TRIM7 inhibitors and their applications

Abstract

This disclosure relates to compositions and methods comprising TRIM7 inhibitors that find applications in the treatment of cancer, including cancers resistant to anti-checkpoint agents, as well as diseases such as infections and inflammatory diseases.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority and interest to U.S. Provisional Patent Application No. 63 / 520,551 filed on 18 August 2023, U.S. Provisional Patent Application No. 63 / 561,076 filed on 4 March 2024, and U.S. Provisional Patent Application No. 63 / 631,138 filed on 8 April 2024, all of which are incorporated herein by reference in their entirety.

[0002] This disclosure relates, in particular, to compositions and methods comprising compounds containing TRIM7 inhibitors that find applications in the treatment of cancer, including cancers resistant to anti-checkpoint agents, infections, and inflammatory diseases.

[0003] Sequence List This application includes a sequence listing submitted in XML format via EFS-Web. The contents of the XML copy named "SHK-085PC_116981-5085-WO_Sequence_Listing," created on August 15, 2024, with a size of 4,096 bytes, are incorporated herein by reference in their entirety. [Background technology]

[0004] Drug resistance remains one of the biggest challenges in cancer treatment. It is found across all types of cancer and all modes of treatment, including molecular targeted therapy, immunotherapy, and chemotherapy. In some patients, the unpredictability of the response delays the initiation of effective treatment. Furthermore, while patients with advanced cancer are given drugs that help shrink the tumor, it is common for the cancer to subsequently develop resistance to those drugs. Unfortunately, there are few effective treatment options available for some patients with cancer resistant to anti-checkpoint therapies. Therefore, there is a need to develop new therapies for patients with drug-resistant cancer to improve outcomes for cancer patients. [Overview of the initiative]

[0005] Accordingly, the present disclosure provides, in part, compositions and methods for treating cancer, including but not limited to cancer resistant to anti-checkpoint agents. Also provided are methods of treating infectious diseases, and infectious and inflammatory diseases. For example, provided are methods of selecting patients for cancer treatment and methods of treating cancer based on the gene expression profile of TRIM7, which is dysregulated in anti-checkpoint resistant cancer.

[0006] In one embodiment, the present disclosure provides a compound of formula (I) or a pharmaceutically acceptable salt thereof.

Chemical Formula

[0007] In formula (I): A is

Chemical Formula

[0008] L is a linking group; R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a , R 5b , R 5c , R 5d , R 5e , R 6a , R 6b , R 6c , R 6d , R 6e , R 7a , R 7b , R 7c , R 7d , R 8 , R 9 , R 10 , R 11a , R 11b , and R11c Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen (halo), cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2; R 12 is H or an unsubstituted alkyl group; R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n1 is an integer between 0 and 5; t is either 1 or 2;

[0009] However, this is subject to the condition that the compound of formula (I) is not any of the compounds of formulas 1001, 1003, 1004, and 1006 to 1009 below.

[0010] [Table 1]

[0011] In some embodiments, the compound is the compound of formula (I), where R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a , R 5b , R 5c , R 5d , R 5e , R 6a , R 6b , R 6c , R 6d , R 6e , R 7a , R 7b , R 7c , R 7d , R 8 , R 9 , R 10 , R 11a , R 11b , and R 11care each independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl (optionally substituted with halogen, unsubstituted or substituted alkyl, and / or unsubstituted or substituted heterocyclyl), unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, halogen, -C(O)R a , -C(O)N(R a )2, -N(R a )2, -N(R a )C(O)R a , and -S(O) t R a . In some embodiments, the compound is a compound of Formula (I), wherein L is a bond, or an unsubstituted or substituted -C 1-10 alkyl-, -O-C 1-10 alkyl-, -C 1-10 alkenyl-, -O-C 1-10 alkenyl-, -C 1-10 cycloalkenyl-, -O-C 1-10 cycloalkenyl-, -C 1-10 alkynyl-, -O-C 1-10 alkynyl-, -C 1-10 aryl-, -O-C 1-10 -, -aryl-, -cycloalkyl-, -heterocyclyl-, -O-, -S-, -S-S-, -S(O) w -, -C(O)-, -C(O)O-, -OC(O)-, -C(O)S-, -SC(O)-, -OC(O)O-, -N(R b )-, -C(O)N(R b )-, -N(R b )C(O)-, -OC(O)N(R b )-, -N(R b )C(O)O-, -SC(O)N(R b )-, -N(R b )C(O)S-, -N(R b )C(O)N(R b )-, -N(R b )C(NR b )N(Rb )-,-N(R b )S(O) w -, -S(O) w N(R b )-,-S(O) w O-, -OS(O) w -, -OS(O) w O-, -O(O)P(OR b )O-, (O)P(O-)3, -O(S)P(OR b It comprises one or more linking groups selected from )O- and (S)P(O-)3, where w is 1 or 2, and R b L is independently hydrogen, optionally substituted alkyl, or optionally substituted aryl, and optionally L is a bond and / or -C(O)- and / or -C(H)(CH2) p C(O)NH2 and / or [ka] Here, p is an integer from 1 to 5, p is arbitrarily 2, and L is arbitrarily [ka] (Here, alkyl can be substituted or unsubstituted.) [ka]

[0012] That is the case.

[0013] In some embodiments, the compound of formula (I) is the compound of formula (10), [ka]

[0014] In formula (10): R 9a , R9b , R 9c , R 9d , and R 9e Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0015] R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n² is an integer between 0 and 5; t is either 1 or 2.

[0016] In some embodiments, the compound of formula (I) is the compound of formula (20) or (21), [ka]

[0017] In equations (20) and (21): n3 is an integer between 0 and 5.

[0018] In some embodiments, the compound of formula (I) is the compound of formula (30) or formula (31), [ka]

[0019] In equations (30) and (31): p is an integer between 0 and 5.

[0020] In some embodiments, the compound of formula (I) is the compound of formula (32), [ka]

[0021] In formula (32): q is an integer between 1 and 3.

[0022] In some embodiments, the compound of formula (I) is the compound of formula (40), [ka]

[0023] In formula (40): n4 is an integer between 0 and 5.

[0024] In some embodiments, the compound of formula (I) is the compound of formula (50), [ka]

[0025] In formula (50): R 10a , R 10b , R 10c , R 10d , and R 10e Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(Ra )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0026] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n5 is an integer between 0 and 5; t is either 1 or 2.

[0027] In some embodiments, the compound of formula (I) is the compound of formula (60), [ka]

[0028] In formula (60): n6 is an integer between 0 and 5.

[0029] In some embodiments, the compound of formula (I) is the compound of formula (70), [ka]

[0030] In formula (70): R 11a and R 11bEach of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0031] R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl.

[0032] In some embodiments, the compound of formula (70) is the compound of formula (700) or formula (701). [ka]

[0033] In some embodiments, the compound of formula (I) is the compound of formula (80) or formula (81), [ka]

[0034] In formula (80): R 11a and R 11b Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0035] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n8 is an integer between 1 and 5;

[0036] [ka] In formula (81): Alk is either unsubstituted or substituted alkyl; R 11a and R 11bEach of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0037] R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl.

[0038] In some embodiments, the compound of formula (80) is the compound of formula (800) or formula (801), or the compound of formula (81) is the compound of formula (802) or formula (803).

[0039] [ka]

[0040] In some embodiments, the compound of formula (I) is one of the compounds of formula (80), formula (81), or formulas (800) to (803), where R 5b and / or R 5c These are, independently, unsubstituted or substituted alkynyls, optionally substituted alkynyls, substituted aryls, substituted heteroaryls, halogens (optionally Br), and -N(R). a )2 (arbitrarily -NH2), and -N(R a )C(O)R a (Optional)

[0041] [ka]

[0042] (Selected from), optionally R 5b teeth

[0043] [ka]

[0044] Selected from, and optionally R 5c teeth

[0045] [ka]

[0046] Selected from. In some embodiments, the compound of formula (I) is one of the compounds of formula (80), formula (81), or formulas (800) to (803), where R 11a and R 11b Each of these is either an unsubstituted alkyl or R 11a and R 11b Each of them operates independently.

[0047] [ka]

[0048] is or R 11a R is selected from H and unsubstituted alkyl groups, 11b teeth

[0049] [ka]

[0050] is or R 11a H is R 11bR is an unsubstituted alkyl, where Y is selected from unsubstituted or substituted alkyls, optionally unsubstituted or substituted C1-C5 alkyls, unsubstituted or substituted aryls, optionally unsubstituted or substituted phenyls, unsubstituted or substituted cycloalkyls, optionally unsubstituted or substituted C3-C7 cycloalkyls, and unsubstituted or substituted alkoxys, optionally unsubstituted or substituted C1-C5 alkoxys, and n7 is an integer from 1 to 3, optionally n7 is 1 or 2. In some embodiments, the compound of formula (I) is one of the compounds of formula (80), formula (81), or formulas (800) to (803), where R 11a and R 11b Each of them operates independently.

[0051] [ka]

[0052] Selected from, and optionally R 11a and R 11b Each of them operates independently.

[0053] [ka]

[0054] Selected from. In some embodiments, the compound of formula (I) is one of the compounds of formula (80), formula (81), or formulas (800) to (803), where R 11a R is selected from H and -CH3, where R 11b teeth

[0055] [ka]

[0056] Selected from, optionally, R 11a R is selected from H and -CH3. 11b teeth

[0057] [ka]

[0058] Selected from. In some embodiments, the compound of formula (I) is one of the compounds of formula (80), formula (81), or formulas (800) to (803), where R 11a R is selected from H and -CH3. 11b teeth

[0059] [ka]

[0060] Selected from. In some embodiments, the compound of formula (I) is one of the compounds of formula (80), formula (81), or formulas (800) to (803), where R 11a H is R 11b is -CH3, or R 11a and R 11b Each of these is -CH3. In some embodiments, the compound of formula (I) is one of the compounds of formula (80), formula (81), or formulas (800) to (803), where n8 is 1.

[0061] In some embodiments, the compound of formula (I) is the compound of formula (82), [ka]

[0062] In formula (82): R 11a , R 11b , R 11c , and R 11dEach of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0063] R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl.

[0064] In some embodiments, the compound of formula (82) is the compound of formula (804) or formula (805). [ka]

[0065] In some embodiments, the compound of formula (I) is the compound of formula (90), [ka]

[0066] In formula (90): n is an integer between 1 and 5.

[0067] In some embodiments, the compound of formula (90) is one of the compounds of formula (900), formula (901), or formula (902). [ka]

[0068] In some embodiments, the compound of formula (I) is one of the compounds of formula (90), formula (900), formula (901), or formula (902), where R 12 is H or -CH3. In some embodiments, the compound of formula (I) is one of the compounds of formula (90), formula (900), formula (901), or formula (902), where R 11a is H or a substituted alkyl, optionally

[0069] [ka]

[0070] And, arbitrarily

[0071] [ka]

[0072] In some embodiments, the compound of formula (I) is one of the compounds of formula (90), formula (900), formula (901), or formula (902), where R 10 -C(O)R a And R can be any a R is selected from unsubstituted alkenyls, substituted alkyls, substituted aryls, and substituted heterocyclines, or R 10 ga-S(O) t R a And arbitrarily, t is 2, R a is a substituted aryl. In some embodiments, the compound of formula (I) is one of the compounds of formula (90), formula (900), formula (901), or formula (902), where R 10 teeth

[0073] [ka]

[0074] Selected from.

[0075] In some embodiments, the compound of formula (I) is any one of the compounds of formula 1002, formula 1005, or formulas 1010 to 1098, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of formula (I) is any one of the compounds of formula 1010, formula 1011, formulas 1020 to 1030, formula 1034, formula 1036, formula 1037, formula 1040, formula 1043, formula 1050, formulas 1053 to 1056, formula 1058, formula 1060, formula 1062, formula 1064, formula 1066, formula 1069, formula 1070, formula 1075, or formula 1084, or a pharmaceutically acceptable salt thereof.

[0076] In another embodiment, the present disclosure provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient: [ka]

[0077] In formula (I): A is

[0078] [ka]

[0079] Selected from;

[0080] L is a linking group;

[0081] R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a , R 5b , R 5c , R 5d , R 5e , R 6a , R 6b , R 6c , R 6d , R6e , R 7a , R 7b , R 7c , R 7d , R 8 , R 9 , R 10 , R 11a , R 11b , and R 11c Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0082] R 12 is H or an unsubstituted alkyl group;

[0083] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl;

[0084] n1 is an integer between 0 and 5;

[0085] t is either 1 or 2.

[0086] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), where R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a , R 5b , R 5c , R 5d , R 5e , R 6a , R 6b , R 6c , R 6d , R 6e , R 7a , R 7b , R 7c , R 7d , R 8 , R 9 , R 10 , R 11a , R 11b , and R 11cEach of these independently consists of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl (optionally substituted with halogen, unsubstituted or substituted alkyl, and / or unsubstituted or substituted heterocyclyl), unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, halogen, -N(R a )2, -C(O)R a ,-C(O)N(R a )2, -N(R a )C(O)R a , and -S(O) t R a Selected from. In some embodiments, the pharmaceutical composition comprises a compound of formula (I), where L is a bond, or unsubstituted or substituted -C 1-10 Alkyl-, -OC 1-10 Alkyl-, -C 1-10 Alkenyl-, -OC 1-10 Alkenyl-, -C 1-10 Cycloalkenyl-, -OC 1-10 Cycloalkenyl-,-C 1-10 Alkinyl-, -OC 1-10 Alkinyl-, -C 1-10 aryl-, -OC 1-10 -, -aryl-, -cycloalkyl-, -heterocyclyl-, -O-, -S-, -SS-, -S(O) w -, -C(O)-, -C(O)O-, -OC(O)-, -C(O)S-, -SC(O)-, -OC(O)O-, -N(R b )-,-C(O)N(R b )-,-N(R b )C(O)-,-OC(O)N(R b )-,-N(R b )C(O)O-, -SC(O)N(R b )-,-N(R b )C(O)S-, -N(R b )C(O)N(R b )-,-N(R b )C(NR b )N(R b)-,-N(R b )S(O) w -, -S(O) w N(R b )-,-S(O) w O-, -OS(O) w -, -OS(O) w O-, -O(O)P(OR b )O-, (O)P(O-)3, -O(S)P(OR b It comprises one or more linking groups selected from )O- and (S)P(O-)3, where w is 1 or 2, and R b L is independently hydrogen, optionally substituted alkyl, or optionally substituted aryl, and optionally L is bonded and / or -C(O)- and / or -C(H)(CH2) p C(O)NH2 and / or

[0087] [ka]

[0088] Here, p is an integer from 1 to 5, p is arbitrarily 2, and L is arbitrarily

[0089] [ka] (Here, alkyl can be substituted or unsubstituted.) [ka] That is the case.

[0090] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), which is a compound of formula (10): [ka]

[0091] In formula (10): R9a , R 9b , R 9c , R 9d , and R 9e Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0092] R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n² is an integer between 0 and 5; t is either 1 or 2.

[0093] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), which is a compound of formula (20) or formula (21): [ka]

[0094] In equations (20) and (21): n3 is an integer between 0 and 5.

[0095] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), which is a compound of formula (30) or formula (31): [ka]

[0096] In equations (30) and (31): p is an integer between 0 and 5.

[0097] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), which is a compound of formula (32). [ka]

[0098] In formula (32): q is an integer between 1 and 3.

[0099] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), which is a compound of formula (40):

[0100] [ka]

[0101] In formula (40): n4 is an integer between 0 and 5.

[0102] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), which is a compound of formula (50): [ka]

[0103] In formula (50): R 10a , R 10b , R 10c , R 10d , and R 10e Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a)2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0104] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n5 is an integer between 0 and 5; t is either 1 or 2.

[0105] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), which is a compound of formula (60). [ka]

[0106] In formula (60): n6 is an integer between 0 and 5.

[0107] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), which is a compound of formula (70): [ka]

[0108] In formula (70): R 11a and R 11bEach of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0109] R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl.

[0110] In some embodiments, the pharmaceutical composition comprises a compound of formula (70), which is a compound of formula (700) or formula (701). [ka]

[0111] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), which is a compound of formula (80) or formula (81). [ka]

[0112] In formula (80): R 11a and R 11b Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(Ra )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0113] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n8 is an integer between 1 and 5;

[0114] [ka]

[0115] In formula (81): Alk is either unsubstituted or substituted alkyl; R 11a and R 11bEach of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0116] R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl.

[0117] In some embodiments, the pharmaceutical composition comprises a compound of formula (800) which is a compound of formula (800) or formula (801), or a compound of formula (81) which is a compound of formula (802) or formula (803). [ka]

[0118] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), which is a compound of formula (82). [ka]

[0119] In formula (82): R 11a , R 11b , R 11c , and R 11d Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a, -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0120] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl.

[0121] In some embodiments, the pharmaceutical composition comprises a compound of formula (82), which is a compound of formula (804) or formula (805). [ka]

[0122] In some embodiments, the pharmaceutical composition comprises a compound of formula (I), which is a compound of formula (90). [ka]

[0123] In formula (90): n is an integer between 1 and 5.

[0124] In some embodiments, the pharmaceutical composition comprises a compound of formula (90), which is a compound of formula (900), formula (901), or formula (902). [ka]

[0125] In some embodiments, the pharmaceutical composition comprises a compound of formula (I) which is one of the compounds of formulas 1001 to 1098, or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition comprises a compound of formula (I) which is one of the compounds of formulas 1010, 1011, 1020 to 1030, 1034, 1036, 1037, 1040, 1043, 1050, 1053 to 1056, 1058, 1060, 1062, 1064, 1066, 1069, 1070, 1075, or 1084, or a pharmaceutically acceptable salt thereof.

[0126] In another embodiment, the Disclosure provides a method for treating cancer, infectious diseases, and inflammatory diseases in subjects requiring treatment, comprising administering a pharmaceutical composition comprising any one compound of formula (I), formula (10), formula (20), formula (21), formula (30) to formula (32), formula (40), formula (50), formula (60), formula (70), formula (80), formula (81), formula (82), formula (90), formula (700), formula (701), formula (800) to formula (805), formula (900), formula (901), or formula (902) to the subject. In some embodiments, cancers include basal cell carcinoma, biliary tract cancer, bladder cancer, bone cancer, brain and central nervous system cancer, breast cancer, peritoneal cancer, cervical cancer, choriocarcinoma, colon and rectum cancer, connective tissue cancer, digestive system cancer, endometrial cancer, esophageal cancer, eye cancer, head and neck cancer, gastric cancer (including gastrointestinal cancer), glioblastoma, hepatocellular carcinoma, liver cancer, carcinoma in situ, kidney cancer, laryngeal cancer, leukemia, liver cancer, lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma), melanoma, myeloma, neuroblastoma, oral cancer (lips, tongue, mouth, and pharynx), ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, rhabdomyosarcoma, rectal cancer, respiratory system cancer, salivary gland cancer, sarcoma, skin cancer, squamous cell carcinoma, and stomach cancer. cancer), testicular cancer, thyroid cancer, uterine or endometrial cancer, urinary tract cancer, vulvar cancer, Hodgkin lymphoma and non-Hodgkin lymphoma, and cellular lymphoma (low-grade / follicular non-Hodgkin lymphoma (NHL), small lymphocytic (SL) NHL, intermediate-grade / follicular NHL, intermediate-grade diffuse NHL, high-grade immunoblastic NHL, high-grade lymphoblastic NHL, high-grade small non-incisional nuclear cell type NHL, giant tumor lesion NHL, The selection includes lymphomas (including mantle cell lymphoma, AIDS-associated lymphoma, and Waldenström macroglobulinemia), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia, chronic myeloid leukemia, and other carcinomas and sarcomas, as well as post-transplant lymphoproliferative disorders (PTLD), and nevus disorders, edema (such as that associated with brain tumors), and abnormal angiogenesis associated with Meigs syndrome.In some embodiments, cancer is defined as chronic lymphocytic leukemia (CLL), acute leukemia, acute lymphoblastic leukemia (ALL), B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), chronic myeloid leukemia (CML), B-cell prelymphocytic leukemia, blastic plasmacytoid dendritic cell tumor, Burkitt lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, hairy cell leukemia, small The cancer is a hematological malignancy selected from the group consisting of cell type or large cell type follicular lymphoma, malignant lymphoproliferative disorders, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndromes, non-Hodgkin lymphoma, Hodgkin lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenström macroglobulinemia, and preleukemia, or combinations thereof. In some embodiments, the cancer is resistant to anti-checkpoint agents. In some embodiments, the anti-checkpoint agent is an antibody, optionally selected from anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, and anti-CTLA antibody. In some embodiments, the antibody is selected from nivolumab (OPDIVO), pembrolizumab (KEYTRUDA), pidilizumab (CT-011, CURE TECH), MK-3475 (MERCK), BMS 936559, MPDL328OA (ROCHE), semiprimab (LIBTAYO), atezolizumab (TECENTRIQ), avelumab (BAVENCIO), and durvalumab (IMFINZI). In some embodiments, the infection is a viral infection.In some embodiments, the viral infection is caused by a virus selected from papillomavirus, herpes simplex virus (HSV), human immunodeficiency virus (HIV), hepatitis virus, Zika virus, yellow fever virus, West Nile virus, dengue virus, Japanese encephalitis virus, St. Louis encephalitis virus, hepatitis C virus, poliovirus, rhinovirus, enterovirus, coxsackievirus, influenza virus, lentivirus, respiratory syncytial virus, human parainfluenza virus, rubravirus (e.g., mumps virus), measles virus, human metapneumovirus, hantavirus, rotavirus, norovirus, and severe acute respiratory syndrome (SARS) virus (e.g., SARS-CoV-2). In some embodiments, the inflammatory disease is an autoimmune disease or condition selected from multiple sclerosis, diabetes mellitus, lupus, celiac disease, Crohn's disease, ulcerative colitis, Guillain-Barré syndrome, scleroderma, Goodpasture syndrome, Wegener's granulomatosis, autoimmune epilepsy, Rasmussen's encephalitis, primary biliary sclerosis, sclerosing cholangitis, autoimmune hepatitis, Addisohn's disease, Hashimoto's thyroiditis, fibromyalgia, Meniere's syndrome; transplant rejection (e.g., prevention of allograft rejection), pernicious anemia, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, Sjögren's syndrome, lupus erythematosus, multiple sclerosis, myasthenia gravis, Reiter's syndrome, Graves' disease, and other autoimmune diseases.

[0127] In yet another embodiment, the Disclosure provides a method for treating anti-checkpoint agent-resistant cancer in a subject requiring treatment, comprising administering a pharmaceutical composition comprising any one compound of formula (I), formula (10), formula (20), formula (21), formula (30) to formula (32), formula (40), formula (50), formula (60), formula (70), formula (80), formula (81), formula (82), formula (90), formula (700), formula (701), formula (800) to formula (805), formula (900), formula (901), or formula (902) to a subject. In some embodiments, the anti-checkpoint agent is an antibody, optionally selected from anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, and anti-CTLA antibody. In some embodiments, the antibody is selected from nivolumab (OPDIVO), pembrolizumab (KEYTRUDA), pidilizumab (CT-011, CURE TECH), MK-3475 (MERCK), BMS 936559, MPDL328OA (ROCHE), semiprimab (LIBTAYO), atezolizumab (TECENTRIQ), avelumab (BAVENCIO), and durvalumab (IMFINZI).

[0128] In yet another embodiment, the present disclosure relates to a method for determining cancer treatment for a patient, (a) Obtaining biological samples from the subject, (b) Evaluate the expression of TRIM7 in biological samples, and (c) Selecting a cancer treatment comprising a pharmaceutical composition comprising any one compound of formula (I), formula (10), formula (20), formula (21), formula (30) to formula (32), formula (40), formula (50), formula (60), formula (70), formula (80), formula (81), formula (82), formula (90), formula (700), formula (701), formula (800) to formula (805), formula (900), formula (901), or formula (902), provided that TRIM7 is upregulated compared to healthy tissue, a biological sample previously obtained from the subject, or another biological sample from a patient known to be sensitive to an anti-checkpoint agent. Includes,

[0129] (d) Optionally, to select a second cancer treatment comprising an anti-checkpoint agent, wherein the anti-checkpoint agent is selected from anti-PD-1 agents, anti-PD-L1 agents, anti-PD-L2 agents, and / or anti-CTLA agents, and optionally, the anti-checkpoint agent is selected from anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, and / or anti-CTLA antibodies. The above method is provided, including the following.

[0130] In yet another embodiment, the present disclosure relates to a method for selecting patients for cancer treatment, (a) Obtaining biological samples from the subject, (b) Evaluate the expression of TRIM7 in biological samples, and (c) Selecting a cancer treatment comprising a pharmaceutical composition containing any one compound of formula (I), formula (10), formula (20), formula (21), formula (30) to formula (32), formula (40), formula (50), formula (60), formula (70), formula (80), formula (81), formula (82), formula (90), formula (700), formula (701), formula (800) to formula (805), formula (900), formula (901), or formula (902), where TRIM7 is upregulated compared to healthy tissue, a biological sample previously obtained from the above subject, or another biological sample from a patient known to be sensitive to an anti-checkpoint agent. Includes,

[0131] (d) Optionally, selecting a second cancer treatment including an anti-checkpoint agent, wherein the anti-checkpoint agent is selected from anti-PD-1 agents, anti-PD-L1 agents, anti-PD-L2 agents, and / or anti-CTLA agents, and optionally, the anti-checkpoint agent is selected from anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, and / or anti-CTLA antibodies. The above method is provided, including the following.

[0132] In yet another embodiment, the present disclosure relates to a method for treating cancer, (a) Obtaining biological samples from the subject, (b) Evaluate the expression of TRIM7 in biological samples, and (c) Administering a cancer treatment comprising a pharmaceutical composition containing any one of the compounds of formula (I), formula (10), formula (20), formula (21), formula (30) to formula (32), formula (40), formula (50), formula (60), formula (70), formula (80), formula (81), formula (82), formula (90), formula (700), formula (701), formula (800) to formula (805), formula (900), formula (901), or formula (902), provided that TRIM7 is upregulated compared to healthy tissue, a biological sample previously obtained from the subject, or another biological sample from a patient known to be sensitive to an anti-checkpoint agent. Includes,

[0133] (d) Optionally administering a second cancer treatment comprising an anti-checkpoint agent, wherein the anti-checkpoint agent is selected from anti-PD-1 agents, anti-PD-L1 agents, anti-PD-L2 agents, and / or anti-CTLA agents, and optionally, the anti-checkpoint agent is selected from anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, and / or anti-CTLA antibodies. The above method is provided, including the following.

[0134] In some embodiments, the biological sample used in any one of the above methods is a fresh tissue sample, a frozen tumor tissue sample, cultured cells, circulating tumor cells, or a formalin-fixed paraffin-embedded tumor tissue sample. In some embodiments, the biological sample used in any one of the above methods is a biopsy sample, which may optionally be selected from endoscopic biopsies, bone marrow biopsies, endoscopic biopsies (e.g., cystoscopy, bronchoscopy, and colonoscopy), needle biopsies (e.g., fine-needle aspiration, core needle biopsies, vacuum-assisted biopsies, X-ray-assisted biopsies, computed tomography (CT)-assisted biopsies, magnetic resonance imaging (MRI)-assisted biopsies, and ultrasound-assisted biopsies), skin biopsies (e.g., shaving biopsies, punch biopsies, and incision biopsies), and surgical biopsies. In some embodiments, the biological sample used in any one of the above methods includes blood, plasma, serum, tears, bone marrow, blood, blood cells, ascites, tissue or fine-needle biopsy specimens, cell-containing bodily fluids, free suspended nucleic acids, sputum, saliva, urine, cerebrospinal fluid, peritoneal fluid, pleural fluid, feces, lymph, gynecological fluid, skin swabs, vaginal swabs, oral swabs, nasal swabs, lavage fluids or lavage fluids such as tube lavage or bronchoalveolar lavage, aspirates, scrapes, bone marrow specimens, tissue biopsy specimens, surgical specimens, feces, other bodily fluids, secretions, and / or excretions, and / or cells derived therefrom. In some embodiments, the biological sample used in any one of the above methods includes at least one tumor cell. In some embodiments, the evaluation used in any one of the above methods is performed by DNA sequencing, RNA sequencing, immunohistochemical staining, Western blotting, in-cell Western blotting, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), and fluorescence-activated cell sequencing (FACS), or a combination thereof.

[0135] In some embodiments, the evaluation used in any one of the above methods is performed by contacting the sample with an agent that specifically binds to TRIM7. In one embodiment, the agent that specifically binds to one or more proteins includes an antibody, an antibody-like molecule, or a binding fragment thereof. In some embodiments, the evaluation used in any one of the above methods is performed by contacting the sample with an agent that specifically binds to one or more nucleic acids of TRIM7. In some embodiments, the agent that specifically binds to one or more nucleic acids is a nucleic acid primer or probe.

[0136] Any aspect or embodiment disclosed herein can be combined with any other aspect or embodiment disclosed herein.

[0137] A patent or application file includes at least one drawing made in color. A copy of this patent or patent application publication, including the color drawing, will be provided by the Patent Office upon request and payment of the required fees. [Brief explanation of the drawing]

[0138] [Figure 1A] Figure 1A shows the in vitro binding of recombinant human (rh) TRIM7 to RACO1 and MSK1 as measured using an assay based on the Meso Scale Discovery (MSD) platform. Figure 1A shows the binding of RACO1 to human TRIM7 compared to CD47, which was used as a negative control. [Figure 1B] Figure 1B shows the in vitro binding of recombinant human (rh) TRIM7 to RACO1 and MSK1 as measured using an assay based on the Meso Scale Discovery (MSD) platform. Figure 1B shows the binding of MSK1 to human TRIM7 compared to CD47, which was used as a negative control. [Figure 2]Figure 2 shows the in vitro binding of recombinant human (rh)TRIM7 to enterovirus 71 2B or enterovirus 71 2BC protein, as measured using an assay based on the Mesoscale Discovery (MSD) platform. Recombinant human RACO1 and recombinant human MSK1 proteins were used as positive controls, and recombinant human CD47 protein was used as a negative control. [Figure 3A] Figure 3A shows that enterovirus 71 2BC protein inhibits the binding of recombinant human (rh)TRIM7 to MSK1 in vitro, as measured using an assay based on the Meso Scale Discovery (MSD) platform. [Figure 3B] Figure 3B shows that enterovirus 71 2BC protein inhibits the binding of recombinant human (rh)TRIM7 to RACO1 in vitro, as measured using an assay based on the Meso Scale Discovery (MSD) platform. [Figure 4] Figure 4 shows the crystal structure of TRIM7 bound to the CVB_2C(319-329) peptide (SVGTTLEALFQ), the C-terminal fragment of the coxsackievirus B3 (CVB3) 2C protein. The upper left panel shows a schematic diagram of the CVB3 C2 protein, indicating the position of the CVB_2C(319-329) peptide. The lower left panel shows the crystal structure of the CVB_2C protein showing the CVB_2C(319-329) peptide, and the crystal structure of the TRIM7 protein forming a complex with the CVB_2C(319-329) peptide. The right panel shows the interactions between the CVB_2C(319-329) peptide and the various amino acids of the TRIM7 protein. [Figure 5] Figure 5 shows a schematic diagram of the molecular simulation-based method used to identify TRIM7 inhibitors, including the compound of Equation 1. [Figure 6]Figure 6 shows the various docked compounds. Underlined compounds have a docking score better than -7, which suggests an estimated affinity constant of less than 100 nM. [Figure 7] Figure 7 shows representative compounds along with their docking scores. [Figure 8A] Figure 8A shows the docking of compound 1009. Figure 8A shows compound 1001 in a situation with the space-filling model of TRIM7 in the background. [Figure 8B] Figure 8B shows the docking of compound 1009. Figure 8B also shows the binding of compound 1001 to TRIM7. [Figure 9A] Figure 9A shows the elucidation of the TRIM7 crystal structure, which partially provided information for the TRIM7 SMI in this disclosure. [Figure 9B] Figure 9B shows the elucidation of the TRIM7 crystal structure, which partially provided information for the TRIM7 SMI in this disclosure. [Figure 9C] Figure 9C shows the elucidation of the TRIM7 crystal structure, which partially provided information for the TRIM7 SMI in this disclosure. [Figure 10] Figure 10 provides data confirming the interaction between TRIM7 and RACO-1, STING, MAVS, and CVB3_2C (wild-type, but not a mutant). [Figure 11] Figure 11 is a scheme illustrating an exemplary workflow for screening and prioritizing candidates. [Figure 12A] Figure 12A provides data from a cell-based activity assay demonstrating that intracellular TRIM7 expression leads to target degradation / stabilization. Figure 12A shows that overexpression of TRIM7(+T7) in 293T cell lines expressing CVB3, MAVS, or STING leads to their degradation. [Figure 12B]Figure 12B provides data from a cell-based activity assay demonstrating that TRIM7 expression in cells leads to target degradation / stabilization. Figure 12B shows an assay in which compound 1028 blocks TRIM7-mediated stabilization of RACO1, resulting in its degradation. [Modes for carrying out the invention]

[0139] This specification discloses TRIM7 inhibitors that are particularly useful for the treatment of diseases, such as cancers including cancers resistant to anti-checkpoint agents, infections, and autoimmune diseases. Drug resistance, whether pre-existing before treatment (endogenous or primary resistance) or developing after treatment (acquired resistance), is a major cause of cancer recurrence, which is one of the leading causes of death. Therefore, a better understanding of the mechanisms of drug resistance is needed to guide future cancer treatments. Anti-PD-1 resistant tumors exhibit paradoxical dysregulation of certain IFNγ-inducible genes, and TRIM7 has been reported to be a driver gene involved in this paradoxical dysregulation and anti-PD-1 resistance. See International Application PCT / US2021 / 061834, which is incorporated in its entirety herein by reference. Therefore, this specification discloses TRIM7 inhibitors that are particularly useful for the treatment of cancers resistant to anti-checkpoint agents. Since TRIM7 is involved in a variety of processes, including tumor growth, innate immunity, and the pathogenesis of viral infections, the TRIM7 inhibitors disclosed herein will find applications in the treatment of cancer, infectious diseases, and autoimmune diseases.

[0140] TRIM7 Tripartite motif (TRIM) proteins are a group of E3 ubiquitin ligases involved in different cellular functions. Many TRIM proteins are induced by type I and type II interferons (IFN-I or IFN-II) or pathogen stimulation in different cell types, including primary immune cells in humans and mice (Rajsbaum et al., "Type I interferon-dependent and-independent expression of tripartite motif proteins in immune cells," Eur J Immunol. 2008;38(3):619-630; Carthagena et al., "Human TRIM gene expression in response to interferons," PLoS One 2009;4(3):e4894). The consensus N-terminal region of TRIM proteins contains a ring finger domain, followed by one or two B-box domains, and a coiled-coil domain (CC). Each TRIM protein has a specific C-terminal domain that confers substrate specificity via protein-protein interactions. The C-terminal domain includes the PRY and / or SPRY domain (B30.2).

[0141] Tripartite motif-containing protein 7 (TRIM7) is known to play a role in tumor cell proliferation, glycogen metabolism, innate immunity (e.g., via IFN induction), and viral pathogenesis (Giraldo et al., "Envelope protein ubiquitination drives entry and pathogenesis of Zika virus," Nature 2020.10.1038 / s41586-020-2457-8; Montori-Grau et al., "GNIP1 E3 ubiquitin ligase is a novel player in regulating glycogen metabolism in skeletal muscle," Metabolism.2018;83:177-187; Lu et al., "E3 ubiquitin ligase tripartite motif 7 positively regulates the TLR4-mediated immune response via its E3 ligase domain in macrophages," Mol Immunol.2019;109:126-133). While not intended to be theoretically constrained, MSK1 is thought to directly phosphorylate TRIM7. TRIM7 has also been shown to function as an E3 ligase that acts by mediating K63-linked polyubiquitination of the AP-1 coactivator RACO-1, leading to the stabilization of the RACO-1 protein (Chakraborty et al., "The E3 ubiquitin ligase TRIM7 mediates c-Jun / AP-1 activation by Ras signaling," Nat Commun. 2015;6:6782). TRIM7 has also been described as negatively regulating responses to DNA viruses by targeting STING for degradation (Yang et al., "RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation," PLoS Pathog. 2020;16(3):e1008387).

[0142] TRIM7 was identified as one of the genes identified as dysregulated in an acquired resistance model to anti-PD-1 antibodies. See International Application PCT / US2021 / 061834, which is incorporated herein by reference in its entirety.

[0143] TRIM7 inhibitors As used herein, the term “alkyl” refers to a branched or unbranched hydrocarbon chain having about 1 to 10 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, 2-methylpentyl, pentyl, hexyl, isohexyl, heptyl, 4,4-dimethylpentyl, octyl, and 2,2,4-trimethylpentyl. “Substitutive alkyl” refers to alkyl groups that are optionally substituted with one or more functional groups attached to such chains, generally including hydroxy, halogen, mercapto or thio, cyano, alkylthio, carboxy, nitro, alkoxy, and optionally substituted alkyl, amino, alkenyl, carboxamide, carbalkoxy, alkynyl, heterocyclyl, aryl, and heteroaryl, and that form alkyl groups such as trifluoromethyl, 3-hydroxyhexyl, 2-carboxypropyl, 2-fluoroethyl, carboxymethyl, cyanobutyl, phenethyl, and benzyl.

[0144] The terms "halogen" or "halo" used herein, either alone or as part of another group, refer to chloro, bromo, fluoro, or iodine.

[0145] The term "alkoxy" refers to alkyl-O-, where alkyl is defined as described above.

[0146] The term "alkylthio" refers to alkyl-S-, where alkyl is defined as described above.

[0147] The term "alkylamino" refers to -NR'R'', where R' and R'' may independently represent H, alkyl, or aryl, all as defined herein.

[0148] The term "alkylcarbonyl" refers to -C(=O)-alkyl, where alkyl is defined as described above.

[0149] The term "carboxy" refers to the -C(=O)OH moiety.

[0150] The term "carbalkoxy" refers to the -C(=O)-O-alkyl portion, where alkyl is defined as described above.

[0151] The term "carboxamido" refers to the -C(=O)-NR'R" portion, where R' and R'' may independently represent H, alkyl, or aryl, all as defined herein.

[0152] The term "alkylsulfonyl" refers to the -S(=O)2-alkyl portion, where alkyl is defined as described above.

[0153] The term "arylsulfonyl" refers to the -S(=O)2-aryl moiety, where aryl is as defined herein. For example, arylsulfonyl can be -S(=O)2-phenyl.

[0154] The term "arylsulfonyloxy" refers to the -OS(=O)2-alkyl portion, where alkyl is defined as described above.

[0155] The term "amino(monoalkylamino-, dialkylamino-)sulfinyl" refers to the -S(=O)NR'R" portion, where R' and R'' may independently represent H, alkyl, or aryl, all as defined herein.

[0156] The term "amino(monoalkylamino-, dialkylamino-)sulfonyl" refers to the -S(=O)2NR'R” portion, where R' and R” may independently represent H, alkyl, or aryl, all as defined herein.

[0157] The term "alkylsulfonylamino" refers to the -NHS(=O)2-alkyl portion, where alkyl is defined as described above.

[0158] The term "hydroxysulfonyloxy" refers to the -OS(=O)2OH portion.

[0159] The term "alkoxysulfonyloxy" refers to the -OS(=O)2O-alkyl portion, where alkyl is defined as described above.

[0160] The term "alkylsulfonyloxy" refers to the -OS(=O)2-alkyl portion, where alkyl is defined as described above.

[0161] The term "hydroxysulfonyl" refers to the -S(=O)2OH portion.

[0162] The term "alkoxysulfonyl" refers to the -S(=O)2O-alkyl portion, where alkyl is defined as previously defined.

[0163] The term "alkylsulfonylalkyl" refers to the -alkyl-S(=O)2-alkyl portion, where each alkyl group may be as defined above.

[0164] The term "amino(monoalkylamino-, dialkylamino-)sulfonylalkyl" refers to the -alkyl-S(=O)2-NR'R” portion, where alkyl is as previously defined, and R' and R” may independently represent H, alkyl, or aryl, all as defined herein.

[0165] The term "amino(monoalkylamino-, dialkylamino-)sulfinylalkyl" refers to the -alkyl-S(=O)-NR'R” portion, where alkyl is as previously defined, and R' and R” may independently represent H, alkyl, or aryl, all as defined herein.

[0166] Unless otherwise indicated, the term “cycloalkyl” as used herein, either alone or as part of another group, means a saturated or partially unsaturated (containing one or more double bonds) cyclic hydrocarbon group comprising one to three rings, including monocyclic alkyl, bicyclic alkyl and tricyclic alkyl groups, having a total of 3 to 20, preferably 3 to 10, carbon atoms forming the rings, and which may be fused to one or two aromatic rings as described for aryl groups, including cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, cyclododecyl, and cyclohexenyl. "Substituted cycloalkyl" includes cycloalkyl groups that are optionally substituted with one or more substituents, such as halogens, alkyls, substituted alkyls, alkoxys, hydroxys, aryls, substituted aryls, aryloxys, cycloalkyls, alkylamides, alkanoylaminos, oxos, acyls, arylcarbonylaminos, aminos, nitros, cyanos, thiols, and / or alkylthios, and / or substituents included in the definition of "substituted alkyl".

[0167] Unless otherwise indicated, the term “alkenyl” as used herein, either by itself or as part of another group, refers to a straight or branched chain having 2 to 20 carbon atoms, preferably 2 to 12 carbon atoms, more preferably 2 to 8 carbon atoms, and containing one or more double bonds in the main chain, including vinyl, 2-propenyl, 3-butenyl, 2-butenyl, 4-pentenyl, 3-pentenyl, 2-hexenyl, 3-hexenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 3-octenyl, 3-nonenyl, 4-decenyl, 3-undecenyl, 4-dodecenyl, 4,8,12-tetradecatrienyl, and the like. “Substitutive alkenyl” includes alkenyl groups optionally substituted with one or more substituents, such as the substituents included in the above definitions of “substituted alkyl” and “substituted cycloalkyl”.

[0168] Unless otherwise indicated, the term “alkynyl” as used herein, either by itself or as part of another group, refers to a linear or branched chain having 2 to 20 carbon atoms, preferably 2 to 12 carbon atoms, more preferably 2 to 8 carbon atoms, and containing one or more triple bonds in the main chain, including 2-propynyl, 3-butynyl, 2-butynyl, 4-pentynyl, 3-pentynyl, 2-hexynyl, 3-hexynyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 3-octinyl, 3-nonynyl, 4-decinyl, 3-undecinyl, 4-dodecinyl, and the like. “Substitutive alkynyl” includes alkynyl groups optionally substituted with one or more substituents, such as the substituents included in the above definitions of “substituted alkyl” and “substituted cycloalkyl”.

[0169] Unless otherwise indicated, the terms “aryl” or “Ar” as used herein, either alone or as part of another group, refer to monocyclic, bicyclic, and / or polycyclic aromatic groups (such as phenyl, or naphthyl, including 1-naphthyl and 2-naphthyl) having 6 to 10 carbon atoms in the ring portion, and may optionally include 1 to 3 additional rings fused to a carbocyclic or heterocyclic ring (e.g., aryl rings, cycloalkyl rings, heteroaryl rings, or cycloheteroalkyl rings, or their substitutions).

[0170] "Substituting aryl" includes halogens, alkyls, haloalkyls (e.g., trifluoromethyl), alkoxys, haloalkoxys (e.g., difluoromethoxy), alkenyls, alkynyls, cycloalkyl-alkyls, cycloheteroalkyls, cycloheteroalkylalkyls, aryls, heteroaryls, arylalkyls, aryloxys, aryloxyalkyls, arylalkoxys, alkoxycarbonyls, alkylcarbonyls, arylcarbonyls, arylalkenyls, aminocarbonylaryls, arylthios, arylsulfinyls, arylazos, heteroarylalkyls, heteroarylalkenyls, heteroaryl-heteroaryls, heteroaryloxys, hydroxys, nitros, cyanos, aminos, ( The aryl group comprises one or more substituted functional groups, such as substituted aminos, thiols, alkylthios, arylthios, heteroarylthios, arylthioalkyls, alkoxyarylthios, alkylaminocarbonyls, arylaminocarbonyls, aminocarbonyls, alkylcarbonyloxys, arylcarbonyloxys, alkylcarbonylaminos, arylcarbonylaminos, arylsulfinyls, arylsulfinylalkyls, arylsulfonylaminos, or arylsulfonaminocarbonyls, and / or any of the alkyl substituents described herein.

[0171] The term "arylalkyl" refers to -alkyl-aryl, where alkyl and aryl are defined as described above.

[0172] Unless otherwise indicated, the term “heteroaryl” as used herein, either alone or as part of another group, refers to a 5- to 7-membered aromatic ring containing one, two, three, or four heteroatoms such as nitrogen, oxygen, or sulfur, and such rings fused to an aryl ring, cycloalkyl ring, heteroaryl ring, or heterocycloalkyl ring (e.g., benzothiophene, indole, quinoline, thiazole, isoxazole, benzothiazole, benzimidazole, isoquinoline, pyridine, pyrimidine, benzopyrone, oxazole, thiazole, pyrazine), and also includes possible N-oxides. “Substitutive heteroaryl” includes heteroaryl groups optionally substituted with one to four substituents, such as the substituents included in the definitions of “substitutive alkyl” and “substitutive cycloalkyl” above. Substituted heteroaryls include condensed heteroaryl groups, such as quinoline, isoquinoline, indole, isoindole, carbazole, acridine, benzopyrene, benzopyrone, benzimidazole, benzofuran, isobenzofuran, phenanthroline, and purine.

[0173] Furthermore, as used herein, the terms “heterocyclo,” “heterocyclic,” “heterocyclyl,” or “heterocyclic ring” refer to a stable, unsubstituted or substituted 5-7 membered monocyclic ring system consisting of a carbon atom and 1-4 heteroatoms selected from N, O, or S, which may be saturated or unsaturated, where the nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen heteroatom may be optionally quaternized. The heterocyclic ring may be bonded at any heteroatom or carbon atom that results in the formation of a stable structure. Examples of such heterocyclic groups include, but are not limited to, piperidinyl, piperazinyl, oxopiperazinyl, oxopyrrolidinyl, oxoazepinyl, azepinyl, pyrrolyl, pyrrolidinyl, benzothiophene, chromone, benzopyrene, benzopyrone, furanyl, thienyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, pyrazinyl, pyrimidinyl, pyridadinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, thiadiazolyl, tetrahydropyranyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, and oxadiazolyl.

[0174] The term "heteroarylalkyl" refers to an alkyl-heteroaryl, where alkyl and heteroaryl are defined above.

[0175] As used herein, the terms "optionally substituted" or "substituted" mean that the chemical part referred to, e.g., alkyl, aryl, and heteroaryl, may be unsubstituted, and also include alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl, heterocycle, substituted heterocycle, heteroaryl, substituted heteroaryl, hydroxyl, amino, substituted amino, alkoxy, substituted alkoxy, halogen, carboxy, nitro, carboxyloxy, substituted carboxyloxy, carboxamide, substituted carboxamide, alkylamino, substituted alkylamino, monoalkylaminosulfinyl, substituted monoalkylaminosulfinyl, dialkylaminosulfinyl, substituted dialkylaminosulfinyl, monoalkylaminosulfonyl, substituted monoalkylaminosulfonyl This includes, but may indicate, one or more groups substituted with a group not limited to these.Examples of chemical parts of formulas (I), (10), (20), (21), (30), (31), (32), (40), (50), (60), (70), (80), (81), (82), (90), (700), (701), (800), (801), (802), (803), (804), (805), (900), (901), (902), or formulas 1001 to 1098, or pharmaceutically acceptable salts thereof, as described herein, include alkyl, alkenyl, alkynyl, cycloalkyl, arylalkyl, aryl, heterocyclic, and heteroaryl compounds. For example, optionally substituted alkyls may include both propyl and 2-chloropropyl. Furthermore, "optionally substituted" also includes embodiments in which the specified one or more substituents have multiple substituents rather than just a single substituent. For example, optionally substituted aryls may include both phenyl and 3-ethyl-5-methyl-6-bromophenyl.

[0176] The compounds of this disclosure may also be administered as salts, which are also within the scope of this disclosure. Medicinally acceptable (i.e., non-toxic and physiologically compatible) salts are preferred. If the compounds of this disclosure have, for example, at least one basic center, they may form acid addition salts. These are formed, for example, by strong inorganic acids such as mineral acids (e.g., sulfuric acid, phosphoric acid, or hydrohalic acid); by strong organic carboxylic acids such as unsubstituted or substituted (by halogens, etc.) alkane carboxylic acids having 1 to 4 carbon atoms (e.g., acetic acid), saturated or unsaturated dicarboxylic acids (e.g., oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid, phthalic acid, or terephthalic acid), hydroxycarboxylic acids (e.g., ascorbic acid, glycolic acid, lactic acid, malic acid, tartaric acid, or citric acid), amino acids (e.g., aspartic acid, glutamic acid, lysine, or arginine), or benzoic acid; or by organic sulfonic acids such as unsubstituted or substituted (by halogens, etc.) (C1-C4) alkyl sulfonic acids or (C1-C4) aryl sulfonic acids (e.g., methyl sulfonic acid or p-toluenesulfonic acid). If desired, corresponding acid addition salts having multiple basic centers may be formed. In embodiments, pharmaceutically acceptable salts are selected from valproic acid, maleic acid, tartaric acid, oxalic acid, pamoic acid, phosphonic acid, benzoic acid, citric acid, salicylic acid, succinic acid, methanesulfonic acid, malic acid, and p-toluenesulfonic acid.

[0177] Compounds of the present disclosure having at least one acidic group (e.g., a carboxylic acid) can also form salts with suitable bases. Representative examples of such salts include metal salts, e.g., alkali metal salts or alkaline earth metal salts (e.g., sodium, potassium, or magnesium salts), salts with ammonia, or salts with organic amines (e.g., morpholine, thiomorpholine, piperidine, pyrrolidine, mono, di, or trihydroxy lower alkylamines, e.g., ethyl-, tert-butyl-, diethyl-, diisopropyl-, triethyl-, tributyl-, or dimethyl-propyl-amine, or mono, di, or trihydroxy lower alkylamines, e.g., mono, di, or triethanolamine). Corresponding internal salts may also be formed.

[0178] For example, specific salts of the compounds described herein that contain a basic group include monohydrochloride, bisulfate, methanesulfonate, phosphate, or nitrate. Furthermore, specific salts of the compounds described herein that contain an acidic group include sodium salt, potassium salt, and magnesium salt, as well as salts with pharmaceutically acceptable organic amines.

[0179] All stereoisomers of the compounds of this disclosure in a mixture, or in either a pure or substantially pure form, are considered to be within the scope of this disclosure. The compounds of this disclosure may have a chiral center on any of the carbon atoms, including any one of the carbon atoms in the substituent. Thus, the compounds of this disclosure may exist in enantiomer or diastereomer forms, or mixtures thereof. Furthermore, when a stereocenter present in a compound of this disclosure is expressed as a racemate, that stereocenter is understood to encompass a racemic mixture of R and S isomers, as well as S and R isomers. Processes for preparing such compounds may utilize racemates, enantiomers, or diastereomers as starting materials. When diastereomer or enantiomer products are prepared, they can be separated by conventional methods, including chromatography, chiral HPLC, fractional crystallization, or distillation. Some of the compounds of this disclosure have groups including alkenyls, iminyls, etc., which may exist in the entgegen (E) conformation or the thusanmene (Z) conformation, and in this case, all geometric forms including both E and Z, cis and trans, and mixtures thereof are within the scope of this disclosure. Therefore, when such geometric isomer products are prepared, they can be separated by conventional methods, such as chromatography, HPLC, distillation, or crystallization.

[0180] In one embodiment, the present disclosure relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof: [ka]

[0181] In formula (I): A is [ka]

[0182] Selected from;

[0183] L is a linking group;

[0184] R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a , R 5b , R 5c , R 5d , R 5e , R 6a , R 6b , R 6c , R 6d , R 6e , R 7a , R 7b , R 7c , R 7d , R 8 , R 9 , R 10 , R 11a , R 11b , and R 11c Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a)C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0185] R 12 is H or an unsubstituted alkyl group;

[0186] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl;

[0187] n1 is an integer between 0 and 5;

[0188] t is either 1 or 2;

[0189] However, the compound of formula (I) is not any of the compounds of formulas 1001, 1003, 1004, and 1006 to 1009 below. [Table 2]

[0190] In one embodiment, R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a, R 5b , R 5c , R 5d , R 5e , R 6a , R 6b , R 6c , R 6d , R 6e , R 7a , R 7b , R 7c , R 7d , R 8 , R 9 , R 10 , R 11a , R 11b , and R 11c Each of these independently consists of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted alkyl, and / or unsubstituted or substituted heterocyclyl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, halogen, -C(O)R a , -N(R a )2, -N(R a )C(O)R a , and -S(O) t R a Selected from. In embodiments, the aryl is a halo-substituted aryl. In embodiments, L is bonded, or unsubstituted or substituted, -C 1-10 Alkyl-, -OC 1-10 Alkyl-, -C 1-10 Alkenyl-, -OC 1-10 Alkenyl-, -C 1-10 Cycloalkenyl-, -OC 1-10 Cycloalkenyl-,-C 1-10 Alkinyl-, -OC 1-10 Alkinyl-, -C 1-10 aryl-, -OC 1-10 -, -aryl-, -cycloalkyl-, -heterocyclyl-, -O-, -S-, -SS-, -S(O) w -, -C(O)-, -C(O)O-, -OC(O)-, -C(O)S-, -SC(O)-, -OC(O)O-, -N(Rb )-,-C(O)N(R b )-,-N(R b )C(O)-,-OC(O)N(R b )-,-N(R b )C(O)O-, -SC(O)N(R b )-,-N(R b )C(O)S-, -N(R b )C(O)N(R b )-,-N(R b )C(NR b )N(R b )-,-N(R b )S(O) w -, -S(O) w N(R b )-,-S(O) w O-, -OS(O) w -, -OS(O) w O-, -O(O)P(OR b )O-, (O)P(O-)3, -O(S)P(OR b (O-) and (S)P(O-)3 comprise one or more linking groups, where w is 1 or 2, and R b L is independently hydrogen, an unsubstituted or substituted alkyl, or an unsubstituted or substituted aryl, and p is an integer from 1 to 5. In embodiments, p is 2. In embodiments, L is a bond. In embodiments, L is -C(O)-. In embodiments, L is -C(H)(CH2) p It is C(O)NH2. In the embodiment, L is

[0191] [ka]

[0192] In this embodiment, L is

[0193] [ka]

[0194] (Here, alkyl is either unsubstituted or substituted). In the embodiment, L is

[0195] [ka]

[0196] In this embodiment, L is

[0197] [ka]

[0198] In this embodiment, L is

[0199] [ka]

[0200] That is the case.

[0201] In this embodiment, A is

[0202] [ka]

[0203] In this embodiment, the compound of formula (I) is the compound of formula (10), [ka]

[0204] In formula (10): R 9a , R 9b , R 9c , R 9d , and R 9eEach of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0205] R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl;

[0206] n² is an integer between 0 and 5;

[0207] t is 1 or 2. In the embodiment, n 2 In this embodiment, R 1a C 1-6 It is alkyl. In one embodiment, R 1a is -CH3. In the embodiment, R 2 H is H. In this embodiment, R 9a , R 9b , R 9c , R 9d , and R 9e Each is independently selected from hydrogen and halo. In embodiments, the halo is F or Cl. In embodiments, R 9a , R 9b , R 9c , R 9d , and R 9e Each of these is hydrogen. In the embodiment, R 9a , R 9d , and R 9e Each of these is hydrogen. In the embodiment, R 9b is Cl. In this embodiment, R 9c It is F.

[0208] In this embodiment, A is [ka]

[0209] In the embodiment, the compound of formula (I) is the compound of formula (20) or (21), [ka]

[0210] In equations (20) and (21): n3 is an integer between 0 and 5. In the embodiment, n3 is 2. In the embodiment, R 4a H is H. In this embodiment, R 4b H is H. In this embodiment, R 3 C 1-6 It is alkyl. In one embodiment, R 3 It is -CH3.

[0211] In the embodiment, the compound of formula (I) is the compound of formula (20) or a pharmaceutically acceptable salt thereof. In the embodiment, the compound of formula (I) is the compound of formula (21) or a pharmaceutically acceptable salt thereof.

[0212] In this embodiment, A is [ka]

[0213] In the embodiment, the compound of formula (I) is the compound of formula (30) or formula (31), [ka]

[0214] In equations (30) and (31): p is an integer from 0 to 5. In the embodiment, p is 2. In the embodiment, R 5a , R 5b , R 5c , R 5d , and R 5e Each is independently selected from hydrogen, an unsubstituted or substituted alkyl group, and a halogen. In embodiments, the alkyl group is -CH3. In embodiments, the halogen group is F or Cl. In embodiments, R 5a , R 5c , R 5d , and R5e Each of these is hydrogen. In the embodiment, R 5d It is -CH3.

[0215] In the embodiment, the compound of formula (I) is the compound of formula (30) or a pharmaceutically acceptable salt thereof. In the embodiment, the compound of formula (I) is the compound of formula (31) or a pharmaceutically acceptable salt thereof.

[0216] In this embodiment, the compound of formula (I) is the compound of formula (32), [ka]

[0217] In equation (32): q is an integer between 1 and 3. In the embodiment, q is 1. In the embodiment, R 5a , R 5b , R 5c , and R 5d Each is independently selected from hydrogen, an unsubstituted or substituted alkyl group, and a halogen. In embodiments, the alkyl group is -CH3. In embodiments, the halogen group is F or Cl. In embodiments, R 5a , R 5b , R 5c , and R 5d These are hydrogen atoms, respectively.

[0218] In this embodiment, the compound of formula (I) is the compound of formula (70), [ka]

[0219] In formula (70): R 11a and R 11beach independently represents hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a , -OC(O)-R a , -SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a , -C(O)SR a , -OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t OR a , -S(O) t N(R a )2, and PO3(R a )2;

[0220] R aIn each appearance, R is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. In the embodiment, R 5a and R 5d These are hydrogen atoms, respectively.

[0221] In this embodiment, the compound of formula (70) is the compound of formula (700) or (701). [ka]

[0222] In the embodiment, the compound of formula (70) is the compound of formula (700) or a pharmaceutically acceptable salt thereof. In the embodiment, the compound of formula (70) is the compound of formula (701) or a pharmaceutically acceptable salt thereof.

[0223] In one embodiment, R 5b These include unsubstituted or substituted alkynyls, substituted aryls, halogens, and -N(R) a )2, and -N(R a )C(O)R a Selected from. In one embodiment, R 5c These include unsubstituted or substituted alkynyls, substituted aryls, halogens, and -N(R) a )2, and -N(R a )C(O)R a Selected from. In an embodiment, the halogen is Br. In an embodiment, the substitution aryl is

[0224] [ka]

[0225] In some embodiments, the substitution aryl is

[0226] [ka]

[0227] In an embodiment, -N(R a )2 is -NH2. In the embodiment, the alkynyl is optionally an unsubstituted alkynyl. In the embodiment, -N(R a )C(O)R a teeth,

[0228] [ka] That is the case.

[0229] In one embodiment, R 11a and R 11b Each of them operates independently. [ka]

[0230] Here, Y is selected from unsubstituted or substituted alkyl, optionally unsubstituted or substituted C1-C5 alkyl, unsubstituted or substituted aryl, optionally unsubstituted or substituted phenyl, unsubstituted or substituted cycloalkyl, optionally unsubstituted or substituted C3-C7 cycloalkyl, and unsubstituted or substituted alkoxy, optionally unsubstituted or substituted C1-C5 alkoxy, and n7 is an integer from 1 to 3, optionally n7 is 1 or 2. In this embodiment, R 11a and R 11b Each of them operates independently.

[0231] [ka] Selected from.

[0232] In some embodiments, R 11a R is selected from H and unsubstituted alkyl groups. 11b teeth, [ka]

[0233] In this embodiment, R 11a is selected from H and -CH3, R 11b teeth,

[0234] [ka] Selected from.

[0235] In one embodiment, R 11a H is R 11b is an unsubstituted alkyl group. In the embodiment, R 11a H is R 11b is -CH3. In the embodiment, R 11a and R 11b Each of these is independently an unsubstituted alkyl. In one embodiment, R 11a and R 11b These are -CH3, respectively.

[0236] In the embodiment, the compound of formula (I) is the compound of formula (80), [ka]

[0237] In formula (80): R 11a and R 11beach independently represents hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a , -OC(O)-R a , -SC(O)-R a , -N(R a )₂, -C(O)R a , -C(O)OR a , -C(O)SR a , -OC(O)N(R a )₂, -C(O)N(R a )₂, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )₂, -N(R a )C(NR a )N(R a )₂, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t OR a , -S(O) t N(R a )₂, and PO₃(R a )₂; and is selected from the foregoing;

[0238] R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl;

[0239] n8 is an integer from 1 to 5. In this embodiment, R 5a and R 5d These are hydrogen atoms. In the embodiment, n8 is 1.

[0240] In the embodiment, the compound of formula (I) is the compound of formula (81), [ka]

[0241] In formula (81): Alk is either unsubstituted or substituted alkyl;

[0242] R 11a and R 11b Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(Ra )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0243] R a In each appearance, R is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. In the embodiment, R 5a and R 5d These are hydrogen atoms, respectively.

[0244] In the embodiment, the compound of formula (80) is the compound of formula (800) or formula (801), or the compound of formula (81) is the compound of formula (802) or formula (803). [ka]

[0245] In the embodiments, the compound of formula (80) is the compound of formula (800) or a pharmaceutically acceptable salt thereof. In the embodiments, the compound of formula (80) is the compound of formula (801) or a pharmaceutically acceptable salt thereof. In the embodiments, the compound of formula (81) is the compound of formula (802) or a pharmaceutically acceptable salt thereof. In the embodiments, the compound of formula (81) is the compound of formula (803) or a pharmaceutically acceptable salt thereof.

[0246] In one embodiment, R 5b These include unsubstituted or substituted alkynyls, substituted heteroaryls, substituted aryls, halogens, and -N(R a )2, and -N(R a )C(O)R a Selected from. In one embodiment, R 5b This is the substitution aryl and -N(R a )C(O)R a Selected from. In one embodiment, R 5c These include unsubstituted or substituted alkynyls, substituted aryls, halogens, and -N(R) a )2, and -N(R a )C(O)R a Selected from, selected from. In this embodiment, R 5c is a substituted aryl. In the embodiment, halo is Br. In the embodiment, the substituted aryl is

[0247] [ka]

[0248] In this embodiment, the substituted aryl is

[0249] [ka]

[0250] In this embodiment, the substituted aryl is

[0251] [ka]

[0252] In this embodiment, the substituted aryl is

[0253] [ka]

[0254] In an embodiment, -N(R a )2 is -NH2. In the embodiment, the alkynyl is optionally an unsubstituted alkynyl. In the embodiment, -N(R a )C(O)R a teeth,

[0255] [ka]

[0256] In an embodiment, -N(R a )C(O)R a teeth,

[0257] [ka]

[0258] In this embodiment, R 5b teeth,

[0259] [ka]

[0260] Selected from. In one embodiment, R 5b teeth,

[0261] [ka]

[0262] Selected from. In one embodiment, R 5c teeth,

[0263] [ka]

[0264] Selected from. In one embodiment, R 5c teeth,

[0265] [ka]

[0266] Selected from. In an embodiment, n8 is 1. In an embodiment, Alk is a C1-C5 alkyl. In an embodiment, Alk is a C1-C3 alkyl. In an embodiment, Alk is methyl. In an embodiment, Alk is an aryl-substituted C1-C5 alkyl. In an embodiment, Alk is

[0267] [ka] That is the case.

[0268] In one embodiment, R 11a and R 11b Each of these is independently an unsubstituted alkyl. In one embodiment, R 11a and R 11b Each of these is independently a C1-C5 alkyl group. In one embodiment, R 11a and R 11b Each of these is independently a C1-C3 alkyl group. In the embodiment, R 11a and R11b Each of these is independently methyl. In one embodiment, R 11a and R 11b Each of them operates independently.

[0269] [ka]

[0270] Here, Y is selected from unsubstituted or substituted alkyl, optionally unsubstituted or substituted C1-C5 alkyl, unsubstituted or substituted aryl, optionally unsubstituted or substituted phenyl, unsubstituted or substituted cycloalkyl, optionally unsubstituted or substituted C3-C7 cycloalkyl, and unsubstituted or substituted alkoxy, optionally unsubstituted or substituted C1-C5 alkoxy, and n7 is an integer from 1 to 3, optionally n7 is 1 or 2. In this embodiment, R 11a and R 11b Each of them operates independently.

[0271] [ka]

[0272] Selected from. In one embodiment, R 11a and R 11b Each of them operates independently.

[0273] [ka]

[0274] Selected from. In one embodiment, R 11a and R 11b Each of them operates independently.

[0275] [ka]

[0276] Selected from.

[0277] In one embodiment, R 11a R is selected from H and unsubstituted alkyl, optionally methyl, 11b teeth,

[0278] [ka]

[0279] In this embodiment, R 11a is selected from H and -CH3, R 11b teeth,

[0280] [ka]

[0281] Selected from. In one embodiment, R 11a is selected from H and -CH3, R 11b teeth,

[0282] [ka]

[0283] Selected from. In one embodiment, R 11a is selected from H and -CH3, R 11b teeth,

[0284] [ka]

[0285] Selected from. In one embodiment, R 11a is selected from H and -CH3, R 11b teeth,

[0286] [ka]

[0287] Selected from.

[0288] In one embodiment, R 11a H is R 11b is an unsubstituted alkyl group. In the embodiment, R 11a H is R 11b is -CH3. In the embodiment, R 11a and R 11b Each of these is independently an unsubstituted alkyl. In one embodiment, R 11a and R 11b These are -CH3, respectively.

[0289] In this embodiment, the compound of formula (I) is the compound of formula (82), [ka]

[0290] In formula (82): R 11a , R 11b , R 11c , and R 11d Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a, -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0291] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl.

[0292] In the embodiment, the compound of formula (82) is the compound of formula (804) or formula (805). [ka]

[0293] In the embodiment, the compound of formula (82) is the compound of formula (804) or a pharmaceutically acceptable salt thereof. In the embodiment, the compound of formula (82) is the compound of formula (805) or a pharmaceutically acceptable salt thereof.

[0294] In one embodiment, R 5b and / or R 5c These are, independently, -OR a And here, R a is an unsubstituted alkyl, optionally -OR a is -OCH3. In the embodiment, R 11a and R 11c These are hydrogen atoms, and R 11b and R 11d Each of these is independently an unsubstituted cycloalkyl. In one embodiment, R 11a and R 11c These are hydrogen atoms, and R 11b and R 11d Each of these is independently a cyclohexyl. In one embodiment, R 11a and R 11c These are hydrogen atoms, and R 11b and R 11d Each of these is independently an unsubstituted cycloalkyl. In one embodiment, R 11a and R 11c These are hydrogen atoms, and R 11b and R 11d Each of these is an alkyl group substituted with a cycloalkyl group. In one embodiment, R 11a and R 11c These are hydrogen atoms, and R 11b and R 11d Each of these is independently a cycloalkyl-substituted -CH2-. In an embodiment, R 11a and R 11c These are hydrogen atoms, and R 11b and R 11d Each of them operates independently.

[0295] [ka]

[0296] That is the case.

[0297] In this embodiment, A is

[0298] [ka]

[0299] In the embodiment, the compound of formula (I) is the compound of formula (90), [ka]

[0300] In formula (90): n is an integer between 1 and 5.

[0301] In the embodiment, the compound of formula (90) is the compound of formula (900), formula (901), or formula (902). [ka]

[0302] In the embodiments, the compound of formula (90) is the compound of formula (900) or a pharmaceutically acceptable salt thereof. In the embodiments, the compound of formula (90) is the compound of formula (901) or a pharmaceutically acceptable salt thereof. In the embodiments, the compound of formula (90) is the compound of formula (902) or a pharmaceutically acceptable salt thereof.

[0303] In one embodiment, R 12 H is H. In this embodiment, R 12 It is -CH3.

[0304] In one embodiment, R 11a H is H. In this embodiment, R 11a is a substituted alkyl group. In the embodiment, R 11a is an aryl-substituted alkyl. In an embodiment, R 11a teeth,

[0305] [ka]

[0306] In this embodiment, R 11a teeth,

[0307] [ka]

[0308] In this embodiment, R 10 is -C(O)R a In this embodiment, R 10 is -C(O)R a And here, R a is an unsubstituted alkenyl. In the embodiment, R 10 teeth,

[0309] [ka]

[0310] In this embodiment, R 10 is -C(O)R a And here, R a is a substituted alkyl group. In the embodiment, R 10 teeth,

[0311] [ka]

[0312] In this embodiment, R 10 teeth,

[0313] [ka]

[0314] In this embodiment, R 10 teeth,

[0315] [ka]

[0316] In this embodiment, R 10 is -C(O)R a And here, R a is a substitution aryl. In the embodiment, R 10 teeth,

[0317] [ka]

[0318] In this embodiment, R 10 is -C(O)R a And here, R a is a substituted heterocyclyl. In the embodiment, R 10 teeth,

[0319] [ka]

[0320] In this embodiment, R 10 is -S(O) t R a In this embodiment, R 10 is -S(O) t R a Here, t is 2. In the embodiment, R 10 is -S(O) t R a And here, t is 2, R a is a substitution aryl. In the embodiment, R 10 teeth,

[0321] [ka]

[0322] In this embodiment, R 10 teeth,

[0323] [ka]

[0324] In this embodiment, R 10 teeth,

[0325] [ka]

[0326] In this embodiment, R 10 teeth,

[0327] [ka]

[0328] In this embodiment, R 10 teeth,

[0329] [ka]

[0330] That is the case.

[0331] In the embodiment, the compound of formula (I) is any one of the following compounds: formula 1002, formula 1005, or formulas 1010 to 1098, or a pharmaceutically acceptable salt thereof.

[0332] [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4] [Table 3-5] [Table 3-6] [Table 3-7] [Table 3-8] [Table 3-9] [Table 3-10]

[0333] In embodiments, the compound of formula (I) is any one of the following compounds: formula 1010, formula 1011, formulas 1020 to 1030, formula 1034, formula 1036, formula 1037, formula 1040, formula 1043, formula 1050, formulas 1053 to 1056, formula 1058, formula 1060, formula 1062, formula 1064, formula 1066, formula 1069, formula 1070, formula 1075, or formula 1084, or a pharmaceutically acceptable salt thereof. [Table 4-1] [Table 4-2] [Table 4-3] [Table 4-4]

[0334] In this embodiment, A is

[0335] [ka]

[0336] In this embodiment, the compound of formula (I) is the compound of formula (40), [ka]

[0337] In equation (40): n4 is an integer between 0 and 5. In the embodiment, n4 is 0. In the embodiment, R 6a , R 6b , R 6c , R 6d , and R 6e Each is independently selected from hydrogen and unsubstituted or substituted alkyl. In embodiments, alkyl is an amide-substituted alkyl and an amide. In embodiments, R 6a , R 6b , R 6c , R 6d , and R 6e Each of them independently consists of hydrogen and [ka]

[0338] Selected from, where r is an integer from 0 to 4. In an embodiment, r is 0. In an embodiment, R 6a , R 6c , R 6d , and R 6e Each of these is hydrogen. In the embodiment, R 6b It is -C(O)NH2.

[0339] In this embodiment, A is [ka]

[0340] In this embodiment, R 8 is an unsubstituted or substituted aryl compound. In the embodiment, the compound of formula (I) is the compound of formula (50),

[0341] [ka]

[0342] In formula (50): R 10a , R 10b , R 10c , R 10d , and R 10e Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0343] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl;

[0344] n5 is an integer between 0 and 5;

[0345] t is 1 or 2. In the embodiment, n5 is 3. In the embodiment, R 7a , R 7b , R 7c , R 7d , R 10a , R 10b , R 10c , R 10d , and R 10eEach is independently selected from hydrogen, an unsubstituted or substituted alkyl group, and a halo. In embodiments, the alkyl group is -CH3. In embodiments, the halo is F or Cl. In embodiments, R 7a , R 7b , R 7c , and R 7d Each of these is hydrogen. In the embodiment, R 10a , R 10b , R 10d , and R 10e Each of these is hydrogen. In the embodiment, R 10c It is F.

[0346] In this embodiment, A is [ka]

[0347] In the embodiment, the compound of formula (I) is the compound of formula (60),

[0348] [ka]

[0349] In equation (60): n6 is an integer from 0 to 5. In the embodiment, n6 is 1. In the embodiment, R 9 H is H.

[0350] In embodiments, the compounds of the present disclosure (e.g., any one compound of formula (I), formula (10), formula (20), formula (21), formula (30), formula (31), formula (32), formula (40), formula (50), formula (60), formula (70), formula (80), formula (81), formula (82), formula (90), formula (700), formula (701), formula (800), formula (801), formula (802), formula (803), formula (804), formula (805), formula (900), formula (901), formula (902), or any one of formulas 1001-1098) are non-covalent inhibitors of TRIM7. In non-limiting examples, the non-covalent inhibitors do not form covalent bonds with the TRIM7 gene product (e.g., covalent bonds with amino acids of the TRIM7 gene product). In embodiments, the compounds of the present disclosure (e.g., any one compound of formula (I), formula (10), formula (20), formula (21), formula (30), formula (31), formula (32), formula (40), formula (50), formula (60), formula (70), formula (80), formula (81), formula (82), formula (90), formula (700), formula (701), formula (800), formula (801), formula (802), formula (803), formula (804), formula (805), formula (900), formula (901), formula (902), or any one of formulas 1001-1098) are covalent inhibitors of TRIM7. In non-limiting examples, the covalent inhibitors can form and / or form covalent bonds with the TRIM7 gene product (e.g., covalent bonds with amino acids of the TRIM7 gene product). Non-limiting examples of covalent TRIM7 inhibitors, as will be understood by those skilled in the art, include compounds comprising one or more moieties capable of forming a covalent bond with the TRIM7 gene product, including, but not limited to, alkenes (e.g., the Michael receptor alkene). Non-limiting examples of alkenes include the -C(O)-CH=CH2 moiety.

[0351] Pharmaceutical composition Aspects of this disclosure include pharmaceutical compositions comprising any of the TRIM7 inhibitors disclosed herein.

[0352] In one embodiment, the present disclosure relates to a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient:

[0353] [ka]

[0354] In formula (I): A is [ka] Selected from;

[0355] L is a linking group;

[0356] R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a , R 5b , R 5c , R 5d , R 5e , R 6a , R 6b , R 6c , R 6d , R 6e , R 7a , R 7b , R 7c , R 7d , R 8 , R 9 , R 10 , R 11a , R 11b , and R 11cEach of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0357] R 12 is H or an unsubstituted alkyl group;

[0358] R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl;

[0359] n1 is an integer between 0 and 5; t is either 1 or 2.

[0360] In one embodiment, R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a , R 5b , R 5c , R 5d , R 5e , R 6a , R 6b , R 6c , R 6d , R 6e , R 7a , R 7b , R 7c , R 7d , R 8 , R 9 , R 10 , R 11a , R 11b , and R 11c Each of these independently consists of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted alkyl, and / or unsubstituted or substituted heterocyclyl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, halogen, -C(O)R a ,-C(O)N(R a )2, -N(R a )2, -N(R a )C(O)R a , and -S(O) t Ra Selected from. In embodiments, the aryl is a halo-substituted aryl. In embodiments, L is bonded, or unsubstituted or substituted, -C 1-10 Alkyl-, -OC 1-10 Alkyl-, -C 1-10 Alkenyl-, -OC 1-10 Alkenyl-, -C 1-10 Cycloalkenyl-, -OC 1-10 Cycloalkenyl-,-C 1-10 Alkinyl-, -OC 1-10 Alkinyl-, -C 1-10 aryl-, -OC 1-10 -, -aryl-, -cycloalkyl-, -heterocyclyl-, -O-, -S-, -SS-, -S(O) w -, -C(O)-, -C(O)O-, -OC(O)-, -C(O)S-, -SC(O)-, -OC(O)O-, -N(R b )-,-C(O)N(R b )-,-N(R b )C(O)-,-OC(O)N(R b )-,-N(R b )C(O)O-, -SC(O)N(R b )-,-N(R b )C(O)S-, -N(R b )C(O)N(R b )-,-N(R b )C(NR b )N(R b )-,-N(R b )S(O) w -, -S(O) w N(R b )-,-S(O) w O-, -OS(O) w -, -OS(O) w O-, -O(O)P(OR b )O-, (O)P(O-)3, -O(S)P(OR b (O-) and (S)P(O-)3 comprise one or more linking groups, where w is 1 or 2, and R bL is independently hydrogen, an unsubstituted or substituted alkyl, or an unsubstituted or substituted aryl, and p is an integer from 1 to 5. In embodiments, p is 2. In embodiments, L is a bond. In embodiments, L is C(O)-. In embodiments, L is -C(H)(CH2) p It is C(O)NH2. In the embodiment, L is

[0361] [ka]

[0362] In this embodiment, L is

[0363] [ka]

[0364] Here, alkyl is either unsubstituted or substituted. In the embodiment, L is

[0365] [ka]

[0366] In this embodiment, L is

[0367] [ka]

[0368] In this embodiment, L is

[0369] [ka]

[0370] That is the case.

[0371] In this embodiment, A is

[0372] [ka]

[0373] In this embodiment, the compound of formula (I) is the compound of formula (10), [ka]

[0374] In formula (10): R 9a , R 9b , R 9c , R 9d , and R 9e Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(Ra )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0375] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl;

[0376] n² is an integer between 0 and 5;

[0377] t is 1 or 2. In the embodiment, n 2 In this embodiment, R 1a C 1-6 It is alkyl. In one embodiment, R 1a is -CH3. In the embodiment, R 2 H is H. In this embodiment, R 9a , R 9b , R 9c , R 9d , and R 9e Each is independently selected from hydrogen and halo. In embodiments, the halo is F or Cl. In embodiments, R 9a , R 9b , R 9c , R 9d , and R 9e Each of these is hydrogen. In the embodiment, R 9a , R 9d , and R 9e Each of these is hydrogen. In the embodiment, R9b is Cl. In this embodiment, R 9c It is F.

[0378] In this embodiment, A is [ka]

[0379] In the embodiment, the compound of formula (I) is the compound of formula (20) or formula (21), [ka]

[0380] In equations (20) and (21): n3 is an integer between 0 and 5. In the embodiment, n3 is 2. In the embodiment, R 4a H is H. In this embodiment, R 4b H is H. In this embodiment, R 3 C 1-6 It is alkyl. In one embodiment, R 3 It is -CH3.

[0381] In the embodiment, the compound of formula (I) is the compound of formula (20) or a pharmaceutically acceptable salt thereof. In the embodiment, the compound of formula (I) is the compound of formula (21) or a pharmaceutically acceptable salt thereof.

[0382] In this embodiment, A is [ka]

[0383] In the embodiment, the compound of formula (I) is the compound of formula (30) or formula (31),

[0384] [ka]

[0385] In equations (30) and (31): p is an integer from 0 to 5. In the embodiment, p is 2. In the embodiment, R 5a , R 5b , R 5c , R 5d , and R 5e Each is independently selected from hydrogen, an unsubstituted or substituted alkyl group, and a halo. In embodiments, the alkyl group is -CH3. In embodiments, the halo is F or Cl. In embodiments, R 5a , R 5c , R 5d , and R 5e Each of these is hydrogen. In the embodiment, R 5d It is -CH3.

[0386] In the embodiment, the compound of formula (I) is the compound of formula (30) or a pharmaceutically acceptable salt thereof. In the embodiment, the compound of formula (I) is the compound of formula (31) or a pharmaceutically acceptable salt thereof.

[0387] In this embodiment, the compound of formula (I) is the compound of formula (32), [ka]

[0388] In equation (32): q is an integer between 1 and 3. In the embodiment, q is 1. In the embodiment, R 5a , R 5b , R 5c , and R 5d Each is independently selected from hydrogen, an unsubstituted or substituted alkyl group, and a halo. In embodiments, the alkyl group is -CH3. In embodiments, the halo is F or Cl. In embodiments, R 5a , R 5b , R 5c , and R 5d These are hydrogen atoms, respectively.

[0389] In this embodiment, the compound of formula (I) is the compound of formula (70), [ka]

[0390] In formula (70): R 11a and R 11b Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0391] R a In each appearance, R is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. In the embodiment, R 5a and R 5d These are hydrogen atoms, respectively. In the embodiment, the compound of formula (70) is the compound of formula (700) or formula (701). [ka]

[0392] In the embodiment, the compound of formula (70) is the compound of formula (700) or a pharmaceutically acceptable salt thereof. In the embodiment, the compound of formula (70) is the compound of formula (701) or a pharmaceutically acceptable salt thereof.

[0393] In one embodiment, R 5b These include unsubstituted or substituted alkynyls, substituted aryls, halogens, and -N(R) a )2, and -N(R a )C(O)R a Selected from. In one embodiment, R 5c These include unsubstituted or substituted alkynyls, substituted aryls, halogens, and -N(R) a )2, and -N(R a )C(O)R a Selected from. In an embodiment, Halo is Br. In an embodiment, -N(R a )2 is -NH2. In the embodiment, the alkynyl is optionally an unsubstituted alkynyl. In the embodiment, -N(R a )C(O)R a teeth,

[0394] [ka]

[0395] In an embodiment, -N(R a )C(O)R a teeth,

[0396] [ka]

[0397] In an embodiment, -N(R a )C(O)R a teeth,

[0398] [ka]

[0399] In an embodiment, -N(R a )C(O)R a teeth,

[0400] [ka]

[0401] In one embodiment, the substitution aryl is

[0402] [ka]

[0403] In one embodiment, the substitution aryl is

[0404] [ka]

[0405] That is the case.

[0406] In one embodiment, R 11a and R 11b Each of them operates independently.

[0407] [ka]

[0408] Here, Y is selected from unsubstituted or substituted alkyl, optionally unsubstituted or substituted C1-C5 alkyl, unsubstituted or substituted aryl, optionally unsubstituted or substituted phenyl, unsubstituted or substituted cycloalkyl, optionally unsubstituted or substituted C3-C7 cycloalkyl, and unsubstituted or substituted alkoxy, optionally unsubstituted or substituted C1-C5 alkoxy, and n7 is an integer from 1 to 3, optionally n7 is 1 or 2. In this embodiment, R 11a and R 11b Each of them operates independently.

[0409] [ka] Selected from.

[0410] In one embodiment, R 11a is selected from H and -CH3, R 11b teeth, [ka] Selected from.

[0411] In one embodiment, R 11a H is R 11b is an unsubstituted alkyl group. In one embodiment, R 11a H is R 11b is -CH3. In the embodiment, R 11a and R 11bEach of these is independently an unsubstituted alkyl group. In one embodiment, R 11a and R 11b These are -CH3, respectively.

[0412] In this embodiment, the compound of formula (I) is the compound of formula (700) or formula (701), where R 5b or R 5c is -N(R a )C(O)R a In this embodiment, the compound of formula (I) is the compound of formula (700) or formula (701), where R 5b or R 5c teeth,

[0413] [ka]

[0414] In this embodiment, the compound of formula (I) is the compound of formula (700) or formula (701), where R 11a teeth,

[0415] [ka]

[0416] n7 is 1, Y is an optionally substituted phenyl, and R 11b H, alkyl, tetrahydropyran, and

[0417] [ka]

[0418] Selected from, where n7 is 1 and Y is an optionally substituted phenyl. In embodiments, the compound of formula (I) is the compound of formula (700) or formula (701), where R 11a and R 11bBoth are independent of each other.

[0419] [ka]

[0420] Here, n7 is 1, Y is an optionally substituted phenyl, where at least one optionally substituted phenyl is substituted with one or more halogens, alkyls, or CX3, where X is a halogen selected from F, Cl, Br, and I. In embodiments, the compound of formula (I) is the compound of formula (700) or formula (701), where R 11a and R 11b Both are independent of each other.

[0421] [ka]

[0422] n7 is 1, Y is an optionally substituted phenyl, and both optionally substituted phenyls are substituted with one or more alkoxys, optionally -OCH3.

[0423] In this embodiment, the compound of formula (I) is the compound of formula (700) or formula (701), where,

[0424] R 5b or R 5c is -N(R a )C(O)R a , at will

[0425] [ka]

[0426] And,

[0427] R 11a teeth,

[0428] [ka]

[0429] Here, n7 is 1, Y is an optionally substituted phenyl, and R 11b H, alkyl, tetrahydropyran, and

[0430] [ka]

[0431] Selected from, where n7 is 1 and Y is an optionally substituted phenyl,

[0432] R 11a and R 11b Each is independent of the others.

[0433] [ka]

[0434] Here, n7 is 1, Y is an optionally substituted phenyl, where at least one optionally substituted phenyl is substituted with one or more halogens, alkyls, or CX3, where X is a halogen selected from F, Cl, Br, and I, or

[0435] R 11a and R 11b Each is independent of the others.

[0436] [ka]

[0437] Here, n7 is 1, and Y is an optionally substituted phenyl, where each optionally substituted phenyl is independently substituted with one or more alkoxys, optionally -OCH3.

[0438] In embodiments, the compound of formula (700) or formula (701) is one of the compounds of formulas 1020-1027, 1029, 1030, or 1078-1081, or a pharmaceutically acceptable salt thereof.

[0439] In the embodiment, the compound of formula (I) is the compound of formula (80),

[0440] [ka]

[0441] In formula (80): R 11a and R 11b Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a, -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0442] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl;

[0443] n8 is an integer from 1 to 5. In this embodiment, R 5a and R 5d These are hydrogen atoms. In the embodiment, n8 is 1.

[0444] In the embodiment, the compound of formula (I) is the compound of formula (81), [ka]

[0445] In formula (81): Alk is either unsubstituted or substituted alkyl;

[0446] R 11a and R 11bEach of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0447] R aIn each appearance, R is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. In the embodiment, R 5a and R 5d These are hydrogen atoms, respectively.

[0448] In the embodiment, the compound of formula (80) is the compound of formula (800), formula (801), formula (802), or formula (803). [ka]

[0449] In the embodiments, the compound of formula (80) is the compound of formula (800) or a pharmaceutically acceptable salt thereof. In the embodiments, the compound of formula (80) is the compound of formula (801) or a pharmaceutically acceptable salt thereof. In the embodiments, the compound of formula (81) is the compound of formula (802) or a pharmaceutically acceptable salt thereof. In the embodiments, the compound of formula (81) is the compound of formula (803) or a pharmaceutically acceptable salt thereof.

[0450] In one embodiment, R 5b These include unsubstituted or substituted alkynyls, substituted heteroaryls, substituted aryls, halogens, and -N(R a )2, and -N(R a )C(O)R a Selected from. In one embodiment, R 5b This is the substitution aryl and -N(R a )C(O)R a Selected from. In one embodiment, R 5c These include unsubstituted or substituted alkynyls, substituted aryls, halogens, and -N(R) a )2, and -N(R a )C(O)R a Selected from, selected from. In this embodiment, R5c is a substituted aryl. In the embodiment, halo is Br. In the embodiment, the substituted aryl is

[0451] [ka]

[0452] In this embodiment, the substituted aryl is

[0453] [ka]

[0454] In this embodiment, the substituted aryl is

[0455] [ka]

[0456] In an embodiment, -N(R a )2 is -NH2. In the embodiment, the alkynyl is optionally an unsubstituted alkynyl. In the embodiment, -N(R a )C(O)R a teeth,

[0457] [ka]

[0458] In an embodiment, -N(R a )C(O)R a teeth,

[0459] [ka]

[0460] In this embodiment, R 5b teeth,

[0461] [ka]

[0462] Selected from. In one embodiment, R 5b teeth,

[0463] [ka]

[0464] Selected from. In one embodiment, R 5c teeth,

[0465] [ka]

[0466] Selected from. In one embodiment, R 5c teeth,

[0467] [ka]

[0468] Selected from. In an embodiment, n8 is 1. In an embodiment, Alk is a C1-C5 alkyl. In an embodiment, Alk is a C1-C3 alkyl. In an embodiment, Alk is methyl. In an embodiment, Alk is an aryl-substituted C1-C5 alkyl. In an embodiment, Alk is

[0469] [ka]

[0470] That is the case.

[0471] In one embodiment, R 11a and R 11b Each of these is independently an unsubstituted alkyl. In one embodiment, R 11a and R 11b Each of these is independently a C1-C5 alkyl group. In one embodiment, R 11a and R 11b Each of these is independently a C1-C3 alkyl group. In the embodiment, R 11a and R 11b Each of these is independently methyl. In one embodiment, R 11a and R 11b Each of them operates independently.

[0472] [ka]

[0473] Here, Y is selected from unsubstituted or substituted alkyl, optionally unsubstituted or substituted C1-C5 alkyl, unsubstituted or substituted aryl, optionally unsubstituted or substituted phenyl, unsubstituted or substituted cycloalkyl, optionally unsubstituted or substituted C3-C7 cycloalkyl, and unsubstituted or substituted alkoxy, optionally unsubstituted or substituted C1-C5 alkoxy, and n7 is an integer from 1 to 3, optionally n7 is 1 or 2. In this embodiment, R 11a and R 11b Each of them operates independently.

[0474] [ka]

[0475] Selected from. In one embodiment, R 11a and R 11b Each of them operates independently.

[0476] [ka]

[0477] Selected from. In one embodiment, R 11a and R 11b Each of them operates independently.

[0478] [ka]

[0479] Selected from.

[0480] In one embodiment, R 11a R is selected from H and unsubstituted alkyl, optionally methyl, 11b teeth,

[0481] [ka]

[0482] In this embodiment, R 11a is selected from H and -CH3, R 11b teeth,

[0483] [ka]

[0484] Selected from. In one embodiment, R 11a is selected from H and -CH3, R 11b teeth,

[0485] [ka]

[0486] Selected from. In one embodiment, R 11a is selected from H and -CH3, R11b teeth,

[0487] [ka]

[0488] Selected from. In one embodiment, R 11a is selected from H and -CH3, R 11b teeth,

[0489] [ka]

[0490] Selected from.

[0491] In this embodiment, the compound of formula (I) is the compound of formula (82), [ka]

[0492] In formula (82): R 11a , R 11b , R 11c , and R 11d Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a, -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0493] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl.

[0494] In the embodiment, the compound of formula (82) is the compound of formula (804) or (805). [ka]

[0495] In the embodiment, the compound of formula (82) is the compound of formula (804) or a pharmaceutically acceptable salt thereof. In the embodiment, the compound of formula (82) is the compound of formula (805) or a pharmaceutically acceptable salt thereof.

[0496] In one embodiment, R 5b and / or R 5c These are, independently, -OR a And here, R a is an unsubstituted alkyl, optionally -OR a is -OCH3. In the embodiment, R 11a and R 11c These are hydrogen atoms, and R 11b and R 11d Each of these is independently an unsubstituted cycloalkyl. In one embodiment, R 11a and R 11c These are hydrogen atoms, and R 11b and R 11d Each of these is independently a cyclohexyl. In one embodiment, R 11a and R 11c These are hydrogen atoms, and R 11b and R 11d Each of these is independently an unsubstituted cycloalkyl. In one embodiment, R 11a and R 11c These are hydrogen atoms, and R 11b and R 11d Each of these is an alkyl group substituted with a cycloalkyl group. In one embodiment, R 11a and R 11c These are hydrogen atoms, and R 11b and R 11d Each of these is independently a cycloalkyl-substituted -CH2-. In an embodiment, R 11a and R 11c These are hydrogen atoms, and R 11b and R 11d Each of them operates independently. [ka] That is the case.

[0497] In embodiments, the compound of formula (800) or formula (801) is any one of the compounds of formulas 1035 to 1037, 1040 to 1045, 1047 to 1051, 1053, 1055 to 1074, 1082, or 1083, or a pharmaceutically acceptable salt thereof.

[0498] In embodiments, the compound of formula (802) or formula (803) is one of the compounds of formula 1046, formula 1052, formula 1054, or formulas 1075-1077, or a pharmaceutically acceptable salt thereof.

[0499] In the embodiment, the compound of formula (804) or formula (805) is the compound of formula 1072 or formula 1073, or a pharmaceutically acceptable salt thereof. In the embodiment, A is

[0500] [ka]

[0501] In the embodiment, the compound of formula (I) is the compound of formula (90),

[0502] [ka]

[0503] In formula (90): n is an integer between 1 and 5.

[0504] In the embodiment, the compound of formula (90) is the compound of formula (900), formula (901), or formula (902). [ka]

[0505] In the embodiments, the compound of formula (90) is the compound of formula (900) or a pharmaceutically acceptable salt thereof. In the embodiments, the compound of formula (90) is the compound of formula (901) or a pharmaceutically acceptable salt thereof. In the embodiments, the compound of formula (90) is the compound of formula (902) or a pharmaceutically acceptable salt thereof.

[0506] In one embodiment, R 12 H is H. In this embodiment, R 12 It is -CH3.

[0507] In one embodiment, R 11a H is H. In this embodiment, R 11a is a substituted alkyl group. In the embodiment, R 11a is an aryl-substituted alkyl. In an embodiment, R 11a teeth,

[0508] [ka]

[0509] In this embodiment, R 10 is -C(O)R a In this embodiment, R 10 is -C(O)R a And here, R a is an unsubstituted alkenyl. In the embodiment, R 10 teeth,

[0510] [ka]

[0511] In this embodiment, R 10 is -C(O)R a And here, R a is a substituted alkyl group. In the embodiment, R 10 teeth,

[0512] [ka]

[0513] In this embodiment, R 10 teeth,

[0514] [ka]

[0515] In this embodiment, R 10 teeth,

[0516] [ka]

[0517] In this embodiment, R 10 is -C(O)R a And here, R a is a substitution aryl. In the embodiment, R 10 teeth,

[0518] [ka]

[0519] In this embodiment, R 10 is -C(O)R a And here, R a is a substituted heterocyclyl. In the embodiment, R 10 teeth,

[0520] [ka]

[0521] In this embodiment, R10 is -S(O) t R a In this embodiment, R 10 is -S(O) t R a Here, t is 2. In the embodiment, R 10 is -S(O) t R a And here, t is 2, R a is a substitution aryl. In the embodiment, R 10 teeth,

[0522] [ka]

[0523] In this embodiment, R 10 teeth,

[0524] [ka]

[0525] In this embodiment, R 10 teeth,

[0526] [ka]

[0527] In this embodiment, R 10 teeth,

[0528] [ka]

[0529] In this embodiment, R 10 teeth,

[0530] [ka]

[0531] That is the case.

[0532] In embodiments, the compound of formula (900), formula (901), or formula (902) is one of the compounds of formulas 1084 to 1098, or a pharmaceutically acceptable salt thereof.

[0533] In the embodiment, the compound of formula (I) is any one of the following compounds: formula 1002, formula 1005, or formulas 1010 to 1098, or a pharmaceutically acceptable salt thereof. [Table 5-1] [Table 5-2] [Table 5-3] [Table 5-4] [Table 5-5] [Table 5-6] [Table 5-7] [Table 5-8] [Table 5-9] [Table 5-10]

[0534] In embodiments, the compound of formula (I) is any one of the following compounds: formula 1010, formula 1011, formulas 1020 to 1030, formula 1034, formula 1036, formula 1037, formula 1040, formula 1043, formula 1050, formulas 1053 to 1056, formula 1058, formula 1060, formula 1062, formula 1064, formula 1066, formula 1069, formula 1070, formula 1075, or formula 1084, or a pharmaceutically acceptable salt thereof. [Table 6-1] [Table 6-2] [Table 6-3] [Table 6-4]

[0535] In this embodiment, A is

[0536] [ka]

[0537] In this embodiment, the compound of formula (I) is the compound of formula (40), [ka]

[0538] In equation (40): n4 is an integer between 0 and 5. In the embodiment, n4 is 0. In the embodiment, R 6a , R 6b , R 6c , R 6d , and R 6e Each is independently selected from hydrogen and unsubstituted or substituted alkyl. In embodiments, alkyl is an amide-substituted alkyl and an amide. In embodiments, R 6a , R 6b , R 6c , R 6d , and R 6e Each of them independently consists of hydrogen and

[0539] [ka]

[0540] Selected from, where r is an integer from 0 to 4. In an embodiment, r is 0. In an embodiment, R 6a , R 6c , R 6d , and R 6e Each of these is hydrogen. In the embodiment, R 6b It is -C(O)NH2.

[0541] In this embodiment, A is

[0542] [ka]

[0543] In this embodiment, R 8 is an unsubstituted or substituted aryl compound. In the embodiment, the compound of formula (I) is the compound of formula (50),

[0544] [ka]

[0545] In formula (50): R 10a , R 10b , R 10c , R 10d , and R 10e Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2;

[0546] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl;

[0547] n5 is an integer between 0 and 5;

[0548] t is 1 or 2. In the embodiment, n5 is 3. In the embodiment, R 7a , R 7b , R 7c , R 7d , R 10a , R 10b , R 10c , R 10d , and R 10e Each is independently selected from hydrogen, an unsubstituted or substituted alkyl group, and a halo. In embodiments, the alkyl group is -CH3. In embodiments, the halo is F or Cl. In embodiments, R 7a , R 7b , R 7c , and R 7d Each of these is hydrogen. In the embodiment, R 10a , R 10b , R 10d , and R 10e Each of these is hydrogen. In the embodiment, R 10c It is F.

[0549] In this embodiment, A is

[0550] [ka]

[0551] In the embodiment, the compound of formula (I) is the compound of formula (60),

[0552] [ka]

[0553] In equation (60): n6 is an integer from 0 to 5. In the embodiment, n6 is 1. In the embodiment, R 9 H is H.

[0554] In the embodiment, the compound of formula (I) is any one of the compounds of formulas 1001 to 1074, or a pharmaceutically acceptable salt thereof.

[0555] In embodiments, the compound of formula (I) is any one of the compounds of formula 1010, formula 1011, formulas 1020 to 1030, formula 1034, formula 1036, formula 1037, formula 1040, formula 1043, formula 1050, formulas 1053 to 1056, formula 1058, formula 1060, formula 1062, formula 1064, formula 1066, formula 1069, formula 1070, formula 1075, or formula 1084, or a pharmaceutically acceptable salt thereof.

[0556] In the embodiments, the pharmaceutical composition is formulated for parenteral administration. In the embodiments, the pharmaceutical composition is formulated for topical administration, skin administration, intradermal administration, intramuscular administration, intraperitoneal administration, intra-articular administration, intravenous administration, subcutaneous administration, intra-arterial administration, or transdermal administration. In the embodiments, the pharmaceutical composition is formulated for topical administration.

[0557] In embodiments, any of the TRIM7 inhibitors (and / or additional agents) disclosed herein are included in a variety of formulations. Any TRIM7 inhibitor (and / or additional agent) described herein may take the form of a liquid, suspension, emulsion, drop, tablet, pill, pellet, capsule, liquid-containing capsule, powder, sustained-release formulation, suppository, emulsion, aerosol, spray, suspension, or any other form suitable for use. In embodiments, the composition is in the form of a capsule (see, for example, U.S. Patent No. 5,698,155). Other examples of suitable pharmaceutical excipients are described in Remington's Pharmaceutical Sciences, pp. 1447–1676 (Alfonso R. Gennaro, ed., 19th edition, 1995), which is incorporated herein by reference.

[0558] In embodiments, the TRIM7 inhibitors disclosed herein may have a sufficiently basic functional group capable of reacting with an inorganic or organic acid to form a pharmaceutically acceptable salt, or a carboxyl group capable of reacting with an inorganic or organic base to form a pharmaceutically acceptable salt. pharmaceutically acceptable acid addition salts are formed from pharmaceutically acceptable acids, as is well known in the art. Such salts include, for example, pharmaceutically acceptable salts described in Journal of Pharmaceutical Science, 66, 2-19 (1977) and The Handbook of Pharmaceutical Salts; Properties, Selection, and Use. PHStahl and CGWermuth (eds.), Verlag, Zurich (Switzerland) 2002, which are incorporated herein by whole reference.

[0559] In embodiments, the compositions disclosed herein are in the form of pharmaceutically acceptable salts.

[0560] Furthermore, any TRIM7 inhibitor disclosed herein can be administered to a subject as a component of a pharmaceutical composition comprising a pharmaceutically acceptable carrier or vehicle. Such a pharmaceutical composition may optionally contain an appropriate amount of pharmaceutically acceptable excipients to provide a form for proper administration. Pharmaceutical excipients may be liquids such as water and oils (including those of petroleum, animal, plant, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, etc.). Examples of pharmaceutical excipients may include saline, acacia gum, gelatin, starch paste, talc, keratin, colloidal silica, urea, etc. In addition, auxiliaries, stabilizers, thickeners, lubricants, and colorants may be used. In embodiments, the pharmaceutically acceptable excipients are sterile when administered to a subject. Water is a useful pharmaceutical excipient when any agent disclosed herein is administered intravenously. Physiological saline and aqueous solutions of dextrose and glycerol can also be used as liquid excipients, particularly for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, wheat flour, chalk, silica gel, sodium stearate, glyceryl monostearate, talc, sodium chloride, skim milk powder, glycerol, propylene glycol, water, and ethanol. Any agent disclosed herein may optionally contain small amounts of wetting agents or emulsifiers, or pH buffers.

[0561] This disclosure includes the disclosed TRIM7 inhibitors in various formulations of pharmaceutical compositions. Any TRIM7 inhibitor disclosed herein may take the form of a liquid, suspension, emulsion, drop, tablet, pill, pellet, capsule, liquid-containing capsule, powder, sustained-release formulation, suppository, emulsion, aerosol, spray, suspension, or any other form suitable for use. DNA or RNA constructs encoding protein sequences may also be used. In embodiments, the composition is in the form of a capsule (see, for example, U.S. Patent No. 5,698,155). Other examples of suitable pharmaceutical excipients are described in Remington's Pharmaceutical Sciences, pp. 1447–1676 (Alfonso R. Gennaro, ed., 19th edition, 1995), which is incorporated herein by reference.

[0562] If necessary, the pharmaceutical composition containing the TRIM7 inhibitor may also contain a solubilizer. These agents can be delivered using a suitable vehicle or delivery device known in the art. The combination therapies outlined herein can be co-delivered in a single delivery vehicle or delivery device. The pharmaceutical composition for administration may optionally contain a local anesthetic, such as lidocaine, to reduce pain at the injection site.

[0563] Pharmaceutical compositions comprising the TRIM7 inhibitors of this disclosure can preferably be provided in unit dosage forms and can be prepared by any method well known in the field of pharmacy. Such methods generally involve the step of associating a therapeutic agent with a carrier constituting one or more auxiliary components. Typically, pharmaceutical compositions are prepared by homogeneously and closely associating a therapeutic agent with a liquid carrier, a finely divided solid carrier, or both, and then, if necessary, forming the product into a dosage form of the desired formulation (e.g., by wet or dry granulation, powder blending, etc., followed by tableting using conventional methods known in the art).

[0564] In embodiments, any TRIM7 inhibitor disclosed herein is formulated according to conventional methods as a pharmaceutical composition suitable for the dosage regimen disclosed herein.

[0565] Dosage, administration, and treatment regimen In one embodiment, any TRIM7 inhibitor (and / or additional agent) described herein is formulated according to a conventional method as a composition suitable for the dosage regime described herein.

[0566] Routes of administration include, for example, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, oral, sublingual, intranasal, intracerebral, vaginal, transdermal, rectal, inhalation, or topical administration (particularly to the ear, nose, eye, or skin). In embodiments, administration is carried out orally or by parenteral injection. In most cases, administration results in the release of any of the agents described herein into the bloodstream.

[0567] Any TRIM7 inhibitor (and / or additional agents) described herein may be administered orally. Such TRIM7 inhibitors (and / or additional agents) may also be administered by any other preferred route, for example, by intravenous infusion or bolus injection, or by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa), and may be administered together with another bioactive agent. Administration may be systemic or topical. Various delivery systems are known and can be used for administration, for example, encapsulation in liposomes, microparticles, microcapsules, capsules, etc.

[0568] In certain embodiments, it may be desirable to administer the agent locally to the area requiring treatment. In one embodiment, for example in the treatment of cancer, the TRIM7 inhibitor (and / or additional agents) is administered to the tumor microenvironment (e.g., cells, molecules, extracellular matrix, and / or blood vessels surrounding and / or supplying nutrients to tumor cells, including, for example, tumor vascular systems, tumor-infiltrating lymphocytes, fibroblast-like reticular cells, endothelial progenitor cells (EPCs), cancer-associated fibroblasts, pericytes, other stromal cells, components of the extracellular matrix (ECM), dendritic cells, antigen-presenting cells, T cells, regulatory T cells, macrophages, neutrophils, and other immune cells located near the tumor) or lymph nodes, and / or targets the tumor microenvironment or lymph nodes. In various embodiments, the TRIM7 inhibitor (and / or additional agents) is administered intratumorally, for example in the treatment of cancer.

[0569] Suitable dosage forms for parenteral administration (e.g., intravenous, intramuscular, intraperitoneal, subcutaneous, and intra-articular injection and infusion) include, for example, liquids, suspensions, dispersants, and emulsions. These may also be manufactured in the form of sterile solid compositions (e.g., lyophilized compositions), which can be dissolved or suspended in a sterile injection medium immediately before use. These may contain, for example, suspensions or dispersants known in the art.

[0570] The dosage and administration schedule of any TRIM7 inhibitor (and / or additional agent) described herein may depend on a variety of parameters, including but not limited to the disease being treated, the subject's overall health condition, and the discretion of the administering physician. Any TRIM7 inhibitor described herein may be administered to subjects in need before administration of any additional agent (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks prior), concurrently with administration, or after administration (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks later). In various embodiments, any TRIM7 inhibitor and additional agents described herein are administered at intervals of 1 minute, 10 minutes, 30 minutes, less than 1 hour, 1 hour, 1 to 2 hours, 2 to 3 hours, 3 to 4 hours, 4 to 5 hours, 5 to 6 hours, 6 to 7 hours, 7 to 8 hours, 8 to 9 hours, 9 to 10 hours, 10 to 11 hours, 11 to 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, or 4 weeks.

[0571] In various embodiments, this disclosure relates to the combined administration of a TRIM7 inhibitor that induces an innate immune response and another TRIM7 inhibitor that induces an adaptive immune response. In such embodiments, the TRIM7 inhibitor that induces an innate immune response may be administered before, concurrently with, or after the administration of the TRIM7 inhibitor that induces an adaptive immune response. For example, the TRIM7 inhibitor may be administered at intervals of 1 minute, 10 minutes, 30 minutes, less than 1 hour, 1 hour, 1 to 2 hours, 2 to 3 hours, 3 to 4 hours, 4 to 5 hours, 5 to 6 hours, 6 to 7 hours, 7 to 8 hours, 8 to 9 hours, 9 to 10 hours, 10 to 11 hours, 11 to 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, or 4 weeks. In an exemplary embodiment, the TRIM7 inhibitor that induces an innate immune response and the TRIM7 inhibitor that induces an adaptive immune response are administered at one-week intervals or every other week (i.e., the TRIM7 inhibitor that induces an adaptive immune response is administered one week after the administration of the TRIM7 inhibitor that induces an innate immune response, and so on).

[0572] The dosage of any TRIM7 inhibitor (and / or additional agents) described herein may depend on several factors, including the severity of the symptoms, whether the symptoms should be treated or prevented, and the age, weight, and health status of the person being treated. Furthermore, pharmacogenomic information (the influence of genotype on the pharmacokinetic, pharmacodynamic, or efficacy profile of the therapeutic agent) for a particular subject may influence the dosage used. Additionally, the exact individual dosage may be adjusted to some extent depending on various factors, including the specific combination of agents administered, the time of administration, the route of administration, the nature of the formulation, the rate of excretion, the specific disease being treated, the severity of the symptoms, and the anatomical site of the disease. Some dose variation may be expected.

[0573] When administering any TRIM7 inhibitor (and / or additional agents) described herein by parenteral injection, the dose may be approximately 0.1 mg to approximately 250 mg per day, approximately 1 mg to approximately 20 mg per day, or approximately 3 mg to approximately 5 mg per day. Generally, when administered orally or parenterally, the dose of any agent described herein may be approximately 0.1 mg to approximately 1500 mg per day, or approximately 0.5 mg to approximately 10 mg per day, or approximately 0.5 mg to approximately 5 mg per day, or approximately 200 mg to approximately 1200 mg per day (for example, approximately 200 mg, approximately 300 mg, approximately 400 mg, approximately 500 mg, approximately 600 mg, approximately 700 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg per day).

[0574] In embodied instances, administration of the TRIM7 inhibitors (and / or additional agents) described herein is by parenteral injection in doses of approximately 0.1 mg to approximately 1500 mg per treatment, or approximately 0.5 mg to approximately 10 mg per treatment, or approximately 0.5 mg to approximately 5 mg per treatment, or approximately 200 mg to approximately 1200 mg per treatment (for example, approximately 200 mg, approximately 300 mg, approximately 400 mg, approximately 500 mg, approximately 600 mg, approximately 700 mg, approximately 800 mg, approximately 900 mg, approximately 1000 mg, approximately 1100 mg, approximately 1200 mg per treatment).

[0575] In embodiments, appropriate doses of the TRIM7 inhibitor (and / or additional agents) are in the range of approximately 0.01 mg to approximately 100 mg per kg of body weight of the subject, or in the range of approximately 0.01 mg to approximately 10 mg per kg of body weight, for example, approximately 0.01 mg / kg, approximately 0.02 mg / kg, approximately 0.03 mg / kg, approximately 0.04 mg / kg, approximately 0.05 mg / kg, approximately 0.06 mg / kg, approximately 0.07 mg / kg, approximately 0.08 mg / kg, approximately 0.09 mg / kg, approximately 0.1 mg / kg, approximately 0.2 mg / kg, approximately 0.3 mg / kg, approximately 0.4 mg / kg, These include approximately 0.5 mg / kg, 0.6 mg / kg, 0.7 mg / kg, 0.8 mg / kg, 0.9 mg / kg, 1 mg / kg, 1.1 mg / kg, 1.2 mg / kg, 1.3 mg / kg, 1.4 mg / kg, 1.5 mg / kg, 1.6 mg / kg, 1.7 mg / kg, 1.8 mg / kg, 1.9 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, and 10 mg / kg, encompassing all values ​​and ranges between them.

[0576] In another embodiment, delivery can be carried out within vesicles, particularly liposomes (see Langer, 1990, Science 249:1527-1533; “Liposomes in the Therapy of Infectious Disease and Cancer” by Treat et al., Lopez-Berestein and Fidler (eds.), Liss, New York, pp. 353-365 (1989)).

[0577] Any TRIM7 inhibitors (and / or additional agents) described herein may be administered by controlled-release or sustained-release means, or by delivery devices well known to those skilled in the art. Examples include, but are not limited to, those described in U.S. Patents No. 3,845,770, No. 3,916,899, No. 3,536,809, No. 3598,123, No. 4008,719, No. 5674,533, No. 5059,595, No. 5591,767, No. 5120,548, No. 5073,543, No. 5639,476, No. 5354,556, and No. 5733,556, each incorporated herein in whole by reference. Such dosage forms, for example, using hydroxypropyl methylcellulose, other polymer matrices, gels, permeable membranes, osmotic systems, multilayer coatings, microparticles, liposomes, microspheres, or combinations thereof, may be useful in providing controlled or sustained release of one or more active ingredients to deliver desired release profiles in varying proportions. Controlled or sustained release of active ingredients may be stimulated by a variety of conditions, including but not limited to changes in pH, changes in temperature, stimulation by light of an appropriate wavelength, enzyme concentration or availability, water concentration or availability, or other physiological conditions or compounds.

[0578] In another embodiment, polymer materials may be used (see also "Medical Applications of Controlled Release," Langer and Wise (eds.), CRC Pres., Boca Raton, Florida (1974); "Controlled Drug Bioavailability," Drug Product Design and Performance, Smolen and Ball (eds.), Wiley, New York (1984); Ranger and Peppas, 1983, J. Macromol. Sci. Rev. Macromol. Chem. 23:61; Levy et al., 1985, Science 228:190; During et al., 1989, Ann. Neurol. 25:351; Howard et al., 1989, J. Neurosurg. 71:105).

[0579] In another embodiment, the controlled-release system may be positioned near the target area to be treated, and therefore require only a portion of the systemic dose (see, for example, Goodson, "Medical Applications of Controlled Release," op. cit., Vol. 2, pp. 115–138 (1984)). Other controlled-release systems may be used, as discussed in Langer's overview, 1990, Science 249:1527–1533.

[0580] Any TRIM7 inhibitor (and / or additional agent) described herein may be administered independently, once to four times daily, or once to four times monthly, or once to six times annually, or once every two, three, four, or five years. The duration of administration may be daily, or monthly, two, three, six months, one, two, or three years, or throughout the lifetime of the subject.

[0581] A drug regimen utilizing any TRIM7 inhibitor (and / or additional agent) described herein may be selected according to various factors, including the type, species, age, weight, sex, and medical condition of the subject, the severity of the condition being treated, the route of administration, the subject's renal or hepatic function, the individual's pharmacological genomic composition, and the specific compound of this disclosure to be employed. Any TRIM7 inhibitor (and / or additional agent) described herein may be administered in once-daily doses, or the total daily dose may be administered in two, three, or four divided doses per day. Furthermore, any TRIM7 inhibitor (and / or additional agent) described herein may be administered continuously rather than intermittently throughout the drug regimen.

[0582] Diseases, treatment methods, and patient selection In one embodiment, the Disclosure relates to a method for treating cancer, infectious diseases, and inflammatory diseases in a subject requiring such treatment, the method comprising administering a pharmaceutical composition of any embodiment disclosed herein to the subject. In accordance with the definition, cancer includes basal cell carcinoma, biliary tract cancer, bladder cancer, bone cancer, brain and central nervous system cancer, breast cancer, peritoneal cancer, cervical cancer, choriocarcinoma, colon and rectum cancer, connective tissue cancer, digestive system cancer, endometrial cancer, esophageal cancer, eye cancer, head and neck cancer, gastric cancer (including gastrointestinal cancer), glioblastoma, hepatocellular carcinoma, liver cancer, carcinoma in situ, kidney cancer, laryngeal cancer, leukemia, liver cancer, lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma), melanoma, myeloma, neuroblastoma, oral cancer (lips, tongue, mouth, and pharynx), ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, rhabdomyosarcoma, rectal cancer, respiratory system cancer, salivary gland cancer, sarcoma, skin cancer, squamous cell carcinoma, and stomach cancer. cancer), testicular cancer, thyroid cancer, uterine or endometrial cancer, urinary tract cancer, vulvar cancer, Hodgkin lymphoma and non-Hodgkin lymphoma, and B-cell lymphoma (low-grade / follicular non-Hodgkin lymphoma (NHL), small lymphocytic (SL) NHL, intermediate-grade / follicular NHL, intermediate-grade diffuse NHL, high-grade immunoblastic NHL, high-grade lymphoblastic NHL, high-grade small non-incisional nuclear cell NHL, giant tumor NHL, The selection includes lymphomas (including mantle cell lymphoma, AIDS-associated lymphoma, and Waldenström macroglobulinemia), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia, chronic myeloid leukemia, and other carcinomas and sarcomas, as well as post-transplant lymphoproliferative disorders (PTLD), and nevus disorders, edema (such as that associated with brain tumors), and abnormal angiogenesis associated with Meigs syndrome.

[0583] In this embodiment, cancer refers to chronic lymphocytic leukemia (CLL), acute leukemia, acute lymphoblastic leukemia (ALL), B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), chronic myeloid leukemia (CML), B-cell prelymphocytic leukemia, blastic plasmacytoid dendritic cell tumor, Burkitt lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, hairy cell leukemia, and small-cell lymphoma. Hematological cancers selected from the group consisting of follicular or large cell lymphoma, malignant lymphoproliferative disorders, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndromes, non-Hodgkin lymphoma, Hodgkin lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenström macroglobulinemia, and preleukemia, or combinations thereof.

[0584] In embodiments, the cancer is resistant to the anti-checkpoint agent. In embodiments, the anti-checkpoint agent is an antibody. In embodiments, the anti-checkpoint agent is an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-PD-L2 antibody, and / or an anti-CTLA antibody. In embodiments, the antibody is selected from nivolumab (OPDIVO), pembrolizumab (KEYTRUDA), pidilizumab (CT-011, CURE TECH), MK-3475 (MERCK), BMS 936559, MPDL328OA (ROCHE), semiprimab (LIBTAYO), atezolizumab (TECENTRIQ), avelumab (BAVENCIO), and durvalumab (IMFINZI).

[0585] In embodiments, the infection is a viral infection. In embodiments, the viral infection is caused by a virus selected from papillomavirus, herpes simplex virus (HSV), human immunodeficiency virus (HIV), hepatitis virus, Zika virus, yellow fever virus, West Nile virus, dengue virus, Japanese encephalitis virus, St. Louis encephalitis virus, hepatitis C virus, poliovirus, rhinovirus, enterovirus, coxsackievirus, influenza virus, lentivirus, respiratory syncytial virus, human parainfluenza virus, rubulavirus (e.g., mumps virus), measles virus, human metapneumovirus, hantavirus, rotavirus, norovirus, and severe acute respiratory syndrome (SARS) virus (e.g., SARS-CoV-2).

[0586] In embodiments, the inflammatory disease is an autoimmune disease or condition selected from multiple sclerosis, diabetes mellitus, lupus, celiac disease, Crohn's disease, ulcerative colitis, Guillain-Barré syndrome, scleroderma, Goodpasture syndrome, Wegener's granulomatosis, autoimmune epilepsy, Rasmussen's encephalitis, primary biliary sclerosis, sclerosing cholangitis, autoimmune hepatitis, Addison's disease, Hashimoto's thyroiditis, fibromyalgia, Meniere's syndrome; transplant rejection (e.g., prevention of allograft rejection), pernicious anemia, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, Sjögren's syndrome, lupus erythematosus, multiple sclerosis, myasthenia gravis, Reiter's syndrome, Graves' disease, and other autoimmune diseases.

[0587] In one embodiment, the Disclosure relates to a method for treating anti-checkpoint drug-resistant cancer in a subject requiring such treatment, the method comprising administering a pharmaceutical composition of any one embodiment disclosed herein to the subject. In the embodiment, the anti-checkpoint drug is an antibody. In the embodiment, the antibody is selected from nivolumab (OPDIVO), pembrolizumab (KEYTRUDA), pidilizumab (CT-011, CURE TECH), MK-3475 (MERCK), BMS 936559, MPDL328OA (ROCHE), cemiplimab (LIBTAYO), atezolizumab (TECENTRIQ), avelumab (BAVENCIO), and durvalumab (IMFINZI).

[0588] In one embodiment, the disclosure relates to a method for treating viral infections, including acute or chronic viral infections, such as visceral viral infections, such as respiratory viral infections, papillomavirus infections, herpes simplex virus (HSV) infections, human immunodeficiency virus (HIV) infections, and hepatitis virus infections. In embodiments, the viral infection is caused by a virus of the family Flaviviridae. In embodiments, the virus of the family Flaviviridae is selected from Zika virus, yellow fever virus, West Nile virus, dengue virus, Japanese encephalitis virus, St. Louis encephalitis virus, and hepatitis C virus. In embodiments, the viral infection is caused by a virus of the family Picornaviridae, such as poliovirus, rhinovirus, enterovirus, and coxsackievirus. In embodiments, the viral infection is caused by a member of the family Orthomyxoviridae, such as influenza virus. In embodiments, the viral infection is caused by a member of the family Retroviridae, such as lentivirus. In embodiments, the viral infection is caused by members of the Paramyxoviridae family, such as respiratory syncytial virus, human parainfluenza virus, rubulavirus (e.g., mumps virus), measles virus, and human metapneumovirus. In embodiments, the viral infection is caused by members of the Bunyaviridae family, such as hantavirus. In embodiments, the viral infection is caused by members of the Reoviridae family, such as rotavirus.

[0589] In one embodiment, the disclosure relates to a method for treating parasitic infections, such as infections caused by protozoa or helminths. In the embodiment, the parasitic infection is caused by a parasitic protozoan. In the embodiment, the parasite is selected from enteric protozoa, tissue protozoa, or blood protozoa. Examples of parasitic protozoa include Entamoeba hystolytica, Giardia lamblia, Cryptosporidium muris, Trypanosomatida gambiense, Trypanosomatida rhodesiense, Trypanosomatida crusi, Leishmania mexicana, Leishmania braziliensis, Leishmania tropica, Leishmania donovani, Toxoplasma gondii, Plasmodium vivax, and Plasmodium ovale. Examples include, but are not limited to, Plasmodium malariae (Platypleura ovale), Plasmodium falciparum (Platypleura malariae), Trichomonas vaginalis, and Histomonas meleagridis. In embodiments, the parasitic infection is caused by helminthic parasites such as nematodes (e.g., Adenophorea).In embodiments, the parasite is selected from the class Seernentea (e.g., whipworm (Trichuris trichiura), human roundworm (Ascaris lumbricoides), human pinworm (Enterobius vermicularis), hookworm (Ancylostoma duodenale), American hookworm (Necator americanus), Strongyloides stercoralis, Wuchereria bancrofti, and guinea pig (Dracunculus medinensis)). In embodiments, the parasite is selected from trematodes (e.g., schistosomiasis, hepatoflumes, enteric flukes, and lung flukes). In embodiments, the parasite is selected from Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum, Fasciola hepatica, Fasciola gigantica, Heterophyes, and Paragonimus westermani. In embodiments, the parasite is selected from tapeworms (e.g., Taenia solium, Taenia saginata, Hymenolepis nana, Echinococcus granulosus).

[0590] In one embodiment, the disclosure relates to a method for treating a bacterial infection. In the embodiment, the bacterial infection is caused by Gram-positive bacteria, Gram-negative bacteria, aerobic and / or anaerobic bacteria. In the embodiment, the bacteria are, but are not limited to, Staphylococcus, Lactobacillus, Streptococcus, Sarcina, Escherichia, Enterobacter, Klebsiella, Pseudomonas, Acinetobacter, Mycobacterium, Proteo The organisms are selected from Proteus, Campylobacter, Citrobacter, Nisseria, Bacillus, Bacteroides, Peptococcus, Clostridium, Salmonella, Shigella, Serratia, Haemophilus, Brucella, and other organisms. In embodiments, the bacteria include, but are not limited to, Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, and Salmonella typhimurium.Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis mirabilis), Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis (parapertussis), Bordetella bronchiseptica, Haemophilus influenzaeHaemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Haemophilus ducreyi, Pasteurella multocida, Pasteurella haemolytica, Branhamella catarrhalis, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae Bacteroides cholerae), Vibrio parahaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Kingella, Moraxella, Gardnerella vaginalis, Bacteroides fragilis, Bacteroides distasonis, Bacteroides 3452A homology group, Bacteroides vulgatus, Bacteroides ovals Bacteroides thetaiotaomicron, Bacteroides uniformisBacteroides eggerthii, Bacteroides splanchnicus, Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus pyogenes The following are selected: Staphylococcus pyogenes, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus intermedius, Staphylococcus hyicus subsp. hyicus, Staphylococcus haemolyticus, Staphylococcus hominis, or Staphylococcus saccharolyticus.

[0591] In one embodiment, the disclosure relates to a method for treating one or more autoimmune diseases or autoimmune disorders. In embodiments, the treatment of an autoimmune disease or autoimmune disorder may include modulating the immune system with the TRIM7 inhibitor to prioritize immunosuppression over immune stimulation. Exemplary autoimmune diseases or autoimmune disorders treatable with the TRIM7 inhibitor include those in which the body's own antigens are targeted in the immune response, such as rheumatoid arthritis, systemic lupus erythematosus, diabetes mellitus, ankylosing spondylitis, Sjögren's syndrome, inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease), multiple sclerosis, sarcoidosis, psoriasis, Graves' disease, Hashimoto's thyroiditis, psoriasis, hypersensitivity reactions (e.g., allergies, hay fever, asthma, and type I hypersensitivity reactions including acute edema), and vasculitis.

[0592] Methods for determining cancer treatment for patients, methods for selecting patients for cancer treatment, and treatment methods. In one embodiment, the Disclosure relates to a method for determining cancer treatment for a patient, the method comprising (a) obtaining a biological sample from a subject, (b) evaluating the biological sample for TRIM7 expression, and (c) selecting a cancer treatment comprising a pharmaceutical composition of any embodiment disclosed herein if TRIM7 is upregulated compared to healthy tissue, a biological sample previously obtained from the subject, or another biological sample from a patient known to be sensitive to an anti-checkpoint agent, and (d) optionally selecting a second cancer treatment comprising an anti-checkpoint agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1 agent, an anti-PD-L1 agent, an anti-PD-L2 agent, and / or an anti-CTLA agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-PD-L2 antibody, and / or an anti-CTLA antibody.

[0593] In one embodiment, the Disclosure relates to a method for selecting a patient for cancer treatment, the method comprising (a) obtaining a biological sample from a subject, (b) evaluating the biological sample for TRIM7 expression, (c) selecting a cancer treatment comprising a pharmaceutical composition of any embodiment disclosed herein if TRIM7 is upregulated compared to healthy tissue, a biological sample previously obtained from the subject, or another biological sample from a patient known to be sensitive to an anti-checkpoint agent, and (d) optionally selecting a second cancer treatment comprising an anti-checkpoint agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1 agent, an anti-PD-L1 agent, an anti-PD-L2 agent, and / or an anti-CTLA agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-PD-L2 antibody, and / or an anti-CTLA antibody.

[0594] In one embodiment, the Disclosure provides a method for treating cancer, comprising (a) obtaining a biological sample from a subject, (b) evaluating the biological sample for TRIM7 expression, and (c) administering a pharmaceutical composition of any embodiment disclosed herein if TRIM7 is upregulated compared to healthy tissue, a biological sample previously obtained from the subject, or another biological sample from a patient known to be sensitive to an anti-checkpoint agent, and (d) optionally administering a second cancer treatment comprising an anti-checkpoint agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1 agent, an anti-PD-L1 agent, an anti-PD-L2 agent, and / or an anti-CTLA agent. In embodiments, the anti-checkpoint agent is selected from an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-PD-L2 antibody, and / or an anti-CTLA antibody.

[0595] In embodiments, the biological sample is a fresh tissue sample, a frozen tumor tissue sample, cultured cells, circulating tumor cells, or a formalin-fixed paraffin-embedded tumor tissue sample. In embodiments, the biological sample is a biopsy sample, which may optionally be selected from endoscopic biopsies, bone marrow biopsies, endoscopic biopsies (e.g., cystoscopy, bronchoscopy, and colonoscopy), needle biopsies (e.g., fine-needle aspiration, core needle biopsy, vacuum-assisted biopsy, X-ray-assisted biopsy, computed tomography (CT)-assisted biopsy, magnetic resonance imaging (MRI)-assisted biopsy, and ultrasound-assisted biopsy), skin biopsies (e.g., shaving biopsy, punch biopsy, and incision biopsy), and surgical biopsies. In embodiments, the biological sample includes body fluids selected from blood, plasma, serum, tears, bone marrow, blood, blood cells, ascites, tissue or fine-needle biopsy samples, cell-containing body fluids, free suspended nucleic acids, sputum, saliva, urine, cerebrospinal fluid, peritoneal fluid, pleural fluid, feces, lymph fluid, gynecological fluids, skin swabs, vaginal swabs, oral swabs, nasal swabs, lavage solutions, or lavage solutions such as tube lavage or bronchoalveolar lavage, aspirates, scrapes, bone marrow specimens, tissue biopsy specimens, surgical specimens, feces, other body fluids, secretions, and / or excretions, and / or cells derived therefrom. In embodiments, the biological sample includes at least one tumor cell.

[0596] In embodiments, evaluation is performed by DNA sequencing, RNA sequencing, immunohistochemical staining, Western blotting, in-cell Western blotting, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), and fluorescence-activated cell sorting (FACS), or a combination thereof. In embodiments, evaluation is performed by contacting the sample with an agent that specifically binds to TRIM7. In embodiments, the agent that specifically binds to one or more proteins includes an antibody, an antibody-like molecule, or a binding fragment thereof. In embodiments, evaluation is performed by contacting the sample with an agent that specifically binds to one or more nucleic acids of TRIM7. In embodiments, the agent that specifically binds to one or more nucleic acids is a nucleic acid primer or probe.

[0597] Combination therapy and conjugation In embodiments, the disclosure provides a method further comprising administering a TRIM7 inhibitor and an additional agent to a subject. In embodiments, the disclosure relates to concomitant administration and / or combination formulation. Any of the compositions described herein may be combined and / or administered in combination.

[0598] In embodiments, any TRIM7 inhibitor described herein acts synergistically when administered in combination with another agent, and is administered at a lower dose than is typically used when such agent is used as monotherapy.

[0599] In embodiments including applications to cancer, this disclosure relates to, but is not limited to, chemotherapeutic agents as additional agents. Examples of chemotherapeutic agents include, but are not limited to,: alkylating agents such as thiotepa and cyclophosphamide (CYTOXAN); alkyl sulfonates such as busulfan, improsulfan, and piposulfan; aziridines such as benzodopa, carbocone, metsuredopa, and uredopa; ethyleneimines and methylmelamines, including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide, and trimethylolmelamine; acetogenins (e.g., bratacin and bratacinone); camptothecin (including its synthetic analog topotecan); bryostatins; karystatins; CC-1065 (including its synthetic analogs adzeresin, karzeresin, and bizeresin); cryptophycins (e.g., cryptophycin 1 and cryptophycin 8); drastatin; duocalmycin (the synthetic analog KW-2189) and CB1-TM1); eleuterobin; pancratistatin; sarcodictiin; spongstatin; chlorambucil, chlornafadin, colophosphamide, estramustine, ifosfamide, mechloretamine, mechloretamine hydrochloride oxide, melphalan, nobenbitin, fenesterine, prednimustine, trophosphamide, uracil mustard and other nitrogenous mustards; carmustine Nitrosoureas such as chlorozotosine, fotemustine, lomustine, nimustine, and ranimustine; Enegyoin antibiotics (e.g., calicheamicin, especially calicheamicin gammaol and calicheamicin omegaol (see, e.g., Agnew, Chem. Intl. Ed. Engl., 33:183-186 (1994)); Dinemycin, including Dinemycin A; Bisphosphonates such as clodronate; Esperamycin;Similarly, antibiotics such as neocardinostatin chromophore and related pigment proteins (enegyoin antibiotic chromophore), acrasinomycin, actinomycin, autoramycin, azaserin, bleomycin, kactinomycin, carabicin, caminomycin, cardinophilin, chromomycin, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, dosolubicin (ADRIAMYCIN) (including morpholino-dosolubicin, cyanomorpholino-dosolubicin, 2-pyrrolino-dosolubicin, and deoxydosolubicin), epirubicin, esorubicin, idarubicin, marcelomycin, mitomycin such as mitomycin C, mycophenolic acid, nogaramycin, olibomycin, peplomycin, potophyllomycin, puromycin, ke Lamycin, rhodorubicin, streptonigrin, streptozocin, tubercidine, ubenimex, dinostatin, zolubicin; antimetabolites such as methotrexate and 5-fluorouracil (5-FU); folate analogs such as denopterin, methotrexate, pteropterin, and trimethrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, and thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, and phloxuridine; androgens such as carsterone, dromostanolone propionate, epithiostanol, mepitiostane, and testactone; antiadrenal agents such as minoglutethimide, mitotane, and trilostane; frolinic acid Folic acid supplements such as acid; acegraton; aldofamide glycosides; aminolevulinic acid; enyluracil; amsacrin; bestlabsil; bisanthren; edatraxate; demecolsin; diazicon; elformitin; eriptinium acetate; epotilon; etogluside; gallium nitrate; hydroxyurea; lentinan; ronidynin; meitansinoids such as meitansin and ansamitosin; mitogwazone; mitoxantrone; mopidammole; nitraerine; pentostatin; fenamet;Pirarubicin; Rosoxantrone; Podophyllic acid; 2-Ethylhydrazide; Procarbazine; PSK polysaccharide complex (JHS Natural Products, Eugene, Oreg.); Lazoxane; Rhizoxin; Sizofuran; Spirogermanium; Tenuazonic acid; Triadicone; 2,2',2”-Trichlorotriethylamine; Trichothecenes (e.g., T-2 toxin, verracurin A, loridine A, and angidin); Urethane; Vindesine; Dacarbazine; Mannomustine; Mitobronitol; Mitractol; Pipobroman; Gacytosine; Arabinoside ("Ara-C"); Cyclophosphamide; Thiotepa; Taxoids, e.g., Paclitaxel (TAXOL) (Bristol-Myers Squibb) Oncology, Princeton, NJ), ABRAXANE (a cremofol-free albumin-engineered nanoparticle formulation of paclitaxel (American Pharmaceutical Partners, Schaumberg, 111.)), and docetaxel (TAXOTERE) (Rhone-Poulenc Rorer, Antony, France); chloranbucil; gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin, oxaliplatin, and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; vinorelbine (NAVELBIN); novantrone; teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; irinotecan (Camptosar, CPT-11) (including therapeutic regimens of irinotecan with 5-FU and leucovorin); topoisomerase inhibitors (RFS 2000); Difluoromethylornithine (DMFO); Retinoids such as retinoic acid; Capecitabine; Combretastatin; Leucovorin (LV); Oxaliplatin (including oxaliplatin treatment regimens (FOLFOX)); Lapatinib (TYKERB);Inhibitors of PKC-α, Raf, H-Ras, EGFR (e.g., erlotinib (Tarceva)), and VEGF-A that reduce cell proliferation, as well as pharmaceutically acceptable salts, acids, or derivatives of any of the above. Furthermore, the treatment method may further include the use of radiation. Furthermore, the treatment method may further include the use of photodynamic therapy.

[0600] In embodiments including, but not limited to, applications to cancer, the additional agents are agents that block, reduce, and / or inhibit the binding of PD-1, and PD-L1 or PD-L2, and / or PD-1 to PD-L1 or PD-L2 (non-limiting examples include nivolumab (ONO-4538 / BMS-936558, MDX1106, OPDIVO, BRISTOL MYERS SQUIBB), pembrolizumab (KEYTRUDA, Merck), MK-3475 (MERCK), BMS 936559 (BRISTOL MYERS) One or more immunomodulators selected from SQUIBB, atezolizumab (TECENTRIQ, GENENTECH), MPDL328OA (ROCHE), agents that increase and / or stimulate CD137 (4-1BB) and / or increase and / or stimulate the binding of CD137 (4-1BB) to one or more 4-1BB ligands (non-limiting examples include urelumab (BMS-663513 and anti-4-1BB antibody)), and agents that increase the activity of CTLA-4 and / or block, reduce, and / or inhibit the binding of CTLA-4 to one or more of AP2M1, CD80, CD86, SHP-2, and PPP2R5A and / or the binding of OX40 to OX40L (non-limiting examples include GBR 830 (GLENMARK), MEDI6469 (MEDIMMUNE)).

[0601] In embodiments, but not limited to, including applications to infectious diseases, this disclosure relates to anti-infective agents as additional agents. In embodiments, the anti-infective agents are antiviral agents, but not limited to, abacavir, acyclovir, adefovir, amprenavir, atazanavir, cidofovir, darunavir, delavirdin, didanosine, docosanol, efavirenz, elvitegravir, emtricitabine, enfvirtide, etravirine, famciclovir, and foscarnet. In embodiments, the antiinfective agent is an antimicrobial agent that includes, but is not limited to, cephalosporin antibiotics (cephalexin, cefuroxime, cefadroxil, cefazolin, cephalothin, cefaclor, cephamandol, cefoxitin, cefprodil, and ceftoviprole); fluoroquinolone antibiotics (cypro, revaquin, floxin, tequin, avelox, and norflox); tetracycline antibiotics (tetracycline, minocycline, oxytetracycline, and doxycycline); penicillin antibiotics (amoxicillin, ampicillin, penicillin V, dicloxacillin, carbenicillin, vancomycin, and methicillin); monobactam antibiotics (aztreonam); and carbapenem antibiotics (ertapenem, doripenem, imipenem / cilastatin, and meropenem). In embodiments, the anti-infective agent includes antimalarial agents (e.g., chloroquine, quinine, mefloquine, primaquine, doxycycline, artemether / lumefantrine, atovaquone / proguanil, sulfadoxine / pyrimethamine), metronidazole, tinidazole, ivermectin, pyrantel pamoate, and albendazole.

[0602] In embodiments including, but not limited to, applications to autoimmunity, additional agents are immunosuppressants. In embodiments, the immunosuppressant is an anti-inflammatory agent such as a steroidal anti-inflammatory agent or a non-steroidal anti-inflammatory drug (NSAID). Steroids, particularly corticosteroids and their synthetic analogs, are well known in the art. Examples of corticosteroids useful in this disclosure include hydroxytriamcinolone, alpha-methyldexamethasone, beta-methylbetamethasone, beclomethasone propionate, betamethasone benzoate, betamethasone dipropionate, betamethasone valerate, clobetasol valerate, desonide, desoxymethasone, dexamethasone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluchlorolone acetonide, flumethasone pivalate, fluocinolone acetonide, fluocinonide, flucortin butyl ester, fluocortolone, fluprednilidene acetate, flulandrenolone, halcinonide, and hydro This includes, but is not limited to, cortisone, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorozone diacetate, fluradrenolone acetonide, medrizone, amsinafel, amsinafid, betamethasone and the remainder of its esters, chloroprednisone, crocorterone, crescinolone, dichlorizone, difluprednate, fluchloronide, flunisolide, fluoromethalone, fluperolon, fluprednisolone, hydrocortisone, meprednisone, paramethasone, prednisolone, prednisone, and beclomethasone propionate. The (NSAIDS) that may be used in this disclosure include, but are not limited to, salicylic acid, acetylsalicylic acid, methyl salicylate, glycol salicylate, salicylmide, benzyl-2,5-diacetoxybenzoic acid, ibuprofen, flindac, naproxen, ketoprofen, etofenamate, phenylbutazone, and indomethacin.In embodiments, immunosuppressants may be cell division inhibitors such as alkylating agents, antimetabolites (e.g., azathioprine, methotrexate), cytotoxic antibiotics, antibodies (e.g., basiliximab, daclizumab, and muromonab), antiimmunophilins (e.g., cyclosporine, tacrolimus, sirolimus), inteferon, opioids, TNF-binding proteins, mycophenolates, and small molecule biological agents (e.g., fingolimod, myriocin).

[0603] In embodiments including, but not limited to, these, additional agents are Kras inhibitors (e.g., Kras G12C inhibitors). In embodiments, the Kras inhibitor is selected from BI2865, MRTX113, sotracib (AMG510), and adagracib (MRTX849).

[0604] In embodiments including, but not limited to, these, additional agents are Braf inhibitors. In embodiments, the Braf inhibitor is selected from vemurafenib, dabrafenib, and encorafenib.

[0605] In embodiments including, but not limited to, these, additional agents are MEK inhibitors. In embodiments, the MEK inhibitor is selected from binimetinib (MEK162), cobimetinib (XL518), selumetinib, and trametinib (GSK1120212).

[0606] In embodiments, the TRIM7 inhibitors (and / or additional agents) described herein include modified derivatives, i.e., derivatives modified by covalent bonding of any type of molecule to the composition such that the covalent bond does not prevent the composition's activity. For example, derivatives include, but are not limited to, compositions modified by glycosylation, lipidation, acetylation, PEGylation, phosphorylation, amidation, derivatization with known protecting / blocking groups, cleavage by proteolysis, linkage to cell ligands or other proteins, among others. Any of the numerous chemical modifications can be carried out by known methods, including, but not limited to, specific chemical cleavage, acetylation, formylation, and metabolic synthesis of turicamycine. Furthermore, derivatives may comprise one or more non-classical amino acids. In yet another embodiment, the TRIM7 inhibitors (and / or additional agents) described herein further include, in exemplary embodiments, cytotoxic agents, including toxins, chemotherapeutic agents, radioisotopes, and agents that induce apoptosis or cell death. Such agents may be conjugated to the compositions described herein.

[0607] The TRIM7 inhibitors (and / or additional agents) described herein may therefore be post-translationally modified to add effector moieties such as chemical linkers, detectable moieties such as fluorescent dyes, enzymes, substrates, bioluminescent substances, radioactive materials, and chemiluminescent moieties, or functional moieties such as streptavidin, avidin, biotin, cytotoxins, cytotoxic agents, and radioactive materials.

[0608] Subject and / or animals In embodiments, the subject and / or animal is a mammal, such as a human, mouse, rat, guinea pig, dog, cat, horse, cattle, pig, rabbit, sheep, or a non-human primate such as a monkey, chimpanzee, or baboon. In embodiments, the subject and / or animal is a non-mammal, such as a zebrafish. In embodiments, the subject and / or animal may include fluorescently tagged cells (e.g., having GFP). In embodiments, the subject and / or animal is a transgenic animal containing fluorescent cells.

[0609] In an embodiment, the subject and / or animal is a human. In an embodiment, the human is a child. In an embodiment, the human is an adult. In an embodiment, the human is an elderly person. In an embodiment, the human may be called a patient.

[0610] In one embodiment, humans are approximately 0 to 6 months old, 6 to 12 months old, 6 to 18 months old, 18 to 36 months old, 1 to 5 years old, 5 to 10 years old, 10 to 15 years old, 15 to 20 years old, 20 to 25 years old, 25 to 30 years old, 30 to 35 years old, and 35 years old. Having an age in the range of approximately 40 years old, approximately 40 to approximately 45 years old, approximately 45 to approximately 50 years old, approximately 50 to approximately 55 years old, approximately 55 to approximately 60 years old, approximately 60 to approximately 65 years old, approximately 65 to approximately 70 years old, approximately 70 to approximately 75 years old, approximately 75 to approximately 80 years old, approximately 80 to approximately 85 years old, approximately 85 to approximately 90 years old, approximately 90 to approximately 95 years old, or approximately 95 to approximately 100 years old.

[0611] In some embodiments, the subject is a non-human animal, and therefore this disclosure relates to veterinary use. In certain embodiments, the non-human animal is a household pet. In other particular embodiments, the non-human animal is a domestic animal.

[0612] kit This disclosure provides a kit that can simplify the administration of any of the agents described herein. An exemplary kit of this disclosure comprises any of the compositions described herein in unit dosage forms. In one embodiment, the unit dosage form may be a container, such as a sterile, pre-filled syringe, containing any of the agents described herein and a pharmaceutically acceptable carrier, diluent, excipient, or vehicle. The kit may further include a label or printed instructions indicating the use of any of the agents described herein. The kit may also include a lid speculum, a local anesthetic, and a cleanser for administration. The kit may also further include one or more additional agents described herein. In one embodiment, the kit includes a container containing an effective amount of a composition of this disclosure and an effective amount of another composition, such as those described herein.

[0613] This disclosure also provides the following specific embodiments:

[0614] Embodiment 1. A compound of formula (I) or a pharmaceutically acceptable salt thereof. [ka] In formula (I): A is [ka] Selected from; L is a linking group; R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a , R 5b , R 5c , R 5d , R 5e , R 6a , R 6b , R 6c , R 6d , R 6e , R7a , R 7b , R 7c , R 7d , R 8 , R 9 , R 10 , R 11a , R 11b , and R 11c Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2; R 12 is H or an unsubstituted alkyl group;

[0615] R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n1 is an integer between 0 and 5; t is either 1 or 2; However, the compound of formula (I) is not any of the compounds of formulas 1001, 1003, 1004, and 1006 to 1009 below. [Table 3]

[0616] Embodiment 2.R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a , R 5b , R 5c , R 5d , R 5e , R 6a , R 6b , R 6c , R 6d , R 6e , R 7a , R 7b , R 7c , R 7d , R 8 , R 9 , R 10 , R 11a , R 11b , and R 11cHowever, each is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl (optionally substituted with halo, unsubstituted or substituted alkyl, and / or unsubstituted or substituted heterocyclyl), unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, halogen, -C(O)R a ,-C(O)N(R a )2, -N(R a )2, -N(R a )C(O)R a , and -S(O) t R a A compound selected from the compound described in Embodiment 1.

[0617] Embodiment 3.L is bonded, or non-substituted or substituted, -C 1-10 Alkyl-, -OC 1-10 Alkyl-, -C 1-10 Alkenyl-, -OC 1-10 Alkenyl-, -C 1-10 Cycloalkenyl-, -OC 1-10 Cycloalkenyl-,-C 1-10 Alkinyl-, -OC 1-10 Alkinyl-, -C 1-10 aryl-, -OC 1-10 -, -aryl-, -cycloalkyl-, -heterocyclyl-, -O-, -S-, -SS-, -S(O) w -, -C(O)-, -C(O)O-, -OC(O)-, -C(O)S-, -SC(O)-, -OC(O)O-, -N(R b )-,-C(O)N(R b )-,-N(R b )C(O)-,-OC(O)N(R b )-,-N(R b )C(O)O-, -SC(O)N(R b )-,-N(R b )C(O)S-, -N(R b )C(O)N(R b )-,-N(R b )C(NRb )N(R b )-,-N(R b )S(O) w -, -S(O) w N(R b )-,-S(O) w O-, -OS(O) w -, -OS(O) w O-, -O(O)P(OR b )O-, (O)P(O-)3, -O(S)P(OR b It comprises one or more linking groups selected from )O- and (S)P(O-)3, where w is 1 or 2, and R b L is independently hydrogen, optionally substituted alkyl, or optionally substituted aryl, and optionally L is bonded and / or -C(O)- and / or -C(H)(CH2) p C(O)NH2 and / or [ka] Here, p is an integer from 1 to 5, p is arbitrarily 2, and L is arbitrarily [ka] (Here, alkyl can be substituted or unsubstituted.) [ka] The compound according to Embodiment 1 or Embodiment 2.

[0618] Embodiment 4. The compound of formula (I) is the compound of formula (10), [ka] In formula (10): R 9a , R 9b , R 9c , R 9d , and R9e Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2; R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n² is an integer between 0 and 5; t is either 1 or 2.

[0619] A compound according to any one of Embodiments 1 to 3.

[0620] Embodiment 5.n 2 The compound according to Embodiment 4, wherein the ratio is 2.

[0621] Embodiment 6.R 1a C 1-6 The compound according to Embodiment 4 or Embodiment 5, which is alkyl and optionally -CH3.

[0622] Embodiment 7.R 2 A compound according to any one of Embodiments 4 to 6, wherein the compound is H.

[0623] Embodiment 8.R 9a , R 9b , R 9c , R 9d , and R 9e However, each compound is independently selected from hydrogen and halogen, and optionally F or Cl, according to any one of Embodiments 4 to 7.

[0624] Embodiment 9.R 9a , R 9b , R 9c , R 9d , and R 9e The compound according to any one of Embodiments 4 to 8, wherein each of these is hydrogen.

[0625] Embodiment 10.R 9a , R 9d , and R 9eHowever, each is hydrogen, and arbitrarily, R 9b is Cl and / or R 9c A compound according to any one of Embodiments 4 to 8, wherein F is present.

[0626] Embodiment 11. The compound of formula (I) is the compound of formula (20) or (21), [ka] In equations (20) and (21): The compound according to any one of Embodiments 1 to 3, wherein n3 is an integer from 0 to 5.

[0627] Embodiment 12. The compound according to Embodiment 11, wherein n3 is 2.

[0628] Embodiment 13.R 4a The compound according to Embodiment 11 or Embodiment 12, wherein is H. The compound according to .

[0629] Embodiment 14.R 4b A compound according to any one of Embodiments 11 to 13, wherein is H.

[0630] Embodiment 15.R 3 C 1-6 A compound according to any one of Embodiments 11 to 13, which is alkyl and optionally -CH3.

[0631] Embodiment 16. The compound of formula (I) is the compound of formula (30) or formula (31), [ka] In equations (30) and (31): The compound according to any one of Embodiments 1 to 3, wherein p is an integer from 0 to 5.

[0632] Embodiment 17. The compound according to Embodiment 16, wherein p is 2.

[0633] Embodiment 18.R 5a , R 5b , R 5c , R 5d , and R 5e The compounds according to Embodiment 16 or Embodiment 17, each independently selected from hydrogen, an unsubstituted or substituted alkyl group, optionally -CH3, and a halogen, optionally F or Cl.

[0634] Embodiment 19.R 5a , R 5c , R 5d , and R 5e However, each is hydrogen, and R can be arbitrarily selected. 5d A compound according to any one of Embodiments 16 to 18, wherein the compound is -CH3.

[0635] Embodiment 20. The compound of formula (I) is the compound of formula (32), [ka] In formula (32): A compound according to any one of Embodiments 1 to 3, wherein q is an integer from 1 to 3.

[0636] Embodiment 21. The compound according to Embodiment 20, wherein q is 1.

[0637] Embodiment 22.R 5a , R 5b , R 5c , and R 5d The compounds according to Embodiment 20 or Embodiment 21, each independently selected from hydrogen, an unsubstituted or substituted alkyl group, optionally -CH3, and a halogen, optionally F or Cl.

[0638] Embodiment 23.R 5a , R 5b , R 5c , and R 5dThe compound described in any one of Embodiments 19 to 21, wherein each of these compounds is hydrogen.

[0639] Embodiment 24. The compound of formula (I) is the compound of formula (40), [ka] In formula (40): The compound according to any one of Embodiments 1 to 3, wherein n4 is an integer from 0 to 5.

[0640] Embodiment 25. The compound according to Embodiment 24, wherein n4 is 0.

[0641] Embodiment 26.R 6a , R 6b , R 6c , R 6d , and R 6e The compounds according to Embodiment 24 or Embodiment 25, each independently selected from hydrogen, an unsubstituted or substituted alkyl group, an optionally amide-substituted alkyl group, and an amide group.

[0642] Embodiment 27.R 6a , R 6b , R 6c , R 6d , and R 6e However, each independently, hydrogen and [ka] A compound selected from any one of Embodiments 24 to 26, where r is an integer from 0 to 4, and optionally r is 0.

[0643] Embodiment 28.R 6a , R 6c , R 6d , and R 6e However, each is hydrogen, and R can be arbitrarily selected. 6b A compound according to any one of Embodiments 24 to 27, wherein is -C(O)NH2.

[0644] Embodiment 29. The compound of formula (I) is the compound of formula (50), [ka] In formula (50): R 10a , R 10b , R 10c , R 10d , and R 10e Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O)t N(R a )2, and PO3(R a ) Selected from 2; R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n5 is an integer between 0 and 5; t is either 1 or 2. A compound according to any one of Embodiments 1 to 3.

[0645] Embodiment 30. The compound according to Embodiment 29, wherein n5 is 3.

[0646] Embodiment 31.R 7a , R 7b , R 7c , R 7d , R 10a , R 10b , R 10c , R 10d , and R 10e The compounds according to Embodiment 29 or Embodiment 30, each independently selected from hydrogen, an unsubstituted or substituted alkyl group, optionally -CH3, and a halogen, optionally F or Cl.

[0647] Embodiment 32.R 7a , R 7b , R 7c , and R 7d The compound described in any one of Embodiments 29 to 31, wherein each of these compounds is hydrogen.

[0648] Embodiment 33.R 10a , R 10b , R 10d , and R 10e However, each is hydrogen, and R can be arbitrarily selected. 10c A compound according to any one of Embodiments 29 to 31, wherein F is present.

[0649] Embodiment 34. The compound of formula (I) is the compound of formula (60), [ka] In formula (60): The compound according to any one of Embodiments 1 to 3, wherein n6 is an integer from 0 to 5.

[0650] The compound according to Embodiment 34, wherein n6 is 1.

[0651] Embodiment 36.R 9 The compound according to Embodiment 34, wherein is H.

[0652] Embodiment 37. The compound of formula (I) is the compound of formula (70), [ka] In formula (70): R 11a and R 11b Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a)2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2; R a In each occurrence, independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. A compound according to any one of Embodiments 1 to 3.

[0653] Embodiment 38. The compound according to Embodiment 37, wherein the compound of formula (70) is the compound of formula (700) or formula (701). [ka]

[0654] Embodiment 39. The compound of formula (I) is the compound of formula (80) or formula (81), [ka] In formula (80): R 11a and R 11bEach of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2; R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n8 is an integer between 1 and 5; [ka] In formula (81): Alk is either unsubstituted or substituted alkyl; R 11a and R 11b Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a)S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2; R a In each occurrence, independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. A compound according to any one of Embodiments 1 to 3.

[0655] Embodiment 40. The compound according to Embodiment 39, wherein the compound of formula (80) is the compound of formula (800) or formula (801), or the compound of formula (81) is the compound of formula (802) or formula (803). [ka]

[0656] Embodiment 41.R 5a and R 5d The compound according to Embodiment 37 or Embodiment 39, wherein each of these is hydrogen.

[0657] Embodiment 42.R 5b and / or R 5c However, each can be independently an unsubstituted or substituted alkynyl, optionally a substituted alkynyl, substituted aryl, substituted heteroaryl, halogen, optionally Br, -N(R) a )2, optionally -NH2, and -N(R a )C(O)R a , at will [ka] Selected from, and optionally R 5b but [ka] Selected from, and optionally R 5c but [ka] A compound selected from any one of Embodiments 37 to 41.

[0658] Embodiment 43.R 11a and R 11b However, each is either an unsubstituted alkyl or R 11a and R 11b However, each is independent of the others. [ka] is or R 11a is selected from H and unsubstituted alkyl, R 11b but [ka]

[0659] is or R 11a H is R 11b The compound according to any one of Embodiments 37 to 42, wherein is an unsubstituted alkyl, where Y is selected from unsubstituted or substituted alkyl, optionally unsubstituted or substituted C1-C5 alkyl, unsubstituted or substituted aryl, optionally unsubstituted or substituted phenyl, unsubstituted or substituted cycloalkyl, optionally unsubstituted or substituted C3-C7 cycloalkyl, and unsubstituted or substituted alkoxy, optionally unsubstituted or substituted C1-C5 alkoxy, and n7 is an integer from 1 to 3, optionally n7 is 1 or 2.

[0660] Embodiment 44.R 11a and R 11b However, each is independent of the others. [ka] Selected from, and optionally R 11a and R 11b However, each is independent of the others. [ka] A compound selected from the compounds described in Embodiment 43.

[0661] Embodiment 45.R 11a is selected from H and -CH3, R 11b but [ka] Selected from, optionally, R 11a is selected from H and -CH3, R 11b but [ka] A compound selected from the compounds described in Embodiment 43.

[0662] Embodiment 46.R 11a is selected from H and -CH3, R 11b but [ka] A compound selected from the compounds described in Embodiment 43.

[0663] Embodiment 47.R 11a H is R 11b Is it -CH3, or R 11a and R 11bThe compound according to Embodiment 43, wherein each of them is -CH3.

[0664] A compound according to any one of Embodiments 39 to 47, wherein Embodiment 48.n8 is 1.

[0665] Embodiment 49. The compound of formula (I) is the compound of formula (82), [ka] In formula (82): R 11a , R 11b , R 11c , and R 11d Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t Ra , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2; R a In each occurrence, independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. A compound according to any one of Embodiments 1 to 3.

[0666] Embodiment 50. The compound according to Embodiment 49, wherein the compound of formula (82) is the compound of formula (804) or formula (805). [ka]

[0667] Embodiment 51.R 5b and / or R 5c However, each is independent of -OR a And here, R a is an unsubstituted alkyl, optionally -OR a The compound according to Embodiment 49 or Embodiment 50, wherein is -OCH3.

[0668] Embodiment 52.R 11a and R11c However, each is hydrogen, and R 11b and R 11d However, each is independently an unsubstituted cycloalkyl, optionally a cyclohexyl; or R 11a and R 11c However, each is hydrogen, and R 11b and R 11d However, each is independently a cycloalkyl-substituted alkyl, optionally [ka] That is, A compound according to any one of Embodiments 49 to 51.

[0669] Embodiment 53. The compound of formula (I) is the compound of formula (90), [ka] In formula (90): A compound according to any one of Embodiments 1 to 3, wherein n is an integer from 1 to 5.

[0670] Embodiment 54. The compound according to Embodiment 53, wherein the compound of formula (90) is the compound of formula (900), formula (901), or formula (902). [ka]

[0671] Embodiment 55.R 12 The compound according to Embodiment 53 or Embodiment 54, wherein is H or -CH3.

[0672] Embodiment 56.R 11a is H or substituted alkyl, optionally [ka] , at will [ka] The compound described in any one of Embodiments 53 to 55.

[0673] Embodiment 57.R 10 -C(O)R aAnd R can be any a R is selected from unsubstituted alkenyls, substituted alkyls, substituted aryls, and substituted heterocyclines, or R 10 ga-S(O) t R a And arbitrarily, t is 2, R a The compound according to any one of Embodiments 53 to 56, wherein is a substituted aryl.

[0674] Embodiment 58.R 10 but [ka] A compound selected from any one of Embodiments 53 to 57.

[0675] Embodiment 59. The compound according to any one of Embodiments 1 to 3 or Embodiments 37 to 58, wherein the compound of formula (I) is one of the compounds of formula 1002, formula 1005, or formulas 1010 to 1098, or a pharmaceutically acceptable salt thereof.

[0676] Embodiment 60. In this embodiment, the compound of formula (I) is one of the compounds of formula 1010, formula 1011, formulas 1020 to 1030, formula 1034, formula 1036, formula 1037, formula 1040, formula 1043, formula 1050, formulas 1053 to 1056, formula 1058, formula 1060, formula 1062, formula 1064, formula 1066, formula 1069, formula 1070, formula 1075, or formula 1084, or a pharmaceutically acceptable salt thereof, as described in any one of Embodiments 1 to 3 or Embodiments 37 to 59.

[0677] Embodiment 61. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. [ka] In formula (I): A is [ka] Selected from; L is a linking group; R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a , R 5b , R 5c , R 5d , R 5e , R 6a , R 6b , R 6c , R 6d , R 6e , R 7a , R 7b , R 7c , R 7d , R 8 , R 9 , R 10 , R 11a , R 11b , and R 11c Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a)C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2; R 12 is H or an unsubstituted alkyl group; R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n1 is an integer between 0 and 5; t is either 1 or 2.

[0678] Embodiment 62.R 1a , R 1b , R 2 , R 3 , R 4a , R 4b , R 5a , R 5b , R 5c , R 5d , R 5e , R 6a , R 6b , R 6c , R 6d , R 6e , R 7a , R 7b , R 7c , R 7d , R 8 , R9 , R 10 , R 11a , R 11b , and R 11c However, each is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl (optionally substituted with halo, unsubstituted or substituted alkyl, and / or unsubstituted or substituted heterocyclyl), unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, halogen, -N(R a )2, -C(O)R a ,-C(O)N(R a )2, -N(R a )C(O)R a , and -S(O) t R a A pharmaceutical composition according to embodiment 61, selected from the above.

[0679] Embodiment 63.L is bonded, or non-substituted or substituted, -C 1-10 Alkyl-, -OC 1-10 Alkyl-, -C1- 10 Alkenyl-, -OC 1-10 Alkenyl-, -C 1-10 Cycloalkenyl-, -OC 1-10 Cycloalkenyl-,-C 1-10 Alkinyl-, -OC 1-10 Alkinyl-, -C 1-10 aryl-, -OC 1-10 -, -aryl-, -cycloalkyl-, -heterocyclyl-, -O-, -S-, -SS-, -S(O) w -, -C(O)-, -C(O)O-, -OC(O)-, -C(O)S-, -SC(O)-, -OC(O)O-, -N(R b )-,-C(O)N(R b )-,-N(R b )C(O)-,-OC(O)N(R b )-,-N(R b )C(O)O-, -SC(O)N(R b )-,-N(R b)C(O)S-, -N(R b )C(O)N(R b )-,-N(R b )C(NR b )N(R b )-,-N(R b )S(O) w -, -S(O) w N(R b )-,-S(O) w O-, -OS(O) w -, -OS(O) w O-, -O(O)P(OR b )O-, (O)P(O-)3, -O(S)P(OR b It comprises one or more linking groups selected from )O- and (S)P(O-)3, where w is 1 or 2, and R b L is independently hydrogen, optionally substituted alkyl, or optionally substituted aryl, and optionally L is bonded and / or -C(O)- and / or -C(H)(CH2) p C(O)NH2 and / or [ka]

[0680] Here, p is an integer from 1 to 5, p is arbitrarily 2, and L is arbitrarily [ka]

[0681] (In this case, alkyl can be substituted or unsubstituted.) [ka] The pharmaceutical composition according to Embodiment 61 or Embodiment 62.

[0682] Embodiment 64. The compound of formula (I) is the compound of formula (10), [ka] In formula (10): R 9a , R 9b , R 9c , R 9d , and R 9e Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2; R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n² is an integer between 0 and 5; t is either 1 or 2. A pharmaceutical composition according to any one of Embodiments 61 to 63.

[0683] Embodiment 65.n 2 The pharmaceutical composition according to Embodiment 64, wherein the ratio is 2.

[0684] Embodiment 66.R 1a C 1-6 A pharmaceutical composition according to Embodiment 64 or Embodiment 65, wherein the composition is alkyl and optionally -CH3.

[0685] Embodiment 67.R 2 A pharmaceutical composition according to any one of Embodiments 64 to 66, wherein is H.

[0686] Embodiment 68.R 9a , R 9b , R 9c , R 9d , and R 9e The pharmaceutical composition according to any one of Embodiments 64 to 67, wherein each is independently selected from hydrogen and halogen, and optionally F or Cl.

[0687] Embodiment 69.R 9a , R 9b , R 9c , R 9d , and R 9e The pharmaceutical composition according to any one of Embodiments 64 to 68, wherein each of these is hydrogen.

[0688] Embodiment 70.R 9a , R 9d , and R 9eHowever, each is hydrogen, and arbitrarily, R 9b is Cl and / or R 9c A pharmaceutical composition according to any one of Embodiments 64 to 69, wherein F.

[0689] Embodiment 71. The compound of formula (I) is a compound of formula (20) or formula (21), [ka] In equations (20) and (21): A pharmaceutical composition according to any one of Embodiments 61 to 63, wherein n3 is an integer from 0 to 5.

[0690] The pharmaceutical composition according to Embodiment 71, wherein Embodiment 72.n3 is 2.

[0691] Embodiment 73.R 4a A pharmaceutical composition according to Embodiment 71 or Embodiment 72, wherein is H.

[0692] Embodiment 74.R 4b A pharmaceutical composition according to any one of Embodiments 71 to 73, wherein is H.

[0693] Embodiment 75.R 3 C 1-6 A pharmaceutical composition according to any one of Embodiments 71 to 74, wherein the composition is alkyl and optionally -CH3.

[0694] Embodiment 76. The compound of formula (I) is a compound of formula (30) or formula (31), [ka] In equations (30) and (31): A pharmaceutical composition according to any one of Embodiments 61 to 63, wherein p is an integer from 0 to 5.

[0695] The pharmaceutical composition according to Embodiment 76, wherein p is 2.

[0696] Embodiment 78.R 5a , R 5b , R 5c , R 5d , and R 5e The pharmaceutical composition according to Embodiment 76 or Embodiment 77, wherein each is independently selected from hydrogen, an unsubstituted or substituted alkyl group, optionally -CH3, and a halogen, optionally F or Cl.

[0697] Embodiment 79.R 5a , R 5c , R 5d , and R 5e However, each is hydrogen, and R can be arbitrarily selected. 5d A pharmaceutical composition according to any one of Embodiments 76 to 78, wherein is -CH3.

[0698] Embodiment 80. The compound of formula (I) is the compound of formula (32), [ka] In formula (32): A pharmaceutical composition according to any one of Embodiments 61 to 63, wherein q is an integer from 1 to 3.

[0699] Embodiment 81. The pharmaceutical composition according to Embodiment 80, wherein q is 1.

[0700] Embodiment 82.R 5a , R 5b , R 5c , and R 5d The pharmaceutical composition according to Embodiment 80 or Embodiment 81, wherein each is independently selected from hydrogen, an unsubstituted or substituted alkyl group, optionally -CH3, and a halogen, optionally F or Cl.

[0701] Embodiment 83.R 5a , R 5b , R 5c , and R 5d The pharmaceutical composition according to any one of Embodiments 80 to 82, wherein each of these is hydrogen.

[0702] Embodiment 84. The compound of formula (I) is the compound of formula (40), [ka] In formula (40): A pharmaceutical composition according to any one of Embodiments 61 to 63, wherein n4 is an integer from 0 to 5.

[0703] The pharmaceutical composition according to Embodiment 84, wherein Embodiment 85.n4 is 0.

[0704] Embodiment 86.R 6a , R 6b , R 6c , R 6d , and R 6e The pharmaceutical composition according to Embodiment 84 or Embodiment 85, wherein each is independently selected from hydrogen, an unsubstituted or substituted alkyl, an optionally amide-substituted alkyl, and an amide.

[0705] Embodiment 87.R 6a , R 6b , R 6c , R 6d , and R 6e However, each independently, hydrogen and [ka] A pharmaceutical composition according to any one of Embodiments 84 to 86, selected from, where r is an integer from 0 to 4, and optionally r is 0.

[0706] Embodiment 88.R 6a , R 6c , R 6d , and R6 e However, each is hydrogen, and R6 is arbitrarily selected. b A pharmaceutical composition according to any one of Embodiments 84 to 87, wherein is -C(O)NH2.

[0707] Embodiment 89. The compound of formula (I) is the compound of formula (50), [ka] In formula (50): R 10a , R 10b , R 10c , R 10d , and R 10e Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a) Selected from 2; R a Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n5 is an integer between 0 and 5; t is either 1 or 2.

[0708] A pharmaceutical composition according to any one of Embodiments 61 to 63.

[0709] The pharmaceutical composition according to Embodiment 89, wherein Embodiment 90.n5 is 3.

[0710] Embodiment 91.R 7a , R 7b , R 7c , R 7d , R 10a , R 10b , R 10c , R 10d , and R 10e The pharmaceutical composition according to Embodiment 89 or Embodiment 90, wherein each is independently selected from hydrogen, an unsubstituted or substituted alkyl group, optionally -CH3, and a halogen, optionally F or Cl.

[0711] Embodiment 92.R 7a , R 7b , R 7c , and R 7d The pharmaceutical composition according to any one of Embodiments 89 to 91, wherein each of these is hydrogen.

[0712] Embodiment 93.R 10a , R 10b , R 10d , and R 10e However, each is hydrogen, and R can be arbitrarily selected. 10c A pharmaceutical composition according to any one of Embodiments 89 to 92, wherein F.

[0713] Embodiment 94. The compound of formula (I) is the compound of formula (60), [ka] In formula (60): The pharmaceutical composition according to any one of Embodiments 61 to 63, wherein n6 is an integer from 0 to 5.

[0714] The pharmaceutical composition according to Embodiment 94, wherein Embodiment 95.n6 is 1.

[0715] Embodiment 96.R 9 A pharmaceutical composition according to Embodiment 94 or Embodiment 95, wherein is H.

[0716] Embodiment 97. The compound of formula (I) is the compound of formula (70), [ka] In formula (70): R 11a and R 11b Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a)2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2; R a In each occurrence, independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. A pharmaceutical composition according to any one of Embodiments 61 to 63.

[0717] Embodiment 98. The pharmaceutical composition according to Embodiment 97, wherein the compound of formula (70) is the compound of formula (700) or formula (701). [ka]

[0718] Embodiment 99. The compound of formula (I) is a compound of formula (80) or formula (81), [ka] In formula (80): R11a and R 11b Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2; R aEach instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n8 is an integer between 1 and 5; [ka] In formula (81): Alk is either unsubstituted or substituted alkyl; R 11a and R 11b Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a)2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a ) Selected from 2; R a In each occurrence, independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. A pharmaceutical composition according to any one of Embodiments 61 to 63.

[0719] Embodiment 100. The pharmaceutical composition according to Embodiment 99, wherein the compound of formula (80) is the compound of formula (800) or formula (801), or the compound of formula (81) is the compound of formula (802) or formula (803). [ka]

[0720] Embodiment 101.R 5a and R 5d The pharmaceutical composition according to Embodiment 97 or Embodiment 99, wherein each of these is hydrogen.

[0721] Embodiment 102.R 5b and / or R 5c However, each can be independently: unsubstituted or substituted alkynyl (optionally substituted alkynyl), substituted aryl, substituted heteroaryl, halogen (optionally Br), -N(R a )2 (arbitrarily -NH2), and -N(R a )C(O)R a , at will [ka] Selected from, and optionally R 5b but [ka] Selected from, and optionally R 5c but [ka] A pharmaceutical composition according to any one of Embodiments 97 to 101, selected from the above.

[0722] Embodiment 103.R 11a and R 11b However, each is either an unsubstituted alkyl or R 11a and R 11b However, each is independent of the others. [ka] is or R 11a is selected from H and unsubstituted alkyl, R 11b but [ka] is or R 11a H is R 11b The pharmaceutical composition according to any one of Embodiments 97 to 102, wherein Y is an unsubstituted alkyl, where Y is selected from unsubstituted or substituted alkyl, optionally unsubstituted or substituted C1-C5 alkyl, unsubstituted or substituted aryl, optionally unsubstituted or substituted phenyl, unsubstituted or substituted cycloalkyl, optionally unsubstituted or substituted C3-C7 cycloalkyl, and unsubstituted or substituted alkoxy, optionally unsubstituted or substituted C1-C5 alkoxy, and n7 is an integer from 1 to 3, optionally n7 is 1 or 2.

[0723] Embodiment 104.R 11a and R 11b However, each is independent of the others. [ka] Selected from, and optionally R 11a and R 11b However, each is independent of the others. [ka] A pharmaceutical composition according to Embodiment 103, selected from the above.

[0724] Embodiment 105.R 11a is selected from H and -CH3, R 11b but [ka] Selected from, optionally, R 11a is selected from H and -CH3, R 11b but [ka]

[0725] A pharmaceutical composition according to Embodiment 103, selected from the above.

[0726] Embodiment 106.R 11a H is R 11b Is it -CH3, or R 11a and R 11b The pharmaceutical composition according to Embodiment 103, wherein each of them is -CH3.

[0727] A pharmaceutical composition according to any one of Embodiments 103 to 106, wherein Embodiment 107.n8 is 1.

[0728] Embodiment 108. The compound of formula (I) is the compound of formula (82), [ka] In formula (82): R 11a , R 11b , R 11c , and R 11d Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR a , -SR a -OC(O)-R a ,-SC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a -C(O)SR a ,-OC(O)N(R a )2, -C(O)N(R a )2, -N(R a )C(O)OR a , -N(R a )C(O)R a , -N(R a )C(O)N(R a )2, -N(R a )C(NR a )N(R a )2, -N(R a )S(O) t R a , -S(O) t R a , -S(O) t Ure a , -S(O) t N(R a )2, and PO3(R a) Selected from 2; R a In each occurrence, independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. A pharmaceutical composition according to any one of Embodiments 61 to 63.

[0729] Embodiment 109. The pharmaceutical composition according to Embodiment 108, wherein the compound of formula (82) is a compound of formula (804) or formula (805). [ka]

[0730] Embodiment 110.R 5b and / or R 5c However, each is independent of -OR a And here, R a is an unsubstituted alkyl, optionally -OR a A pharmaceutical composition according to Embodiment 108 or Embodiment 109, wherein is -OCH3.

[0731] Embodiment 111.R 11a and R 11c However, each is hydrogen, and R 11b and R 11d However, each is independently an unsubstituted cycloalkyl, optionally a cyclohexyl; or R 11a and R11c However, each is hydrogen, and R 11b and R 11d However, each is independently a cycloalkyl-substituted alkyl, optionally [ka] The pharmaceutical composition described in any one of Embodiments 108 to 110.

[0732] Embodiment 112. The compound of formula (I) is the compound of formula (90), [ka] In formula (90): A pharmaceutical composition according to any one of Embodiments 61 to 63, wherein n is an integer from 1 to 5.

[0733] Embodiment 113. The pharmaceutical composition according to Embodiment 112, wherein the compound of formula (90) is a compound of formula (900), formula (901), or formula (902). [ka]

[0734] Embodiment 114.R 12 A pharmaceutical composition according to Embodiment 112 or Embodiment 113, wherein is H or -CH3.

[0735] Embodiment 115.R 11a is H or a substituted alkyl, optionally [ka] The pharmaceutical composition according to any one of Embodiments 112 to 114.

[0736] Embodiment 116.R 10 -C(O)R a And R can be any a R is selected from unsubstituted alkenyls, substituted alkyls, substituted aryls, and substituted heterocyclines, or R 10 ga-S(O) t R a And arbitrarily, t is 2, R aA pharmaceutical composition according to any one of Embodiments 112 to 115, wherein is a substituted aryl.

[0737] Embodiment 117.R 10 but [ka] A pharmaceutical composition according to any one of embodiments 112 to 116, selected from among them.

[0738] Embodiment 118. The pharmaceutical composition according to Embodiment 61, wherein the compound of formula (I) is any one of the compounds from formulas 1001 to 1098, or a pharmaceutically acceptable salt thereof.

[0739] Embodiment 119. The pharmaceutical composition according to Embodiment 61, wherein the compound of formula (I) is any one compound of formula 1010, formula 1011, formulas 1020 to 1030, formula 1034, formula 1036, formula 1037, formula 1040, formula 1043, formula 1050, formulas 1053 to 1056, formula 1058, formula 1060, formula 1062, formula 1064, formula 1066, 1069, formula 1070, formula 1075, or formula 1084, or a pharmaceutically acceptable salt thereof.

[0740] Embodiment 120. A method for treating cancer, an infection, or an inflammatory disease in a subject requiring treatment, comprising administering a pharmaceutical composition described in any one of Embodiments 61 to 119 to the subject.

[0741] Embodiment 121. Cancers include basal cell carcinoma, biliary tract cancer, bladder cancer, bone cancer, brain and central nervous system cancer, breast cancer, peritoneal cancer, cervical cancer, choriocarcinoma, colon and rectum cancer, connective tissue cancer, digestive system cancer, endometrial cancer, esophageal cancer, eye cancer, head and neck cancer, gastric cancer (including gastrointestinal cancer), glioblastoma, hepatocellular carcinoma, liver cancer, carcinoma in situ, kidney cancer, laryngeal cancer, leukemia, liver cancer, lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma), melanoma, myeloma, neuroblastoma, oral cancer (lips, tongue, mouth, and pharynx), ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, rhabdomyosarcoma, rectal cancer, respiratory system cancer, salivary gland cancer, sarcoma, skin cancer, squamous cell carcinoma, and stomach cancer. Cancer, testicular cancer, thyroid cancer, uterine or endometrial cancer, urinary tract cancer, vulvar cancer, Hodgkin lymphoma and non-Hodgkin lymphoma, and B-cell lymphoma (low-grade / follicular non-Hodgkin lymphoma (NHL), small lymphocytic (SL) NHL, intermediate-grade / follicular NHL, intermediate-grade diffuse NHL, high-grade immunoblastic NHL, high-grade lymphoblastic NHL, high-grade small non-incisional nuclear cell type NHL, giant tumor lesion NHL, mantle cell lymphoma The method according to Embodiment 120, selected from lymphomas (including lymphoma, AIDS-associated lymphoma, and Waldenström macroglobulinemia), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia, chronic myeloid leukemia, and other carcinomas and sarcomas, and post-transplant lymphoproliferative disorders (PTLD), as well as nevus disorders, edema (such as that associated with brain tumors), and abnormal angiogenesis associated with Meigs syndrome.

[0742] Embodiment 122. Cancer is chronic lymphocytic leukemia (CLL), acute leukemia, acute lymphoblastic leukemia (ALL), B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), chronic myeloid leukemia (CML), B-cell prelymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell or large cell follicular The method according to Embodiment 120 or 121, wherein the hematological cancer is selected from the group consisting of leukemia, malignant lymphoproliferative disorders, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndromes, non-Hodgkin lymphoma, Hodgkin lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenström macroglobulinemia, and preleukemia, or combinations thereof.

[0743] Embodiment 123. The method according to any one of Embodiments 120 to 122, wherein the cancer is resistant to an anti-checkpoint agent.

[0744] Embodiment 124. The method according to any one of Embodiments 120 to 123, wherein the anti-checkpoint agent is an antibody, optionally selected from anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, and anti-CTLA antibody.

[0745] Embodiment 125. The method according to Embodiment 124, wherein the antibody is selected from nivolumab (OPDIVO), pembrolizumab (KEYTRUDA), pidilizumab (CT-011, CURE TECH), MK-3475 (MERCK), BMS 936559, MPDL328OA (ROCHE), semiprimab (LIBTAYO), atezolizumab (TECENTRIQ), avelumab (BAVENCIO), and durvalumab (IMFINZI).

[0746] Embodiment 126. The method according to Embodiment 120, wherein the infectious disease is a viral infection.

[0747] Embodiment 127. The method according to Embodiment 126, wherein the viral infection is caused by a virus selected from papillomavirus, herpes simplex virus (HSV), human immunodeficiency virus (HIV), hepatitis virus, Zika virus, yellow fever virus, West Nile virus, dengue virus, Japanese encephalitis virus, St. Louis encephalitis virus, hepatitis C virus, poliovirus, rhinovirus, enterovirus, coxsackievirus, influenza virus, lentivirus, respiratory syncytial virus, human parainfluenza virus, rubravirus (e.g., mumps virus), measles virus, human metapneumovirus, hantavirus, rotavirus, norovirus, and severe acute respiratory syndrome (SARS) virus (e.g., SARS-CoV-2).

[0748] Embodiment 128. The method according to Embodiment 120, wherein the inflammatory disease is an autoimmune disease or condition selected from multiple sclerosis, diabetes mellitus, lupus, celiac disease, Crohn's disease, ulcerative colitis, Guillain-Barré syndrome, scleroderma, Goodpasture syndrome, Wegener's granulomatosis, autoimmune epilepsy, Rasmussen's encephalitis, primary biliary sclerosis, sclerosing cholangitis, autoimmune hepatitis, Addison's disease, Hashimoto's thyroiditis, fibromyalgia, Meniere's syndrome; transplant rejection (e.g., prevention of allograft rejection), pernicious anemia, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, Sjögren's syndrome, lupus erythematosus, multiple sclerosis, myasthenia gravis, Reiter's syndrome, Graves' disease, and other autoimmune diseases.

[0749] Embodiment 129. A method for treating cancer resistant to anti-checkpoint agents in a subject requiring such treatment, comprising administering a pharmaceutical composition described in any one of Embodiments 61 to 119 to the subject.

[0750] Embodiment 130. The method according to Embodiment 129, wherein the anti-checkpoint agent is an antibody, optionally selected from anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, and anti-CTLA antibody.

[0751] Embodiment 131. The method according to Embodiment 130, wherein the antibody is selected from nivolumab (OPDIVO), pembrolizumab (KEYTRUDA), pidilizumab (CT-011, CURE TECH), MK-3475 (MERCK), BMS 936559, MPDL328OA (ROCHE), semiprimab (LIBTAYO), atezolizumab (TECENTRIQ), avelumab (BAVENCIO), and durvalumab (IMFINZI).

[0752] Embodiment 132. (a) Obtaining a biological sample from the subject, (b) Evaluate the expression of TRIM7 in biological samples, and (c) Select a cancer treatment comprising the pharmaceutical composition described in any one of Embodiments 61 to 119 if TRIM7 is upregulated compared to healthy tissue, a biological sample previously obtained from the subject, or another biological sample from a patient known to be sensitive to an anti-checkpoint agent. Includes, (d) Optionally, selecting a second cancer treatment including an anti-checkpoint agent, wherein the anti-checkpoint agent is selected from anti-PD-1 agents, anti-PD-L1 agents, anti-PD-L2 agents, and / or anti-CTLA agents, and optionally, the anti-checkpoint agent is selected from anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, and / or anti-CTLA antibodies. A method for determining cancer treatment for a patient, including the treatment of cancer.

[0753] Embodiment 133. (a) Obtaining biological samples from the subject, (b) Evaluate the expression of TRIM7 in biological samples, and (c) Select a cancer treatment comprising the pharmaceutical composition described in any one of Embodiments 61 to 119 if TRIM7 is upregulated compared to healthy tissue, a biological sample previously obtained from the subject, or another biological sample from a patient known to be sensitive to an anti-checkpoint agent. Includes, (d) Optionally, selecting a second cancer treatment including an anti-checkpoint agent, wherein the anti-checkpoint agent is selected from anti-PD-1 agents, anti-PD-L1 agents, anti-PD-L2 agents, and / or anti-CTLA agents, and optionally, the anti-checkpoint agent is selected from anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, and / or anti-CTLA antibodies. Methods for selecting patients for cancer treatment, including those mentioned above.

[0754] Embodiment 134. (a) Obtaining biological samples from the subject, (b) Evaluate the expression of TRIM7 in biological samples, and (c) Administering a cancer treatment comprising the pharmaceutical composition described in any one of Embodiments 61 to 119, provided that TRIM7 is upregulated compared to healthy tissue, a biological sample previously obtained from the subject, or another biological sample from a patient known to be sensitive to an anti-checkpoint agent. Includes, (d) Optionally administer a second cancer treatment comprising an anti-checkpoint agent, wherein the anti-checkpoint agent is selected from anti-PD-1 agents, anti-PD-L1 agents, anti-PD-L2 agents, and / or anti-CTLA agents, and optionally, the anti-checkpoint agent is selected from anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, and / or anti-CTLA antibodies. Methods for treating cancer, including [specific methods / techniques].

[0755] Embodiment 135. The method according to any one of Embodiments 132 to 134, wherein the biological sample is a fresh tissue sample, a frozen tumor tissue sample, cultured cells, circulating tumor cells, or a formalin-fixed paraffin-embedded tumor tissue sample.

[0756] Embodiment 136. The method according to any one of Embodiments 132 to 135, wherein the biological specimen is a biopsy specimen, and optionally the biopsy specimen is selected from endoscopic biopsy, bone marrow biopsy, endoscopic biopsy (e.g., cystoscopy, bronchoscopy, and colonoscopy), needle biopsy (e.g., fine-needle aspiration, core needle biopsy, vacuum-assisted biopsy, X-ray-assisted biopsy, computed tomography (CT)-assisted biopsy, magnetic resonance imaging (MRI)-assisted biopsy, and ultrasound-assisted biopsy), skin biopsy (e.g., shaving biopsy, punch biopsy, and incision biopsy), and surgical biopsy.

[0757] Embodiment 137. The method according to any one of Embodiments 132 to 136, wherein the biological sample comprises blood, plasma, serum, tears, bone marrow, blood, blood cells, ascites, tissue or fine-needle biopsy specimens, cell-containing bodily fluids, free suspended nucleic acids, sputum, saliva, urine, cerebrospinal fluid, peritoneal fluid, pleural fluid, feces, lymphatic fluid, gynecological fluids, skin swabs, vaginal swabs, oral swabs, nasal swabs, lavage solutions or lavage solutions such as tube lavage or bronchoalveolar lavage, aspirates, scrapes, bone marrow specimens, tissue biopsy specimens, surgical specimens, feces, other bodily fluids, secretions, and / or excretions, and / or cells derived therefrom.

[0758] Embodiment 138. The method according to any one of Embodiments 132 to 137, wherein the biological sample comprises at least one tumor cell.

[0759] Embodiment 139. The method according to any one of Embodiments 132 to 138, wherein evaluation is performed by DNA sequencing, RNA sequencing, immunohistochemical staining, Western blotting, in-cell Western blotting, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), and fluorescence-activated cell sorting (FACS), or a combination thereof.

[0760] Embodiment 140. The method according to any one of Embodiments 132 to 139, wherein evaluation is performed by contacting the sample with an agent that specifically binds to TRIM7.

[0761] The method according to Embodiment 140, wherein the agent that specifically binds to multiple proteins, as in Embodiment 141.1, includes an antibody, an antibody-like molecule, or a binding fragment thereof.

[0762] Embodiment 142. The method according to any one of Embodiments 132 to 141, wherein evaluation is performed by contacting the sample with an agent that specifically binds to one or more nucleic acids of TRIM7.

[0763] The method according to Embodiment 142, wherein the agent that specifically binds to multiple nucleic acids, as in Embodiment 143.1, is a nucleic acid primer or probe.

[0764] Any aspect or embodiment described herein can be combined with any other aspect or embodiment disclosed herein.

[0765] The present disclosure is further illustrated in the following embodiments, which do not limit the scope of the present disclosure as set forth in the claims. [Examples]

[0766] The examples herein are provided to illustrate the advantages and benefits of the Disclosure and to further assist those skilled in the art in preparing or using the TRIM7 inhibitors of the Disclosure. The examples herein are also presented to more fully illustrate preferred embodiments of the Disclosure. The examples should not be construed as limiting the scope of the Disclosure as defined by the appended claims. The examples may include or incorporate any of the above-described variations, aspects, or embodiments of the Disclosure. Each of the above-described variations, aspects, or embodiments may further include or incorporate any or all other variations, aspects, or embodiments of the Disclosure.

[0767] Example 1: Binding of recombinant human TRIM7 protein to RACO1 and MSK1 While we do not wish to be constrained by theory, it is thought that MSK1 directly phosphorylates tripartite motif-containing 7 (TRIM7). Again, while we do not wish to be constrained by theory, it is thought that TRIM7 can ubiquitinate proteins such as RACO1, mitochondrial anti-viral signaling protein (MAVS), and interferon gene stimulator (STING), which in turn impairs host immune interferon responsiveness.

[0768] The binding of TRIM7 protein to RACO1 and MSK1 was investigated using an assay based on a mesoscale discovery (MSD) platform. Briefly, recombinant human TRIM7 protein was immobilized on a plate. Gradual doses of RACO1, MSK1, or CD47 protein were added to the plate so that they could be captured by the plate-bound recombinant TRIM7 protein. The RACO1 or MSK1 protein captured by the plate-bound TRIM7 protein was detected using an anti-human RACO1 antibody or anti-human MSK1 antibody and a SULFO-TAG conjugate secondary antibody. As shown in Figure 1A, the RACO1 protein bound to the plate-bound recombinant TRIM7 protein in a dose-dependent manner. In contrast, the CD47 protein showed only a background signal (Figure 1A). Similarly, as shown in Figure 1B, the MSK1 protein bound to the plate-bound recombinant TRIM7 protein in a dose-dependent manner. In contrast, the CD47 protein showed only a background signal (Figure 1B).

[0769] These results, in particular, demonstrate that the TRIM7 protein disclosed herein specifically binds to the RACO1 and MSK1 proteins.

[0770] Example 2: Binding of recombinant human TRIM7 protein to enterovirus 71 2BC protein The binding of TRIM7 protein to enterovirus 71 2B / C and 2C proteins was investigated using an assay based on the mesoscale discovery (MSD) platform. For this experiment, recombinant human RACO1 protein and recombinant human MSK1 protein were used as positive controls, and recombinant human CD47 protein was used as a negative control. Briefly, recombinant human RACO1 protein, MSK1 protein, CD47 protein, enterovirus 71 2B protein, or enterovirus 71 2BC protein were immobilized on a plate. Gradual amounts of recombinant human TRIM7 protein were added to the plate so that it could be captured by plate-bound RACO1 protein, MSK1 protein, CD47 protein, enterovirus 71 2B protein, or enterovirus 71 2BC protein. TRIM7 protein, captured by plate-bound RACO1 protein, MSK1 protein, CD47 protein, enterovirus 71 2B protein, or enterovirus 71 2BC protein, was detected using an anti-human TRIM7 antibody and a SULFO-TAG conjugate secondary antibody. As shown in Figure 2, TRIM7 was able to bind to plate-bound enterovirus 71 2B / C protein in a dose-dependent manner. As expected, TRIM7 was able to bind to plate-bound RACO1 and MSK1 proteins but not to CD47 protein (Figure 2). The degree of TRIM7 binding to enterovirus 71 2B / C protein was similar to the binding levels to MSK1 and RACO1. In contrast, TRIM7 did not significantly bind to the 2B portion of the viral protein (Figure 2).

[0771] These results, in particular, demonstrate that the TRIM7 protein disclosed herein specifically binds to the enterovirus 71 2B / C protein.

[0772] Example 3: Enterovirus 71 2BC protein inhibits the binding of recombinant human TRIM7 protein to RACO1 and MSK1. The effect of enterovirus 712B / C protein on the binding of TRIM7 protein to recombinant human RACO1 or MSK1 protein was investigated using an assay based on a mesoscale discovery (MSD) platform. Briefly, recombinant human TRIM7 protein was immobilized on a plate. Enterovirus 712B / C protein was added to the plate in increasing amounts so that it would be captured by the plate-bound recombinant TRIM7 protein. Recombinant human MSK1 protein was added to the plate in or out of the presence of 5 μg / ml enterovirus 712B / C protein. Binding was then detected using an anti-MSK1 antibody and a SULFO-TAG conjugate secondary antibody. As shown in Figure 3A, TRIM7 could be detected using MSK1 protein / anti-MSK1 antibody. Interestingly, the signal level decreased when detection was performed in the presence of 5 μg / ml enterovirus 712B / C protein (Figure 3A). These results, in particular, demonstrate that enterovirus 71 2BC protein inhibits the binding of recombinant human TRIM7 protein to MSK1.

[0773] In another similar experiment, recombinant human TRIM7 protein was immobilized on a plate. Enterovirus 71 2B / C protein was added to the plate in increasing amounts so that it would be captured by the plate-bound recombinant TRIM7 protein. Recombinant human RACO1 protein was added to the plate in or out of the presence of 5 μg / ml enterovirus 71 2B / C protein. Binding was then detected using an anti-RACO1 antibody and a SULFO-TAG conjugate secondary antibody. As shown in Figure 3B, TRIM7 could be detected using RACO1 protein / anti-RACO1 antibody. Interestingly, the signal level decreased when detection was performed in the presence of 5 μg / ml enterovirus 71 2B / C protein (Figure 3B). These results, among other things, demonstrate that enterovirus 71 2BC protein inhibits the binding of recombinant human TRIM7 protein to RACO1.

[0774] Example 4: Identification of TRIM7 inhibitors based on molecular modeling The crystal structure of TRIM7 has been elucidated (Munoz Sosa, et al., Crystal structure and mutational analysis of the human Trim7 B30.2 domain provide insights into the molecular basis of its binding to glycogenin-1, J Biol Chem 2021;296:100772). In the crystal structure, malonic acid is bound to the pocket. The crystal structure of TRIM7 bound to the CVB_2C(319~329) peptide (SVGTTLEALFQ) has also been elucidated (Liang et al., Structural insights into the viral proteins binding by Trim7 reveal a general C-terminal glutamine recognition mechanism, bioRxiv 2022.03.24.485560). Figure 4 (upper left panel) shows a schematic diagram of the CVB3 C2 protein, indicating the position of the CVB_2C(319~329) peptide. Figure 4 (lower left panel) shows the crystal structure of the CVB_2C protein exhibiting the CVB_2C(319-329) peptide, and the crystal structure of the TRIM7 protein complexed with the CVB_2C(319-329) peptide. Figure 4 (right panel) shows the interaction between the CVB_2C(319-329) peptide and various amino acids of the TRIM7 protein. This crystal structure shows that glutamine-specific interactions are observed with the CVB_2C peptide, which is inserted into the positively charged groove of the TRIM7 PRY-SPRY domain.

[0775] Based on available crystal structures, homology models were constructed for TRIM7 with the CVB3_2C peptide (TTLEALFQ), GNI peptide (RKLDTYLQ), or the abbreviated peptide (Ac-ALFQ). The homology models revealed the interaction between the carboxyl group of the C-terminal glutamine of the CVB3_2C peptide and the TRIM7 protein (Figure 5). Additional hydrophobic interactions with Phe or Leu at the second-to-last amino acid were also observed (Figure 5). Based on these interactions, conformationally restricted, rigid small molecule compounds containing a carboxyl group and specific aromatic moieties that dock well intramolecularly were identified. These included the compound of formula (I).

[0776] Figure 5 shows a schematic diagram of the molecular simulation-based method used to identify TRIM7 inhibitors, including the compound of Equation 1. Figure 6 shows the various docked compounds. Underlined compounds have docking scores better than -7, which suggests estimated affinity constants of less than 100 nM. Representative compounds are shown in Figure 7 along with their docking scores. Based on this model, compound 1001 can bind to TRIM7 (Figure 8A). This binding is stabilized, in particular, by hydrophobic stacking interactions (Figure 8B).

[0777] These results, in particular, indicate that the compound of formula (I) is likely to inhibit the binding of recombinant human TRIM7 protein to MSK1. Therefore, the compound of formula (I) is a TRIM7 inhibitor and is useful in the methods disclosed herein.

[0778] Example 5: Inhibition of recombinant human TRIM7 protein binding to RACO1 and MSK1 The effect of the compound of formula (I) on the binding of TRIM7 protein to recombinant human RACO1 or MSK1 protein was investigated using an assay based on a mesoscale discovery (MSD) platform. Briefly, recombinant human TRIM7 protein was immobilized on a plate. The compound of formula (I) (e.g., compound 1001) was added to the plate in incremental amounts so that it would be captured by the plate-bound recombinant TRIM7 protein. Recombinant human RACO1 and / or MSK1 proteins were added to the plate in or out of the presence of the compound of formula (I) (e.g., compound 1001). Binding was then detected using an anti-RACO1 antibody and / or anti-MSK1 antibody in combination with a SULFO-TAG conjugate secondary antibody. In the absence of the compound of formula (I), TRIM7 was expected to show binding to RACO1 and / or MSK1 proteins (see Figures 1A and 1B). When detection is performed in the presence of the compound of formula (I), TRIM7 is expected to show a decrease in binding to RACO1 and / or MSK1 proteins.

[0779] These results, in particular, will demonstrate that the compound of formula (I) inhibits the binding of recombinant human TRIM7 protein to RACO1 and / or MSK1 proteins. Therefore, the compound of formula (I) is a TRIM7 inhibitor and is useful in the methods disclosed herein.

[0780] Example 6: Compound IC of the present disclosure 50 data This example demonstrates the IC of the compound disclosed by the TRIM7 fluorescence polarization (FP) coupling assay. 50 Provides data that shows values.

[0781] A TRIM7 fluorescence polarization (FP) binding assay was performed on the compounds disclosed herein. The assay was performed using the C-terminal nine amino acids (GATLEALFQ (SEQ ID NO: 1)) of a fluorescently labeled viral peptide (CVB3), which has been previously shown to interact with the same TRIM7-PrySpry(324-511) domain (Ru, Y. et al., Proc. Natl. Acad. Sci. USA, 2022, 119(3): e2203218119), and incubated with His-TRIM7-PrySpry(324-511) for 22 hours. An unlabeled version of the same peptide, a shortened version of this peptide (LFQ only), or a small molecule inhibitor (SMI) was added to compete for binding to the same docking pocket of the fluorescently labeled peptide. The loss of fluorescence signal due to dissociation of the labeled peptide due to competition was quantified. The results are shown in the table below, and IC 50 The following applies: +++=IC 50 <15μM ++=15μM <IC 50 <100μM +=IC 50 >100μM N / A = Compound not tested [Table 8-1] [Table 8-2]

[0782] Example 7: Covalent TRIM7 inhibitor of the present disclosure This example provides data showing the relative IC50 values ​​of the compounds of this disclosure, calculated at 4 hours and 22 hours using a TRIM7 fluorescence polarization (FP) binding assay. While we do not wish to be bound by any particular theory, the improved IC50 determined at 22 hours, compared to the IC50 determined for compounds 1013 and 1012, indicates that the compounds covalently bind to TRIM7 over time, thereby improving their ability to inhibit genes. The IC50 values ​​at 22 hours for each compound tested are shown in the table below. 50 The value is IC over 4 hours. 50 This is a relative value to the value (relative IC over 4 hours). 50 (Assume the value is 1).

[0783] [Table 4]

[0784] Example 8: Compound IC of the present disclosure 50 data A TRIM7 fluorescence polarization (FP) binding assay was performed on the compounds disclosed herein. The assay was performed using the C-terminal nine amino acids (GATLEALFQ (SEQ ID NO: 1)) of a fluorescently labeled viral peptide (CVB3) previously shown to interact with the same TRIM7-PrySpry(324-511) domain. This peptide was incubated with His-TRIM7-PrySpry(324-511) for 1.5 hours, 4 hours, or 22 hours. An unlabeled version of the same peptide, a shortened version of this peptide (LFQ only), or a small molecule inhibitor (SMI) was added to compete for binding to the same docking pocket of the fluorescently labeled peptide. The loss of fluorescence signal due to dissociation of the labeled peptide due to competition was quantified. The results are shown in the table below, and IC 50 The following applies: +++=IC 50 <15μM ++=15μM <IC 50 <100μM +=IC 50 >100μM N / A = Compound not tested Table 10-1 Table 10-2 Table 10-3 Table 10-4 Table 10-5 Table 10-6 Table 10-7 Table 10-8 Table 10-9 Table 10-10 Table 10-11

[0785] Example 9: Interaction between the SMI of this disclosure and TRIM7 TRIM7 is primarily described in virology, where it ubiquitinates viral proteins (e.g., CVB3_2BC, EV71, and SARS-CoV-2) and targets them for degradation (Figure 9A). The crystal structure of the C-terminal PrySpry domain of TRIM7 has recently been elucidated, identifying the major pocket where viral binding can occur (Figure 9B). The crystal structure of TRIM7 with viral peptides has also been elucidated, identifying the major cysteine ​​within the binding pocket that can be utilized for covalent bonding (Figure 9C). Importantly, the C-terminal amino acid of the viral CVB3_2C has been shown to interact specifically within this pocket, and this amino acid motif is conserved in the native proteins GN1 and RACO-1. ​​These structural findings have partially contributed to the small molecule inhibition of TRIM7.

[0786] Recombinant proteins were generated to facilitate the development of small molecule inhibitors (SMIs) and to validate their binding / functional activity. Interactions between TRIM7 and RACO-1, STING, MAVS, and CVB3_2C (WT but not a mutant form) were confirmed (Figure 10). Using these findings, various compounds in this disclosure were screened through a series of binding / activity assays and prioritized for further chemical modification (Figure 11).

[0787] Table 1 provides binding data for several compounds of this disclosure to the PrySpry domain. Binding was qualitatively evaluated and scored as *, **, ***, or **** based on whether the correct SMI mass value was detected after incubation with TRIM7_PrySpry (full scan) and whether the intended interaction at C501 within the binding pocket was confirmed (peptide mapping).

[0788] Legend: Scores of * or ** indicate that some binding was detected, but further optimization of the assay is needed. Scores of *** or **** indicate reliable binding. ND indicates that the compound was not tested.

[0789] Table 1. Binding data of the compounds disclosed herein to the PrySpry domain. [Table 5]

[0790] Figures 12A and 12B show cell-based activity assays demonstrating that intracellular TRIM7 expression leads to target degradation / stabilization. Figure 12A shows that overexpression of TRIM7 (+T7) in 293T cell lines expressing CVB3, MAVS, or STING leads to their degradation, consistent with previous studies. Figure 12B shows that overexpression of RACO-1 alone leads to autoubiquitination and degradation. Co-expression of TRIM7 with RACO1 stabilizes RACO1. TRIM7 SMIs, such as compound 1028, exhibit different activity that inhibits TRIM7-mediated RACO1 stabilization, resulting in RACO1 degradation.

[0791] Example 10: Compound IC of the present disclosure 50 value This example provides data showing the IC50 value of compound 1028 of the present disclosure by TRIM7 fluorescence polarization (FP) coupling assay.

[0792] A TRIM7 fluorescence polarization (FP) binding assay was performed on compound 1028. The assay was performed using the C-terminal nine amino acids (GATLEALFQ (SEQ ID NO: 1)) of a fluorescently labeled viral peptide (CVB3) that has been previously shown to interact with the same TRIM7-PrySpry(324-511) domain (Ru, Y. et al., Proc. Natl. Acad. Sci. USA, 2022, 119(3): e2203218119). This peptide was incubated with His-TRIM7-PrySpry(324-511) for 30 minutes. An unlabeled version of the same peptide, a shortened version of the peptide (LFQ only), or a small molecule inhibitor (SMI) was added and incubated for 1.5 hours to compete for binding of the fluorescently labeled peptide to the same docking pocket. The disappearance of the fluorescence signal due to dissociation of the labeled peptide due to competition was quantified. The results are shown in the table below, and IC 50 The following applies: Legend: +++=IC 50 <15μM ++=15μM <IC 50 <100μM +=IC 50 >100μM

[0793] [Table 6]

[0794] Example 11: In vivo antitumor activity of compound (I) in combination with a Kras inhibitor The efficacy of the compound of formula (I) in combination with a Kras inhibitor will be evaluated. Briefly, 500,000 mouse colon cancer CT26 cells will be inoculated into the posterior flank of BALB / C mice. The average tumor volume will be 80-100 mm. 3When the mice reach a certain stage (indicating day 0), they are randomly assigned to one of the following four treatment groups. Each group of mice receives either (1) a vehicle-only control, (2) the compound of formula (I) alone, (3) a Kras inhibitor alone, or (4) a combination of the compound of formula (I) and a Kras inhibitor. Administration is performed on days 0, 3, 6, 9, 12, and 15. Tumors are measured daily using electronic calipers and plotted using GraphPad Prism software. Tumor growth in each treatment group is evaluated by plotting the tumor growth curve of the individual mouse, the mean tumor growth curve of the treatment group, the mean tumor size on the example day, and / or a Kaplan-Meier plot.

[0795] The results are expected to indicate, in particular, that the combination of the compound of formula (I) and the Kras inhibitor exhibits higher antitumor activity compared to either treatment alone.

[0796] Example 12: In vivo antitumor activity of the compound of formula (I) in combination with a Braf inhibitor The efficacy of the compound of formula (I) in combination with a Braf inhibitor will be evaluated. Briefly, 500,000 mouse colon cancer CT26 cells will be inoculated into the posterior flank of BALB / C mice. The average tumor volume will be 80-100 mm. 3 When the mice reach a certain stage (day 0), they are randomly assigned to one of the following four treatment groups. Each group of mice receives either (1) a vehicle-only control, (2) the compound of formula (I) alone, (3) a Braf inhibitor alone, or (4) a combination of the compound of formula (I) and a Braf inhibitor. Administration is performed on days 0, 3, 6, 9, 12, and 15. Tumors are measured daily using electronic calipers and plotted using GraphPad Prism software. Tumor growth in each treatment group is evaluated by plotting the tumor growth curve of the individual mouse, the mean tumor growth curve of the treatment group, the mean tumor size on the example day, and / or a Kaplan-Meier plot.

[0797] The results are expected to indicate, in particular, that the combination of the compound of formula (I) and a Braf inhibitor exhibits higher antitumor activity compared to either treatment alone.

[0798] Example 13: In vivo antitumor activity of compound (I) in combination with a MEK inhibitor The efficacy of the compound of formula (I) in combination with a MEK inhibitor will be evaluated. Briefly, 500,000 mouse colon cancer CT26 cells will be inoculated into the posterior flank of BALB / C mice. The average tumor volume will be 80-100 mm. 3 When the mice reach a certain stage (day 0), they are randomly assigned to one of the following four treatment groups. Each group of mice receives either (1) a vehicle-only control, (2) the compound of formula (I) alone, (3) a MEK inhibitor alone, or (4) a combination of the compound of formula (I) and a MEK inhibitor. Administration is performed on days 0, 3, 6, 9, 12, and 15. Tumors are measured daily using electronic calipers and plotted using GraphPad Prism software. Tumor growth in each treatment group is evaluated by plotting the tumor growth curve of the individual mouse, the mean tumor growth curve of the treatment group, the mean tumor size on the example day, and / or a Kaplan-Meier plot.

[0799] The results are expected to indicate, in particular, that the combination of the compound of formula (I) and a MEK inhibitor exhibits higher antitumor activity compared to either treatment alone.

[0800] Example 14: Compound IC of the present disclosure 50 data This example demonstrates the IC of the compound disclosed by the TRIM7 fluorescence polarization (FP) coupling assay. 50 Provides data that shows values.

[0801] A TRIM7 fluorescence polarization (FP) binding assay was performed on the compounds disclosed herein. The assay was performed using the C-terminal nine amino acids (GATLEALFQ (SEQ ID NO: 1)) of a fluorescently labeled viral peptide (CVB3) that has been previously shown to interact with the same TRIM7-PrySpry(324-511) domain (Ru, Y. et al., Proc. Natl. Acad. Sci. USA, 2022, 119(3): e2203218119). This was incubated with His-TRIM7-PrySpry(324-511) for 30 minutes, 1.5 hours, 4 hours, or 22 hours. An unlabeled version of the same peptide, a shortened version of this peptide (LFQ only), or a small molecule inhibitor (SMI) was added to compete for binding to the same docking pocket of the fluorescently labeled peptide. The loss of fluorescence signal due to dissociation of the labeled peptide due to competition was quantified. The results are shown in the table below, and IC 50 The following applies: Legend: +++=IC 50 <15μM ++=15μM <IC 50 <100μM +=IC 50 >100μM N / A = Compound not tested

[0802] [Table 13-1] [Table 13-2] [Table 13-3] [Table 13-4] [Table 13-5]

[0803] Example 15 Synthesis of 5-acrylamido-2-(dibenzylcarbamoyl)benzoic acid (compound 1010): [ka]

[0804] [ka]

[0805] Preparation of 2-(dibenzylcarbamoyl)-5-nitrobenzoic acid and 2-(dibenzylcarbamoyl)-4-nitrobenzoic acid (Int-1a) (Step 1): 5-nitroisobenzofuran-1,3-dione (2.0 g, 10.4 mmol) and bis(benzylamine) (2.0 g, 10.4 mmol, 1.0 equivalent) were placed in THF (25 ml), and the solution was stirred at room temperature for 18 hours. The solution was concentrated to obtain a 1:1 mixture of the desired product as a clear oil (4.0 g, 100% yield). 1 H NMR (400MHz, DMSO-d6) δ ppm 8.63(d, J=2.4Hz, 1H), 8.43-8.40(m, 1H), 8.27(d, J=2.4Hz, 1H), 8.17(d, J=3.2 Hz, 1H), 8.04(J=2.4Hz, 1H), 7.74(d, J=8.0Hz, 1H), 7.35-7.05(m, 20H), 4.23(br s, 2H), 4.18(br s, 2H). LCMS EI-MS m / z:=391.0[M+H] + .

[0806] [ka]

[0807] Preparation of 5-amino-2-(dibenzylcarbamoyl)benzoic acid (Int-1b) (Step 2): A mixture of 2-(dibenzylcarbamoyl)-5-nitrobenzoic acid and 2-(dibenzylcarbamoyl)-4-nitrobenzoic acid (Int-1a) (1.50 g, 3.84 mmol) was placed in ethanol (38 ml), to which Pd / C (0.3 g, 20 wt%) was added. The suspension was held under a hydrogen balloon for 24 hours. The insoluble catalyst was removed by Celite filtration, and the filtrate was concentrated. The residue was purified by preparative reverse-phase HPLC using water / acetonitrile containing 0.05% TFA to obtain two products. The structure of the title compound was assigned to the compound that eluted faster (0.8 g, 40% yield) based on 2D NMR analysis. 1 H NMR (400MHz, DMSO-d6) δ ppm 7.65-7.25(m, 8H), 7.20-7.15(m, 3H), 7.10-7.05(m, 1H), 6.73(d, J=8.4Hz, 1H), 4.54(s, 2H), 4.21(s, 2H), 4.00-3.00(br, 2H). LCMS EI-MS m / z:=361.2[M+H] + .

[0808] [ka]

[0809] Preparation of 5-acrylamido-2-(dibenzylcarbamoyl)benzoic acid (compound 1010) (Step 3): 5-amino-2-[bis(benzyl)carbamoyl]benzoic acid-trifluoroacetic acid (1 / 1) (100 mg, 0.20 mmol) was added to 1 N sodium hydroxide solution (2.0 ml), and acryloyl chloride (0.05 ml, 0.60 mmol, 3.0 equivalents) was added. The solution was stirred at room temperature for 3 hours. The reaction was stopped by adding 1 N hydrochloric acid, which resulted in the formation of a white solid precipitate. The solid was recovered by filtration and then purified by preparative reverse-phase HPLC using water / acetonitrile containing 0.05% TFA to obtain the title compound as a white powder (46 mg, yield 55%). 1H NMR (400MHz, METHANOL-d4) δ ppm 8.37(d, J=2.0Hz, 1H), 7.95(dd, J=8.4Hz, 2.0Hz, 1H), 7.50-7.10(m, 11Hz), 6.50-6.30(m, 2H), 5.80(dd, J=8.8Hz, 3.2Hz, 1H), 4.70(br s, 2H), 4.26(s, 2H). LCMS EI-MS m / z:=415.1[M+H] + .

[0810] Example 16 Synthesis of 4-acrylamido-2-(dibenzylcarbamoyl)benzoic acid (compound 1011): [ka]

[0811] 4-Acrylamide-2-(dibenzylcarbamoyl)benzoic acid (compound 1011) was synthesized from 4-amino-2-(dibenzylcarbamoyl)benzoic acid (Int-1c) (80 mg, 0.02 mmol) and acryloyl chloride (0.04 ml, 0.05 mmol) according to the procedure described in step 3 of the synthesis of compound 1010, to obtain the title compound (20 mg, yield 21%). 1 H NMR (400MHz, METHANOL-d4) δ=8.07(d, J=8.6Hz, 1H), 7.88(d, J=2.0Hz, 1H), 7.75(dd, J=2.1, 8.6Hz, 1H) , 7.39-7.22(m, 8H), 7.14(d, J=6.6Hz, 2H), 6.43(d, J=2.4Hz, 2H), 5.82(dd, J=4.7, 7.1Hz, 1H), 4.23(br s, 2H). LCMS EI-MS m / z:=415.1[M+H] + .

[0812] Example 17 Synthesis of 5-acrylamido-2-(diisobutylcarbamoyl)benzoic acid (compound 1012): [ka]

[0813] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-(diisobutylcarbamoyl)benzoic acid (compound 1012) was synthesized from 5-nitroisobenzofuran-1,3-dione (2.0 g, 10.4 mmol) and diisobutylamine (1.3 g, 10.4 mmol, 1.0 equivalent) to obtain the title compound (15 mg, 28% yield). 1 H NMR (400MHz, METHANOL-d4) δ ppm 8.33(d, J=2.0Hz, 1H), 7.98(dd, J=8.2, 2.0Hz, 1H), 7.27(d, J=8.0Hz, 2H), 6.50-6.40(m, 4H), 5.81(dd, J=9.2, 3.2Hz, 2H), 3.3 7(d, J=7.8Hz, 2H), 2.98(d, J=7.8Hz, 2H), 2.25-2.15(m, 1H), 1.85-1.70(m, 1H), 1.02(d, J=6.4Hz, 6H), 0.77(d, J=6.4Hz, 6H). LCMS EI-MS m / z:=347.1[M+H] + .

[0814] Example 18 Synthesis of 4-acrylamido-2-(diisobutylcarbamoyl)benzoic acid (compound 1013): [ka]

[0815] Following the procedure described in steps 1-3 for the synthesis of compound 1011, 4-acrylamido-2-(diisobutylcarbamoyl)benzoic acid (compound 1013) was synthesized from 5-nitroisobenzofuran-1,3-dione (2.0 g, 10.4 mmol) and diisobutylamine (1.3 g, 10.4 mmol, 1.0 equivalent) to obtain the title compound (13 mg, 20% yield). 1H NMR (400MHz, METHANOL-d4) δ ppm 8.03(d, J=8.4Hz, 1H), 7.80-7.40(m, 2H), 6.50-6.30(m, 2H), 5.81(dd, J=8.4, 3.2Hz, 1H), 3.75(d, J=7.6Hz , 2H), 3.00(br, s, 2H), 2.25-2.20(m, 1H), 1.95-1.85(m, 1H), 1.03(d, J=6.4Hz, 6H), 0.79(d, J=6.4Hz, 6H). LCMS EI-MS m / z:=347.1[M+H] + .

[0816] Example 19 Synthesis of 4-bromo-2-(diisobutylcarbamoyl)benzoic acid (compound 1014): [ka]

[0817] 4-Bromo-2-(diisobutylcarbamoyl)benzoic acid (compound 1014) was synthesized from 5-bromoisobenzofuran-1,3-dione (1.6 g, 8.3 mmol) and diisobutylamine (1.1 g, 8.3 mmol, 1.0 equivalent) according to the procedure described in step 1 of the synthesis of compound 1011, to obtain the title compound (900 mg, yield 47%). 1 H NMR (400MHz, CDCl3)δ ppm 8.11(s, 1H), 7.62(d, J=8.2Hz, 1H), 7.55(d, J=8.2Hz, 1H), 3.75(d, J=7.6Hz, 2H), 3.00(br, s, 2H), 2.25-2.20(m, 1H), 1.95-1.85(m, 1H), 1.03(d, J=6.4Hz, 6H), 0.79(d, J=6.4Hz, 6H). LCMS EI-MS m / z:=432.1, 434.1[M+H] + .

[0818] Example 20 Synthesis of 5-amino-2-((cyclohexylmethyl)(2-methoxyethyl)carbamoyl)benzoic acid (compound 1015): [ka]

[0819] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-amino-2-((cyclohexylmethyl)(2-methoxyethyl)carbamoyl)benzoic acid (compound 1015) was synthesized from 5-nitroisobenzofuran-1,3-dione (2.0 g, 10.4 mmol) and N-(cyclohexylmethyl)-2-methoxyethane-1-amine (1.8 g, 10.4 mmol, 1.0 equivalent) to obtain the title compound (160 mg, yield 56%). 1 H NMR (400MHz, METHANOL-d4) δ=7.80(d, J=8.6Hz, 1H), 6.67(dd, J=2.3, 8.6Hz, 1H), 6.46(dd, J=2.3, 10.7Hz, 1H), 3.75- 3.62(m, 2H), 3.57-3.32(m, 4H), 3.29-3.17(m, 2H), 3.11-2.99(m, 1H), 2.99-2.83(m, 1H), 1.99-1.80(m, 2H), 1.76(br d, J=12.4Hz, 1H), 1.71-1.52(m, 4H), 1.38-1.10(m, 3H), 1.08-1.00(m, 1H), 0.69(br t, J=10.6Hz, 1H). LCMS EI-MS m / z:=335.2[M+H] + .

[0820] Example 21 Synthesis of 4-amino-2-((cyclohexylmethyl)(2-methoxyethyl)carbamoyl)benzoic acid (compound 1016): [ka]

[0821] Following the procedure described in steps 1-3 for the synthesis of compound 1011, 4-amino-2-((cyclohexylmethyl)(2-methoxyethyl)carbamoyl)benzoic acid (compound 1016) was synthesized from 5-nitroisobenzofuran-1,3-dione (2.0 g, 10.4 mmol) and N-(cyclohexylmethyl)-2-methoxyethane-1-amine (1.8 g, 10.4 mmol, 1.0 equivalent) to obtain the title compound (150 mg, yield 29%). 1 H NMR (400MHz, METHANOL-d4)δ=7.50(s, 1H), 7.15-7.01(m, 2H), 3.69-3.62(m, 2H), 3.38-3.36(m, 3H), 3.29-3 .15(m, 2H), 1.89-1.73(m, 3H), 1.71-1.56(m, 4H), 1.35-1.14(m, 3H), 1.11-0.97(m, 2H), 0.72-0.57(m, 1H). LCMS EI-MS m / z:=335.2[M+H] + .

[0822] Example 22 Synthesis of 2-(diisobutylcarbamoyl)-5-ethynylbenzoic acid (compound 1017): [ka]

[0823] Int-2a was prepared as described for compound 1014. Int-2b was prepared from Int-2a using thionyl chloride in methanol. Int-2c was prepared from Int-2b using TMS-acetylene, Pd(PPh3)4, and copper(I) iodide in triethylamine. Compound 1017 was prepared from Int-2c using aqueous sodium hydroxide solution to obtain the title compound (15 mg, 9% yield). 1H NMR (400MHz, METHANOL-d4) δ=8.10(s, 1H), 7.71(dd, J=1.4, 7.9Hz, 1H), 7.30(d, J=7.9Hz, 1H), 3.70(s, 1H), 3.43-3.32(m, 2H), 2.95(br s, 2H), 2.19(quind, J=6.8, 13.7Hz, 1H), 1.85(quind, J=6.9, 13.7Hz, 1H), 1.02(d, J=6.6Hz, 6H), 0.77(d, J=6.6Hz, 6H). LCMS EI-MS m / z:=302.1[M+H] + .

[0824] Example 23 Synthesis of 4-amino-2-(dibenzylcarbamoyl)benzoic acid (compound 1018): [ka]

[0825] Following the procedure described in steps 1-2 for the synthesis of compound 1010, 4-amino-2-(dibenzylcarbamoyl)benzoic acid (compound 1018) was synthesized from 5-nitroisobenzofuran-1,3-dione (2.0 g, 10.4 mmol) and N,N-dibenzylamine (2.2 g, 10.4 mmol, 1.0 equivalent) to obtain the title compound (100 mg, 30% yield). 1 H NMR (400MHz, DMSO-d6) δ ppm 7.55-7.25(m, 8H), 7.20-7.15(3H), 7.10-7.00(m, 1H), 6.73(d, J=8.4Hz, 1H), 4.54(br 2H), 4.21(s, 2H), 4.00-3.70(br 1H). LCMS EI-MS m / z:=361.1[M+H] + .

[0826] Example 24 Synthesis of 5-amino-2-(dibenzylcarbamoyl)benzoic acid (compound 1019): [ka]

[0827] Following the procedure described in steps 1-3 for the synthesis of compound 1011, 5-amino-2-(dibenzylcarbamoyl)benzoic acid (compound 1019) was synthesized from 5-nitroisobenzofuran-1,3-dione (2.0 g, 10.4 mmol) and N,N-dibenzylamine (2.2 g, 10.4 mmol, 1.0 equivalent) to obtain the title compound (150 mg). 1 H NMR (400MHz, DMSO-d6) δ ppm 7.75-7.50(m, 8H), 7.25-7.20(3H), 7.10-7.00(m, 1H), 6.52(d, J=8.0Hz, 1H), 4.50(br 2H), 3.95(s, 2H), 4.00-3.70(br 1H). LCMS EI-MS m / z:=361.1[M+H] + .

[0828] Example 25 Synthesis of 5-acrylamido-2-((4-chlorobenzyl)carbamoyl)benzoic acid (compound 1020): [ka]

[0829] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-((4-chlorobenzyl)carbamoyl)benzoic acid (compound 1020) was synthesized from 5-nitroisobenzofuran-1,3-dione (0.4 g, 2.1 mmol) and 4-chlorobenzylamine (0.3 g, 2.1 mmol, 1.0 equivalent), yielding the title compound (12 mg). LCMS EI-MS m / z:=359.1[M+H] + .

[0830] Example 26 Synthesis of 5-acrylamido-2-(benzyl(4-methylbenzyl)carbamoyl)benzoic acid (compound 1021): [ka]

[0831] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-(benzyl(4-methylbenzyl)carbamoyl)benzoic acid (compound 1021) was synthesized from 5-nitroisobenzofuran-1,3-dione (2.0 g, 10.4 mmol) and N-benzyl-1-(p-tolyl)methaneamine (2.2 g, 10.4 mmol, 1.0 equivalent), yielding the title compound (18 mg). 1 H NMR (400MHz, METHANOL-d4) δ=8.37(s, 1H), 7.95(t, J=7.0Hz, 1H), 7.41-7.21(m, 6H), 7.17- 7.08(m, 3H), 7.01(d, J=8.0Hz, 1H), 6.47-6.35(m, 2H), 5.80(dd, J=2.2, 8.8Hz, 1H), 4.22(br d, J=12.3Hz, 2H), 2.32(d, J=11.1Hz, 3H). LCMS EI-MS m / z:=429.1[M+H] + .

[0832] Example 27 Synthesis of 5-acrylamido-2-(benzyl(4-methylbenzyl)carbamoyl)benzoic acid (compound 1023): [ka]

[0833] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-(benzyl(4-methylbenzyl)carbamoyl)benzoic acid (compound 1023) was synthesized from 5-nitroisobenzofuran-1,3-dione (320 mg, 1.6 mmol) and bis[(p-chlorophenyl)methyl]amine (440 g, 1.6 mmol, 1.0 equivalent) to obtain the title compound (10 mg, 19% yield). 1H NMR(400MHz, DMSO-d6)δ ppm 13.45(br s, 1H), 10.44(s, 1H), 8.28(d, J=2.4Hz, 1H), 7.90(d, J=2.4Hz, 1H), 7.51-7.35(m, 7H) , 7.25-7.15(m, 2H), 6.45-6.40(m, 1H), 6.37-6.30(m, 1H), 5.80-5.75(m, 1H), 4.60(br s, 2H), 4.19(s, 2H). LCMS EI-MS m / z:=484.1[M+H] + .

[0834] Example 28 Synthesis of 5-acrylamido-2-(bis(3-fluoro-4-(trifluoromethyl)benzyl)carbamoyl)benzoic acid (compound 1024): [ka]

[0835] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-(bis(3-fluoro-4-(trifluoromethyl)benzyl)carbamoyl)benzoic acid (compound 1024) was synthesized from 5-nitroisobenzofuran-1,3-dione (170 mg, 0.9 mmol) and bis(3-fluoro-4-(trifluoromethyl)benzyl)amine (320 g, 0.9 mmol, 1.0 equivalent) to obtain the title compound (10 mg, yield 17%). 1 H NMR(400MHz, DMSO-d6)δ ppm 13.60(br s, 1H), 10.46(s, 1H), 8.31(d, J=2.0Hz, 1H), 7.94-7.92(m, 1H), 7.80-7.20 (m, 7H), 6.51-6.43(m, 1H), 6.34-6.26(m, 1H), 5.85-5.80(m, 1H), 4.75(br s, 2H), 4.42(s, 2H). LCMS EI-MS m / z:=587.0[M+H] + .

[0836] Example 29 Synthesis of 5-acrylamido-2-(bis(4-methoxybenzyl)carbamoyl)benzoic acid (compound 1025): [ka]

[0837] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-(bis(4-methoxybenzyl)carbamoyl)benzoic acid (compound 1025) was synthesized from 5-nitroisobenzofuran-1,3-dione (350 mg, 1.8 mmol) and bis(4-methoxybenzyl)amine (466 mg, 1.8 mmol, 1.0 equivalent) to obtain the title compound (30 mg, yield 11%). 1 H NMR(400MHz, DMSO-d6)δ ppm 13.45(br s, 1H), 10.44(s, 1H), 8.27(s, 1H), 7.91(d, J=2.0Hz, 1H), 7.40-6.90(m, 9H), 6.50-6.30(m, 2H), 5.82-5.80(m, 1H), 4.50(br s, 2H), 4.07(s, 2H), 3.75(s, 3H), 3.74(s, 3H). LCMS EI-MS m / z:=475.2[M+H] + .

[0838] Example 30 Synthesis of 5-acrylamido-2-(benzyl(4-fluorobenzyl)carbamoyl)benzoic acid (compound 1027): [ka]

[0839] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-(benzyl(4-fluorobenzyl)carbamoyl)benzoic acid (compound 1027) was synthesized from 5-nitroisobenzofuran-1,3-dione (180 mg, 0.9 mmol) and (benzyl)[(p-fluorophenyl)methyl]amine (200 mg, 0.9 mmol, 1.0 equivalent) to obtain the title compound (40 mg, yield 9%). 1 H NMR(400MHz, DMSO-d6)δ ppm 13.44(br s, 1H), 10.44(d, J=2.1Hz, 1H), 8.28(s, 1H), 7.88-7.96(m, 1H), 7.25-7.43(m, 6 H), 7.09-7.22(m, 4H), 6.40(dd, J=10.1, 1.8Hz, 1H), 6.25-6.34(m, 1H), 5.80(br d, J=10.1Hz, 1H), 4.52(s, 2H), 4.19(s, 2H). LCMS EI-MS m / z:=433.1[M+H] + .

[0840] Example 31 Synthesis of 5-acrylamido-2-(benzyl((tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)benzoic acid (compound 1028): [ka]

[0841] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-(benzyl((tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)benzoic acid (compound 1028) was synthesized from 5-nitroisobenzofuran-1,3-dione (1.5 g, 7.8 mmol) and benzyl[(oxan-4-yl)methyl]amine (1.6 g, 7.8 mmol, 1.0 equivalent) to obtain the title compound (10 mg, yield 15%). 1H NMR (400MHz, METHANOL-d4) δ ppm 8.41-8.37(m, 2H), 7.91(dd, J=2.1, 8.4Hz, 1H), 7.52(d, J=7.3Hz, 2H), 7.41-7.27(m, 9H), 7 .23(d, J=7.1Hz, 3H), 6.49-6.37(m, 4H), 5.82(dd, J=3.1, 8.5Hz, 2H), 4.43(s, 3H), 3.95(br dd, J=3.0, 11.4Hz, 3H), 3.51-3.35(m, 5H), 3.31-3.12(m, 3H), 2.68(s, 1H), 1.78(br d, J=11.1Hz, 4H). LCMS EI-MS m / z:=423.1[M+H] + .

[0842] Example 32 Synthesis of 5-acrylamido-2-((3-fluoro-4-(trifluoromethyl)benzyl)((tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)benzoic acid (compound 1029): [ka]

[0843] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-((3-fluoro-4-(trifluoromethyl)benzyl)((tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)benzoic acid (compound 1029) was synthesized from 5-nitroisobenzofuran-1,3-dione (670 mg, 3.4 mmol) and {[3-fluoro-4-(trifluoromethyl)phenyl]methyl}[(oxan-4-yl)methyl]amine (1.0 g, 3.4 mmol, 1.0 equivalent), yielding the title compound (35 mg, 17% yield). 1H NMR (400MHz, DMSO-d6)δ ppm 13.4(br s, 1H), 10.43(d, J=28Hz, 1H), 8.31(d, J=2.0Hz, 1H), 8.10-7.20(m, 5H), 6.50-6.20(m, 2H), 5.80-5.75(m, 1H), 4.82(br s, 1H), 4.45(s, 1H), 3.30-3.00(m, 4H), 2.10-1.80(m, 1H), 1.80-1.70(m, 1H), 1.50-1.40(m, 1H), 1.20-1.10(m, 2H), 0.90-0.80(m, 2H). LCMS EI-MS m / z:=509.1[M+H] + .

[0844] Example 33 Synthesis of 5-acrylamido-2-((4-methoxybenzyl)((tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)benzoic acid (compound 1030): [ka]

[0845] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-((4-methoxybenzyl)((tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)benzoic acid (compound 1030) was synthesized from 5-nitroisobenzofuran-1,3-dione (1.5 g, 7.8 mmol) and [(p-methoxyphenyl)methyl][(tetrahydro-2H-pyran-4-yl)methyl]amine (1.8 g, 7.8 mmol, 1.0 equivalent), yielding the title compound (35 mg). LCMS EI-MS m / z:=453.1[M+H] + .

[0846] Example 34 Synthesis of 5-acrylamido-2-((cyclohexylmethyl)(2-methoxyethyl)carbamoyl)benzoic acid (compound 1031): [ka]

[0847] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-((cyclohexylmethyl)(2-methoxyethyl)carbamoyl)benzoic acid (compound 1031) was synthesized from 5-nitroisobenzofuran-1,3-dione (1.5 g, 7.8 mmol) and (cyclohexylmethyl)(2-methoxyethyl)amine (1.3 g, 7.8 mmol, 1.0 equivalent), yielding the title compound (35 mg). 1 H NMR (400MHz, METHANOL-d4)δ=8.33(dd, J=1.6, 8.3Hz, 1H), 7.97(t, J=6.7Hz, 1H), 7. 27(t, J=8.9Hz, 1H), 6.49-6.36(m, 2H), 5.81(dd, J=1.9, 9.1Hz, 1H), 3.77-3.60(m, 2H) ), 3.44-3.36(m, 3H), 3.35-3.29(m, 3H), 3.23(s, 1H), 3.14-2.92(m, 1H), 1.96-1.82 (m, 1H), 1.81-1.56(m, 5H), 1.34-1.14(m, 2H), 1.12-0.98(m, 1H), 0.73-0.58(m, 1H). LCMS EI-MS m / z:=389.1[M+H] + .

[0848] Example 35 Synthesis of 5-acrylamido-2-(benzyl(4-methoxybenzyl)carbamoyl)benzoic acid (compound 1032): [ka]

[0849] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-(benzyl(4-methoxybenzyl)carbamoyl)benzoic acid (compound 1032) was synthesized from 5-nitroisobenzofuran-1,3-dione (1.5 g, 7.8 mmol) and N-benzyl-1-(4-methoxyphenyl)methaneamine (1.8 g, 7.8 mmol, 1.0 equivalent) to obtain the title compound (4 mg, yield 6%). 1H NMR (400MHz, METHANOL-d4) δ=8.43-8.30(m, 1H), 8.02-7.85(m, 1H), 7.44-7.20(m, 7H), 7.18-7.08(m, 1H), 7.07-6.96 (m, 1H), 6.92-6.75(m, 2H), 6.49-6.32(m, 2H), 5.85-5.70(m, 1H), 4.28-4.12(m, 3H), 3.86-3.66(m, 4H), 3.34(s, 4H). LCMS EI-MS m / z:=445.1[M+H] + .

[0850] Example 36 Synthesis of 5-acrylamido-2-(dibenzylcarbamoyl)benzoic acid (compound 1033): [ka]

[0851] Following the procedure described in steps 1-3 for the synthesis of compound 1010, 5-acrylamido-2-(dibenzylcarbamoyl)benzoic acid (compound 1033) was synthesized from 5-nitroisobenzofuran-1,3-dione (2.0 g, 10.4 mmol) and dibenzylamine (2.0 g, 10.4 mmol, 1.0 equivalent), yielding the title compound (6 mg). 1 H NMR (400MHz, METHANOL-d4) δ=8.30(d, J=2.1Hz, 1H), 7.86(dd, J=2.1, 8.3Hz, 1H), 7.38-7.23(m, 9H), 7.12(d, J =6.8Hz, 2H), 4.84-4.57(m, 2H), 4.24(s, 2H), 3.37-3.32(m, 1H), 2.40(q, J=7.6Hz, 2H), 1.19(t, J=7.6Hz, 3H). LCMS EI-MS m / z:=429.1[M+H] + .

[0852] Example 37 Synthesis of 2-(5-acrylamido-2-(benzyl(methyl)carbamoyl)phenyl)acetic acid (compound 1034): [ka]

[0853] Synthesis of ethyl 2-(2-(benzyl(methyl)carbamoyl)-5-bromophenyl)acetate (Int-3b): A solution of 4-bromo-2-(2-ethoxy-2-oxoethyl)benzoic acid (1.8 g, 6.1 mmol) in dichloro...

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof. 【Chemistry 1】 In formula (I): A is, 【Chemistry 2】 Selected from; L is a linking group; R １ａ , R １ｂ , R ２ , R ３ , R ４ａ , R ４ｂ , R ５ａ , R ５ｂ , R ５ｃ , R ５ｄ , R ５ｅ , R ６ａ , R ６ｂ , R ６ｃ , R ６ｄ , R ６ｅ , R ７ａ , R ７ｂ , R ７ｃ , R ７ｄ , R ８ , R ９ , R １０ , R １１ａ , R １１ｂ , and R １１ｃ are each independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ )C(O)OR ａ , -N(R ａ )C(O)R ａ , -N(R ａ )C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R １２ is H or an unsubstituted alkyl; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n １ is an integer between 0 and 5; t is either 1 or 2; However, this is subject to the condition that the compound of formula (I) is not any of the following compounds: formulas 1001, 1003, 1004, and formulas 1006 to 1009. Table 1

2. R １ａ , R １ｂ , R ２ , R ３ , R ４ａ , R ４ｂ , R ５ａ , R ５ｂ , R ５ｃ , R ５ｄ , R ５ｅ , R ６ａ , R ６ｂ , R ６ｃ , R ６ｄ , R ６ｅ , R ７ａ , R ７ｂ , R ７ｃ , R ７ｄ , R ８ , R ９ , R １０ , R １１ａ , R １１ｂ , and R １１ｃ are each independently selected from the group consisting of hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl (optionally substituted with halogen, unsubstituted or substituted alkyl, and / or unsubstituted or substituted heterocyclyl), unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, halogen, -C(O)R ａ , -C(O)N(R ａ ) ２ , -N(R ａ ) ２ , -N(R ａ )C(O)R ａ , and -S(O) ｔ R ａ The compound according to claim 1.

3. L is either a bond, or non-substituted or substituted -C １－１０ Alkyl-, -O-C １－１０ Alkyl-, -C １－１０ Alkenyl-,-O-C １－１０ Alkenyl-, -C １－１０ Cycloalkenyl-,-O-C １－１０ Cycloalkenyl-,-C １－１０ Alkinyl-,-O-C １－１０ Alkinyl-, -C １－１０ Arial-, -O-C １－１０ -, -aryl-, -cycloalkyl-, -heterocyclyl-, -O-, -S-, -S-S-, -S(O) ｗ -, -C(O)-, -C(O)O-, -OC(O)-, -C(O)S-, -SC(O)-, -OC(O)O-, -N(R ｂ )-, -C(O)N(R ｂ )-,-N(R ｂ )C(O)-, -OC(O)N(R ｂ )-,-N(R ｂ )C(O)O-, -SC(O)N(R ｂ )-,-N(R ｂ )C(O)S-,-N(R ｂ ) C(O)N(R ｂ )-,-N(R ｂ ) C (NR ｂ )N(R ｂ )-,-N(R ｂ ) S(O) ｗ -, -S(O) ｗ N(R) ｂ )-,-S(O) ｗ O-, -OS(O) ｗ -, -OS(O) ｗ O-, -O(O)P(OR ｂ )O-, (O)P(O-) ３ , -O(S)P(OR ｂ )O-, and (S)P(O-) ３ It includes one or more linking groups selected from, Here, w is 1 or 2, and R ｂ L is independently hydrogen, optionally substituted alkyl, or optionally substituted aryl, and optionally L is a bond and / or -C(O)- and / or -C(H)(CH ２ ) ｐ C(O)NH ２ and / or 【Transformation 3】 And, Here, p is an integer from 1 to 5, and optionally p is 2, and optionally L is 【Chemistry 4】 or 【Transformation 5】 And, The compound according to claim 1 or claim 2, wherein the alkyl is substituted or unsubstituted.

4. The compound according to any one of claims 1 to 3, wherein the compound of formula (I) is the compound of formula (10). 【Transformation 6】 In formula (10): R ９ａ , R ９ｂ , R ９ｃ , R ９ｄ , and R ９ｅ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n ２ is an integer between 0 and 5; t is either 1 or 2.

5. The compound according to any one of claims 1 to 3, wherein the compound of formula (I) is the compound of formula (20) or (21). 【Transformation 7】 In equations (20) and (21): n ３ is an integer between 0 and 5.

6. The compound according to any one of claims 1 to 3, wherein the compound of formula (I) is the compound of formula (30) or (31). 【Transformation 8】 In equations (30) and (31): p is an integer between 0 and 5.

7. The compound according to any one of claims 1 to 3, wherein the compound of formula (I) is the compound of formula (32). 【Chemistry 9】 In formula (32): q is an integer between 1 and 3.

8. The compound according to any one of claims 1 to 3, wherein the compound of formula (I) is the compound of formula (40). 【Chemistry 10】 In formula (40): n ４ is an integer between 0 and 5.

9. The compound according to any one of claims 1 to 3, wherein the compound of formula (I) is the compound of formula (50). 【Chemistry 11】 In formula (50): R １０ａ , R １０ｂ , R １０ｃ , R １０ｄ , and R １０ｅ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n ５ is an integer between 0 and 5; t is either 1 or 2.

10. The compound according to any one of claims 1 to 3, wherein the compound of formula (I) is the compound of formula (60). 【Chemistry 12】 In formula (60): n ６ is an integer between 0 and 5.

11. The compound according to any one of claims 1 to 3, wherein the compound of formula (I) is the compound of formula (70). 【Chemistry 13】 In formula (70): R １１ａ and R １１ｂ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl.

12. The compound according to claim 11, wherein the compound of formula (70) is the compound of formula (700) or formula (701). 【Chemistry 14】

13. The compound according to any one of claims 1 to 3, wherein the compound of formula (I) is the compound of formula (80) or formula (81). 【Chemistry 15】 In formula (80): R １１ａ and R １１ｂ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n ８ is an integer between 1 and 5; 【Chemistry 16】 In formula (81): Alk is either an unsubstituted or substituted alkyl group; R １１ａ and R １１ｂ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl.

14. The compound according to claim 13, wherein the compound of formula (80) is the compound of formula (800) or formula (801), or the compound of formula (81) is the compound of formula (802) or formula (803). 【Chemistry 17】

15. R ５ｂ and / or R ５ｃ However, each is independently selected from unsubstituted or substituted alkynyls, and optionally substituted alkynyls, substituted aryls, substituted heteroaryls, halogens (optionally Br), -N(R) ａ ) ２ (optionally - NH ２ ), and -N(R ａ ) C(O)R ａ Selected from, optionally, [Chemistry 18] And, Optionally, R ５ｂ teeth, 【Chemistry 19】 Selected from, Optionally, R ５ｃ teeth, 【Chemistry 20】 A compound according to any one of claims 11 to 14, selected from among them.

16. R １１ａ and R １１ｂ However, each is either an unsubstituted alkyl group or R １１ａ and R １１ｂ However, each is independent of the others. 【Chemistry 21】 is or R １１ａ R is selected from H and unsubstituted alkyl, １１ｂ but, 【Chemistry 22】 is or R １１ａ H is R １１ｂ C is an unsubstituted alkyl group, where Y is an unsubstituted or substituted alkyl group, and optionally an unsubstituted or substituted C. １ ~C ５ Alkyl, unsubstituted or substituted aryl, optionally unsubstituted or substituted phenyl, unsubstituted or substituted cycloalkyl, optionally unsubstituted or substituted C ３ ~C ７ Cycloalkyl, and unsubstituted or substituted alkoxy, optionally unsubstituted or substituted C １ ~C ５ Selected from alkoxy, n ７ n is an integer between 1 and 3, and can be any integer (optionally) n ７ is 1 or 2, Optionally, R １１ａ and R １１ｂ Each of them operates independently. 【Chemistry 23】 Selected from, Optionally, R １１ａ and R １１ｂ Each is independent of the others. 【Chemistry 24】 A compound according to any one of claims 11 to 15, selected from the above.

17. R １１ａ H and -CH ３ Selected from, R １１ｂ but, 【Chemistry 25】 Selected from, Optionally, R １１ａ H and -CH ３ Selected from, R １１ｂ but, 【Chemistry 26】 Selected from, Optionally, R １１ａ H and -CH ３ Selected from, R １１ｂ but, 【Chemistry 27】 Selected from, Optionally, R １１ａ H is R １１ｂ ga-CH ３ is or R １１ａ and R １１ｂ Each of these is -CH ３ The compound according to claim 16.

18. The compound according to any one of claims 1 to 3, wherein the compound of formula (I) is the compound of formula (82). 【Chemistry 28】 In formula (82): R １１ａ , R １１ｂ , R １１ｃ , and R １１ｄ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl.

19. The compound according to claim 18, wherein the compound of formula (82) is a compound of formula (804) or formula (805). 【Chemistry 29】

20. The compound according to any one of claims 1 to 3, wherein the compound of formula (I) is the compound of formula (90). 【Transformation 30】 In formula (90): n is an integer between 1 and 5.

21. The compound according to claim 20, wherein the compound of formula (90) is a compound of formula (900), formula (901), or formula (902). 【Chemistry 31】

22. R １１ａ is H or a substituted alkyl, optionally, 【Chemistry 32】 optionally, 【Transformation 33】 The compound according to claim 20 or claim 21.

23. R １０ ga-C(O)R ａ And, optionally, R ａ R is selected from unsubstituted alkenyls, substituted alkyls, substituted aryls, and substituted heterocyclyls, or R １０ ga-S(O) ｔ R ａ And optionally, t is 2, R ａ is a substitution aryl, and optionally R １０ but 【Transformation 34】 A compound according to any one of claims 20 to 22, selected from among.

24. The compound of formula (I) is any one of the following compounds: formula 1002, formula 1005, formula 1010 to formula 1098, or a pharmaceutically acceptable salt thereof, according to any one of claims 1 to 3 or claims 11 to 23. Table 2-1 Table 2-2 Table 2-3 Table 2-4 Table 2-5 Table 2-6 Table 2-7 Table 2-8 Table 2-9 Table 2-10

25. The compound according to any one of claims 1 to 3 or claims 11 to 24, wherein the compound of formula (I) is any one of the following compounds: formula 1010, formula 1011, formulas 1020 to 1030, formula 1034, formula 1036, formula 1037, formula 1040, formula 1043, formula 1050, formulas 1053 to 1056, formula 1058, formula 1060, formula 1062, formula 1064, formula 1066, formula 1069, formula 1070, formula 1075, or formula 1084, or a pharmaceutically acceptable salt thereof. Table 3-1 Table 3-2 Table 3-3 Table 3-4

26. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. 【Chemistry 35】 In formula (I): A is, 【Transformation 36】 Selected from; L is a linking group; R １ａ , R １ｂ , R ２ , R ３ , R ４ａ , R ４ｂ , R ５ａ , R ５ｂ , R ５ｃ , R ５ｄ , R ５ｅ , R ６ａ , R ６ｂ , R ６ｃ , R ６ｄ , R ６ｅ , R ７ａ , R ７ｂ , R ７ｃ , R ７ｄ , R ８ , R ９ , R １０ , R １１ａ , R １１ｂ , and R １１ｃ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R １２ is H or an unsubstituted alkyl; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n １ is an integer between 0 and 5; t is either 1 or 2.

27. The pharmaceutical composition according to claim 26, wherein the compound of formula (I) is the compound of formula (10). 【Chemistry 37】 In formula (10): R ９ａ , R ９ｂ , R ９ｃ , R ９ｄ , and R ９ｅ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n ２ is an integer between 0 and 5; t is either 1 or 2.

28. The pharmaceutical composition according to claim 26, wherein the compound of formula (I) is the compound of formula (20) or formula (21). 【Chemistry 38】 In equations (20) and (21): n ３ is an integer between 0 and 5.

29. The pharmaceutical composition according to claim 26, wherein the compound of formula (I) is the compound of formula (30) or formula (31). 【Chemistry 39】 In equations (30) and (31): p is an integer between 0 and 5.

30. The pharmaceutical composition according to claim 26, wherein the compound of formula (I) is the compound of formula (32). 【Chemistry 40】 In formula (32): q is an integer between 1 and 3.

31. The pharmaceutical composition according to claim 26, wherein the compound of formula (I) is the compound of formula (40). 【Chemistry 41】 In formula (40): n ４ is an integer between 0 and 5.

32. The pharmaceutical composition according to claim 26, wherein the compound of formula (I) is the compound of formula (50). 【Chemistry 42】 In formula (50): R １０ａ , R １０ｂ , R １０ｃ , R １０ｄ , and R １０ｅ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n ５ is an integer between 0 and 5; t is either 1 or 2.

33. The pharmaceutical composition according to claim 26, wherein the compound of formula (I) is the compound of formula (60). 【Chemistry 43】 In formula (60): n ６ is an integer between 0 and 5.

34. The pharmaceutical composition according to claim 26, wherein the compound of formula (I) is the compound of formula (70). 【Chemistry 44】 In formula (70): R １１ａ and R １１ｂ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. Optionally, the compound of formula (70) is a compound of formula (700) or formula (701). 【Chemistry 45】

35. The pharmaceutical composition according to claim 26, wherein the compound of formula (I) is a compound of formula (80) or formula (81). 【Chemistry 46】 In formula (80): R １１ａ and R １１ｂ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl; n ８ is an integer between 1 and 5; 【Chemistry 47】 In formula (81): Alk is either unsubstituted or substituted alkyl; R １１ａ and R １１ｂ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. Optionally, the compound of formula (80) is the compound of formula (800) or formula (801), or the compound of formula (81) is the compound of formula (802) or formula (803). 【Chemistry 48】

36. The pharmaceutical composition according to claim 26, wherein the compound of formula (I) is the compound of formula (82). 【Chemistry 49】 In formula (82): R １１ａ , R １１ｂ , R １１ｃ , and R １１ｄ Each of these is independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted cycloalkylalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroarylalkyl, hydroxy, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, -OR ａ , -SR ａ , -OC(O)-R ａ , -SC(O)-R ａ , -N(R ａ ) ２ , -C(O)R ａ , -C(O)OR ａ , -C(O)SR ａ , -OC(O)N(R ａ ) ２ , -C(O)N(R ａ ) ２ , -N(R ａ ) C(O)OR ａ , -N(R ａ ) C(O)R ａ , -N(R ａ ) C(O)N(R ａ ) ２ , -N(R ａ ) C (NR ａ )N(R ａ ) ２ , -N(R ａ ) S(O) ｔ R ａ , -S(O) ｔ R ａ , -S(O) ｔ OR ａ , -S(O) ｔ N(R) ａ ) ２ , and PO ３ (R ａ ) ２ Selected from; R ａ Each instance is independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted haloalkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, and unsubstituted or substituted heteroarylalkyl. Optionally, the compound of formula (82) is a compound of formula (804) or (805). [Transformation 50]

37. The pharmaceutical composition according to claim 26, wherein the compound of formula (I) is the compound of formula (90). 【Chemistry 51】 In formula (90): n is an integer from 1 to 5, and optionally, the compound of formula (90) is a compound of formula (900), formula (901), or formula (902). 【Chemistry 52】

38. The pharmaceutical composition according to claim 26 or any one of claims 34 to 37, wherein the compound of formula (I) is any one of the following compounds from formulas 1001 to 1098, or a pharmaceutically acceptable salt thereof. Table 4-1 Table 4-2 Table 4-3 Table 4-4 Table 4-5 Table 4-6 Table 4-7 Table 4-8 Table 4-9 Table 4-10

39. The pharmaceutical composition according to claim 26 or any one of claims 34 to 38, wherein the compound of formula (I) is any one of the following compounds: formula 1010, formula 1011, formulas 1020 to 1030, formula 1034, formula 1036, formula 1037, formula 1040, formula 1043, formula 1050, formulas 1053 to 1056, formula 1058, formula 1060, formula 1062, formula 1064, formula 1066, formula 1069, formula 1070, formula 1075, or formula 1084, or a pharmaceutically acceptable salt thereof. Table 5-1 Table 5-2 Table 5-3 Table 5-4

40. A method for treating cancer, an infectious disease, or an inflammatory disease in a subject requiring treatment, comprising administering to the subject a pharmaceutical composition according to any one of claims 26 to 39, wherein the cancer is optionally resistant to an anti-checkpoint agent, optionally the anti-checkpoint agent is an antibody, and optionally selected from anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, and anti-CTLA antibody.

41. The aforementioned cancers include basal cell carcinoma, biliary tract cancer, bladder cancer, bone cancer, brain and central nervous system cancer, breast cancer, peritoneal cancer, cervical cancer, choriocarcinoma, colon and rectum cancer, connective tissue cancer, digestive system cancer, endometrial cancer, esophageal cancer, eye cancer, head and neck cancer, gastric cancer (including gastrointestinal cancer), glioblastoma, hepatocellular carcinoma, liver cancer, carcinoma in situ, kidney cancer, laryngeal cancer, leukemia, liver cancer, lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma), melanoma, myeloma, neuroblastoma, oral cancer (lips, tongue, mouth, and pharynx), ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, rhabdomyosarcoma, rectal cancer, respiratory system cancer, salivary gland cancer, sarcoma, skin cancer, squamous cell carcinoma, and stomach cancer. Cancer, testicular cancer, thyroid cancer, uterine or endometrial cancer, urinary tract cancer, vulvar cancer, Hodgkin lymphoma and non-Hodgkin lymphoma, and B-cell lymphoma (low-grade / follicular non-Hodgkin lymphoma (NHL), small lymphocytic (SL) NHL, intermediate-grade / follicular NHL, intermediate-grade diffuse NHL, high-grade immunoblastic NHL, high-grade lymphoblastic NHL, high-grade small non-incisional nuclear cell NHL, giant tumor NHL, mantle cell The method according to claim 40, comprising lymphomas (including lymphoma, AIDS-associated lymphoma, and Waldenström macroglobulinemia), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia, chronic myeloid leukemia, and other carcinomas and sarcomas, and post-transplant lymphoproliferative disorders (PTLD), as well as nevus disorders, edema (such as that associated with brain tumors), and abnormal angiogenesis associated with Meigs syndrome.

42. The aforementioned cancers include chronic lymphocytic leukemia (CLL), acute leukemia, acute lymphocytic leukemia (ALL), B-cell acute lymphocytic leukemia (B-ALL), T-cell acute lymphocytic leukemia (T-ALL), chronic myeloid leukemia (CML), B-cell prelymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell or large cell follicular lymphoma. The method according to claim 40 or claim 41, wherein the hematological cancer is selected from the group consisting of parkorma, malignant lymphoproliferative disorders, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndromes, non-Hodgkin lymphoma, Hodgkin lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenström macroglobulinemia, and preleukemia, or combinations thereof.

43. The method according to claim 40, wherein the infection is a viral infection, and optionally the viral infection is caused by a virus selected from papillomavirus, herpes simplex virus (HSV), human immunodeficiency virus (HIV), hepatitis virus, Zika virus, yellow fever virus, West Nile virus, dengue virus, Japanese encephalitis virus, St. Louis encephalitis virus, hepatitis C virus, poliovirus, rhinovirus, enterovirus, coxsackievirus, influenza virus, lentivirus, respiratory syncytial virus, human parainfluenza virus, rubravirus (e.g., mumps virus), measles virus, human metapneumovirus, hantavirus, rotavirus, norovirus, and severe acute respiratory syndrome (SARS) virus (e.g., SARS-CoV-2).

44. The method according to claim 40, wherein the inflammatory disease is an autoimmune disease or condition selected from multiple sclerosis, diabetes mellitus, lupus, celiac disease, Crohn's disease, ulcerative colitis, Guillain-Barré syndrome, scleroderma, Goodpasture syndrome, Wegener's granulomatosis, autoimmune epilepsy, Rasmussen's encephalitis, primary biliary sclerosis, sclerosing cholangitis, autoimmune hepatitis, Addisohn's disease, Hashimoto's thyroiditis, fibromyalgia, Meniere's syndrome; transplant rejection (e.g., prevention of allograft rejection), pernicious anemia, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, Sjögren's syndrome, lupus erythematosus, multiple sclerosis, myasthenia gravis, Reiter's syndrome, Graves' disease, and other autoimmune diseases.

45. A method for treating an anti-checkpoint drug-resistant cancer in a subject requiring treatment, comprising administering to the subject a pharmaceutical composition according to any one of claims 26 to 39.

46. (a) Obtaining biological samples from the subject, (b) Evaluate the expression of TRIM7 in the biological sample, and (c) Selecting a cancer treatment comprising the pharmaceutical composition according to any one of claims 26 to 39, where the TRIM 7 is upregulated compared to healthy tissue, a biological sample previously obtained from the subject, or another biological sample from a patient known to be sensitive to an anti-checkpoint agent. Includes, (d) Optionally, selecting a second cancer treatment comprising an anti-checkpoint agent, wherein the anti-checkpoint agent is selected from anti-PD-1 agents, anti-PD-L1 agents, anti-PD-L2 agents, and / or anti-CTLA agents, and optionally, the anti-checkpoint agent is selected from anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, and / or anti-CTLA antibodies. including, A method for determining cancer treatment for a patient.

47. (a) Obtaining biological samples from the subject, (b) Evaluate the expression of TRIM7 in the biological sample, and (c) Selecting a cancer treatment comprising the pharmaceutical composition according to any one of claims 26 to 39, where the TRIM 7 is upregulated compared to healthy tissue, a biological sample previously obtained from the subject, or another biological sample from a patient known to be sensitive to an anti-checkpoint agent. Includes, (d) Optionally, selecting a second cancer treatment comprising an anti-checkpoint agent, wherein the anti-checkpoint agent is selected from anti-PD-1 agents, anti-PD-L1 agents, anti-PD-L2 agents, and / or anti-CTLA agents, and optionally, the anti-checkpoint agent is selected from anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, and / or anti-CTLA antibodies. including, A method for selecting patients for cancer treatment.

48. (a) Obtaining biological samples from the subject, (b) Evaluate the expression of TRIM7 in the biological sample, and (c) Administering a cancer treatment comprising the pharmaceutical composition according to any one of claims 26 to 39, provided that TRIM 7 is upregulated compared to healthy tissue, a biological sample previously obtained from the subject, or another biological sample from a patient known to be sensitive to an anti-checkpoint agent. Includes, (d) Optionally administering a second cancer treatment comprising an anti-checkpoint agent, wherein the anti-checkpoint agent is selected from anti-PD-1, anti-PD-L1, anti-PD-L2, and / or anti-CTLA agents, and optionally the anti-checkpoint agent is selected from anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, and / or anti-CTLA antibody. including, Methods for treating cancer.

49. The method according to any one of claims 46 to 48, wherein the biological sample is a fresh tissue sample, a frozen tumor tissue sample, cultured cells, circulating tumor cells, or a formalin-fixed paraffin-embedded tumor tissue sample.

50. The biological sample is a biopsy sample, and optionally the biopsy sample is selected from endoscopic biopsy, bone marrow biopsy, endoscopic biopsy (e.g., cystoscopy, bronchoscopy, and colonoscopy), needle biopsy (e.g., fine-needle aspiration, core needle biopsy, vacuum-assisted biopsy, X-ray-assisted biopsy, computed tomography (CT)-assisted biopsy, magnetic resonance imaging (MRI)-assisted biopsy, and ultrasound-assisted biopsy), skin biopsy (e.g., shaving biopsy, punch biopsy, and incision biopsy), and surgical biopsy, and optionally the biological sample is blood, plasma, serum, tear fluid, tears, bone marrow, blood The method according to any one of claims 46 to 48, comprising, , blood cells, ascites, tissue or fine-needle biopsy specimens, cell-containing bodily fluids, free suspended nucleic acids, sputum, saliva, urine, cerebrospinal fluid, peritoneal fluid, pleural fluid, feces, lymphatic fluid, gynecological fluids, skin swabs, vaginal swabs, oral swabs, nasal swabs, lavage solutions or lavage solutions such as tube lavage or bronchoalveolar lavage, aspirates, scrapes, bone marrow specimens, tissue biopsy specimens, surgical specimens, feces, other bodily fluids, secretions and / or excretions, and / or cells derived therefrom, wherein optionally the biological specimen comprises at least one tumor cell.

51. The method according to any one of claims 46 to 50, wherein the evaluation is performed by DNA sequencing, RNA sequencing, immunohistochemical staining, Western blotting, in-cell Western blotting, immunofluorescence staining, ELISA, and fluorescence-activated cell sorting (FACS), or by a combination thereof, or the evaluation is performed by contacting the sample with an agent that specifically binds to TRIM7, and optionally the agent that specifically binds to one or more proteins comprises an antibody, an antibody-like molecule, or a binding fragment thereof, or the evaluation is performed by contacting the sample with an agent that specifically binds to one or more nucleic acids of TRIM7, and optionally the agent that specifically binds to one or more nucleic acids is a nucleic acid primer or probe.

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