamantan-1-yl)phenyl)-3-nitrobenzamide (Intermediate-VIII) The title compound (1.6 g, 96%) was synthesized from Intermediate-I.1 (1 g, 4.4 mmol, 1 equiv.) and 3-nitrobenzoyl chloride (0.82 g, 4.4 mmol, 1 equiv.) using a procedure similar to that of Intermediate-IV. LC-MS: m / z 377.2 (M+H) +

[0350] The following intermediates were prepared by similar procedures to Intermediate-VIII using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 14-1] [Table 14-2]

[0351] Intermediate-IX: [ka]

[0352] Step-a: Synthesis of (3R,5R)-1-(3-chloro-4-(4-nitrophenoxy)phenyl)adamantane (Intermediate-IX) To a solution of 4-fluoronitrobenzene (0.6 mL, 5.7 mmol) and Intermediate-I.25 (1.5 g, 6.84 mmol, 1.2 equiv.) in DMSO (10 mL), potassium carbonate (1.57 g, 11.4 mmol, 2 equiv.) was added and stirred at room temperature overnight. The reaction mass was poured into cold water, and the resulting solid was filtered and dried to give the title compound as an off-white solid (2 g, 91%). 1 H NMR(400MHz,DMSO-d6)δ8.26(d,J=9.3Hz,2H),7.58(s,1H),7.47(d,J=2.0Hz,1H), 7.32(d,J=8.8Hz,1H),7.1(d,J=8.3Hz,2H),2.07(bs,2H),1.89(s,6H),1.7(s,6H). LC-MS:m / z 382.0(MH) -

[0353] The following intermediates were prepared by similar procedures to Intermediate-IX using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 15-1] [Table 15-2] [Table 15-3]

[0354] Intermediate-X: [ka]

[0355] Step-a: Synthesis of (3r,5r,7r)-1-(3-chloro-4-methylphenyl)adamantane (Xa) To a solution of (3r,5r,7r)-1-(p-tolyl)adamantane (2 g, 8.8 mmol) in acetic acid, N-chlorosuccinimide was added portionwise over 30 minutes. The reaction mass was heated at 75° C. overnight. The reaction mass was poured into cold water, and the resulting solid was filtered off and dried under vacuum. The title compound was obtained as a white solid (2.2 g, 96%). 1 H NMR (400MHz, DMSO-d6) δ7.31 (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).

[0356] Step b: Synthesis of (3r,5r,7r)-1-(4-(bromomethyl)-3-chlorophenyl)adamantane (Xb) To a solution of compound Xa (1 g, 3.8 mmol) in carbon tetrachloride (40 mL), bromine (0.61 g, 3.8 mmol) was added dropwise, and benzoyl peroxide (catalyst) was added. The reaction mass was heated to reflux overnight. After concentration under vacuum, the crude product was purified by column chromatography to give the title product as an off-white solid (0.5 g, 38%). 1 H NMR (400MHz, DMSO-d6) δ7.38(d,J=8.0Hz,2H),7.24(m,1H),4.58(s,2H),2.10(s,3H),1.81(s,6H),1.72(s,6H).

[0357] Step c: Synthesis of 1-(4-((3R,5R)-adamantan-1-yl)-2-chlorobenzyl)-4-nitro-1H-pyrazole (Intermediate-X) This intermediate was prepared by the same procedure described for Intermediate-III using Intermediate-Xb (0.3 g, 0.88 mmol, 1 equiv.) and 4-nitropyrazole (0.12 g, 1.06 mmol, 1.2 equiv.) to afford the title product as an off-white solid (0.3 g, 91%). 1H NMR(400MHz,DMSO-d6)δ8.99(s,1H),8.28(s,1H),7.41(d,J=2.0Hz,1H),7.35(dd,J1=1.9Hz ,J2=8.3Hz,1H),7.21(d,J=8.3Hz,1H),5.47(s,2H),2.04(s,3H),1.83(s,6H),1.72(s,6H).

[0358] The following intermediates were prepared by similar procedures to Intermediate-X using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 16-1] [Table 16-2]

[0359] Intermediate-XI: [ka]

[0360] 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 equiv.) in THF:water (50 mL + 50 mL), ammonium chloride (19.42 g, 36.6 mmol, 20 equiv.) was added, followed by zinc dust (11.91 g, 183 mmol, 10 equiv.) and stirred at room temperature for 16 hours. The 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 under vacuum. The crude product was washed with n-pentane and dried under vacuum to give the desired product as a yellow gum (5.9 g, 91%), which was used in the next step without further purification. 1H NMR(400MHz,DMSO-d6)δ7.20(d,J=1.9Hz,1H)7.04(dd,J1=2.0Hz,J2=8.3Hz,1H),6.84(d,J=8.8Hz,2H),6.78(s, LC-MS:m / z 353.1(M+H) +

[0361] The following intermediates were prepared by similar procedures to Intermediate-XI using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 17-1] [Table 17-2] [Table 17-3] [Table 17-4] [Table 17-5] [Table 17-6] [Table 17-7] [Table 17-8] [Table 17-9] [Table 17-10] [Table 17-11] [Table 17-12] [Table 17-13] [Table 17-14] [Table 17-15] [Table 17-16] [Table 17-17] [Table 17-18] [Table 17-19] [Table 17-20] [Table 17-21]

[0362] Intermediate-XII: [ka]

[0363] 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 equiv.) and methyl 2-chloronicotinate (4.27 g, 25 mmol, 1.1 equiv.) in toluene (100 mL) was degassed by bubbling nitrogen gas through it for 5 minutes. Cesium carbonate (11.1 g, 34.1 mmol, 1.5 equiv.) was added, followed by palladium acetate (0.5 g, 2.27 mmol, 0.1 equiv.) and rac.BINAP (2.12 g, 3.41 mmol, 0.15 equiv.), and the mixture was degassed again for 5 minutes. The reaction mixture was heated at 110 °C with stirring for 16 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through Celite. The organic layer was adsorbed onto silica and purified by flash column chromatography. The desired product was eluted with 10% ethyl acetate in hexane. Concentration in vacuo gave a yellow solid (5.4 g, 49%). 1 H NMR(400MHz,DMSO-d6)δ9.93(s,1H),8.37(dd,J1=2.0Hz,J2=4.4Hz,1H),8.22(dd,J1=2.0Hz,J2=7.6Hz,1H),7.55(d,J=8.8Hz,2H),7.41(s,1H),7 .31(d,J=1.6Hz,1H),7.19-7.12(m,2H),7.04(d,J=8.8Hz,2H),6.84-6.8 1(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) +

[0364] The following intermediates were prepared by similar procedures to Intermediate-XII using appropriate reactants and reagents with suitable Pd catalyst and ligand in the presence of suitable solvent and under suitable reaction conditions. [Table 18-1] [Table 18-2] [Table 18-3] [Table 18-4]

Table 18-5

Table 18-6

Table 18-7

Table 18-8

Table 18-9

Table 18-10

Table 18-11

Table 18-12

Table 18-13

Table 18-14

Table 18-15

Table 18-16

Table 18-17

Table 18-18

Table 18-19

Table 18-20

Table 18-21

Table 18-22

Table 18-23

Table 18-24

Table 18-25

Table 18-26

Table 18-27

Table 18-28

Table 18-29

Table 18-30

Table 18-31

Table 18-32

Table 18-33

Table 18-34

Table 18-35

Table 18-36

Table 18-37

Table 18-38

Table 18-39

Table 18-40

Table 18-41

Table 18-42

Table 18-43

Table 18-44

Table 18-45

Table 18-46

Table 18-47

Table 18-48

Table 18-49

Table 18-50

Table 18-51

Table 18-52

[0365] Intermediate-XIII:

change

[0366] Step-a: Synthesis of methyl 2-((1,4-dioxaspiro[4.5]decan-8-yl)amino)benzoate (XIIIa) To 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), acetic acid (20 mL) was added and stirred at room temperature for 2 hours. The reaction mass was cooled to 0° C., sodium triacetoxyborohydride (6.3 g, 30 mmol, 1.5 eq.) was added and stirred at room temperature for 36 hours. Saturated bicarbonate solution was added to the reaction mass, extracted with dichloromethane, and purified by Combiflash to give the title product (1.01 g, 17%). 1 H NMR(400MHz,DMSO-d6)δ7.77(d,J=7.6Hz,1H),7.71(d,J=7.6Hz,1H),7.39-7.35(m,1H),6.83(d,J=8.8Hz,1H),6.57-6.53 LC-MS:m / z 292.0(M+H) +

[0367] Step b: Synthesis of methyl 2-((4-oxocyclohexyl)amino)benzoate (XIIIb) To a solution of compound XIIIa (1.01 g, 3.4 mmol, 1 equiv.) in acetone (30 mL), 2N HCl (10 mL) was added and stirred at room temperature overnight. The reaction mass was extracted with ethyl acetate from water and concentrated under vacuum. The crude product was used without further purification. 1H NMR(400MHz,DMSO-d6)δ7.81(dd,J1=0.8Hz,J2=7.6Hz,1H),7.75(d,J=7.6Hz,1H),6.94(d,J=8.8Hz,1H),6.59(t, LC-MS:m / z 248.2(M+H) +

[0368] Step c: Synthesis of methyl 2-((4-((4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)amino)cyclohexyl)amino)benzoate (Intermediate-XIII) To 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), sodium triacetoxyborohydride (1.28 g, 6.06 mmol, 3 eq.) was added and heated at 80° C. for 16 h. The reaction mass was extracted with ethyl acetate from saturated bicarbonate and brine and concentrated under vacuum. The crude product was purified by Combiflash to give the title compound as a pale pink liquid (0.67 g, 67%). LC-MS: m / z 493.3 (M+H) +

[0369] The following intermediates were prepared by similar procedures to Intermediate-XIII using appropriate reactants and reagents in the presence of suitable solvents and suitable reaction conditions. [Table 19-1] [Table 19-2] [Table 19-3]

[0370] Intermediate-XIV: [ka]

[0371] 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 min. TFA (3 mL) was added dropwise and stirred at room temperature for 16 h. The reaction mass was concentrated under vacuum. The crude product was triturated with n-pentane and dried under vacuum to give the title product as a pale green solid (2.0 g, 80%). 1 H NMR(400MHz,DMSO-d6)δ12.58(s,1H),9.40(s,1H),7.93(dd,J1=1.6Hz,J2=8.0Hz,1H),7.87(dd,J1=2.0 Hz,J2=6.8Hz,2H),7.52-7.46(m,2H),7.26(d,J=8.8Hz,2H),7.01-6.97(m,1H),3.84(s,3H),LC-MS:m / z 272.1(M+H) +

[0372] Alternative or general procedure for the synthesis of the corresponding carboxylic acid compounds with methyl and ethyl esters: To a solution of the ester (1 mmol) in THF:MeOH:HO (4 + 4 + 2 mL) was added LiOH.HO (5 mmol) and stirred at room temperature for 16 h. The reaction mass was concentrated under vacuum, diluted with water, and acidified to pH 5 with 2 N HCl. The resulting precipitate was filtered and dried under vacuum. The solid was washed with a 10% ether in hexane mixture and dried to give the desired acid.

[0373] The following intermediates were prepared by similar procedures to Intermediate-XIV using appropriate reactants and reagents in the presence of suitable solvents and suitable reaction conditions. [Table 20-1] [Table 20-2] [Table 20-3] [Table 20-4]

[0374] Intermediate-XV: [ka]

[0375] 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.) was added followed by DIPEA (0.39 mL, 2.22 mmol, 3 eq.) and stirred at room temperature for 16 hours. The reaction mass was slowly added to ice water under stirring. The resulting precipitate was filtered, washed twice with cold water, then twice with n-pentane, and dried under vacuum to give the title compound as a cream-colored solid (0.35 g, 98%). 1 H NMR(400MHz,DMSO-d6)δ10.01(s,1H),9.43(s,1H),7.96-7.91(m,3H),7.69(d,J=8.4Hz,2H),7.54-7.49(m,1H),7.45(d ,J=8.0Hz,1H),7.34-7.31(m,4H),6.95(t,J=6.8Hz,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) +

[0376] The following intermediates were prepared by similar procedures to Intermediate-XV using appropriate reactants and reagents in the presence of suitable solvents and suitable reaction conditions. [Table 21-1]

Table 21-2

Table 21-3

Table 21-4

Table 21-5

Table 21-6

Table 21-7

Table 21-8

Table 21-9

Table 21-10

Table 21-11

Table 21-12

Table 21-13

Table 21-14

Table 21-15

[0377] Intermediate-XVI:

change

[0378] 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 0° C., and triethylamine (0.66 g, 6.6 mmol, 3 eq.) was added followed by 4-acetamidobenzenesulfonyl chloride (0.51 g, 2.2 mmol) and stirred at room temperature for 3 hours. The reaction mass was concentrated under vacuum and cold water was added. The resulting solid was filtered and dried under vacuum to give the title product (0.88 g, 94%). LC-MS: m / z 425.1 (M+H). +

[0379] The following intermediates were prepared by similar procedures to Intermediate-XVI using appropriate reactants and reagents in the presence of suitable solvents and suitable reaction conditions. [Table 22-1] [Table 22-2]

[0380] Intermediate-XVII: [ka]

[0381] 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 equiv.) by a procedure similar to that described for Intermediate-I from Ib to afford the title product as a white solid (0.75 g, 98%). 1H NMR(400MHz,DMSO-d6)δ9.73(s,1H),7.38(d,J=8.8Hz,2H),7.17(d,J=8.8Hz,2H),6.98(d,J=8. 8Hz,2H),6.52(d,J=8.8Hz,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) +

[0382] The following intermediates were prepared by similar procedures to Intermediate-XVII using appropriate reactants and reagents in the presence of suitable solvents and suitable reaction conditions. [Table 23]

[0383] Intermediate-XVIII: [ka]

[0384] 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 that described for Intermediate-II. 1 H NMR(400MHz,DMSO-d6)δ10.01(s,1H),9.31(s,1H),7.89(d,J=8.4Hz,1H),7.63(d,J=8.4Hz,2H),7.50(t,J=7.6Hz,1H),7. 42(d,J=8.0Hz,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) +

[0385] The following intermediates were prepared by similar procedures to Intermediate-XVIII using appropriate reactants and reagents with suitable Pd catalyst and ligand in the presence of suitable solvent and under suitable reaction conditions. [Table 24-1] [Table 24-2] [Table 24-3]

[0386] Intermediate-XIX: [ka]

[0387] Step-a: Synthesis of phenyl (4-((3r,5r,7r)-adamantan-1-yl)phenyl)carbamate (XIXa) To 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, triethylamine (0.44 g, 4.4 mmol, 2 eq.) was added and stirred at room temperature for 2 hours. The reaction mixture was washed with water, concentrated in vacuo, and purified by Combiflash to give the title compound as a white solid (0.48 g, 63%). 1 H NMR(400MHz,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) +

[0388] 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 equiv.) and methyl 2-(4-aminophenyl)amino)nicotinate (0.2 g, 0.82 mmol, 1 equiv.) were taken in THF (20 mL), triethylamine (0.8 mL) was added, and the mixture was refluxed overnight. The reaction mass was concentrated under vacuum, and the crude product obtained was washed twice with n-hexane and dried under vacuum. The crude product was taken on without further purification. 1 H NMR(400MHz,DMSO-d6)δ9.96(s,1H),8.52(d,J=14.0Hz,2H),8.38-8.37(m,1H),7.76(d,J=8.4Hz,2H),7.41-7.35(m,4H), 7.25(d,J=8.4Hz,2H),6.84(dd,J1=4.4Hz,J2=8.0Hz,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) +

[0389] The following intermediates were prepared by similar procedures to Intermediate-XIX using appropriate reactants and reagents in the presence of suitable solvents and suitable reaction conditions. [Table 25]

[0390] Intermediate-XIX.4: [ka]

[0391] Step-a: Synthesis of methyl ((4-((4-((3R,5S)-adamantan-1-yl)-2-chlorophenyl)amino)phenyl)carbamoyl)prophosphate (XIX.4) To a solution of Intermediate-XI (0.1 g, 0.283 mmol, 1 equiv) in DCM (10 mL) at 0° C., triphosgene (0.084 g, 0.283 mmol, 1 equiv) was added dropwise and stirred at 0° C. for 1 h. This solution was added to a solution of methyl prophosphate (0.056 g, 0.32 mmol, 1.2 equiv) in DCM (10 mL) and stirred at 0° C. for 1 h. Quenched with saturated bicarbonate solution, extracted with DCM, and purified by column chromatography to give the title product as a light brown solid (0.13 g, 90%). 1 H NMR(400MHz,DMSO-d6)δ8.18(s,1H),7.34(d,J=8.8Hz,2H),7.28(d,J=2.0Hz,1H) ,7.26(s,1H),7.14(dd,J1=2.0Hz,J2=8.0Hz,1H),7.04(d,J=8.8Hz,1H),6.96(d, J=9.6Hz,2H),4.37-4.34(m,1H),3.62(s,3H),3.56-3.46(m,2H),2.21-2.14(m,1 H),2.03(s,3H),1.98-1.84(m,3H),1.81(d,J=2.4Hz,6H),1.71(s,6H);LC-MS:m / z 508.4(M+H) +

[0392] The following intermediates were prepared by similar procedures to Intermediate-XIX.4 using the appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. [Table 26]

[0393] Intermediate-XX: [ka]

[0394] 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 equiv.) in DMF (80 mL) was cooled to 0° C. and sodium hydride (1.06 g, 44.2 mmol, 5 equiv.) was added portionwise and stirred for 15 minutes. Methyl iodide (6.3 g, 44.2 mmol, 5 equiv.) was added dropwise and the reaction mass was heated at 80° C. in a sealed tube for 16 hours. The reaction mass was cooled to room temperature and poured into cold water. The precipitated solid was filtered and dried. The crude product was adsorbed onto silica and purified by Combiflash to give the title product as a pale yellow solid (3 g, 70.7%). 1 H NMR(400MHz,DMSO-d6)δ7.65(dd,J1=2.0Hz,J2=8.0Hz,1H),7.60(t,J=7.6Hz ,1H),7.33(d,J=7.6Hz,1H),7.26(t,J=7.2Hz,1H),7.13(d,J=8.8Hz,2H),6.9 0(d,J=8.8Hz,2H),6.67(d,J=8.8Hz,2H),6.59(d,J=8.8Hz,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) +

[0395] The following intermediates were prepared by similar procedures to Intermediate-XX using appropriate reactants and reagents in the presence of suitable solvents and suitable reaction conditions. [Table 27-1] [Table 27-2] [Table 27-3] [Table 27-4] [Table 27-5] [Table 27-6]

[0396] The following compounds were prepared by similar procedures to Intermediate-VI using appropriate reactants and reagents with suitable Pd catalyst and ligand in the presence of suitable solvent and under suitable reaction conditions. [Table 28-1] [Table 28-2] [Table 28-3] [Table 28-4] [Table 28-5] [Table 28-6] [Table 28-7] [Table 28-8]

[0397] The following compounds were prepared by similar procedures to Intermediate-XIII using appropriate reactants and reagents in the presence of suitable solvents and suitable reaction conditions. [Table 29-1] [Table 29-2]

[0398] The following compounds were prepared by similar procedures to Intermediate-XI using appropriate reactants and reagents in the presence of suitable solvents and suitable reaction conditions. [Table 30]

[0399] The following compounds were prepared by a similar procedure to Intermediate-XIX using appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions. [Table 31]

[0400] Synthesis of 2-((4-((4-((3R,5R)-adamantan-1-yl)phenyl)amino)phenyl)amino)benzoic acid (Compound-24 (CP-55)) [ka]

[0401] To a solution of Intermediate-VI (8.5 g, 16.5 mmol, 1 equiv.) in THF:MeOH:HO (40 mL + 40 mL + 20 mL) was added LiOH×HO (3.3 g, 82.4 mmol, 5 equiv.) and stirred at room temperature for 16 hours. The reaction mass was concentrated under vacuum, diluted with water, and acidified to pH 5 with 2 N HCl. The resulting precipitate was filtered and dried under vacuum. The solid was washed with a 10% ether in hexane mixture and dried to give the title product as an off-white solid (5.5 g, 67%). 1 H NMR(400MHz,DMSO-d6)δ12.99(s,1H),9.42(s,1H),8.00(s,1H),7.85(d,J=6.8Hz,1H),7.32(t,1H),7.21(d ,J=8.8Hz,2H),7.11-6.96(m,7H),6.67(t,J=3.4Hz,1H),2.08(s,3H),1.83(s,6H),1.72(s,6H);LC-MS:m / z 438.4(M+H) +

[0402] The following compounds were prepared by procedures similar to those described for Compound-24, using appropriate reactants and reagents in the presence of suitable solvents and appropriate reaction conditions. The physicochemical properties of the compounds are also summarized. [Table 32-1] [Table 32-2] [Table 32-3] [Table 32-4] [Table 32-5] [Table 32-6] [Table 32-7] [Table 32-8] [Table 32-9] [Table 32-10] [Table 32-11] [Table 32-12] [Table 32-13] [Table 32-14] [Table 32-15]

Table 32-16

Table 32-17

Table 32-18

Table 32-19

Table 32-20

Table 32-21

Table 32-22

Table 32-23

Table 32-24

Table 32-25

Table 32-26

Table 32-27

Table 32-28

Table 32-29

Table 32-30

Table 32-31

Table 32-32

Table 32-33

Table 32-34

Table 32-35

Table 32-36

Table 32-37

Table 32-38

Table 32-39

Table 32-40

Table 32-41

Table 32-42

Table 32-43

Table 32-44

Table 32-45

Table 32-46

Table 32-47

Table 32-48

Table 32-49

Table 32-50

Table 32-51

Table 32-52

Table 32-53

Table 32-54

Table 32-55

Table 32-56

Table 32-57

Table 32-58

Table 32-59

Table 32-60

Table 32-61

Table 32-62

Table 32-63

Table 32-64

Table 32-65

Table 32-66

Table 32-67

Table 32-68

Table 32-69

Table 32-70

Table 32-71

Table 32-72

Table 32-73

Table 32-74

Table 32-75

Table 32-76

Table 32-77

Table 32-78

Table 32-79

Table 32-80

Table 32-81

Table 32-82

Table 32-83

Table 32-84

Table 32-85

Table 32-86

Table 32-87

Table 32-88

Table 32-89

Table 32-90

Table 32-91

Table 32-92

Table 32-93

Table 32-94

Table 32-95

Table 32-96

Table 32-97

Table 32-98

Table 32-99

Table 32-100

Table 32-101

Table 32-102

Table 32-103

Table 32-104

Table 32-105

Table 32-106

Table 32-107

Table 32-108

Table 32-109

Table 32-110

Table 32-111

Table 32-112

Table 32-113

Table 32-114

Table 32-115

Table 32-116

Table 32-117

Table 32-118

Table 32-119

Table 32-120

Table 32-121

Table 32-122

Table 32-123

Table 32-124

Table 32-125

Table 32-126

Table 32-127

Table 32-128

Table 32-129

Table 32-130

Table 32-131

Table 32-132

Table 32-133

Table 32-134

Table 32-135

Table 32-136

Table 32-137

Table 32-138

Table 32-139

Table 32-140

Table 32-141

Table 32-142

Table 32-143

Table 32-144

Table 32-145

Table 32-146

Table 32-147

[0403] The following compounds were prepared by a similar procedure to Intermediate-XV using appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions. [Table 33-1] [Table 33-2] [Table 33-3] [Table 33-4] [Table 33-5]

[0404] The following compounds were prepared by a similar procedure to Intermediate-XIV using appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions. [Table 34-1] [Table 34-2] [Table 34-3] [Table 34-4]

[0405] Synthesis of 2-((4-((4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)amino)phenyl)carbamoyl)benzoic acid (Compound-293) (CP-119): [ka]

[0406] Step (i): A solution of Intermediate-XI (0.05 g, 0.16 mmol, 1 equiv.) and phthalic anhydride (0.024 g, 0.16 mmol, 1 equiv.) in DCM was stirred at room temperature for 2 h. The resulting precipitate was filtered and dried under vacuum to give the title product as a pale yellow solid (0.01 g, 12.5%). 1H NMR(400MHz,DMSO-d6)δ12.98(s,1H),10.17(s,1H),7.86(d,J=7.8Hz,1H),7.63(d,J=7.3Hz,1H),7.57-7.52(m,4H), 7.41(s,1H),7.31(d,J=1.6Hz,1H),7.17-7.12(m,2H),7.04(d,J=8.8Hz,2H),2.05(s,3H),1.83(s,6H),1.72(s,6H). LC-MS:m / z 501.1(M+H) +2

[0407] The following compounds were prepared by procedures similar to those for Compound 293 using the appropriate reactants and reagents in the presence of suitable solvents and suitable reaction conditions. [Table 35-1] [Table 35-2] [Table 35-3] [Table 35-4] [Table 35-5]

[0408] Experimental procedures and physicochemical characteristics of compound CP-453 Intermediates: [ka]

[0409] The above intermediate was prepared by the same procedure as 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 give the title product as a brown solid (0.05 g, 22%). 1H NMR (400MHz, DMSO-d6): δ8.79(s,1H),7.54-7.52(m,1H),7.44-7.42(m,1H),7.28-6.98(m,9H),3.85(s,3H),3.8 0(d,J=2.4Hz,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=6.4Hz,6H).

[0410] Final compound: [ka]

[0411] The above compound was prepared by the same procedure as that described for Compound-24, by using suitable reagents in the presence of suitable solvents and appropriate reaction conditions. The physicochemical properties of the compound are also summarized. 1 H NMR(400MHz,DMSO-d6):δ13.10(s,1H),9.12(s,1H),7.37(d,J=2.0Hz,1H),7.23( d,J=8.4Hz,2H),7.10(d,J=9.2Hz,2H),7.05(dd,J1=2.8Hz,J2=9.2Hz,2H),6.97(d ,J=8.8Hz,2H),6.89(d,J=8.8Hz,2H),3.68(d,J=6.4Hz,2H),3.21(s,3H),2.04(s, 3H),2.01-1.98(m,1H),1.83(d,J=2.6Hz,6H),1.72(s,6H),0.97(d,J=6.8Hz,6H). LC-MS: 525.3 (M+H) +

[0412] Biological assays In vitro palmitoylation Recombinant GST-TEAD2 or His6TEAD2 (500 ng) protein was preincubated with the indicated compounds for 15 min, then incubated with 1 μM alkyne palmitoyl-5CoA (Cayman Chemical) for 30 min or 50 mM MES (pH 6.4), followed by a click reaction with biotin azide as previously described (Zheng, B. et al., J. Am. Chem. Soc., 2013, 135, 7082-7085). Click reactions were performed at room temperature for 1 h in 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.

[0413] The reaction was 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 analyzed by SDS-PAGE, and Western blots were performed by independently probing with streptavidin-HRP and histidine-HRP antibodies. Band intensities from streptavidin blots were quantified using a BIORAD Gel doc system, and the percentage of inhibition of Tead2 autopalmitoylation was determined by comparison with DMSO control-treated samples.

[0414] These compounds were tested for their activity in inhibiting TEAD2 palmitoylation in the above assay, and compound data are provided in the table below as the percentage of inhibition of TEAD2 palmitoylation by compounds at a concentration of 10 μM.

[0415] Cell proliferation HuH7 cells (or other cells) are cultured in DMEM supplemented with 10% FBS. The cells are seeded in 96-well plates at a density of 5000 cells / well. After the cells are allowed to attach to the wells, compounds in DMSO solution (1% DMSO concentration) are added to the cells using serial dilutions to the indicated final concentrations. The cells are further incubated for 3 days. Cell viability is then determined using CellTiter Glo, MTT, or crystal violet staining. Inhibition curves are plotted using GraphPad.

[0416] qRT-PCR YAP target gene expression was analyzed using a LightCycler 480 (Roche). Total RNA was isolated from cells using TRIzol (Life Technologies) and then used to generate cDNA using the Transcriptor First Strand cDNA Synthesis Kit (Roche). The resulting cDNA was then used in a reaction with the LightCycler 480 SYBR Green I Master Mix (Roche) containing probes for detecting CTGF or CYR61, and GAPDH.

[0417] CMP assay 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM) reacts with the thiol of CoA liberated in the enzymatic reaction, giving a fluorescent signal (excitation approximately 350-380, emission approximately 460-480). This assay detects the product (free CoA) generated from palmitoyl-CoA as a method for detecting enzymatic activity. Therefore, test compounds that inhibit TEAD activity can block the CPM fluorescent signal.

[0418] TEAD2 / 4 protein (10 μL of a 50 ng / μL solution) and test compound solutions (0.5 μL, varying concentrations) were preincubated at room temperature for 30 minutes. 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 thoroughly mixed using a pipette. The solution was then incubated in the dark at room temperature for 30 to 120 minutes, and fluorescence was detected at 350 nm every 30 minutes until the fluorescence signal was saturated. The IC value of the compound's ability to inhibit fluorescence was calculated. 50 is calculated from the result.

[0419] The results of the biological assays are shown in FIGS. 3 to 12 and Tables 1 and 2.

[0420] Compounds active as TEAD palmitoylation inhibitors Exemplary compounds were tested for their activity in inhibiting TEAD2 palmitoylation in the above assays and in the CMP assay. Compound data are provided in Table 1 as the percentage of inhibition of TEAD2 palmitoylation at a compound concentration of 10 μM or the IC50 in the CMP assay. [Table 36-1] [Table 36-2] [Table 36-3] [Table 37-1] [Table 37-2] [Table 37-3]

Table 37-4

Table 37-5

Table 37-6

Table 37-7

Table 37-8

Table 37-9

Table 37-10

Table 37-11

Table 37-12

Table 37-13

Table 37-14

Table 37-15

Table 37-16

Table 37-17

Table 37-18

Table 37-19

Table 37-20

Table 37-21

Table 37-22

Table 37-23

Table 37-24

Table 37-25

Table 37-26

Table 37-27

Table 37-28

Table 37-29

Table 37-30

Table 37-31

Table 37-32

Table 37-33

Table 37-34

Table 38-1

Table 38-2

Table 38-3

Table 38-4

Table 38-5

Table 38-6

Table 38-7

Table 38-8

Table 38-9

Table 38-10

Table 38-11

Table 38-12

Table 38-13

Table 38-14

Table 38-15

Table 38-16

Table 38-17

Table 38-18

Table 38-19

Table 38-20

[0421] In addition to those described herein, various modifications of the present invention will become 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 cited in this application, including but not limited to all patents, patent applications, and publications, is hereby incorporated by reference in its entirety. The present invention includes the following embodiments. [Claim 1] Compounds of formula (I) [ka] (In the formula, L 1 does not exist or does not have the formula N(R N ) or C(O) groups, D is a group of formula (D1), (D2), (D3), (D4), (D5), (D6), or (D7), [ka] m is 1, 2, or 3; A 1 But 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- to 10-membered heteroaryl, 4- to 10-membered heterocycloalkyl, (C 1~3 alkylene)-5 to 10-membered heteroaryl, or (C 1~3 alkylene)-4 to 10-membered heterocycloalkyl, and A 1 (C 1~3 alkylene)-C(O)R 1 Group (C 1~3 alkylene) groups are unsubstituted or each independently selected from halogen, OR a1 , N.R. c1 R d1 , N.R. a1 (CO)(C 1~6 alkyl), and NR a1 (CO)O(C 1~6 alkyl), and A 1 The 5- to 10-membered heteroaryl, 4- to 10-membered heterocycloalkyl, (C 1~3 alkylene)-5 to 10-membered heteroaryl, or (C 1~3 alkylene)-4 to 10-membered heterocycloalkyl are unsubstituted or each independently selected from halogen, OR a1 , S.R. a1 , C(O)OR a1 , N.R. c1 R d1 , and C(O)NR c1 R d1 and is substituted by 1, 2, 3, 4, or 5 substituents selected from L 2 does not exist or does not have the formula N(R N ), O, or C(O), L 3 does not exist or has the formula CH 2 , C≡C, N(R N ), or a C(O) group, Each R N However, independently, H, C 1~6 Alkyl, C(O)C 1~6 Alkyl, or C(O)OC 1~6 is alkyl, R 1 But H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, Cy 1A , OH, O.C. 1~6 Alkyl, OCy 1A , O(C 1~3 (Alkylenyl)Cy 1A , N.H. 2 , N.H.C. 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 and R 1 Forming C 1~6 Each alkyl is unsubstituted or each independently selected from halogen, OR a1 , S.R. a1 , and N.R. c1 R d1 and is substituted by 1, 2, 3, 4, or 5 substituents selected from Cy 1A But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 1A Forming C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or contains 0, 1, or 2 Cy 1B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, ORa1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl; Each Cy 1B But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 1B Forming C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently is unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl; A 2 But, CR 2 or N, A 3 But, CR 3 or N, A 4 But, CR 4 or N, A 5 But, CR 5 or N, A 6 But, CR 6 or N, A 7 But, CR 7 or N, A 8 But, CR 8 or N, A 9 But, CR 9 or N, A 10 But, CR 10 or N, A D41 However, CH, C(C 1~6 alkyl), or N, A D42 But CH 2 , NH, or NC 1~6 is alkyl, R 2 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 3 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 4 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from1~6 is alkyl, R 5 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 6 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , S(O) 2 R b1 , S(O) 2 NR c1 R d1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 7 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 Rd1 , 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, Cy 7A But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 7A Forming C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or 7B ,OCy 7B , NHCy 7B , and C(O)NHCy 7B and 0, 1, or 2 substituents selected from, each independently, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl; Each Cy 7B But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 7B Forming C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently is unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, ORa1 , S.R. a1 , N.R. c1 R d1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl; R 8 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 , S.R. a1 , N.R. c1 R d1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, Cy 8A But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 8A Forming C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or 8B ,OCy 8B , NHCy 8B , and C(O)NHCy 8B and 0, 1, or 2 substituents selected from, each independently, unsubstituted C1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl; Each Cy 8B But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy 8B Forming C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently is unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl; R 9 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , N.R. c1 C(O)R b1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 10 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R.a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, Cy D71 But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 14-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy D71 Forming C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or D72 , C.H. 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, or 2 substituents selected from, each independently, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S(hal) 5 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R. c1R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 Alkyl or C 2~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkenyl; Each Cy D72 But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy D72 Forming C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently is 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, ORa1, SRa1, NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently, C 6~10 Aryl, C 3~15 Cycloalkyl, 4-10 membered heterocycloalkyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 and wherein said C is substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl, 6~10 Aryl, C 3~15 cycloalkyl, and 4- to 10-membered heterocycloalkyl are each optionally independently selected from C 1~6 Alkyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)ORa1 , and C(O)NR c1 R d1 and is substituted with 1, 2, or 3 substituents selected from R a1 、R b1 、R c1 , and R d1 However, independently, 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 form a 4- to 10-membered unsubstituted heterocycloalkyl ring, or independently, C 1~6 Alkyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , and C(O)NR c1 R d1 forming a heterocyclic ring substituted with 1, 2, or 3 substituents selected from however, L 1 But, L 2 is C(O), the formula N(R N ) group, L 1 But, L 2 is N(R N ), then a group of formula C(O), L 2 does not exist or L 1 is C(O), then the formula N(R N ) group, L 2 does not exist or L 1 is N(R N ) is a group of formula C(O), A D41 But, A D42 is NH or NC 1~6 If it is alkyl, CH, C(C 1~6 alkyl), A D42 But, A D41 is NH or NC 1~6 If it is alkyl, CH 2 and A 2 、A 3 、A 4 , and A 5 At most two of are N, A 6 、A 7 、A 8 、A 9 , and A 10 At most two of are N, R 1 exists and 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 But 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 7 A, 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 But Cy 8A ,OCy 8A , O(C 1~3 (Alkylenyl)Cy 8A , C(O)OCy8A , 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 or a pharmaceutically acceptable salt thereof. [Claim 2] R 6 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 7 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 8 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. 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 each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, R 9 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 is alkyl, Cy D71 But C 6~10 Aryl, C3~15 cycloalkyl, 5- to 14-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; Cy D71 Forming C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or D72 , C.H. 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, or 2 substituents selected from, each independently, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 Alkyl or C 2~6 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkenyl; Each Cy D72 But C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl; CyD72 Forming C 6~10 Aryl, C 3~15 Each of the cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is unsubstituted or each independently is unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~15 Cycloalkyl, halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R. c1 R d1 C substituted by 1, 2, or 3 substituents selected from 1~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl; R a1 、R b1 、R c1 , and R d1 However, independently, 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 and R 1 and R 2 together with the nitrogen atom to which they are both attached form a 4-10 membered unsubstituted heterocycloalkyl ring. [Claim 3] L 1 But N(R N 3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein: [Claim 4] L 1 3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein is C(O). [Claim 5] 5. The compound according to claim 1, wherein D is a group of formula (D1), or a pharmaceutically acceptable salt thereof. [Claim 6] 5. The compound according to claim 1, wherein D is a group of formula (D2), or a pharmaceutically acceptable salt thereof. [Claim 7] 5. The compound according to claim 1, wherein D is a group of formula (D3), or a pharmaceutically acceptable salt thereof. [Claim 8] A 1 But C(O)R 1 8. The compound according to claim 1, wherein: [Claim 9] A 1 However, (C 1~3 alkylene)-C(O)R 1 and A 1 (C 1~3 alkylene)-C(O)R 1 Group (C 1~3 alkylene) groups are unsubstituted or each independently selected from halogen, OR a1 , N.R. c1 R d1 , N.R. a1 (CO)(C 1~6 alkyl), and NR a1 (CO)O(C 1~6 6. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is substituted by 0, 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, methyl, methyl, methylamino ... [Claim 10] A 1 However, (C 1~3 alkylene)-C(O)R 1 and A 1 (C 1~3 alkylene)-C(O)R1 Group (C 1~3 alkylene) group is NR c1 R d1 , N.R. a1 (CO)(C 1~6 alkyl), or NR a1 (CO)O(C 1~6 alkyl), e.g., CH 2 CH(NH 2 8. The compound of claim 7, or a pharmaceutically acceptable salt thereof, wherein: [Claim 11] A 1 6. The compound according to claim 1, wherein is CN, or a pharmaceutically acceptable salt thereof. [Claim 12] A 1 But NO 2 6. The compound according to claim 1, wherein: [Claim 13] A 1 are unsubstituted or each independently a halogen, OR a1 , S.R. a1 , C(O)OR a1 , N.R. c1 R d1 , and C(O)NR c1 R d1 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, each substituted by 0, 1, 2, 3, 4, or 5 substituents selected from 1~3 alkylene)-5 to 10-membered heteroaryl, or (C 1~3 6. The compound according to claim 1, wherein the aryl group is 4-10-membered heterocycloalkyl, or a pharmaceutically acceptable salt thereof. [Claim 14] A 1 are unsubstituted or each independently a halogen, OR a1 , S.R. a1 , C(O)OR a1 , N.R. c1 R d1 , and C(O)NR c1 R d1 S(O) is substituted by 1, 2, 3, 4, or 5 substituents selected from 2 R 1 , NHC(O)R 1 , NH(C 1~3 alkylene)-C(O)R 1 , 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CH 2 (5-10 membered heteroaryl), or CH 2 (4- to 10-membered heterocycloalkyl), or a pharmaceutically acceptable salt thereof. [Claim 15] A 2 But, CR 2 15. The compound according to any one of claims 1 to 14, wherein: [Claim 16] R 2 is H, or a pharmaceutically acceptable salt thereof. [Claim 17] A 2 is N, or a pharmaceutically acceptable salt thereof. [Claim 18] A 3 But, CR 3 18. The compound according to any one of claims 1 to 17, or a pharmaceutically acceptable salt thereof, wherein: [Claim 19] R 3 But H, C 1~6 Alkyl, or C 1~6 20. The compound of claim 18, or a pharmaceutically acceptable salt thereof, which is haloalkyl. [Claim 20] R 3 19. The compound of claim 18, or a pharmaceutically acceptable salt thereof, wherein is H, methyl, or trifluoroethyl. [Claim 21] R 3 is H, or a pharmaceutically acceptable salt thereof. [Claim 22] A 3 is N, or a pharmaceutically acceptable salt thereof. [Claim 23] A 4 But, CR 4 23. The compound according to any one of claims 1 to 22, or a pharmaceutically acceptable salt thereof, wherein: [Claim 24] R4 is H, or a pharmaceutically acceptable salt thereof. [Claim 25] A 4 23. The compound according to any one of claims 1 to 22, wherein is N, or a pharmaceutically acceptable salt thereof. [Claim 26] A 5 But, CR 5 26. The compound according to any one of claims 1 to 25, wherein: [Claim 27] R 5 is H, or a pharmaceutically acceptable salt thereof. [Claim 28] A 5 is N, or a pharmaceutically acceptable salt thereof. [Claim 29] A 2 But, CR 2 and A 3 But, CR 3 and A 4 But, CR 4 and A 5 But, CR 5 15. The compound according to any one of claims 1 to 14, wherein: [Claim 30] A 2 But, CR 2 and A 3 But, CR 3 and A 4 But, CR 4 and A 5 The compound according to any one of claims 1 to 14, wherein is N, or a pharmaceutically acceptable salt thereof. [Claim 31] 5. The compound according to claim 1, wherein D is a group of formula (D4), or a pharmaceutically acceptable salt thereof. [Claim 32] A D41 32. The compound of claim 31, or a pharmaceutically acceptable salt thereof, wherein: [Claim 33] A D41 But C(C 1~6 32. The compound of claim 31, or a pharmaceutically acceptable salt thereof, wherein: [Claim 34] A D41 is N, or a pharmaceutically acceptable salt thereof. [Claim 35] A D42 35. The compound according to any one of claims 31 to 34, or a pharmaceutically acceptable salt thereof, wherein is NH. [Claim 36] A D42 But NC 1~6 35. The compound according to any one of claims 31 to 34, or a pharmaceutically acceptable salt thereof, which is alkyl. [Claim 37] A D42 But CH 2 37. The compound according to any one of claims 31 to 36, or a pharmaceutically acceptable salt thereof, wherein: [Claim 38] 38. The compound according to any one of claims 31 to 37, wherein m is 1, or a pharmaceutically acceptable salt thereof. [Claim 39] 38. The compound according to any one of claims 31 to 37, wherein m is 2, or a pharmaceutically acceptable salt thereof. [Claim 40] 38. The compound according to any one of claims 31 to 37, wherein m is 3, or a pharmaceutically acceptable salt thereof. [Claim 41] 5. The compound according to claim 1, wherein D is a group of formula (D5), or a pharmaceutically acceptable salt thereof. [Claim 42] 42. The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein m is 1. [Claim 43] 42. The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein m is 2. [Claim 44] 42. The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein m is 3. [Claim 45] 5. The compound according to claim 1, wherein D is a group of formula (D6), or a pharmaceutically acceptable salt thereof. [Claim 46] 46. ​​The compound of claim 45, or a pharmaceutically acceptable salt thereof, wherein m is 1. [Claim 47] 46. ​​The compound of claim 45, or a pharmaceutically acceptable salt thereof, wherein m is 2. [Claim 48] 46. ​​The compound of claim 45, or a pharmaceutically acceptable salt thereof, wherein m is 3. [Claim 49] R 1 But H, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, Cy 1A , OH, O.C. 1~6 Alkyl, OCy 1A , O(C 1~3 (Alkylenyl)Cy 1A , N.H. 2 , N.H.C. 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 49. The compound according to any one of claims 1 to 10 or 15 to 48, or a pharmaceutically acceptable salt thereof, wherein: [Claim 50] R 1 But 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 48. The compound of claim 47, wherein: [Claim 51] R 1 But NHCy 1A 48. The compound of claim 47, wherein: [Claim 52] R 1 But C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, Cy 1A , OH, or OC 1~6 49. The compound according to any one of claims 1 to 10 or 15 to 48, or a pharmaceutically acceptable salt thereof, which is alkyl. [Claim 53] R 1 53. The compound of claim 52, or a pharmaceutically acceptable salt thereof, wherein is OH. [Claim 54] R 1 is a group of one of the following formulae:

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Claims

1. A compound of the formula 【Chemistry 1】 (In the formula, R Ｎ is H, R 1 is OH; A 3 is CR 3 ; A 5 is CH or N; A ７ is CH or N; A １０ is CH or N; R3 is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , N.R. ｃ１ R ｄ１ , C(O)OR ａ１ , C(O)NR ｃ１ R ｄ１ or each independently is halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ C substituted by 1, 2, or 3 substituents selected from １～６ is alkyl, R 8 is Cy 8A , OCy 8A , O(C 1-3 alkylene)Cy 8A , NHCy 8A , NH(C 1-3 alkylene)Cy 8A , N(C 1-6 alkyl)Cy 8A , N(C 1-6 alkyl)(C 1-3 alkylene)Cy 8A ; Cy 8A is a group of one of the following formulae: 【Chemistry 2】 R ａ１ , R ｂ１ , R ｃ１ , and R ｄ１ Each independently represents 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, however, 【Chemistry 200】 ), or a pharma- ceutically acceptable salt thereof.

2. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, wherein R3 is H, C1-6 alkyl, or C1-6 haloalkyl.

3. The compound of claim 2, or a pharma- ceutically acceptable salt thereof, wherein R3 is H.

4. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, wherein A5 is CH.

5. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, wherein A5 is N.

6. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, wherein A7 is CH.

7. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, wherein A7 is N.

8. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, wherein R8 is NHCy8A.

9. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, wherein Cy8A is a group of one of the following formulae: embedded image 【Chemistry 3】 10. The compound according to claim 1, or a pharma- ceutically acceptable salt thereof, wherein A10 is CH.

11. The compound according to claim 1, or a pharma- ceutically acceptable salt thereof, wherein A10 is N.

12. 【Catalogue 116】 【change】 1. A compound selected from the group consisting of: or a pharma- ceutically acceptable salt thereof.

13. A pharmaceutical composition comprising a compound according to any one of claims 1 to 12, or a pharma- ceutically acceptable salt thereof, and at least one pharma- ceutically acceptable carrier.

14. A pharmaceutical composition for treating cancer, comprising a compound according to any one of claims 1 to 12, or a pharma- ceutically acceptable salt thereof, or a composition according to claim 14.

15. 14. Use of a compound according to any one of claims 1 to 12, or a pharma- ceutically acceptable salt thereof, or a composition according to claim 13, in the manufacture of a medicament for treating cancer.

16. The pharmaceutical composition of claim 14, wherein the cancer is a solid tumor or a hematological cancer.

17. 15. The pharmaceutical composition of claim 14, wherein the cancer is prostate cancer, colon cancer, esophageal cancer, endometrial cancer, ovarian cancer, uterine cancer, kidney cancer, liver cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, head and neck cancer, thyroid cancer, glioblastoma, sarcoma, bladder cancer, lymphoma, leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, diffuse large B-cell lymphoma, mantle cell lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, or multiple myeloma.

18. 15. The pharmaceutical composition of claim 14, wherein the cancer is hepatocellular carcinoma, medulloblastoma, cutaneous squamous cell carcinoma, lung cancer, pancreatic cancer, esophageal cancer, liver cancer, colon cancer, melanoma, or bladder melanoma.

19. The use of claim 15, wherein the cancer is a solid tumor or a blood cancer.

20. The use of claim 15, wherein the cancer is prostate cancer, colon cancer, esophageal cancer, endometrial cancer, ovarian cancer, uterine cancer, kidney cancer, liver cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, head and neck cancer, thyroid cancer, glioblastoma, sarcoma, bladder cancer, lymphoma, leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, diffuse large B-cell lymphoma, mantle cell lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, or multiple myeloma.

21. The use of claim 15, wherein the cancer is hepatocellular carcinoma, medulloblastoma, cutaneous squamous cell carcinoma, lung cancer, pancreatic cancer, esophageal cancer, liver cancer, colon cancer, melanoma, or bladder melanoma.

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