Substituted heteroalgebras and their uses

Abstract

This disclosure provides compounds and pharmaceutically acceptable salts thereof, as well as methods for using them. These compounds and methods have a wide range of applications as therapeutic, diagnostic, and research tools. In particular, the subject compositions and methods are useful for reducing the output of signaling pathways of oncogenic proteins.

Description

[Background technology]

[0001] cross reference This application claims the interests of U.S. Provisional Patent Application No. 63 / 506,493 filed on 6 June 2023, U.S. Provisional Patent Application No. 63 / 582,474 filed on 13 September 2023, and U.S. Provisional Patent Application No. 63 / 597,315 filed on 8 November 2023, each of which is incorporated herein by reference in its entirety.

[0002] Sequence List This application includes a sequence listing submitted electronically in XML format, the entirety of which is incorporated herein by reference. The XML copy, created on 31 May 2024, is named 56690_770_601_SL.xml and has a size of 13,994 bytes.

[0003] Cancer (e.g., tumors, neoplasms, metastases) is the second leading cause of death worldwide, with an estimated 10 million deaths annually. Most cancers are characterized by mutations in one or more proteins involved in various signaling pathways, which lead to the uncontrolled proliferation of cancer cells. In some cases, it is known that approximately 25-30 percent of tumors have rat sarcoma (Ras) mutations. In particular, mutations in the Kirsten Ras oncogene (K-Ras) are among the most frequently detected Ras mutations in human cancers, including lung adenocarcinoma (LUAD) and pancreatic ductal adenocarcinoma (PDAC).

[0004] The Ras protein has long been considered "undruggable," partly due to its high affinity for its substrate, guanosine-5'-triphosphate (GTP), and / or its smooth surface lacking any obvious target regions. Certain G12C Ras gene mutations have been identified as drug-leading targets, with numerous G12C-specific inhibitors being developed. However, because G12C mutations in Ras exhibit a much lower incidence compared to other known Ras mutations such as G12D and G12V, the therapeutic applications of these drugs remain limited. Lack of drug resistance and durability further restricts these therapeutics. [Overview of the project]

[0005] Therefore, there remains a considerable need for the design of novel therapeutic and diagnostic methods that can specifically target Ras, including wild-type Ras, Ras variants, and / or related proteins, and reduce Ras signaling output. Of particular interest are Ras inhibitors for the treatment of Ras-related diseases (e.g., cancer), including pan-Ras inhibitors capable of inhibiting two or more Ras variants and / or wild-type Ras, as well as mutant-selective inhibitors that target mutant Ras proteins such as Ras G12D, G12C, G12S, G13D, and / or G12V. Such compositions and methods may be particularly useful for treating a variety of diseases, including but not limited to cancer and neoplasms. This disclosure addresses these needs and provides further advantages applicable to the diagnosis, prognosis, and / or treatment of a diverse range of diseases.

[0006] In one embodiment, a compound of formula (I): [ka] Or a pharmaceutically acceptable salt or solvate thereof is provided, in the formula, Ring A is a single ring C 7-10 Selected from carbon rings and monocyclic 7-10 membered heterocycles, X 1is selected from C(R 1 ), C(R 1 )2, N, N(R 1b ), O, S, S(O), S(O)2, and C(O), X 2 is selected from C(R 2 ), C(R 2 )2, N, N(R 2b ), O, S, S(O), S(O)2, and C(O), X 3 is selected from C(R 3 ), C(R 3 )2, N, N(R 3b ), O, S, S(O), S(O)2, and C(O), X 4 is selected from C, C(R 4 ) and N, X 5 is selected from C, C(R 5 ) and N, X 6 is selected from C(R 6 ), C(R 6 )2, N, N(R 6b ), O, S, S(O), S(O)2, and C(O), X 7 is selected from C(R 7 ), C(R 7 )(R 7a ) and N(R 7b ), X 8 is selected from C(R 8 ), C(R 8 )2, N, N(R 8b ), O, S, S(O), S(O)2, and C(O), X 13 is selected from C, C(R 13a ) and N, X 14 is selected from C, C(R 14a ) and N, R 7 is -L 7a -R 17 and R 7b is -L 7b -R 17And, L 7a is a bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, L 7b is a bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 membered heteroalkylene, 3-4 membered heteroalkene, 3-4 membered heteroalkylene, -C(O)- and -C(O)N(R) 12 )- Selected from, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, R 9 is, -L19 -R 19 -L 19a -R 19a and L 19 is a bond, C 1-4 alkylene, C 2-4 alkenylene, C 2-4 alkynylene, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenylene, 3- to 4-membered heteroalkynylene, -O-, -N(R 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​)-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, R 19a teeth, i) A five-membered heteroaryl containing one or more ring nitrogen atoms, wherein the five-membered heteroaryl is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 Those that are optionally replaced by, and ii) A 5- to 12-membered heterocycle containing 3 or 4 ring nitrogen atoms, wherein the 5- to 12-membered heterocycle contains one or more R 20 Selected from those that are optionally replaced by, R 1b , R 2b , R 3b , R 6b , and R 8b These are independently hydrogen, -CN, and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12(Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -C(O)OR 12 , -C(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7a , R 8 , R 13a , R 14a , and R 17 These are independent of each other, for each entity: hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12(Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, R12 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 member heterocycle), C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Alkyl-(3-12 member heterocycle) is one or more R 20 It is optionally replaced by, R 13 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, and C 1-6 R selected from haloalkyls or added to the same nitrogen atom 12 and R 13 is one or more R 20 It forms a 3- to 10-membered complex ring that can be optionally substituted with, R 20 These are independent of each other, for each entity: halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 )-, and -S(=O)(=NR 22 )N(R 22 )(R 23 ) is selected from C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are halogens, oxo, -CN, and C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 ) is optionally substituted with one or more substituents independently selected from the original, R 21 These are independent of each other, for each entity, hydrogen, halogen, and C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 member heterocycles) or two R 21 However, they are grouped together with the carbon atoms to which they are added and C 3-12 They form a carbon ring or a 3- to 12-membered heterocycle, each of which is a halogen, C 1-3 Alkyl, C 1-3 Optionally substituted with one or more substituents independently selected from haloalkyl and -OH groups, R 22 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 member heterocycles), R 23These are independent of each other, for each existence, hydrogen and C 1-6 R selected from alkyl groups or added to the same nitrogen atom 22 and R 23 However, it forms a 3- to 10-membered complex ring, R 29 These are independent of each other, for each entity: halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 Two R atoms are optionally substituted and attached to the same atom. 29 They are selectively linked together to form oxos, n29 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13, and each [ka] These independently represent single or double bonds in which all valencies are satisfied.

[0007] In embodiments of the compound of formula I, L 19a C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )-, and -P(O)(R12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced.

[0008] In embodiments of the compound of formula I, the compound has formula (IA): [ka] or a pharmaceutically acceptable salt or solvate thereof, in the formula, X 9 C(R 9 ), C(R 9 )(R 9a ), and N(R 9 ) are selected from, X 10 C(R 10 ), C(R 10 )2, N, N(R 10b ), selected from O, S, S(O), S(O)2, and C(O), X 11 C(R 11 ), C(R 11 )2, N, N(R 11b ), selected from O, S, S(O), S(O)2, and C(O), X 12 is, -X 12a -, -X 12a -X 12b -, -X 12a -X 12b -X 12c -, and -X 12a -X 12b -X 12c -X 12d - Select from, X 12a X 5 Directly coupled, X 12a , X 12b , X 12c , and X 12d Independently, C(R12a ), C(R 12a )2, N, N(R 12b ), selected from O, S, S(O), S(O)2, and C(O), R 19a is a 5-membered heteroaryl containing one or more ring nitrogen atoms, and a 5-membered heteroaryl is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally replaced by, R 10b , R 11b , and R 12b These are independently hydrogen, -CN, and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -C(O)OR 12 , -C(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, R 9a , R 10 , R 11 , and R 12a These are independent of each other, for each entity: hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, and each [ka] These independently represent single or double bonds in which all valencies are satisfied.

[0009] In embodiments of compounds of formula I, IA, II, or IIA, R 19a is a 5-membered heteroaryl having one or two ring nitrogen atoms, in which case the 5-membered heteroaryl is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally replaced.

[0010] In embodiments of compounds of formula I, IA, II, or IIA, R 19a R is selected from pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl, in this case, 19a R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally replaced.

[0011] In embodiments of compounds of formula I, IA, II, or IIA, R19a R is selected from pyrrolyl, imidazolyl, and pyrazolyl, in this case, 19a R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally replaced.

[0012] In embodiments of the compound of formula I, the compound has formula (IB): [ka] or a pharmaceutically acceptable salt or solvate thereof, in the formula, X 9 C(R 9 ), C(R 9 )(R 9a ), and N(R 9 ) are selected from, X 10 C(R 10 ), C(R 10 )2, N, N(R 10b ), selected from O, S, S(O), S(O)2, and C(O), X 11 C(R 11 ), C(R 11 )2, N, N(R 11b ), selected from O, S, S(O), S(O)2, and C(O), X 12 is, -X 12a -, -X 12a -X 12b -, -X 12a -X 12b -X 12c -, and -X 12a -X 12b -X 12c -X 12d - Select from, X 12a X 5 Directly coupled, X 12a , X 12b , X 12c , and X 12d Independently, C(R 12a ), C(R12a )2, N, N(R 12b ), selected from O, S, S(O), S(O)2, and C(O), R 19a is a 5- to 12-membered heterocycle containing 3 or 4 ring nitrogen atoms, in which case the 5- to 12-membered heterocycle is one or more R 20 It is optionally replaced by, R 10b , R 11b , and R 12b These are independently hydrogen, -CN, and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -C(O)OR 12 , -C(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) have 1, 2, or 3 R 20 It is optionally replaced by, R 9a , R 10 , R 11 , and R 12a These are independent of each other, for each entity: hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, and each [ka] These independently represent single or double bonds in which all valencies are satisfied.

[0013] In embodiments of compounds of formula I, IB, II, or IIA, R 19a R is a non-aromatic 5-12 membered heterocycle containing 3 or 4 ring nitrogen atoms, in this case, 19a is one or more R 20 It is optionally replaced.

[0014] In embodiments of compounds of formula I, IB, II, or IIA, R 19a R is a 5-12 member heteroaryl compound containing 3 or 4 ring nitrogen atoms, in this case, 19a is one or more R 20 It is optionally replaced.

[0015] In embodiments of compounds of formula I, IB, II, or IIA, R 19a R is a 9-12 member heteroaryl compound containing 3 or 4 ring nitrogen atoms, in this case, 19a is one or more R 20 It is optionally replaced.

[0016] In embodiments of compounds of formula I, IA, IB, II, or IIA, R19a R is a 5-6 member heteroaryl compound containing 3 or 4 ring nitrogen atoms, in this case, 19a is one or more R 20 It is optionally replaced.

[0017] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a R is selected from triazolyl and tetrazolyl, in this case, 19a is one or more R 20 It is optionally replaced.

[0018] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a R is selected from 1,2,3-triazolyl and 1,2,4-triazolyl, in this case, 19a is one or more R 20 It is optionally replaced.

[0019] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a is halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Optionally substituted with one or more substituents independently selected from alkynyl, 2-6 membered heteroalkyl, 3-6 membered heteroalkenyl, and 3-6 membered heteroalkynyl, in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynnyl, 2-6 membered heteroalkyl, 3-6 membered heteroalkenyl, and 3-6 membered heteroalkynyl are halogens, oxo, -CN, and C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21)2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 It is optionally substituted with one or more substituents independently selected from ).

[0020] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a These are halogen, -CN, and C 1-6 It is optionally substituted with one or more substituents independently selected from the alkyl, in this case, C 1-6 Alkyls are halogens, oxo, -CN, and -OR 22 , -SR 22 , and -N(R 22 )(R 23 It is optionally substituted with one or more substituents independently selected from ).

[0021] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a It is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, and -I.

[0022] In embodiments of the compounds of Formula I, IA, IB, II, or IIA, R 19a is one R selected from -F and -Cl 20 and is optionally substituted.

[0023] In embodiments of the compounds of Formula I, IA, IB, II, or IIA, R 19a is

Chemical formula

[0024] In embodiments of the compounds of Formula I, IA, IB, II, or IIA, R 19a is

Chemical formula

[0025] In embodiments of the compounds of Formula I, IA, IB, II, or IIA, L 19a is -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S(O)2-, -S(O)-, -P(O)(R 12 )-, -N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-, -S(O)2N(R 12 )-, -S(O)N(R 12 )-, and -P(O)(R 12 )N(R 12 )- selected from.

[0026] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a The molecule is selected from -C(O)-, -S(O)2-, and -S(O)-.

[0027] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a -C(O)- and -N(R 12 )C(O)- is selected.

[0028] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a It is -C(O)-.

[0029] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 Monoring C is optionally substituted by 3-8 It is a carbon ring.

[0030] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 Monocyclic non-aromatic C is optionally substituted. 4-6 It is a carbon ring.

[0031] In embodiments of the compounds of formulas I, IA, and IB, R 19 is one or more R 20 It is a phenyl compound that is optionally substituted.

[0032] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monoring 3- to 8-membered complex ring that can be optionally substituted with .

[0033] In embodiments of the compounds of formulas I, IA, and IB, R 19 is one or more R 20 It is a monocyclic five-membered heteroaryl that can be optionally substituted.

[0034] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic non-aromatic 4- to 5-membered heterocyclic ring that can be optionally substituted.

[0035] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is selected from azetidinil and pyrrolidinil, in which case azetidinil and pyrrolidinil are one or more R 20 It is optionally replaced.

[0036] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 It is optionally substituted with one or more substituents independently selected from alkyl-(3-12 membered heterocycle), in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Alkyl-(3-12 member heterocycle) is associated with halogens, oxo, -CN, and C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 It is optionally substituted with one or more substituents independently selected from ).

[0037] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 C 1-4 Alkyl and C 3-4 It is optionally substituted with one or more substituents independently selected from the carbon ring, in this case, C 3-4 The carbon ring is composed of halogens and C 1-4 It is optionally substituted with one or more substituents independently selected from the alkyl group.

[0038] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 It is optionally substituted with an unsubstituted methyl group.

[0039] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19 It is a combination.

[0040] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19 is unsubstituted C 1-2 It is alkylene.

[0041] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19 It is an unsubstituted methylene group.

[0042] In embodiments of compounds of formula IA, IB, or IIA, X 9 N(R) 9 )

[0043] In embodiments of compounds of formula IA, IB, or IIA, X 10 C(R 10 )2.

[0044] In embodiments of compounds of formula IA, IB, or IIA, X 10 CH(R 10 )

[0045] In embodiments of compounds of formula IA, IB, or IIA, X 10 This is CH2.

[0046] In embodiments of compounds of formula IA, IB, or IIA, R 10 For each existence, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-12 A carbon ring and a 3- to 12-membered heterocycle are independently selected, in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-12 Carbon rings and 3- to 12-membered heterocycles have one or more R 20 It is optionally replaced.

[0047] In embodiments of compounds of formula IA, IB, or IIA, R 10 For each existence, C1-4 Alkyl, C 2-3 Alkenil, C 2-3 Alkinyl, C 3-5 A carbon ring and a 3- to 5-membered heterocycle are independently selected, in this case, C 1-4 Alkyl, C 2-3 Alkenil, C 2-3 Alkinyl, C 3-5 Carbon rings and 3- to 5-membered heterocycles have one or more R 20 It is optionally replaced.

[0048] In embodiments of compounds of formula IA, IB, or IIA, R 10 For each existence, C 1-4 Alkyl, C 2-3 Alkenil, C 2-3 Alkinyl, C 3-5 A carbon ring and a 3- to 5-membered heterocycle are independently selected, in this case, C 1-4 Alkyl, C 2-3 Alkenil, C 2-3 Alkinyl, C 3-5 Carbon rings and 3- to 5-membered heterocycles have one or more R selected from halogens, -OH, and -CN. 20 It is optionally replaced.

[0049] In embodiments of compounds of formula IA, IB, or IIA, R 10 For each existence, non-substitution C 1-4 Alkyl, unsubstituted C 2-3 Alkenyl, unsubstituted C 2-3 Alkinyl, unsubstituted C 3-5 They are independently selected from carboelectric rings and unsubstituted 3- to 5-membered heterocycles.

[0050] In embodiments of compounds of formula IA, IB, or IIA, R 10 For each existence, [ka] It is selected independently of others.

[0051] In embodiments of the compounds of formula IA, IB, or IIA, X 11 is C(R 11 )2.

[0052] In embodiments of the compounds of formula IA, IB, or IIA, X 11 is CH(R 11 ).

[0053] In embodiments of the compounds of formula IA, IB, or IIA, X 11 is CH2.

[0054] In embodiments of the compounds of formula IA, IB, or IIA, R 11 is, for each occurrence, independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 carbocycle, and 3- to 12-member heterocycle, where C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 carbocycle, and 3- to 12-member heterocycle are optionally substituted with one or more R 20 . "

[0055] In embodiments of the compounds of formula IA, IB, or IIA, R 11 is, for each occurrence, independently selected from C 1-4 alkyl, C 2-3 alkenyl, C 2-3 alkynyl, C 3-5 carbocycle, and 3- to 5-member heterocycle, where C 1-4 alkyl, C 2-3 alkenyl, C 2-3 alkynyl, C 3-5 carbocycle, and 3- to 5-member heterocycle are optionally substituted with one or more R 20 .

[0056] In embodiments of the compounds of formula IA, IB, or IIA, R 11 is, for each occurrence, unsubstituted C 1-4Alkyl, unsubstituted C 2-3 Alkenyl, unsubstituted C 2-3 Alkinyl, unsubstituted C 3-5 They are independently selected from carboelectric rings and unsubstituted 3- to 5-membered heterocycles.

[0057] In embodiments of compounds of formula IA, IB, or IIA, X 12 is, -X 12a - is

[0058] In embodiments of compounds of formula IA, IB, or IIA, X 12a It is O.

[0059] In embodiments of compounds of formula I, IA, IB, II, or IIA, X 1 It is N.

[0060] In embodiments of compounds of formula I, IA, IB, II, or IIA, X 2 C(R 2 )

[0061] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 2 is -OR 12 That is the case.

[0062] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 2 is -O(C 1-3 Alkylene (4-10 membered heterocycle), in this case the 4-10 membered heterocycle is a halogen, C 1-3 Alkyl, C 1-3 Haloalkyl and =C(R 21 ) is optionally substituted with 1, 2, or 3 substituents independently selected from 2.

[0063] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 2 teeth, [ka] [ka] Selected from.

[0064] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 2 teeth, [ka] Selected from.

[0065] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 2 teeth, [ka] Selected from.

[0066] In embodiments of compounds of formula I, IA, IB, II, or IIA, X 3 It is N.

[0067] In embodiments of compounds of formula I, IA, IB, II, or IIA, X 4 It is C.

[0068] In embodiments of compounds of formula I, IA, IB, II, or IIA, X 5 It is C.

[0069] In embodiments of compounds of formula I, IA, IB, II, or IIA, X 6 C(R 6 )

[0070] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 6 For each entity, it is selected independently from hydrogen and halogens.

[0071] In embodiments of compounds of formula I, IA, IB, II, or IIA, X 6 It is N.

[0072] In embodiments of compounds of formula I, IA, IB, II, or IIA, X 6 N(R) 6b )

[0073] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 6b It is an unsubstituted cyclopropyl compound.

[0074] In embodiments of compounds of formula I, IA, IB, II, or IIA, X 7 C(R 7 )

[0075] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 7a It is a combination.

[0076] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 17 C 6-12 Selected from carbon rings and 5-12 membered heterocycles, C 6-12 Carbon rings and 5-12 membered heterocycles have one or more R 20 It is optionally replaced.

[0077] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 17 is selected from phenyl, pyridyl, naphthyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzothienyl, indazolyl, and benzoxazolyl, in which case phenyl, pyridyl, naphthyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzothienyl, indazolyl, and benzoxazolyl is one or more R 20 It is optionally replaced.

[0078] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 17 teeth, [ka] selected from, wherein Q 1 , Q 3 , and Q 5 are independently selected from N and C(R 1q ), Q 4 and Q 6 are independently selected from O, S, C(R 1q )2 and N(R 1r ), Y 4 , Y 5 , Y 6 , Y 9 , and Y 10 are independently selected from C(R 1q ) and N, Y 7 and Y 8 are independently selected from C(R 1q ), C(R 1q )2, N, and N(R 1r ), Y 13 is a bond, C(R 1q ), N, C(O), C(R 1q )2, C(O)C(R 1q )2, C(R 1q )2C(R 1q )2, C(R 1q )2N(R 1r ), and N(R 1r ), Y 14 , Y 15 , Y 17 , and Y 18 are independently selected from C(O), C(R 1q ), N, C(R 1q )2, and N(R 1r ), Y 16 is selected from C, N, and C(R 1q ), Each R 1q is hydrogen, halogen, -CN, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 2-6 member heteroalkyl, 2-6 member heteroalkenyl, 2-6 member heteroalkynyl, -C0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected independently of C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 2-6 member heteroalkenyl, 2-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20Either it is optionally substituted, or two R atoms are bonded to the same carbon. 1q These are linked together to form a 3- to 10-membered complex ring or C 3-10 It forms a carbon ring, a 3-10 membered heterocycle and C 3-10 A carbon ring is one or more R 20 Either it is optionally substituted, or two R atoms are bonded to adjacent atoms. 1q These are linked together to form a 3- to 10-membered complex ring or C 3-10 It forms a carbon ring, a 3-10 membered heterocycle and C 3-10 A carbon ring is one or more R 20 It is either optionally replaced by one R 1q and one R 1r These are linked together to form a 3- to 10-membered complex ring or C 3-10 It forms a carbon ring, a 3-10 membered heterocycle and C 3-10 A carbon ring is one or more R 20 It is optionally replaced by, Each R 1r is hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynnyls, 3-10 membered heterocycles, and C 3-10 Selected independently from the carbon ring, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynnyls, 3-10 membered heterocycles, and C 3-10 A carbon ring is one or more R 20 It is optionally replaced by, and each [ka] These independently represent single or double bonds in which all valencies are satisfied.

[0079] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 17 teeth, [ka] [ka] [ka] [ka] Selected from.

[0080] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 17 teeth, [ka] Selected from.

[0081] In embodiments of compounds of formula I, IA, IB, II, or IIA, X 8 C(R 8 )

[0082] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 8 It is a halogen.

[0083] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 8 It is -F.

[0084] In embodiments of compounds of formula I, IA, IB, II, or IIA, the compound has the following formula: [ka]

[0085] In embodiments of compounds of formula IA, IB, or IIA, the compound has the following formula: [ka] X 6 C(R 6 ), C(R 6 )2, N, and N(R 6b ) are selected from, X 7C(R 7 ) and N(R 7b ) are selected from, X 8 C(R 8 ) and C(R 8 ) Selected from 2, and L 7a L is a bond, 7b It is a combination.

[0086] In embodiments of compounds of formula IA, IB, or IIA, the compound has the following formula: [ka]

[0087] In one embodiment, formula BL BE A compound having -E is provided, in which, B is a monovalent form of the compound described herein, L BE This is a covalent linker bonded to B and E, E is a monovalent form of the decomposition accelerator.

[0088] formula BL BEIn embodiments of the compound -E, the decomposition accelerators are E3A, mdm2, APC, EDD1, SOCS / BC-box / eloBC / CUL5 / RING, LNXp80, CBX4, CBLL1, HACE1, HECTD1, HECTD2, HECTD3, HECTD4, HECW1, HECW2, HERC1, HERC2, HERC3, HERC4, HER5, HERC6, HUWE1, ITCH, NEDD4, NEDD4L, PPIL2, PRPF19, PIAS1, PIAS2, PI AS3, PIAS4, RANBP2, RNF4, RBX1, SMURF1, SMURF2, STUB1, TOPORS, TRIP12, UBE3A, UBE3B, UBE3C, UBE3D, UBE4A, UBE4B, UBOX5, UBR5, VHL (von-Hippel-Lindau ubiquitin ligase), WWP1, WWP2, Parkin, MKRN1, CMA (chaperone-mediated autophagy) autophage), SCFb-TRCP (Skip-Cullin-F box (beta-TRCP) ubiquitin complex), b-TRCP (b-transducing repeat-containing protein), cIAP1 (cell inhibitor of apoptosis protein 1), APC / C (late-stage accelerating complex / cyclosome), CRBN (cereblon), CUL4-RBX1-DDB1-CRBN (CRL4 CRBN It is possible to bind to proteins selected from ubiquitin ligase, XIAP, IAP, KEAP1, DCAF15, RNF114, DCAF16, AhR, SOCS2, KLHL12, UBR2, SPOP, KLHL3, KLHL20, KLHDC2, SPSB1, SPSB2, SPSB4, SOCS6, FBXO4, FBXO31, BTRC, FBW7, CDC20, PML, TRIM21, TRIM24, TRIM33, GID4, abadomide, iverdimide, and CC-885.

[0089] In embodiments of the compound of formula IB-LBE-E, the degradation accelerator can bind to proteins selected from UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2DR, UBE2E1, UBE2E2, UBE2E3, UBE2F, UBE2G1, UBE2G2, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2K, UBE2L3, UBE2L6, UBE2L1, UBE2L2, UBE2L4, UBE2M, UBE2N, UBE2O, UBE2Q1, UBE2Q2, UBE2R1, UBE2R2, UBE2S, UBE2T, UBE2U, UBE2V1, UBE2V2, UBE2W, UBE2Z, ATG3, BIRC6, and UFC1.

[0090] formula BL BE In the embodiment of compound -E, L BE is, -L BE1 -L BE2 -L BE3 -L BE4 -L BE5 -and, L BE1 , L BE2 , L BE3 , L BE4 , and L BE5 These are independently, bonded, -O-, -N(R 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -S(O)2N(R 12 )-,-S(O)N(R 12 )-,-N(R 12 )S(O)-, -N(R 12 )S(O)2-, C 1-6 Alkylene, (-OC 1-6 Alkyl) z -, (-C 1-6 Alkyl-O) z -, C 2-6 Alkenylene, C 2-6 Alkinylene, C 1-6 Haloalkylene, C 3-12 Cycloalkylene, C 1-11 Heterocycloalkylene, C6-12 Arirene, or C 1-11 It is a heteroarylene, C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkinylene, C 1-6 Haloalkylene, C 3-12 Cycloalkylene, C 1-11 Heterocycloalkylene, C 6-12 Arirene, or C 1-11 Heteroarrenes have one, two, or three R 20 It is optionally replaced by (-OC 1-6 Alkyl) z - and (-C 1-6 Alkyl-O) z - Each C 1-6 Alkyls have one, two, or three R's. 20 It is optionally replaced by, and z is an independent integer between 0 and 10.

[0091] formula BL BE In the embodiment of compound -E, L BE is -(O-C2 alkyl) z - and z is an integer between 1 and 10.

[0092] formula BL BE In the embodiment of compound -E, L BE is -(C2alkyl-O-) z - and z is an integer between 1 and 10.

[0093] formula BL BE In the embodiment of compound -E, L BE is, -(CH2) zz1 L BE2 (CH2O) zz2 -and in this case, L BE2 This refers to the bonding of 5-membered or 6-membered heterocycloalkylenes or heteroarylenes, phenylenes, and -C. 2-4 The element is an alkynylene, -SO2- or -NH-, and zz1 and zz2 are independent integers between 0 and 10.

[0094] formula BL BE In the embodiment of compound -E, L BE is, -(CH2) zz1 (CH2O) zz2 -In this case, zz1 and zz2 are each independent integers between 0 and 10.

[0095] formula BL BE In the embodiment of compound -E, L BE This is a PEG linker.

[0096] formula BL BE -In the embodiment of compound E, E is [ka] It is a monovalent form of the compound selected from the above.

[0097] In one embodiment, a pharmaceutical composition is provided comprising the substance described herein or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

[0098] In one embodiment, a method for modifying a Ras mutant protein is provided, which comprises contacting the Ras mutant protein with an effective amount of a compound, salt, or solvate described herein.

[0099] In embodiments of the methods described herein, the modified Ras mutant protein exhibits reduced output of Ras signaling.

[0100] In embodiments of the methods described herein, the reduction in Ras signaling output is demonstrated by one or more outputs selected from (i) an increase in the steady-state level of GDP-bound modified protein, (ii) a decrease in the steady-state level of GTP-bound modified protein, (iii) a decrease in phosphorylated AKTs473, (iv) a decrease in phosphorylated ERK T202 / Y204, (v) a decrease in phosphorylated S6 S235 / 236, (vi) a decrease in cell proliferation of tumor cells expressing the Ras G12S mutant protein, and (vii) a decrease in Ras interaction with Ras pathway signaling proteins.

[0101] In embodiments of the methods described herein, the Ras mutant protein contains an amino acid sequence in SEQ ID NO: 4 having a serine residue corresponding to position 12 of SEQ ID NO: 1.

[0102] In embodiments of the methods described herein, the Ras mutant protein comprises the amino acid sequence of SEQ ID NO: 4.

[0103] In embodiments of the methods described herein, the modified Ras mutant protein comprises the amino acid sequence of SEQ ID NO: 1, or a fragment thereof containing a serine residue corresponding to position 12 of SEQ ID NO: 1, wherein the compound selectively labels a serine residue compared to (i) an aspartic acid residue of the K-Ras G12D mutant protein, the aspartic acid corresponding to position 12 of SEQ ID NO: 2, (ii) a valine residue of the K-Ras G12V mutant protein, the valine corresponding to position 12 of SEQ ID NO: 3, and / or (iii) a glycine residue of the K-Ras wild-type protein, the glycine corresponding to position 12 of SEQ ID NO: 1.

[0104] In embodiments of the methods described herein, when analyzed under equivalent conditions, the compound selectively labels serine residues at least twice.

[0105] In embodiments of the methods described herein, when analyzed under equivalent conditions, the compound selectively labels serine residues at least 5-fold.

[0106] In embodiments of the methods described herein, contact occurs in vivo.

[0107] In one embodiment, a method is provided for treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof.

[0108] In one embodiment, a method is provided for treating a cancer containing a Ras mutant protein in a subject, the method comprising inhibiting the Ras mutant protein in the subject by administering a compound described herein to the subject, characterized in that, upon contact with the Ras mutant protein, the compound causes the Ras mutant protein to exhibit a decrease in the output of Ras signaling.

[0109] In embodiments of the methods described herein, cancer is a solid tumor or a hematological cancer.

[0110] In embodiments of the methods described herein, the cancer comprises a K-Ras G12S mutant protein.

[0111] In one embodiment, a method is provided for modulating the signaling output of a Ras protein, the method comprising contacting the Ras protein with an effective amount of one of the compounds described herein, or a pharmaceutically acceptable salt or solvate thereof, thereby modulating the signaling output of the Ras protein.

[0112] In one embodiment, a method is provided for inhibiting cell proliferation, which includes administering an effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, to cells expressing the Ras protein, thereby inhibiting the proliferation of said cells.

[0113] In embodiments of the methods described herein, the method includes administering an additional agent.

[0114] In embodiments of the methods described herein, additional agents include: (1) MEK inhibitors, (2) inhibitors of epidermal growth factor receptor (EGFR) and / or its variants, (3) immunotherapeutic agents, (4) taxanes, (5) antimetabolites, (6) inhibitors of FGFR1 and / or FGFR2 and / or FGFR3 and / or their variants, (7) mitotic kinase inhibitors, (8) anti-angiogenic agents, (9) topoisomerase inhibitors, (10) platinum-containing compounds, (11) inhibitors of c-MET and / or its variants, (12) inhibitors of BCR-ABL and / or its variants, (13) inhibitors of ErbB2 (Her2) and / or its variants, (14) inhibitors of AXL and / or its variants, (15) NTRK1 and / or its variants Inhibitors of different organisms, (16) RET and / or its variants, (17) A-Raf and / or B-Raf and / or C-Raf and / or their variants, (18) ERK and / or its variants, (19) MDM2 inhibitors, (20) mTOR inhibitors, (21) IGF1 / 2 and / or IGF1-R inhibitors, (22) CDK9 inhibitors, (23) Farnesyltransferase inhibitors, (24) SHIP pathway inhibitors, (25) SRC inhibitors, (26) JAK inhibitors, (27) PARP inhibitors, (28) ROS1 inhibitors, (29) SHP pathway inhibitors, (30) Src, FLT3, HDAC, VEGFR, PDGFR, LCK, Bcr-Abl or AKT inhibitors, (31) Kras (32) G12C inhibitors, (33) SHC inhibitors, (34) GAB inhibitors, (35) PI-3 kinase inhibitors, (36) MARPK inhibitors, (37) CDK4 / 6 inhibitors, (38) MAPK inhibitors, (39) SHP2 inhibitors, (40) checkpoint immunoblockers, (41) SOS1 inhibitors, or (42) SOS2 inhibitors.

[0115] In embodiments of the methods described herein, additional agents include RMC-4630, ERAS-601, [ka] Includes an inhibitor of SHP2 selected from the following.

[0116] In embodiments of the methods described herein, additional agents include RMC-5845, BI-1701963, [ka] Includes an SOS inhibitor selected from among the following.

[0117] In embodiments of the methods described herein, additional agents include EGFR inhibitors selected from afatinib, erlotinib, gefitinib, lapatinib, cetuximab, panitumumab, osimertinib, olmutinib, and EGF-816.

[0118] In embodiments of the methods described herein, additional agents include MEK inhibitors selected from trametinib, cobimetinib, binimetinib, selumetinib, refametinib, and AZD6244.

[0119] In embodiments of the methods described herein, additional agents include ERK inhibitors selected from urixerutinib, MK-8353, LTT462, AZD0364, SCH772984, BIX02189, LY3214996, and laboxerutinib.

[0120] In embodiments of the methods described herein, the additional agent comprises a CDK4 / 6 inhibitor selected from palbociclib, ribociclib, and abemaciclib.

[0121] In embodiments of the methods described herein, additional agents include inhibitors of BRAF selected from sorafenib, vemurafenib, dabrafenib, encorafenib, regorafenib, and GDC-879.

[0122] Reference All publications, patents, and patent applications referenced herein are incorporated by reference to the same extent as any individual publication, patent, or patent application is specifically and individually indicated to be incorporated by reference. [Brief explanation of the drawing]

[0123] Novel features of the present invention are described in detail in the appended claims. A better understanding of the features and advantages of the present invention can be obtained by referring to the following detailed description which includes exemplary embodiments and accompanying drawings in which the principles of the present invention are utilized.

[0124] [Figure 1] Figure 1 shows the top-to-bottom sequence alignment of various wild-type Ras proteins, including K-Ras, H-Ras, N-Ras, RalA, and RalB. [Modes for carrying out the invention]

[0125] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which this disclosure belongs. If there are multiple definitions of a term herein, the definition in this section shall prevail. All patents, patent applications, publications, and published nucleotide and amino acid sequences (e.g., sequences available in GenBank or other databases) referenced herein are incorporated by reference. Chemical structures are named herein in accordance with the IUPAC agreement as implemented in the ChemDraw® software (Perkin Elmer, Inc., Cambridge, MA). Section headings used herein are merely structural and should not be construed as limiting the subject matter described. Where used herein and in the claims, the singular forms “a,” “an,” and “the” also include plural references unless the context clearly indicates otherwise. Furthermore, the use of the term “including,” as with other forms such as “include,” “includes,” and “included,” is not limited to these. The section headings used in this specification are for structural purposes only and should not be interpreted as limiting the subject matter described herein.

[0126] When used in conjunction with chemical parts such as alkyl, alkenyl, or alkynyl, "C x-y " or "C x -C y The term "C" means a group containing x to y carbon atoms in the chain. For example, "C x-y The term "alkyl" refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain and branched-chain alkyl groups, that contain x to y carbon atoms in their chain.

[0127] "Alkyl" refers to substituted or unsubstituted saturated hydrocarbon groups, including linear and branched alkyl groups. Alkyl groups consist of 1 to 12 carbon atoms (for example, C 1-12 Alkyl), for example, 1 to 8 carbon atoms (C 1-8Alkyl) or 1 to 6 carbon atoms (C 1-6 The molecule may contain alkyl groups. Exemplary alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, septyl, octyl, nonyl, and decyl. The alkyl group is attached to the rest of the molecule by a single bond. Unless otherwise expressly stated herein, the alkyl group is optionally substituted with one or more substituents, such as substituents described herein.

[0128] The term "haloalkyl" refers to an alkyl group that is substituted with one or more halogens. Examples of haloalkyl groups include trifluoromethyl, difluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, and 1,2-dibromoethyl.

[0129] "Alkenyl" refers to a substituted or unsubstituted hydrocarbon group that contains a linear or branched alkenyl group containing at least one double bond. An alkenyl group has 2 to 12 carbon atoms (for example, C 2-12 Alkenyls), for example, 2 to 8 carbon atoms (C 2-8 Alkenyl) or 2-6 carbon atoms (C) 2-6 The material may contain an alkenyl group. Examples of alkenyl groups include ethenyl (i.e., vinyl), propa-1-enyl, buta-1-enyl, penta-1-enyl, and penta-1,4-dienyl. Unless otherwise specified herein, the alkenyl group may be optionally substituted with one or more substituents, such as those described herein.

[0130] "Alkynyl" refers to a substituted or unsubstituted hydrocarbon group containing a linear or branched alkynyl group with at least one triple bond. An alkynyl group has 2 to 12 carbon atoms (e.g., C 2-12 Alkynyl), for example, 2 to 8 carbon atoms (C 2-8Alkynyl) or 2-6 carbon atoms (C) 2-6 The material may contain an alkynyl group. Examples of alkynyl groups include ethynyl, propynyl, butynyl, pentynyl, and hexynyl. Unless otherwise specified herein, the alkynyl group may be optionally substituted with one or more substituents, such as those described herein.

[0131] "Alkylene" or "alkylene chain" consists of 1 to 12 carbon atoms (for example, C 1-12 Alkylenes), for example, 1 to 8 carbon atoms (C) 1-8 Alkylene) or 1 to 6 carbon atoms (C) 1-6 This refers to substituted or unsubstituted divalent saturated hydrocarbon groups, including linear alkylene groups and branched alkylene groups containing alkylene. Examples of alkylene groups include methylene, ethylene, propylene, and n-butylene. Similarly, "alkenylene" and "alkynylene" refer to the alkylene groups defined above, each containing one or more carbon-carbon double or triple bonds. The bonding sites of the alkylene, alkenylene, or alkynylene chains to the rest of the molecule may be via one carbon or any two carbons of the chain. Unless otherwise specified herein, the alkylene, alkenylene, or alkynylene groups are optionally substituted with one or more substituents, such as those described herein.

[0132] "Heteroalkyl," "heteroalkenyl," and "heteroalkynyl" refer to substituted or unsubstituted alkyl, alkenyl, and alkynyl groups, respectively, in which one or more carbon atoms, e.g., 1, 2, or 3, are substituted with heteroatoms such as O, N, P, Si, S, or combinations thereof. Any nitrogen, phosphorus, and sulfur heteroatoms present in the chain may be optionally oxidized, and any nitrogen heteroatom may be optionally quaternized. Where a numerical range is specified, it refers to the total chain length. For example, a 3- to 8-membered heteroalkyl group has a chain length of 3 to 8 atoms. Connection to the rest of the molecule may occur via any heteroatoms or carbons in the heteroalkyl chain, heteroalkenyl chain, or heteroalkynyl chain. Unless otherwise specified herein, heteroalkyl groups, heteroalkenyl groups, or heteroalkynyl groups are optionally substituted with one or more substituents, such as substituents described herein.

[0133] "Heteroalkylene," "heteroalkenylene," and "heteroalkylynylene" refer to substituted or unsubstituted alkylene, alkenylene, and alkylylene groups, respectively, in which one or more carbon atoms, e.g., 1, 2, or 3, are substituted with heteroatoms such as O, N, P, Si, S, or combinations thereof. Any nitrogen, phosphorus, and sulfur heteroatoms present in the chain may be optionally oxidized, and any nitrogen heteroatom may be optionally quaternized. If a numerical range is specified, it refers to the total chain length. For example, a 3- to 8-membered heteroalkylene group has a chain length of 3 to 8 atoms. Bonding sites of a heteroalkylene, heteroalkenylene, or heteroalkylynylene chain to the rest of the molecule may be via one heteroatom or one carbon in the heteroalkylene, heteroalkenylene, or heteroalkylynylene chain, or via any two heteroatoms, any two carbons, or any one heteroatom and any one carbon. Unless otherwise specified herein, heteroalkylene, heteroalkenylene, or heteroalkylynylene groups are optionally substituted with one or more substituents, such as substituents described herein.

[0134] A "carbon ring" refers to a saturated, unsaturated, or aromatic ring in which each atom of the ring is a carbon atom. 3-10 Monocyclic ring, C 5-12 Bicyclic ring, C 5-18 polycyclic ring, C 5-12 Spirocyclic rings, and C 5-12 It may include a bridging ring. Each ring in the bicyclic or polycyclic carbocyclic ring may be selected from saturated, unsaturated, and aromatic rings. The polycyclic carbocyclic ring contains a number of rings equal to the minimum number of cleavage required to convert the carbocyclic ring into an acyclic skeleton (e.g., bicyclic, tricyclic, tetracyclic, etc.). In some embodiments, the carbocyclic ring is C 6-10 C such as aryl 6-12 It is an aryl group. In some embodiments, the carbon ring is C 3-12 It is a cycloalkyl group. In some embodiments, the carbon ring is C 5-12It is a cycloalkenyl group. In exemplary embodiments, an aromatic ring, for example, phenyl, may be condensed to a saturated or unsaturated ring, for example, cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic rings is included in the definition of a carbocyclic ring, as long as the valence allows. A carbocyclic ring may include a fused ring, a bridging ring, a spirocyclic ring, a saturated ring, an unsaturated ring, an aromatic ring, or any combination thereof. Exemplary carbocyclic rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantly, phenyl, indanyl, and naphthyl. Unless otherwise specified herein, a carbocyclic ring may be substituted with one or more substituents, such as substituents described herein.

[0135] A "heterocycle" refers to a saturated, unsaturated, or aromatic ring containing one or more heteroatoms, e.g., 1, 2, 3, or 4 heteroatoms selected from O, S, P, and N. Heterocycles include 3- to 10-membered monocyclic rings, 5- to 12-membered bicyclic rings, 5- to 18-membered polycyclic rings, 5- to 12-membered spirocyclic rings, and 5- to 12-membered bridging rings. Each ring in bicyclic and polycyclic heterocycles may be selected from saturated, unsaturated, and aromatic rings. Polycyclic heterocycles contain a number of rings equal to the minimum number of cleavage required to convert the heterocycle into an acyclic skeleton (e.g., bicyclic, tricyclic, tetracyclic, etc.). Heterocycles may be bonded to the rest of the molecule via any atom of the heterocycle, such as a carbon or nitrogen atom of the heterocycle, as long as the valence allows. In some embodiments, the heterocycle is a 5- to 10-membered heteroaryl group, e.g., a 5 or 6-membered heteroaryl. In some embodiments, the heterocycle is a 3- to 12-membered heterocycloalkyl group. The heterocycle may include a fused ring, a crosslinked ring, a spirocyclic ring, a saturated ring, an unsaturated ring, an aromatic ring, or any combination thereof. In exemplary embodiments, the heterocycle, for example, pyridyl, may be fused to a saturated or unsaturated ring, for example, cyclohexane, cyclopentane, or cyclohexene. Examples of exemplary heterocycles include pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, pyrimidinyl, pyridadinyl, pyrazinyl, thiophenyl, oxazolyl, thiazolyl, morpholinyl, indazolyl, indolyl, benzothienyl, benzoxazolyl, and quinolinyl. Unless otherwise specified herein, the heterocycle may be substituted with one or more substituents, such as substituents described herein.

[0136] A "heteroaryl" refers to an aromatic ring containing one or more heteroatoms, e.g., one, two, three, or four heteroatoms selected from O, S, and N. Heteroaryls include 5-10 membered monocyclic rings, 6-12 membered bicyclic rings, 6-18 membered polycyclic rings, 5-12 membered spirocyclic rings, and 6-12 membered bridging rings. As used herein, heteroaryl rings may be selected from monocyclic, bicyclic, or polycyclic systems, including fused rings, spirocyclic rings, and bridging ring systems, in which case at least one of the rings in the ring system is aromatic and contains at least one heteroatom. Polycyclic heteroaryls contain a number of rings equal to the minimum number of cleavage required to convert the heteroaryl to an acyclic skeleton (e.g., bicyclic, tricyclic, tetracyclic, etc.). Heteroatoms in a heteroaryl may be oxidized. If one or more nitrogen atoms are present, they may be quaternized. Heteroaryl groups may be bonded to the rest of the molecule via any atom of the heteroaryl, such as a carbon or nitrogen atom of the heteroaryl, as long as the valence allows. Examples of heteroaryl groups include, but are not limited to, azepinyl, benzimidazolyl, benzisothiazolyl, benzisoxazolyl, benzofuranyl, benzothiazolyl, benzothiophenyl, benzoxazolyl, furanyl, imidazolyl, indazolyl, indolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, purinyl, pyrazinyl, pyrazolidinyl, pyrazolyl, pyridadinyl, pyridazolyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydroquinolinyl, thiadiazolyl, thiazolyl, and thienyl groups. Unless otherwise specified herein, heteroaryl groups may be substituted with one or more substituents, such as those described herein.

[0137] Unless otherwise stated, hydrogen atoms are implied to be necessary to satisfy the valence requirements in the structures depicted herein.

[0138] A wavy line drawn across the joint or at the end of the joint. [ka] Or a dashed line connection [ka] The terms are used interchangeably in this specification to indicate a break in bonding or the occurrence of bonding. For example, structure [ka] In R 7 but, [ka] If it is 2-fluoro-6-hydroxyphenyl, then R 7 teeth, [ka] It can be depicted as such.

[0139] The term “substitution” refers to a portion of a structure having substituents that substitute for hydrogen atoms on one or more carbon atoms or heteroatoms. It will be understood that “substitution” or “substituted with” implicitly implies that such substitution conforms to the acceptable valencies of the substituted atom and substituent, and that the substitution results in a stable compound that does not undergo spontaneous transformation, such as rearrangement, cyclization, or elimination. As used herein, the term substitution is intended to include all acceptable substituents of an organic compound. In broad embodiments, acceptable substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of an organic compound. There may be one or more acceptable substituents for a given organic compound, and they may be identical or different. For the purposes of this disclosure, a heteroatom, such as nitrogen, may have any of the acceptable substituents of the organic compounds described herein that satisfy the valency of the heteroatom.

[0140] The compounds disclosed herein, for example, compounds of formula I, IA, IB, II, or IIA, are optionally substituted with one or more substituents selected from the following, for example, one, two, or three substituents: Halogen, oxo, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 2-6 member heteroalkenyl, 2-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 )-, and -S(=O)(=NR 22 )N(R 22 )(R 23 ) and in this case, C1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 2-6 member heteroalkenyl, 2-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle),-(2-6 member heteroalkyl)-(3-12 member heterocycle), C 3-12 Carbon rings and 3- to 12-membered heterocycles are halogens, oxo, -CN, and C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23) is optionally substituted with one or more substituents independently selected from the original, R 21 These are independent of each other, for each entity, hydrogen, halogen, and C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 membered heterocycle), or two R 21 However, they are grouped together with the carbon atoms to which they are added and C 3-12 They form a carbon ring or a 3- to 12-membered heterocycle, each of which is a halogen, C 1-3 Alkyl, C 1-3 Optionally substituted with one, two, or three substituents independently selected from haloalkyl and -OH groups, R 22 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 membered heterocycle), in this case, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3-12 member heterocycle) is associated with halogens and C 1-6 Selected independently of alkyl, and R 23 These are independent of each other, for each existence, hydrogen and C 1-6 R selected from alkyl groups or added to the same nitrogen atom 22 and R 23 However, it forms a 3- to 10-membered heterocyclic ring.

[0141] In some embodiments, the compounds disclosed herein, for example, compounds of formula I, IA, IB, II, or IIA, are optionally substituted with one or more substituents selected from the following, for example, one, two, or three substituents: Halogen, Oxo, -CN, C1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 2-6 member heteroalkenyl, 2-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 , and -S(O)2N(R 22 )(R 23 )-and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 2-6 member heteroalkenyl, 2-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6Alkyl-(3-12 member heterocycle),-(2-6 member heteroalkyl)-(3-12 member heterocycle), C 3-12 Carbon rings and 3- to 12-membered heterocycles are halogens, oxo, -CN, and C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , and =C(R 21 ) Optionally substituted with one or more substituents independently selected from 2, R 21 These are independent of each other, for each entity, hydrogen, halogen, and C 1-6 Alkyl, and C 1-6 Selected from haloalkyls, R 22 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 membered heterocycle), in this case, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3-12 member heterocycle) is associated with halogens and C 1-6 Selected independently of alkyl, R 23 These are independent of each other, for each existence, hydrogen and C 1-6 R selected from alkyl groups or added to the same nitrogen atom 22 and R 23 However, it forms a 3- to 10-membered heterocyclic ring.

[0142] In some embodiments, the compounds disclosed herein, for example, compounds of formula I, IA, IB, II, or IIA, are halogens, oxo, =NH, -CN, -NO2, C 1-6 Alkyl, C2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Carbocycle, -CH2-(C 3-10 One or more substituents selected from a carbon ring, a 3- to 10-membered heterocycle, -CH2-(3- to 10-membered heterocycle), -OH, -OCH3, -OCH2CH3, -NH2, -NHCH3, and -NHCH2CH3, for example, optionally substituted by 1, 2, or 3 substituents, in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-10 Carbocycle, -CH2-(C 3-10 Carbon rings, 3- to 10-membered heterocycles, and -CH2-(3- to 10-membered heterocycles) are optionally substituted with 1, 2, or 3 groups independently selected from halogens, oxo, =NH, -CN, -NO2, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -OH, -OCH3, -OCH2CH3, -NH2, -NHCH3, and -NHCH2CH3.

[0143] It will be understood by those skilled in the art that, where appropriate, the substituents themselves may be substituted. Unless specifically stated as “unsubstituted,” references to chemical parts herein should be understood to include substituted variants. For example, references to “heteroaryl” groups or parts implicitly include both substituted and unsubstituted variants.

[0144] Where divalent substituents are specified herein by their conventional chemical formulas written from left to right, they are intended to encompass isomers resulting from describing the structure from right to left; for example, -CH2O- is intended to also encompass -OCH2-.

[0145] "Optional" or "optionally" means that the event or situation described afterward may or may not occur, and the description includes both cases where the event or situation occurs and cases where it does not. For example, a base that is "optionally substituted" may be either non-substituted or substituted.

[0146] The compounds of this disclosure also include crystalline and amorphous forms of those compounds, pharmaceutically acceptable salts, and active metabolites having the same type of activity, which include, for example, polymorphs, pseudopolymorphs, solvates, hydrates, non-solvated polymorphs (including anhydrous forms), conformational polymorphs, amorphous forms of the compounds, and mixtures thereof.

[0147] The compounds described herein may exhibit their natural isotopic abundance, or one or more atoms may be artificially enriched into specific isotopes having the same atomic number but with atomic masses or mass numbers different from those primarily found in nature. All isotopic variations of the compounds disclosed herein, whether radioactive or not, are included within the scope of this disclosure. For example, hydrogen, 1 H (protium), 2 H (deuterium), and 3 It has three natural isotopes represented by H (tritium). Protium is the most abundant isotope of hydrogen in nature. Deuterium enrichment may result in certain therapeutic benefits, such as increased in vivo half-life and / or exposure, or may provide compounds useful for investigating in vivo drug elimination and metabolic pathways. Examples of isotopes that may be incorporated into the compounds of this disclosure include: 2 H, 3 H, 13 C, 14 C, 15 N, 18 O, 17 O, 35 S, 36 Cl, and 18F is one example, but is not limited to these. Of particular note are the tritium or carbon-14-rich compounds of formulas I, IA, IB, II, or IIA, which can be used in tissue distribution studies, and the deuterium-rich compounds of the disclosure that produce compounds with high metabolic stability at metabolic sites, and which can be used, for example, in positron emission topography (PET) studies. 11 C, 18 F, 15 O, and 13 These are compounds of formula I, IA, IB, II, or IIA that are rich in positron-emitting isotopes such as N. Isotopic-enriched compounds can be prepared by conventional techniques known to those skilled in the art.

[0148] As used herein, the terms “formula,” “having a formula,” or “having a structure” are not intended to be limiting, but are used in the same manner as the term “including.” For example, if a structure is illustrated, it is understood that all stereoisomers and tautomers are included unless otherwise stated.

[0149] Certain compounds described herein contain one or more chiral centers, and thus can give rise to enantiomers, diastereomers, and other stereoisomeric forms, the chiral centers of which may be defined as (R)- or (S)- from the viewpoint of absolute stereochemistry. In some embodiments, in order to optimize the therapeutic activity of the compounds of this disclosure, for example to treat fibrosis, it may be desirable for the carbon atoms to have a specific configuration (e.g., (R,R), (S,S), (S,R), or (R,S)) or to be enriched with stereoisomeric forms having such configurations. The compounds of this disclosure may be provided as racemic mixtures. Accordingly, this disclosure relates to racemic mixtures, pure stereoisomers (e.g., enantiomers and diastereomers), stereoisomer-enriched mixtures, etc., unless otherwise indicated. When a chemical structure is illustrated herein without any stereochemistry, it is understood that all possible stereoisomers are encompassed by such structure. Similarly, where a particular stereoisomer is shown or named herein, a person skilled in the art will understand, unless otherwise suggested, that small amounts of other stereoisomers may be present in the compositions of this disclosure, provided that the usefulness of the composition as a whole is not diminished by the presence of such other isomers. Individual stereoisomers can be obtained by a number of methods known in the art, including preparation using chiral synthons or chiral reagents, resolution using chiral chromatography with a suitable chiral stationary phase or support, or chemical conversion of them into diastereomers, separation of the diastereoisomers by conventional means such as chromatography or recrystallization, and then regeneration of the original stereoisomers.

[0150] Furthermore, where applicable, all cis-trans or E / Z isomers (geometric isomers), tautomers, and topoisomers of the compounds described herein are included in the scope of this disclosure unless otherwise specified.

[0151] The term “pharmaceutically acceptable” refers to a substance that, when used in the composition and method of the subject, is not biologically or otherwise unacceptable. For example, the term “pharmaceutically acceptable carrier” refers to a substance such as an adjuvant, excipient, flow enhancer, sweetener, diluent, preservative, pigment, colorant, flavor enhancer, surfactant, humectant, dispersant, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier that can be incorporated into a composition and administered to a patient without causing unacceptable biological effects or interacting with other components of the composition in an unacceptable manner. Such pharmaceutically acceptable substances typically include substances that meet the required standards of toxicological and manufacturing testing and have been identified as appropriate inactive ingredients by the U.S. Food and Drug Administration.

[0152] The terms “salt” and “pharmaceutically acceptable salt” refer to salts prepared from a base or acid. Pharmaceutically acceptable salts are suitable for administration to patients, such as mammals (e.g., salts that have acceptable mammalian safety for a given drug regimen). Salts can be formed from inorganic bases, organic bases, inorganic acids, and organic acids. Furthermore, if a compound contains both a basic moiety, such as an amine, pyridine, or imidazole, and an acidic moiety, such as a carboxylic acid or tetrazole, a zwitterion may be formed, which, as used herein, is included in the term “salt.” Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0153] "Pharmacologically acceptable acid addition salts" refer to salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, and phosphorous acid, which retain the biological effects and properties of the free base and are not biologically or otherwise undesirable. Salts formed with organic acids such as aliphatic mono and dicarboxylic acids, phenyl-substituted alkanes, hydroxyalkanoates, alkanedioates, aromatic acids, and aliphatic and aromatic sulfonic acids are also included, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid. Therefore, exemplary salts include sulfates, disulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, trifluoroacetates, propionates, caprylates, isobutyrates, oxalates, malonates, succinates, suberates, sebacinates, fumarates, maleates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, phthalates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, malates, tartrates, and methanesulfonates. Amino acid salts such as alginates, glucons, and galacturons are also considered (see, for example, Berge SM et al., “Pharmaceutical Salts,” Journal of Pharmaceutical Science, 66:1-19 (1997)). Acid addition salts of basic compounds are prepared in some embodiments by contacting the free base form with a sufficient amount of the desired acid to produce the salt, according to methods and techniques familiar to those skilled in the art.

[0154] A "pharmaceutically acceptable base addition salt" refers to a salt that retains the biological efficacy and characteristics of a free acid and is not biologically or otherwise undesirable. These salts are prepared by adding an inorganic or organic base to a free acid. In some embodiments, pharmaceutically acceptable base addition salts are formed from metals or amines such as alkali metals and alkaline earth metals or organic amines. Examples of salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, and aluminum salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, N,N-dibenzylethylenediamine, chloroprocaine, hydravamin, choline, betaine, ethylenediamine, ethylenedianiline, N-methylglucamine, glucosamine, methylglucamine, theobromine, purine, piperazine, piperidine, N-ethylpiperidine, and polyamine resins. See the book by Berge et al. cited above.

[0155] The term “effective dose” or “therapeutic effective dose” refers to the amount of agent sufficient to produce a beneficial or desired result. The therapeutic effective dose may vary depending on one or more of the following: the subject and disease being treated, the subject’s weight and age, the severity of the disease, the mode of administration, etc., which can be readily determined by those skilled in the art. An effective dose of the active agent may be administered in single or multiple doses. Components may be described herein as having at least an effective dose, or at least an effective dose, such as those relevant to a specific target or purpose, such as any of those described herein. The term “effective dose” also applies to doses that will provide an image for detection by a suitable imaging method. The specific dose may vary depending on one or more of the particular agent selected, the administration regimen to be followed, whether or not it is administered concomitantly with other compounds, the timing of administration, the tissue being imaged, and the physical delivery system to which the agent is carried.

[0156] As used herein, “to treat” or “to treat” means an approach to obtain a beneficial or desirable outcome with respect to a disease, disorder, or medical condition (such as cancer) in a subject, including but not limited to: (a) preventing the onset of the disease or medical condition, e.g., preventing recurrence of the disease or medical condition, or prophylactic treatment in a subject susceptible to the disease or medical condition; (b) improving the disease or medical condition, e.g., eliminating or causing regression of the disease or medical condition in a subject; (c) suppressing the disease or medical condition, e.g., slowing or halting its progression in a subject; or (d) reducing the symptoms of the disease or medical condition in a subject. For example, “to treat cancer” includes preventing the onset of cancer, improving cancer, suppressing cancer, and reducing the symptoms of cancer. The therapeutic benefit is achieved by the elimination or improvement of one or more physiological symptoms associated with the underlying disorder, so that improvement is observed in the subject, even though the subject may still be suffering from the underlying disorder.

[0157] When the term “therapeutic effect” is used herein, it encompasses the therapeutic and / or preventive benefits described above. Preventive effects include delaying or eliminating the onset of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, delaying, halting, or reversing the progression of a disease or condition, or any combination thereof.

[0158] The terms “antagonist” and “inhibitor” are used interchangeably and refer to compounds that have the ability to inhibit the biological function (e.g., activity, expression, binding, protein-protein interactions) of a target protein (e.g., K-Ras). Therefore, the terms “antagonist” and “inhibitor” are defined in relation to the biological role of the target protein. Preferred antagonists as used herein are compounds that specifically interact with the target (e.g., bind), but also specifically inhibit the biological activity of the target protein by interacting with other members of the signaling pathway to which the target protein is a member.

[0159] The term "selective inhibition" or "selectively inhibiting" refers to the ability of a bioactive agent to preferentially reduce target signaling activity compared to extratarget signaling activity, either through direct or indirect interaction with the target.

[0160] The terms “subject” and “patient” refer to mammals, such as humans and other animals. The methods described herein may be useful for both human therapeutic and veterinary applications. In some embodiments, the subject is a mammal, such as a human. “Mammals” include humans, as well as both domesticated animals, such as laboratory animals and pets (e.g., cats, dogs, pigs, cows, sheep, goats, horses, rabbits), and non-domesticated animals such as wildlife.

[0161] The terms "therapeutic agent," "therapeutic drug," or "treatment agent" are used interchangeably and refer to molecules or compounds that, when administered to a subject, produce some beneficial effect. Beneficial effects include enabling diagnostic determination, improving a disease, symptom, disorder, or pathological condition, reducing or preventing the onset of a disease, symptom, disorder, or condition, and substantially counteracting a disease, symptom, disorder, or pathological condition.

[0162] The terms “polypeptide,” “peptide,” and “protein” are used interchangeably herein to refer to polymers of amino acids of any length. Polymers may be linear or branched, may contain modified amino acids, and may be interrupted by non-amino acids. These terms also encompass any other operations on modified amino acid polymers, such as the formation of disulfide bonds, glycosylation, lipidation, acetylation, phosphorylation, or binding with labeling components. As used herein, the term “amino acid” refers to any amino acid, whether natural and / or unnatural or synthetic, including glycine and both D or L optical isomers, as well as amino acid analogs and peptide mimetic compounds.

[0163] The terms “polynucleotide,” “nucleotide sequence,” “nucleic acid,” and “oligonucleotide” are used interchangeably. They refer to polymeric forms of nucleotides of any length, which are either deoxyribonucleotides or ribonucleotides, or analogues thereof. Polynucleotides can have any three-dimensional structure and can perform any known or unknown function. Non-limiting examples of polynucleotides include: coding or non-coding regions of genes or gene fragments, loci (groups of loci) defined from linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, small interfering RNA (siRNA), small hairpin RNA (shRNA), microRNA (miRNA), ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers. The polynucleotide may contain one or more modified nucleotides, such as methylated nucleotides and nucleotide analogs, e.g., peptide nucleic acids (PNA), morpholino and locked nucleic acids (LNA), glycol nucleic acids (GNA), threose nucleic acids (TNA), 2'-fluoro, 2'-OMe, and phosphorothiolated DNA. If present, modifications to the nucleotide structure may be made before or after polymer construction. The nucleotide sequence may be interrupted by non-nucleotide components. The polynucleotide may be further modified after polymerization, such as by binding to labeling components or other binding targets.

[0164] In this specification, “expression” refers to the process by which a polynucleotide is transcribed from a DNA template (to mRNA or other RNA transcripts, etc.), and / or the process by which the transcribed mRNA is subsequently translated into peptides, polypeptides, or proteins. The transcripts and encoded polypeptides may be collectively referred to as “gene products.” If the polynucleotide is derived from genomic DNA, expression may include the splicing of mRNA in eukaryotic cells.

[0165] An "antigen" is a portion or molecule containing an epitope that also specifically binds to an antibody. An "antigen-binding unit" can be the whole or a fragment (or group of fragments) of a full-length antibody, its structural variant, its functional variant, or a combination thereof. Full-length antibodies can be, for example, monoclonal antibodies, recombinant antibodies, chimeric antibodies, deimmunized antibodies, humanized antibodies, and human antibodies. Examples of full-length antibody fragments include variable heavy chains (VH), variable light chains (VL), and heavy chains (VHH or VL) found in camelids such as camels, llamas, and alpacas. H H) Examples include, but are not limited to, single-domain antibodies (sdAb, e.g., "nanobody") containing heavy chains (V-NAR domains) found in sharks, a single antigen-binding domain, Fv, Fd, Fab, Fab', F(ab')2, and "r IgG" (or semi-antibodies). Examples of modified antibody fragments include, but are not limited to, scFv, di-scFv, or bi(s)-scFv, scFv-Fc, scFv-zipper, scFab, Fab2, Fab3, diabodies, single-chain diabodies, tandem diabodies (Tandab's), tandem di-scFv, tandem tri-scFv, minibodies (e.g., (VH-VL-CH3)2, (scFv-CH3)2, ((scFv)2-CH3+CH3), ((scFv)2-CH3), or (scFv-CH3-scFv)2), and multibodies (e.g., triabodies or tetrabodies).

[0166] The terms “antibody” and “antibody group” include any antigen-binding unit, including but not limited to monoclonal antibodies, human antibodies, humanized antibodies, camelized antibodies, chimeric antibodies, and other epitope-binding fragments.

[0167] The term "prodrug" refers to a compound that can be converted under physiological conditions or by solvation to a biologically active compound as described herein (e.g., a compound of formula I, IA, IB, II, or IIA). Therefore, the term "prodrug" refers to a precursor of a pharmaceutically acceptable biologically active compound. A prodrug is inactive when administered to a subject but is converted in vivo to an active compound, for example, by hydrolysis. Prodrug compounds often offer advantages in mammalian organisms, such as solubility, histocompatibility, or delayed release (see, for example, Bundgard, H., Design of Prodrugs (1985), pp. 7-9, 21-24 (Elsevier, Amsterdam), Higuchi, T., et al., “Pro-drugs as Novel Delivery Systems,” (1987) ACSSymposium Series, Vol. 14, and Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, each of which is fully incorporated herein by reference). The term “prodrug” also means any covalent carrier that releases the active compound in vivo when such a prodrug is administered to a mammalian subject. Prodrugs of active compounds described herein are typically prepared by modifying functional groups present in the active compound so that the modification can be cleaved into the parent active compound, either through routine procedures or in vivo. Examples of prodrugs include compounds in which a hydroxyl group, amino group, or mercapto group is cleaved when the prodrug of the active compound is administered to a mammalian subject, thereby forming a free hydroxyl group, a free amino group, or a free mercapto group, respectively. Examples of prodrugs include, but are not limited to, acetic acid, formic acid, and benzoic acid derivatives of hydroxyl functional groups in the active compound, or acetamide, formamide, and benzamide derivatives of amine functional groups.

[0168] The term "in vivo" refers to events that occur within the body of the subject. The term "ex vivo" refers to events that initially occur outside the body of the subject in order to later apply them in vivo within the body of the subject. For example, ex vivo preparation may include preparing cells outside the body of the subject for the purpose of introducing the prepared cells into the body of the same or different subject. The term "in vitro" refers to events that occur outside the body of the subject. For example, an in vitro assay encompasses any assay performed outside the body of the subject. In vitro assays include cell-based assays in which living or dead cells are used. In vitro assays also include cell-free assays that do not use intact cells.

[0169] This disclosure also means that it encompasses in vivo metabolites of the disclosed compounds. Such products may arise, for example, from oxidation, reduction, hydrolysis, amidation, esterification, etc., of the administered compound, primarily due to enzymatic processes. Thus, this disclosure includes compounds produced by processes that involve administering the compounds disclosed herein to mammals for a period of time sufficient to obtain their metabolites. Such products are typically identified by administering the radiolabeled compounds of this disclosure to animals such as rats, mice, guinea pigs, monkeys, or humans in a detectable dose, allowing sufficient time for metabolism to occur, and then isolating the converted products from urine, blood, or other biological samples.

[0170] The term "Ras" or "RAS" refers to proteins of the rat sarcoma (Ras) superfamily of low molecular weight GTPases, such as the Ras subfamily. The Ras superfamily includes, but is not limited to, the Ras subfamily, Rho subfamily, Rab subfamily, Rap subfamily, Arf subfamily, Ran subfamily, Rheb subfamily, RGK subfamily, Rit subfamily, Miro subfamily, and unclassified subfamilies. In some embodiments, the Ras protein is selected from the group consisting of KRAS (also used interchangeably herein as K-Ras, K-ras, and Kras), HRAS (or H-Ras), NRAS (or N-Ras), MRAS (or M-Ras), ERAS (or E-Ras), RRAS2 (or R-Ras2), RALA (or RalA), RALB (or RalB), RIT1, and any combination thereof, for example, KRAS, HRAS, NRAS, RALA, RALB, and any combination thereof.

[0171] As used interchangeably herein, the terms “mutant Ras” and “Ras variant” refer to a Ras protein having one or more amino acid mutations relative to a common reference sequence such as the wild-type (WT) sequence. In some embodiments, the mutant Ras is selected from mutant KRAS, mutant HRAS, mutant NRAS, mutant MRAS, mutant ERAS, mutant RRAS2, mutant RALA, mutant RALB, mutant RIT1, and any combination thereof, for example, from mutant KRAS, mutant HRAS, mutant NRAS, mutant RALA, mutant RALB, and any combination thereof. In some embodiments, the mutation may be an introduced mutation, a naturally occurring mutation, or a mutation that does not exist naturally. In some embodiments, the mutation may be a substitution (e.g., a substituted amino acid), an insertion (e.g., the addition of one or more amino acids), or a deletion (e.g., the removal of one or more amino acids). In some embodiments, two or more mutations may be consecutive, discontinuous, or a combination thereof. In some embodiments, the mutation may be located at any position in Ras. In some embodiments, when optimally aligned, mutations may be present at positions 12, 13, 62, 92, 95, and 96 of Ras relative to SEQ ID NO: 1 (e.g., Y96D), or in any combination thereof. In some embodiments, a mutant Ras may contain approximately or at least approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 mutations. In some embodiments, a mutant Ras may contain up to approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 mutations.In some embodiments, the mutant Ras has a length of approximately or up to approximately 500, 400, 300, 250, 240, 233, 230, 220, 219, 210, 208, 206, 204, 200, 195, 190, 189, 188, 187, 186, 185, 180, 175, 174, 173, 172, 171, 170, 169, 168, 167, 166, 165, 160, 155, 150, 125, 100, 90, 80, 70, 60, 50 amino acids, or fewer than 50 amino acids. In some embodiments, the mutant amino acids are proteolytic amino acids, native amino acids, standard amino acids, non-standard amino acids, non-canonical amino acids, essential amino acids, non-essential amino acids, or non-native amino acids. In some embodiments, the mutant amino acid has a positively charged side chain, a negatively charged side chain, a polar uncharged side chain, a nonpolar side chain, a hydrophobic side chain, a hydrophilic side chain, an aliphatic side chain, an aromatic side chain, a cyclic side chain, an acyclic side chain, a basic side chain, or an acidic side chain. In some embodiments, the mutation includes a reactive moiety. In some embodiments, the substituted amino acid includes a reactive moiety. In some embodiments, mutant Ras can be further modified, such as by binding to a detectable label. In some embodiments, mutant Ras is a full-length polypeptide or a cleaved polypeptide. For example, mutant Ras may be a cleaved polypeptide containing residues 1-169 or residues 11-183 (e.g., residues 11-183 of mutant RALA or mutant RALB).

[0172] As used herein, when applied to amino acid residues in polypeptide sequences, the terms “corresponding to” or “correspond to” refer to the correspondence of the amino acid relative to a reference sequence when optimally aligned (for example, considering gaps, insertions, and mismatches, alignment may be the primary sequence alignment or the three-dimensional structural alignment of a folded protein). For example, the serine residue in the K-Ras G12S mutant refers to the serine corresponding to residue 12 of SEQ ID NO: 4, which can function as a reference sequence. For example, the aspartic acid residue in the K-Ras G12D mutant refers to the aspartic acid corresponding to residue 12 of SEQ ID NO: 2, which can function as a reference sequence. If an amino acid in a mutant Ras protein corresponds to a certain amino acid position in a wild-type Ras protein, the amino acid in the mutant Ras protein may be a different amino acid (for example, G12D, where the G at position 12 in the wild-type Ras protein is replaced with aspartic acid at position 12 of SEQ ID NO: 1), but it will be understood that the mutant amino acid is in the position corresponding to the wild-type amino acid (for example, in SEQ ID NO: 1). In embodiments, the modified Ras mutant proteins disclosed herein may include cleavage at the C-terminus or cleavage at the N-terminus prior to a serine residue. The serine residue in such N-terminal cleavage variants is still considered to correspond to position 12 of SEQ ID NO: 1. Furthermore, the aspartic acid residue at position 12 of SEQ ID NO: 2 finds the corresponding residue in SEQ ID NOs: 6 and 8.

[0173] Where used interchangeably herein, the terms “Switch II pocket” and “Switch II binding pocket” refer to the binding pocket formed beneath the “Switch II” loop of the Ras. In some embodiments, the Switch II pocket is located between the central beta sheet (β sheet) and the alpha (α)2 and α3 helices of the Ras. In some embodiments, the Switch II binding pocket is located at approximately or at least approximately 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 nanometers (nm) or higher from the 12th, 60th, 99th, or any combination thereof. In some embodiments, the Switch II binding pocket is located at positions 12, 60, 99, or any combination thereof, at up to approximately 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 nm, or higher. In some examples, the Switch II pocket may be formed upon binding to a small molecule (e.g., a small molecule inhibitor). Alternatively, the Switch II pocket may be formed before binding to a small molecule.

[0174] In some embodiments, the Switch II pocket of Ras contains 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more amino acid residues, or contains 3 to 15 residues selected from the group consisting of V7, V9, G10, G12, G12X variants (e.g., G12C, G12S, G12D, or G12V) of SEQ ID NO: 1, K14, K16, P34, T58, A59, G60, Q61, E62, E63, Y64, S65, R68, D69, M72, D92, H95, Y96, Q99, I100, R102, and V103, or contains the corresponding amino acid residues of the HRAS protein or NRAS protein. In some embodiments, the Switch II pocket of Ras contains 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 amino acid residues selected from the group consisting of G10, G12, G12X variants of SEQ ID NO: 1 (e.g., G12C, G12S, G12D, or G12V), K16, P34, T58, A59, E62, R68, D69, H95, Q99, R102, and V103, or contains the corresponding amino acid residues of the HRAS protein or NRAS protein.

[0175] As used herein, the term “leaving group” refers to an atom or group that leaves the residual or major part of a substrate in a particular reaction. The residual or major part of a substrate is also referred to herein as a “staying group.”

[0176] compound In one embodiment, a compound of formula (I): [ka] Or a pharmaceutically acceptable salt or solvate thereof is provided, in the formula, Ring A is a single ring C 7-10 Selected from carbon rings and monocyclic 7-10 membered heterocycles, X 1 C(R 1 ), C(R 1 )2, N, N(R1b ), selected from O, S, S(O), S(O)2, and C(O), X 2 C(R 2 ), C(R 2 )2, N, N(R 2b ), selected from O, S, S(O), S(O)2, and C(O), X 3 C(R 3 ), C(R 3 )2, N, N(R 3b ), selected from O, S, S(O), S(O)2, and C(O), X 4 C, C(R 4 ) and N are selected, X 5 C, C(R 5 ) and N are selected, X 6 C(R 6 ), C(R 6 )2, N, N(R 6b ), selected from O, S, S(O), S(O)2, and C(O), X 7 C(R 7 ), C(R 7 )(R 7a ) and N(R 7b ) are selected from, X 8 C(R 8 ), C(R 8 )2, N, N(R 8b ), selected from O, S, S(O), S(O)2, and C(O), X 13 C, C(R 13a ) and N are selected, X 14 C, C(R 14a ) and N are selected, R 7 is, -L 7a -R 17 And R 7b is, -L 7b -R 17 And, L 7a is a bond, C1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, L 7b is a bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 membered heteroalkylene, 3-4 membered heteroalkene, 3-4 membered heteroalkylene, -C(O)- and -C(O)N(R) 12 )- Selected from, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, R 9 is, -L 19 -R 19 -L 19a -R19a And, L 19 is a bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R 12 ) Selected from O-, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, R 19 This is a single ring C 3-8 Selected from carbon rings and monocyclic 3- to 8-membered heterocycles, in this case monocyclic C 3-8 Carbon rings and monocyclic 3- to 8-membered heterocycles contain one or more R 20 It is optionally replaced by, L 19a is a bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12)-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, R 19a teeth, i) A five-membered heteroaryl containing one or more ring nitrogen atoms, wherein the five-membered heteroaryl is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 Those that are optionally replaced by, and ii) A 5- to 12-membered heterocycle containing 3 or 4 ring nitrogen atoms, wherein the 5- to 12-membered heterocycle contains one or more R 20 Selected from those that are optionally replaced by, R 1b , R 2b , R 3b , R 6b , and R 8b These are independently hydrogen, -CN, and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -C(O)OR 12 , -C(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7a , R 8 , R 13a , R 14a , and R 17 These are independent of each other, for each entity: hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, R 12 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, C 2-6Alkenil, C 2-6 Alkinyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 member heterocycle), C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Alkyl-(3-12 member heterocycle) is one or more R 20 It is optionally replaced by, R 13 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, and C 1-6 R selected from haloalkyls or added to the same nitrogen atom 12 and R 13 is one or more R 20 It forms a 3- to 10-membered complex ring that can be optionally substituted with, R 20 These are independent of each other, for each entity: halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22, -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 )-, and -S(=O)(=NR 22 )N(R 22 )(R 23 ) is selected from C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are halogens, oxo, -CN, and C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22, -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 ) is optionally substituted with one or more substituents independently selected from the original, R 21 These are independent of each other, for each entity, hydrogen, halogen, and C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 member heterocycles) or two R 21 However, they are grouped together with the carbon atoms to which they are added and C 3-12 They form a carbon ring or a 3- to 12-membered heterocycle, each of which is a halogen, C 1-3 Alkyl, C 1-3 Optionally substituted with one or more substituents independently selected from haloalkyl and -OH groups, R 22 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 member heterocycles), R 23 These are independent of each other, for each existence, hydrogen and C 1-6 R selected from alkyl groups or added to the same nitrogen atom22 and R 23 However, it forms a 3- to 10-membered complex ring, R 29 These are independent of each other, for each entity: halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 Two R atoms are optionally substituted and attached to the same atom. 29 They are selectively linked together to form oxos, n29 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13, and each [ka] These independently represent single or double bonds in which all valencies are satisfied.

[0177] In this specification, a reference to ring A means the shortest path between two bonding points with ring A (i.e., -X of formula I). 5 -X 13 -X 4 It contains only those atoms of the ring or ring system shown in ). For example, in compounds (a) and (b) shown below, ring A is (a) a 7-membered monocyclic heterocycle, or (b) a 7-membered monocyclic carbon ring. [ka]

[0178] In embodiments of the compound of formula I, the compound has formula (IA): [ka] or a pharmaceutically acceptable salt or solvate thereof, in the formula, X 9 C(R 9 ), C(R 9 )(R 9a ), and N(R 9 ) are selected from, X 10 C(R 10 ), C(R 10 )2, N, N(R 10b ), selected from O, S, S(O), S(O)2, and C(O), X 11 C(R 11 ), C(R 11 )2, N, N(R 11b ), selected from O, S, S(O), S(O)2, and C(O), X 12 is, -X 12a -, -X 12a -X 12b -, -X 12a -X 12b -X 12c -, and -X 12a -X 12b -X 12c -X 12d - Select from, X 12a X 5 Directly coupled, X 12a , X 12b , X 12c , and X 12d Independently, C(R 12a ), C(R 12a )2, N, N(R 12b ), selected from O, S, S(O), S(O)2, and C(O), R 19a is a 5-membered heteroaryl containing one or more ring nitrogen atoms, and a 5-membered heteroaryl is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally replaced by, R 10b , R 11b , and R 12b These are independently hydrogen, -CN, and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12(Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -C(O)OR 12 , -C(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, R 9a , R 10 , R 11 , and R 12a These are independent of each other, for each entity: hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, and each [ka] These independently represent single or double bonds in which all valencies are satisfied.

[0179] In embodiments of the compound of formula I, the compound has formula (IB): [ka] or a pharmaceutically acceptable salt or solvate thereof, in the formula, X 9 C(R 9 ), C(R 9 )(R 9a ), and N(R 9 ) are selected from, X 10 C(R 10 ), C(R 10 )2, N, N(R 10b ), selected from O, S, S(O), S(O)2, and C(O), X 11 C(R 11 ), C(R 11 )2, N, N(R 11b ), selected from O, S, S(O), S(O)2, and C(O), X 12 is, -X 12a -, -X 12a -X 12b -, -X 12a -X 12b -X 12c -, and -X 12a -X 12b -X 12c -X 12d - Select from, X 12a X 5 Directly coupled, X 12a , X 12b , X 12c , and X 12d Independently, C(R 12a ), C(R 12a )2, N, N(R 12b ), selected from O, S, S(O), S(O)2, and C(O), R 19a is a 5- to 12-membered heterocycle containing 3 or 4 ring nitrogen atoms, in which case the 5- to 12-membered heterocycle is one or more R 20It is optionally replaced by, R 10b , R 11b , and R 12b These are independently hydrogen, -CN, and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -C(O)OR 12 , -C(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) have 1, 2, or 3 R 20 It is optionally replaced by, R 9a , R 10 , R 11 , and R 12a These are independent of each other, for each entity: hydrogen, halogen, -CN, C 1-6 Alkyl, C2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, and each [ka] These independently represent single or double bonds in which all valencies are satisfied.

[0180] In one embodiment, a compound of formula (II): [ka] Or a pharmaceutically acceptable salt or solvate thereof is provided, in the formula, Ring A is a single ring C 7-10 Selected from carbon rings and monocyclic 7-10 membered heterocycles, X 1 C(R 1 ), C(R 1 )2, N, N(R 1b ), selected from O, S, S(O), S(O)2, and C(O), X 2 C(R 2 ), C(R 2 )2, N, N(R 2b ), selected from O, S, S(O), S(O)2, and C(O), X 3 C(R 3 ), C(R 3 )2, N, N(R 3b ), selected from O, S, S(O), S(O)2, and C(O), X 4 C, C(R 4 ) and N are selected, X 5 C, C(R 5 ) and N are selected, X 6 C(R 6 ), C(R 6 )2, N, N(R 6b), selected from O, S, S(O), S(O)2, and C(O), X 7 C(R 7 ), C(R 7 )(R 7a ) and N(R 7b ) are selected from, X 8 C(R 8 ), C(R 8 )2, N, N(R 8b ), selected from O, S, S(O), S(O)2, and C(O), X 13 C, C(R 13a ) and N are selected, X 14 C, C(R 14a ) and N are selected, R 7 is, -L 7a -R 17 And R 7b is, -L 7b -R 17 And, L 7a is a bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R 12 ) Selected from O-, in this case, C 1-4Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, L 7b is a bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 membered heteroalkylene, 3-4 membered heteroalkene, 3-4 membered heteroalkylene, -C(O)- and -C(O)N(R) 12 )- Selected from, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, R 17 C 3-12 Selected from carbon rings and 3- to 12-membered heterocycles, in this case, C 3-12 Carbon rings and 3- to 12-membered heterocycles have one or more R 20 It is optionally replaced by, R 9 is, -L 19 -R 19 -L 19a -R 19a And, L 19 is a bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12)P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-, -OS(O)2-, -OS(O)-, -OP(O)(R 12 )-, -S(O)2O-, -S(O)O-, and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, R 19 This is a non-aromatic monocyclic C 4-8 Selected from carbocyclic and non-aromatic monocyclic 3- to 8-membered heterocycles, in this case the non-aromatic monocyclic C 4-8 Carbon rings and non-aromatic monocyclic 3- to 8-membered heterocycles contain one or more R 20 It is optionally replaced by, L 19a is a bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R 12) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, R 19a Halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, R 1b , R 2b , R 3b , R 6b , and R 8b These are independently hydrogen, -CN, and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -C(O)OR 12 , -C(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7a , R 8 , R 13a , and R 14a These are independent of each other, for each entity: hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, R 12 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 member heterocycle), C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Alkyl-(3-12 member heterocycle) is one or more R 20 It is optionally replaced by, R 13 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, and C 1-6 R selected from haloalkyls or added to the same nitrogen atom 12 and R13 is one or more R 20 It forms a 3- to 10-membered complex ring that can be optionally substituted with, R 20 These are independent of each other, for each entity: halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 )-, and -S(=O)(=NR 22 )N(R 22 )(R 23 ) is selected from C 1-6Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are halogens, oxo, -CN, and C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23) is optionally substituted with one or more substituents independently selected from the original, R 21 These are independent of each other, for each entity, hydrogen, halogen, and C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 member heterocycles) or two R 21 However, they are grouped together with the carbon atoms to which they are added and C 3-12 They form a carbon ring or a 3- to 12-membered heterocycle, each of which is a halogen, C 1-3 Alkyl, C 1-3 Optionally substituted with one or more substituents independently selected from haloalkyl and -OH groups, R 22 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 member heterocycles), R 23 These are independent of each other, for each existence, hydrogen and C 1-6 R selected from alkyl groups or added to the same nitrogen atom 22 and R 23 However, it forms a 3- to 10-membered heterocyclic ring, and R 29 These are independent of each other, for each entity: halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12)(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 Two R atoms are optionally substituted and attached to the same atom. 29 They are selectively linked together to form oxos, n29 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13, and each [ka] These independently represent single or double bonds in which all valencies are satisfied.

[0181] In embodiments of the compound of formula II, the compound has formula (IIA): [ka] or a pharmaceutically acceptable salt or solvate thereof, in the formula, X 9 C(R 9 ), C(R 9 )(R 9a ), and N(R 9 ) are selected from, X 10 C(R 10 ), C(R 10 )2, N, N(R 10b ), selected from O, S, S(O), S(O)2, and C(O), X 11 C(R 11 ), C(R 11 )2, N, N(R 11b ), selected from O, S, S(O), S(O)2, and C(O), X 12 is, -X 12a -, -X 12a -X 12b -, -X 12a -X 12b -X 12c -, and -X 12a -X 12b -X 12c -X 12d - Select from, X 12a X 5 Directly coupled, X 12a , X 12b , X 12c , and X 12d Independently, C(R 12a ), C(R 12a )2, N, N(R 12b ), selected from O, S, S(O), S(O)2, and C(O), R 10b , R11b , and R 12b These are independently hydrogen, -CN, and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -C(O)OR 12 , -C(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, R 9a , R 10 , R 11 , and R 12a These are independent of each other, for each entity: hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, and each [ka] These independently represent single or double bonds in which all valencies are satisfied.

[0182] In one embodiment, a compound of formula (V): [ka] Or a pharmaceutically acceptable salt or solvate thereof is provided, in the formula, Ring A is a single ring C 7-10 Carbon rings, monocyclic 7-10 membered heterocyclic rings, fused bicyclic C rings 8-12 Selected from carbon rings and fused bicyclic 8-12 membered heterocycles, X 1 C(R 1 ), C(R 1 )2, N, N(R 1b ), selected from O, S, S(O), S(O)2, and C(O), X 2 C(R 2 ), C(R 2 )2, N, N(R 2b ), selected from O, S, S(O), S(O)2, and C(O), X 3 C(R 3 ), C(R 3 )2, N, N(R 3b ), selected from O, S, S(O), S(O)2, and C(O), X 4 C, C(R 4 ) and N are selected, X 5 C, C(R 5 ) and N are selected, X 6 C(R 6 ), C(R 6 )2, N, N(R 6b), selected from O, S, S(O), S(O)2, and C(O), X 7 C(R 7 ), C(R 7 )(R 7a ) and N(R 7b ) are selected from, X 8 C(R 8 ), C(R 8 )2, N, N(R 8b ), selected from O, S, S(O), S(O)2, and C(O), X 13 C, C(R 13a ) and N are selected, X 14 C, C(R 14a ) and N are selected, R 7 is, -L 7a -R 17 And R 7b is, -L 7b -R 17 And, L 7a is a bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R 12 ) Selected from O-, in this case, C 1-4Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, L 7b is a bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 membered heteroalkylene, 3-4 membered heteroalkene, 3-4 membered heteroalkylene, -C(O)- and -C(O)N(R) 12 )- Selected from, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, R 9 is, -L 19 -L 19a -R 19a And, L 19 is a bond, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Selected from alkynylene, 2-4 membered heteroalkylene, 3-4 membered heteroalkynylene, and 3-4 membered heteroalkylene, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, L 19a -C(O)- and -N(R 12 )Selected from C(O)-, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a L via a nitrogen ring atom 19aIt is directly bonded to C(O) and R 19a is one or more R 20 It is optionally replaced by, R 1b , R 2b , R 3b , R 6b , and R 8b These are independently hydrogen, -CN, and C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -C(O)OR 12 , -C(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, R 1 , R 2 , R3 , R 4 , R 5 , R 6 , R 7a , R 8 , R 13a , R 14a , and R 17 These are independent of each other, for each entity: hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally replaced by, R 12 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 member heterocycle), C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Alkyl-(3-12 member heterocycle) is one or more R 20 It is optionally replaced by, R 13 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, and C 1-6 R selected from haloalkyls or added to the same nitrogen atom 12 and R 13 is one or more R 20 It forms a 3- to 10-membered complex ring that can be optionally substituted with, R 20 These are independent of each other, for each entity: halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12(Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 )-, and -S(=O)(=NR 22 )N(R 22 )(R 23 ) is selected from C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are halogens, oxo, -CN, and C 1-6Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 ) is optionally substituted with one or more substituents independently selected from the original, R 21 These are independent of each other, for each entity, hydrogen, halogen, and C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 member heterocycles) or two R 21 However, they are grouped together with the carbon atoms to which they are added and C 3-12They form a carbon ring or a 3- to 12-membered heterocycle, each of which is a halogen, C 1-3 Alkyl, C 1-3 Optionally substituted with one or more substituents independently selected from haloalkyl and -OH groups, R 22 These are independent of each other, for each entity, hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Selected from alkyl-(3-12 member heterocycles), R 23 These are independent of each other, for each existence, hydrogen and C 1-6 R selected from alkyl groups or added to the same nitrogen atom 22 and R 23 However, it forms a 3- to 10-membered complex ring, R 29 These are independent of each other, for each entity: halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 Two R atoms are optionally substituted and attached to the same atom. 29 They are selectively linked together to form oxos, n29 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13, and each [ka] These independently represent single or double bonds in which all valencies are satisfied.

[0183] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0184] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka] X 6 C(R 6 ), C(R 6 )2, N, and N(R 6b ) are selected from, X 7 C(R 7 ) and N(R 7b ) are selected from, X 8 C(R 8 ) and C(R 8 ) Selected from 2, and L 7a L is a bond, 7b It is a combination.

[0185] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0186] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0187] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0188] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0189] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0190] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0191] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0192] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0193] In embodiments of the compounds of formulas IA, IB, and IIA, the compounds are: [ka] n30 is selected from 0, 1, or 2. In some embodiments, n30 is 0. In some embodiments, n30 is 1. In some embodiments, n30 is 2.

[0194] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0195] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0196] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0197] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka] [ka]

[0198] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0199] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0200] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0201] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0202] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0203] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka] X 6 C(R 6 ), C(R 6 )2, N, and N(R 6b ) are selected from, X 7 C(R 7 ) and N(R 7b ) are selected from, X 8 C(R 8 ) and C(R 8 ) Selected from 2, and L 7a L is a bond, 7b It is a combination.

[0204] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0205] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0206] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0207] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0208] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0209] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka]

[0210] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0211] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0212] In embodiments of the compounds of formulas IA, IB, and IIA, the compounds are: [ka] n30 is selected from 0, 1, or 2. In some embodiments, n30 is 0. In some embodiments, n30 is 1. In some embodiments, n30 is 2.

[0213] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka] [ka]

[0214] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0215] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0216] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from the following: [ka]

[0217] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka] In the formulas, all variables are as described in formulas I, IA, IB, II, IIA, V, or their embodiments.

[0218] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka] In the formulas, all variables are as described in formulas I, IA, IB, II, IIA, V, or their embodiments.

[0219] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: [ka] X 6 C(R 6 ), C(R 6 )2, N, and N(R 6b ) are selected from, X 7 C(R 7 ) and N(R 7b ) are selected from, X 8 C(R 8 ) and C(R 8 ) Selected from 2, and L 7a is a bond, L 7b It is a combination, In this case, all other variables are as described for formulas I, IA, IB, II, IIA, V, or their embodiments.

[0220] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound is [ka] The formula has an expression selected from, where R 12a R is selected from hydrogen and unsubstituted methyl groups. 6The first element is selected from halogens and -CF3, and all other variables are as described for formulas I, IA, IB, II, IIA, V, or their embodiments.

[0221] In embodiments of compounds of formula IA, IB, or IIA, the compound is: [ka] Selected from, all variables in the formula are as described for formulas IA, IB, IIA, or their embodiments.

[0222] In embodiments of compounds of formula IA, IB, or IIA, the compound is: [ka] Selected from, in the formula, R 12a R is selected from hydrogen and unsubstituted methyl groups. 6 It is selected from halogen and -CF3, R 17 teeth, [ka] Selected from, all other variables are as described for formulas IA, IB, IIA, or their embodiments.

[0223] In embodiments of the compounds of formula I, II, or V, ring A is a monocyclic C7 carbon ring. In embodiments of the compounds of formula I, II, or V, ring A is a monocyclic C8 carbon ring. In embodiments of the compounds of formula I, II, or V, ring A is a monocyclic C9 carbon ring. In embodiments of the compounds of formula I, II, or V, ring A is a monocyclic C 10 It is a carbon ring.

[0224] In embodiments of the compounds of formula I, II, or V, ring A is a partially unsaturated monocyclic C7 carbon ring. In embodiments of the compounds of formula I, II, or V, ring A is a partially unsaturated monocyclic C8 carbon ring. In embodiments of the compounds of formula I, II, or V, ring A is a partially unsaturated monocyclic C9 carbon ring. In embodiments of the compounds of formula I, II, or V, ring A is a partially unsaturated monocyclic C 10 It is a carbon ring.

[0225] In embodiments of the compounds of formula I, II, or V, ring A is a monocyclic 7-membered heterocycle. In embodiments of the compounds of formula I, II, or V, ring A is a monocyclic 8-membered heterocycle. In embodiments of the compounds of formula I, II, or V, ring A is a monocyclic 9-membered heterocycle. In embodiments of the compounds of formula I or II, ring A is a monocyclic 10-membered heterocycle.

[0226] In embodiments of the compounds of formula I, II, or V, ring A is a partially unsaturated monocyclic 7-membered heterocycle. In embodiments of the compounds of formula I, II, or V, ring A is a partially unsaturated monocyclic 8-membered heterocycle. In embodiments of the compounds of formula I, II, or V, ring A is a partially unsaturated monocyclic 9-membered heterocycle. In embodiments of the compounds of formula I, II, or V, ring A is a partially unsaturated monocyclic 10-membered heterocycle.

[0227] In embodiments of the compound of formula V, ring A is a condensed bicyclic C 8-12It is a carbon ring. In embodiments of the compound of formula V, ring A is a fused bicyclic carbon ring containing a C7 carbon ring and a C5 carbon ring. In embodiments of the compound of formula V, ring A is a fused bicyclic carbon ring containing a C8 carbon ring and a C5 carbon ring. In embodiments of the compound of formula V, ring A is a fused bicyclic carbon ring containing a C7 carbon ring and a C6 carbon ring. In embodiments of the compound of formula V, ring A is a fused bicyclic carbon ring containing a C8 carbon ring and a C6 carbon ring. In embodiments of the compound of formula V, ring A is a fused bicyclic 8-12 membered heterocycle. In embodiments of the compound of formula V, ring A is a fused bicyclic heterocycle containing a 7 membered ring and a 5 membered ring. In embodiments of the compound of formula V, ring A is a fused bicyclic heterocycle containing an 8 membered ring and a 5 membered ring. In embodiments of the compound of formula V, ring A is a fused bicyclic heterocycle containing a 7 membered ring and a 6 membered ring. In embodiments of the compound of formula V, ring A is a fused bicyclic heterocycle containing a 7-membered ring and a 7-membered ring. In embodiments of the compound of formula V, ring A is a fused bicyclic heterocycle containing an 8-membered ring and a 6-membered ring. In embodiments of the compound of formula V, ring A is a fused bicyclic heterocycle containing a 7-membered ring and a 5-membered ring.

[0228] In embodiments of compounds of formula I, II, or V, n29 is selected from 0, 1, and 2. In embodiments of compounds of formula I, II, or V, n29 is 0. In embodiments of compounds of formula I, II, or V, n29 is 1. In embodiments of compounds of formula I, II, or V, n29 is 2. In embodiments of compounds of formula I, II, or V, n29 is 3. In embodiments of compounds of formula I, II, or V, n29 is 4. In embodiments of compounds of formula I, II, or V, n29 is 5. In embodiments of compounds of formula I, II, or V, n29 is 6. In embodiments of compounds of formula I, II, or V, n29 is 7. In embodiments of compounds of formula I, II, or V, n29 is 8. In embodiments of compounds of formula I, II, or V, n29 is 9. In embodiments of compounds of formula I, II, or V, n29 is 10. In embodiments of compounds of formula I, II, or V, n29 is 11. In embodiments of compounds of formula I, II, or V, n29 is 12. In embodiments of compounds of formula I, II, or V, n29 is 13.

[0229] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 is N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 N(R) 1b )

[0230] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 1b C 3-12 Selected from carbon rings and 3- to 12-membered heterocycles, in this case, C 3-12 Carbon rings and 3- to 12-membered heterocycles have one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 1b is one or more R 20It is a phenyl that is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 1b is one or more R 20 It is a pyridyl that is optionally substituted.

[0231] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 C(R 2 ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 is C(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 N(R) 2b )

[0232] In some embodiments, the compound is of formula I, IA, IB, II, IIA, or V, R 2 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 3-10 Carbon rings, 3-10 membered heterocycles, -OR 12 , and -N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 3-10 A carbon ring or a 3- to 10-membered heterocycle contains one or more R 20 It is optionally replaced by R. In some embodiments, 2 is hydrogen, -(C 0-3 Alkylene)-O-(C 0-3 Alkylene)-R 20 , C 1-3 Selected from alkyl groups and 3- to 10-membered heterocycles, in this case, C 0-3 Alkylene, C 1-3 Alkyl and 3- to 10-membered heterocycles each have one or more R 20 It is optionally replaced by R. In some embodiments, 2 is hydrogen, C 1-3 Alkyl, -OR 12 , and selected from 3- to 10-membered complex rings, in this case C1-3 Alkyl and 3- to 10-membered heterocycles each have one or more R 20 It is optionally replaced by R. In some embodiments, 2 is OR 12 In some embodiments, R 2 is -O(C 1-3 Alkylene (4-10 membered heterocycle), in this case the 4-10 membered heterocycle is a halogen, C 1-3 Alkyl, C 1-3 Haloalkyl and =C(R 21 ) is optionally substituted with one or more substituents independently selected from 2. In some embodiments, R 2 is -O(C 1-3 Alkylene (4-10 membered heterocycle), in this case the 4-10 membered heterocycle is a halogen, C 1-3 Alkyl, C 1-3 Haloalkyl and =C(R 21 ) Optionally substituted with one or more substituents independently selected from 2, R 21 For each entity, hydrogen, halogen, and C 1-3 Selected independently of alkyl. In some embodiments, R 2 is one or more R 20 -OCH2 (hexahydro-1H-pyrrolidine) is optionally substituted. In some embodiments, R 2 is halogen, C 1-3 Alkyl, C 1-3 Haloalkyl and =C(R 21 -OCH2 (hexahydro-1H-pyrrolidine) is optionally substituted with one or more substituents independently selected from )2, in this case, R 21 For each entity, hydrogen, halogen, and C 1-3 It is selected independently of alkyl.

[0233] In some embodiments, the compound of formula I, IA, IB, II, IIA, or V is R 2 teeth, [ka] [ka] Selected from. In some embodiments, R 2 teeth, [ka] Selected from. In some embodiments, R 2 teeth, [ka] Selected from. In some embodiments, R 2 is one or more R 20 It is optionally replaced by [ka] In some embodiments, R 2 teeth, [ka] For example, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] In some embodiments, R 2 teeth, [ka] Selected from, for example, [ka] That is the case.

[0234] In some embodiments, the compound of formula I, IA, IB, II, IIA, or V is R 2 These are halogen, oxo, and C 1-6 Alkyl, -OR 22 , -N(R 22 )(R 23 ), =C(R 21 )2, and -OC(O)N(R 22 )(R 23 ) is substituted with 1, 2, 3, or 4 substituents independently selected from ), in this case C 1-6 Alkyls are halogens, -CN, -OR 22 , -N(R 22 )(R 23 ), and -OC(O)N(R 22 )(R 23 ) is optionally substituted with one or more substituents independently selected from ). In some embodiments, R 2 is halogen, C 1-3 Alkyl, C 1-3 Haloalkyl and =C(R 21 ) is substituted with 1, 2, 3, or 4 substituents independently selected from 2, in this case, R 21 For each entity, hydrogen, halogen, and C 1-3 Selected independently of alkyl. In some embodiments, R 2is halogen, C 1-3 Alkyl, C 1-3 It is substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl, =CH2, =CHF, and =CF2. In some embodiments, R 2 These are replaced with halogens such as fluorine.

[0235] In some embodiments, the compound is of formula I, IA, IB, II, IIA, or V, R 2b is hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 3-10 Selected from carbon rings and 3- to 10-membered heterocycles, in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 3-10 A carbon ring or a 3- to 10-membered heterocycle contains one or more R 20 It is optionally replaced by R. In some embodiments, 2b is hydrogen, -(C 0-3 Alkylene)-O-(C 0-3 Alkylene)-R 20 , C 1-3 Selected from alkyl groups and 3- to 10-membered heterocycles, in this case, C 0-3 Alkylene, C 1-3 Alkyl and 3- to 10-membered heterocycles each have one or more R 20 It is optionally replaced by R. In some embodiments, 2b is hydrogen, C 1-3 Selected from alkyl groups and 3- to 10-membered heterocycles, in this case, C 1-3 Alkyl and 3- to 10-membered heterocycles each have one or more R 20 It is optionally replaced.

[0236] In some embodiments, for compounds of formula I, IA, IB, II, IIA, or V, R 2b teeth, [ka] Selected from.

[0237] In some embodiments, the compound of formula I, IA, IB, II, IIA, or V is R 2b These are halogen, oxo, and C 1-6 Alkyl, -OR 22 , -N(R 22 )(R 23 ), =C(R 21 )2, and -OC(O)N(R 22 )(R 23 ) is substituted with 1, 2, 3, or 4 substituents independently selected from ), in this case C 1-6 Alkyls are halogens, -CN, -OR 22 , -N(R 22 )(R 23 ), and -OC(O)N(R 22 )(R 23 ) is optionally substituted with one or more substituents independently selected from ). In some embodiments, R 2b is halogen, C 1-3 Alkyl, C 1-3 Haloalkyl and =C(R 21 ) is substituted with 1, 2, 3, or 4 substituents independently selected from 2, in this case, R 21 For each entity, hydrogen, halogen, and C 1-3 Selected independently of alkyl. In some embodiments, R 2b is halogen, C 1-3 Alkyl, C 1-3 It is substituted with 1, 2, 3, or 4 substituents independently selected from haloalkyl, =CH2, =CHF, and =CF2. In some embodiments, R 2 These are replaced with halogens such as fluorine.

[0238] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 is N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 C(R 3 )

[0239] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R3 For each entity, hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl and C 2-6 Selected independently of alkinyl, in this case, C 1-6 Alkyl, C 2-6 Alkenyl and C 2-6 Alkinyl is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 3 It is -CN.

[0240] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 4 It is C.

[0241] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 5 It is C.

[0242] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 C(R 6 ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6 For each presence, is independently selected from hydrogen and halogens. In embodiments of compounds of formulas I, IA, IB, II, IIA, or V, R 6 is one or more R 20 It is a methyl atom that is optionally substituted. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6 is a methyl compound independently substituted with one or more halogens. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6 is -CF3. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6 is -Cl. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6is N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 N(R) 6b ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6b is an unsubstituted cyclopropyl. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6b C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 It is an alkinyl, and in this case, C 1-6 Alkyl, C 2-6 Alkenyl and C 2-6 Alkinyl is one or more R 20 It is optionally substituted with (for example, CN, halogen, F, or Cl).

[0243] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 7 C(R 7 ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 7 N(R) 7b )

[0244] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 7 is, -R 17 In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 7b is, -R 17 That is the case.

[0245] In some embodiments, for compounds of formula I, IA, IB, II, IIA, or V, R 17 C 6-12 Selected from aryls and 5- to 12-membered heteroaryls, each of which contains one or more R 20 It is optionally replaced by R. In some embodiments, 17 C 10 Selected from aryls and 9-membered heteroaryls, each of which contains one or more R 20It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 17 is selected from phenyl, pyridyl, naphthyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzothienyl, indazolyl, and benzoxazolyl, in which case phenyl, pyridyl, naphthyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzothienyl, indazolyl, and benzoxazolyl is one or more R 20 It is optionally replaced by R. In some embodiments, 17 These are selected from naphthalenyl and benzothiophenyl, each of which contains one or more R 20 It is optionally replaced by R. In some embodiments, 17 C 3-10 Cycloalkyl, 3-10 member heterocycloalkyl, C 6-10 Selected from aryls and 5-10 member heteroaryls, each of which contains one or more R 20 It is optionally replaced by R. In some embodiments, 17 This is a biring C 4-10 Cycloalkyl, bicyclic 4-10 member heterocycloalkyl, bicyclic C 7-10 Selected from aryls and bicyclic 7-10 member heteroaryls, each of which contains one or more R 20 It is optionally replaced by R. In some embodiments, 17 This is a bridged biring C 4-10 Cycloalkyl, cross-linked bicyclic 4-10 membered heterocycloalkyl, cross-linked bicyclic C 7-10 Selected from aryls and bridged bicyclic 7-10 membered heteroaryls, each of which contains one or more R 20 It is optionally replaced by R. In some embodiments, 17 This is a condensed biring C 4-10 Cycloalkyl, condensed bicyclic 4-10 member heterocycloalkyl, condensed bicyclic C 7-10 Selected from aryls and condensed bicyclic 7-10 member heteroaryls, each of which has one or more R 20 It is optionally replaced by R. In some embodiments,17 C 6-10 Selected from aryls and 5-10 membered heteroaryls, each having 1, 2, 3, 4, or 5 R 20 It is optionally replaced by R. In some embodiments, 17 These are selected from naphthyl, isoquinolinyl, indazolyl, benzothiazolyl, benzothiophenyl, phenyl, and pyridinyl, each of which contains one or more R 20 It is optionally replaced by R. In some embodiments, 17 Halogen, -CN, C 1-3 Alkyl, C 1-3 Haloalkyl, C 2-3 Alkenil, C 2-3 Alkinyl, -OR 22 , -N(R 22 )(R 23 ), and C 3-6 It is substituted with 1, 2, 3, or 4 substituents independently selected from the cycloalkyl group. In some embodiments, R 17 These are selected from C6 aryls and 6-membered heteroaryls, each having 1, 2, 3, 4, or 5 R 20 It is replaced by R. In some embodiments, 17 is one or more R 20 For example, 1, 2, 3, 4, 5, 6, or 7 R 20 It is optionally replaced.

[0246] In some embodiments, for compounds of formula I, IA, IB, II, IIA, or V, R 17 teeth, [ka] Selected from, in the formula, Q 1 Q 3 , and Q 5 N and C(R 1q ) were selected independently of, Q 4 and Q 6 O, S, C(R 1q )2 and N(R 1r ) were selected independently of, Y 4 , Y 5 , Y 6 , Y 9 , and Y 10 C(R 1q ) and N are selected independently, Y 7 and Y 8 C(R 1q ), C(R 1q )2, N, and N(R 1r ) were selected independently of, Y 13 is a bond, C(R 1q ), N, C(O), C(R 1q )2, C(O)C(R 1q )2, C(R 1q )2C(R 1q )2, C(R 1q )2N(R 1r ), and N(R 1r ) are selected from, Y 14 , Y 15 , Y 17 , and Y 18 C(O), C(R 1q ), N, C(R 1q )2, and N(R 1r ) were selected independently of, Y 16 C, N, and C(R 1q ) are selected from, Each R 1q Hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 2-6 member heteroalkenyl, 2-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected independently of C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 2-6 member heteroalkenyl, 2-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 Two R atoms are optionally substituted or bonded to the same carbon. 1q These are linked together to form a 3- to 10-membered complex ring or C 3-10 It forms a carbon ring, in this case a 3-10 membered heterocycle and C 3-10 A carbon ring is one or more R 20 Two R atoms are optionally substituted or bonded to adjacent atoms. 1q These are linked together to form a 3- to 10-membered complex ring or C3-10 It forms a carbon ring, in this case a 3-10 membered heterocycle and C 3-10 A carbon ring is one or more R 20 It is optionally replaced by, or one R 1q and one R 1r These are linked together to form a 3- to 10-membered complex ring, in which case the 3- to 10-membered complex ring has one or more R 20 It is optionally replaced by, Each R 1r is hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynnyls, 3-10 membered heterocycles, and C 3-10 Selected independently from the carbon ring, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynnyls, 3-10 membered heterocycles, and C 3-10 A carbon ring is one or more R 20 It is optionally replaced by, and [ka] This indicates a single or double bond in which all valencies are satisfied.

[0247] In some embodiments, R 17 teeth, [ka] Selected from. In some embodiments, R 17 teeth, [ka] Selected from. In some embodiments, R 17 teeth, [ka] Selected from. In some embodiments, R 17 teeth, [ka] Selected from.

[0248] In some embodiments, the compound of formula I, IA, IB, II, IIA, or V is R 17 teeth, [ka] [ka] [ka] [ka] Selected from.

[0249] In some embodiments, for compounds of formula I, IA, IB, II, IIA, or V, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] Selected from. In some embodiments, R 17 teeth, [ka] Selected from. In some embodiments, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] That is the case.

[0250] In some embodiments, for compounds of formula I, IA, IB, II, IIA, or V, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] Selected from. In some embodiments, R 17 teeth, [ka] Selected from. In some embodiments, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] That is the case.

[0251] In some embodiments, R 17 teeth, [ka] [ka] [ka] [ka] Selected from.

[0252] In some embodiments, R 17 teeth, [ka] Selected from. In some embodiments, R 17 teeth, [ka] Selected from. In some embodiments, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] In some embodiments, R 17 teeth, [ka] Selected from.

[0253] In some embodiments, for compounds of formula I, IA, IB, II, IIA, or V, R 17 Halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-6 Cycloalkyl, -OR 22 , -SR 22 , and -N(R 22 )(R 23 ) is substituted with 1, 2, 3, or 4 substituents independently selected from, in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl and C 3-6 Cycloalkyls are halogens, C 1-6 Alkyl, C 1-6 Haloalkyl and -OR 22 It is optionally substituted with one, two, or three substituents independently selected from R. In some embodiments, R 17 Halogen, -CN, C 1-3 Alkyl, C 2-3 Alkenil, C 2-3 Alkinyl, -OR 22 , and -N(R 22 )(R 23 ) is substituted with 1, 2, 3, or 4 substituents independently selected from ). In some embodiments, R 17 R is substituted with 1, 2, 3, or 4 substituents independently selected from halogen, -CN, -CH3, -C≡CH, -OH, and -NH2. In some embodiments, R 17 These are replaced with -F, -CN, and -NH2. In some embodiments, R 17 These are substituted with -F, -C≡CH, and -OH. In some embodiments, R 17These are replaced with -CF3, -CH3, and -NH2. In some embodiments, R 17 These are replaced with -CF3 and -NH2. In some embodiments, R 17 These are replaced with -CF3, -CH3, -F and -NH2. In some embodiments, R 17 These are replaced with -CF3, -F, and -NH2. In some embodiments, R 17 It is substituted with 1, 2, 3, or 4 substituents independently selected from halogen, -CH3, -CH2CH3, -CH=CH2, -CF3, -C≡CH, -OH, -NH2, and -cyclopropyl.

[0254] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 7a is a bond. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 7b It is a combination.

[0255] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 C(R 8 ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 C(R 8 )2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 is C(H)2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 8 is a halogen. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 8 is -F. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6 is -Cl, and R 8 is -F. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6 is -CF3, and R 8 is -F. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6is hydrogen, and R 8 It is -F.

[0256] In embodiments of compounds of formula IA, IB, or IIA, X 9 N(R) 9 ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 9 is, -R 19 -L 19a -R 19a That is the case.

[0257] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 N is X 2 C(R 2 ) and X 3 N is X 4 C is X 5 C is X 6 C(R 6 ) and X 7 C(R 7 ) and X 8 C(R 8 ) and X 13 C is C, and X 14 is C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 N is X 2 C(R 2 ) and X 3 N is X 4 C is X 5 C is X 6 is C(Cl), and X 7 C(R 7 ) and X 8 C(F) and X 13 C is C, and X 14 is C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 N is X 2 C(R 2 ) and X 3 N is X 4C is X 5 C is X 6 N is X 7 C(R 7 ) and X 8 C(R 8 ) and X 13 C is C, and X 14 is C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 N is X 2 C(R 2 ) and X 3 N is X 4 C is X 5 C is X 6 N is X 7 C(R 7 ) and X 8 C(F) and X 13 C is C, and X 14 is C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 N is X 2 C(R 2 ) and X 3 N is X 4 C is X 5 CH is, X 6 It is C(H)2, and X 7 N(R) 7b ) and X 8 It is C(H)2, and X 13 C is C, and X 14 is C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 N is X 2 C(R 2 ) and X 3 N is X 4 C is X 5 C(R 5 ) and X 6 C(R 6 )2, X 7 N(R) 7b ) and X 8C(R 8 )2, X 13 C is C, and X 14 is C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 C(R 1 ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 C(R 1 )2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 is N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 N(R) 1b ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 is O. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 is S. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 is S(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 is S(O)2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 is C(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 C(R 2 ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 C(R 2 )2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 is N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 N(R) 2b ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 is O. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2is S. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 is S(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 is S(O)2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 is C(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 C(R 3 ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 C(R 3 )2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 is N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 N(R) 3b ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 is O. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 is S. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 is S(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 is S(O)2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 is C(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 4 is C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 4 C(R 4 ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 4 is N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 5is C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 5 C(R 5 ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 5 is N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 C(R 6 ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 C(R 6 )2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 is N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 N(R) 6b ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 is O. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 is S. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 is S(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 is S(O)2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 is C(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 7 C(R 7 ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 7 C(R 7 )(R 7a ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 7 N(R) 7b ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 C(R 8) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 C(R 8 )2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 is N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 N(R) 8b ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 is O. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 is S. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 is S(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 is S(O)2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 is C(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 13 is C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 13 C(R 13a ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 13 is N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 14 is C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 14 C(R 14a ) is. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 14 is N. In embodiments of compounds of formula IA, IB, or IIA, X 9 C(R 9 ) is. In embodiments of compounds of formula IA, IB, or IIA, X 9 C(R 9 )(R 9a) is. In embodiments of compounds of formula IA, IB, or IIA, X 9 N(R) 9 ) is. In embodiments of compounds of formula IA, IB, or IIA, X 10 C(R 10 ) is. In embodiments of compounds of formula IA, IB, or IIA, X 10 C(R 10 )2. In embodiments of compounds of formula IA, IB, or IIA, X 10 is N. In embodiments of compounds of formula IA, IB, or IIA, X 10 N(R) 10b ) is. In embodiments of compounds of formula IA, IB, or IIA, X 10 is O. In embodiments of compounds of formula IA, IB, or IIA, X 10 is S. In embodiments of compounds of formula IA, IB, or IIA, X 10 is S(O). In embodiments of compounds of formula IA, IB, or IIA, X 10 is, S(O )2. In embodiments of compounds of formula IA, IB, or IIA, X 10 is C(O). In embodiments of compounds of formula IA, IB, or IIA, X 11 C(R 11 ) is. In embodiments of compounds of formula IA, IB, or IIA, X 11 C(R 11 )2. In embodiments of compounds of formula IA, IB, or IIA, X 11 is N. In embodiments of compounds of formula IA, IB, or IIA, X 11 N(R) 11b ) is. In embodiments of compounds of formula IA, IB, or IIA, X 11 is O. In embodiments of compounds of formula IA, IB, or IIA, X 11 is S. In embodiments of compounds of formula IA, IB, or IIA, X 11 is S(O). In embodiments of compounds of formula IA, IB, or IIA, X 11is S(O)2. In embodiments of compounds of formula IA, IB, or IIA, X 11 is C(O). In embodiments of compounds of formula IA, IB, or IIA, X 12a C(R 12a ) is. In embodiments of compounds of formula IA, IB, or IIA, X 12a C(R 12a )2. In embodiments of compounds of formula IA, IB, or IIA, X 12a is N. In embodiments of compounds of formula IA, IB, or IIA, X 12a N(R) 12b ) is. In embodiments of compounds of formula IA, IB, or IIA, X 12a is O. In embodiments of compounds of formula IA, IB, or IIA, X 12a is S. In embodiments of compounds of formula IA, IB, or IIA, X 12a is S(O). In embodiments of compounds of formula IA, IB, or IIA, X 12a is S(O)2. In embodiments of compounds of formula IA, IB, or IIA, X 12a is C(O). In embodiments of compounds of formula IA, IB, or IIA, X 12b C(R 12a ) is. In embodiments of compounds of formula IA, IB, or IIA, X 12b C(R 12a )2. In embodiments of compounds of formula IA, IB, or IIA, X 12b is N. In embodiments of compounds of formula IA, IB, or IIA, X 12b N(R) 12b ) is. In embodiments of compounds of formula IA, IB, or IIA, X 12b is O. In embodiments of compounds of formula IA, IB, or IIA, X 12b is S. In embodiments of compounds of formula IA, IB, or IIA, X 12b is S(O). In embodiments of compounds of formula IA, IB, or IIA, X 12bis S(O)2. In embodiments of compounds of formula IA, IB, or IIA, X 12b is C(O). In embodiments of compounds of formula IA, IB, or IIA, X 12c C(R 12a ) is. In embodiments of compounds of formula IA, IB, or IIA, X 12c C(R 12a )2. In embodiments of compounds of formula IA, IB, or IIA, X 12c is N. In embodiments of compounds of formula IA, IB, or IIA, X 12c N(R) 12b ) is. In embodiments of compounds of formula IA, IB, or IIA, X 12c is O. In embodiments of compounds of formula IA, IB, or IIA, X 12c is S. In embodiments of compounds of formula IA, IB, or IIA, X 12c is S(O). In embodiments of compounds of formula IA, IB, or IIA, X 12c is S(O)2. In embodiments of compounds of formula IA, IB, or IIA, X 12c is C(O). In embodiments of compounds of formula IA, IB, or IIA, X 12d C(R 12a ) is. In embodiments of compounds of formula IA, IB, or IIA, X 12d C(R 12a )2. In embodiments of compounds of formula IA, IB, or IIA, X 12d is N. In embodiments of compounds of formula IA, IB, or IIA, X 12d N(R) 12b ) is. In embodiments of compounds of formula IA, IB, or IIA, X 12d is O. In embodiments of compounds of formula IA, IB, or IIA, X 12d is S. In embodiments of compounds of formula IA, IB, or IIA, X 12d is S(O). In embodiments of compounds of formula IA, IB, or IIA, X 12dis S(O)2. In embodiments of compounds of formula IA, IB, or IIA, X 12d It is C(O).

[0258] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19 is unsubstituted C 1-2 It is an alkylene. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19 is an unsubstituted methylene group. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19 It is a combination.

[0259] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19a C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )-, and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced.

[0260] In embodiments of compounds of formula I, IA, or IB, R 19 is one or more R 20 Monoring C is optionally substituted by 3-8 It is a carbocyclic compound. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 Monocyclic non-aromatic C is optionally substituted. 4-8 It is a carbocyclic compound. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 Monocyclic non-aromatic C is optionally substituted. 4-6 It is a carbocyclic compound. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 Monocyclic non-aromatic C is optionally substituted. 4-5 It is a carbocyclic compound. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic non-aromatic C4 carbon ring that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic non-aromatic C5 carbon ring that is optionally substituted. In embodiments of the compounds of formulas I, IA, and IB, R 19 is one or more R 20 It is a phenyl that is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic 3- to 8-membered heterocycle that is optionally substituted. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic non-aromatic 4-5 membered heterocycle that is optionally substituted. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20It is a monocyclic non-aromatic four-membered heterocycle that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic non-aromatic five-membered heterocycle that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 The compounds are selected from cyclopropyl, cyclobutyl, cyclopentyl, aziridine, azetidine, and pyrrolidine, each of which is C 1-3 It is optionally substituted with an alkyl group. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 The compounds are selected from cyclopropyl, cyclobutyl, cyclopentyl, aziridine, azetidine, and pyrrolidine, each of which is C 3-4 Optionally substituted with a cycloalkyl group, in this case C 3-4 The cycloalkyl group is optionally substituted with methyl. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 C 1-3 It is a cyclobutyl compound optionally substituted with an alkyl group. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is a cyclobutyl that is optionally substituted with cyclopropyl, in which case the cyclopropyl is optionally substituted with methyl. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is a cyclobutyl that is optionally substituted with cyclopropyl, in which case the cyclopropyl is substituted with methyl. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 C 1-3 It is a cyclopentyl that is optionally substituted with an alkyl group. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 C 1-3 It is an alkyl-substituted cyclopentyl. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 This is a methyl-substituted cyclopentyl.

[0261] In embodiments of the compounds of formulas I, IA, and IB, R 19 is one or more R 20 It is a monocyclic 5-6 member heteroaryl that is optionally substituted. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic non-aromatic 4-5 membered heterocycle that is optionally substituted. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is selected from azetidinil and pyrrolidinil, in which case azetidinil and pyrrolidinil are one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 It is optionally substituted with one or more substituents independently selected from alkyl-(3-12 membered heterocycle), in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Alkyl-(3-12 member heterocycle) is associated with halogens, oxo, -CN, and C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 22 , -SR 22 , -N(R 22 )(R 23 ), =NR 22 , =C(R 21)2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 ) is optionally substituted with one or more substituents independently selected from ). In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 C 1-4 Alkyl and C 3-4 It is optionally substituted with one or more substituents independently selected from the carbon ring, in this case, C 3-4 The carbon ring is composed of halogens and C 1-4 It is optionally substituted with one or more substituents independently selected from the alkyl group. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 It is optionally substituted with an unsubstituted methyl group.

[0262] In embodiments of compounds of formula I, IA, or IB, R 19 is one or more R 20 It is a monocyclic C3 carbon ring that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R19 is one or more R 20 It is a monocyclic C4 carbon ring that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic C5 carbon ring that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic C6 carbon ring that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic C7 carbon ring that is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic C8 carbon ring that can be optionally substituted.

[0263] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 Monoring C is substituted by 3-8 It is a carbocyclic compound. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic C3 carbon ring substituted with. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic C4 carbon ring substituted with. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic C5 carbon ring substituted with. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic C6 carbon ring substituted with. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20It is a monocyclic C7 carbon ring substituted with. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic C8 carbon ring that is substituted with [another compound].

[0264] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic three-membered heterocycle that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic four-membered heterocycle that can be optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic five-membered heterocycle that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic six-membered heterocycle that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic 7-membered heterocycle that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monoring 8-membered complex ring that can be optionally substituted with .

[0265] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic 3- to 8-membered heterocycle substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic three-membered heterocycle substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20It is a monocyclic four-membered heterocycle substituted with . In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic five-membered heterocycle substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic six-membered heterocycle substituted with . In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monocyclic 7-membered heterocycle substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a monoring 8-membered complex ring that is substituted by [a specific element].

[0266] In embodiments of compounds of formula I, IA, or IB, R 19 is one or more R 20 It is a non-aromatic monocyclic C3 carbon ring that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic C4 carbon ring that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic C5 carbon ring that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic C6 carbon ring that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic C7 carbon ring that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic C8 carbon ring that can be optionally substituted.

[0267] In embodiments of compounds of formula I, IA, or IB, R 19 is one or more R 20 Non-aromatic monocyclic C is substituted with 3-8 It is a carbocyclic compound. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 Non-aromatic monocyclic C is substituted with 4-8 It is a carbon ring. In embodiments of compounds of formula I, IA, or IB, R 19 is one or more R 20 It is a non-aromatic monocyclic C3 carbon ring substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic C4 carbon ring substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic C5 carbon ring substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic C6 carbon ring substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic C7 carbon ring substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic C8 carbon ring that is substituted with [a specific compound].

[0268] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic three-membered heterocycle that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic four-membered heterocycle that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19is one or more R 20 It is a non-aromatic monocyclic five-membered heterocycle that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic six-membered heterocycle that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic 7-membered heterocycle that is optionally substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic 8-membered heterocyclic ring that can be optionally substituted with .

[0269] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic 3- to 8-membered heterocycle substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic three-membered heterocycle substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic four-membered heterocycle substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic five-membered heterocycle substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic six-membered heterocycle substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic 7-membered heterocycle substituted with R. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 is one or more R 20 It is a non-aromatic monocyclic 8-membered heterocyclic ring that is substituted with [a specific compound].

[0270] In embodiments of compounds of formula I, IA, IB, II, or IIA, -L 19 -R 19 -L 19a -R 19a teeth, [ka] Selected from, in the formula, W 1 , W 3 , W 4 , and W 5 These are independent of each other, and for each existence, N(R) 20b ), C(R 20a )2, C(O), O, S(O), and S(O)2 are selected, W 2 N and C(R 20a ) are selected from, n1 is independently selected from 0, 1, 2, 3, 4, 5, and 6. n3 is independently selected from 0, 1, 2, 3, 4, and 5. In the formula, the sum of n1 and n3 is selected from 1, 2, 3, 4, 5, and 6; n4 and n5 are independently selected from 0, 1, 2, 3, and 4, respectively. The sum of n4 and n5 is selected from 0, 1, 2, 3 and 4, and R 20a , R 20b , R 20c , R 20d , R 20e , and R 20f For each entity, hydrogen and R 20 It is selected independently of others.

[0271] In multiple embodiments, R 20a , R 20c , R 20d , R 20e , and R 20f For each of these entities, hydrogen, halogen, -OH, -CN, and C are present. 1-6 Alkyl, and C 3-6Selected independently from cycloalkyl, in this case, C 1-6 Alkyl and C 3-6 Cycloalkyls include halogens, -OH, -CN, and C. 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is optionally substituted with one or more substituents selected from cycloalkyl groups.

[0272] In multiple embodiments, R 20b For each entity, hydrogen, C 1-6 Alkyl, and C 3-6 Selected independently from cycloalkyl, in this case, C 1-6 Alkyl and C 3-6 Cycloalkyls include halogens, -OH, -CN, and C. 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is optionally substituted with one or more substituents selected from cycloalkyl groups.

[0273] In some embodiments, W 1 N(R) 20b ), C(R 20a )2, C(O), O, S(O), and S(O)2 are independently selected. In some embodiments, W 1 Independently, C(R 20a )2. In some embodiments, W 1 CH(R) is independent of CH(R) 20a ) is. In some embodiments, W 1 Independently, is C(H)2. In some embodiments, W 1 is independently selected from C(O), S(O), and S(O)2. In some embodiments, W 1 These are independently C(O).

[0274] In some embodiments, W 2 Independently, N. In some embodiments, W 2 Independently, C(R 20a ) is. In some embodiments, W2 It is independently CH.

[0275] In some embodiments, W 3 N(R) 20b ), C(R 20a )2, C(O), O, S(O), and S(O)2 are independently selected. In some embodiments, W 3 Independently, C(R 20a )2. In some embodiments, W 3 CH(R) is independent of CH(R) 20a ) is. In some embodiments, W 3 Independently, is C(H)2. In some embodiments, W 3 is independently selected from C(O), S(O), and S(O)2. In some embodiments, W 3 Independently, C(O). In some embodiments, W 3 These are independently O.

[0276] In some embodiments, W 4 N(R) 20b ), C(R 20a )2, C(O), O, S(O), and S(O)2 are independently selected. In some embodiments, W 4 Independently, C(R 20a )2. In some embodiments, W 4 CH(R) is independent of CH(R) 20a ) is. In some embodiments, W 4 Independently, is C(H)2. In some embodiments, W 4 is independently selected from C(O), S(O), and S(O)2. In some embodiments, W 4 These are independently C(O).

[0277] In some embodiments, W 5 N(R) 20b ), C(R 20a )2, C(O), O, S(O), and S(O)2 are independently selected. In some embodiments, W 5 Independently, C(R20a )2. In some embodiments, W 5 CH(R) is independent of CH(R) 20a ) is. In some embodiments, W 5 Independently, is C(H)2. In some embodiments, W 5 is independently selected from C(O), S(O), and S(O)2. In some embodiments, W 5 These are independently C(O).

[0278] In multiple embodiments, n1 is 0. In multiple embodiments, n1 is 1. In multiple embodiments, n1 is 2. In multiple embodiments, n1 is 3. In multiple embodiments, n1 is 4. In multiple embodiments, n1 is 5. In multiple embodiments, n1 is 6. In multiple embodiments, n3 is 0. In multiple embodiments, n3 is 1. In multiple embodiments, n3 is 2. In multiple embodiments, n3 is 3. In multiple embodiments, n3 is 4. In multiple embodiments, n3 is 5. In multiple embodiments, n1 is 1 and n3 is 1. In multiple embodiments, n1 is 1 and n3 is 2. In multiple embodiments, n1 is 1 and n3 is 3. In multiple embodiments, n1 is 1 and n3 is 4. In multiple embodiments, n1 is 2 and n3 is 1. In multiple embodiments, n1 is 2 and n3 is 2. In multiple embodiments, n1 is 2 and n3 is 3. In multiple embodiments, n1 is 2 and n3 is 4. In multiple embodiments, n1 is 1 or 2. In multiple embodiments, n3 is 1 or 2. In multiple embodiments, n4 is 0 or 1. In multiple embodiments, n5 is 0 or 1.

[0279] In multiple embodiments, n4 is 0. In multiple embodiments, n4 is 1. In multiple embodiments, n4 is 2. In multiple embodiments, n4 is 3. In multiple embodiments, n4 is 4. In multiple embodiments, n5 is 0. In multiple embodiments, n5 is 1. In multiple embodiments, n5 is 2. In multiple embodiments, n5 is 3. In multiple embodiments, n5 is 4. In multiple embodiments, n4 is 1 and n5 is 1. In multiple embodiments, n4 is 1 and n5 is 2. In multiple embodiments, n4 is 1 and n5 is 3. In multiple embodiments, n4 is 2 and n5 is 1. In multiple embodiments, n4 is 2 and n5 is 2.

[0280] In embodiments of compounds of formula I, IA, IB, II, or IIA, -L 19 -R 19 -L 19a -R 19a teeth, [ka] Selected from.

[0281] In embodiments of compounds of formula I, IA, IB, II, or IIA, -L 19 -R 19 -L 19a -R 19a teeth, [ka] Selected from.

[0282] In embodiments of compounds of formula I, IA, IB, II, or IIA, -L 19 -R 19 -L 19a -R 19a teeth, [ka] [ka] Selected from.

[0283] In embodiments of compounds of formula I, IA, IB, II, or IIA, -L 19 -R 19 -L 19a -R 19a teeth, [ka] Selected from.

[0284] The individual embodiments described herein, or combinations thereof, are applicable to compounds of formula I, IA, IB, II, IIA, or V, or their pharmaceutically acceptable salts or solvates. It should be understood that the values ​​of the variables are listed as embodiments of compounds of formula I, IA, IB, II, IIA, V, or any other formula, and that such values ​​of the variables can be combined with any compound having a formula selected from the formulas (e.g., without numerical or labeling) of formula I, IA, IB, II, IIA, V, or any other compound, which are themselves listed as embodiments of compounds of formula I, IA, IB, II, IIA, and / or V, and are therefore subformulas of formula I, IA, IB, II, IIA, and / or V.

[0285] In multiple embodiments, R 20a R is independently hydrogen. In some embodiments, R 20a R is independently a halogen. In some embodiments, R 20a R is independently -OH. In several embodiments, R 20a Independently, R is -CN. In some embodiments, R 20a These are independent, non-substituted C 1-6 It is alkyl. In some embodiments, R 20a These are independent, non-substituted C 3-6 It is a cycloalkyl group.

[0286] In multiple embodiments, R 20aR is independently an unsubstituted methyl group. In several embodiments, R 20a R is independently unsubstituted ethyl. In several embodiments, R 20a R is independently an unsubstituted propyl. In some embodiments, R 20a R is independently an unsubstituted isopropyl. In some embodiments, R 20a R is independently unsubstituted butyl. In several embodiments, R 20a It is independently unsubstituted tert-butyl.

[0287] In multiple embodiments, R 20a These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a methyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20a These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Ethyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20a These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a propyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20a These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is an isopropyl compound that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20a These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6It is a butyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20a These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a tert-butyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0288] In multiple embodiments, R 20a R is independently an unsubstituted cyclopropyl. In several embodiments, R 20a R is independently unsubstituted cyclobutyl. In some embodiments, R 20a These are independently unsubstituted cyclopentyl compounds.

[0289] In multiple embodiments, R 20a These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a cyclopropyl that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20a It is independent of one C 1-3 It is a cyclopropyl that is optionally substituted with an alkyl group. In several embodiments, R 20a R is independently a cyclopropyl that is optionally substituted with one methyl group. In several embodiments, R 20a These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Cyclobutyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20a These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6This is a cyclopentyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0290] In multiple embodiments, R 20b R is independently hydrogen. In some embodiments, R 20b These are independent, non-substituted C 1-6 It is alkyl. In some embodiments, R 20b These are independent, non-substituted C 3-6 It is a cycloalkyl group.

[0291] In multiple embodiments, R 20b R is independently an unsubstituted methyl group. In several embodiments, R 20b R is independently unsubstituted ethyl. In several embodiments, R 20b R is independently an unsubstituted propyl. In some embodiments, R 20b R is independently an unsubstituted isopropyl. In some embodiments, R 20b R is independently unsubstituted butyl. In several embodiments, R 20b It is independently unsubstituted tert-butyl.

[0292] In multiple embodiments, R 20b These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a methyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20b These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Ethyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20b These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6It is a propyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20b These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is an isopropyl compound that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20b These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a butyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20b These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a tert-butyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0293] In multiple embodiments, R 20b R is independently an unsubstituted cyclopropyl. In several embodiments, R 20b R is independently unsubstituted cyclobutyl. In some embodiments, R 20b These are independently unsubstituted cyclopentyl compounds.

[0294] In multiple embodiments, R 20b These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a cyclopropyl that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20b It is independent of one C 1-3 It is a cyclopropyl that is optionally substituted with an alkyl group. In several embodiments, R 20bR is independently a cyclopropyl that is optionally substituted with one methyl group. In several embodiments, R 20b These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Cyclobutyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20b These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a cyclopentyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0295] In multiple embodiments, R 20c R is independently hydrogen. In some embodiments, R 20c R is independently a halogen. In some embodiments, R 20c R is independently -OH. In several embodiments, R 20c Independently, R is -CN. In some embodiments, R 20c These are independent, non-substituted C 1-6 It is alkyl. In some embodiments, R 20c These are independent, non-substituted C 3-6 It is a cycloalkyl group.

[0296] In multiple embodiments, R 20c R is independently an unsubstituted methyl group. In several embodiments, R 20c R is independently unsubstituted ethyl. In several embodiments, R 20c R is independently an unsubstituted propyl. In some embodiments, R 20c R is independently an unsubstituted isopropyl. In some embodiments, R 20c R is independently unsubstituted butyl. In several embodiments, R 20c It is independently unsubstituted tert-butyl.

[0297] In multiple embodiments, R 20c These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a methyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20c These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Ethyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20c These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a propyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20c These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is an isopropyl compound that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20c These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a butyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20c These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a tert-butyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0298] In multiple embodiments, R 20cR is independently an unsubstituted cyclopropyl. In several embodiments, R 20c R is independently unsubstituted cyclobutyl. In some embodiments, R 20c These are independently unsubstituted cyclopentyl compounds.

[0299] In multiple embodiments, R 20c These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a cyclopropyl that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20c It is independent of one C 1-3 It is a cyclopropyl that is optionally substituted with an alkyl group. In several embodiments, R 20c R is independently a cyclopropyl that is optionally substituted with one methyl group. In several embodiments, R 20c These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Cyclobutyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20c These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a cyclopentyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0300] In multiple embodiments, R 20d R is independently hydrogen. In some embodiments, R 20d R is independently a halogen. In some embodiments, R 20d R is independently -OH. In several embodiments, R 20d Independently, R is -CN. In some embodiments, R 20d These are independent, non-substituted C 1-6It is alkyl. In some embodiments, R 20d These are independent, non-substituted C 3-6 It is a cycloalkyl group.

[0301] In multiple embodiments, R 20d R is independently an unsubstituted methyl group. In several embodiments, R 20d R is independently unsubstituted ethyl. In several embodiments, R 20d R is independently an unsubstituted propyl. In some embodiments, R 20d R is independently an unsubstituted isopropyl. In some embodiments, R 20d R is independently unsubstituted butyl. In several embodiments, R 20d It is independently unsubstituted tert-butyl.

[0302] In multiple embodiments, R 20d These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a methyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20d These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Ethyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20d These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a propyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20d These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6It is an isopropyl compound that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20d These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a butyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20d These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a tert-butyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0303] In multiple embodiments, R 20d R is independently an unsubstituted cyclopropyl. In several embodiments, R 20d R is independently unsubstituted cyclobutyl. In some embodiments, R 20d These are independently unsubstituted cyclopentyl compounds.

[0304] In multiple embodiments, R 20d These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a cyclopropyl that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20d It is independent of one C 1-3 It is a cyclopropyl that is optionally substituted with an alkyl group. In several embodiments, R 20d R is independently a cyclopropyl that is optionally substituted with one methyl group. In several embodiments, R 20d These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6Cyclobutyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20d These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a cyclopentyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0305] In multiple embodiments, R 20e R is independently hydrogen. In some embodiments, R 20e R is independently a halogen. In some embodiments, R 20e R is independently -OH. In several embodiments, R 20e Independently, R is -CN. In some embodiments, R 20e These are independent, non-substituted C 1-6 It is alkyl. In some embodiments, R 20e These are independent, non-substituted C 3-6 It is a cycloalkyl group.

[0306] In multiple embodiments, R 20e R is independently an unsubstituted methyl group. In several embodiments, R 20e R is independently unsubstituted ethyl. In several embodiments, R 20e R is independently an unsubstituted propyl. In some embodiments, R 20e R is independently an unsubstituted isopropyl. In some embodiments, R 20e R is independently unsubstituted butyl. In several embodiments, R 20e It is independently unsubstituted tert-butyl.

[0307] In multiple embodiments, R 20e These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6It is a methyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20e These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Ethyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20e These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a propyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20e These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is an isopropyl compound that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20e These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a butyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20e These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a tert-butyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0308] In multiple embodiments, R 20e R is independently an unsubstituted cyclopropyl. In several embodiments, R 20e R is independently unsubstituted cyclobutyl. In some embodiments, R 20e These are independently unsubstituted cyclopentyl compounds.

[0309] In multiple embodiments, R 20e These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a cyclopropyl that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20e It is independent of one C 1-3 It is a cyclopropyl that is optionally substituted with an alkyl group. In several embodiments, R 20e R is independently a cyclopropyl that is optionally substituted with one methyl group. In several embodiments, R 20e These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Cyclobutyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20e These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a cyclopentyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0310] In multiple embodiments, R 20f R is independently hydrogen. In some embodiments, R 20f R is independently a halogen. In some embodiments, R 20f R is independently -OH. In several embodiments, R 20f Independently, R is -CN. In some embodiments, R 20f These are independent, non-substituted C 1-6 It is alkyl. In some embodiments, R 20f These are independent, non-substituted C 3-6 It is a cycloalkyl group.

[0311] In multiple embodiments, R 20f R is independently an unsubstituted methyl group. In several embodiments, R 20f R is independently unsubstituted ethyl. In several embodiments, R 20f R is independently an unsubstituted propyl. In some embodiments, R 20f R is independently an unsubstituted isopropyl. In some embodiments, R 20f R is independently unsubstituted butyl. In several embodiments, R 20f It is independently unsubstituted tert-butyl.

[0312] In multiple embodiments, R 20f These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a methyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20f These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Ethyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20f These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a propyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20f These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is an isopropyl compound that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20f These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C3-6 It is a butyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20f These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a tert-butyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0313] In multiple embodiments, R 20f R is independently an unsubstituted cyclopropyl. In several embodiments, R 20f R is independently unsubstituted cyclobutyl. In some embodiments, R 20f These are independently unsubstituted cyclopentyl compounds.

[0314] In multiple embodiments, R 20f These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a cyclopropyl that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20f It is independent of one C 1-3 It is a cyclopropyl that is optionally substituted with an alkyl group. In several embodiments, R 20f R is independently a cyclopropyl that is optionally substituted with one methyl group. In several embodiments, R 20f These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Cyclobutyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20f These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6This is a cyclopentyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0315] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )-, and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(H)-, -C(O)-, -N(H)C(O)-, -C(O)N(H)-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12)-, -N(H)S(O)2-, -N(H)S(O)-, -N(H)P(O)(R 12 )-, -S(O)2N(H)-, -S(O)N(H)-, -P(O)(R 12 )N(H)-, -OP(O)(R 12 )-, and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Selected from alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkynylene, 3-4 member heteroalkylene, -O-, -N(CH3)-, -C(O)-, -N(CH3)C(O)-, -C(O)N(CH3)-, -S-, -S(O)2-, -S(O)-, -P(O)(CH3)-, -N(CH3)S(O)2-, -N(CH3)S(O)-, -N(CH3)P(O)(CH3)-, -S(O)2N(CH3)-, -S(O)N(CH3)-, -P(O)(CH3)N(CH3)-, -OP(O)(CH3)-, and -P(O)(CH3)O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced.

[0316] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-, and -P(O)(R 12 )N(R 12 )- Selected from. In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a L is selected from -C(O)-, -S(O)2-, and -S(O)-. In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a -C(O)- and -N(R 12 Selected from )C(O)-. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19a is -N(R 12 )C(O)-. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19a is -N(H)C(O)-. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19a is -N(CH3)C(O)-. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19a It is -C(O)-.

[0317] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )-, and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a is -N(R 12 )C(O)-, -C(O)N(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-, and -P(O)(R 12 )N(R 12 )- Selected from. In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a These are -C(O)-, -S(O)2-, -S(O)-, and -P(O)(R 12 )- Selected from.

[0318] In embodiments of compounds of formula I, IA, II, IIA, or V, R 19a is a 5-membered heteroaryl having one or two ring nitrogen atoms, in which case the 5-membered heteroaryl is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, II, IIA, or V, R 19aR is selected from pyrrolyl, imidazolyl, and pyrazolyl, in this case, 19a R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a R is a non-aromatic 5-12 membered heterocycle containing 3 or 4 ring nitrogen atoms, in this case, 19a is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a R is a 5-12 member heteroaryl compound containing 3 or 4 ring nitrogen atoms, in this case, 19a is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a R is a 9-12 member heteroaryl compound containing 3 or 4 ring nitrogen atoms, in this case, 19a is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a R is a 5-6 member heteroaryl compound containing 3 or 4 ring nitrogen atoms, in this case, 19a is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a R is selected from triazolyl and tetrazolyl, in this case, 19a is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a R is selected from triazolyl and tetrazolyl, in this case, 19a R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a R is selected from triazolyl and imidazolyl, in this case, 19a R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a R is selected from 1,2,3-triazolyl and 1,2,4-triazolyl, in this case, 19a is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a R is selected from 1,2,3-triazolyl and 1,2,4-triazolyl, in this case, 19a R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a is halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Optionally substituted with one or more substituents independently selected from alkynyl, 2-6 membered heteroalkyl, 3-6 membered heteroalkenyl, and 3-6 membered heteroalkynyl, in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynnyl, 2-6 membered heteroalkyl, 3-6 membered heteroalkenyl, and 3-6 membered heteroalkynyl are halogens, oxo, -CN, and C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 22 , -SR 22 , -N(R22 )(R 23 ), =NR 22 , =C(R 21 )2, -C(O)OR 22 ,-OC(O)N(R 22 )(R 23 ), -N(R 22 )C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)OR 22 , -N(R 22 )S(O)2R 22 , -C(O)R 22 ,-S(O)R 22 -OC(O)R 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -N(R 22 )C(O)R 22 -S(O)2R 22 -S(O)(NR 22 )R 22 -S(O)2N(R 22 )(R 23 ), and -S(=O)(=NR 22 )N(R 22 )(R 23 ) is optionally substituted with one or more substituents independently selected from ). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a These are halogen, -CN, and C 1-6 It is optionally substituted with one or more substituents independently selected from the alkyl, in this case, C 1-6 Alkyls are halogens, oxo, -CN, and -OR 22 , -SR 22 , and -N(R 22 )(R 23 ) is optionally substituted with one or more substituents independently selected from ). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19aR is optionally substituted with one or more substituents independently selected from -F, -Cl, -Br, and -I. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a This is one R selected from -F and -Cl. 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a teeth, [ka] Selected from, in this case, R 20g R20 h , R 20i , and R 20j For each entity, hydrogen and R 20 It is selected independently of others.

[0319] In multiple embodiments, R 20g These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a methyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20g These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Ethyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20g These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a propyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20g These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6It is an isopropyl compound that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20g These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a butyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20g These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a tert-butyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0320] In multiple embodiments, R 20g R is independently an unsubstituted cyclopropyl. In several embodiments, R 20g R is independently unsubstituted cyclobutyl. In some embodiments, R 20g These are independently unsubstituted cyclopentyl compounds.

[0321] In multiple embodiments, R 20g These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a cyclopropyl that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20g It is independent of one C 1-3 It is a cyclopropyl that is optionally substituted with an alkyl group. In several embodiments, R 20g R is independently a cyclopropyl that is optionally substituted with one methyl group. In several embodiments, R 20g These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6Cyclobutyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20g These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Cyclopentyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20g R is independently a halogen. In some embodiments, R 20g Independently, F. In some embodiments, R 20g Independently, is Cl. In some embodiments, R 20g Independently, is I. In some embodiments, R 20g Independently, is Br. In some embodiments, R 20g R is independently an unsubstituted methyl group. In several embodiments, R 20g R is independently unsubstituted ethyl. In several embodiments, R 20g R is independently an unsubstituted isopropyl. In some embodiments, R 20g R is independently unsubstituted tert-butyl. In several embodiments, R 20g R is independently CN. In some embodiments, R 20g R is independently CF3. In some embodiments, R 20g R is independently -CHF2. In some embodiments, R 20g Independently, is -CH2CN. In some embodiments, R 20g R is independently -CH2OH. In several embodiments, R 20g Independently, is -CH2F. In some embodiments, R 20g R is independently -CH2Cl. In some embodiments, R 20g Independently, R is -CH2I. In some embodiments, R 20g R is independently -CH2Br. In some embodiments, R 20g It is hydrogen independently.

[0322] In multiple embodiments, R 20h These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a methyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20h These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Ethyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20h These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a propyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20h These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is an isopropyl compound that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20h These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a butyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20h These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a tert-butyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0323] In multiple embodiments, R20h R is independently an unsubstituted cyclopropyl. In several embodiments, R 20h R is independently unsubstituted cyclobutyl. In some embodiments, R 20h These are independently unsubstituted cyclopentyl compounds.

[0324] In multiple embodiments, R 20h These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a cyclopropyl that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20h It is independent of one C 1-3 It is a cyclopropyl that is optionally substituted with an alkyl group. In several embodiments, R 20h R is independently a cyclopropyl that is optionally substituted with one methyl group. In several embodiments, R 20h These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Cyclobutyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20h These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Cyclopentyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20h R is independently a halogen. In some embodiments, R 20h Independently, F. In some embodiments, R 20h Independently, is Cl. In some embodiments, R 20h Independently, is I. In some embodiments, R 20h Independently, is Br. In some embodiments, R 20hR is independently an unsubstituted methyl group. In several embodiments, R 20h R is independently unsubstituted ethyl. In several embodiments, R 20h R is independently an unsubstituted isopropyl. In some embodiments, R 20h R is independently unsubstituted tert-butyl. In several embodiments, R 20h R is independently CN. In some embodiments, R 20h R is independently CF3. In some embodiments, R 20h R is independently -CHF2. In some embodiments, R 20h Independently, is -CH2CN. In some embodiments, R 20h R is independently -CH2OH. In several embodiments, R 20h Independently, is -CH2F. In some embodiments, R 20h R is independently -CH2Cl. In some embodiments, R 20h Independently, R is -CH2I. In some embodiments, R 20h R is independently -CH2Br. In some embodiments, R 20h It is hydrogen independently.

[0325] In multiple embodiments, R 20i These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a methyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20i These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Ethyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20i These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6It is a propyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20i These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is an isopropyl compound that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20i These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a butyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20i These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 This is a tert-butyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0326] In multiple embodiments, R 20i R is independently an unsubstituted cyclopropyl. In several embodiments, R 20i R is independently unsubstituted cyclobutyl. In some embodiments, R 20i These are independently unsubstituted cyclopentyl compounds.

[0327] In multiple embodiments, R 20i These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a cyclopropyl that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20i It is independent of one C 1-3 It is a cyclopropyl that is optionally substituted with an alkyl group. In several embodiments, R 20iR is independently a cyclopropyl that is optionally substituted with one methyl group. In several embodiments, R 20i These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Cyclobutyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20i These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Cyclopentyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20i R is independently a halogen. In some embodiments, R 20i Independently, F. In some embodiments, R 20i Independently, is Cl. In some embodiments, R 20i Independently, is I. In some embodiments, R 20i Independently, is Br. In some embodiments, R 20i R is independently an unsubstituted methyl group. In several embodiments, R 20i R is independently unsubstituted ethyl. In several embodiments, R 20i R is independently an unsubstituted isopropyl. In some embodiments, R 20i R is independently unsubstituted tert-butyl. In several embodiments, R 20i R is independently CN. In some embodiments, R 20i R is independently CF3. In some embodiments, R 20i R is independently -CHF2. In some embodiments, R 20i Independently, is -CH2CN. In some embodiments, R 20i R is independently -CH2OH. In several embodiments, R 20i Independently, is -CH2F. In some embodiments, R 20iR is independently -CH2Cl. In some embodiments, R 20i Independently, R is -CH2I. In some embodiments, R 20i R is independently -CH2Br. In some embodiments, R 20i It is hydrogen independently.

[0328] In multiple embodiments, R 20j These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a methyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20j These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Ethyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20j These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a propyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20j These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is an isopropyl compound that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20j These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a butyl molecule optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20j These are independently halogen, -OH, -CN, and C 1-3Alkyl, C 1-3 Haloalkyl and C 3-6 This is a tert-butyl molecule that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group.

[0329] In multiple embodiments, R 20j R is independently an unsubstituted cyclopropyl. In several embodiments, R 20j R is independently unsubstituted cyclobutyl. In some embodiments, R 20j These are independently unsubstituted cyclopentyl compounds.

[0330] In multiple embodiments, R 20j These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a cyclopropyl that is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20j It is independent of one C 1-3 It is a cyclopropyl that is optionally substituted with an alkyl group. In several embodiments, R 20j R is independently a cyclopropyl that is optionally substituted with one methyl group. In several embodiments, R 20j These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Cyclobutyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20j These are independently halogen, -OH, -CN, and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Cyclopentyl is optionally substituted with one, two, or three substituents independently selected from the cycloalkyl group. In several embodiments, R 20j R is independently a halogen. In some embodiments, R 20jIndependently, F. In some embodiments, R 20j Independently, is Cl. In some embodiments, R 20j Independently, is I. In some embodiments, R 20j Independently, is Br. In some embodiments, R 20j R is independently an unsubstituted methyl group. In several embodiments, R 20j R is independently unsubstituted ethyl. In several embodiments, R 20j R is independently an unsubstituted isopropyl. In some embodiments, R 20j R is independently unsubstituted tert-butyl. In several embodiments, R 20j R is independently CN. In some embodiments, R 20j R is independently CF3. In some embodiments, R 20j R is independently -CHF2. In some embodiments, R 20j Independently, is -CH2CN. In some embodiments, R 20j R is independently -CH2OH. In several embodiments, R 20j Independently, is -CH2F. In some embodiments, R 20j R is independently -CH2Cl. In some embodiments, R 20j Independently, R is -CH2I. In some embodiments, R 20j R is independently -CH2Br. In some embodiments, R 20j It is hydrogen independently.

[0331] In embodiments of formulas I, IA, IB, II, IIA, or V, R 19a teeth, [ka] Selected from.

[0332] In embodiments of formulas I, IA, IB, II, IIA, or V, R 19aThese are selected from imidazole-1-yl and 1,2,4-triazole-1-yl, each of which contains one or more R 20 It is optionally substituted by. In embodiments of formulas I, IA, IB, II, IIA, or V, R 19a is one or more R 20 It is an imidazole-1-yl which is optionally substituted with. In embodiments of formulas I, IA, IB, II, IIA, or V, R 19a is one or more R 20 It is a 1,2,4-triazole-1-yl which is optionally substituted. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a R is selected from imidazole-1-yl and 1,2,4-triazole-1-yl, in this case, 19a is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a R is selected from imidazole-1-yl and 1,2,4-triazole-1-yl, in this case, 19a R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally substituted by. In embodiments of formulas I, IA, IB, II, IIA, or V, R 19a teeth, [ka] Selected from: In embodiments of formulas I, IA, IB, II, IIA, or V, R 19a teeth, [ka] Selected from, each of them is one or more R 20k It is optionally substituted by. In embodiments of formulas I, IA, IB, II, IIA, or V, R 19a teeth, [ka] Selected from, each of them is one or more R 20k It is optionally replaced.

[0333] In embodiments of formulas I, IA, IB, II, IIA, or V, R 19a teeth, [ka] Selected from, each of them is one or more R 20k It is optionally replaced.

[0334] In embodiments of formulas I, IA, IB, II, IIA, or V, R 19a teeth, [ka] Selected from, each of them is one or more R 20k It is optionally replaced.

[0335] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a teeth, [ka] Selected from.

[0336] In embodiments of compounds of formula II or IIA, R 19a Halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle), -(2-6 member heteroalkyl)-(3-12 member heterocycle), -OR 12 , -SR 12 , -N(R 12 )(R13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 , -C(O)R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)R 12 -S(O)2R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R 20 It is optionally substituted with. In embodiments of the compound of formula II or IIA, R 19a C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Selected from alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, and 3-6 member heteroalkynyl, in this case, C 1-6 Alkyl, C2-6 Alkenil, C 2-6 Alkynnyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, and 3-6 member heteroalkynyl are one or more R 20 It is optionally replaced.

[0337] In embodiments of compounds of formula II or IIA, R 19a is selected from C2 alkenyls and C2 alkynyls, in which case C2 alkenyls and C2 alkynyls are one or more R 20 It is optionally substituted with. In embodiments of the compound of formula II or IIA, R 19a is a -(3- to 12-membered complex ring), and in this case, -(3- to 12-membered complex ring) is one or more R 20 It is optionally substituted with. In embodiments of the compound of formula II or IIA, R 19a is a 5-membered heteroaryl, in which case the 5-membered heteroaryl is one or more R 20 It is optionally substituted with. In embodiments of the compound of formula II or IIA, R 19a This is a methyl molecule substituted with one halogen selected from Cl and F.

[0338] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a is a 5-membered heteroaryl compound containing one or more nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20It is replaced by. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is replaced by. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a is a 5-membered heteroaryl compound containing three or four ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It will be replaced with.

[0339] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a This is a five-membered heterocycle containing three or four ring nitrogen atoms, in which case the five-membered heterocycle has one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a This is a five-membered heterocycle containing three or four ring nitrogen atoms, in which case the five-membered heterocycle has one or more R 20 It is replaced by. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a This is a six-membered heterocycle containing three or four ring nitrogen atoms, in which case the six-membered heterocycle has one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a This is a six-membered heterocycle containing three or four ring nitrogen atoms, in which case the six-membered heterocycle has one or more R 20 It is substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a This is a 7-membered heterocycle containing three or four ring nitrogen atoms, in which case the 7-membered heterocycle has one or more R 20It is optionally substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a This is a 7-membered heterocycle containing three or four ring nitrogen atoms, in which case the 7-membered heterocycle has one or more R 20 It is substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a This is an 8-membered heterocycle containing three or four ring nitrogen atoms, in which case the 8-membered heterocycle has one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a This is an 8-membered heterocycle containing three or four ring nitrogen atoms, in which case the 8-membered heterocycle has one or more R 20 It is substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a This is a nine-membered heterocycle containing three or four ring nitrogen atoms, in which case the nine-membered heterocycle has one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a This is a nine-membered heterocycle containing three or four ring nitrogen atoms, in which case the nine-membered heterocycle has one or more R 20 It is substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a is a 10-membered heterocycle containing three or four ring nitrogen atoms, in which case the 10-membered heterocycle is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a is a 10-membered heterocycle containing three or four ring nitrogen atoms, in which case the 10-membered heterocycle is one or more R 20 It is substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a is an 11-membered heterocycle containing three or four ring nitrogen atoms, in which case the 11-membered heterocycle contains one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19ais an 11-membered heterocycle containing three or four ring nitrogen atoms, in which case the 11-membered heterocycle contains one or more R 20 It is substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a is a 12-membered heterocycle containing three or four ring nitrogen atoms, in which case the 12-membered heterocycle is one or more R 20 It is optionally substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a is a 12-membered heterocycle containing three or four ring nitrogen atoms, in which case the 12-membered heterocycle is one or more R 20 It is substituted with. In embodiments of compounds of formula I, IB, II, or IIA, R 19a This is a 5- to 12-membered heterocycle containing three or four ring nitrogen atoms, in which case the 12-membered heterocycle contains one or more R 20 It will be replaced with.

[0340] In embodiments of compounds of formula II or IIA, -L 19a -R 19a teeth, [ka] Selected from, in this case, R a For each entity, hydrogen, C 1-6 Alkyl, carboxy, C 1-6 Carboalkoxy, phenyl, C 2-7 Carboalkyl, R c -(C(R b )2) z -, R c -(C(R b )2) w -M-(C(R b )2) r -, (R d )(R e )CH-M-(C(R b )2) r -, and Het-J 3 -(C(R b )2) r -Selected independently of, R b For each entity, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-6 Cycloalkyl, C 2-7 Carboalkyl, C 2-7 Carboxyalkyls, phenyls, and phenyls, C13 1-6 Alkoxy, trifluoromethyl, amino, C 1-3 Alkylamino, C 2-6 Dialkylamino, nitro, azide, halomethyl, C 2-7 Alkoxymethyl, C 2-7 Alkanoyloxymethyl, C 1-6 Alkylthio, hydroxy, carboxyl, C 2-7 Carboalkoxy, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, C 1-6 Alkanoylamino, or C 1-6 Selected independently of alkyl, R c For each entity, -NR b R b and -OR b Selected independently from, R d and R e Each is independent of the other, -(C(R b )2) r -NR b R b and -(C(R b )2) r -OR b Selected from, J 1 For each entity, it is independently selected from hydrogen, chlorine, fluorine, and bromine. J 2 C 1-6 Selected from alkyl and hydrogen, For each existence, M is -N(R b )-, -O-, -N[(C(R b )2) w -NR b R b]-, and -N[(C(R b )2) w -OR b ]- Selected independently from, J 3 For each existence, -N(R b )-, -O-, and independently selected from the bonds, Het, for each presence, is R on carbon or nitrogen. b It is optionally monosubstituted or disubstituted, and -CH2OR on carbon. b The heterocycle is independently selected from a heterocycle that is optionally monosubstituted, in which case the heterocycle is selected from morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, piperazine, tetrahydrofuran, and tetrahydropyran. Each r is an independent integer between 1 and 4. Each w is an independent integer between 2 and 4. x is either 0 or 1. y is an integer from 0 to 4, and Each z is an independent integer between 1 and 6. In this case, the sum of x + y is an integer between 2 and 4.

[0341] In embodiments of compounds of formula II or IIA, -L 19a -R 19a teeth, [ka] Selected from, each of them has one or more R as long as the valence allows. 20 It is optionally replaced by R b For each element, hydrogen, hydroxyl, and C are present. 1-6 Alkoxy, and C 1-6 It is selected independently of alkyl.

[0342] In embodiments of the compound of formula II or IIA, i. L19 C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, and ii. -L 19a -R 19a teeth, [ka] Selected from, in this case, R a For each entity, hydrogen, C 1-6 Alkyl, carboxy, C 1-6 Carboalkoxy, phenyl, C 2-7 Carboalkyl, R c -(C(R b )2) z -, R c -(C(R b )2) w -M-(C(R b )2) r-, (R d )(R e )CH-M-(C(R b )2) r -, and Het-J 3 -(C(R b )2) r -Selected independently of, R b For each entity, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-6 Cycloalkyl, C 2-7 Carboalkyl, C 2-7 Carboxyalkyls, phenyls, and phenyls, C13 1-6 Alkoxy, trifluoromethyl, amino, C 1-3 Alkylamino, C 2-6 Dialkylamino, nitro, azide, halomethyl, C 2-7 Alkoxymethyl, C 2-7 Alkanoyloxymethyl, C 1-6 Alkylthio, hydroxy, carboxyl, C 2-7 Carboalkoxy, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, C 1-6 Alkanoylamino, or C 1-6 Selected independently of alkyl, R c For each entity, -NR b R b and -OR b Selected independently from, R d and R e Each is independent of the other, -(C(R b )2) r -NR b R b and -(C(R b )2) r -OR b Selected from, J 1 For each entity, it is independently selected from hydrogen, chlorine, fluorine, and bromine. J2 C 1-6 Selected from alkyl and hydrogen, For each existence, M is -N(R b )-, -O-, -N[(C(R b )2) w -NR b R b ]-, and -N[(C(R b )2) w -OR b ]- Selected independently from, J 3 For each existence, -N(R b )-, -O-, and independently selected from the bonds, Het, for each presence, is R on carbon or nitrogen. b It is optionally monosubstituted or disubstituted, and -CH2OR on carbon. b The heterocycle is independently selected from a heterocycle that is optionally monosubstituted, in which case the heterocycle is selected from morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, piperazine, tetrahydrofuran, and tetrahydropyran. Each r is an independent integer between 1 and 4. Each w is an independent integer between 2 and 4. x is either 0 or 1. y is an integer from 0 to 4, and Each z is an independent integer between 1 and 6. In this case, the sum of x + y is an integer between 2 and 4.

[0343] In embodiments of the compound of formula II or IIA, i. L 19 C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, and ii. -L 19a -R 19a teeth, [ka] Selected from, in this case, R a For each entity, hydrogen, C 1-6 Alkyl, carboxy, C 1-6 Carboalkoxy, phenyl, C 2-7 Carboalkyl, R c -(C(R b )2) z -, R c -(C(R b )2) w -M-(C(R b )2) r -, (R d )(R e )CH-M-(C(R b )2) r -, and Het-J 3 -(C(R b )2) r -Selected independently of, R b For each entity, hydrogen, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-6 Cycloalkyl, C 2-7 Carboalkyl, C 2-7 Carboxyalkyls, phenyls, and phenyls, C13 1-6 Alkoxy, trifluoromethyl, amino, C 1-3 Alkylamino, C 2-6 Dialkylamino, nitro, azide, halomethyl, C 2-7 Alkoxymethyl, C 2-7 Alkanoyloxymethyl, C 1-6 Alkylthio, hydroxy, carboxyl, C 2-7 Carboalkoxy, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, C 1-6 Alkanoylamino, or C 1-6 Selected independently of alkyl, R c For each entity, -NR b R b and -OR b Selected independently from, R d and R e Each is independent of the other, -(C(R b )2) r -NR b R b and -(C(R b )2) r -OR b Selected from, J 1 For each entity, it is independently selected from hydrogen, chlorine, fluorine, and bromine. J 2 C 1-6 Selected from alkyl and hydrogen, For each existence, M is -N(R b )-, -O-, -N[(C(R b )2) w -NR b Rb ]-, and -N[(C(R b )2) w -OR b ]- Selected independently from, J 3 For each existence, -N(R b )-, -O-, and independently selected from the bonds, Het, for each presence, is R on carbon or nitrogen. b It is optionally monosubstituted or disubstituted, and -CH2OR on carbon. b The heterocycle is independently selected from a heterocycle that is optionally monosubstituted, in which case the heterocycle is selected from morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, piperazine, tetrahydrofuran, and tetrahydropyran. Each r is an independent integer between 1 and 4. Each w is an independent integer between 2 and 4. x is either 0 or 1. y is an integer from 0 to 4, and Each z is an independent integer between 1 and 6. In this case, the sum of x + y is an integer between 2 and 4.

[0344] In embodiments of the compound of formula II or IIA, i. L 19 C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, and ii. -L 19a -R 19a teeth, [ka] Selected from, each of them has one or more R as long as the valence allows. 20 It is optionally replaced by R b For each element, hydrogen, hydroxyl, and C are present. 1-6 Alkoxy, and C 1-6 It is selected independently of alkyl.

[0345] In embodiments of compounds of formula II or IIA, L 19 C 2-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 3-4 member heteroalkynylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )-, and -P(O)(R 12 ) Selected from O-, in this case, C 2-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 3-4 member heteroalkenylenes, and 3-4 member heteroalkenylenes are one or more R 20 It is optionally replaced.

[0346] In embodiments of the compound of formula II or IIA, i. L 19 C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R 12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, and ii. -L 19a C 2-4Alkenylene, C 2-4 Alkynylene, 3-4 member heteroalkynylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -S-, -S(O)2-, -S(O)-, -P(O)R 12 -, -N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)R 12 -, -S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)R 12 N(R 12 )-,-OP(O)R 12 -, and -P(O)R 12 Selected from O-, in this case, C 2-4 Alkenylene, C 2-4 Alkynylenes, 3-4 member heteroalkenylenes, and 3-4 member heteroalkenylenes are one or more R 20 It is optionally replaced by, and iii. R 19a C 1-6 Haloalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, 3-6 member heteroalkenyl, 3-6 member heteroalkenyl, -C 0-6 Alkyl-(C 4-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(5-12 member heterocycle), -(2-6 member heteroalkyl)-(5-12 member heterocycle), -SR 12 , -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 12 )C(O)N(R 12 )(R 13 ), -N(R 12 )C(O)OR 12 , -N(R 12 )S(O)2R 12 ,-S(O)R 12 -OC(O)R 12 ,-C(O)C(O)N(R 12)(R 13 ), -N(R 12 )C(O)R 12 -S(O)(NR 12 )R 12 -S(O)2N(R 12 )(R 13 ), and -S(=O)(=NR 12 )N(R 12 )(R 13 ) is selected from, and in this case, C 1-6 Haloalkyl, C 2-6 Alkenil, C 2-6 Alkinyl, 3-6 member heteroalkenyl, 3-6 member heteroalkenyl, -C 0-6 Alkyl-(C 4-12 (Carbon ring), -(2-6 member heteroalkyl)-(C 3-12 carbocycle), -C 0-6 Alkyl-(5-12 member heterocycle) and -(2-6 member heteroalkyl)-(5-12 member heterocycle) are one or more R 20 It is optionally replaced.

[0347] In embodiments of compounds of formula I, IA, IB, II, or IIA, i. L 19 C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) 12 )-, -C(O)-, -N(R 12 )C(O)-, -C(O)N(R 12 )-, -S-, -S(O)2-, -S(O)-, -P(O)(R 12 )-,-N(R 12 )S(O)2-, -N(R 12 )S(O)-, -N(R 12 )P(O)(R 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-,-P(O)(R 12 )N(R 12 )-,-OP(O)(R 12 )- and -P(O)(R12 ) Selected from O-, in this case, C 1-4 Alkylene, C 2-4 Alkenylene, C 2-4 Alkynylenes, 2-4 membered heteroalkylenes, 3-4 membered heteroalkenes, and 3-4 membered heteroalkynylenes are one or more R 20 It is optionally replaced by, ii. X 12 is, -X 12a -and, iii. R 19 is one or more R 20 It is a monocyclic 3- to 8-membered heterocyclic ring that is substituted with, and iv. R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally replaced.

[0348] In embodiments of compounds of formula I, IA, IB, II, or IIA, i. R 19 is one or more R 20 It is a C1 alkylene that is optionally substituted, ii. X 12 is, -X 12a -and, iii. R 19 is one or more R 20 It is a monocyclic 3- to 8-membered heterocyclic ring that is substituted with, and iv. R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally replaced.

[0349] In embodiments of compounds of formula I, IA, IB, II, or IIA, i. L19 It is an unsubstituted C1 alkylene, ii. X 12 is, -X 12a -and, iii. R 19 is one or more R 20 It is a monocyclic 3- to 8-membered heterocyclic ring that is substituted with, and iv. R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a L via a nitrogen ring atom 19a Directly coupled to R 19a is one or more R 20 It is optionally replaced.

[0350] In embodiments of formula II or IIA, R 19a This is a three-membered heterocycle containing one ring nitrogen atom, in which case the three-membered heterocycle has one, two, or three R atoms. 20 It is optionally substituted with. In embodiments of formula II or IIA, R 19a C is a three-membered heterocycle containing one ring nitrogen atom, in which case the three-membered heterocycle is optionally substituted with one, two, or three halogens. 1-6 It is optionally substituted with an alkyl group. In embodiments of formula II or IIA, R 19a This is a three-membered heterocycle containing one ring nitrogen atom, and in this case, the three-membered heterocycle is C 1-6 Optionally substituted with alkyl, C 1-6 The alkyl group is optionally substituted with one, two, or three F atoms. In embodiments of formula II or IIA, R 19a This is a three-membered heterocycle containing one ring nitrogen atom, in which case the three-membered heterocycle is optionally substituted with methyl atoms, and the methyl atoms are optionally substituted with one, two, or three halogens.

[0351] In embodiments of formula II or IIA, R 19aC is a three-membered heterocycle containing one ring nitrogen atom, in which case the three-membered heterocycle is optionally substituted with one, two, or three halogens. 3-5 It is optionally substituted with a non-aromatic carbon ring. In embodiments of formula II or IIA, R 19a This is a three-membered heterocycle containing one ring nitrogen atom, in which case the three-membered heterocycle is optionally substituted with one, two, or three F atoms. 3-5 It is optionally substituted with a non-aromatic carbon ring. In embodiments of formula II or IIA, R 19a R is a three-membered heterocycle containing one ring nitrogen atom, in which case the three-membered heterocycle is optionally substituted with cyclopropyl which is optionally substituted with one, two, or three halogens. In embodiments of formula II or IIA, R 19a This is a three-membered heterocycle containing one ring nitrogen atom, in which case the three-membered heterocycle is optionally substituted with cyclopropyl atoms which are optionally substituted with one, two, or three F atoms.

[0352] In embodiments of formula II or IIA, R 19a This is a three-membered heterocycle containing one ring nitrogen atom, and in this case, the three-membered heterocycle is C 1-6 Alkyl and C 3-5 It is optionally substituted with one or more substituents selected from non-aromatic carbon rings. In embodiments of formula II or IIA, R 19a This is a three-membered heterocycle containing one ring nitrogen atom, and in this case, the three-membered heterocycle is C 1-6 Alkyl and C 3-5 Optionally substituted with one or more substituents selected from non-aromatic carbon rings, C 1-6 Alkyl and C 3-5 The non-aromatic carbon ring is optionally substituted with a halogen. In embodiments of formula II or IIA, R 19a This is a three-membered heterocycle containing one ring nitrogen atom, in which case the three-membered heterocycle is optionally substituted with one or more substituents selected from methyl and cyclopropyl, and the methyl and cyclopropyl substituents are optionally substituted with halogens.

[0353] In embodiments of formula II or IIA, R 19a teeth, [ka] Selected from, in the formula, each R 20 They are independently selected and differ by choice.

[0354] In the embodiment of the above formula, R 19a teeth, [ka] Selected from, in the formula, each R 20 They are independently selected and differ by choice.

[0355] In the embodiment of the above formula, R 19a teeth, [ka] Selected from, in the formula, each R 20 They are independently selected and differ by choice.

[0356] In the embodiment of the above formula, R 19a teeth, [ka] Selected from, in the formula, each R 20 They are independently selected and differ by choice.

[0357] In the embodiment of the above formula, R 19a teeth, [ka] Selected from, in the formula, each R 20 They are independently selected and differ by choice.

[0358] In the embodiment of the above formula, R 19a teeth, [ka] Selected from.

[0359] In the embodiment of the above formula, each R 20 R is independently a halogen. In the embodiment of the above formula, each R 20 R is independently an oxo. In the embodiment of the above formula, each R 20 R is independently -CN. In the embodiment of the above formula, each R 20 C 1-6 It is alkyl. In the embodiment of the above formula, each R 20 C 2-6 It is an alkenyl. In the embodiment of the above formula, each R 20 C 2-6 It is an alkynyl. In the embodiment of the above formula, each R 20 C 3-12 It is a carbon ring. In the embodiment of the above formula, each R 20 C 2-11 It is a complex algebra. In the embodiment of the above formula, each R 20 C 6-12 It is aryl. In the embodiment of the above formula, each R 20 C 1-11 It is a heteroaryl compound. In the embodiment of the above formula, each R 20 These are independent, -OR 22 In the embodiment of the above formula, each R 20 -SR 22 In the embodiment of the above formula, each R 20 These are independent of -N(R 22 )(R 23 )

[0360] In the embodiment of the above formula, each R 20 R is independently -OH. In the embodiment of the above formula, each R 20 R is independently -SH. In the embodiment of the above formula, each R 20 It is independently -NH2.

[0361] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f is an unsubstituted methyl group, and R 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 It is alkyl, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This is one or more halogens, -CN, or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0362] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f is an unsubstituted methyl group, and R 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 It is alkyl, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19aIt is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0363] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f is an unsubstituted methyl group, and R 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 It is alkyl, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkyl and unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0364] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f R is selected from methyl-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl. 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0365] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f R is selected from methyl-substituted cyclopropyl, -CH2OCH3-substituted cyclopropyl, -CH2CN-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl. 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl, and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, in this case, C 1-3 Alkyl is C 1-3 Optionally substituted with alkoxy or CN, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19aIt is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0366] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f R is selected from methyl-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl. 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0367] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20fR is selected from methyl-substituted cyclopropyl, -CH2OCH3-substituted cyclopropyl, -CH2CN-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl. 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl, and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, in this case, C 1-3 Alkyl is C 1-3 Optionally substituted with alkoxy or CN, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0368] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f R is selected from methyl-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl. 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl and C 1-3C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0369] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f R is selected from methyl-substituted cyclopropyl, -CH2OCH3-substituted cyclopropyl, -CH2CN-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl. 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl, and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, in this case, C 1-3 Alkyl is C 1-3 Optionally substituted with alkoxy or CN, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkoxy or unsubstituted C 1-3It is optionally substituted with a haloalkyl group.

[0370] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f R is selected from methyl-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl. 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0371] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f R is selected from methyl-substituted cyclopropyl, -CH2OCH3-substituted cyclopropyl, -CH2CN-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl. 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl, and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, in this case, C 1-3 Alkyl is C 1-3 Optionally substituted with alkoxy or CN, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0372] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f R is selected from methyl-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl. 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19aIt is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0373] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f R is selected from methyl-substituted cyclopropyl, -CH2OCH3-substituted cyclopropyl, -CH2CN-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl. 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl, and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, in this case, C 1-3 Alkyl is C 1-3 Optionally substituted with alkoxy or CN, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0374] In multiple embodiments, -L 19 -R 19 -L 19a -R19a teeth, [ka] In some embodiments, R 19a teeth, [ka] Selected from. In some embodiments, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0375] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 19a teeth, [ka] Selected from. In some embodiments, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0376] In multiple embodiments, -L 19 -R 19 -L 19a-R 19a teeth, [ka] In some embodiments, R 20 is an unsubstituted methyl group, and R 19a teeth, [ka] Selected from. In some embodiments, R 20 is unsubstituted C 1-3 Selected from alkyl, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a It is optionally substituted with one or more halogens.

[0377] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20 is an unsubstituted methyl group, and R 19a teeth, [ka] Selected from. In some embodiments, R 20 is unsubstituted C 1-3 Selected from alkyl, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0378] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 19a teeth, [ka] Selected from. In some embodiments, R 19a This is unsubstituted cyclopentenyl, unsubstituted C 2-3 Alkinyl and C 2-3 Selected from Alkenil, in this case, C 2-3 The alkenyl is optionally substituted with one or more halogens, -CN, unsubstituted cyclopropyl, or -N(CH3)2. In several embodiments, R 19a is unsubstituted C 4-6 Non-aromatic carbocycle, unsubstituted C 2-3 Alkinyl and C 2-3 Selected from Alkenil, in this case, C 2-3 Alkenyls are one or more halogens, -CN, and unsubstituted C. 3-4 Non-aromatic carbon rings, or -N(C 1-3 It is optionally substituted with alkyl(2).

[0379] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f R is selected from methyl-substituted cyclopropyl and unsubstituted methyl. 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl, and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, R 19a This is unsubstituted cyclopentenyl, unsubstituted C 2-3 Alkynyl and C, optionally substituted with one or more halogens, -CN, unsubstituted cyclopropyl, or -N(CH3)2. 2-3 Selected from alkenyls. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl, and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, R 19a is unsubstituted C 4-6 Non-aromatic carbocycle, unsubstituted C 2-3 Alkynyl, and one or more halogens, -CN, unsubstituted C 3-4 Non-aromatic carbon rings, or -N(C 1-3 C is optionally substituted with alkyl)2. 2-3 Selected from Alkenil.

[0380] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f R is selected from methyl-substituted cyclopropyl and unsubstituted methyl. 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl, and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, R 19a This is unsubstituted cyclopentenyl, unsubstituted C 2-3Alkynyl and C, optionally substituted with one or more halogens, -CN, unsubstituted cyclopropyl, or -N(CH3). 2-3 Selected from alkenyls. In some embodiments, R 20f is unsubstituted C 1-3 Alkyl, and C 1-3 C substituted with alkyl 3-4 Selected from non-aromatic carbon rings, R 19a is unsubstituted C 4-6 Non-aromatic carbocycle, unsubstituted C 2-3 Alkynyl, and one or more halogens, -CN, unsubstituted C 3-4 Non-aromatic carbon rings, or -N(C 1-3 C is optionally substituted with alkyl)2. 2-3 Selected from Alkenil.

[0381] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f is an unsubstituted methyl group, and R 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 It is alkyl, R 19a This is unsubstituted cyclopentenyl, unsubstituted C 2-3 Alkynyl and C, optionally substituted with one or more halogens, -CN, unsubstituted cyclopropyl, or -N(CH3)2. 2-3 Selected from alkenyls. In some embodiments, R 20f is unsubstituted C 1-3 It is alkyl, R 19a is unsubstituted C 4-6 Non-aromatic carbocycle, unsubstituted C 2-3 Alkynyl, and one or more halogens, -CN, unsubstituted C3-4 Non-aromatic carbon rings, or -N(C 1-3 C is optionally substituted with alkyl)2. 2-3 Selected from Alkenil.

[0382] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, -L 19a -R 19a is an unsubstituted methyl group. In several embodiments, -L 19a -R 19a is unsubstituted C 1-3 It is alkyl.

[0383] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 19a teeth, [ka] Selected from. In some embodiments, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0384] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 19a teeth, [ka] Selected from. In some embodiments, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0385] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f is an unsubstituted methyl group, and R 19a teeth, [ka] Selected from. In some embodiments, R 20f is unsubstituted C 1-3 It is alkyl, R 19a is a 5-membered heteroaryl compound containing one or more ring nitrogen atoms, in which case the 5-membered heteroaryl compound is R 19a It is directly bonded to -C(O)- via the cyclic nitrogen atom, R 19a This includes one or more halogens, -CN, and unsubstituted C. 1-3 Alkoxy or unsubstituted C 1-3 It is optionally substituted with a haloalkyl group.

[0386] In multiple embodiments, -L 19 -R 19 -L 19a -R 19a teeth, [ka] In some embodiments, R 20f is an unsubstituted methyl group, and R 19a teeth, [ka] Selected from. In ...

Claims

1. Compounds having the following formula: 【Chemistry 1】 or a pharmaceutically acceptable salt or solvate thereof, wherein the formula, X １ N and C(R １ ) are selected from, X ３ N and C(R ３ ) are selected from, X ５ C is, X ６ is C(R ６ ) and N are selected, X ８ is selected from C(R ８ ), and N, X １０ is C(R １０ ) ２ And, X １１ is C(R １１ ) ２ And, X １２ is, -X １２ａ -, -X １２ａ -X １２ｂ -, -X １２ａ -X １２ｂ -X １２ｃ -, and -X １２ａ -X １２ｂ -X １２ｃ -X １２ｄ - Selected from, X １２ａ is, X ５ Directly coupled, X １２ａ , X １２ｂ , X １２ｃ , and X １２ｄ O, C(R) are independent of each other. １２ａ ) ２ , and N(R １２ｂ ) are selected from, R ９ is, -L １９ -R １９ -L １９ａ -R １９ａ And, L １９ C １－４ Alkylene, C ２－４ Alkenylene, C ２－４ Alkynylene, 2-4 member heteroalkylene, 3-4 member heteroalkenylene, 3-4 member heteroalkynylene, -O-, -N(R) １２ )-, -C(O)-, -N(R １２ )C(O)-, -C(O)N(R １２ )-, -S-, -S(O) ２ -, -S(O)-, -P(O)(R １２ )-,-N(R １２ ) S(O) ２ -, -N(R １２ )S(O)-,-N(R １２ ) P(O)(R １２ )-,-S(O) ２ N(R) １２ )-,-S(O)N(R １２ )-,-P(O)(R １２ )N(R １２ )-,-OP(O)(R １２ ) - and - P(O)(R １２ ) Selected from O-, C １－４ Alkylene, C ２－４ Alkenylene, C ２－４ Alkynylene, 2-4 membered heteroalkylene, 3-4 membered heteroalkene, and 3-4 membered heteroalkylene are one or more R ２０ It is optionally replaced by, R １９ These are monocyclic 3- to 8-membered heterocyclic rings and monocyclic C ３－８ Selected from carbon rings, the monocyclic 3- to 8-membered heterocyclic rings and monocyclic C ３－８ A carbon ring has one or more R ２０ It is optionally replaced by, L １９ａ is -C(O)-, a bond, C １－４ alkylene, C ２－４ alkenylene, C ２－４ alkynylene, 2 - 4 member heteroalkylene, 3 - 4 member heteroalkenylene, 3 - 4 member heteroalkynylene, -O-, -N(R １２ )-, -N(R １２ )(O)-C-, -C(O)N(R １２ )-, -S-, -S(O) ２ -,-S(O)-,-P(O)(R １２ )-,-N(R １２ )S(O) ２ -,-N(R １２ )(O)-S-,-N(R １２ )(O)-P(R １２ )-,-S(O) ２ N(R １２ )-,-S(O)N(R １２ )-,-P(O)(R １２ )N(R １２ )-,-OP(O)(R １２ )- and -P(O)(R １２ )O- selected from, C １－４ alkylene, C ２－４ alkenylene, C ２－４ alkynylene, 2 - 4 member heteroalkylene, 3 - 4 member heteroalkenylene, and 3 - 4 member heteroalkynylene are optionally substituted with one or more R ２０ s, R １９ａ is a 5-membered heteroaryl containing one or more ring nitrogen atoms, and the 5-membered heteroaryl is R １９ａ directly bonded to L via a ring nitrogen atom, R １９ａ is optionally substituted with one or more R １９ａ and ２０ ​ Each R １２ｂ These are independently hydrogen, -CN, and C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), - (2-6 member heteroalkyl) - (C ３－１２ carbocycle), -C ０－６ Alkyl-(3-12 member heterocycle),-(2-6 member heteroalkyl)-(3-12 member heterocycle),-C(O)OR １２ , -C(O)R １２ , -C(O)N(R １２ ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N(R) １２ ) (Caution １３ ), and -S (=O) (=NR １２ )N(R １２ ) (Caution １３ ) is selected from C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), - (2-6 member heteroalkyl) - (C ３－１２ carbocycle), -C ０－６ Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R ２０ It is optionally replaced by, R １ , R ２ , R ３ , R ６ , R ８ , R １０ , R １１ , R １２ａ , and R １７ These are independent of each other, for each entity: hydrogen, halogen, -CN, C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), - (2-6 member heteroalkyl) - (C ３－１２ carbocycle), -C ０－６ Alkyl-(3-12 member heterocycle),-(2-6 member heteroalkyl)-(3-12 member heterocycle),-OR １２ ,-SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １２ ) C(O)N(R １２ ) (Caution １３ ), -N(R １２ ) C(O)OR １２ , -N(R １２ ) S(O) ２ R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -C(O)N(R １２ ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N(R) １２ ) (Caution １３ ), and -S (=O) (=NR １２ )N(R １２ ) (Caution １３ ) is selected from C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), - (2-6 member heteroalkyl) - (C ３－１２ carbocycle), -C ０－６ Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R ２０ It is optionally replaced by, R １２ These are independent of each other, for each entity, hydrogen, C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkinyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), and -C ０－６ Selected from alkyl- (3-12 membered heterocycles), C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkinyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), and -C ０－６ Alkyl- (3-12 membered heterocycle) is one or more R ２０ It is optionally replaced by, R １３ These are independent of each other, for each entity, hydrogen, C １－６ Alkyl and C １－６ R selected from haloalkyl groups or added to the same nitrogen atom １２ and R １３ is one or more R ２０ It forms a 3- to 10-membered complex ring that can be optionally substituted, R ２０ These are independent of each other, for each entity: halogen, oxo, -CN, C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), - (2-6 member heteroalkyl) - (C ３－１２ carbocycle), -C ０－６ Alkyl-(3-12 member heterocycle),-(2-6 member heteroalkyl)-(3-12 member heterocycle),-OR ２２ ,-SR ２２ , -N(R ２２ ) (Caution ２３ ), = NR ２２ , = C(R ２１ ) ２ , -C(O)OR ２２ , -OC(O)N(R ２２ ) (Caution ２３ ), -N(R ２２ ) C(O)N(R ２２ ) (Caution ２３ ), -N(R ２２ ) C(O)OR ２２ , -N(R ２２ ) S(O) ２ R ２２ , -C(O)R ２２ , -S(O)R ２２ , -OC(O)R ２２ , -C(O)N(R ２２ ) (Caution ２３ ), -C(O)C(O)N(R ２２ ) (Caution ２３ ), -N(R ２２ ) C(O)R ２２ , -S(O) ２ R ２２ , -S(O)(NR ２２ ) R ２２ , -S(O) ２ N(R) ２２ ) (Caution ２３ )-, and -S(=O)(=NR ２２ )N(R ２２ ) (Caution ２３ ) is selected from C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), - (2-6 member heteroalkyl) - (C ３－１２ carbocycle), -C ０－６ Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are halogens, oxo, -CN, C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Alkoxy, C １－６ Haloalkoxy, -OR ２２ ,-SR ２２ , -N(R ２２ ) (Caution ２３ ), = NR ２２ , = C(R ２１ ) ２ , -C(O)OR ２２ , -OC(O)N(R ２２ ) (Caution ２３ ), -N(R ２２ ) C(O)N(R ２２ ) (Caution ２３ ), -N(R ２２ ) C(O)OR ２２ , -N(R ２２ ) S(O) ２ R ２２ , -C(O)R ２２ , -S(O)R ２２ , -OC(O)R ２２ , -C(O)N(R ２２ ) (Caution ２３ ), -C(O)C(O)N(R ２２ ) (Caution ２３ ), -N(R ２２ ) C(O)R ２２ , -S(O) ２ R ２２ , -S(O)(NR ２２ ) R ２２ , -S(O) ２ N(R) ２２ ) (Caution ２３ ), and -S (=O) (=NR ２２ )N(R ２２ ) (Caution ２３ ) is optionally substituted with one or more substituents independently selected from the original, R ２１ These are independent of each other, for each entity, hydrogen, halogen, and C １－６ Alkyl, C １－６ Haloalkyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), and -C ０－６ Selected from alkyl- (3- to 12-membered heterocycles), or two R ２１ However, when those are added together with the carbon atoms to which they are added, C ３－１２ They form a carbon ring or a 3- to 12-membered heterocycle, each of which is a halogen, C １－３ Alkyl, C １－３ Optionally substituted with one or more substituents independently selected from haloalkyl and -OH groups, R ２２ These are independent of each other, for each entity, hydrogen, C １－６ Alkyl, C １－６ Haloalkyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), and -C ０－６ Selected from alkyl- (3-12 membered heterocycles), R ２３ These are independent of each other, for each existence, hydrogen and C １－６ R selected from alkyl groups or added to the same nitrogen atom ２２ and R ２３ However, it forms a 3- to 10-membered heterocycle, and each 【Chemistry 2】 A compound is one that independently exhibits a single or double bond in which all valencies are satisfied.

2. R １９ａ is a five-membered heteroaryl compound containing two, three, or four ring nitrogen atoms, and the five-membered heteroaryl compound is R １９ａ L via the cyclic nitrogen atom １９ａ Directly coupled to R １９ａ is one or more R ２０ The compound according to claim 1, which is optionally substituted with

3. R １９ａ It is imidazolyl, and R １９ａ R １９ａ L via the cyclic nitrogen atom １９ａ Directly coupled to R １９ａ is one or more R ２０ The compound according to any one of claims 1 to 2, which is optionally substituted with

4. R １９ａ It is pyrazolyl, and R １９ａ R １９ａ L via the cyclic nitrogen atom １９ａ Directly coupled to R １９ａ is one or more R ２０ The compound according to any one of claims 1 to 2, which is optionally substituted with

5. R １９ａ It is triazolyl, and R １９ａ R １９ａ L via the cyclic nitrogen atom １９ａ Directly coupled to R １９ａ is one or more R ２０ The compound according to any one of claims 1 to 2, which is optionally substituted with

6. R １９ａ It is 1,2,4-triazolyl, and R １９ａ R １９ａ L via the cyclic nitrogen atom １９ａ Directly coupled to R １９ａ is one or more R ２０ The compound according to any one of claims 1 to 2, which is optionally substituted with

7. R １９ａ These are halogens, -CN, and C １－６ Optionally substituted with one or more substituents independently selected from the alkyl group, C １－６ Alkyl is a halogen, oxo, -CN, -OR ２２ ,-SR ２２ , and -N(R ２２ ) (Caution ２３ The compound according to any one of claims 1 to 6, which is optionally substituted with one or more substituents independently selected from ).

8. R １９ａ is one R selected from -F and -Cl. ２０ A compound according to any one of claims 1 to 6, which is optionally substituted with.

9. L １９ａ is -C(O)-, -N(R １２ )C(O)-, -C(O)N(R １２ )-,-S(O) ２ -, -S(O)-, -P(O)(R １２ )-,-N(R １２ ) S(O) ２ -, -N(R １２ )S(O)-,-N(R １２ ) P(O)(R １２ )-,-S(O) ２ N(R) １２ )-,-S(O)N(R １２ )-, and-P(O)(R １２ )N(R １２ A compound selected from any one of claims 1 to 8.

10. L １９ａ is -N(R １２ The compound according to any one of claims 1 to 8, wherein it is C(O)-.

11. L １９ａ The compound according to any one of claims 1 to 8, wherein is -C(O)-.

12. R １９ is one or more R ２０ Monoring C is optionally substituted by ３－８ A compound according to any one of claims 1 to 11, wherein the compound is a carbon ring.

13. R １９ is one or more R ２０ Monocyclic non-aromatic C is optionally substituted. ４－６ A compound according to any one of claims 1 to 11, wherein the compound is a carbon ring.

14. R １９ is one or more R ２０ The compound according to any one of claims 1 to 11, wherein the compound is a monocyclic 3- to 8-membered heterocyclic ring that is optionally substituted.

15. R １９ is one or more R ２０ The compound according to any one of claims 1 to 11, wherein the compound is a monocyclic non-aromatic 4- to 5-membered heterocycle that is optionally substituted.

16. R １９ is selected from azetidinil and pyrrolidinil, and the azetidinil and pyrrolidinil are one or more R ２０ The compound according to any one of claims 1 to 11, which is optionally substituted with.

17. R １９ The compound according to any one of claims 1 to 16, wherein the compound is optionally substituted with an unsubstituted methyl group.

18. L １９ The compound according to any one of claims 1 to 17, wherein the compound is a bond.

19. L １９ is unsubstituted C １－２ The compound according to any one of claims 1 to 17, wherein it is an alkylene.

20. L １９ The compound according to any one of claims 1 to 17, wherein is an unsubstituted methylene group.

21. X １０ CH(R １０ The compound according to any one of claims 1 to 20, which is:

22. X １０ CH ２ The compound according to any one of claims 1 to 20.

23. R １０ For each entity, hydrogen, C １－４ Alkyl, C ２－３ Alkenil, C ２－３ Alkinyl, C ３－５ A carbon ring and a 3- to 5-membered heterocycle are independently selected, C １－４ Alkyl, C ２－３ Alkenil, C ２－３ Alkinyl, C ３－５ Carbon rings and 3- to 5-membered heterocycles have one or more R ２０ The compound according to any one of claims 1 to 21, which is optionally substituted with.

24. R １０ For each entity, hydrogen, 【Transformation 3】 A compound according to any one of claims 1 to 21, independently selected from the above.

25. X １１ CH(R １１ The compound according to any one of claims 1 to 24, which is:

26. X １１ CH ２ The compound according to any one of claims 1 to 24.

27. R １１ For each entity, hydrogen, C １－４ Alkyl, C ２－３ Alkenil, C ２－３ Alkinyl, C ３－５ A carbon ring and a 3- to 5-membered heterocycle are independently selected, C １－４ Alkyl, C ２－３ Alkenil, C ２－３ Alkinyl, C ３－５ Carbon rings and 3- to 5-membered heterocycles have one or more R ２０ The compound according to any one of claims 1 to 25, which is optionally substituted with.

28. X １２ is, -X １２ａ - The compound according to any one of claims 1 to 27.

29. X １２ The compound according to any one of claims 1 to 28, wherein is O.

30. X １２ is -CH(R １２ａ The compound according to any one of claims 1 to 28, wherein the compound is:

31. X １ The compound according to any one of claims 1 to 30, wherein is N.

32. R ２ is, -OR １２ The compound according to any one of claims 1 to 31.

33. R ２ is -O(C １－３ Alkylenes (non-aromatic 4-10 membered heterocycles) are non-aromatic 4-10 membered heterocycles, and halogens, C １－３ Alkyl, C １－３ Haloalkyl and =C(R ２１ ) ２ The compound according to any one of claims 1 to 32, which is optionally substituted with one, two, or three substituents independently selected from the compound.

34. R ２ is -O(C １－３ Alkylene)-(non-aromatic C) ３－５ carbocycle)-(C １－３ Alkylene)-(non-aromatic 4-10 membered heterocycle), and the non-aromatic 4-10 membered heterocycle is a halogen, C １－３ Alkyl, C １－３ Haloalkyl and =C(R ２１ ) ２ The compound according to any one of claims 1 to 32, which is optionally substituted with one, two, or three substituents independently selected from the compound.

35. R ２ teeth, 【Chemistry 4-1】 【Chemistry 4-2】 A compound according to any one of claims 1 to 31, selected from the above.

36. R ２ teeth, 【Transformation 5】 A compound according to any one of claims 1 to 31, selected from the above.

37. X ３ The compound according to any one of claims 1 to 36, wherein is N.

38. X ６ is C(R ６ The compound according to any one of claims 1 to 37, which is:

39. R ６ These are hydrogen, halogens, and C １－３ A compound according to any one of claims 1 to 38, selected from haloalkyls.

40. R ６ The compound according to any one of claims 1 to 38, wherein is -Cl.

41. R ６ -CF ３ The compound according to any one of claims 1 to 38.

42. X ６ The compound according to any one of claims 1 to 37, wherein is N.

43. R １７ C ６－１２ Selected from carbon rings and 5- to 12-membered heterocycles, C ６－１２ Carbon rings and 5- to 12-membered heterocycles have one or more R ２０ A compound according to any one of claims 1 to 42, which is optionally substituted with.

44. R １７ is selected from phenyl, pyridyl, naphthyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzothienyl, indazolyl, and benzoxazolyl, and phenyl, pyridyl, naphthyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzothienyl, indazolyl, and benzoxazolyl is one or more R ２０ A compound according to any one of claims 1 to 42, which is optionally substituted with.

45. R １７ teeth, 【Transformation 6】 Selected from, in the formula, Q １ Q ３ , and Q ５ N and C(R １ｑ ) were selected independently of, Q ４ and Q ６ O, S, C(R) １ｑ ) ２ and N(R １ｒ ) were selected independently of, Y ４ , Y ５ , Y ６ , Y ９ , and Y １０ is C(R １ｑ ) and N are selected independently, Y ７ and Y ８ is C(R １ｑ ), C (R １ｑ ) ２ , N, and N(R １ｒ ) were selected independently of, Y １３ is a bond, C(R １ｑ ), N, C(O), C(R １ｑ ) ２ , C(O)C(R １ｑ ) ２ , C(R １ｑ ) ２ C(R １ｑ ) ２ , C(R １ｑ ) ２ N(R) １ｒ ), and N(R １ｒ ) are selected from, Y １４ , Y １５ , Y １７ , and Y １８ C(O), C(R) １ｑ ), N, C (R １ｑ ) ２ , and N(R １ｒ ) were selected independently of, Y １６ C, N, and C(R １ｑ ) are selected from, Each R １ｑ is hydrogen, halogen, -CN, C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 2-6 member heteroalkyl, 2-6 member heteroalkenyl, 2-6 member heteroalkynyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), - (2-6 member heteroalkyl) - (C ３－１２ carbocycle), -C ０－６ Alkyl-(3-12 member heterocycle),-(2-6 member heteroalkyl)-(3-12 member heterocycle),-OR １２ , -SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １２ ) C(O)N(R １２ ) (Caution １３ ), -N(R １２ ) C(O)OR １２ , -N(R １２ ) S(O) ２ R １２ , -C(O)R １２ , -S(O)R １２ , -OC(O)R １２ , -C(O)N(R １２ ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １２ ) C(O)R １２ , -S(O) ２ R １２ , -S(O)(NR １２ ) R １２ , -S(O) ２ N(R) １２ ) (Caution １３ ), and -S (=O) (=NR １２ )N(R １２ ) (Caution １３ ) is selected independently of C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 2-6 member heteroalkyl, 2-6 member heteroalkenyl, 2-6 member heteroalkynyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), - (2-6 member heteroalkyl) - (C ３－１２ carbocycle), -C ０－６ Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are one or more R ２０ Either it is optionally substituted, or two R atoms are bonded to the same carbon. １ｑ These are linked together to form a 3- to 10-membered heterogeneous ring or C ３－１０ It forms a carbon ring, and consists of a 3- to 10-membered heterocycle and C ３－１０ A carbon ring has one or more R ２０ Either two R atoms are optionally substituted, or bonded to adjacent atoms. １ｑ These are linked together to form a 3- to 10-membered heterogeneous ring or C ３－１０ It forms a carbon ring, and consists of a 3- to 10-membered heterocycle and C ３－１０ A carbon ring has one or more R ２０ It is either optionally replaced by one R １ｑ and one R １ｒ These are linked together to form a 3- to 10-membered heterogeneous ring or C ３－１０ It forms a carbon ring, and consists of a 3- to 10-membered heterocycle and C ３－１０ A carbon ring has one or more R ２０ It is optionally replaced by, Each R １ｒ is hydrogen, C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkynnyls, 3- to 10-membered heterocycles, and C ３－１０ Selected independently from the carbon ring, C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkynnyls, 3- to 10-membered heterocycles, and C ３－１０ A carbon ring has one or more R ２０ It is optionally replaced by, and each 【Transformation 7】 The compound according to any one of claims 1 to 42, wherein each independently exhibits a single bond or a double bond in which all valencies are satisfied.

46. R １７ teeth, 【Chemistry 8-1】 【Chemistry 8-2】 【Chemistry 8-3】 【Chemistry 8-4】 【Chemistry 8-5】 A compound according to any one of claims 1 to 42, selected from the above.

47. X ８ is C(R ８ The compound according to any one of claims 1 to 46.

48. R ８ The compound according to any one of claims 1 to 47, wherein is a halogen.

49. R ８ The compound according to any one of claims 1 to 48, wherein is -F.

50. Compounds having the following formulas: 【Chemistry 9】 or a pharmaceutically acceptable salt or solvate thereof, wherein the formula, X ６ is C(R ６ ) and N are selected, R ６ is hydrogen, halogen, -CN, C １－３ Alkyl, C ２－３ Alkenyl and C ２－３ Selected from Alkinyl, C １－３ Alkyl, C ２－３ Alkenyl and C ２－３ Each alkynyl has one, two, or three R's ２０ It is optionally replaced by, R １０ , R １１ , and R １２ａ These are, independently, hydrogen, halogen, -CN, and C. １－３ Alkyl, C ２－３ Alkenil, C ２－３ Alkinyl and C ３－６ Selected from the carbon ring, C １－３ Alkyl, C ２－３ Alkenil, C ２－３ Alkinyl and C ３－６ Each carbon ring has one, two, or three R atoms. ２０ It is optionally replaced by, R １２ These are independent of each other, for each entity, hydrogen, C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkinyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), and -C ０－６ Selected from alkyl- (3-12 membered heterocycles), C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkinyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), and -C ０－６ Alkyl- (3-12 membered heterocycle) is one or more R ２０ It is optionally replaced by, R ８ It is a halogen, R ９ teeth, 【Chemistry 10-1】 【Chemistry 10-2】 Selected from, R ２０ｆ C １－６ Alkyl and C ３－６ Selected from the carbon ring, C １－６ Alkyl and C ３－６ Each carbon ring has one, two, or three R atoms. ２０ It is optionally replaced by, R １７ teeth, 【Chemistry 11】 Selected from, in the formula, Q ３ is C(CN), Q ４ It is selected from O and S, Y ４ , Y ５ , Y ６ , Y ９ , and Y １０ is C(R １ｑ ) and N are selected independently, Y １４ , Y １５ , Y １７ , and Y １８ C(R) １ｑ ) and Each R １ｑ These are independently hydrogen, halogen, -CN, and C １－３ Alkyl, C １－３ Haloalkyl, C ２－３ Alkenil, C ２－３ Alkynyl, 2-4 membered heteroalkyl, 2-4 membered heteroalkenyl, 2-4 membered heteroalkynyl, -C ０－６ Alkyl-(C) ３－５ carbocycle), -C ０－６ Alkyl-(3-5 membered heterocycle),-OH,-NH ２ , and -C(O)CH ３ Selected from, R ２ is -O(C １－３ Alkylenes (non-aromatic 4-10 membered heterocycles) are non-aromatic 4-10 membered heterocycles, and halogens, C １－３ Alkyl, C １－３ Haloalkyl and =C(R ２１ ) ２ R is optionally substituted with one or more substituents independently selected from R. ２１ For each entity, hydrogen, halogen, and C １－３ Selected independently of alkyl, and L １９ａ is -N(R １２ ) C(O)-, R １９ａ is a five-membered heteroaryl containing one or more ring nitrogen atoms, and the five-membered heteroaryl is R １９ａ It is directly bonded to -C(O)- via the cyclic nitrogen atom, R １９ａ These are halogens, -CN, and unsubstituted C. １－３ Alkyl and unsubstituted C １－３ Optionally substituted with one or more substituents independently selected from the haloalkyl group, R ２０ These are independent of each other, for each entity: halogen, oxo, -CN, C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), - (2-6 member heteroalkyl) - (C ３－１２ carbocycle), -C ０－６ Alkyl-(3-12 member heterocycle),-(2-6 member heteroalkyl)-(3-12 member heterocycle),-OR ２２ , -SR ２２ , -N(R ２２ ) (Caution ２３ ), = NR ２２ , = C(R ２１ ) ２ , -C(O)OR ２２ , -OC(O)N(R ２２ ) (Caution ２３ ), -N(R ２２ ) C(O)N(R ２２ ) (Caution ２３ ), -N(R ２２ ) C(O)OR ２２ , -N(R ２２ ) S(O) ２ R ２２ , -C(O)R ２２ , -S(O)R ２２ , -OC(O)R ２２ , -C(O)N(R ２２ ) (Caution ２３ ), -C(O)C(O)N(R ２２ ) (Caution ２３ ), -N(R ２２ ) C(O)R ２２ , -S(O) ２ R ２２ , -S(O)(NR ２２ ) R ２２ , -S(O) ２ N(R) ２２ ) (Caution ２３ )-, and -S(=O)(=NR ２２ )N(R ２２ ) (Caution ２３ ) is selected from C １－６ Alkyl, C ２－６ Alkenil, C ２－６ Alkynyl, 2-6 member heteroalkyl, 3-6 member heteroalkenyl, 3-6 member heteroalkynyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), - (2-6 member heteroalkyl) - (C ３－１２ carbocycle), -C ０－６ Alkyl-(3-12 member heterocycle) and -(2-6 member heteroalkyl)-(3-12 member heterocycle) are halogens, oxo, -CN, C １－６ Alkyl, C １－６ Haloalkyl, C １－６ Hydroxyalkyl, C １－６ Alkoxy, C １－６ Haloalkoxy, -OR ２２ ,-SR ２２ , -N(R ２２ ) (Caution ２３ ), = NR ２２ , = C(R ２１ ) ２ , -C(O)OR ２２ , -OC(O)N(R ２２ ) (Caution ２３ ), -N(R ２２ ) C(O)N(R ２２ ) (Caution ２３ ), -N(R ２２ ) C(O)OR ２２ , -N(R ２２ ) S(O) ２ R ２２ , -C(O)R ２２ , -S(O)R ２２ , -OC(O)R ２２ , -C(O)N(R ２２ ) (Caution ２３ ), -C(O)C(O)N(R ２２ ) (Caution ２３ ), -N(R ２２ ) C(O)R ２２ , -S(O) ２ R ２２ , -S(O)(NR ２２ ) R ２２ , -S(O) ２ N(R) ２２ ) (Caution ２３ ), and -S (=O) (=NR ２２ )N(R ２２ ) (Caution ２３ ) is optionally substituted with one or more substituents independently selected from the original, R ２１ These are independent of each other, for each entity, hydrogen, halogen, and C １－６ Alkyl, C １－６ Haloalkyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), and -C ０－６ Selected from alkyl- (3- to 12-membered heterocycles), or two R ２１ However, when those are added together with the carbon atoms to which they are added, C ３－１２ They form a carbon ring or a 3- to 12-membered heterocycle, each of which is a halogen, C １－３ Alkyl, C １－３ Optionally substituted with one or more substituents independently selected from haloalkyl and -OH groups, R ２２ These are independent of each other, for each entity, hydrogen, C １－６ Alkyl, C １－６ Haloalkyl, -C ０－６ Alkyl-(C) ３－１２ (Carbon ring), and -C ０－６ Selected from alkyl- (3-12 membered heterocycles), R ２３ These are independent of each other, for each existence, hydrogen and C １－６ R selected from alkyl groups or added to the same nitrogen atom ２２ and R ２３ However, it forms a 3- to 10-membered heterocycle, and each 【Chemistry 12】 A compound is one that independently exhibits a single or double bond in which all valencies are satisfied.

51. R ９ teeth, 【Chemistry 13】 The compound according to claim 50.

52. R ９ teeth, 【Chemistry 14】 The compound according to claim 50.

53. R １１ and R １２ａ Each of them independently produces hydrogen and -CH ３ Selected from, R ２０ｆ is unsubstituted C １－３ It is alkyl, R １７ teeth, 【Chemistry 15】 Selected from, R ２ teeth, 【Chemistry 16】 Selected from, and R １９ａ is a five-membered heteroaryl containing one or more ring nitrogen atoms, and the five-membered heteroaryl is R １９ａ It is directly bonded to -C(O)- via the cyclic nitrogen atom, R １９ａ These are halogens, -CN, and unsubstituted C. １－３ Alkyl and unsubstituted C １－３ The compound according to any one of claims 50 to 52, which is optionally substituted with one or more substituents independently selected from the haloalkyl group.

54. R １９ａ teeth, 【Chemistry 17】 A compound selected from any one of claims 1 and 9 to 53.

55. formula [Chemistry 18] The compound according to any one of claims 1 and 50, or having a pharmaceutically acceptable salt or solvate thereof.

56. A pharmaceutical composition comprising a compound according to any one of claims 1 to 55, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

57. A method for modifying a Ras mutant protein, comprising contacting the Ras mutant protein with an effective amount of a compound, salt, or solvate described in any one of claims 1 to 55.

58. The method according to claim 57, wherein the modified Ras mutant protein exhibits reduced output of Ras signaling.

59. The method according to claim 58, wherein the reduction in Ras signaling output is demonstrated by one or more outputs selected from (i) an increase in the steady-state level of the GDP-bound modified protein, (ii) a decrease in the steady-state level of the GTP-bound modified protein, (iii) a decrease in phosphorylated AKTs473, (iv) a decrease in phosphorylated ERK T202 / Y204, (v) a decrease in phosphorylated S6 S235 / 236, (vi) a decrease in the proliferation of tumor cells expressing the Ras G12S mutant protein, and (vii) a decrease in Ras interaction with Ras pathway signaling proteins.

60. The method according to any one of claims 57 to 59, wherein the contact occurs in vivo.

61. A method for treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 55, or a pharmaceutically acceptable salt or solvate thereof.

62. A method for treating cancer containing a Ras mutant protein in a subject, comprising administering a compound according to any one of claims 1 to 55 to the subject to inhibit the Ras mutant protein in the subject, wherein, upon contact with the Ras mutant protein, the compound causes the Ras mutant protein to exhibit a decrease in the output of Ras signaling.

63. The method according to claim 61 or 62, wherein the cancer is a solid tumor or a hematological cancer.

64. The method according to any one of claims 61 to 63, wherein the cancer comprises the K-Ras G12S mutant protein.

65. A method for regulating the signaling output of a Ras protein, comprising contacting the Ras protein with an effective amount of a compound according to any one of claims 1 to 55, or a pharmaceutically acceptable salt or solvate thereof, thereby regulating the signaling output of the Ras protein.

66. A method for inhibiting cell proliferation, comprising administering an effective amount of a compound according to any one of claims 1 to 55, or a pharmaceutically acceptable salt or solvate thereof, to cells expressing the Ras protein, thereby inhibiting the proliferation of the cells.

67. The method according to any one of claims 57 to 66, comprising administering an additional agent.

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