Novel small molecule inhibitors of TEAD transcription factors

Abstract

To provide compounds that inhibit the activity of the TEAD transcription factor and are useful in the treatment of diseases related to the activity of TEAD transcription factor including, e.g., cancer and other diseases.SOLUTION: The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof.SELECTED DRAWING: Figure 1-1

Description

[Technical Field]

[0001] Priority claims This application is a continuation of U.S. patent application Ser. No. 62 / 819,347, filed March 15, 2019. No. 60 / 699,999, filed on May 1, 2003, the entire contents of which are incorporated herein by reference.

[0002] Government support This invention was made possible through grant number 1R01CA18153 awarded by the National Institutes of Health. This work was made with government support under R01DK107651 and R01DK107651. The U.S. Government is not responsible for this invention. clearly have certain rights.

[0003] This application relates to pharmaceutically useful compounds. This disclosure relates to new compounds, as well as their The present invention provides compositions and methods of use for the self-palmitoylation of TEAD transcription factors. inhibits transcriptional activation and thus inhibits the activity of TEAD transcription factors, including, for example, cancer and other diseases. It is useful in treating diseases related to [Background technology]

[0004] Hippo signaling plays a key role in organ size control and tumor suppression Signal transduction is mediated by a core kinase complex that includes the MST1 / 2 and Lats1 / 2 kinases. scade, YAP / TAZ phosphorylation, cytoplasmic retention, and inhibition 3 This leads to Physiological or pathological inactivation of these kinases results in YAP / TAZ dephosphorylation and nuclear Subsequently, nuclear YAP / TAZ binds to TEA domain transcription factors (e.g., TEA domain transcription factors in mammals) and accumulates in the nucleus. binds to TEAD1-4, or Scalloped in Drosophila, and targets genes The TEAD-YAP complex mediates the normal development of skin, muscle, lung, and liver. TEAD regulates the expression of TEAD and is an oncogenic factor that is amplified in many human cancers. , as a tumor suppressor by competing with YAP / TAZ for TEAD binding. TEADs can bind to Vgll4, which is involved in Hippo It is essential for regulating the transcriptional output of the pathway. Targeting TEAD-YAP This may be a promising therapeutic approach for diseases with a deregulated Hippo pathway. However, it remains difficult to directly inhibit transcription factors using small molecules. Understanding the regulation of TEADs may reveal new therapeutic opportunities for drug discovery.

[0005] Post-translational S-palmitoylation is the 16-carbon palmitoylation via a reversible thioester bond. Many palmitoylated proteins are found in the proteome. Dynamic S-palmitoylation has been identified in Src family kinases. Trafficking and membrane localization of many proteins, including enzymes, GTPases, and synaptic adhesion molecules Asp-His-His-Cys (DHH) plays an important role in regulating the function of the C) Family proteins are evolutionarily conserved proteins called palmitoyl acyltransferases. S-palmitoylation is mediated by the enzyme S-palmitoylation of hydroxybenzoates (PATs). The protein binds directly to palmitoyl-coenzyme A (CoA) and is PAT-independent. However, autopalmitoylation can occur without any specific mechanism. The majority of reported examples of self-palmitoylation are This is observed under unphysiologically high concentrations of palmitoyl-CoA (>100 μM). In contrast, only a few proteins, including the yeast transporter protein Bet3, bind palmitoyltransferase. It is self-palmitoylated under physiological concentrations of acetyl-CoA (1-10 μM). To identify additional autopalmitoylated proteins and their regulation and function It is important to understand this. 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: do.

[0007] The present disclosure also provides a compound of formula (I), or a pharmaceutically acceptable salt thereof, and at least The composition also includes a 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. do.

[0009] The details of one or more embodiments are set forth in the description below. Other features, objects, and aspects of the present invention are set forth in the description below. Advantages will be apparent from the description and 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" and their grammatical equivalents are Unless expressly stated otherwise, it is understood that the phrase "without limitation" follows.

[0012] Unless the context clearly dictates otherwise, the singular forms "a," "an," and "the" Contains multiple demonstratives.

[0013] The term "about" means "approximately" (e.g., approximately plus or minus a stated value). 10%).

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

[0015] Through proteomic and biochemical studies, TEAD transcription factors have been identified as evolutionarily conserved. It has been confirmed that TEADs are palmitoylated at the cysteine ​​residues in the nucleoside analogs. At high concentrations of palmitoyl-CoA, PAT-independent autopalmitoylation can be achieved. The crystal structure of lipid-bound TEAD reveals a novel ligand-binding site in TEAD. Furthermore, autopalmitoylation revealed the role of TE in vitro and in vivo. It plays an important role in regulating AD-YAP association and their physiological functions. Therefore, palmitoylation of TEADs is important in regulating the Hippo pathway transcription complex. Fulfill your role.

[0016] The discovery of a new ligand-binding site in TEAD may explain the mechanism of TEAD self-palmitoylation. Without being bound by any theory, the ligand is a binds to the phospholipid-binding pocket and mediates TEAD-YAP interaction, cancer cell proliferation, and migration Therefore, direct inhibition of TEAD autopalmitoylation activity is , are 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 the formula (D1), (D2), (D3), (D4), (D5), (D6), or ( D7), [ka] m is 1, 2, or 3; A 1But 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, 5~1 0-membered heteroaryl, 4- to 10-membered heterocycloalkyl, (C 1~3 Alkylene)-5~ 10-membered heteroaryl, or (C 1~3 (alkylene)-4 to 10-membered heterocycloalkyl A 1 Form (C 1~3 alkylene)-C(O)R 1 Group (C 1~3 Archi The phenylene groups are unsubstituted or each independently selected from halogen, OR a1 , N.R. c1 R d 1 , N.R. a1 (CO)(C 1~6 alkyl), and NR a1 (CO)O(CC 1~6 a and substituted by 1, 2, 3, 4, or 5 substituents selected from , 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 The 10-membered heterocycloalkyl is unsubstituted or independently selected from the group consisting of halogen, O, R 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 C(O) It is the basis, 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 1 A , OH, O.C. 1~6 Alkyl, OCy 1A , O(C 1~3 (Alkylenyl)Cy 1A , N H2, 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 Al Kill)(C 1~3 (Alkylenyl)Cy 1A and R 1 Form C 1~6 Each of the alkyl each is unsubstituted or each independently represents a 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 And, Cy 1A But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered heteroaromatic aryl, or 4- to 10-membered heterocycloalkyl; Cy 1A Form C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered hexaaryl Each tetracycloalkyl 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 Al Quinoline, 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 and substituted by one, two, or three substituents selected from C 1~6 and 0, 1, 2, 3, 4, or 5 substituents selected from alkyl. has been replaced by Each Cy 1B But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered hetero aryl, or 4- to 10-membered heterocycloalkyl; Cy 1B Form C 6~1 0 aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered Each heterocycloalkyl is unsubstituted or 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 , 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 Selected from C substituted by 1, 2, or 3 substituents 1~6 Selected from alkyl is substituted by 1, 2, 3, 4, or 5 substituents selected from the group consisting of 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 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 , or each independently, halogen, C 1~6 Hello Lukil, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, if C substituted with at least three substituents 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) c1 R d1 , or each independently a halogen, C 1~6 Hello Aruki Le, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Select from 1, 2, or C substituted by 3 substituents 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, ORa1 , 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 Hello Lukil, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, if C substituted with at least three substituents 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 Hello Lukil, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, if C substituted with at least three substituents 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)2NR 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 Alkireni 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 7 A , 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 C1 substituted by 1, 2, or 3 substituents selected from ~6 is alkyl, R 7 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 , S(O)NR c1 R d1 , C(O)NR c1 R d1 , Cy 7A ,OCy 7 A , 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 halo Gen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Choose from C substituted with 1, 2, or 3 substituents selected from 1~6 It is an alkyl , Cy 7A But C6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered heteroaromatic aryl, or 4- to 10-membered heterocycloalkyl; Cy 7A Form C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered hexaaryl Each tetracycloalkyl is unsubstituted or is a Cy 7B ,OCy 7B , NHCy 7B , and C(O)NHCy 7B 0, 1, or 2 substituents selected from and 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 Halo Alkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, C substituted by one or three substituents 1~6 0, 1, 2 selected from alkyl , 3, 4, or 5 substituents; Each Cy 7B But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered hetero aryl, or 4- to 10-membered heterocycloalkyl; Cy 7B Form C 6~1 0 aryl, C3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered Each 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 substituted by 1, 2, or 3 substituents selected from C 1~6 alkyl is replaced by 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. a 1 , 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 8 A )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(C1 ~6 Alkyl)Cy 8A , C(O)N(C 1~6 Alkyl)(C 1~3 Alkylenyl)C y 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 alkyl, Cy 8A But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered heteroaromatic aryl, or 4- to 10-membered heterocycloalkyl; Cy 8A Form C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered hexaaryl Each tetracycloalkyl is unsubstituted or is a Cy 8B ,OCy 8B , NHCy 8B , and C(O)NHCy 8B 0, 1, or 2 substituents selected from and 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 Halo Alkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, C substituted by one or three substituents 1~6 0, 1, 2 selected from alkyl , 3, 4, or 5 substituents; Each Cy 8B But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered hetero aryl, or 4- to 10-membered heterocycloalkyl; Cy 8B Form C 6~1 0 aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered Each 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 , line each independently represents a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and NR 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; And, 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. c 1 C(O)R b1 , C(O)OR a1 , C(O)NR c1 R d1 , or each independently: Halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 mosquito C substituted by 1, 2, or 3 substituents selected from 1~6 With alkyl can be, R 10 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 , or each independently a halogen, C 1~6 Halo Alkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, C substituted by one or three substituents 1~6 is alkyl, Cy D71 But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-14 membered hetero aryl, or 4- to 10-membered heterocycloalkyl; Cy D71 Form C 6~ 10 Aryl, C 3~15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 Each membered heterocycloalkyl is unsubstituted or D72 , CH2Cy D7 2 ,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, 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 Hello Lukil, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R. c1 R d1 Choose from C substituted by 1, 2, or 3 substituents 1~6 Alkyl or C 2~6 by 0, 1, 2, 3, 4, or 5 substituents selected from alkenyl It has been replaced, Each Cy D72 But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered heptane aryl, or 4- to 10-membered heterocycloalkyl; Cy D72 Forming C6 ~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 1 Each of the 0-membered heterocycloalkyls is unsubstituted or each independently is an unsubstituted C ~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 Hello Aruki Le, CN, ORa1, SRa1, NR c1 R d1 , C(O)OR a1 , C(O)NR c1 R d1 and each independently, C6~10 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 One, two, or three of the following can be selected: C substituted by a substituent 1~6 1, 2, 3, 4, or 5 selected from alkyl is substituted by 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 1, 2, or 3 substitutions selected from is substituted with a group, 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, C1 ~6 Alkylamino-C 1~6 Alkylene, di(C 1~6 Alkyl)amino-C 1~6 a Lukiren, C 1~6 Alkoxy-C 1~6 Alkylene, C 6~10 Aryl, C 2~6 a Alkenyl, and C 2~6 alkynyl; or R c1 and R d1 But together with the nitrogen atom to which they are bonded, a 0-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 substituted with 1, 2, or 3 substituents selected from Although it forms a heterocyclic ring as shown 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 ) is the basis the law of nature, L 2 does not exist or L 1 is N(R N ) is a group of formula C(O) the law of nature, A D41 But, A D42 is NH or NC 1~6 If it is alkyl, CH, C(C1 ~6 alkyl), A D42 But, A D41 is NH or NC 1~6 When it is alkyl, it is CH2; A2 , 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 , N.H. Cy 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)O Cy 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 a (Alkylenyl)Cy 7A , C(O)N(C 1~6 Alkyl)Cy 7A , or C(O)N (C 1~6 Alkyl)(C1~3 (Alkylenyl)Cy 7A or R 8 But Cy 8A ,OCy 8A , O(C 1~3 (Alkylenyl)Cy 8A , C(O)O Cy 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 a (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 (provided that 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 compound represented by the formula (D1), (D2), (D3), (D4), (D5), (D6), or (D 7), [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, 5-10 4-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (C 1~3 Alkylene)-5~1 0-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 Alkire The hydroxyl 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 Archi and is substituted by 1, 2, 3, 4, or 5 substituents selected from TsuA 1 5- to 10-membered heteroaryl, 4- to 10-membered heterocycloalkyl, (C1 ~3 alkylene)-5 to 10-membered heteroaryl, or (C 1~3 Alkylene)-4~1 The 0-membered heterocycloalkyl is unsubstituted or independently selected from the group consisting of halogen, OR a 1 , S.R. a1 , C(O)OR a1 , N.R. c1 R d1 , and C(O)NR c1 R d1from substituted with 1, 2, 3, 4, or 5 selected substituents; 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 C(O) group and 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. 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 Archi (C 1~3 (Alkylenyl)Cy 1A and R 1 Form C 1~6 Each of the alkyl are unsubstituted or each independently a 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 the law of nature, Cy 1A But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered heteroaryl or 4- to 10-membered heterocycloalkyl; Cy 1A Form C 6~10 a Lille, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heteroaryl Each of the cycloalkyls 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 Archi Ni, 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 ,oh Yo and NR c1 R d1 substituted by one, two, or three substituents selected from RuC 1~6 by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl It has been replaced, Each Cy 1B But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered heteroaromatic aryl, or 4- to 10-membered heterocycloalkyl; Cy 1B Form C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered hexaaryl Each tetracycloalkyl is unsubstituted or each independently an unsubstituted C 1~6 a Lukil, C2~6 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 Selected from C substituted by 1, 2, or 3 substituents 1~6 alkyl is substituted by 1, 2, 3, 4, or 5 substituents, 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 C1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, ha Rogen, 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 Haloal Kill, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1, 2, or C is substituted by three substituents 1~6 is alkyl, R 3 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, ha Rogen, 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 Haloal Kill, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1, 2, or C is substituted by three substituents 1~6 is alkyl, R 4 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, ha Rogen, C. 1~6 Haloalkyl, CN, ORa1 , 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 Haloal Kill, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1, 2, or C is substituted by three substituents 1~6 is alkyl, R 5 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, ha Rogen, 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 Haloal Kill, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1, 2, or C is substituted by three substituents 1~6 is alkyl, R 6 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, ha Rogen, C. 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O) OR a1 , C(O)NRc1 R d1 , or each independently a halogen, C 1~6 Haloal Kill, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1, 2, or C is substituted by three substituents 1~6 is alkyl, R 7 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, ha Rogen, 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 , N.H. Cy 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 Alkire Nil)Cy 7A , C(O)NHCy 7A , C(O)NH(C 1~3 (Alkylenyl)Cy 7 A , C(O)N(C 1~6 Alkyl)Cy 7A , C(O)N(C1~6 Alkyl)(C1 ~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 1, 2, or 3 selected from C is substituted by the substituent 1~6 is alkyl, Cy 7A But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered heteroaryl or 4- to 10-membered heterocycloalkyl; Cy 7A Form C 6~10 a Lille, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heteroaryl Each of the cycloalkyls is unsubstituted or 7B ,OCy 7B , NHCy 7 B , and C(O)NHCy 7B 0, 1, or 2 substituents selected from 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 Hello Lukil, CN, OR a1 , S.R. a1 , and N.R. c1 R d1Selected from 1, 2, if C substituted with at least three substituents 1~6 0, 1, 2 selected from alkyl, substituted with 3, 4, or 5 substituents; Each Cy 7B But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered heteroaromatic aryl, or 4- to 10-membered heterocycloalkyl; Cy 7B Form C 6~10 Aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered hexaaryl Each tetracycloalkyl is unsubstituted or each independently an unsubstituted C 1~6 a Lukil, 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 Standing, 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 a 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, ha Rogen, C. 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1R d1 , C(O) OR a1 , C(O)NR c1 R d1 , Cy 8A , OH, OCy 8A , O(C 1~3 Archi Renil)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(C1 ~6 Alkyl)Cy 8A , N(C(O)C 1~6 Alkyl)Cy 8A , SO2NHCy 8 A , 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 Haloal Kill, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1, 2, or C is substituted by three substituents 1~6 is alkyl, Cy 8A But C 6~10Aryl, C 3~15 Cycloalkyl, 5-10 membered heteroaryl or 4- to 10-membered heterocycloalkyl; Cy 8A Form C 6~10 a Lille, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heteroaryl Each of the cycloalkyls is unsubstituted or 8B ,OCy 8B , NHCy 8 B , and C(O)NHCy 8B 0, 1, or 2 substituents selected from 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 Hello Lukil, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, if C substituted with at least three substituents 1~6 0, 1, 2 selected from alkyl, substituted with 3, 4, or 5 substituents; Each Cy 8B But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered heteroaromatic aryl, or 4- to 10-membered heterocycloalkyl; Cy 8B Form C 6~10 Aryl, C3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered hexaaryl Each tetracycloalkyl is unsubstituted or each independently an unsubstituted C 1~6 a Lukil, 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 C1 substituted by 1, 2, or 3 substituents selected from ~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkyl And, R 9 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, ha Rogen, 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 Haloal Kill, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1, 2, or C is substituted by three substituents 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 Hello Lukil, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, if C substituted with at least three substituents 1~6 is alkyl, Cy D71 But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-14 membered heteroaromatic aryl, or 4- to 10-membered heterocycloalkyl; Cy D71 Form C 6~1 0 aryl, C 3~15 cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered Each heterocycloalkyl is unsubstituted or 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)N HCy D72 and 0, 1, or 2 substituents selected from substitution 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 , C(O)OR a1 , and N.R. c1 R d1 Selected from 1, 2, if C substituted with at least three substituents 1~6 Alkyl or C 2~6 Alkenyl and is substituted by 0, 1, 2, 3, 4, or 5 substituents selected from Each Cy D72 But C 6~10 Aryl, C 3~15 Cycloalkyl, 5-10 membered hetero aryl, or 4- to 10-membered heterocycloalkyl; Cy D72 Form C 6~ 10 Aryl, C 3~15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 each of the membered heterocycloalkyls is unsubstituted or each independently is an unsubstituted C 1~ 6 alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~15 Cycloalkyl, halo Rogen, C. 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O) ORa1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Hello Lukil, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R. c1 R d1 Choose from C substituted by 1, 2, or 3 substituents 1~6 Select from alkyl and is substituted by 1, 2, 3, 4, or 5 substituents, R a1 , R b1 , R c1 , and R d1 However, independently, H, C 1~6 Alkyl, H O.C. 1~6 Alkylene, C 1~6 Alkoxy-C 1~6 Alkylene, C 6~10 Ally Lu, C 2~6 Alkenyl, and C 2~6 alkynyl; or R c1 and R d1 But together with the nitrogen atom to which they are bonded, forming a 1-membered unsubstituted heterocycloalkyl ring), or a pharmaceutically acceptable salt thereof provide. 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 ) is the basis , 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 ,OCy 1A , O(C 1~3 (Alkylenyl)Cy 1A , N.H.C. y 1A , NH(C 1~3 (Alkylenyl)Cy 1A , N(C 1~6 Alkyl)Cy 1A ,too Or N(C 1~6 Alkyl)(C 1~3 (Alkylenyl)Cy 1A or R 7 Cy 7A ,OCy 7A , O(C 1~3 (Alkylenyl)Cy 7A , C(O)OC y 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 Al Cylenil)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 ,OCy 8A , O(C 1~3 (Alkylenyl)Cy 8A , C(O)OC y 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 Al Cylenil)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 (provided that 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, A1 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 The alkylene group is unsubstituted or, each independently, 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 is substituted with 0, 1, 2, 3, 4, or 5 substituents selected from the group consisting of methyl, ...

[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 1~6 alkyl), e.g., CH2CH(NH2)C(O)OH do.

[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 d 1 substituted by 0, 1, 2, 3, 4, or 5 substituents selected from 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 heterocyclo It is alkyl.

[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 d 1 substituted by 1, 2, 3, 4, or 5 substituents selected from 10-membered heteroaryl, 4-10-membered heterocycloalkyl, CH2(5-10-membered heteroaryl) aryl), or CH2(4- to 10-membered heterocycloalkyl).

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

[0040] In some embodiments, R 2 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 Hello Aruki It is.

[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, A5 is N.

[0053] In some embodiments, A 2 is CR 2 and A 3 is CR 3 and A 4 is C R 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 C R 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 (e.g., phenyl) be.

[0084] In some embodiments, Cy D71 is C 3~15 Cycloalkyl (e.g., cyclo propyl).

[0085] In some embodiments, Cy D71 is a 5- to 10-membered heteroaryl (e.g., triaryl) azoles, pyridines, dihydropyrido[2,1-b]pyrimidin-2-ones, 3,4-dihydropyridin-2-ones, benzo[d]isothiazole-1,1-dioxide, 2H-isothiazole Indazole, pyrazole, dioxolane, pyrrole, indole, imidazole, benz imidazole).

[0086] In some embodiments, Cy D71 is a 4- to 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 Shik The 5- to 10-membered heteroalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is a non- It is a substitution.

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

[0089] In some embodiments, Cy D71 Form C 6~10 Aryl, C 3~15 Shik The 5- to 10-membered heteroalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is Independently, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halo Gen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , C(O)O R a1 , C(O)NR c1 R d1 and each independently a halogen, C 1~6 Haloal Kill, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R. c1 R d1 Selected from C substituted by 1, 2, or 3 substituents 1~6 Alkyl or C 2~6 substituted by 1, 2, 3, 4, or 5 substituents selected from alkenyl; It is being done.

[0090] In some embodiments, Cy D71 Form C 6~10 Aryl, C 3~15 Shik C cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl y 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)C y D72 , and C(O)NHCy D72 and 0, 1, or 2 substituents selected from So it is replaced.

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

[0092] In some embodiments, Cy D72 is C 3~15 Cycloalkyl (e.g., cyclo propyl).

[0093] In some embodiments, Cy D72is a 5- to 10-membered heteroaryl (e.g., triaryl) azoles, pyridines, dihydropyrido[2,1-b]pyrimidin-2-ones, 3,4-dihydropyridin-2-ones, benzo[d]isothiazole-1,1-dioxide, 2H-isothiazole Indazole, pyrazole, dioxolane, pyrrole, indole, imidazole, benz imidazole).

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

[0095] In some embodiments, Cy D72 Form C 6~10 Aryl, C 3~15 Shik The 5- to 10-membered heteroalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl is a non- It is a substitution.

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

[0097] In some embodiments, Cy D72 Form C 6~10 Aryl, C 3~15 Shik C cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heterocycloalkyl 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~15 cycloalkyl , 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 and each independently a halogen, C 1~6 Ha Roalkyl, CN, OR a1 , S.R. a1 , C(O)OR a1 , and N.R. c1 R d1 from C substituted with one, two, or three selected substituents 1~6 From alkyl It is substituted with 0, 1, or 2 selected substituents.

[0098] In some embodiments, R 1 is H, C 1~6 Alkyl, C 2~6 Alkenyl, C2 ~6 Alkynyl, Cy 1A , OH, O.C. 1~6 Alkyl, OCy 1A , O(C 1~3 Al Cylenil)Cy 1A , NH2, NHC 1~6 Alkyl, N(C 1~6 alkyl)2, NH Cy 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 )Cy1A , NHCy 1A , NH(C 1~3 (Alkylenyl)Cy 1A , N(C 1~6 Al Kill)Cy 1A , or N(C 1~6 Alkyl)(C 1~3 (Alkylenyl)Cy 1A Yes do.

[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 a Lukenil, C 2~6 Alkynyl, Cy 1A , OH, or OC 1~6 Alkyl (e.g., 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 Selected from C substituted with 1, 2, or 3 substituents 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 , or 0, 1, or 2 Cy 1B and each independently an unsubstituted C 1~6 Al Kill, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, C N, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Ha Roalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, or C substituted by three substituents 1~6 0, 1, selected from alkyl It is a phenyl substituted with 2, 3, 4, or 5 substituents.

[0106] In some embodiments, Cy 1A is C 6~10 Aryl, e.g., unsubstituted or , or one Cy 1B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 a Lukenil, C 2~6Alkynyl, 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 1, 2, or 3 positions selected from C substituted by a substituent 1~6 alkyl selected from 0, 1, 2, 3, 4, if Preferably, the phenyl is substituted with five substituents.

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

[0108] In some embodiments, each Cy 1B are unsubstituted or, each independently, unsubstituted. exchange C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Ha Roalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently halo Gen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Choose from C substituted with 1, 2, or 3 substituents selected from 1~6 Select from alkyl C is substituted by 1, 2, 3, 4, or 5 substituents selected from3~15 S Chloroalkyl (e.g., C 3~10 Cycloalkyl, for example, adamantyl, for example, a damant-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) be.

[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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1, and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R.a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R.a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1Ais 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 , SR a1 , and N.R. c1 R d1 by one, two, or three substituents selected from Substituted C 1~6 0, 1, 2, 3, 4, or 5 substituents selected from alkyl C, substituted by a substituent 3~15 Cycloalkyl (e.g., C 3~10 Cycloa alkyl, for example, adamantyl, for example, adamant-1-yl). In this embodiment, Cy 1A are unsubstituted or, each independently, an unsubstituted C 1~6 Archi Lu, 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 Ha Roalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, or C substituted by three substituents 1~6 1, 2, selected from alkyl C substituted with 3, 4, or 5 substituents 3~15 Cycloalkyl (e.g. For example, C 3~10 Cycloalkyl, for example, adamantyl, for example, adamant-1-yl In some embodiments, Cy 1A is the unsubstituted C 3~15 Cycloalkyl( For example, C 3~10 Cycloalkyl, for example, adamantyl, for example, adamant-1- In some embodiments, Cy 1A is adamantyl, e.g., unsubstituted 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 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 mosquito C substituted by 1, 2, or 3 substituents selected from 1~6 With alkyl can be, R 8 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 ,or each independently a halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N R c1 R d1 C1 substituted by 1, 2, or 3 substituents selected from ~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 , N.H. Cy 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 7 A , 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(C 1~6 Al Kill)Cy 7A , or N(C 1~6 Alkyl)(C 1~3 (Alkylenyl)Cy 7A Yes do.

[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 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 7 B , OH, OCy 7B , O(C 1~3 (Alkylenyl)Cy7B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 7 B , OH, OCy 7B , O(C 1~3 (Alkylenyl)Cy7B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 , or 0, 1, or 2 Cy7B and each independently an unsubstituted C 1~6 Al Kill, C 2~6 Alkenyl, C 2~6 Alkynyl, halogen, C 1~6 Haloalkyl, C N, OR a1 , S.R. a1 , N.R. c1 R d1 and each independently a halogen, C 1~6 Ha Roalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, or C substituted by three substituents 1~6 0, 1, selected from alkyl It is a phenyl substituted with 2, 3, 4, or 5 substituents.

[0131] In some embodiments, Cy 7A is C 6~10 Aryl, e.g., unsubstituted or , or one Cy 7B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 a Lukenil, 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 1, 2, or 3 positions selected from C substituted by a substituent 1~6 alkyl selected from 0, 1, 2, 3, 4, if Preferably, the phenyl is substituted with five substituents.

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

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

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

[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 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, ORa1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 , Cy8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 B , 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 halogen, C1 ~6Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 Rd1 , Cy 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 7A is 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 , SR a1 , and N.R. c1 R d1 by one, two, or three substituents selected from Substituted C 1~6 0, 1, 2, 3, 4, or 5 substituents selected from alkyl C, substituted by a substituent 3~15 Cycloalkyl (e.g., C 3~10 Cycloa alkyl, for example, adamantyl, for example, adamant-1-yl). In this embodiment, Cy 7A are unsubstituted or, each independently, an unsubstituted C 1~6 Archi Lu, 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 Ha Roalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, or C substituted by three substituents 1~6 01, 2 selected from alkyl , substituted by 3, 4, or 5 substituents, C 3~15 Cycloalkyl( For example, C 3~10 Cycloalkyl, for example, adamantyl, for example, adamant-1- In some embodiments, Cy 7A is the unsubstituted C 3~15 cycloalkyl (For example, C 3~10 Cycloalkyl, for example, adamantyl, for example, adamant-1 In some embodiments, Cy 7Ais an 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 C1 substituted by 1, 2, or 3 substituents selected from ~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 C1 substituted by 1, 2, or 3 substituents selected from ~6 It is alkyl.

[0139] In some embodiments, A 1 is CR 1 and A 2 is CR 2 and A 3 is C R 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 C R 4 and A 5 is N and A 6 is CR 6 and A 8 is CR 8 and A 9 teeth , C.R. 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 8Cy 8A ,OCy 8A , O(C 1~3 Alkylenyl )Cy 8A , C(O)OCy 8A , C(O)O(C 1~3 (Alkylenyl)Cy 8A , N.H. Cy 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 8 A , or C(O)N(C 1~6 Alkyl)(C 1~3 (Alkylenyl)Cy 8A is.

[0145] In some embodiments, R 8 Cy 8A ,OCy 8A , O(C 1~3 Alkylenyl )Cy 8A , NHCy 8A , NH(C 1~3 (Alkylenyl)Cy 8A , N(C 1~6 Al Kill)Cy 8A , or N(C 1~6 Alkyl)(C 1~3 (Alkylenyl)Cy 8A Yes do.

[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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 1~6 is alkyl, R 83 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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 1~6 It is alkyl.

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

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

[0154] In some embodiments, Cy 8A is C 6~10 Aryl, e.g., unsubstituted or , or one Cy 8B and each independently an unsubstituted C 1~6 Alkyl, C 2~6 a Lukenil, 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 1, 2, or 3 positions selected from C substituted by a substituent 1~6 alkyl selected from 0, 1, 2, 3, 4, if Preferably, the phenyl is substituted with five substituents.

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

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

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

[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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 1~6 is alkyl, R 82 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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 A , 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(C1~ 6 alkyl)(C 1~3 (Alkylenyl)Cy 8A or each independently halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 1~6 is alkyl, R 85 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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 1~6 is alkyl, R 88 H, unsubstituted C 1~6 Alkyl, C 2~6Alkenyl, C 2~6 Alkynyl, Halogen, C 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , Cy 8 A , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 , SR a1 , and N.R. c1 R d1 by one, two, or three substituents selected from Substituted C 1~6 0, 1, 2, 3, 4, or 5 substituents selected from alkyl C, substituted by a substituent 3~15 Cycloalkyl (e.g., C 3~10 Cycloa alkyl, for example, adamantyl, for example, adamant-1-yl). In this embodiment, Cy 8A are unsubstituted or, each independently, an unsubstituted C 1~6 Archi Lu, 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 Ha Roalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 Selected from 1, 2, or C substituted by three substituents 1~6 01, 2 selected from alkyl , substituted by 3, 4, or 5 substituents, C 3~15 Cycloalkyl( For example, C 3~10 Cycloalkyl, for example, adamantyl, for example, adamant-1- In some embodiments, Cy 8A is the unsubstituted C 3~15cycloalkyl (For example, C 3~10 Cycloalkyl, for example, adamantyl, for example, adamant-1 In some embodiments, Cy 8A is an adamantyl, e.g., unsubstituted or substituted adamant-1-yl. In some embodiments, , Cy 8A is 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, ha Rogen, C. 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , or each Independently, 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 alkyl, R 7 H, unsubstituted C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, ha Rogen, C. 1~6 Haloalkyl, CN, OR a1 , S.R. a1 , N.R. c1 R d1 , or each Independently, 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 alkyl.

[0162] In some embodiments, A 1 is CR 1 and A 2 is CR 2 and A 3 is C R 3 and A 4 is CR 4 and A 5 is CR 5 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 1 0 is.

[0163] In some embodiments, A 1 is CR 1 and A 3 is CR 3 and A 4 is C R 4 and A 5 is N and A 6 is CR 6 and A 7 is CR 7 and A 8 teeth , C.R. 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 Hello Aruki It is.

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

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

[0169] In some embodiments, A 9 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 has one of the following formulas (I-1) to (I-60): is a compound of [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 , A1 0 , Cy 1A , Cy 1B , Cy 7A , Cy 7B , Cy 8A , Cy 8B , L 1 , and L 2 is a compound of formula (I) or As defined above with respect to any of the 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 , Cy1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 Rd1 , Cy 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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. c1R d1 , Cy 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 1 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 1~6 is alkyl, 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 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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. c1R d1 , Cy 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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. c1R d1 , Cy 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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. c1R d1 , Cy 7 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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. c1R d1 , Cy 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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. c1R d1 , Cy 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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 8 B , 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 halogen, C1 ~6 Haloalkyl, CN, OR a1 , S.R. a1 , and N.R. c1 R d1 1 to be selected , 2, or 3 substituted C 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, each independently, H, C 1~6 Alkyl, HO-C 1~6 Alkylene, C 1~6 Alkoxy-C 1~6 Al Killen, C. 6~10 Aryl, C 2~6 Alkenyl, and C 2~6 Select from alkynyl will be done.

[0180] In some embodiments, the compound is one of the following formulas, or a pharmaceutical formulation thereof: It is a commercially acceptable salt. [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0181] In some embodiments, the compound is one of the following formulas, or a pharmaceutical formulation thereof: It is a commercially acceptable salt. [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

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

[0183] Certain features of the invention are described, for clarity, in the context of separate embodiments. It is further understood that may also be provided in combination in a single embodiment. (Note that these embodiments may be combined as described in multiple dependent forms.) Conversely, the present invention, which is described in the context of a single embodiment for the sake of brevity, The various features of the invention may be provided separately or in any suitable subcombination. Therefore, the features described as embodiments of compounds of formula (I) can be combined in any suitable combination. It is contemplated that the compounds may be combined in any combination.

[0184] At various places in the present specification, certain features of compounds are disclosed in groups or ranges. Such disclosure also encompasses each and every member of such groups and ranges, and each individual portion thereof. It is specifically intended to include subcombinations. For example, "C 1~6 "Alkyl" The term includes methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl, and C6 alkyl. It is specifically intended to disclose kills individually (without limitation).

[0185] The term "n-membered," where N is an integer, typically refers to a moiety where n is the number of ring-forming atoms. For example, piperidinyl is a 6-membered heterocycloalkyl. pyrazolyl is an example of a 5-membered heteroaryl ring, and pyridyl is an example of a 6-membered heteroaryl ring. An example of a 10-membered cycloaryl ring is 1,2,3,4-tetrahydro-naphthalene. Examples of alkyl groups include: carbocyclic rings (e.g., aryl or cycloalkyl); When the term is used to refer to a heterocycle, all of the ring atoms are carbon atoms. When used to refer to a heterocyclic ring (e.g., heteroaryl or heterocycloalkyl), In this case, one or more of the ring atoms (e.g., 1, 2, 3, or 4) may be a heteroatom (e.g., , nitrogen, oxygen, or sulfur), and the remainder (e.g., n-1, n-2, n-3, or n -4) is a carbon atom.

[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 each of the forms individually. When a Markush variable is required, the Markush variable listed in the group is understood to be a linking group. For example, if a structure requires a linking group and the Markush group definition for that variable includes "Alkyl" Where "alkyl" or "aryl" is listed, "alkyl" or "aryl" Each is understood to represent a linking alkylene or arylene group.

[0187] The term "substituted" refers to an atom or group of atoms that is a "substituent" attached to another group. The term "substituted" means to formally replace hydrogen unless otherwise indicated. Unless otherwise specified, any level of substitution where such substitution is permitted, e.g., mono-, di-, tri- The substituents are independently selected and the substitutions are chemically Substitution at a given atom is limited by valence. It is to be understood that the term "optionally substituted" refers to either unsubstituted or The term "substituted" means that a hydrogen atom has been removed and replaced. A single divalent substituent, e.g., oxo, means that it is replaced by two One hydrogen atom can be replaced.

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

[0189] The term "alkyl" used alone or in combination with other terms means a straight-chain or refers to a saturated hydrocarbon group which may be branched. n~m The term "alkyl" refers to n to m An alkyl group formally refers to an alkyl group having 1 to 10 carbon atoms attached to the rest of the compound. It corresponds to an alkane with one C-H bond replaced by the point of attachment of the alkyl group. In some embodiments, an alkyl group has 1 to 6 carbon atoms, 1 to 4 carbon atoms, 1 Contains up to 3 carbon atoms, or 1 to 2 carbon atoms. Examples of alkyl moieties include methyl ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl Chemical groups such as sec-butyl; 2-methyl-1-butyl, n-pentyl, 3-pentyl Higher homologues such as propyl, n-hexyl, and 1,2,2-trimethylpropyl are also included. Not limited to:

[0190] The term "alkenyl" used alone or in combination with other terms, means one or more refers to a straight-chain or branched hydrocarbon group corresponding to the alkyl group with a double carbon-carbon bond above An alkenyl group is formally defined as a group in which one C-H bond is the attachment of the alkenyl group to the rest of the compound. It corresponds to an alkene replaced by a dot. n~m The term "alkenyl" It refers to an alkenyl group having n to m carbon atoms. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. Examples of alkenyl groups include: , ethenyl, n-propenyl, isopropenyl, n-butenyl, sec-butenyl, etc. Examples include, but are not limited to:

[0191] The term "alkynyl" used alone or in combination with other terms, means one or more refers to a straight-chain or branched hydrocarbon group corresponding to the alkyl group with a triple carbon-carbon bond above The alkynyl group is formally replaced by the point of attachment of the alkyl group to the remainder of the compound. It corresponds to an alkyne with one C—H bond. n~m The term "alkynyl" refers to an alkynyl group having n to m carbon atoms. Examples of alkynyl groups include ethynyl , propyn-1-yl, propyn-2-yl, and the like. In some embodiments, the alkynyl moiety has 2 to 6, 2 to 4, or 2 to 3 carbon atoms. Contains elementary atoms.

[0192] The term "alkylene" used alone or in combination with other terms means a divalent Refers to an alkyl linking group. An alkylene group is formally defined as the attachment of an alkylene group to the remainder of a compound. It corresponds to an alkane with two C-H bonds replaced by an alkane bond. n~m The term "alkylene" refers to an alkylene group having n to m carbon atoms. Examples of aryl groups include ethane-1,2-diyl, propane-1,3-diyl, and propane-1,3-diyl. ,2-diyl, butane-1,4-diyl, butane-1,3-diyl, butane-1,2-diyl yl, 2-methyl-propane-1,3-diyl, and the like. .

[0193] The term "alkoxy" used alone or in combination with other terms means a group of the formula -O "C" refers to the group -alkyl, where alkyl is as defined above. n~m Alcoki The term "alkoxy" refers to an alkoxy group in which the alkyl group has n to m carbon atoms. Suitable alkoxy groups include methoxy, ethoxy, propoxy (e.g., n-propoxy) and the like. 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 use of "halo" or "halogen" when used alone or in combination with other terms The term refers to fluoro, chloro, bromo, and iodo.

[0195] The term "haloalkyl" refers to a group in which one or more of the hydrogen atoms is replaced by a halogen atom. "C" refers to the alkyl group that has been replaced. n~m The term "haloalkyl" refers to n to m alkyl groups. and at least 1 to a maximum of {2(n~m)+1} halogen atoms C n~m The alkyl groups may be the same or different. In some embodiments, the halogen atom is a fluoro atom. The haloalkyl group has 1 to 6 or 1 to 4 carbon atoms. Examples of haloalkyl groups include C Examples include F3, C2F5, CHF2, CCl3, CHCl2, and C2Cl5. In some embodiments, the haloalkyl group is a fluoroalkyl group.

[0196] The term "haloalkoxy", used alone or in combination with other terms, means a group of the formula "C" refers to the group -O-haloalkyl, where haloalkyl is as defined above. n ~m The term "haloalkoxy" refers to a haloalkoxy group whose haloalkyl group has n to m carbon atoms. An example of a haloalkoxy group is trifluoromethoxy. In some embodiments, the haloalkoxy group is 1 to 6, 1 to 4, or 1 to 6. It has 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" used alone or in combination with other terms means C(O ) refers to the C(=O)- group.

[0200] The term "carbonyl" used alone or in combination with other terms means -C( =O)- group.

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

[0202] The term "oxo" refers to a group that forms a carbonyl group or a sulfoxide or As a divalent substituent attached to a heteroatom forming a sulfone group or an N-oxide group refers to the oxygen in

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

[0204] The term "aryl" used alone or in combination with other terms means a monocyclic or or polycyclic (e.g., having 2, 3, or 4 fused rings) It refers to the group "C n~m The term "aryl" refers to an aryl having n to m ring carbon atoms. Aryl groups include, for example, phenyl, naphthyl, indenyl, etc. In some embodiments, the aryl group has 6 to 10 carbon atoms. In the above formula, the aryl group is phenyl.

[0205] The term "arylalkylenyl" used alone or in combination with other terms is an aryl group, as defined herein, attached to an alkylene group, as defined herein. It refers to "C n~m Aryl C o~p The term "alkylenyl" refers to a group of o to p carbon atoms. an aryl group having n to m ring carbon atoms attached to an alkylene group having The arylalkylenyl group refers to, for example, benzyl, phenethyl, etc. etc.

[0206] The terms "heteroaryl" or "heteroaromatic" used alone or in combination with other terms The term "aromatic" refers to a group containing at least one heteroatom selected from sulfur, oxygen, and nitrogen. In some embodiments, heterocyclic aromatic rings are monocyclic or polycyclic aromatic heterocycles having 1 or 2 ring members. In some embodiments, the heteroaryl is a 5- or 6-membered monocyclic heteroaryl ring. Heteroaryl is monocyclic or bicyclic and independently contains nitrogen, sulfur, and oxygen. 5-10 membered C having 1, 2, 3, or 4 heteroatom ring members selected from 1~ 9 heteroaryl. In some embodiments, any of the heteroaryl moieties A ring-forming N can be an N-oxide. In some embodiments, a heteroaryl is a carbon-containing heteroaryl. 5 to 10 ring atoms, including an atom, and independently selected from nitrogen, sulfur, and oxygen In some embodiments, the heteroatom ring members are 1, 2, 3, or 4. The heteroaryl is independently selected from 5 to 6 ring atoms and nitrogen, sulfur, and oxygen. In some embodiments, the heteroatom ring has 1, 2, 3, or 4 heteroatom ring members selected from the group consisting of: Heteroaryl is a heteroaryl consisting of 5 to 6 ring atoms and, independently, nitrogen, sulfur, and oxygen. In some embodiments, the heteroatom ring has one or two selected heteroatom ring members. The aryl is a 5- or 6-membered heteroaryl ring. Examples of heteroaryl groups include: , pyridine, pyrimidine, pyrazine, pyridazine, pyrrole, pyrazole, azolyl, o Xazole, thiazole, imidazole, furan, thiophene, quinoline, isoquinoline , indole, benzothiophene, benzofuran, benzisoxazole, imidazo[1 ,2-b]thiazoles, imidazo[1,2-b]pyridazines, purines, furopyridines (e.g. furo[3,2-b]pyridine), thienopyridine (e.g., thieno[3,2-b] pyridine), and the like, but are not limited to these.

[0207] A 5-membered heteroaryl ring is a heteroaryl group having 5 ring atoms, and one or more ( For example, 1, 2, 3, or 4) of the ring atoms are independently selected from N, O, and S. Exemplary 5-membered heteroaryls include thienyl, furyl, pyrrolyl, imidazoline, and the like. aryl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, isoxazolyl, 1 ,2,3-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-o 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 is an example.

[0208] A 6-membered heteroaryl ring is a heteroaryl group having 6 ring atoms, and one or more ( For example, 1, 2, or 3) of the ring atoms are independently selected from N, O, and S. Exemplary 6-membered heteroaryls include pyridyl, pyrazinyl, pyrimidinyl, trimethylsilyl, and the like. azinyl, and pyridazinyl.

[0209] The term "heteroarylalkylenyl" used alone or in combination with other terms The term refers to a heterocyclic group, as defined herein, attached to an alkylene group, as defined herein. n- to m-membered heteroaryl group. o~p The term "alkylenyl" Heteroaryl groups having nm to m ring atoms attached to alkylene groups having o to p carbon atoms Heteroarylalkylenyl groups include, for example, pyridylmethyl, pyridyl Includes ethyl, etc.

[0210] The term "cycloalkyl," used alone or in combination with other terms, means a ring non-aromatic, saturated, monocyclic, bicyclic, or polycyclic, including substituted alkyl and alkenyl groups Refers to a hydrocarbon ring system. n~m The term "cycloalkyl" refers to a ring of n to m carbon atoms. The cycloalkyl group may be monocyclic or polycyclic (e.g., Cycloalkyl groups may include groups having 2, 3, or 4 fused rings and spirocyclic rings. may 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 ) may have some In this embodiment, 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 the form, the cycloalkyl group is C 3~6 It is a monocyclic cycloalkyl group. The ring-forming carbon atoms of the cycloalkyl group may be optionally substituted by oxo or sulfido. Examples of cycloalkyl groups include cycloalkylidene. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexyl Cyclohexenyl, cyclohexadienyl, norbornyl, norpinyl, bicyclo[2.1 Examples include bicyclo[1.1.1]hexanyl, bicyclo[1.1.1]pentanyl, and adamantyl. In some embodiments, cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, The definition of cycloalkyl is cycloalkyl, cyclopentyl, cyclohexyl, or cyclohexyl. one or more aromatic rings fused to (i.e., sharing a bond with) the cycloalkyl ring Ring-containing moieties, such as benzo or thienyl derivatives of cyclopentane, cyclohexane, etc. Also included are derivatives such as indanyl or tetrahydronaphthyl. The cycloalkyl group may be attached through any ring-forming atom, including ring-forming atoms of a fused aromatic ring. obtain.

[0211] The term "arylalkylenyl" used alone or in combination with other terms represents a cycloalkyl group, as defined herein, attached to an alkylene group, as defined herein. Refers to the kill group. n~m Cycloalkyl C o~p The term "alkylenyl" means an alkylenyl group. A cycloalkyl group having n to m ring carbon atoms attached to an alkylene group having n to m carbon atoms. The cycloalkyl alkylenyl group refers to a cycloalkyl alkylenyl group having an alkyl group. , for example, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclo Includes hexylmethyl, etc.

[0212] The term "heterocycloalkyl" used alone or in combination with other terms may optionally contain one or more alkenylene groups as part of the ring structure, and independently having at least one heteroatom ring member selected from nitrogen, sulfur, oxygen, and phosphorus; a non-aromatic ring having 4 to 10 ring members, 4 to 7 ring members, or 4 to 6 ring members; Heterocycloalkyl refers to monocyclic 4-, 5-, 6-, and 7-membered heterocyclic ring systems. Heterocycloalkyl groups include monocyclic or bicyclic (e.g., In some embodiments, the ring system may include a ring system having two fused or bridged rings. wherein the heterocycloalkyl groups are independently selected from nitrogen, sulfur, and oxygen; It is a monocyclic group having 2 or 3 heteroatoms. Examples of heterocycloalkyl groups are: Examples include azetidine, pyrrolidine, piperidine, piperazine, morpholine, and thiomorpholine. , pyran, azepane, tetrahydropyran, tetrahydrofuran, dihydropyran, dihydrofuran Ring-forming carbon atoms and heteroatoms of heterocycloalkyl groups is optionally oxo or sulfide (e.g., C(=O), S(=O), C(S), or S(=O)2, etc.), or the nitrogen atom may be quaternized. A heterocycloalkyl group can be attached via a ring-forming carbon atom or a ring-forming heteroatom. In some embodiments, the heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, the heterocycloalkyl group contains 0 to 2 double bonds. The definition of heterocycloalkyl also includes fused (i.e., Moieties having one or more aromatic rings (i.e., having a common bond with a cycloalkyl ring), e.g. Examples include benzo or thienyl derivatives of piperidine, morpholine, azepine, etc. A heterocycloalkyl group containing fused aromatic rings is a heterocyclic group containing any of the ring-forming atoms of the fused aromatic rings. Examples of heterocycloalkyl groups include 1,2,3 ,4-Tetrahydroquinoline, dihydrobenzofuran, azetidine, azepane, diazepam (e.g., 1,4-diazepane), pyrrolidine, piperidine, piperazine, morpholine , thiomorpholine, pyran, tetrahydrofuran, and di- and tetra-hydropyrans Examples include:

[0213] When used alone or in combination with other terms, "heterocycloalkylalkylenyl" refers to " refers to a group, as defined herein, attached to an alkylene group, as defined herein. "n- to m-membered heterocycloalkyl C" refers to a heterocycloalkyl group having n to m members. o~p Alkireni The term "alkyl" refers to an alkylene group having n to m ring atoms attached to an alkylene group having o to p carbon atoms. Heteroarylalkyl groups include, for example, tetrahydropyransyl groups. Contains trihydrofurylmethyl.

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

[0215] The compounds described herein can be asymmetric (e.g., have one or more stereocenters). Unless otherwise stated, all stereoisomers, including enantiomers and diastereoisomers, are Isomers are contemplated. Compounds of the invention that contain asymmetrically substituted carbon atoms may be present in optically active forms. It can be isolated in optically active form from optically inactive starting materials. Methods on how to prepare the forms include by resolution of the racemic mixture or stereoselective synthesis. In the compounds described herein, olefins, C= Many geometric isomers of N-double bonds can also exist, and all such stable isomers are Cis and trans geometric isomers of the compounds of the present invention are contemplated in the present invention. As described, they may be isolated as a mixture of isomers or as separated isomeric forms.

[0216] Resolution of racemic mixtures of compounds can be achieved by any of a number of methods known in the art. One method is to use a chiral compound that is an optically active salt-forming organic acid. Suitable resolving agents for fractional recrystallization include fractional recrystallization using distilled water, tartaric acid, distilled water, and the like. D- and L-forms of acetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, and lactic acid or various optically active camphor acids such as β-camphorsulfonic acid Other resolving agents suitable for fractional crystallization include α-methylbenzylamine. stereomerically pure forms (e.g., S and R forms, or diastereoisomerically pure forms) of (in various forms), 2-phenylglycinol, norephedrine, ephedrine, N-methyl Examples include phendrine, cyclohexylethylamine, and 1,2-diaminocyclohexane. can be.

[0217] Resolution of racemic mixtures can also be carried out using optically active resolving agents, such as dinitrobenzoylphenyl methyl ether. This can be carried out by elution onto a column packed with lysine. A suitable elution solvent composition is It can be determined by one skilled in the art.

[0218] In some embodiments, the compounds of the present invention have the (R) configuration. The compound has the (S) configuration. In compounds with two or more chiral centers, Unless otherwise noted, each chiral center in a compound is independently (R) or (S). Good too.

[0219] The compounds of the present invention also include tautomeric forms. Tautomeric forms are those which are substituted by a single bond and an adjacent bond. Tautomeric forms result from the exchange of a double bond with an alkyl group and the accompanying migration of a proton. The term "prototropic" refers to isomeric protonation states with identical empirical formulas and total charges. Examples of prototropic tautomers include ketone-enol pairs, Amide-imidic acid pairs, lactam-lactim pairs, enamine-imine pairs, and proton- cyclic forms which can occupy more than one position of the heterocyclic ring system, e.g., 1H- and 3H- Imidazole, 1H-, 2H-, and 4H-1,2,4-triazole, 1H- and 2H-isoindole, and 1H- and 2H-pyrazole. The forms can be in equilibrium or can be sterically locked into one form by appropriate substitution. do.

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

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

[0222] All compounds and their pharmaceutically acceptable salts may be present in aqueous solutions containing water and other substances such as solvents (e.g., It may be found in or isolated from other solid forms (e.g., hydrates and solvates). When the compound described herein and its salts are For example, the compound may be in the form of a solvate, including a hydrate. The compound may be in any form, such as a polymorph or solvate. The compounds and methods herein may be in the form of solid state compounds, unless otherwise specified. References to the compounds and salts thereof should be understood to encompass any solid state forms of the compounds. do.

[0223] In some embodiments, the compounds of the present invention or salts thereof are substantially isolated. "Qualitatively isolated" means that the compound is at least partially isolated from the environment in which it was formed or detected. Partial separation means that the compound of the present invention is partially or substantially separated. The substantial separation may include a composition enriched in the compound of the present invention, or a salt thereof. At least about 50% by weight, at least about 60% by weight, at least about 70% by weight, at least at least about 80% by weight, at least about 90% by weight, at least about 95% by weight, at least about 97% by weight % by weight, or at least about 99% by weight of the composition.

[0224] The phrase "pharmaceutically acceptable" means, within the scope of sound medical judgment, a substance that is not undue in toxicity, irritation, or toxicity. contact with human and animal tissues without any allergic reaction, or other problems or complications compounds, materials, and compositions that are suitable for use in combination with other The term "composition" is used herein to refer to a composition, and / or dosage form.

[0225] The expressions "ambient temperature" and "room temperature" are understood in the art and generally refer to temperatures at which a reaction may proceed. The reaction temperature is close to room temperature, for example, about 20°C to about 30°C. Refers to the degree.

[0226] The present invention also includes salts of the compounds described herein, particularly pharmaceutically acceptable salts. The term "pharmaceutically acceptable salt" refers to derivatives of the disclosed compounds, wherein the parent compound is , modified by converting an existing acid or base moiety into its salt form. Examples of acceptable salts include mineral or organic acid salts of basic residues such as amines, carbohydrates, and the like. Examples of suitable salts include, but are not limited to, alkali or organic salts of acidic residues such as carboxylic acids. The pharmaceutically acceptable salts of the present invention include, for example, salts formed from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present invention include non-toxic salts of the parent compound which may be prepared by conventional chemical methods. They can be synthesized by various methods from parent compounds that contain a basic or acidic moiety. Generally, such salts are prepared by dissolving the free acid or base form of these compounds in an appropriate stoichiometric amount. React with an appropriate base or acid in water or an organic solvent, or in a mixture of the two. Generally, ethers, ethyl acetate, alcohols (e.g., methyl ethanol, isopropanol, or butanol) or acetonitrile Non-aqueous media such as (MeCN) are preferred. A list of suitable salts can be found in Remington 's Pharmaceutical Sciences,17th Ed.,(Mac k Publishing Company, Easton, 1985), p.1418 , Berge et al., J.Pharm.Sci.,1977,66(1),1- 19, and Stahl et al., Handbook of Pharmaceu tical Salts:Properties,Selection,and Use , (Wiley, 2002). In some embodiments, the methods described herein are The compounds described include N-oxide forms.

[0227] The following abbreviations may be used herein: AcOH (acetic acid), AcO (acetic anhydride), Al2O3 (aluminum oxide), aq. (aqueous), atm. (atmosphere), Boc(t- butoxycarbonyl), Boc2O (di-tert-butyl dicarbonate), BOP( (Benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexa fluorophosphate), br (broad), c-Pr (cyclopropyl), Cbz (carbo Benzyl), 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-diisopropyl propylethylamine), DMAP (4-dimethylaminopyridine), DMF (N,N-dimethylpyridine) Methylformamide), DMSO (dimethyl sulfoxide), Et (ethyl), EtOA c (ethyl acetate), EtOH (ethanol), Fmoc (9-fluorenylmethylmethacrylate) carbonyl), g (grams), h (hours), H2 (hydrogen gas), H2O2 (hydrogen peroxide) ), HATU(N,N,N',N'-tetramethyl-O-(7-azabenzotriazole) -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·H2 O (tripotassium phosphate hydrate), LCMS (liquid chromatography-mass spectrometry), Li AlH4 (lithium tetrahydrogen aluminate), LiBH4 (lithium tetrahydrogen borate), LiO H (lithium hydroxide), LiOH·H2O (lithium hydroxide monohydrate), m (multiplet), M (mol), mCPBA (m-chloroperbenzoic acid), Me (methyl), MeCN (acetone) Nitrile), MeOH (methanol), MgSO4 (magnesium sulfate), MS (mass sieve) analysis), mg (milligram), min. (minute), mL (milliliter), mmol (millimoles) N (normal), N2 (nitrogen gas), NaHCO3 (sodium bicarbonate), NaIO4 (sodium metaperiodate), NaN3 (sodium azide), NaOH (sodium hydroxide) sodium), Na2SO4 (sodium sulfate), n-Bu (n-butyl), n-BuLi( n-butyllithium), NH4Cl (ammonium chloride), NH4OH (ammonium hydroxide um), nM (nanomolar), 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-butylphosphine)palladium), pM (picomole), Pd(P Ph3)4 (tetrakis(triphenylphosphine)palladium(0)), PPh3 (tetrakis(triphenylphosphine)palladium(0)) triphenylphosphine), psi (pounds per square inch), PTFE (polytetrafluoroethylene fluoroethylene), RP-HPLC (reversed-phase high-performance liquid chromatography), rt( room temperature), s (singlet), t (triplet or tertiary), tert (tertiary), tt (triplet triplet) singlet), TBAF (tetra-n-butylammonium fluoride), t-Bu(tert- butyl), TEA (triethylamine), TFA (trifluoroacetic acid), THF (tetrafluoroethylene) hydrofuran), μg (micrograms), μL (microliters), μm (micro mol), wt% (weight percent).

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

[0229] Reactions for preparing the compounds of the present invention can be readily selected by one skilled in the art of organic synthesis. The reaction may be carried out in a suitable solvent, depending on the temperature at which the reaction is carried out, e.g. The starting materials (reactants), intermediates, or A given reaction may involve one solvent or two or more solvents. Depending on the particular reaction step, it may be carried out in a mixture of solvents. A suitable solvent can be selected by one skilled in the art.

[0230] Preparation of compounds of the invention can involve the protection and deprotection of various chemical groups. The need for protection, and the selection of appropriate protecting groups can be readily determined by one 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 C hemistry:Reactions, Mechanisms, and Struct ure, 6th Ed. (Wiley, 2007), Peturssion et al. .,“Protecting Groups in Carbohydrate Che mistry,” J. Chem. Educ., 1997, 74(11), 1297, and and Wuts et al., Protective Groups in Organi. c Synthesis, 4th Ed., (Wiley, 2006) .

[0231] The reaction may 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 by spectroscopic means such as spectrophotometry (e.g., UV-visible), mass spectroscopy, and High-performance liquid chromatography (HPLC) or thin-layer chromatography (TLC) It can be monitored by chromatographic methods such as

[0232] The following schemes provide general guidance regarding preparing compounds of the invention. Those skilled in the art will appreciate that the preparations shown in the schemes are well suited for preparing various compounds of the present invention. It will be understood that the compounds may be modified or optimized using general knowledge of organic chemistry. cormorant.

[0233] Compounds of formula (I) can be prepared by coupling an aniline of formula (II) with a compound of formula III and ##STR00002## where L is bromine or is a suitable leaving group which may contain a halogen such as iodine, or a sulfonate group (also alkyl or aryl sulfonates, e.g., methanesulfonate, trifluoromethane sulfonate, benzenesulfonate, p-toluenesulfonate, or naphthalene The reaction is carried out in the presence of a base such as potassium carbonate and copper(I) iodide or copper(I) oxide. The reaction can be carried out in the presence of a copper salt, such as copper(I). The reaction can also be carried out in the presence of a suitable organometallic catalyst. Using Buchwald-Hartwig cross-coupling conditions, for example, in the presence of Suitable solvents for the reaction include tetrahydrofuran, 1,4- Preferred solvents include dioxane, toluene, or 1,2-dichlorobenzene. , 1,2-dichlorobenzene. The reaction is typically carried out at temperatures between 0 and 200°C, e.g. The reaction can be carried out at a temperature of 100 to 150°C.

[0234] The present disclosure relates, inter alia, to the preparation of certain particular compounds according to formula (Ia) by the route shown in Scheme 1. Methods for making certain compounds of formula (I) are provided. [ka]

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

[0236] Certain compounds of formula (I) are useful as intermediates in the synthesis of other compounds of formula (I). For example, a compound 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 Alkireni Cy 1A , N(C 1~6 Alkyl)Cy 1A , or N(C 1~6 Alkyl)(C1 ~3 (Alkylenyl)Cy 1A via hydrolysis of the ester or amide group using A compound of formula (I) 1 is OH) can be synthesized.

[0237] The processes described are not exclusive means of synthesizing the compounds of the present invention, but rather are intended to encompass a wide range of synthetic methods. The repertoire of organic reactions potentially available for the synthesis of compounds of the present invention is It will be understood by those skilled in the art that the skilled artisan will know how to select and carry out an appropriate synthetic route. Suitable methods for synthesizing starting materials, intermediates, and products are described in the following references: Advances in Heterocyclic Chemistry,Vols.1-107(Elsevi er,1963-2012), Journal of Heterocyclic Ch. emistry Vols.1-49(Journal of Heterocycli c Chemistry,1964-2012), Carreira,et al.(E d.)Science of Synthesis,Vols.1-48(2001-2 010)and Knowledge Updates KU2010 / 1-4;201 1 / 1-4;2012 / 1-2(Thieme,2001-2012), Katritz ky,et al.(Ed.)Comprehensive Organic Func tional Group Transformations,(Pergamon P ress, 1996), Katritzky et al. (Ed.); Compreh ensive Organic Functional Group Transform mations II (Elsevier, 2nd Edition, 2004), Ka tritzky et al. (Ed.), Comprehensive Hetero cyclic Chemistry (Pergamon Press, 1984), Ka tritzky et al., Comprehensive Heterocycli c Chemistry II, (Pergamon Press, 1996), Smi th et al.,March's Advanced Organic Chemistry stry:Reactions, Mechanisms, and Structures, 6th Ed. (Wiley, 2007), Trost et al. (Ed.), Co. mprehensive Organic Synthesis(Pergamon P ress, 1991).

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

[0239] Thus, the present disclosure provides a method for administering to an individual (e.g., a patient) in need of treatment a therapeutically effective amount or Dosage of a compound of formula (I), or any of its embodiments, or a pharmaceutical composition thereof and administering to an individual a compound that is capable of inhibiting a TEAD transcription factor-associated disease or disorder. The present disclosure also provides methods for treating TEAD transcription factor-associated diseases or disorders. a compound of formula (I), or any of its embodiments, or a pharmaceutical composition thereof, for Compositions are also provided. Also provided are pharmaceutical compositions for treating TEAD transcription factor-associated diseases or disorders. A compound of formula (I) or any of its embodiments, or a pharmaceutical composition thereof, in the manufacture The disease or disorder may be a TEAD1, TEAD2, TEAD3, or TEAD4 gene. , or a disease or disorder associated with TEAD4.

[0240] TEAD transcription factor-associated diseases involve the overexpression and / or abnormal activity levels of TEs. Any disease, disorder, or condition that is directly or indirectly associated with the expression or activity of an AD transcription factor Abnormal activity levels can include conditions in normal, healthy tissues or cells. The activity level can be determined by comparing it to the activity level in diseased cells. TEAD transcription factor-related diseases can be prevented and improved by regulating TEAD transcription factor activity. It can also include any disease, disorder, or condition that can be improved, inhibited, or cured. In some embodiments, the disease is characterized by abnormal activity or expression of a TEAD transcription factor (e.g., TEAD transcription factor-associated disorders are characterized by the expression or activation of TEAD transcription factors. It can also refer to any disease, disorder, or condition in which modulating a transcription factor is beneficial.

[0241] TEAD transcription factor-associated 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, and uterine cancer. Endometrial cancer, ovarian cancer, uterine cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer, breast cancer, and lung cancer Other TEAD metastases include cancer of the head and neck, thyroid cancer, glioblastoma, sarcoma, and bladder cancer. Transcription factor-related diseases include hepatocellular carcinoma, medulloblastoma, squamous cell carcinoma of the skin, lung cancer, pancreatic cancer, These include esophageal cancer, liver cancer, colon cancer, melanoma, or bladder melanoma. Factor-related diseases include blood cancers, such as lymphoma, acute lymphoblastic leukemia (ALL), Acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (C ML), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, non-Hodgkin lymphoma Hodgkin's lymphoma (relapsed non-Hodgkin's lymphoma, refractory non-Hodgkin's lymphoma, and relapsed Also includes follicular non-Hodgkin's lymphoma, Hodgkin's lymphoma, and multiple myeloma. do.

[0242] Cancer is characterized by abnormal proliferation of cancer cells expressing one or more TEADs, e.g., TEAD1, TEAD2, TEAD3, TEAD4, TEAD5, TEAD6, TEAD7, TEAD8, TEAD9, TEAD10, TEAD11, TEAD12, TEAD13, TEAD14, TEAD15, TEAD16, TEAD17, TEAD18, TEAD19, TEAD11, TEAD111, TEAD112, TEAD13, TEAD14, TEAD15, TEAD16, TEAD17, TEAD18, TEAD19, TEAD19, TEAD113, TEAD19, TEAD114, TEAD115, TEAD116, TEAD117, TEAD12, TEAD13, TEAD14 2, TEAD3, and / or TEAD4-expressing cancers The method may involve detecting cancer cells in an individual with one or more TEADs, e.g., TEAs. Regarding the expression of one or more of TEAD1, TEAD2, TEAD3, and / or TEAD4 and whether the cancer expresses TEAD1, TEAD2, TEAD3, and / or and determining that the cancer expresses TEAD4 according to the methods described herein. This can include treating

[0243] The terms "individual" and "patient", used interchangeably, refer to a mammal, preferably a mice, rats, other rodents, rabbits, dogs, cats, pigs, cattle, sheep, horses, or It refers to any animal, including primates, most preferably humans.

[0244] The phrase "therapeutically effective amount" refers to the amount of a substance or compound sought by a researcher, veterinarian, physician, or other clinician. Induce a biological or pharmaceutical response in the tissue, system, animal, individual, or human being in which it is administered. This refers to the amount of an active compound or pharmaceutical agent that is released.

[0245] The term "treat" or "treatment" refers to (1) inhibiting a disease, e.g., in an individual experiencing or exhibiting the pathology or symptomatology of a condition, or disorder Inhibiting a disease, condition, or disorder (i.e., further reduction of pathology and / or symptomology) (2) ameliorating the disease, e.g., reducing disease severity; or experiencing the pathology or symptomatology of a disease, condition, or disorder, such as reducing ameliorating a disease, condition, or disorder in an individual who is or exhibits a disease, condition, or disorder (i.e., pathology and In one embodiment, the treatment The treatment or treatment may be to prevent or reduce the risk of developing a disease, e.g. For example, a person may be predisposed to a disease, condition, or disorder but has not yet experienced the pathology or symptomatology of that disease. develop a disease, condition, or disorder in individuals who have not previously experienced or exhibited the disease, condition, or disorder This includes preventing or reducing risk.

[0246] Combination therapy Cancer cell proliferation and survival can be influenced by multiple signaling pathways. Therefore, it is useful to combine different chemotherapeutic agents to treat such conditions. The use of combination therapy reduces the likelihood of drug resistance developing in a cell population and / or improves the efficacy of treatment. This may reduce the toxicity of the treatment.

[0247] The compounds may be administered in combination with one or more anti-cancer agents, such as chemotherapeutic agents. Examples of legal drugs include abarelix, aldesleukin, alemtuzumab, and alitretinoin. Insulin, allopurinol, altretamine, anastrozole, arsenic trioxide, asparaginase azepam, azacitidine, bevacizumab, bexarotene, bleomycin, bortezomib, Lutezomib, intravenous busulfan, oral busulfan, calsterone, capecitabine, Carboplatin, cetuximab, chlorambucil, cisplatin, cladribine, clotrimazole arabine, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, darte Parin sodium, dasatinib, daunorubicin, decitabine, denileukin, denileukin Quindifutiox, dexrazoxane, docetaxel, doxorubicin, propionic acid Dromostanolone, eculizumab, epirubicin, erlotinib, estramustine, Etoposide citrate, etoposide, exemestane, fentanyl citrate, filgrasti Floxuridine, fludarabine, fluorouracil, fulvestrant, geficitin Nib, gemcitabine, gemtuzumab ozogamicin, goserelin acetate, histrelin acetate , ibritumomab tiuxetan, idarubicin, ifosfamide, imatinib mesylate, Interferon α2a, irinotecan, lapatinib ditosylate, lenalidomide, letrozole Lozole, leucovorin, leuprolide acetate, levamisole, lomustine, mechlorethamine megestrol acetate, melphalan, mercaptopurine, methotrexate, methoxamine Salen, mitomycin C, mitotane, mitoxantrone, phenpropionate nandro Lon, nelarabine, nofetumomab, oxaliplatin, paclitaxel, pamidronate panitumumab, pegaspargase, pegfilgrastim, pemetrexed dihydrate um, pentostatin, pipobroman, plicamycin, procarbazine, quinacrine, Rasburicase, rituximab, ruxolitinib, sorafenib, streptozocin, Nitinib, sunitinib maleate, tamoxifen, temozolomide, teniposide, test Lactone, thalidomide, thioguanine, thiotepa, topotecan, toremifene, toxin Momab, trastuzumab, tretinoin, uracil mustard, barbican, vinbras These include vincristine, vinorelbine, vorinostat, and zoledronate. can be.

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

[0249] VI. Formulation, Dosage Forms, and Administration When employed as pharmaceuticals, the compounds of the present invention may be administered in the form of pharmaceutical compositions. Accordingly, the present disclosure provides a compound of formula (I), or a pharmaceutically acceptable salt thereof, or and at least one pharmaceutically acceptable carrier. These compositions can be prepared by methods well known in the pharmaceutical art and can be used for topical administration. or by various routes depending on whether systemic treatment is indicated and the area to be treated Administration can be topical (transdermal, epidermal, ophthalmic), as well as intranasal, intravaginal, and rectal delivery, including mucosal delivery; pulmonary delivery (e.g., by aerosol delivery, including by powder or aerosol delivery); It can be administered orally (by inhalation or insufflation of a sol, intratracheal or intranasal), orally or parenterally. Parenteral administration may be intravenous, intraarterial, subcutaneous, intraperitoneal, intramuscular, or by injection or infusion, or Parenteral administration includes intracranial, e.g., intrathecal or intraventricular administration. For local administration, the dosage may be in the form of a small amount of fluid or, for example, by a continuous perfusion pump. Pharmaceutical compositions and formulations for the treatment of rheumatoid arthritis include transdermal patches, ointments, lotions, creams, gels, drops, and the like. Conventional pharmaceutical carriers, aqueous, powder or In some cases, an oily or oily base, thickener, or the like may be necessary or desirable.

[0250] The present invention includes, as an active ingredient, a pharmaceutical composition comprising a pharmaceutical composition in combination with one or more pharmaceutically acceptable carriers (excipients). Also included are pharmaceutical compositions containing the compounds of the present invention, or pharmaceutically acceptable salts thereof. In some embodiments, the compositions are suitable for topical administration. In preparation, the active ingredient is typically mixed with, diluted by, or 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 acts as a vehicle, carrier, or or a solid, semi-solid, or liquid substance acting as a medium. The substance may be a tablet, pill, powder, lozenge, sachet, cachet, elixir, suspension, emulsion, solution, Syrups, aerosols (as solids or in liquid media), e.g., up to 10% by weight of active Ointments, soft and hard gelatin capsules, suppositories, sterile injectable solutions, and non-steroidal anti-inflammatory drugs containing the compound are available. It may be in the form of a packed powder.

[0251] When preparing a formulation, the active compound is milled to obtain the appropriate particle size before combining with other ingredients. If the active compound is substantially insoluble, it may be dissolved in water at 200 mesh. If the active compound is substantially water soluble, the particle size can be reduced to a particle size of less than 1000 mg. Milling may be performed to, for example, about 40 mesh to provide a substantially uniform distribution in the formulation. It is possible.

[0252] The compounds of the present invention may be milled using known milling procedures, such as wet milling, to form tablets and The finely divided (nano) particles of the compounds of the present invention can be obtained in particle sizes suitable for pharmaceutical formulations and other pharmaceutical formulations. The preparations may be prepared by processes known in the art, for example, WO See 2002 / 000196.

[0253] Some examples of suitable excipients include lactose, dextrose, sucrose, Rubitol, mannitol, starch, acacia gum, calcium phosphate, alginate , tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolide In addition, the formulation contains Contains lubricants, wetting agents, emulsifiers and additives such as talc, magnesium stearate, and mineral oil. and suspending agents, preservatives such as methyl and propylhydroxybenzoates, sweeteners, and The compositions of the present invention can be prepared using procedures known in the art. and providing rapid, sustained, or delayed release of the active ingredient after administration to a patient. It can be formulated to

[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. Contains about 2% silicon dioxide w / w.

[0255] In some embodiments, the composition comprises at least one compound described herein, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier. In some embodiments, the composition is a sustained release composition. at least one compound, or a pharmaceutically acceptable salt thereof, and microcrystalline cellulose , lactose monohydrate, hydroxypropyl methylcellulose, and polyethylene oxide In some embodiments, the composition comprises at least one component selected from the group consisting of benzoyl benzoates, ... 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 of the ingredients described herein. a compound, or a pharmaceutically acceptable salt thereof, and microcrystalline cellulose, lactose In some embodiments, the composition comprises a sucralose monohydrate, a sucralose monohydrate, and polyethylene oxide. In some embodiments, the microcrystalline cellulose further comprises magnesium tearate or silicon dioxide. The crystalline cellulose is Avicel PH102™. The lactose monohydrate is Fast-flo 316™. In the form, hydroxypropyl methylcellulose is hydroxypropyl methylcellulose 2208 K4M (e.g., Methocel K4M Premier™) and and / or hydroxypropyl methylcellulose 2208 K100LV (e.g., M In some embodiments, polyethylene The oxide is polyethylene oxide WSR 1105 (e.g., Polyox WSR1 105 (trademark).

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

[0257] The compositions may be formulated in unit dosage form, each dosage being from about 5 to about 1,000 mg (1 g), More typically, it contains from about 100 mg to about 500 mg of the active ingredient. Each dose contains about 10 mg of the active ingredient. In some embodiments, each dose contains about 5 mg of the active ingredient. In some embodiments, each dose contains about 25 mg of the active ingredient. The term "unit dosage form" refers to a unit dosage for human subjects and other mammals. "Primary" refers to physically discrete units suitable for use as pharmaceutical compositions, each unit being capable of producing the desired product in association with suitable pharmaceutical excipients. It contains a predetermined amount of active substance calculated to produce a therapeutic effect.

[0258] The components used to formulate the 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). For consumption, the composition preferably contains a suitable Manufactured or formulated under standards of good manufacturing practice. For example, suitable formulations are sterile and / or or substantially isotonic and / or meets all Good Manufacturing Practices of the U.S. Food and Drug Administration This allows for full compliance with regulations.

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

[0260] The therapeutic dosage of a compound of the present invention will vary depending, for example, on the particular application for which the treatment is being administered, the manner in which the compound is administered, These may vary according to the formula, the patient's health and condition, and the judgment of the prescribing physician. The proportion or concentration of a compound of the invention in the solution may depend on factors such as dosage, chemical characteristics (e.g., hydrophobicity), and The dosage may vary depending on several factors, including the dosage and route of administration. For example, compounds of the present invention may be administered parenterally. For administration, the compound is provided in a physiologically buffered aqueous solution containing about 0.1 to about 10% w / v of the compound. Some typical dosage ranges are from about 1 μg to about 1 g per kg of body weight per day. In some embodiments, the dose range is about 0.01 ml per kg of body weight per day. The dosage ranges from 100 mg to about 100 mg. The dosage depends on the type and progression of the disease or disorder, the specific patient, and the dosage. The overall health of the patient, the relative biological availability of the selected compounds, the formulation of excipients, etc. The effective dose may depend on variables such as the dosage and route of administration. Dose-response curves derived from animal model test systems can be extrapolated.

[0261] To prepare solid compositions such as tablets, the main active ingredient is mixed with pharmaceutical excipients, Solid preformulation compositions are formed containing a homogeneous mixture of the compounds of the present invention. When referring to a composition as homogeneous, it is understood that the composition may be in the form of tablets, pills, capsules, and the like. The active ingredient is typically present in a quantity greater than the total weight of the composition so that it can be easily subdivided into equally effective unit dosage forms. This solid preformulation is then dispersed evenly throughout the body, for example, in a concentration of from about 0.1 to about 1000 mg of glycerol. It is subdivided into unit dosage forms of the type described above containing 1000 mg of the active ingredient of the present invention.

[0262] The tablets or pills of the present invention may be coated or otherwise compounded to provide the advantage of prolonged action. For example, a tablet or pill may be provided as an inner dosage form. containing inner dosage and outer dosage components. The latter forms a capsule that covers the former. The two components are resistant to disintegration in the stomach. and allows its internal components to pass intact into the duodenum or delay release. Various substances can be separated by such enteric layers. Such materials may be used in layers or coatings, and include some polymeric acids. , as well as polymeric acids and substances such as shellac, cetyl alcohol, and cellulose acetate. Contains a mixture of qualities.

[0263] The compounds and compositions of the present invention may be incorporated into liquids for oral or injectable administration. Forms 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 may be prepared in pharmaceutically acceptable aqueous or organic solvents, or These include solutions and suspensions in mixtures thereof, as well as powders. may include suitable pharmaceutically acceptable excipients as described above. In some cases, the compositions are administered by the oral or nasal respiratory route for local or systemic effect. The composition may be nebulized by use of an inert gas. The nebulized solution is then directly ejected from the nebulizing device. The nebulizer may be inhaled directly or the nebulizer device may be attached to a face mask, obturator, or intermittent positive pressure device. The solution, suspension, or powder compositions may be prepared in any suitable manner. The agent may be administered orally or nasally from a device that delivers the agent.

[0265] Topical formulations may include one or more conventional carriers. In some embodiments, ointments are prepared by adding water. For example, liquid paraffin, polyoxyethylene alkyl ether, propylene glycol The cream may contain one or more hydrophobic carriers selected from the group consisting of ethanol, white petrolatum, etc. The composition may comprise water, glycerol, and one or more other components, such as glycerin monohydrate. Monostearate, PEG-glycerin monostearate, and cetylstearyl The gel may be based on a combination of isopropyl alcohol and water. and preferably, other components such as glycerol, hydroxyethyl cellulose, etc. In some embodiments, the topical formulation contains 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 invention. Optionally, associated with indications for the treatment of a selected indication, e.g., psoriasis or other skin conditions. The topical formulations may be suitably packaged, for example, in 100 g tubes.

[0266] The amount of compound or composition administered to a patient may vary depending on the type of treatment being administered, such as prophylactic or therapeutic. It varies depending on the purpose of administration, the condition of the patient, the mode of administration, etc. In therapeutic applications, the composition is used to treat a disease. and sufficient to cure or at least partially arrest the symptoms of its complications. An effective dose may be administered to a patient already suffering from a disease in an amount that is indicative of the disease state being treated, e.g. The doctor's judgment is based on factors such as the severity of the disease, the patient's age, weight, and general condition. Depends on the decision.

[0267] The compositions administered to a patient can be in the form of pharmaceutical compositions described above. The aqueous solution may be sterilized by conventional sterilization techniques, or may be sterile filtered. The preparation may be packaged or lyophilized for use up to 2 weeks, although lyophilized preparations may be packaged or lyophilized for use up to 2 weeks prior to administration. The compound is combined with a sterile aqueous carrier. The pH of the compound preparation is typically between 3 and 11, more preferably between 11 and 11. Preferably, it will be 5 to 9, and most preferably 7 to 8. It will be appreciated that the use of some of the formulations will result in the formation of pharmaceutical salts.

[0268] The therapeutic dosage of a compound of the present invention will vary depending, for example, on the particular application for which the treatment is being administered, the manner in which the compound is administered, These may vary according to the formula, the patient's health and condition, and the judgment of the prescribing physician. The proportion or concentration of a compound of the invention in the solution may depend on factors such as dosage, chemical characteristics (e.g., hydrophobicity), and The dosage may vary depending on several factors, including the dosage and route of administration. For example, compounds of the present invention may be administered parenterally. For administration, the compound is provided in a physiologically buffered aqueous solution containing about 0.1 to about 10% w / v of the compound. Some typical dosage ranges are from about 1 μg to about 1 g per kg of body weight per day. In some embodiments, the dose range is about 0.01 ml per kg of body weight per day. The dosage ranges from 100 mg to about 100 mg. The dosage depends on the type and progression of the disease or disorder, the specific patient, and the dosage. The overall health of the patient, the relative biological availability of the selected compounds, the formulation of excipients, etc. The effective dose may depend on variables such as the dosage and route of administration. Dose-response curves derived from animal model test systems can be extrapolated.

[0269] IV. Labeled Compounds and Assay Methods The compounds of the present invention are useful in investigating biological processes in normal and abnormal tissues. Therefore, another aspect of the present invention is to provide not only imaging techniques but also Localization of TEAD transcription factors in tissue samples, including human, both in vitro and in vivo Identification of TEAD transcription factor ligands by labeling and quantification, and inhibitory binding of labeled compounds The labeled compounds of the present invention (radiolabeled, fluorescently labeled, etc.) may also be useful in assays for etc. Accordingly, the present invention includes assays containing such labeled compounds. .

[0270] The present invention further includes isotopically labeled compounds of the present invention. A compound is one in which one or more atoms are typically found in nature (i.e., naturally occurring). ) atomic mass or mass number is replaced by an atom having a different atomic mass or mass number The compounds of the present invention are those which are substituted or unsubstituted. Suitable radionuclides include: 3 H (also written as T for tritium), 11 C. 1 3 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 13 1 The radiolabeled compounds include, but are not limited to, I. The radionuclide will depend on the particular application of the radiolabeled compound. For example, in vitro labeling and and in the case of competitive assays, 3 H, 14 C. 82 Br, 125 I, 131I, 35 Incorporating S For radioimaging applications, compounds containing: 11 C. 18 F , 125 I, 123 I, 124 I, 131 I, 75 Br, 76 Br, or 77 Br is the best is also useful.

[0271] A "radiolabel" or "labeled compound" is a chemical compound that incorporates at least one radionuclide. It is understood that in some embodiments the radionuclide is 3 H, 14 C , 125 I, 35 S, and 82 In some embodiments, the aryl group is selected from the group consisting of Br. In organic compounds, the compound incorporates one, two, or three deuterium atoms. Synthetic methods for incorporating the bodies are known in the art.

[0272] Specifically, the labeled compounds of the present invention can be used in screening assays to identify compounds. and / or can be evaluated, for example, by labeling newly synthesized or identified The compound (i.e., the test compound) contacts the TEAD transcription factor through tracking of the label. By monitoring the concentration fluctuations of the TEAD transcription factors, we can identify the TEAD transcription factors that bind to the TEAD transcription factors. For example, a test compound (label) can be evaluated for its ability to bind to TEAD transcription factors (i.e., by its ability to reduce the binding of another compound known to bind to it (i.e., the reference compound). Therefore, the binding of TEAD transcription factors to the target compound can be evaluated. The ability of a test compound to bind directly correlates with its binding affinity. In a screening assay, the standard compound is labeled and the test compound is unlabeled. To evaluate the competition between the standard and test compounds, the concentration of the labeled standard compound was The degree of binding is monitored, thereby ascertaining the relative binding affinity of the test compounds.

[0273] V. Kit The present disclosure also relates to the treatment or administration of TEAD transcription factor-associated diseases or disorders, such as, for example, cancer. and pharmaceutical kits useful for prophylaxis, which comprise a therapeutically effective amount of a compound of formula (I), or and one or more containers containing a pharmaceutical composition comprising any of the embodiments. Such kits may include, for example, one or more pharmaceutical Various conventional pharmaceutical kit components, such as a container with an acceptable carrier, additional containers, etc. The injection may further include one or more of the following: The amounts of components to be given, guidelines for administration, and / or mixing of the components Instructions providing guidelines for the use of the kit may also be included.

[0274] The present invention will now be described in more detail with the aid of specific examples. The following examples are provided for illustrative purposes only. It is provided for illustrative purposes only and is not intended to limit the invention in any manner. Various non-critical parameters can be changed or modified to produce essentially the same results. will be easily recognized. [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 i infinity)LCMS-SQD 6120 / Single quad, and Shi madzu 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-diisopropylethyl ether) amine), DMAP (dimethylaminopyridine), (DMSO-d6 (deuterated DMSO) , d (doublet), dd (doublet of doublet), Fe (iron powder), g or gm (gram), H ATU(1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4 ,5-b]pyridinium 3-oxodohexafluorophosphate), H or H2 (water element), H2O (water), HCl (hydrochloric acid), h or hr (hours), Hz (hertz), HPL C (high performance liquid chromatography), J (coupling constant), LiOH (lithium hydroxide) (mmol), MeOH (methanol), mmol (millimol), M (mol), mL (milliliter) mg (milligram), m (multiple), mm (millimeter), 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), T FA (trifluoroacetic acid), TLC (thin layer chromatography), THF (tetrahydrofuran) furan), t (triplet), rac.BINAP ((±)-2,2'-bis(diphenylphosphine) Pd2dba3 (tris(dibenzylidene acetonitrile) t)dipalladium(0)), XPhos (2-dicyclohexylphosphino-2',4 ',6'-triisopropylbiphenyl), in vacuo, eq. ), ppt (precipitate), NA (not available).

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

[0280] of iodide (1 mmol) and amine (1 mmol) in 1,2-dichlorobenzene The solution was added under nitrogen atmosphere with potassium carbonate (1.5 mmol) followed by copper iodide (0.05 mmol). The resulting mixture was stirred at room temperature for 1 hour and then heated at 180°C for 2 days. After the reaction was complete, the resulting mixture was diluted with dichloromethane (50 mL) and The organic solution was dried over MgSO4, concentrated in vacuo, and diluted with hexane / acetic acid. Ethyl acetate (pure hexane to a gradient of 20 / 1 hexane / ethyl acetate) was used as the eluent. The product was purified by flash column chromatography in 40-69% yield.

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

[0282] In the case of compound 2a, 1 H NMR(500MHz,CDCl3):δ9.46(s,1 H),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 3 25.1) and 2e (M+H 443.1) were confirmed by mass spectrometry (LC-MS / ESI). The retention factor (R of 0.3 using pure hexane as the eluent) was also f ) and matched by TLC. Ta.

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

[0285] The required amine (1 mmol) and chloronicotinate (1 mmol) were dissolved in ethylene glycol. The resulting mixture was dissolved in ethanol and then heated at 140° C. for 24 hours. The organic solution was diluted with ethyl acetate (50 mL) and washed with 3 x 20 mL of water. Dry, concentrate under vacuum, and then mix with hexane / ethyl acetate (pure hexane to 15 / 1 hex). The elution was carried out by flash column chromatography using a gradient of ethanol / ethyl acetate as the eluent. The yield was 55-59%.

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

[0287] The cross-coupling procedures used to prepare some exemplary compounds are shown below. Shown in Figure 4. [ka]

[0288] In an oven-dried Schlenk tube, add amine (1 mmol) and bromide (1 mm t-BuONa (1. After stirring for 5 minutes, Pd2(dba)3 (0.05 mmol) and Bu3P (0.075 mmol) were added under a nitrogen atmosphere. The mixture was stirred at 50°C for 24 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (50 mL). The organic solution was dried over MgSO4 and concentrated in vacuo. hexane / ethyl acetate (gradient from pure hexane to 10 / 1 hexane / ethyl acetate) The eluate was purified by flash column chromatography to give the desired product. The yield was 42-55%.

[0289] In the case of compound 3a, 1 H NMR(500MHz,CDCl3):δ9.45(s,1 H),8.01(s,1H),7.5-7.7.30(m,2H),7.2-7.1(m ,2H),6.98(s,1H),6.8(s,1H),6.78-6.26(m,4H ),5.99(s,1H),3.90(s,3H),2.23-1.97(m,15H) ppm

[0290] In the case of compound 3c, 1 H NMR(500MHz,CDCl3):δ9.45(s,1 H),8.01(s,1H),7.45-7.23(d,2H),7.23-7.01( m,6H),6.98-7.01(d,2H),6.94(s,1H),3.93(s, 3H),5.99(s,1H)2.21-1.98(m,15H)ppm For compound 3d, 1 H NMR(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 procedures used to prepare some exemplary compounds are shown below. Shown in Figure 5. [ka]

[0292] In an oven-dried Schlenk tube, add amine (1 mmol) and bromide (1 mm t-BuONa (1. After stirring for 5 minutes, Pd2(dba)3 (0.05 mmol) and Bu3P (0.075 mmol) were added under a nitrogen atmosphere. The mixture was stirred at 50°C for 24 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (50 mL). The organic solution was dried over MgSO4 and concentrated in vacuo. hexane / ethyl acetate (gradient from pure hexane to 10 / 1 hexane / ethyl acetate) The eluate was purified by flash column chromatography to give the desired product. The yield was 50-54%.

[0293] For compound 3f, 1 H NMR(500MHz,CDCl3):δ9.45(s,1 H),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. LC-MS / Compound 3g confirmed by ESI (M+H 468.57).

[0294] The cross-coupling procedures used to prepare some exemplary compounds are shown below. Shown in Figure 6. [ka]

[0295] In an oven-dried Schlenk tube, add amine (1 mmol) and bromide (1 mm t-BuONa (1. After stirring for 5 minutes, Pd2(dba)3 (0.05 mmol) and Bu3P (0.075 mmol) were added under a nitrogen atmosphere. The mixture was stirred at 50°C for 24 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (50 mL). The organic solution was dried over MgSO4 and concentrated in vacuo. hexane / ethyl acetate (gradient from pure hexane to 10 / 1 hexane / ethyl acetate) The eluate was purified by flash column chromatography to give the desired product. (Yield 39-55%).

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

[0297] For compound 3e, 1 H NMR(500MHz,CDCl3):δ9.46(s,1 H),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),2.2 3-1.97(m,15H)ppm.

[0298] Carboxylic acid compounds can be subjected to hydrolysis reactions as shown in Schemes 7, 8, 9, and 10. , and was prepared according to the following experimental procedure. [ka]

[0299] To a solution of the ester (1 mmol) in ethanol (10 mL), add 2 mmol of 2N N A solution of NaOH was added and the mixture was heated at 40°C for 24-48 hours. The mixture was cooled to room temperature, acidified with 2N hydrochloride solution, and extracted three times with 10 mL of ethyl acetate. The solution was dried over MgSO4, concentrated under vacuum, and diluted with hexane / ethyl acetate (pure hexane to Flash column chromatography was performed using a 5 / 1 hexane / ethyl acetate gradient as the eluent. Purification by column chromatography gave the desired product in 70-79% yield.

[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), add 2 mmol of 2N N A solution of NaOH was added and the mixture was heated at 40°C for 24-48 hours. The mixture was cooled to room temperature, acidified with 2N hydrochloride solution, and extracted three times with 10 mL of ethyl acetate. The solution was dried over MgSO4, concentrated under vacuum, and diluted with hexane / ethyl acetate (pure hexane to Flash column chromatography was performed using a 5 / 1 hexane / ethyl acetate gradient as the eluent. Purification by column chromatography gave the desired product in 80-83% yield.

[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), add 2 mmol of 2N N A solution of NaOH was added and the mixture was heated at 40°C for 24-48 hours. The mixture was cooled to room temperature, acidified with 2N hydrochloride solution, and extracted three times with 10 mL of ethyl acetate. The solution was dried over MgSO4, concentrated under vacuum, and diluted with hexane / ethyl acetate (pure hexane to Flash column chromatography was performed using a 5 / 1 hexane / ethyl acetate gradient as the eluent. Purification by column chromatography gave the desired product in 73-87% yield.

[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] The carboxylic acid compound is converted to a vinyl ketone compound as shown in Scheme 11, and the following The experimental procedure was carried out as follows. [ka]

[0312] The acid was converted to the Weinreb amide. The acid (0.1 mm H NMR) in dichloromethane (1 mL) was To a solution of 1000 mg of 1,000 sulphite, triethylamine (0.25 mmol) was added followed by Weinreb amine (0.25 mmol). Salt (0.2 mmol) and HATU (0.2 mmol) were added, and the mixture was stirred at room temperature for 16 hours. After the reaction was complete, water was added and the mixture was extracted three times with 10 mL of ethyl acetate. Dry with 04, concentrate under vacuum, and dilute with hexane / ethyl acetate (pure hexane to 5 / 1 hexane). The eluent was a flash column chromatography (a gradient of ethyl acetate / ethyl acetate). Purification thereafter gave the desired product.

[0313] An ice-cold solution of Weinreb amide (1 mmol) in anhydrous THF (10 mL) was added to TH Add 4 mL of a 1 M vinylmagnesium bromide solution in F and warm to room temperature. After completion of the reaction, Stir for 4 hours, quench with 1N hydrochloride solution at 0°C, and extract three times with 10 mL of ethyl acetate. The organic solution was dried over MgSO4, concentrated in vacuo, and purified with hexane / ethyl acetate (pure A flash column was used as the eluent (a gradient of hexane to 5 / 1 hexane / ethyl acetate). Purification by column chromatography gave the desired product in 42-57% yield.

[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 exemplified compounds can be synthesized and characterized as described below. Cut. [ka] Intermediate-I

[0317] Step-a: N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl ) Synthesis of acetamide (Ia) Acetanilide (50 g, 3 mL) in 1,1,2,2-tetrachloroethane (300 mL) To a solution of 1-bromoadamantane (87.5 g, 406 m mol, 1.1 eq) was added and stirred for 5 min. mol, 0.5 equivalents) was added and stirred at 100°C for 36 hours. The reaction mixture was cooled to room temperature. The residue was cooled and the excess tetrachloroethane was removed by concentration under vacuum. The organic layer was dissolved in ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate. The resulting product was adsorbed onto silica and purified by flash column chromatography to give the following: The title product was obtained 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 can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by the same procedure as Intermediate-Ia using [Table 1]

[0319] Step b: N-(4-((3r,5r,7r)-adamantan-1-yl)-2-chloro Synthesis of (Ib)(phenyl)acetamide (Ib) N-(4-((3r,5r,7r)-adamantane)- to a solution of (1-yl)phenyl)acetamide (25 g, 92.8 mmol, 1.0 equiv.) To the mixture 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 hours. Excess DMF was removed by concentration in vacuo. The residue was dissolved in ethyl acetate and washed with water and brine. Dry over aqueous sodium sulfate and concentrate under vacuum to obtain a 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 can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by the same procedure as Intermediate-Ib using [Table 2]

[0321] Step c: 4-((3r,5r,7r)-adamantan-1-yl)-2-chloroaniline Synthesis of Phosphorus (Intermediate-I) N-(4-((3r,5r,7r)-adamantane-1)-one in methanol (150 mL) -yl)-2-chlorophenyl)acetamide (17 g, 56 mmol, 1.0 equiv.) To the solution was added concentrated HCl (150 mL) and refluxed at 100° C. for 8 hours. The ethanol was removed under vacuum. The resulting white ppt. was filtered off. The filtered solid was washed with sodium bicarbonate and The desired product was obtained as a white solid. (13g, 88%) 1 H 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 can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by the same procedure as Intermediate-I using 1,4-dimethyl-2,4-dichloro-1,4-dichloro ... [Table 3]

[0323] The following intermediates can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: was prepared using a procedure similar to that described in the literature. [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: Methyl 2-((4-bromophenyl)amino)benzoate (Intermediate-II) Synthesis of Methyl 2-iodobenzoate (30 g, 114.5 mmol) in toluene (500 mL) , 1.0 equiv.) and 4-bromoaniline (19.3 g, 114.5 mmol, 1.0 equiv.) To the solution of 100g of cesium carbonate (49g, 150mmol, 1.3eq), The mixture was degassed for 15 minutes with a sieve. Palladium acetate (1.28 g, 5.7 mmol, 0.05 equiv.) and rac.BINAP (3.56 g, 5.7 mmol, 0.05 eq.) were added, and 5 The reaction mass was degassed for 16 hours at 110°C. The reaction mass was filtered through Celite and vacuum The mixture was concentrated under reduced pressure 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(d d,J1=2.0Hz,J2=8.3Hz,1H),7.51(d,J=2.9Hz,2 H),7.48(t,J=1.9Hz,1H),7.26(d,J=7.8Hz,1H) ,7.21(d,J=4.9Hz,2H),6.87(t,J=1.0Hz,1H),3 .84(s,3H);LC-MS:m / z 307.9(M+H) 2+

[0326] The following intermediates can be reacted with suitable Pd and Fe in the presence of a suitable solvent and under suitable reaction conditions: Using appropriate reactants and reagents with catalysts and ligands, intermediate-II can be prepared in the same manner. It was prepared by the procedure of [Table 5-1] [Table 5-2] [Table 5-3] [Table 5-4] [Table 5-5]

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

[0328] Step-a: 2-((5-bromopyrimidin-2-yl)(tert-butoxycarbonyl) Synthesis of methyl (amino)benzoate (II.28) Dissolution of Intermediate-II.3 (1.3 g, 4.3 mmol, 1 equiv.) in THF (30 mL) The solution contained DMAP (0.1 g, 0.84 mmol, 0.2 equivalents), pyridine (0.67 g, 8.7 mmol, 2 eq), anhydrous Boc (1.38 g, 6.3 mmol, 1.5 eq) The reaction mass was concentrated under vacuum and purified by CombiFlash. The title product was obtained as an off-white solid (1.4 g, 82%). S: m / z 408.2 (M+H) + The following intermediates can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by a similar procedure to Intermediate-II.28 using 2-methyl-2-propanol. [Table 6]

[0329] The following intermediates are reacted with a suitable Pd catalyst and Using the appropriate reactants and reagents with the ligand, the compound can be prepared by the same procedure as for intermediate-II. It was prepared as follows. [Table 7]

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

[0331] Step-a: Ethyl 2-(5-bromo-1H-indazol-1-yl)acetate and 2 Ethyl (5-bromo-2H-indazol-2-yl)acetate (IIIa and IIIb ) synthesis 5-Bromo-1H-indazole (1 g, 5.1 mmHg) in acetonitrile (25 mL) ol, 1.0 equiv.) was added to a solution of 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.) The reaction mass was concentrated under vacuum and washed with water and then added with silica gel. The mixture was adsorbed onto silica gel and purified by CombiFlash to give the title product 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 can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by a similar procedure to Intermediate-IIIa and IIIb using 1,2-dimethyl-2,4-dichloro-1,4-dichloro ... [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) Methyl 2-aminobenzoate (5 g, 33.1 mmol, 1.0 mL) in DCM (50 mL) To a solution of 11 g (108 mmol, 3 equiv.) of 4-bromo-2-methyl-2-propanol (2 equiv.), triethylamine (11 g, 108 mmol, 3 equiv.) was added, followed by 4-bromo-2-methyl-2-propanol (2 equiv.). bromobenzoyl chloride (7.2 g, 33.1 mmol, 1.0 equiv.) was added and the mixture was stirred at room temperature. Stirred overnight. The reaction mixture was extracted with ethyl acetate from water and concentrated in vacuo. 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 can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by the same procedure as Intermediate-IV using 1,4-dimethyl-2,4-dichloro ... [Table 9]

[0338] Intermediate-V: [ka]

[0339] Step-a: 2-((4-bromophenyl)(methyl)amino) methyl nicotinate (medium Synthesis of Intermediate-V): Intermediate-II.10 (0.4 g, 1.3 mmol, 1.0 equiv) in DMF (3 mL) To the solution was added sodium hydride (50%, 0.16 g, 3.9 mmol, 3 equiv.). The mixture was stirred for 10 minutes. Iodomethane (0.25 mL, 3.9 mmol, 3 equiv.) was added dropwise. The mixture was stirred in a sealed tube at room temperature overnight. The reaction mass was poured into water, extracted with ethyl acetate, and evaporated in vacuo. 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,1 H),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 can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by the same procedure as Intermediate-V using [Table 10-1] [Table 10-2]

[0341] Intermediate-VI: [ka]

[0342] Step-a: 2-((4-((4-((3R,5R)-adamantan-1-yl)phenyl)- Synthesis of methyl (phenyl)amino)phenyl)amino)benzoate (Intermediate-VI): Intermediate-II (0.5 g, 1.63 mmol, 1.0 equiv) in toluene (10 mL) and Intermediate-I.1 (0.37 g, 1.63 mmol, 1.0 equiv.) were heated under N2 gas The mixture was degassed for 15 minutes using a vacuum pump. Pd2dba3 (0.12 g, 0.13 mmol, 0.08 equiv.) ) and XPhos (0.16 g, 0.326 mmol, 0.2 equiv.) were added and the mixture was stirred for 5 min. The reaction mass was heated at 110° C. for 16 hours. The reaction mass was filtered through Celite and evaporated 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=8.8Hz,2H),7.12-6. 96(m,7H),6.69(t,J=6.8Hz,1H),3.85(s,3H),2 .04(s,3H),1.83(s,6H),1.72(s,6H);LC-MS:m / z 452.4(M+H) +

[0343] The following intermediates are reacted with a suitable Pd catalyst and Using the appropriate reactants and reagents with the ligand, the compound was synthesized by the same procedure as intermediate-VI. It was prepared as follows. [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:

change

[0345] Step d: 4-((3R,5R)-adamantan-1-yl)-2-chloro-N-(4 Synthesis of (-nitrophenyl)aniline (Intermediate-VII) Intermediate-I (8.5 g, 32.5 mmol, 1 equiv.) in toluene (100 mL) A solution of 4-bromonitrobenzene (6.57 g, 32.5 mmol, 1 equiv.) was heated under nitrogen The mixture was degassed by bubbling gas 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.), The mixture was degassed again for 5 minutes, and the reaction mixture was heated at 110° C. for 16 hours under stirring. Cool to room temperature, dilute with ethyl acetate and filter through Celite. The organic layer was adsorbed onto silica. The desired product was obtained by elution with hexane and purified by flash column chromatography. Elution with 5-10% ethyl acetate in water was performed. Concentration in vacuo gave a dark yellow oil (7 g, 57%). obtained. 1 H NMR(400MHz,DMSO-d6)δ8.98(s,1H),8.09-8 .07(m,2H),7.44(s,1H),7.38(s,2H),6.83-6.7 9(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 are reacted with a suitable Pd catalyst and Using the appropriate reactants and reagents with the ligand, the compound can be prepared by the same procedure as intermediate-VII. It was prepared as follows. [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 are reacted with a suitable Pd catalyst and Using the appropriate reactants and reagents, the ligand can be synthesized by the same procedure as for intermediate-V. Prepared. [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: N-(4-((3R,5R)-adamantan-1-yl)phenyl)-3 Synthesis of -nitrobenzamide (intermediate-VIII) Using the same procedure as for Intermediate-IV, Intermediate-I.1 (1 g, 4.4 mmol, 1 eq.) was obtained. amount) and 3-nitrobenzoyl chloride (0.82 g, 4.4 mmol, 1 equiv.) The title compound (1.6 g, 96%) was synthesized. LC-MS: m / z 377.2 (M+H ) +

[0350] The following intermediates can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by a similar procedure to Intermediate-VIII using 1,4-dimethyl-2,4-dichloro-1,4-dichloro ... [Table 14-1] [Table 14-2]

[0351] Intermediate-IX: [ka]

[0352] Step-a: (3R,5R)-1-(3-chloro-4-(4-nitrophenoxy)phenoxy)phenyl Synthesis of (Nyl)adamantane (Intermediate-IX) 4-Fluoronitrobenzene (0.6 mL, 5.7 mmol) in DMSO (10 mL) ) and Intermediate-I.25 (1.5 g, 6.84 mmol, 1.2 equiv.) was added to a solution of carbonate Potassium (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. Obtained as a 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(M- H) -

[0353] The following intermediates can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by a similar procedure to Intermediate-IX using 1,4-dimethyl-2,4-dichloro-1,4-dichloro ... [Table 15-1] [Table 15-2] [Table 15-3]

[0354] Intermediate-X: [ka]

[0355] Step-a: (3r,5r,7r)-1-(3-chloro-4-methylphenyl) adamantane Synthesis of pentane (Xa) (3r,5r,7r)-1-(p-tolyl)adamantane (2 g, 8.8 mm) in acetic acid To a solution of 75 ml of N-chlorosuccinimide was added in portions over 30 minutes. The mixture was heated at °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 (400MH z,DMSO-d6)δ7.31(d,J=1.9Hz,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: (3r,5r,7r)-1-(4-(bromomethyl)-3-chlorophenyl) ) Synthesis of Adamantane (Xb) To a solution of compound Xa (1 g, 3.8 mmol) in carbon tetrachloride (40 mL) was added bromine (0 0.61 g, 3.8 mmol) was added dropwise, followed by the addition of benzoyl peroxide (catalyst). The mixture was concentrated under vacuum and the crude product was purified by column chromatography. to give the title product as an off-white solid (0.5 g, 38%) . 1H NMR(400MHz,DMSO-d6)δ7.38(d,J=8.0Hz,2 H),7.24(m,1H),4.58(s,2H),2.10(s,3H),1.81 (s,6H),1.72(s,6H).

[0357] Step c: 1-(4-((3R,5R)-adamantan-1-yl)-2-chlorobene Synthesis of (4-nitro-1H-pyrazole)-4-nitro-1H-pyrazole (Intermediate-X) This intermediate was reacted with intermediate-Xb (0.3 g, 0.88 mmol, 1 equiv.) and 4-nitrobenzoate. lopyrazole (0.12 g, 1.06 mmol, 1.2 equivalents) to prepare Intermediate-III The title product was prepared by a similar procedure as described for 0.3g, 91%). 1 H NMR (400 MHz, DMSO-d6) δ 8.9 9(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=8.3 Hz,1H),5.47(s,2H),2.04(s,3H),1.83(s,6H), 1.72(s,6H).

[0358] The following intermediates can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by a similar procedure to Intermediate-X using 1,4-dimethyl-2-propanol. [Table 16-1] [Table 16-2]

[0359] Intermediate-XI: [ka]

[0360] Step-a: N1-(4-((3R,5R)-adamantan-1-yl)-2-chloro Synthesis of (phenyl)benzene-1,4-diamine (Intermediate-XI) Intermediate-VII (7 g, 18.3 mmol, 1 ammonium chloride (19.42 g, 36.6 mmol, 20 equiv.), followed by Zinc dust (11.91 g, 183 mmol, 10 equiv.) was added and the mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate and filtered through Celite. The filtrate was diluted with water, followed by The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The 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. 1 H 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,1H),6.72(d,J=8.8Hz,1H), 6.54(d,J=8.8Hz,2H),4.85(s,2H),2.02(s,3H) ,1.78(s,6H),1.70(s,6H);LC-MS:m / z 353.1(M +H) +

[0361] The following intermediates can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by a similar procedure to Intermediate-XI using HCl. [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

[0362] Intermediate-XII: [ka]

[0363] Step-a: 2-((4-((4-((3r,5r,7r)-adamantan-1-yl )-2-chlorophenyl)amino)phenyl)amino)nicotinic acid methyl ester (Intermediate-XI Synthesis of I) Intermediate-XI (8 g, 22.72 mmol, 1 equiv.) in toluene (100 mL) A solution of methyl 2-chloronicotinate (4.27 g, 25 mmol, 1.1 equiv.) and 2-chloronicotinate (4.27 g, 25 mmol, 1.1 equiv.) was added to nitrogen. The mixture was degassed by bubbling nitrogen gas for 5 minutes. Cesium carbonate (11.1 g, 34.1 m mol, 1.5 equiv.), followed by palladium acetate (0.5 g, 2.27 mmol, 0.1 equiv. amount), and rac.BINAP (2.12 g, 3.41 mmol, 0.15 equiv.) were added. The reaction mixture was heated at 110°C for 16 hours under stirring. The mixture was cooled to room temperature, diluted with ethyl acetate and filtered through Celite. The desired product was obtained by adsorption onto HCl and purified by flash column chromatography. Elution with 10% ethyl acetate in hexanes. Concentration in vacuo gave a yellow solid (5.4 g, 49%). 1H NMR(400MHz,DMSO-d6)δ9.93(s,1H),8.37(d d,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),6.84-6.81(m,1H),3.89(s ,3H),2.04(s,3H),1.83(s,6H),1.72(s,6H);LC -MS: m / z 488.1 (M+H) +

[0364] The following intermediates are reacted with a suitable Pd catalyst and Using the appropriate reactants and reagents with the ligand, the compound can be prepared by the same procedure as intermediate-XII. It was prepared as follows. [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

[0365] Intermediate-XIII: [ka]

[0366] Step-a: 2-((1,4-dioxaspiro[4.5]decan-8-yl)amino) Synthesis of methyl benzoate (XIIIa) Methyl anthranilate (3 g, 20 mmol, 1 equiv.) in dichloroethane (50 mL) ) and 1,4-cyclohexanedione monoethylene acetal (4.6 g, 30 mmol) Acetic acid (20 mL) was added to a solution of 1,2-dichloromethane (1.5 eq.) and stirred at room temperature for 2 hours. Cool to 0 °C and add sodium triacetoxyborohydride (6.3 g, 30 mmol, 1 0.5 equivalents) was added and stirred at room temperature for 36 hours. Saturated bicarbonate solution was added to the reaction mass and the mixture was stirred at room temperature for 36 hours. Extraction with methyl ether and purification by CombiFlash gave the title product (1.01 g, 1 7%). 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),6.8 3(d,J=8.8Hz,1H),6.57-6.53(m,1H),3.87(s,4 H),3.78(s,3H),3.60-3.58(m,1H),1.95-1.90( m,2H),1.70-1.61(m,4H),1.60-1.48(m,2H);LC -MS: m / z 292.0 (M+H) +

[0367] Step b: Methyl 2-((4-oxocyclohexyl)amino)benzoate (XIIIb ) synthesis Compound XIIIa (1.01 g, 3.4 mmol, 1 equiv.) in acetone (30 mL) To the solution was added 2N HCl (10 mL) and stirred at room temperature overnight. The reaction mass was dissolved in ethyl acetate. The crude product was used without further purification. 1 H 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,J=7.6Hz,1H),3.97-3.95( m,1H),3.79(s,3H),2.57-2.53(m,2H),2.29-2. 19(m,4H),1.77-1.72(m,2H);LC-MS:m / z 248.2 (M+H) +

[0368] Step c: 2-((4-((4-((3r,5r,7r)-adamantan-1-yl) Methyl (2-chlorophenyl)amino)cyclohexyl)amino)benzoate (Intermediate-X Synthesis of III) Compound XIIIb (0.5 g, 2.02 mmol, 1 equiv.) in acetic acid (10 mL) A solution of 1,2-dichloro-2,4-dichloro-1,4 ... Sodium boronate (1.28 g, 6.06 mmol, 3 equiv.) was added and the mixture was heated at 80°C for 16 hours. The reaction mass was extracted with ethyl acetate from saturated bicarbonate and brine and heated under vacuum. The crude product was purified by Combiflash to give the title compound as a pale pink Obtained as a liquid (0.67 g, 67%). LC-MS: m / z 493.3 (M+H) +

[0369] The following intermediates were synthesized using the appropriate reactants and reagents in suitable solvents and under suitable reaction conditions: Prepared by a similar procedure to Intermediate-XIII in the presence of HCl. [Table 19-1] [Table 19-2] [Table 19-3]

[0370] Intermediate-XIV: [ka]

[0371] Step-a: 4-((2-(methoxycarbonyl)phenyl)amino)benzoic acid (intermediate Synthesis of benzophenone-XIV A solution of Intermediate-II.20 (3 g, 9.1 mmol, 1 equiv) in DCM (30 mL) The mixture was cooled in ice for 10 minutes. TFA (3 mL) was added dropwise and the mixture was stirred at room temperature for 16 hours. The reaction mass was concentrated under vacuum. The crude product was triturated with n-pentane and dried under vacuum to give the title compound. The product was obtained 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=2.0Hz,J2=6.8Hz,2H),7.52-7.46(m,2H ),7.26(d,J=8.8Hz,2H),7.01-6.97(m,1H),3.8 4(s,3H), LC-MS: m / z 272.1(M+H) +

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

[0373] The following intermediates were synthesized using the appropriate reactants and reagents in suitable solvents and under suitable reaction conditions: Prepared by a similar procedure to Intermediate-XIV in the presence of HCl. [Table 20-1] [Table 20-2] [Table 20-3] [Table 20-4]

[0374] Intermediate-XV: [ka]

[0375] Step-a: 2-((4-((4-((3R,5S)-adamantan-1-yl)phenyl)- Synthesis of methyl (phenyl)carbamoyl)phenyl)amino)benzoate (Intermediate-XV) Compound XIV (0.2 g, 0.74 mmol, 1 eq.) and Intermediate-I.1 (0.1 A solution of HATU (0.34 g, 0.81 mmol, 1.1 equiv.) was cooled in ice. g, 0.89 mmol, 1.2 equiv.), followed by DIPEA (0.39 mL, 2.22 mm ol, 3 eq.) was added and stirred at room temperature for 16 hours. The reaction mass was slowly poured into ice water under stirring. The resulting precipitate was filtered and washed twice with cold water and then twice with n-pentane. and dried under vacuum to give the title compound as a cream-coloured solid (0.35 g, 98%) Got it. 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 synthesized using the appropriate reactants and reagents in suitable solvents and under suitable reaction conditions: Prepared by a similar procedure to Intermediate-XV in the presence of HCl. [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: [ka]

[0378] Step-a: N-(4-(N-(4-((3r,5r,7r)-adamantan-1-yl) Synthesis of (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 (0.66g, 6.6mmol, 3eq) was added, followed by 4-Acetamidobenzenesulfonyl chloride (0.51 g, 2.2 mmol) was added. The mixture was stirred at room temperature for 3 hours. The reaction mass was concentrated under vacuum and cold water was added. The resulting solid was filtered. Filtered and dried under vacuum to give the title product (0.88 g, 94%). LC-MS: / z 425.1(M+H) +

[0379] The following intermediates were synthesized using the appropriate reactants and reagents in suitable solvents and under suitable reaction conditions: Prepared by the same procedure as Intermediate-XVI in the presence of HCl. [Table 22-1] [Table 22-2]

[0380] Intermediate-XVII: [ka]

[0381] Step-a: N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl Synthesis of 4-aminobenzenesulfonamide (Intermediate-XVII) This compound was prepared from intermediate Ib by a procedure similar to that described for intermediate I from Ib. The title product was prepared from intermediate-XVI (0.85 g, 2 mmol, 1 equiv.) as a white solid. The compound was obtained as a compound (0.75 g, 98%). 1 H 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 synthesized using the appropriate reactants and reagents in suitable solvents and under suitable reaction conditions: Prepared by a similar procedure to Intermediate-XVII in the presence of 2,4-dimethyl-3,4-trimethyl-2 ... [Table 23]

[0383] Intermediate-XVIII: [ka]

[0384] Step-a: 2-((4-(N-(4-((3R,5R)-adamantan-1-yl) Methyl phenyl)sulfamoyl)phenyl)amino)benzoate (Intermediate-XVIII) Synthesis of Intermediate-XVIII can be prepared by the same procedure as described for Intermediate-II. -XVII and methyl 2-bromobenzoate. 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 are reacted with a suitable Pd catalyst and Similar procedures to intermediate-XVIII using appropriate reactants and reagents with the ligand was prepared by [Table 24-1] [Table 24-2] [Table 24-3]

[0386] Intermediate-XIX: [ka]

[0387] Step-a: (4-((3r,5r,7r)-adamantan-1-yl)phenyl)ca Synthesis of phenyl carbamate (XIXa) Intermediate-I.1 (0.5 g, 2.2 mmol, 1 equiv.) and chloroformate in DCM To a solution of phenyl (0.42 g, 2.64 mmol, 1.2 equiv.), triethylamine (0 The reaction mixture was added with 100 ml of HCl (0.44 g, 4.4 mmol, 2 equivalents) and stirred at room temperature for 2 hours. The mixture was washed with HCl, concentrated in vacuo and purified by CombiFlash to give the title compound as a white solid. The compound was obtained as a compound (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: 2-((4-(3-(4-((3R,5R)-adamantan-1-yl)) Synthesis of methyl (phenyl)ureido)phenyl)amino)nicotinate (intermediate-XIX) Intermediate-XIXa (0.285 g, 0.82 mmol, 1 equiv.) and 2-(4-aminopropyl)- Methyl ((phenyl)amino)nicotinate (0.2 g, 0.82 mmol, 1 equiv.) was dissolved in TH The mixture was taken up in F (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. 1H 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 synthesized using the appropriate reactants and reagents in suitable solvents and under suitable reaction conditions: Prepared by a similar procedure to Intermediate-XIX in the presence of [Table 25]

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

[0391] Step-a: ((4-((4-((3R,5S)-adamantan-1-yl)-2-chloride Synthesis of methyl (amino)phenyl)carbamoyl)proline (XIX.4) Growth 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 The solution was stirred at 0°C for 1 hour. This solution was dissolved in DCM (10 mL) to give methyl prophosphate (0.056%). g, 0.32 mmol, 1.2 equiv) and stirred at 0°C for 1 hour. Quenched with acid solution, extracted with DCM and purified by column chromatography to give the The title product was obtained 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,1 H),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,1H),2.03(s,3H),1.98-1.84(m,3H),1.8 1(d,J=2.4Hz,6H),1.71(s,6H);LC-MS:m / z 508 .4(M+H) +

[0392] The following intermediates can be prepared by reacting the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by a similar procedure to Intermediate-XIX.4 using [Table 26]

[0393] Intermediate-XX: [ka]

[0394] Step-a: 2-((4-((4-((3R,5R)-adamantan-1-yl)phenyl)- (methyl)amino)phenyl)(methyl)amino)benzoic acid methyl ester (Intermediate-XX) ) synthesis A solution of Intermediate-VI (4 g, 8.85 mmol, 1 equiv.) in DMF (80 mL) was added to 0 Cool to °C and add sodium hydride (1.06 g, 44.2 mmol, 5 equiv) in portions. Methyl iodide (6.3 g, 44.2 mmol, 5 equiv.) was added dropwise and stirred for 15 min. The reaction mass was heated in a sealed tube at 80°C for 16 hours. The reaction mass was cooled to room temperature and Poured into water. The precipitated solid was filtered and dried. The crude product was adsorbed onto silica Purification by Combiflash gave the title product as a pale yellow solid (3 g, 70.7%). And got it. 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),6.90(d,J=8.8Hz,2H),6.67(d,J=8.8 Hz,2H),6.59(d,J=8.8Hz,2H),3.55(s,3H),3.2 0(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 synthesized using the appropriate reactants and reagents in suitable solvents and under suitable reaction conditions: Prepared by a similar procedure to Intermediate-XX in the presence of [Table 27-1] [Table 27-2] [Table 27-3] [Table 27-4] [Table 27-5] [Table 27-6]

[0396] The following compounds are reacted with a suitable Pd catalyst and Using the appropriate reactants and reagents with the ligand, the compound was synthesized by the same procedure as intermediate-VI. It was prepared as follows. [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 synthesized using the appropriate reactants and reagents in suitable solvents and under suitable reaction conditions: Prepared by a similar procedure to Intermediate-XIII in the presence of HCl. [Table 29-1] [Table 29-2]

[0398] The following compounds were synthesized using the appropriate reactants and reagents in suitable solvents and under suitable reaction conditions: Prepared by the same procedure as Intermediate-XI in the presence of HCl. [Table 30]

[0399] The following compounds were synthesized using the appropriate reactants and reagents in suitable solvents and under suitable reaction conditions: Prepared by a similar procedure to Intermediate-XIX in the presence of [Table 31]

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

[0401] Intermediate-VI (8.5 g, 1 6.5 mmol, 1 equiv.) was added to a solution of LiOH×HO (3.3 g, 82.4 mmol, 5 equivalents) was added and stirred at room temperature for 16 hours. The reaction mass was concentrated under vacuum, diluted with water and The mixture was acidified with N HCl to pH 5. 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 off-white. Obtained as a light yellow 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,6 H),1.72(s,6H);LC-MS:m / z 438.4(M+H) +

[0402] The following compounds are reacted with the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Compound-24 was prepared by a procedure similar to that described for Compound-24 using the compound The physiochemical properties of the compounds have also been 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

Table 32-148

Table 32-149

Table 32-150

Table 32-151

Table 32-152

Table 32-153

Table 32-154

Table 32-155

Table 32-156

Table 32-157

Table 32-158

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

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

[0405] 2-((4-((4-((3r,5r,7r)-adamantan-1-yl)-2-chloro (phenyl)amino)phenyl)carbamoyl)benzoic acid (compound-293) (CP-11 9) Synthesis of: [ka]

[0406] Step (i): Intermediate-XI (0.05 g, 0.16 mmol, 1 equiv) in DCM and phthalic anhydride (0.024 g, 0.16 mmol, 1 equiv.) at room temperature. The resulting precipitate was filtered and dried under vacuum to give the title product as a pale yellow solid. The compound was obtained as a compound (0.01 g, 12.5%). 1 H 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=8.8H z,2H),2.05(s,3H),1.83(s,6H),1.72(s,6H). L C-MS: m / z 501.1 (M+H) +2

[0407] The following compounds are reacted with the appropriate reactants and reagents in the presence of a suitable solvent and suitable reaction conditions: Prepared by a similar procedure to compound 293 using [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 reacted with Intermediate-XI.16 (0.145 g, 0.43 mmol, 1 eq.) and and methyl 2-bromo-5-isobutoxybenzoate (0.125 g, 0.43 mmol, 1 (equivalent) to prepare the title compound by the same procedure as in Intermediate-XII. The product was obtained as a brown solid (0.05 g, 22%). 1 H NMR (400 MHz, DM SO-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. 80(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),0.9 7(d,J=6.4Hz,6H).

[0410] Final compound: [ka]

[0411] The compound can be prepared by reacting the compound with a suitable reagent in the presence of a suitable solvent and suitable reaction conditions. Compound-24 was prepared by the same procedure as that described for Compound-24. The chemical properties are also summarized. 1H 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). L.C. -MS:525.3(M+H) +

[0412] Biological assays In vitro palmitoylation Recombinant GST-TEAD2 or His6TEAD2 (500 ng) protein was Preincubate with compounds at the indicated concentrations for 15 min, then incubate with 1 μM alkyne palmitate. Mitoyl-5CoA (Cayman Chemical) for 30 min or 50 mM M Incubation with ES (pH 6.4) followed by cleavage with biotin azide as previously described. A cyclohexane reaction was carried out (Zheng, B. et al., J. Am. Chem. Soc., 2002). The click reaction was carried out in the presence of 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 The reaction was carried out in 1 mM TBTA, 1 mM CuSO4, and 1 mM HCl at room temperature for 1 hour.

[0413] The reaction was quenched with 12 μL of 6× SDS sample loading buffer (50 mM Tris-HCl, pH 7.0). 6.8, 6% SDS, 48% glycerol, 0.03% bromophenol blue, 30 The reaction was terminated by the addition of 10 mM EDTA, 9% MeSH. Western blots were analyzed by streptavidin-HRP and histidine-HRP assays independently. The results were obtained from streptavidin blots by probing with streptavidin-HRP antibodies. The band intensities were quantified using the BIORAD Gel doc system and the Te The percentage of inhibition of ad2 autopalmitoylation was compared to DMSO control treated samples. This is determined by:

[0414] These compounds were compared for their activity in inhibiting TEAD2 palmitoylation in the above assays. Compound data show the effect of TEAD2 palmitoyltransferase (TEAD2P) on the activity of compounds at a concentration of 10 μM. The results as percentage of inhibition of thiazolination are provided in the table below.

[0415] Cell proliferation HuH7 cells (or other cells) are cultured in DMEM supplemented with 10% FBS. Cells are seeded into 96-well plates at a density of 5000 cells / well. Cells are allowed to adhere to the wells. Afterwards, the compounds in DMSO solution (1% DMSO concentration) were serially diluted to the indicated final concentrations. The cells were further incubated for 3 days. Viability was assessed using CellTiter Glo, MTT, or crystal violet staining. The inhibition curves are plotted by using GraphPad.

[0416] qRT-PCR YAP target gene expression was analyzed using a LightCycler 480 (Roche). Total RNA was extracted from cells using TRIzol (Life Technologies). The first strand cDNA was isolated from the The resulting cDNA was then used to generate cDNA using a synthesis kit (Roche). cDNA was prepared with probes to detect CTGF or CYR61, and GAPDH. LightCycler 480 SYBR Green I Master Mix (Roc He) was used in the reaction.

[0417] CMP assay 7-Diethylamino acid reacts with the thiol of CoA released in the enzymatic reaction to give a fluorescent signal Amino-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM) (excitation about 3 This assay is used to detect enzyme activity. The product (free CoA) generated from palmitoyl-CoA is detected. Test compounds that inhibit TEAD activity can block the CMP fluorescence signal.

[0418] TEAD2 / 4 protein (10 μL of a 50 ng / μL solution) and a solution of test compound (0.5 μL, variable concentrations) were pre-incubated at room temperature for 30 minutes. MES pH 6 4 buffer (6.5 μL of a 50 mM solution), EDTA (1 μL of a 20 mM solution), palmitoyltransferase (PMT), Toluyl-CoA (1 μL of a 20 μM solution), and 7-diethylamino-3-(4'-methylamino)-CoA (1 μL of a 20 μM solution), Mixture prepared from tetrahydrofuran (1 μL of a 10 μM solution) The solution was then added to the chamber and the resulting mixture was mixed thoroughly using a pipette. Incubate at room temperature for 30-120 minutes in the dark, every 30 minutes until the fluorescent signal is saturated. The fluorescence was detected at 350 nm. The IC 50 and the result is Calculated from.

[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 are those that bind to TEAD2 palmitoyltransferase in the above assays and in the CMP assay. Compound data were collected at a concentration of 10 μM of compound or Percentage of inhibition of TEAD2 palmitoylation by IC50 in CMP assay The data are provided in Table 1. [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

Table 38-21

Table 38-22

[0421] Various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description. Such modifications also fall within the scope of the appended claims. All patents, patent applications, and publications cited in this application are hereby incorporated by reference. Each of the references, including but not limited to, is incorporated herein by reference in its entirety. do.

Claims

1. Compounds of formula (I) 【Chemical 1】 (In the formula, L １ does not exist or has the formula N(R Ｎ ) or C(O) group, D is a group represented by the formula (D1), (D2), (D3), (D4), (D5), (D6), or ( D7), 【Chemistry 2】 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 , C.N., N.O. ２ , 5 to 1 0-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 A １ (C １～３ alkylene)-C(O)R １ Group (C １～３ a 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 And A １ The 5- to 10-membered heteroaryl, 4- to 10-membered heterocycloalkyl Lu, (C １～３ alkylene)-5 to 10-membered heteroaryl, or (C １～３ Alkylene )-4 to 10-membered heterocycloalkyl are unsubstituted or each independently a halogen atom; N, 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 has the formula N(R Ｎ ), O, or C(O) groups; L ３ does not exist or has the formula CH ２ , C≡C, N(R Ｎ ), or C(O) It is the basis, 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 １ Ａ , OH, OC 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 Al Kill) (C １～３ (alkylenyl)Cy １Ａ and R １ The C forming １～６ Alkyl are unsubstituted or each independently a halogen, OR ａ１ , S.R. ａ１ , and and NR ｃ１ R ｄ１ substituted by 1, 2, 3, 4, or 5 substituents selected from It is Cy １Ａ But C ６～１０ Aryl, C ３～１５ Cycloalkyl, 5- to 10-membered heteroaromatic group aryl, or 4- to 10-membered heterocycloalkyl; Cy １Ａ The C forming ６～ １０ Aryl, C ３～１５ cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heteroaryl Each of the membered heterocycloalkyls 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. ａ １ , and N.R. ｃ１ R ｄ１ substituted by 1, 2, or 3 substituents selected from C １～６ 0, 1, 2, 3, 4, or 5 substituents selected from alkyl is replaced by Each Cy １Ｂ But C ６～１０ Aryl, C ３～１５ Cycloalkyl, 5-10 membered hetero aryl, or 4- to 10-membered heterocycloalkyl; Cy １Ｂ The C forming ６ ～１０ Aryl, C ３～１５ cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heteroaryl Each of the 0-membered heterocycloalkyls is unsubstituted or each independently is unsubstituted C １ ～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, halogen, C １～６ Haloal Kill, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ and each independently halo Gen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ Choose from C substituted by 1, 2, or 3 substituents selected from １～６ Select from alkyl substituted with 1, 2, 3, 4, or 5 substituents selected from 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 But CH, C(C １～６ alkyl), or N; A Ｄ４２ But CH ２ , NH, or NC １～６ is alkyl, R ２ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Hello Lukil, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ Selected from 1, 2, if C substituted by at least three substituents １～６ is alkyl, R ３ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Hello Lukil, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ Selected from 1, 2, if C substituted by at least three substituents １～６ is alkyl, R ４ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Hello Lukil, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ Selected from 1, 2, if C substituted by at least three substituents １～６ is alkyl, R ５ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Hello Lukil, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ Selected from 1, 2, if C substituted by at least three substituents １～６ is alkyl, R ６ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , S(O) ２ R ｂ１ , S ( O) ２ NR ｃ１ R ｄ１ 、NR ｃ１ R ｄ１ 、C(O)OR ａ１ 、C(O)NR ｃ１ R ｄ１ 、 Cy ７Ａ , 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 Alkireni 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 ７ Ａ , 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 represents 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 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 、S(O) ２ NR ｃ１ R ｄ１ 、C(O)NR ｃ１ R ｄ１ 、Cy ７Ａ 、OCy ７ Ａ , 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 halo Gen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ Choose from C substituted by 1, 2, or 3 substituents selected from １～６ It is an alkyl 、 Cy ７Ａ But C ６～１０ Aryl, C ３～１５ Cycloalkyl, 5- to 10-membered heteroaromatic group aryl, or 4- to 10-membered heterocycloalkyl; Cy ７Ａ The C forming ６～ １０ Aryl, C ３～１５ cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heteroaryl Each of the membered heterocycloalkyls is unsubstituted or ７Ｂ , O.C.y. ７Ｂ , N.H. Cy ７Ｂ , and C(O)NHCy ７Ｂ 0, 1, or 2 substituents selected from: and each independently an unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Archi Nyl, 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 1, 2 selected from or C substituted by three substituents １～６ 0, 1 selected from alkyl , 2, 3, 4, or 5 substituents; Each Cy ７Ｂ But C ６～１０ Aryl, C ３～１５ Cycloalkyl, 5-10 membered hetero aryl, or 4- to 10-membered heterocycloalkyl; Cy ７Ｂ The C forming ６ ～１０ Aryl, C ３～１５ cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heteroaryl Each of the 0-membered heterocycloalkyls is unsubstituted or each independently is unsubstituted C １ ～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, halogen, C １～６ Haloal Kill, CN, OR ａ１ , S.R. ａ１ , N.R. ｃ１ R ｄ１ , C(O)NR ｃ１ R ｄ１ , and each independently represents 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 And, R ８ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , S(O) ２ NR ｃ１ R ｄ１ , S.R. ａ １ 、NR ｃ１ R ｄ１ 、NR ｃ１ S(O) ２ R ｂ１ 、C(O)OR ａ１ 、C(O)NR ｃ１ R ｄ１ , Cy ８Ａ ,OH,OCy ８Ａ , O(C １～３ (alkylenyl)Cy ８Ａ , C(O) O.C.y. ８Ａ , C(O)O(C １～３ (alkylenyl)Cy ８Ａ , NHCy ８Ａ , N(Cy ８ Ａ ) ２ , NH(C １～３ (alkylenyl)Cy ８Ａ , N(C １～６ alkyl)Cy ８Ａ , N (C(O)C １～６ alkyl)Cy ８Ａ , S.O. 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)C y ８Ａ or each independently a halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ substituted by 1, 2, or 3 substituents selected from C １～６ is alkyl, Cy ８Ａ But C ６～１０ Aryl, C ３～１５ Cycloalkyl, 5- to 10-membered heteroaromatic group aryl, or 4- to 10-membered heterocycloalkyl; Cy ８Ａ The C forming ６～ １０ Aryl, C ３～１５ cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heteroaryl Each of the membered heterocycloalkyls is unsubstituted or ８Ｂ , O.C.y. ８Ｂ , N.H. Cy ８Ｂ , and C(O)NHCy ８Ｂ 0, 1, or 2 substituents selected from: and each independently an unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Archi Nyl, 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 1, 2 selected from or C substituted by three substituents １～６ 0, 1 selected from alkyl , 2, 3, 4, or 5 substituents; Each Cy ８Ｂ But C ６～１０ Aryl, C ３～１５ Cycloalkyl, 5-10 membered hetero aryl, or 4- to 10-membered heterocycloalkyl; Cy ８Ｂ The C forming ６ ～１０ Aryl, C ３～１５ cycloalkyl, 5- to 10-membered heteroaryl, or 4- to 10-membered heteroaryl Each of the 0-membered heterocycloalkyls is unsubstituted or each independently is unsubstituted C １ ～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, halogen, C １～６ Haloal キル、CN、OR ａ１ 、SR ａ１ 、NR ｃ１ R ｄ１ 、C(O)OR ａ１ 、C(O)NR ｃ １ R ｄ１ and each independently a halogen, C １～６ Haloalkyl, CN, OR ａ１ , SR ａ１ , and N.R. ｃ１ R ｄ１ by one, two, or three substituents selected from Substituted C １～６ 1, 2, 3, 4, or 5 substituents selected from alkyl is replaced by R ９ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , N.R. ｃ１ R ｄ１ , N.R. ｃ １ C(O)R ｂ１ , C(O)OR ａ１ , C(O)NR ｃ１ R ｄ１ , or each independently: Halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ mosquito C substituted by 1, 2, or 3 substituents selected from １～６ With alkyl can be, R １０ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, ha Rogen, 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 Haloal Kill, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ 1, 2, or is substituted by three substituents １～６ is alkyl, Cy Ｄ７１ But C ６～１０ Aryl, C ３～１５ Cycloalkyl, 5-14 membered hetero aryl, or 4- to 10-membered heterocycloalkyl; Cy Ｄ７１ The C forming ６～１０ Aryl, C ３～１５ cycloalkyl, 5- to 10-membered heteroaryl, or 4- Each 10-membered heterocycloalkyl is unsubstituted or Ｄ７２ , C.H. ２ Cy 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 and 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 Ha alkyl, CN, OR ａ１ , S.R. ａ１ , C(O)OR ａ１ , and N.R. ｃ１ R ｄ１ from C substituted with 1, 2, or 3 selected substituents １～６ If alkyl Kuha C ２～６ alkenyl; is replaced by Each Cy Ｄ７２ But C ６～１０ Aryl, C ３～１５ Cycloalkyl, 5- to 10-membered heptane aryl, or 4- to 10-membered heterocycloalkyl; Cy Ｄ７２ forming C ６～１０ Aryl, C ３～１５ cycloalkyl, 5- to 10-membered heteroaryl, or 4 each of the 1 to 10-membered heterocycloalkyls 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- to 10-membered heterocycloalkyl, halogen, C １～６ Hello Rukill, 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- to 10-membered heterocycloalkyl, halogen, C １～６ Haloalkyl, CN, OR ａ１ , SR ａ１ , C(O)OR ａ１ , and N.R. ｃ１ R ｄ１ 1, 2, or 3 selected from C substituted by substituents １～６ alkyl is substituted with five substituents, ６～１０ Aryl, C ３～１５ Cycloa alkyl, and 4- to 10-membered heterocycloalkyl are each optionally independently selected from C １～６ a 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 1, 2, or 3 selected from is substituted with substituents, R ａ１ , R ｂ１ , R ｃ１ , and R ｄ１ are each 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 a Rukylen, C １～６ Alkoxy-C １～６ Alkylene, C ６～１０ Aryl, C ２～６ a alkenyl, and C ２～６ alkynyl; or R ｃ１ and R ｄ１ But together with the nitrogen atom to which they are both bonded, a 0-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 is substituted with 1, 2, or 3 substituents selected from Although it forms a heterocyclic ring, 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 is not present or L １ is C(O), the formula N(R Ｎ ) is the basis the law of nature, L ２ is not present or L １ is N (R Ｎ ) is a group of formula C(O) the law of nature, A Ｄ４１ But, A Ｄ４２ is NH or NC １～６ When it is alkyl, it is CH, C(C １ ～６ alkyl), A Ｄ４２ But, A Ｄ４１ is NH or NC １～６ When 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 , O.C.y. １Ａ , O(C １～３ (alkylenyl)Cy １Ａ , N.H. Cy 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 , O.C.y. ７Ａ , O(C １～３ (alkylenyl)Cy ７Ａ , C(O)O Cy 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 a (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 , O.C.y. ８Ａ , O(C １～３ (alkylenyl)Cy ８Ａ , C(O)O Cy 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 a (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 (provided that or a pharmaceutically acceptable salt thereof.

2. R ６ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Hello Lukil, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ Selected from 1, 2, if C substituted by at least three substituents １～６ is alkyl, R ７ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , N.R. ｃ１ R ｄ１ , C(O ) OR ａ１ , C(O)NR ｃ１ R ｄ１ , Cy ７Ａ , O.C.y. ７Ａ , O(C １～３ Alkireni Cy ７Ａ , C(O)OCy ７Ａ , C(O)O(C １～３ (alkylenyl)Cy ７Ａ , N HCy 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 Archi Renyl)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 , C.N., O.R. ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ 1, 2, or 3 selected from C substituted by substituents １～６ is alkyl, R ８ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.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 アル Cylenyl)Cy ８Ａ , C(O)OCy ８Ａ , C(O)O(C １～３ (alkylenyl)Cy ８ Ａ , 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 , S.O. ２ NHCy ８Ａ , N(C １～６ alkyl) (C １～３ (alkylenyl)Cy ８Ａ , C(O)NHCy ８ Ａ , 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 Hello Lukil, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ Selected from 1, 2, if C substituted by at least three substituents １～６ is alkyl, R ９ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Hello Lukil, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ Selected from 1, 2, if C substituted by at least three substituents １～６ is alkyl, Cy Ｄ７１ But C ６～１０ Aryl, C ３～１５ Cycloalkyl, 5-14 membered hetero aryl, or 4- to 10-membered heterocycloalkyl; Cy Ｄ７１ The C forming ６～１０ Aryl, C ３～１５ cycloalkyl, 5- to 10-membered heteroaryl, or 4- Each 10-membered heterocycloalkyl is unsubstituted or Ｄ７２ , C.H. ２ Cy 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 and 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 1, 2 selected from or C substituted by three substituents １～６ Alkyl or C ２～６ Al substituted by 0, 1, 2, 3, 4, or 5 substituents selected from: the law of nature, Each Cy Ｄ７２ But C ６～１０ Aryl, C ３～１５ Cycloalkyl, 5- to 10-membered heptane aryl, or 4- to 10-membered heterocycloalkyl; Cy Ｄ７２ forming C ６～１０ Aryl, C ３～１５ cycloalkyl, 5- to 10-membered heteroaryl, or 4 each of the 1 to 10-membered heterocycloalkyls is unsubstituted or each independently is unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～１５ Cycloalkane Ru, 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 mosquito C substituted by 1, 2, or 3 substituents selected from １～６ Alkyl or and is substituted by 1, 2, 3, 4, or 5 substituents selected from R ａ１ , R ｂ１ , R ｃ１ , and R ｄ１ are each independently H, C １～６ Alkyl, HO-C １～６ Alkylene, C １～６ Alkoxy-C １～６ Alkylene, C ６～１０ Ants Ru, C ２～６ alkenyl, and C ２～６ alkynyl; or R ｃ１ and R ｄ１ But together with the nitrogen atom to which they are both bonded, The compound of claim 1 , which forms a 0-membered unsubstituted heterocycloalkyl ring.

3. L １ But N(R Ｎ 3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, Acceptable salts.

4. L １ is C(O), or a pharmaceutically acceptable salt thereof. Acceptable salt.

5. 5. A compound according to any one of claims 1 to 4, wherein D is a group of formula (D1) A pharmaceutically acceptable salt of

6. 5. A compound according to any one of claims 1 to 4, wherein D is a group of formula (D2) A pharmaceutically acceptable salt of

7. A compound according to any one of claims 1 to 4, wherein D is a group of formula (D3) A pharmaceutically acceptable salt of

8. A １ But C(O)R １ The compound according to any one of claims 1 to 7, A pharmaceutically acceptable salt of

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 The alkylene group is unsubstituted or are each independently a halogen, OR ａ１ , N.R. ｃ１ R ｄ１ , N.R. ａ１ (CO)(C １～６ a Lukil), and N.R. ａ１ (CO)O(C １～６ alkyl) 6. The compound according to claim 1, wherein the compound is substituted with 3, 4, or 5 substituents. The compound described, or a pharmaceutically acceptable salt thereof.

10. 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) group is NR ｃ１ R ｄ１ , N.R. ａ１ (CO)(C １～６ alkyl), or NR ａ１ (CO)O(C １～６ alkyl), For example, CH ２ CH(NH ２ )C(O)OH. The compound, or a pharmaceutically acceptable salt thereof.

11. A １ is CN, or a pharmaceutical composition thereof. Acceptable salts.

12. A １ But NO ２ The compound according to any one of claims 1 to 5, or a pharmaceutical composition thereof, A commercially acceptable salt.

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

6. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof.

14. A １ are unsubstituted or each independently represent a halogen, OR ａ１ , S.R. ａ１ , C( O) OR ａ１ , N.R. ｃ１ R ｄ１ , and C(O)NR ｃ１ R ｄ１ 1, 2, selected from S(O) substituted by 3, 4, or 5 substituents ２ R １ , NHC(O) R １ , NH(C １～３ alkylene)-C(O)R １ , 5- to 10-membered heteroaryl, 4-1 0-membered heterocycloalkyl, CH ２ (5- to 10-membered heteroaryl), or CH ２ (4~ 10-membered heterocycloalkyl), or a pharmaceutically acceptable salt thereof. Acceptable salt.

15. A ２ But, CR ２ The compound according to any one of claims 1 to 14, or a drug thereof, A physiologically acceptable salt.

16. R ２ 16. The compound of claim 15, wherein is H, or a pharmaceutically acceptable salt thereof.

17. A ２ is N, or a pharmaceutical composition thereof Acceptable salts.

18. A ３ But, CR ３ The compound according to any one of claims 1 to 17, or a drug thereof, A physiologically acceptable salt.

19. R ３ But H, C １～６ Alkyl, or C １～６ 19. The compound according to claim 18, wherein the alkyl group is haloalkyl. The compound or a pharmaceutically acceptable salt thereof.

20. R ３ is H, methyl, or trifluoroethyl; or a pharmaceutically acceptable salt thereof.

21. R ３ 19. The compound of claim 18, wherein is H, or a pharmaceutically acceptable salt thereof.

22. A ３ is N, or a pharmaceutical composition thereof Acceptable salts.

23. A ４ But, CR ４ The compound according to any one of claims 1 to 22, or a drug thereof, A physiologically acceptable salt.

24. R ４ 24. The compound of claim 23, wherein is H, or a pharmaceutically acceptable salt thereof.

25. A ４ is N, or a pharmaceutical composition thereof Acceptable salts.

26. A ５ But, CR ５ The compound according to any one of claims 1 to 25, or a drug thereof, A physiologically acceptable salt.

27. R ５ 27. The compound of claim 26, wherein is H, or a pharmaceutically acceptable salt thereof.

28. A ５ is N, or a pharmaceutical composition thereof Acceptable salts.

29. A ２ But, CR ２ and A ３ But, CR ３ and A ４ But, CR ４ and A ５ But, CR ５ The compound according to any one of claims 1 to 14, which is Salt.

30. A ２ But, CR ２ and A ３ But, CR ３ and A ４ But, CR ４ and A ５ But in N 15. The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt thereof. 。

31. A compound according to any one of claims 1 to 4, wherein D is a group of formula (D4) A pharmaceutically acceptable salt of

32. A Ｄ４１ is CH, or a pharmaceutically acceptable salt thereof. salt.

33. A Ｄ４１ But C (C １～６ 32. The compound of claim 31, wherein Pharmaceutically acceptable salts.

34. A Ｄ４１ is N, or a pharmaceutically acceptable salt thereof. 。

35. A Ｄ４２ is NH, or a compound according to any one of claims 31 to 34 A pharmaceutically acceptable salt of

36. A Ｄ４２ But NC １～６ The compound according to any one of claims 31 to 34, which is alkyl. or a pharmaceutically acceptable salt thereof.

37. A Ｄ４２ But CH ２ A compound according to any one of claims 31 to 36, which is and pharmaceutically acceptable salts thereof.

38. The compound according to any one of claims 31 to 37, wherein m is 1, or a pharmaceutical composition thereof. Acceptable salts.

39. The compound according to any one of claims 31 to 37, wherein m is 2, or a pharmaceutical composition thereof. Acceptable salts.

40. The compound according to any one of claims 31 to 37, wherein m is 3, or a pharmaceutical composition thereof. Acceptable salts.

41. A compound according to any one of claims 1 to 4, wherein D is a group of formula (D5) A pharmaceutically acceptable salt of

42. 42. The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein m is 1.

43. 42. The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein m is 2.

44. 42. The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein m is 3.

45. A compound according to any one of claims 1 to 4, wherein D is a group of formula (D6) A pharmaceutically acceptable salt of

46. 46. ​​The compound of claim 45, or a pharmaceutically acceptable salt thereof, wherein m is 1.

47. 46. ​​The compound of claim 45, or a pharmaceutically acceptable salt thereof, wherein m is 2.

48. 46. ​​The compound of claim 45, or a pharmaceutically acceptable salt thereof, wherein m is 3.

49. R １ But H, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Cy １Ａ , OH, OC １～６ Alkyl, OCy １Ａ , O(C １～３ (alkylenyl)Cy １Ａ , 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 Archi (C １～３ (alkylenyl)Cy １Ａ Any one of claims 1 to 10 or 15 to 48, A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof.

50. R １ But 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 The compound according to claim 47, or a pharmaceutically acceptable salt thereof.

51. R １ However, NHCy １Ａ 48. The compound of claim 47, Salt that can be used.

52. R １ But C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Cy １Ａ , O H or OC １～６ Any one of claims 1 to 10 or 15 to 48, wherein the alkyl is Item 1. The compound according to item 1, or a pharmaceutically acceptable salt thereof.

53. R １ 53. The compound of claim 52, or a pharmaceutically acceptable salt thereof, wherein is OH.

54. R １ is a group of one of the following formulae: 【Chemistry 3】 During the ceremony, R １１ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １２ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １３ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １４ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １５ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １６ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １７ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １８ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ alkyl. 51, or a pharmaceutically acceptable salt thereof.

55. R １ is a group of one of the following formulae: A physiologically acceptable salt. 【Chemistry 4】

56. Cy １Ａ But C ６～１０ Aryl, e.g., unsubstituted or 0, 1, or Two 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 , NR ｃ１ R ｄ１ and each independently a halogen, C １～６ Haloalkyl, CN, OR ａ １ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ by one, two, or three substituents selected from C is substituted with １～６ 0, 1, 2, 3, 4, or 5 selected from alkyl phenyl substituted by a substituent of any one of claims 1 to 10 or 15 to 51.

10. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof.

57. Cy １Ａ But 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 Archi Nyl, 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 ,oh Call NR ｃ１ R ｄ１ and substituted by one, two, or three substituents selected from RuC １～６ by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl; 57. The compound of claim 56, wherein the compound is substituted phenyl, or a pharmaceutically acceptable salt thereof. Salt that can be used.

58. Cy １Ａ But C ６～１０ Aryl, e.g., unsubstituted or containing one Cy １Ｂ to 57. The compound of claim 56, wherein the compound is phenyl substituted by Acceptable salts.

59. Each Cy １Ｂ 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 ａ １ , S.R. ａ１ , N.R. ｃ１ R ｄ１ and each independently a halogen, C １～６ Hello Aruki Lu, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ 1, 2, or C substituted by 3 substituents １～６ 1, 2, 3, 4 selected from alkyl, or substituted by 5 substituents, C ３～１５ Cycloalkyl (e.g., C ３～１０ cycloalkyl, for example, adamantyl, for example, adamant-1-yl) A compound according to any one of claims 1 to 10, 15 to 51, or 56 to 58, or a pharmaceutically acceptable salt thereof.

60. Each Cy １Ｂ is unsubstituted C ３～１５ Cycloalkyl (e.g., C ３～１０ cycloalkyl , for example, adamantyl, for example, adamant-1-yl) according to claim 59. The compound, or a pharmaceutically acceptable salt thereof.

61. Cy １Ａ is a group of one of the following formulae: 【Chemistry 5】 During the ceremony, R １１ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １２ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １３ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １４ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １５ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １６ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １７ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １８ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ alkyl. A compound according to any one of claims 1 to 10 and 15 to 51, or a pharmaceutically acceptable salt thereof. 。

62. Cy １Ａ is a group of one of the following formulae: A pharmaceutically acceptable salt of 【Chemistry 6】

63. Cy １Ａ is unsubstituted or contains 0, 1, or 2 Cy １Ｂ , and each Independently, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, halogen N, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , N.R. ｃ１ R ｄ１ , and each Independently, halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ １ 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; There is C ３～１５ Cycloalkyl (e.g., C ３～１０ Cycloalkyl, e.g., adamantane Any one of claims 1 to 10 and 15 to 51, wherein the alkyl group is butyl, for example, adamant-1-yl.

1. The compound according to claim 1, or a pharmaceutically acceptable salt thereof.

64. R ７ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , N.R. ｃ１ R ｄ１ ,or Halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ mosquito C substituted by 1, 2, or 3 substituents selected from １～６ With alkyl can be, R ８ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , N.R. ｃ１ R ｄ１ ,or each independently represents 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 The compound of any one of claims 50, 51, or 54 to 63, which is alkyl. or a pharmaceutically acceptable salt thereof.

65. R ７ is H and R ８ is H, or a pharmaceutical composition thereof Acceptable salts.

66. L ２ A compound according to any one of claims 1 to 65, or a pharmaceutical composition thereof, in which A commercially acceptable salt.

67. L ２ But N(R Ｎ ) a compound according to any one of claims 1 or 4 to 65, or a pharmaceutically acceptable salt thereof.

68. L ２ is C(O). or a pharmaceutically acceptable salt thereof.

69. Each R Ｎ is H, or a pharmaceutical composition thereof. A commercially acceptable salt.

70. A ６ But, CR ６ The compound according to any one of claims 1 to 67, or a drug thereof, A physiologically acceptable salt.

71. R ６ is H, or a pharmaceutically acceptable salt thereof.

72. A ６ is N, or a pharmaceutical composition thereof Acceptable salts.

73. A ７ But, CR ７ The compound according to any one of claims 1 to 72, or a drug thereof, A physiologically acceptable salt.

74. R ７ is H, or a pharmaceutically acceptable salt thereof.

75. R ７ But Cy ７Ａ , O.C.y. ７Ａ , O(C １～３ (alkylenyl)Cy ７Ａ , C(O)OC y 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 Al Cylenyl)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 74. The compound of claim 73, or a pharmaceutically acceptable salt thereof.

76. R ７ But Cy ７Ａ , O.C.y. ７Ａ , O(C １～３ (alkylenyl)Cy ７Ａ , NHCy ７Ａ , NH(C １～３ (alkylenyl)Cy ７Ａ , N(C １～６ alkyl)Cy ７Ａ , or N (C １～６ alkyl) (C １～３ (alkylenyl)Cy ７Ａ The compound according to claim 73, or a pharmaceutically acceptable salt thereof.

77. R ７ However, NHCy ７Ａ 74. The compound of claim 73, wherein: Salt that can be used.

78. R ７ is a group of one of the following formulae: 【Chemistry 7】 During the ceremony, R ７１ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７２ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７３ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７４ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７５ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７６ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７７ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７８ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ alkyl.

78. The compound according to claim 77, or a pharmaceutically acceptable salt thereof.

79. R ７ is a group of one of the following formulae: A physiologically acceptable salt. 【Chemistry 8】

80. Cy ７Ａ But C ６～１０ Aryl, e.g., unsubstituted or 0, 1, or Two 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 , NR ｃ１ R ｄ１ and each independently a halogen, C １～６ Haloalkyl, CN, OR ａ １ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ by one, two, or three substituents selected from C is substituted with １～６ 0, 1, 2, 3, 4, or 5 selected from alkyl and Claims 1 to 63, 66 to 73, and 78. The compound according to any one of claims 75 to 77, or a pharmaceutically acceptable salt thereof.

81. Cy ７Ａ But 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 Archi Nyl, 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 ,oh Call NR ｃ１ R ｄ１ and substituted by one, two, or three substituents selected from RuC １～６ by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl; 81. The compound of claim 80, which is substituted phenyl, or a pharmaceutically acceptable salt thereof. Salt that can be used.

82. Cy ７Ａ But C ６～１０ Aryl, e.g., unsubstituted or containing one Cy ７Ｂ to 82. The compound of claim 81, wherein R is phenyl substituted by R, ... Acceptable salts.

83. Each Cy7 Ｂ 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 ａ １ , S.R. ａ１ , N.R. ｃ１ R ｄ１ and each independently a halogen, C １～６ Hello Aruki Lu, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ 1, 2, or C substituted by 3 substituents １～６ 1, 2, 3, 4 selected from alkyl, or substituted by 5 substituents, C ３～１５ Cycloalkyl (e.g., C ３～１０ cycloalkyl, for example, adamantyl, for example, adamant-1-yl) The method according to any one of claims 1 to 63, 66 to 73, 75 to 77, and 80 to 82, or a pharmaceutically acceptable salt thereof.

84. Each Cy ７Ｂ is unsubstituted C ３～１５ Cycloalkyl (e.g., C ３～１０ cycloalkyl , for example, adamantyl, for example, adamant-1-yl) according to claim 83 The compound, or a pharmaceutically acceptable salt thereof.

85. Cy ７Ａ is a group of one of the following formulae: 【Chemistry 9】 During the ceremony, R ７１ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７２ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７３ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７４ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７５ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７６ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７７ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７８ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ alkyl. The compound according to any one of claims 1 to 63, 66 to 73, 75 to 77, and 80 to 84. or a pharmaceutically acceptable salt thereof.

86. Cy ７Ａ 86. The compound of claim 85, wherein is a group of one of the following formulae: A pharmaceutically acceptable salt of 【Chemistry 10】

87. Cy ７Ａ is unsubstituted or contains 0, 1, or 2 Cy ７Ｂ , and each Independently, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, halogen N, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , N.R. ｃ１ R ｄ１ , and each independently Standing, 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 a and substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl, Ru, C ３～１５ Cycloalkyl (e.g., C ３～１０ Cycloalkyl, for example, adaman Claims 1 to 63, 66 to 73, and 7 are alkyl groups such as adamant-1-yl.

78. The compound according to any one of claims 5 to 77, or a pharmaceutically acceptable salt thereof.

88. R １ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , N.R. ｃ１ R ｄ１ ,or each independently represents 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 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 ,or each independently represents 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 The compound of any one of claims 75 to 87, or a pharmaceutical composition thereof, wherein A commercially acceptable salt.

89. A １ But, CR １ and A ２ But, CR ２ and A ３ But, CR ３ and A ４ But, CR ４ and A ５ But, CR ５ and A ６ But, CR ６ and A ８ But, CR ８ and A ９ But, CR ９ and A １０ But, CR １０ 89. The compound of claim 88, which is Pharmaceutically acceptable salts.

90. A １ But, CR １ and A ３ But, CR ３ and A ４ But, CR ４ and A ５ But in N Yes, A ６ But, CR ６ and A ８ But, CR ８ and A ９ But, CR ９ and A １０ but , C.R. １０ 89. The compound of claim 88, which is: or a pharmaceutically acceptable salt thereof.

91. A ７ is N, or a pharmaceutical composition thereof Acceptable salts.

92. A ８ But, CR ８ The compound according to any one of claims 1 to 91, or a drug thereof, A physiologically acceptable salt.

93. R ８ is H, or a pharmaceutically acceptable salt thereof.

94. R ８ But Cy ８Ａ , O.C.y. ８Ａ , O(C １～３ (alkylenyl)Cy ８Ａ , C(O)OC y 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 Al Cylenyl)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 93. The compound of claim 92, or a pharmaceutically acceptable salt thereof.

95. R ８ But 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 The compound according to claim 92, or a pharmaceutically acceptable salt thereof.

96. R ８ However, NHCy ８Ａ 96. The compound of claim 95, Salt that can be used.

97. R ８ is a group of one of the following formulae: 【Chemistry 11】 During the ceremony, R ８１ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８２ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８３ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８４ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８５ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８６ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８７ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８８ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ alkyl. 96, or a pharmaceutically acceptable salt thereof.

98. R ８ is a group of one of the following formulas, or a drug thereof: A physiologically acceptable salt. 【Chemistry 12】

99. Cy ８Ａ But C ６～１０ Aryl, e.g., unsubstituted or 0, 1, or Two 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 , NR ｃ１ Rd1 and each independently represent a halogen, C １～６ Haloalkyl, CN, OR ａ １ , SR a1 , and NR c1 R d1 , C is substituted with １～６ 0, 1, 2, 3, 4, or 5 selected from alkyl phenyl substituted by a substituent of any one of claims 1 to 63, 66 to 87, and 91; 92, or any one of 94 to 96, or a pharmaceutically acceptable salt thereof Salt.

100. Cy ８Ａ But 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 Archi Nyl, 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 ,oh Call NR ｃ１ R ｄ１ and substituted by one, two, or three substituents selected from RuC １～６ by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl; 100. The compound of claim 99, which is substituted phenyl, or a pharmaceutically acceptable salt thereof. Salt that can be used.

101. Cy ８Ａ But C ６～１０ Aryl, e.g., unsubstituted or containing one Cy ８Ｂ to 101. The compound of claim 100, wherein the compound is phenyl substituted by Acceptable salts.

102. 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 ａ １ , S.R. ａ１ , N.R. ｃ１ R ｄ１ and each independently a halogen, C １～６ Hello Aruki Lu, CN, OR ａ１ , S.R. ａ１ , and N.R. ｃ１ R ｄ１ 1, 2, or C substituted by 3 substituents １～６ 1, 2, 3, 4 selected from alkyl, or substituted by 5 substituents, C ３～１５ Cycloalkyl (e.g., C ３～１０ cycloalkyl, for example, adamantyl, for example, adamant-1-yl) Any of claims 1 to 63, 66 to 87, 91, 92, 94 to 96, or 99 to 101. A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof.

103. Each Cy ８Ｂ is unsubstituted C ３～１５ Cycloalkyl (e.g., C ３～１０ cycloalkyl , for example, adamantyl, for example, adamant-1-yl) according to claim 102 or a pharmaceutically acceptable salt thereof.

104. Cy ８Ａ is a group of one of the following formulae: 【Chemistry 13】 During the ceremony, R ８１ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８２ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８３ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８４ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８５ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８６ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８７ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８８ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ alkyl. The compound according to any one of claims 1 to 63, 66 to 87, 91, 92, or 94 to 96. or a pharmaceutically acceptable salt thereof.

105. Cy ８Ａ is a group of one of the following formulae: and pharmaceutically acceptable salts thereof. 【Chemistry 14】

106. Cy ８Ａ is unsubstituted or contains 0, 1, or 2 Cy ８Ｂ , and each Independently, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, halogen N, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , N.R. ｃ１ R ｄ１ , and each independently Standing, 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 a and substituted by 0, 1, 2, 3, 4, or 5 substituents selected from alkyl, Ru, C ３～１５ Cycloalkyl (e.g., C ３～１０ Cycloalkyl, for example, adaman 1-methyl, for example, adamant-1-yl), claims 1 to 63, 66 to 87, 91, 9 2, or any one of 94 to 96, or a pharmaceutically acceptable salt thereof salt.

107. R １ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, Halogen, C １～６ Haloalkyl, CN, OR ａ１ , S.R. ａ１ , N.R. ｃ１ R ｄ１ ,or each independently represents 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 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 ,or each independently represents 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 The compound according to any one of claims 90 to 100, or a drug thereof, which is alkyl. A physiologically acceptable salt.

108. A １ But, CR １ and A ２ But, CR ２ and A ３ But, CR ３ and A ４ But, CR ４ and A ５ But, CR ５ and A ６ But, CR ６ and A ７ But, CR ７ and A ８ But, CR ８ and A ９ But, CR ９ and A １０ But, CR １０ Claim 107: The compound described, or a pharmaceutically acceptable salt thereof.

109. A １ But, CR １ and A ３ But, CR ３ and A ４ But, CR ４ and A ５ But in N Yes, A ６ But, CR ６ and A ７ But, CR ７ and A ８ But, CR ８ and A ９ but, CR ９ and A １０ But, CR １０ 108. The compound of claim 107, or a drug thereof, A physiologically acceptable salt.

110. A ８ is N, or a pharmaceutical composition thereof Acceptable salts.

111. A ９ But, CR ９ or a compound according to any one of claims 1 to 109, which is Pharmaceutically acceptable salts.

112. R ９ But H, C １～６ Alkyl, or C １～６ haloalkyl The compound described, or a pharmaceutically acceptable salt thereof.

113. R ９ is H, methyl, or trifluoroethyl. or a pharmaceutically acceptable salt thereof.

114. R ９ is H, or a pharmaceutically acceptable salt thereof.

115. A ９ is N, or a pharmaceutical composition thereof A commercially acceptable salt.

116. A １０ But, CR １０ or a compound according to any one of claims 1 to 114, and pharmaceutically acceptable salts thereof.

117. R １０ is H, or a pharmaceutically acceptable salt thereof. 。

118. A １０ is N, or a drug thereof A physiologically acceptable salt.

119. The compound is one of the compounds of the following formulae (I-1) to (I-60): 【Chemistry 15-1】 【Chemistry 15-2】 【Chemistry 15-3】 【Chemistry 15-4】 【Chemistry 15-5】 【Chemistry 15-6】 【Chemistry 15-7】 During the ceremony, R １ 、R ２ 、R ３ 、R ４ 、R ５ 、R ６ 、R ７ 、R ８ 、R ９ 、R １０ 、R Ｎ 、A １ 、A ２ 、A ３ 、A ４ 、A ５ 、A ６ 、A ７ 、A ８ 、A ９ 、A １０ 、Cy １Ａ 、Cy １Ｂ 、Cy ７ Ａ , Cy ７Ｂ , Cy ８Ａ , Cy ８Ｂ , L １ , and L ２ is as defined in claim 1 can be, L ７ is absent or is O, NH, or N(C １～６ alkyl), L ８ is absent or is O, NH, or N(C １～６ alkyl), R １１ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １２ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １３ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １４ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １５ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １６ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １７ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R １８ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７１ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７２ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７３ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７４ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７５ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７６ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７７ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ７８ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８１ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８２ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８３ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８４ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８５ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８６ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８７ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ is alkyl, R ８８ is H, unsubstituted C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl , halogen, C １～６ Haloalkyl, CN, OR ａ１ , 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 Selected from C substituted by 1, 2, or 3 substituents １～６ alkyl.

1. The compound according to claim 1, or a pharmaceutically acceptable salt thereof.

120. R １ is OH, or a pharmaceutically acceptable salt thereof. 。

121. R １ But, O.C. １～６ 120. The compound of claim 119, which is alkyl (e.g., OMe). or a pharmaceutically acceptable salt thereof.

122. R １ But C ２～６ 120. The compound of claim 119, which is alkenyl (e.g., vinyl). or a pharmaceutically acceptable salt thereof.

123. L ７ is NH, or a compound according to any one of claims 119 to 122 A pharmaceutically acceptable salt of

124. L ８ is NH, or a compound according to any one of claims 119 to 122 A pharmaceutically acceptable salt of

125. 10. The compound of claim 1, wherein the compound is a compound of one of the following formulas: is a pharmaceutically acceptable salt thereof. 【Chemistry 16-1】 【Chemistry 16-2】 【Chemistry 16-3】 【Chemistry 16-4】 【Chemistry 16-5】 【Chemistry 16-6】 【Chemistry 16-7】 【Chemistry 16-8】 【Chemistry 16-9】 【Chemistry 16-10】 【Chemistry 16-11】 【Chemistry 16-12】 【Chemistry 16-13】 【Chemistry 16-14】 【Chemistry 16-15】 【Chemistry 16-16】 【Chemistry 16-17】 【Chemistry 16-18】 【Chemistry 16-19】 【16-20】 【Chemistry 16-21】 【Chemistry 16-22】

126. 2. The compound of formula (I) of claim 1, wherein the compound is selected from any one of the following compounds:

1. The compound according to claim 1, or a pharmaceutically acceptable salt thereof. 【Chemistry 17-1】 【Chemistry 17-2】 【Chemistry 17-3】 【Chemistry 17-4】 【Chemistry 17-5】 【Chemistry 17-6】 【Chemistry 17-7】 【Chemistry 17-8】 【Chemistry 17-9】 【Chemistry 17-10】 【Chemistry 17-11】 【Chemistry 17-12】

127. A compound according to any one of claims 1 to 126, or a pharmaceutically acceptable salt thereof. and at least one pharmaceutically acceptable carrier.

128. A method for inhibiting palmitoylation of a TEAD transcription factor, comprising:

127. The compound according to any one of claims 1 to 126, or a pharmaceutically acceptable salt thereof. or the composition of claim 127.

129. A method for treating a disease or condition associated with the activity of a TEAD transcription factor, comprising: A therapeutically effective amount of any one of claims 1 to 126 is administered to a patient in need of such treatment. or a pharmaceutically acceptable salt thereof, or the composition of claim 127. The method includes providing.

130. A method of treating cancer, comprising administering to a patient in need of such treatment a therapeutically effective amount of A compound according to any one of items 1 to 126, or a pharmaceutically acceptable salt thereof, comprising administering the composition of claim 127.

131. 131. The method of claim 130, wherein the cancer is a solid tumor or a blood cancer.

132. The cancer is 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, Bladder cancer, sarcoma, bladder cancer, lymphoma, leukemia, acute lymphoblastic leukemia, acute myeloid leukemia , chronic lymphocytic leukemia, chronic myeloid leukemia, diffuse large B-cell lymphoma, mantle lymphoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, or multiple myeloma; 132. The method of claim 130 or 131.

133. The cancer is hepatocellular carcinoma, medulloblastoma, cutaneous squamous cell carcinoma, lung cancer, pancreatic cancer, esophageal cancer, 132. The method of claim 130 or 131, wherein the cancer is liver cancer, colon cancer, melanoma, or bladder melanoma. How to do it.

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