Substituted heterocyclic compound and use thereof

Abstract

The present disclosure provides compounds and pharmaceutically acceptable salts thereof, and methods of using the same. The compounds and methods have a range of uses as therapeutic, diagnostic and research tools. In particular, the subject compositions and methods are used to reduce signal transduction output of oncogenic proteins.

Description

Cross-references

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

[0002] This application contains a sequence list, which is electronically submitted in XML format and is incorporated herein by reference in its entirety. The XML copy was created on May 31, 2024, named 56690_770_601_SL.xml, and is 13,994 bytes in size. Background Technology

[0003] Cancer (e.g., tumors, growths, metastases) is the second leading cause of death worldwide, estimated to kill approximately 10 million people each year. Many types of cancer are marked by mutations in one or more proteins involved in various signaling pathways, which lead to the uncontrolled growth of cancer cells. In some cases, approximately 25% to 30% of tumors are known to contain rat sarcoma (Ras) mutations. In particular, mutations in the Kirsten Ras oncogene (K-Ras) are among the most common Ras mutations detected in human cancers, including lung adenocarcinoma (LUAD) and pancreatic ductal adenocarcinoma (PDAC).

[0004] Ras proteins have long been considered "undruggable," partly due to their high affinity for their substrate guanosine-5'-triphosphate (GTP) and / or their smooth surface lacking any apparent target region. Specific G12C Ras gene mutations have been identified as druggable targets, and numerous G12C-specific inhibitors have been developed. However, the application of such therapies remains limited because the G12C mutation in Ras exhibits a much lower prevalence compared to other known Ras mutations, such as G12D and G12V. Drug resistance and lack of persistence further restrict the use of such therapies. Summary of the Invention

[0005] In light of the foregoing, there remains a significant need for novel therapeutic and diagnostic designs that can specifically target Ras (including wild-type Ras, mutant Ras, and / or Ras-related proteins) to reduce Ras signaling output. Of particular interest are Ras inhibitors (including pan-Ras inhibitors capable of inhibiting two or more Ras mutants and / or wild-type Ras) for the treatment of Ras-related diseases (e.g., cancer), as well as mutant-selective inhibitors targeting mutant Ras proteins (such as Ras G12D, G12C, G12S, G13D, and / or G12V). Such compositions and methods can be particularly useful for the treatment of a wide range of diseases, including but not limited to cancer and neoplastic conditions. This disclosure addresses these needs and provides additional advantages for the diagnosis, prognosis, and treatment of a variety of diseases.

[0006] On one hand, a compound of formula (I) is provided: , Or a pharmaceutically acceptable salt or solvate thereof, wherein: Ring A is selected from single ring C 7-10 Carbon rings and monocyclic heterocycles with 7 to 10 membered members; X 1 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 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 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 Selected from C, C(R) 4 ) and N; X 5 Selected from C, C(R) 5 ) and N; X 6 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 Selected from C(R) 7), C(R 7 (R) 7a ) and N(R 7b ); X 8 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 Selected from C, C(R) 13a ) and N; X 14 Selected from C, C(R) 14a ) and N; R 7 Yes -L 7a -R 17 ;R 7b Yes -L 7b -R 17 ; L 7a Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; L 7b Selected from key, C 1-4 Alkylene, C 2-4imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -C(O)- and -C(O)N(R) 12 )-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; R 9 Yes -L 19 -R 19 -L 19a -R 19a ; L 19 Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; R 19 Selected from monocyclic C 3-8 Carbon rings and monocyclic 3- to 8-membered heterocycles, of which monocyclic C 3-8 Carbon rings and monocyclic 3- to 8-membered heterocycles are optionally separated by one or more R 20 replace; L 19aSelected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; R 19a Selected from: i) A 5-membered heteroaryl group comprising one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is obtained through R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a Optionally by one or more R 20 Replace; and ii) A 5- to 12-membered heterocycle comprising three or four cyclic nitrogen atoms, wherein the 5- to 12-membered heterocycle is optionally separated by one or more R atoms. 20 replace; R 1b R 2b R 3b R 6b and R 8b Independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12(Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 1 R 2 R 3 R 4 R 5 R 6 R 7a R 8 R 13a R 14a and R 17 Each time it appears, it is independently selected from hydrogen, halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 12 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3- to 12-membered heterocyclic), wherein C 1-6 Alkyl, C 2-6 alkenyl, C2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl (3- to 12-membered heterocycle) optionally surrounded by one or more R 20 replace; R 13 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl; or R attached to the same nitrogen atom 12 and R 13 Formed optionally by one or more R 20 Replacement of 3- to 10-membered heterocycles; R 20 Each time it appears, it is independently selected from halogen, oxo, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ); where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -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 ); R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3- to 12-membered heterocycles) or two R 21 Together with the carbon atoms they are attached to, they form C 3-12 Carbon rings or 3- to 12-membered heterocycles, wherein C 3-12 The carbon ring or 3- to 12-membered heterocycles are each optionally selected independently from halogens, C 1-3 Alkyl, C 1-3 Substitution with haloalkyl groups and -OH groups; R 22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Alkyl groups (3- to 12-membered heterocycles); R 23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R atoms bonded to the same nitrogen atom 22 and R 23 Formation of 3- to 10-membered heterocycles; R 29 Each time it appears, it is independently selected from halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Substitution; and where two R atoms connected to the same atom 29 Optional linkage to form an oxo group; n29 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13; and Each Independently represent single or double bonds, such that all valences are satisfied.

[0007] In embodiments of the compound of formula I, L 19a Selected from C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace.

[0008] In embodiments of the compound of formula I, the compound has formula (IA): , Or a pharmaceutically acceptable salt or solvate thereof, wherein: X 9 Selected from C(R) 9 ), C(R 9 (R) 9a ) and N(R 9 ); X 10 Selected from C(R) 10 ), C(R 10 )2、N、N(R 10b ), O, S, S(O), S(O)2 and C(O); X 11 Selected from C(R) 11 ), C(R 11 )2、N、N(R 11b ), O, S, S(O), S(O)2 and C(O); X 12 Selected from -X 12a -、-X 12a -X 12b -、-X 12a -X 12b -X 12c -and-X12a -X 12b -X 12c -X 12d -; where X 12a With X 5 Direct bonding; X 12a X 12b X 12c and X 12d Independently selected from C(R) 12a ), C(R 12a )2、N、N(R 12b ), O, S, S(O), S(O)2 and C(O); R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a Optionally by one or more R 20 replace; R 10b R 11b and R 12b Independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 9a R 10 R 11 and R 12a Each time it appears, it is independently selected from hydrogen, halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Replace; and Each Independently represent single or double bonds, such that all valences are satisfied.

[0009] In embodiments of compounds of formula I, IA, II, or IIA, R 19a It is a 5-membered heteroaryl group having one or two cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a Optionally by one or more R 20 replace.

[0010] In embodiments of compounds of formula I, IA, II, or IIA, R 19a Selected from pyrrole, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl; wherein R 19a Through R 19a cyclic nitrogen atom and L 19a Direct bonding; and where R 19a Optionally by one or more R 20 replace.

[0011] In embodiments of compounds of formula I, IA, II, or IIA, R 19a Selected from pyrrole, imidazolyl, and pyrazolyl; wherein R 19a Through R 19a cyclic nitrogen atom and L 19a Direct bonding; and where R 19a Optionally by one or more R 20 replace.

[0012] In embodiments of the compound of formula I, the compound has formula (IB): , Or a pharmaceutically acceptable salt or solvate thereof, wherein: X 9 Selected from C(R) 9 ), C(R 9 (R) 9a ) and N(R 9 ); X 10 Selected from C(R) 10 ), C(R 10 )2、N、N(R 10b ), O, S, S(O), S(O)2 and C(O); X 11 Selected from C(R) 11 ), C(R 11 )2、N、N(R 11b ), O, S, S(O), S(O)2 and C(O); X 12 Selected from -X 12a -、-X 12a -X 12b -、-X 12a -X 12b -X 12c -and-X 12a -X 12b -X 12c -X 12d -; where X 12a With X 5 Direct bonding; X 12a X 12b X 12c and X 12d Independently selected from C(R) 12a ), C(R 12a )2、N、N(R 12b ), O, S, S(O), S(O)2 and C(O); R 19a It is a 5- to 12-membered heterocycle containing three or four cyclic nitrogen atoms, wherein the 5- to 12-membered heterocycle is optionally separated by one or more R atoms. 20 replace; R 10b R 11b and R 12b Independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) are optionally separated by one, two or three R 20 replace; R 9a R 10 R 11 and R 12a Each time it appears, it is independently selected from hydrogen, halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Replace; and Each Independently represent single or double bonds, such that all valences are satisfied.

[0013] In embodiments of compounds of formula I, IB, II, or IIA, R 19a It is a non-aromatic 5- to 12-membered heterocycle containing three or four cyclic nitrogen atoms; wherein R 19a Optionally by one or more R 20 replace.

[0014] In embodiments of compounds of formula I, IB, II, or IIA, R 19a It is a 5- to 12-membered heteroaryl group containing three or four cyclic nitrogen atoms; wherein R 19a Optionally by one or more R 20 replace.

[0015] In embodiments of compounds of formula I, IB, II, or IIA, R 19a It is a 9- to 12-membered heteroaryl group containing three or four cyclic nitrogen atoms; wherein R 19a Optionally by one or more R 20 replace.

[0016] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a It is a 5- to 6-membered heteroaryl group containing three or four cyclic nitrogen atoms; wherein R 19a Optionally by one or more R 20 replace.

[0017] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a Selected from triazolyl and tetrazolyl; wherein R 19a Optionally by one or more R 20 replace.

[0018] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a Selected from 1,2,3-triazolyl and 1,2,4-triazolyl; wherein R 19a Optionally by one or more R 20 replace.

[0019] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a Optionally substituted by one or more substituents independently selected from the following: halogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl and 3- to 6-membered heterokynyl; wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, and 3- to 6-membered heteroynyl groups are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -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 ).

[0020] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a Optionally selected by one or more independently chosen from halogens, -CN and C 1-6 Alkyl substituents, wherein C 1-6 The alkyl group is optionally selected independently from one or more halogens, oxo groups, -CN groups, and -OR groups. 22 -SR 22 and -N(R) 22 (R) 23 Substituents of ) are used for substitution.

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

[0022] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a Optionally, it is selected by an R chosen from -F and -Cl. 20 replace.

[0023] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a Selected from ;where R 20g R 20h R 20i and R 20j Each time it appears, it is independently selected from hydrogen and R. 20 .

[0024] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19a Selected from .

[0025] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a Selected from -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 )-.

[0026] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a 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 Selected from -C(O)- and -N(R)- 12 )C(O)-.

[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 It is optionally controlled by one or more R 20 Replaced monocyclic C 3-8 Carbon ring.

[0030] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19It is optionally controlled by one or more R 20 Substituted monocyclic nonaromatic C 4-6 Carbon ring.

[0031] In embodiments of compounds of formulas I, IA, and IB, R 19 It is optionally controlled by one or more R 20 Substituted phenyl groups.

[0032] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 It is optionally controlled by one or more R 20 Replaced monocyclic 3- to 8-membered heterocyclic rings.

[0033] In embodiments of compounds of formulas I, IA, and IB, R 19 It is optionally controlled by one or more R 20 Substituted monocyclic 5-membered heteroaryl group.

[0034] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 It is optionally controlled by one or more R 20 The replaced monocyclic non-aromatic 4- to 5-membered heterocycles.

[0035] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 Selected from aziridine and pyrrolidinyl; wherein the aziridine and pyrrolidinyl are optionally separated by one or more R 20 replace.

[0036] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 Optionally substituted by one or more substituents independently selected from the following: C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3- to 12-membered heterocyclic rings); wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 The alkyl group (3- to 12-membered heterocycle) is optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -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 ).

[0037] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 Optionally selected by one or more independently chosen from C 1-4 Alkyl and C 3-4 Substituents on the carbocyclic ring; where C 3-4 The carbon ring is optionally composed of one or more independently selected from halogens and C. 1-4 Alkyl substituents.

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

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

[0040] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19 It is unreplaced C 1-2 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 It is N(R) 9 ).

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

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

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

[0046] In embodiments of compounds of formula IA, IB, or IIA, R 10 Each time it appears, it is independently selected from C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Carbon rings and 3- to 12-membered heterocycles, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Carbon rings and 3- to 12-membered heterocycles are optionally separated by one or more R 20 replace.

[0047] In embodiments of compounds of formula IA, IB, or IIA, R 10 Each time it appears, it is independently selected from C. 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 3-5 Carbon rings and 3- to 5-membered heterocycles, of which C 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 3-5The carbon ring and 3- to 5-membered heterocycles are optionally separated by one or more R 20 replace.

[0048] In embodiments of compounds of formula IA, IB, or IIA, R 10 Each time it appears, it is independently selected from C. 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 3-5 Carbon rings and 3- to 5-membered heterocycles, of which C 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 3-5 The carbon ring and 3- to 5-membered heterocycles are optionally separated by one or more R groups selected from halogens, -OH, and -CN. 20 replace.

[0049] In embodiments of compounds of formula IA, IB, or IIA, R 10 Each occurrence is independently selected from unsubstituted C. 1-4 Alkyl, unsubstituted C 2-3 alkenyl, unsubstituted C 2-3 Alkyne group, unsubstituted C 3-5 Carbon rings and unsubstituted 3- to 5-membered heterocycles.

[0050] In embodiments of compounds of formula IA, IB, or IIA, R 10 Selected independently each time it appears. .

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

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

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

[0054] In embodiments of compounds of formula IA, IB, or IIA, R 11 Each time it appears, it is independently selected from C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Carbon rings and 3- to 12-membered heterocycles, of which C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-12 Carbon rings and 3- to 12-membered heterocycles are optionally separated by one or more R 20 replace.

[0055] In embodiments of compounds of formula IA, IB, or IIA, R 11 Each time it appears, it is independently selected from C. 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 3-5 Carbon rings and 3- to 5-membered heterocycles, of which C 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 3-5 The carbon ring and 3- to 5-membered heterocycles are optionally separated by one or more R 20 replace.

[0056] In embodiments of compounds of formula IA, IB, or IIA, R 11 Each occurrence is independently selected from unsubstituted C. 1-4 Alkyl, unsubstituted C 2-3 alkenyl, unsubstituted C 2-3 Alkyne group, unsubstituted C 3-5 Carbon rings and unsubstituted 3- to 5-membered heterocycles.

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

[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 It is C(R) 2 ).

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

[0062] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 2 It is -O(C) 1-3 Alkylene (4- to 10-membered heterocycles), wherein the 4- to 10-membered heterocycles are optionally selected by one, two, or three independently selected from halogens, C 1-3Alkyl, C 1-3 Halogenated alkyl groups and =C(R) 21 Substituents of )2.

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

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

[0065] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 2 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's C.

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

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

[0070] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 6 Each time it appears, it is independently selected from hydrogen and halogen.

[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 It is N(R) 6b ).

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

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

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

[0076] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 17 Selected from C 6-12 Carbon rings and 5- to 12-membered heterocycles, of which C 6-12 Carbon rings and 5- to 12-membered heterocycles are optionally separated by one or more R 20 replace.

[0077] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 17 The group is selected from phenyl, pyridyl, naphthyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzothiaphenyl, indazole, and benzoxazolyl, wherein phenyl, pyridyl, naphthyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzothiaphenyl, indazole, and benzoxazolyl are optionally separated by one or more R 20 replace.

[0078] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 17 Selected from: ,in: Q 1 Q 3 and Q 5 Independently selected from N and C(R) 1q ); Q 4 and Q 6 Independently selected from O, S, C(R) 1q )2 and N(R 1r ); Y 4 Y 5 Y 6 Y 9 and Y 10 Independently selected from C(R) 1q ) and N; Y 7 and Y 8 Independently selected from C(R) 1q ), C(R 1q 2. N and N(R) 1r ); Y 13Selected from key, 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 Independently selected from C(O) and C(R) 1q ), N, C(R) 1q )2 and N(R 1r ); Y 16 Selected from C, N and C(R) 1q ); Each R 1q Independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Substitution; or two Rs bonded to the same carbon atom 1q Linkages form 3- to 10-membered heterocycles or C 3-10 Carbon rings, including 3- to 10-membered heterocycles and C 3-10 The carbon ring is optionally divided by one or more R 20 Substitution; or bonding to two adjacent R atoms 1q Linkages form 3- to 10-membered heterocycles or C 3-10 Carbon rings, including 3- to 10-membered heterocycles and C 3-10 The carbon ring is optionally divided by one or more R 20 Replace; or an R 1q And an R 1r The connection forms 3- to 10-membered heterocycles or C 3-10 Carbon rings, including 3- to 10-membered heterocycles and C 3-10 The carbon ring is optionally divided by one or more R 20 replace; Each R 1r Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne groups, 3- to 10-membered heterocycles and C 3-10 Carbon ring, where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne groups, 3- to 10-membered heterocycles and C 3-10 The carbon ring is optionally divided by one or more R 20 Replace; and Each Independently represent single or double bonds, such that all valences are satisfied.

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

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

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

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

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

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

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

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

[0087] On the one hand, a BL-like structure is provided. BE Compounds with -E, wherein: B is the monovalent form of the compound described in this article; L BE It is a covalent joint bonded to B and E; and E represents the unit valence of the degradation enhancer.

[0088] In BL BE In embodiments of the -E compound, the degradation enhancer is capable of binding to proteins selected from: 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, PIAS3, 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), SCFb-TRCP (jumping-hysteresis-F-box (β-TRCP) ubiquitin complex), b-TRCP (protein containing β-transduction repeat sequence), cIAP1 (apoptosis inhibitor protein 1), APC / C (late mitosis promotion complex / cycle body), CRBN (cereblon), CUL4-RBX1-DDB1-CRBN (CRL4) CRBN 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, avadomide, iberdomide, and CC-885.

[0089] In embodiments of the compound of formula I B-LBE-E, the degradation enhancer is capable of binding to proteins selected from the following: 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] In BL BE In the embodiments of the -E compound, L BE Yes -L BE1 -L BE2 -L BE3 -L BE4 -L BE5 -; L BE1 L BE2 L BE3 L BE4 and L BE5 Independently, it is a bond, -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 imidene group, C 2-6 Ethyne group, C 1-6 Halogenated alkylene, C 3-12 Cycloalkylene, C 1-11 Heterocyclic alkylene, C 6-12 aryl or C 1-11 heteroaryl, of which C 1-6 Alkylene, C 2-6 imidene group, C2-6 Ethyne group, C 1-6 Halogenated alkylene, C 3-12 Cycloalkylene, C 1-11 Heterocyclic alkylene, C 6-12 aryl or C 1-11 The heteroaryl group is optionally surrounded by one, two or three Rs 20 Replace; and where (-OC) 1-6 alkyl) z - and (-C 1-6 alkyl-O) z - Each C 1-6 Alkyl groups are optionally surrounded by one, two, or three R groups. 20 Replace; and z is an integer from 0 to 10 independently.

[0091] In BL BE In the embodiments of the -E compound, L BE It is -(O-C2 alkyl)z- and z is an integer from 1 to 10.

[0092] In BL BE In the embodiments of the -E compound, L BE It is -(C2alkyl-O-)z- and z is an integer from 1 to 10.

[0093] In BL BE In the embodiments of the -E compound, L BE It is -(CH2) zz1 L BE2 (CH2O) zz2 -, where L BE2 It is a bond, a 5- or 6-membered heterocyclic alkylene or heteroarylene, a phenylene, or a -C bond. 2-4 The group is alkynyl, -SO2-, or -NH-; and zz1 and zz2 are independently integers from 0 to 10.

[0094] In BL BE In the embodiments of the -E compound, L BE It is -(CH2) zz1 (CH2O) zz2 - where zz1 and zz2 are each an independent integer from 0 to 10.

[0095] In BL BE In the embodiments of the -E compound, L BE It is a PEG connector.

[0096] In BL BE In embodiments of compounds with -E, E is a monovalent form selected from the following compounds: .

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

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

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

[0100] In embodiments of the methods described herein, reduced Ras signaling output is demonstrated by one or more of the following outputs: (i) an increase in the steady-state level of GDP-bound modified proteins; (ii) a decrease in the steady-state level of GTP-bound modified proteins; (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 growth of tumor cells expressing Ras G12S mutant proteins; and (vii) a decrease in Ras interactions with Ras pathway signaling proteins.

[0101] In an embodiment of the method described herein, the Ras mutant protein comprises the amino acid sequence of SEQ ID No. 4, which has a serine residue corresponding to position 12 of SEQ ID No. 1.

[0102] In an embodiment of the method described herein, the Ras mutant protein comprises the amino acid sequence of SEQ ID No. 4.

[0103] In embodiments of the method described herein, the modified Ras mutant protein comprises the amino acid sequence of SEQ ID No. 1, or a fragment thereof comprising a serine residue corresponding to position 12 of SEQ ID No. 1, and wherein the compound selectively labels serine residues as 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 method described herein, when measured under comparable conditions, the compound exhibits at least a 2-fold selective labeling of serine residues.

[0105] In embodiments of the method described herein, when measured under comparable conditions, the compound exhibits at least a 5-fold selective labeling of serine residues.

[0106] In the implementation of the method described herein, contact occurs within the body.

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

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

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

[0110] In an implementation of the method described herein, the cancer contains a K-Ras G12S mutant protein.

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

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

[0113] In an implementation of the method described herein, the method includes the application of an additional agent.

[0114] In embodiments of the methods described herein, additional agents include (1) inhibitors of MEK; (2) inhibitors of epidermal growth factor receptor (EGFR) and / or its mutants; (3) immunotherapeutic agents; (4) taxane; (5) antimetabolites; (6) inhibitors of FGFR1 and / or FGFR2 and / or FGFR3 and / or their mutants; (7) mitotic kinase inhibitors; (8) anti-angiogenic drugs; (9) topoisomerase inhibitors; (10) platinum-containing compounds; (11) inhibitors of c-MET and / or its mutants; (12) inhibitors of BCR-ABL and / or its mutants; (13) inhibitors of ErbB2 (Her2) and / or its mutants; (14) inhibitors of AXL and / or its mutants; (15) inhibitors of NTRK1 and / or its mutants; (16) inhibitors of RET and / or its mutants; (17) Inhibitors of A-Raf and / or B-Raf and / or C-Raf and / or their mutants; (18) Inhibitors of ERK and / or their mutants; (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 G12C inhibitors; (32) SHC inhibitors; (33) GAB inhibitors; (34) PI-3 kinase inhibitors; (35) MARPK inhibitors; (36) CDK4 / 6 inhibitors; (37) MAPK inhibitors; (38) SHP2 inhibitors; (39) checkpoint immune blockers; (40) SOS1 inhibitors; or (41) SOS2 inhibitors.

[0115] In embodiments of the method described herein, additional reagents include those selected from RMC-4630, ERAS-601, Inhibitors of SHP2.

[0116] In embodiments of the method described herein, additional reagents include those selected from RMC-5845, BI-1701963, Inhibitors of SOS.

[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, refamatetinib, and AZD6244.

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

[0120] In embodiments of the methods described herein, additional agents include CDK4 / 6 inhibitors selected from palbociclib, ribociclib, and abemaciclib.

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

[0122] All publications, patents and patent applications mentioned in this specification are incorporated herein by reference, just as each individual publication, patent or patent application is specifically and individually indicated to be incorporated herein by reference. Attached Figure Description

[0123] The novel features of the invention are specifically set forth in the appended claims. A better understanding of the features and advantages of the invention will be obtained by referring to the following detailed description and accompanying drawings, which illustrate exemplary embodiments in which the principles of the invention are utilized, in which: Figure 1Sequence alignments of various wild-type Ras proteins, including K-Ras, H-Ras, N-Ras, RalA, and RalB, are described from top to bottom. Detailed Implementation

[0124] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. If multiple definitions exist for terms herein, those defined 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) mentioned herein are incorporated herein by reference. Chemical structures herein are based on, as stated in ChemDraw... ® Naming conventions are used in the software (Perkin Elmer, Inc., Cambridge, MA). Section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described. As used in the specification and claims, the singular forms “a / an” and “the” include the plural referent unless the context clearly specifies otherwise. Furthermore, the use of the term “including” and other forms such as “include,” “includes,” and “included” is not limited. Section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described.

[0125] Term "C" x-y "or "C x -C y When used in conjunction with chemical moieties such as alkyl, alkenyl, or ynyl, it means to include groups containing x to y carbons in the chain. For example, the term "C x-y "Alkyl" refers to a substituted or unsubstituted saturated hydrocarbon group, including straight-chain alkyl and branched alkyl groups containing x to y carbons in the chain.

[0126] "Alkyl" refers to a substituted or unsubstituted saturated hydrocarbon group, including straight-chain and branched alkyl groups. Alkyl groups can contain 1 to 12 carbon atoms (e.g., C12). 1-12 Alkyl groups, such as those with 1 to 8 carbon atoms (C 1-8 Alkyl groups or 1 to 6 carbon atoms (C 1-6 Alkyl groups. Exemplary alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, and decyl. The alkyl group is attached to the remainder of the molecule by a single bond. Unless otherwise specified in the specification, the alkyl group may optionally be substituted with one or more substituents (such as those described herein).

[0127] "Halogenated alkyl" refers to an alkyl group that is substituted with one or more halogens. Exemplary halogenated alkyl groups include trifluoromethyl, difluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, and 1,2-dibromoethyl.

[0128] "Alkenyl" refers to a substituted or unsubstituted hydrocarbon group containing at least one double bond, including straight-chain and branched alkenyl groups. Alkenyl groups can contain 2 to 12 carbon atoms (e.g., C12). 2-12 Alkenyl), such as 2 to 8 carbon atoms (C 2-8 alkenyl) or 2 to 6 carbon atoms (C 2-6 Alkenyl groups. Exemplary alkenyl groups include ethenyl (i.e., vinyl), propenyl, butenyl, pentenyl, pent-1,4-dienyl, etc. Unless otherwise specifically stated in the specification, alkenyl groups may optionally be substituted with one or more substituents (such as those described herein).

[0129] "Alynyl" refers to a substituted or unsubstituted hydrocarbon group containing at least one triple bond, including straight-chain and branched alkynyl groups. Alynyl groups can contain 2 to 12 carbon atoms (e.g., C12, C23, C12, C23, C24 ...23, C24, C23, C24, C25, C26, C27, C28, C29, C29 2-12 Alkyne group), such as 2 to 8 carbon atoms (C 2-8 (alkynyl group) or 2 to 6 carbon atoms (C 2-6 Alynyl group. Exemplary alkynyl groups include ethynyl, propynyl, butynyl, pentylyl, hexynyl, etc. Unless otherwise specifically stated in the specification, the alkynyl group may optionally be substituted by one or more substituents (such as those described herein).

[0130] "alkylene" or "alkylene chain" refers to a substituted or unsubstituted divalent saturated hydrocarbon group, including straight-chain alkylene and branched-chain alkylene, which contains 1 to 12 carbon atoms (e.g., C12). 1-12 Alkylenes, such as those with 1 to 8 carbon atoms (C 1-8 Alkylene or 1 to 6 carbon atoms (C 1-6 Alkylenes. Exemplary alkylenes include methylene, ethylene, propylene, and n-butylene. Similarly, "alkenylene" and "ynyneene" refer to alkylenes as defined above, each containing one or more carbon-carbon double or triple bonds. The connection point between the alkylene, alkenyl, or ynyneene chain and the rest of the molecule can be through one or any two carbons in the chain. Unless otherwise specifically stated in the specification, alkylene, alkenyl, or ynyneenes may optionally be substituted with one or more substituents (such as those described herein).

[0131] “Heteroalkyl,” “heteroalkenyl,” and “heteroyneyl” refer to substituted or unsubstituted alkyl, alkenyl, and ynyl groups, respectively, in which one or more (such as 1, 2, or 3) carbon atoms 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 optionally be oxidized, and any nitrogen heteroatom may optionally be quaternized. If given, numerical ranges refer to the total chain length. For example, 3- to 8-membered heteroalkyl groups have chain lengths of 3 to 8 atoms. Connection to the remainder of the molecule can be made by heteroatoms or carbons in the heteroalkyl, heteroalkenyl, or heteroyneyl chain. Unless otherwise specifically stated in the specification, heteroalkyl, heteroalkenyl, or heteroyne groups are optionally substituted with one or more substituents (such as those described herein).

[0132] “Hypoalkylene,” “heteroenylene,” and “heteroynylene” refer to substituted or unsubstituted alkylene, alkenylene, and ynylene groups, respectively, in which one or more (such as 1, 2, or 3) carbon atoms 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 optionally be oxidized, and any nitrogen heteroatom may optionally be quaternized. If given, numerical ranges refer to the total chain length. For example, 3- to 8-membered heteroalkylene groups have chain lengths of 3 to 8 atoms. The connection point between the heteroalkylene, alkenylene, or ynylene group and the rest of the molecule may be through one heteroatom or one carbon atom in the heteroalkylene, alkenylene, or ynylene group, or any two heteroatoms, any two carbons, or any one heteroatom and any one carbon. Unless otherwise specifically stated in the specification, the heteroalkylene, alkenylene, or ynylene group may optionally be substituted with one or more substituents (such as those described herein).

[0133] A "carbon ring" refers to a saturated ring, unsaturated ring, or aromatic ring, where each atom of the ring is a carbon atom. Carbon rings can include C atoms. 3-10 Single ring, C 5-12 Double ring, C 5-18 Multi-ring, C 5-12 Spiral rings and C 5-12 Bridged rings. Each ring of a bicyclic or polycyclic carbon ring can be selected from saturated rings, unsaturated rings, and aromatic rings. Polycyclic carbon rings contain one or more rings, the number of which equals the minimum shear number required to convert the carbon ring into an acyclic skeleton (e.g., bicyclic, tricyclic, tetracyclic, etc.). In some embodiments, the carbon ring is C 6-12 Aryl, such as C 6-10 Aryl. In some embodiments, the carbide ring is C. 3-12 Cycloalkyl. In some embodiments, the carbide ring is C10. 5-12Cycloalkenyl. In exemplary embodiments, an aromatic ring (e.g., phenyl) may be fused with a saturated or unsaturated ring (e.g., cyclohexane, cyclopentane, or cyclohexene). Any combination of saturated, unsaturated, and aromatic rings is included in the definition of a carbocyclic ring, provided the valence allows. A carbocyclic ring may include fused rings, bridged rings, spirocyclic rings, saturated rings, unsaturated rings, aromatic rings, or any combination thereof. Exemplary carbocyclic rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Unless otherwise specifically stated in the specification, the carbocyclic ring may optionally be substituted with one or more substituents (such as those described herein).

[0134] A "heterocycle" refers to a saturated, unsaturated, or aromatic ring containing one or more heteroatoms, such as 1, 2, 3, or 4 heteroatoms selected from O, S, P, and N. Heterocycles can 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 bridged rings. Each ring of a bicyclic or polycyclic heterocycle can be selected from saturated, unsaturated, and aromatic rings. A polycyclic heterocycle contains one or more rings, the number of which is equal to the minimum shear number required to convert the heterocycle into an acyclic skeleton (e.g., bicyclic, tricyclic, tetracyclic, etc.). If valence permits, the heterocycle can be attached to the rest of the molecule by any atom of the heterocycle, such as a carbon or nitrogen atom. In some embodiments, the heterocycle is a 5- to 10-membered heteroaryl, such as a 5- or 6-membered heteroaryl. In some embodiments, the heterocycle is a 3- to 12-membered heterocyclic alkyl. Heterocyclic rings can include fused rings, bridged rings, spirocyclic rings, saturated rings, unsaturated rings, aromatic rings, or any combination thereof. In exemplary embodiments, the heterocyclic ring (e.g., pyridinyl) may be fused with a saturated or unsaturated ring (e.g., cyclohexane, cyclopentane, or cyclohexene). Exemplary heterocyclic rings include pyrrolidinyl, pyrrolidinyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, pyrimidinyl, pyrazinyl, thiophenyl, oxazolyl, thiazolyl, morpholinyl, indazole, indolyl, benzothiophenyl, benzoxazolyl, and quinolinyl. Unless otherwise specifically stated in the specification, the heterocyclic ring may optionally be substituted with one or more substituents (such as those described herein).

[0135] "Heteroaryl" refers to an aromatic ring containing at least one heteroatom, such as 1, 2, 3, or 4 heteroatoms selected from O, S, and N. Heteroaryls can include 5- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, 6- to 18-membered polycyclic rings, 5- to 12-membered spirocyclic rings, and 6- to 12-membered bridged rings. As used herein, the heteroaryl ring can be selected from monocyclic, bicyclic, or polycyclic systems—including fused ring systems, spirocyclic systems, and bridged ring systems—where at least one ring in the ring system is aromatic and contains at least one heteroatom. Polycyclic heteroaryls contain one or more rings, the number of which equals the minimum cleavage number (e.g., bicyclic, tricyclic, tetracyclic, etc.) required to convert the heteroaryl to an acyclic skeleton. The heteroatoms in the heteroaryl may optionally be oxidized. One or more nitrogen atoms (if present) may optionally be quaternized. If the valence allows, the heteroaryl can be attached to the rest of the molecule by any atom of the heteroaryl, such as a carbon or nitrogen atom of the heteroaryl. Examples of heteroaryl groups include, but are not limited to, azaheptenyl, benzimidazolyl, benzisisothiazolyl, benzisisooxazolyl, benzofuranyl, benzothiazolyl, benzothiophenyl, benzooxazolyl, furanyl, imidazolyl, indazole, indolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, purinyl, pyrazinyl, pyrazolylalkyl, pyrazolyl, pyridinyl, pyridinyl, pyridinyl, pyrimidinyl, pyrroleyl, quinazolinyl, quinolinyl, quinoxalolinyl, tetrahydroquinolinyl, thiadiazolyl, thiazolyl, and thiophenyl. Unless otherwise specifically stated in the specification, heteroaryl groups may optionally be substituted with one or more substituents (such as those described herein).

[0136] Unless otherwise stated, hydrogen atoms are implicitly included in the structure described herein as necessary to satisfy the valence requirements.

[0137] A wavy line drawn across a key or at the end of a key. "or dashed key" "These terms can be used interchangeably in this document to indicate where a key break or connection occurs. For example, in a structure..." In the middle, if R 7 Such as In 2-fluoro-6-hydroxyphenyl, then R 7 It can be described as " " "or" ".

[0138] The term "substituted" refers to a portion of a structure having a substituent that replaces hydrogen atom on one or more carbon or heteroatoms. It should be understood that "substituted" or "replaced by" includes the implicit limiting condition that such substitution meets the permissible valence of the substituted atom and the substituent, and that the substitution produces a stable compound, for example, which does not spontaneously undergo transformations such as rearrangement, cyclization, elimination, etc. As used herein, the term "substituted" is contemplated to include all permissible substituents in organic compounds. In a broad sense, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents in organic compounds. For a suitable organic compound, permissible substituents may be one or more, and may be the same or different. For the purposes of this disclosure, heteroatoms such as nitrogen may have any permissible substituent in organic compounds that meet the valence of heteroatoms as described herein.

[0139] The compounds disclosed herein, such as those of formula I, IA, IB, II, or IIA, are optionally substituted by one or more substituents, such as 1, 2, or 3 selected from the following: Halogen, Oxide, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ); where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), C 3-12 The carbocyclic ring and the 3- to 12-membered heterocycle are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -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 ); R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3- to 12-membered heterocyclic rings), or two R groups 21 Together with the carbon atoms they are attached to, they form C 3-12 Carbon rings or 3- to 12-membered heterocycles, wherein C 3-12 The carbon ring or 3- to 12-membered heterocycles are each optionally selected by one, two, or three independently from halogens, C 1-3 Alkyl, C 1-3 Substitution with haloalkyl groups and -OH groups; R 22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3- to 12-membered heterocyclic), wherein -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl groups (3- to 12-membered heterocycles) are optionally separated by one, two, or three independently selected from halogens and C. 1-6 Alkyl groups are substituted; and R 23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R atoms bonded to the same nitrogen atom 22 and R 23 Formation of 3- to 10-membered heterocycles.

[0140] In some embodiments, the compounds disclosed herein, such as those of formula I, IA, IB, II, or IIA, are optionally substituted with one or more substituents selected from: Halogen, Oxide, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 )-, where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), C 3-12 The carbocyclic ring and the 3- to 12-membered heterocycle are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -OR 22 -SR 22 -N(R) 22 (R) 23 =NR 22 and = C(R) 21 )2; R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl and C 1-6 Halogenated alkyl groups; R 22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3- to 12-membered heterocyclic), wherein -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl groups (3- to 12-membered heterocycles) are optionally separated by one, two, or three independently selected from halogens and C. 1-6 Alkyl group substitution; R 23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R atoms bonded to the same nitrogen atom 22 and R 23 Formation of 3- to 10-membered heterocycles.

[0141] In some embodiments, the compounds disclosed herein, such as those of formula I, IA, IB, II, or IIA, are optionally substituted with one or more substituents selected from: halogen, oxo, =NH, -CN, -NO2, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbon ring, -CH2-(C 3-10a carbocyclic ring), a 3- to 10-membered heterocyclic ring, -CH2-(a 3- to 10-membered heterocyclic ring), -OH, -OCH3, -OCH2CH3, -NH2, -NHCH3, and -NHCH2CH3, wherein C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 a carbocyclic ring, -CH2-(C 3-10 a carbocyclic ring), a 3- to 10-membered heterocyclic ring, and -CH2-(a 3- to 10-membered heterocyclic ring) are optionally substituted by one, two, or three groups independently selected from halogen, oxo, =NH, -CN, -NO2, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -OH, -OCH3, -OCH2CH3, -NH2, -NHCH3, and -NHCH2CH3.

[0142] Those skilled in the art will understand that, if appropriate, the substituents themselves may be substituted. Unless specifically stated as "unsubstituted", chemical moieties mentioned herein should be understood to include substituted variants. For example, the mention of a "heteroaryl" group or moiety implicitly includes both substituted and unsubstituted variants.

[0143] In the case where divalent substituents are specified herein by their conventional chemical formulas written from left to right, they are intended to cover isomers resulting from writing the structure from right to left. For example, -CH2O- is also intended to cover -OCH2-.

[0144] "Optional" or "optionally" means that the subsequent described event or situation may or may not occur, and the description includes cases where the event or situation occurs and cases where the event or situation does not occur. For example, an "optionally substituted" group may be unsubstituted or substituted.

[0145] The compounds of the present disclosure also include crystalline and amorphous forms of these compounds, pharmaceutically acceptable salts, and active metabolites having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, unsolvated polymorphs (including dehydrates), conformational polymorphs, amorphous forms of the compounds, and mixtures thereof.

[0146] The compounds described herein may be presented in their natural isotopic abundances, or one or more of the atoms may be artificially enriched with a specific isotope that has the same atomic number but a different atomic mass or mass number from the atomic mass or mass number predominantly found in nature. All isotopic variants of the compounds of the present disclosure, whether radioactive or not, are encompassed within the scope of the present disclosure. For example, hydrogen has three naturally occurring isotopes, designated as 1 H (protium), 2 H (deuterium), and3 H (tritium). Tritium is the most abundant hydrogen isotope in nature. Enrichment of deuterium can provide certain therapeutic advantages, such as increased in vivo half-life and / or exposure, or can provide compounds for studying in vivo drug elimination and metabolic pathways. Examples of isotopes that can be incorporated into the compounds of this disclosure include, but are not limited to, those mentioned above. 2 H, 3 H, 13 C 14 C 15 N、 18 O、 17 O、 35 S, 36 Cl and 18 F. Of particular interest are compounds enriched in tritium or carbon-14 of formulas I, IA, IB, II, or IIA, which can be used, for example, for tissue distribution studies; compounds enriched in deuterium (particularly at metabolic sites) of this disclosure, which produce, for example, compounds with higher metabolic stability; and compounds enriched in positron-emitting isotopes such as 11 C 18 F, 15 O and 13 Compounds of formula I, IA, IB, II, or IIA of N can be used, for example, in positron emission tomography (PET) studies. Compounds enriched with isotopes can be prepared using conventional techniques well known to those skilled in the art.

[0147] As used herein, the phrases “of a form,” “having a form,” or “having a structure” are not intended to be restrictive and are used in the same manner as the commonly used term “comprising.” For example, if a structure is described, it should be understood to encompass all stereoisomers and tautomers unless otherwise stated.

[0148] Some of the compounds described herein contain one or more asymmetric centers and are therefore capable of producing enantiomers, diastereomers, and other stereoisomers, the asymmetric centers of which may be defined as (R)- or (S)- according to absolute stereochemistry. In some embodiments, to optimize the therapeutic activity of the compounds of this disclosure, for example, to treat cancer, it may be necessary for the carbon atoms to have a specific configuration (e.g., (R,R), (S,S), (S,R), or (R,S)) or to be enriched in stereoisomers having such configurations. The compounds of this disclosure may be provided as racemic mixtures. Therefore, unless otherwise stated, this disclosure relates to racemic mixtures, pure stereoisomers (e.g., enantiomers and diastereomers), mixtures enriched in stereoisomers, etc. When a chemical structure without any stereochemistry is described herein, it should be understood that all possible stereoisomers are covered by such structures. Similarly, when specific stereoisomers are shown or named herein, those skilled in the art will understand that, unless otherwise stated, small amounts of other stereoisomers may be present in the compositions disclosed herein, provided that the presence of such other isomers does not negate the utility of the composition as a whole. Individual stereoisomers can be obtained by many methods known in the art, including preparation using chiral synthons or chiral reagents, resolution using chiral chromatography utilizing a suitable chiral stationary phase or support, or separation of diastereomers by conventional means such as chromatography or recrystallization, and regeneration of the original stereoisomers.

[0149] Additionally, where applicable, unless otherwise stated, all cis-trans or cis-trans compounds described herein are not part of the standard. E / Z Isomers (geometric isomers), tautomers, and topological isomers are all included within the scope of this disclosure.

[0150] The term "pharmaceutically acceptable" means a material that is not biologically or otherwise unacceptable when used in the subject composition and methods. For example, the term "pharmaceutically acceptable carrier" refers to materials such as excipients, glidants, sweeteners, diluents, preservatives, dyes, colorants, flavor enhancers, surfactants, wetting agents, dispersants, suspending agents, stabilizers, isotonic agents, solvents, or emulsifiers 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 materials generally meet the requirements of toxicological and manufacturing testing standards and include those materials that have been determined by the U.S. Food and Drug Administration to be suitable inactive ingredients.

[0151] The terms "salt" and "pharmaceutically acceptable salt" refer to salts prepared from bases or acids. Pharmaceutically acceptable salts are suitable for administration to patients such as mammals (e.g., salts with acceptable mammalian safety for a given dosage regimen). Salts can be formed from inorganic bases, organic bases, inorganic acids, and organic acids. Furthermore, when a compound contains both a basic moiety (such as an amine, pyridine, or imidazole) and an acidic moiety (such as a carboxylic acid or tetraazole), zwitterions can be formed and included in the term "salt" as used herein. Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0152] "Pharmaceutically acceptable acid addition salts" refer to salts that retain the biological effectiveness and properties of the free base, are not biologically or otherwise undesirable, and are formed from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphorous acid, etc. This also includes salts formed from organic acids such as aliphatic monocarboxylic acids and dicarboxylic acids, phenyl-substituted alkanes, hydroxyalkanes, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, etc., including, 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, salicylic acid, etc. Therefore, exemplary salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, trifluoroacetates, propionates, caprylates, isobutyrates, oxalates, malonates, succinates, caprylates, sebacic acid salts, fumarates, maleates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, phthalates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, malates, tartrates, methanesulfonates, etc. Salts of amino acids such as arginine salts, gluconates, and galacturons are also considered (see, for example, Berge SM et al., "Pharmaceutical Salts"). Journal of Pharmaceutical Science, 66:1-19 (1997)). In some embodiments, the acid addition salt of a basic compound is prepared by contacting a sufficient amount of the desired acid with a free base form to produce a salt, according to methods and techniques familiar to a skilled craftsman.

[0153] "Pharmaceutically acceptable base addition salts" refer to salts that retain the bioavailability and properties of the free acid and are 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 using metals or amines such as alkali metals and alkaline earth metals or organic amines. 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, and procaine. N,N -Dibenzylethylenediamine, chloroprocaine, hydrabamine, choline, betaine, ethylenediamine, ethylenediphenylamine N methyl-reduced glucosamine, glucosamine, methylglucosamine, theobromine, purine, piperazine, piperidine, N -Ethylpiperidine, polyamine resins, etc. See Berge et al. (ibid.).

[0154] The term "effective amount" or "therapeutic effective amount" refers to the amount of a pharmaceutical agent sufficient to achieve a beneficial or desired result. Therapeutic effective amounts can vary based on one or more of the following: the subject and disease condition being treated, the subject's weight and age, the severity of the disease condition, the method of administration, etc., which can be readily determined by those skilled in the art. An effective amount of an active pharmaceutical agent can be administered in a single dose or in multiple doses. A component can be described herein as having at least an effective amount, such as an amount associated with a specific target or purpose as described herein. The term "effective amount" also applies to the dose that will provide a detection image via a suitable imaging method. A specific dose can vary based on one or more of the following: the specific pharmaceutical agent selected, the dosing regimen to be followed, whether it is administered in combination with other compounds, the time of administration, the tissue to be imaged, and the physical delivery system in which it is carried.

[0155] As used herein, “treating” or “treatment” means a method used to obtain a beneficial or desired outcome for a subject’s disease, symptom, or medical condition (such as cancer), including but not limited to: (a) preventing the occurrence of the disease or medical condition, such as preventing the recurrence of the disease or medical condition, or providing preventative treatment to a subject susceptible to the disease or medical condition; (b) improving the disease or medical condition, such as eliminating or resolving the subject’s disease or medical condition; (c) suppressing the disease or medical condition, such as slowing or halting the progression of the subject’s disease or medical condition; or (d) alleviating the symptoms of the subject’s disease or medical condition. For example, “treating cancer” would include preventing the occurrence of cancer, improving cancer, suppressing cancer, and alleviating the symptoms of cancer. Furthermore, a therapeutic benefit is achieved by eradicating or improving one or more of the physiological symptoms associated with an underlying condition, such that improvement is observed in the subject, even though the subject may still have the underlying condition.

[0156] As used herein, the term "therapeutic effect" encompasses the therapeutic benefits 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, slowing, stopping, or reversing the progression of a disease or condition, or any combination thereof.

[0157] The terms “antagonist” and “inhibitor” are used interchangeably, and they refer to compounds that have the ability to inhibit the biological functions (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 the context of the biological function of the target protein. While the preferred antagonists herein interact specifically with the target (e.g., bind to the target), compounds that inhibit the biological activity of a target protein by interacting with other members of a signal transduction pathway, wherein the target protein is a member of that signal transduction pathway, are also specifically included within this definition.

[0158] The term "selective inhibition" or "selective inhibition" refers to the ability of a bioactive drug to preferentially reduce the target signal transduction activity compared to off-target signal transduction activity through direct or indirect interaction with the target.

[0159] The terms "object" and "patient" refer to animals, such as mammals, like humans. The methods described herein can be used for both human treatment and veterinary applications. In some embodiments, the object is a mammal, such as a human. "Mammalian" includes humans and livestock, such as laboratory animals and domestic pets (e.g., cats, dogs, pigs, cattle, sheep, goats, horses, rabbits), as well as non-livestock animals, such as wild animals.

[0160] The terms "therapeutic agent," "therapeutic capable agent," or "treatment agent" are used interchangeably and refer to a molecule or compound that imparts a beneficial effect when applied to a subject. Beneficial effects include enabling a diagnosis; improving a disease, symptom, condition, or pathological state; reducing or preventing the onset of a disease, symptom, condition, or pathological state; and generally combating a disease, symptom, condition, or pathological state.

[0161] The terms “polypeptide,” “peptide,” and “protein” are used interchangeably herein and refer to a polymer of amino acids of any length. This polymer may be linear or branched, may contain modified amino acids, and may be interrupted by non-amino acid components. The term also encompasses amino acid polymers that have been modified (e.g., by disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeled component). As used herein, the term “amino acid” refers to natural and / or non-natural or synthetic amino acids, including glycine and its D or L optical isomers, as well as amino acid analogs and peptide mimics.

[0162] The terms “polynucleotide,” “nucleotide sequence,” “nucleic acid,” and “oligonucleotide” are used interchangeably. They refer to polymeric forms of nucleotides or their analogues of deoxyribonucleotides or ribonucleotides of any length. Polynucleotides can have any three-dimensional structure and can perform any known or unknown function. The following are non-limiting examples of polynucleotides: coding or non-coding regions of genes or gene segments, loci (loci / locus) defined by linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, short interfering RNA (siRNA), short hairpin RNA (shRNA), microRNA (miRNA), ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA with any sequence, isolated RNA with any sequence, nucleic acid probes, and primers. Polynucleotides can contain one or more modified nucleotides, such as methylated nucleotides and nucleotide analogs, such as peptide nucleic acids (PNAs), morpholino oligonucleotides and locked nucleic acids (LNAs), glycerol nucleic acids (GNAs), threonine nucleic acids (TNAs), 2'-fluoronucleotides, 2'-OMe nucleic acids, and phosphorylated DNA. If present, modifications to the nucleotide structure can be conferred before or after polymer assembly. The sequence of the nucleotides can be interrupted by non-nucleotide components. Polynucleotides can be further modified after polymerization, such as by conjugation with labeled components or other conjugation targets.

[0163] As used herein, “expression” refers to the process by which polynucleotides are transcribed from a DNA template (such as into mRNA or other RNA transcripts) and / or the transcribed mRNA is subsequently translated into peptides, polypeptides, or proteins. Transcripts and encoded polypeptides can be collectively referred to as “gene products.” If the polynucleotides are derived from genomic DNA, expression can include the splicing of mRNA in eukaryotic cells.

[0164] An "antigen" is a part or molecule of an antibody that contains an epitope and therefore specifically binds to it. An "antigen-binding unit" can be the whole or a fragment (or multiple fragments) of a full-length antibody, a structural variant of it, a functional variant of it, 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 fragments of full-length antibodies can include, but are not limited to, variable heavy chains (VH), variable light chains (VL), and heavy chains (VHH or VL) found in camelidae animals such as camels, llamas, and alpacas. H H), heavy chains (V-NAR domains) found in sharks, single-domain antibodies (sdAbs, such as “nanobodies”) containing a single antigen-binding domain, Fv, Fd, Fab, Fab', F(ab')2 and “r IgG” (or haptens). Examples of modified fragments of antibodies may include, but are not limited to, scFv, di-scFv or bi(s)-scFv, scFv-Fc, scFv-zipper, scFab, Fab2, Fab3, diabody, single-chain bifunctional antibody, tandem bifunctional antibody, tandem di-scFv, tandem tri-scFv, minibody (e.g., (VH-VL-CH3)2, (scFv-CH3)2, ((scFv)2-CH3+CH3), ((scFv)2-CH3) or (scFv-CH3-scFv)2, and multibody (e.g., triabody or tetrabody).

[0165] The terms “antibody” and “antibodies” encompass any antigen-binding unit, including but not limited to: monoclonal antibodies, human antibodies, humanized antibodies, camel-derived antibodies, chimeric antibodies, and any other epitope-binding fragments.

[0166] “Prodrug” means a compound that can be converted into the bioactive compound described herein (e.g., formula I, IA, IB, II, or IIA) under physiological conditions or by solvent degradation. Therefore, the term “prodrug” refers to a precursor of a pharmaceutically acceptable bioactive compound. In some respects, a prodrug is inactive when administered to a subject, but is converted into the active compound in vivo, for example, by hydrolysis. Prodrug compounds often offer advantages in mammalian organisms such as solubility, tissue compatibility, 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) ACS Symposium Series, Vol. 14; and Bioreversible Carriers in Drug Design, edited by Edward B. Roche, American Pharmaceutical Association and Pergamon Press, each incorporated herein by reference in its entirety). The term "prodrug" also refers to any covalently bonded carrier that, when administered to a mammalian subject, releases the active compound in vivo. As described herein, prodrugs of active compounds are typically prepared by modifying functional groups present in the active compound in such a manner that the modification is cleaved into the parent active compound under conventional procedures or in vivo. Prodrugs include compounds in which a hydroxyl, amino, or thiol group is bonded to any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl, free amino, or free thiol group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate, and benzoate derivatives of the hydroxyl functional group in the active compound, or acetamide, formamide, and benzamide derivatives of the amine functional group.

[0167] The term "in vivo" refers to an event that occurs within the body of an object. The term "ex vivo" refers to an event that first occurs outside the body of an object, intended for subsequent application inside the body. For example, ex vivo preparation may involve preparing cells outside the body of an object for the purpose of introducing the prepared cells into the body of the same or different objects. The term "in vitro" refers to an event that occurs outside the body of an object. For example, in vitro assays cover any assay performed outside the body of an object. In vitro assays cover cell-based assays in which live or dead cells are used. In vitro assays also cover cell-free assays in which intact cells are not used.

[0168] This disclosure also refers to the in vivo metabolites of the disclosed compounds. Such products can be generated, for example, by oxidation, reduction, hydrolysis, amidation, esterification, etc., of the applied compound, primarily due to enzymatic processes. Therefore, this disclosure includes compounds produced by a method comprising administering the disclosed compound to a mammal for a duration sufficient to produce its metabolites. Such products are typically identified by administering the radiolabeled compound of this disclosure at a detectable dose to an animal (such as a rat, mouse, guinea pig, monkey, or human), allowing sufficient time for metabolism, and isolating its metabolites from urine, blood, or other biological samples.

[0169] The term "Ras" or "RAS" refers to proteins in the Rat Sarcoma (Ras) superfamily of small GTPases, such as proteins in 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 KRAS (which may also be used interchangeably herein as K-Ras, K-ras, or 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, such as those selected from KRAS, HRAS, NRAS, RALA, RALB, and any combination thereof.

[0170] As may be used interchangeably herein, the terms "mutant Ras" and "Ras mutant" refer to a Ras protein having one or more amino acid mutations relative to a common reference sequence such as a wild-type (WT) sequence. In some embodiments, 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. In some embodiments, the mutation can be an introduced mutation, a naturally occurring mutation, or a non-naturally occurring mutation. In some embodiments, the mutation can 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 can be sequential, discontinuous, or a combination thereof. In some embodiments, the mutation may be present at any location on Ras. In some embodiments, when optimally aligned, the mutation may be present at position 12, 13, 62, 92, 95, 96 (e.g., Y96D), or any combination thereof, relative to Ras of SEQ ID No. 1. In some embodiments, the mutant Ras may contain about or at least about 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, 50, or more than 50 mutations. In some embodiments, the mutant Ras may contain up to about 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 about or at most about 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 or less amino acids. In some embodiments, the mutated amino acids are protein amino acids, natural amino acids, standard amino acids, non-standard amino acids, atypical amino acids, essential amino acids, non-essential amino acids or non-natural amino acids.In some embodiments, the mutated 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, the mutant Ras can be further modified, such as by conjugation with a detectable tag. In some embodiments, the mutant Ras is a full-length or truncated polypeptide. For example, the mutant Ras can be a truncated polypeptide containing residues 1-169 or residues 11-183 (e.g., residues 11-183 of mutant RALA or mutant RALB).

[0171] As used herein, the terms "corresponding to" or "corresponds to" when applied to amino acid residues in a polypeptide sequence refer to the correspondence of such amino acids to a reference sequence when optimal alignment is achieved (e.g., considering gaps, insertions, and mismatches; where the alignment can be a primary sequence alignment of a folded protein or a three-dimensional structure alignment). For example, a serine residue in the K-Ras G12S mutant refers to the serine residue at residue 12 of SEQ ID No. 4 (which can be used as a reference sequence). Similarly, an aspartic acid residue in the K-Ras G12D mutant refers to the aspartic acid residue at residue 12 of SEQ ID No. 2 (which can be used as a reference sequence). When the amino acids of the mutant Ras protein correspond to the amino acid positions in the WTRras protein, it should be understood that although the amino acids of the mutant Ras protein can be different amino acids (e.g., G12D, where the wild-type G at position 12 is replaced by aspartic acid at position 12 of SEQ ID No. 1), the mutant amino acid is located at the position corresponding to the wild-type amino acid (e.g., SEQ ID No. 1). In embodiments, the modified Ras mutant proteins disclosed herein may include a C-terminal truncation preceding a serine residue or an N-terminal truncation. The serine residue in such N-terminated modified mutants 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 has corresponding residues found in SEQ ID No. 6 and 8.

[0172] The terms “Switch II pocket” and “switch II binding pocket”, used interchangeably herein, refer to the binding pocket formed below the “Switch II” ring of Ras. In some embodiments, the Switch II pocket is located between the central β-fold (β-fold) of Ras and the α2 and α3 helices. In some embodiments, the Switch II binding pocket is located at a position 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 more from the 12th, 60th, 99th, or any combination thereof. In some embodiments, the Switch II binding pocket is located at a position at most about 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 nm or more from the 12th, 60th, 99th, or any combination thereof. In some cases, the Switch II pocket may form after binding to a small molecule (e.g., a small molecule inhibitor). Alternatively, the Switch II pocket may form before binding to a small molecule.

[0173] In some embodiments, the Switch II pocket of Ras contains three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen or more amino acid residues, or contains three to fifteen residues selected from: V7, V9, G10, G12, G12X mutants of SEQ ID NO. 1 (e.g., G12C, G12S, G12D or G12V), K14, K16, P34, T58, A59, G60, Q61, E62, E63, Y64, S65, R68, D69, M72, D92, H95, Y96, Q99, I100, R102 and V103, or corresponding amino acid residues of HRAS or NRAS proteins. In some embodiments, the Switch II pocket of Ras contains three, four, five, six, seven, eight, nine, ten, eleven, or twelve amino acid residues selected from the G10, G12, G12X mutants (e.g., G12C, G12S, G12D, or G12V), K16, P34, T58, A59, E62, R68, D69, H95, Q99, R102, and V103 of SEQ ID NO. 1, or the corresponding amino acid residues of HRAS or NRAS proteins.

[0174] As used herein, the term "leaving group" refers to an atom or group that detaches from the residue or bulk of the substrate during a particular reaction. The residue or bulk of the substrate is also referred to herein as a "retaining group".

[0175] compound On one hand, a compound of formula (I) is provided: , Or a pharmaceutically acceptable salt or solvate thereof, wherein: Ring A is selected from single ring C 7-10 Carbon rings and monocyclic heterocycles with 7 to 10 membered members; X 1 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 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 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 Selected from C, C(R) 4 ) and N; X 5 Selected from C, C(R) 5 ) and N; X 6 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 Selected from C(R) 7 ), C(R 7 (R) 7a ) and N(R 7b ); X 8 Selected from C(R) 8 ), C(R 8 )2、N、N(R 8b ), O, S, S(O), S(O)2 and C(O); X 13Selected from C, C(R) 13a ) and N; X 14 Selected from C, C(R) 14a ) and N; R 7 Yes -L 7a -R 17 ;R 7b Yes -L 7b -R 17 ; L 7a Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; L 7b Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -C(O)- and -C(O)N(R) 12 )-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups.20 replace; R 9 Yes -L 19 -R 19 -L 19a -R 19a ; L 19 Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; R 19 Selected from monocyclic C 3-8 Carbon rings and monocyclic 3- to 8-membered heterocycles, of which monocyclic C 3-8 Carbon rings and monocyclic 3- to 8-membered heterocycles are optionally separated by one or more R 20 replace; L 19a Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; R 19a Selected from: i) A 5-membered heteroaryl group comprising one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is obtained through R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a Optionally by one or more R 20 Replace; and ii) A 5- to 12-membered heterocycle comprising three or four cyclic nitrogen atoms, wherein the 5- to 12-membered heterocycle is optionally separated by one or more R atoms. 20 replace; R 1b R 2b R 3b R 6b and R 8b Independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 1 R 2 R 3 R 4 R 5 R 6 R 7a R 8 R 13a R 14a and R 17 Each time it appears, it is independently selected from hydrogen, halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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(R12 )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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 12 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3- to 12-membered heterocyclic), wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl (3- to 12-membered heterocycle) optionally surrounded by one or more R 20 replace; R 13 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl and C 1-6Haloalkyl; or R attached to the same nitrogen atom 12 and R 13 Formed optionally by one or more R 20 Replacement of 3- to 10-membered heterocycles; R 20 Each time it appears, it is independently selected from halogen, oxo, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ); where C 1-6 Alkyl, C 2-6 alkenyl, C2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -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 ); R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Haloalkyl, -C0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3- to 12-membered heterocycles) or two R 21 Together with the carbon atoms they are attached to, they form C 3-12 Carbon rings or 3- to 12-membered heterocycles, wherein C 3-12 The carbon ring or 3- to 12-membered heterocycles are each optionally selected independently from halogens, C 1-3 Alkyl, C 1-3 Substitution with haloalkyl groups and -OH groups; R 22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Alkyl groups (3- to 12-membered heterocycles); R 23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R atoms bonded to the same nitrogen atom 22 and R 23 Formation of 3- to 10-membered heterocycles; R 29 Each time it appears, it is independently selected from halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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)R12 -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Substitution; and where two R atoms connected to the same atom 29 Optional linkage to form an oxo group; n29 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13; and Each Independently represent single or double bonds, such that all valences are satisfied.

[0176] In this article, references to ring A only include those atoms in the described ring or ring system that lie on the shortest path between the two points connected to ring A (i.e., -X in Equation I). 5 -X 13 -X 4 For example, in compounds (a) and (b) shown in the figure below, ring A is (a) a 7-membered monocyclic heterocycle or (b) a 7-membered monocyclic carbon ring.

[0177] .

[0178] In embodiments of the compound of formula I, the compound has formula (IA): , Or a pharmaceutically acceptable salt or solvate thereof, wherein: X9 Selected from C(R) 9 ), C(R 9 (R) 9a ) and N(R 9 ); X 10 Selected from C(R) 10 ), C(R 10 )2、N、N(R 10b ), O, S, S(O), S(O)2 and C(O); X 11 Selected from C(R) 11 ), C(R 11 )2、N、N(R 11b ), O, S, S(O), S(O)2 and C(O); X 12 Selected from -X 12a -、-X 12a -X 12b -、-X 12a -X 12b -X 12c -and-X 12a -X 12b -X 12c -X 12d -; where X 12a With X 5 Direct bonding; X 12a X 12b X 12c and X 12d Independently selected from C(R) 12a ), C(R 12a )2、N、N(R 12b ), O, S, S(O), S(O)2 and C(O); R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a Optionally by one or more R 20 replace; R 10b R 11b and R 12b Independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12(Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 9a R 10 R 11 and R 12a Each time it appears, it is independently selected from hydrogen, halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Replace; and Each Independently represent single or double bonds, such that all valences are satisfied.

[0179] In embodiments of the compound of formula I, the compound has formula (IB): , Or a pharmaceutically acceptable salt or solvate thereof, wherein: X 9 Selected from C(R) 9 ), C(R 9 (R) 9a ) and N(R 9 ); X 10 Selected from C(R)10 ), C(R 10 )2、N、N(R 10b ), O, S, S(O), S(O)2 and C(O); X 11 Selected from C(R) 11 ), C(R 11 )2、N、N(R 11b ), O, S, S(O), S(O)2 and C(O); X 12 Selected from -X 12a -、-X 12a -X 12b -、-X 12a -X 12b -X 12c -and-X 12a -X 12b -X 12c -X 12d -; where X 12a With X 5 Direct bonding; X 12a X 12b X 12c and X 12d Independently selected from C(R) 12a ), C(R 12a )2、N、N(R 12b ), O, S, S(O), S(O)2 and C(O); R 19a It is a 5- to 12-membered heterocycle containing three or four cyclic nitrogen atoms, wherein the 5- to 12-membered heterocycle is optionally separated by one or more R atoms. 20 replace; R 10b R 11b and R 12b Independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) are optionally separated by one, two or three R 20 replace; R 9a R 10 R 11 and R 12a Each time it appears, it is independently selected from hydrogen, halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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)R12 -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Replace; and Each Independently represent single or double bonds, such that all valences are satisfied.

[0180] On one hand, a compound of formula (II) is provided: , Or a pharmaceutically acceptable salt or solvate thereof, wherein: Ring A is selected from single ring C 7-10 Carbon rings and monocyclic heterocycles with 7 to 10 membered members; X 1 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 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 Selected from C(R) 3 ), C(R3 )2、N、N(R 3b ), O, S, S(O), S(O)2 and C(O); X 4 Selected from C, C(R) 4 ) and N; X 5 Selected from C, C(R) 5 ) and N; X 6 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 Selected from C(R) 7 ), C(R 7 (R) 7a ) and N(R 7b ); X 8 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 Selected from C, C(R) 13a ) and N; X 14 Selected from C, C(R) 14a ) and N; R 7 Yes -L 7a -R 17 ;R 7b Yes -L 7b -R 17 ; L 7a Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; L 7b Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -C(O)- and -C(O)N(R) 12 )-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; R 17 Selected independently from C 3-12 Carbon rings and 3- to 12-membered heterocycles, of which C 3-12 Carbon rings and 3- to 12-membered heterocycles are optionally separated by one or more R 20 replace; R 9 Yes -L 19 -R 19 -L 19a -R 19a ; L 19 Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )-, -OS(O)2-, -OS(O)-, -OP(O)(R 12 )-, -S(O)2O-, -S(O)O-, and -P(O)(R 12 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; R 19 Selected from non-aromatic monocyclic C4-8 carbon rings and non-aromatic monocyclic 3- to 8-membered heterocycles, wherein the non-aromatic monocyclic C4-8 carbon rings and non-aromatic monocyclic 3- to 8-membered heterocycles are optionally separated by one or more R 20 replace; L 19a Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; R 19a Selected from halogens, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 1b R 2b R 3b R 6b and R 8b Independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 1 R 2 R 3 R 4 R 5 R 6 R 7a R 8 R13a and R 14a Each time it appears, it is independently selected from hydrogen, halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 12 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3- to 12-membered heterocyclic), wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl (3- to 12-membered heterocycle) optionally surrounded by one or more R 20 replace; R 13 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl; or R attached to the same nitrogen atom 12 and R 13 Formed optionally by one or more R 20 Replacement of 3- to 10-membered heterocycles; R 20 Each time it appears, it is independently selected from halogen, oxo, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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(R22 )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 ); where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -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 ); R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3- to 12-membered heterocycles) or two R 21 Together with the carbon atoms they are attached to, they form C 3-12 Carbon rings or 3- to 12-membered heterocycles, wherein C 3-12 The carbon ring or 3- to 12-membered heterocycles are each optionally selected independently from halogens, C 1-3 Alkyl, C 1-3 Substitution with haloalkyl groups and -OH groups; R 22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Alkyl groups (3- to 12-membered heterocycles); R 23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R atoms bonded to the same nitrogen atom 22 and R 23 Formation of 3- to 10-membered heterocycles; and R 29 Each time it appears, it is independently selected from halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Substitution; and where two R atoms connected to the same atom29 Optional linkage to form an oxo group; n29 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13; and Each Independently represent single or double bonds, such that all valences are satisfied.

[0181] In embodiments of the compound of formula II, the compound has formula (IIA): , Or a pharmaceutically acceptable salt or solvate thereof, wherein: X 9 Selected from C(R) 9 ), C(R 9 (R) 9a ) and N(R 9 ); X 10 Selected from C(R) 10 ), C(R 10 )2、N、N(R 10b ), O, S, S(O), S(O)2 and C(O); X 11 Selected from C(R) 11 ), C(R 11 )2、N、N(R 11b ), O, S, S(O), S(O)2 and C(O); X 12 Selected from -X 12a -、-X 12a -X 12b -、-X 12a -X 12b -X 12c -and-X 12a -X 12b -X 12c -X 12d -; where X 12a With X 5 Direct bonding; X 12a X 12b X 12c and X 12d Independently selected from C(R) 12a ), C(R 12a )2、N、N(R 12b ), O, S, S(O), S(O)2 and C(O); R 10b R 11b and R 12b Independently selected from hydrogen, -CN, C1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 9a R 10 R 11 and R 12a Each time it appears, it is independently selected from hydrogen, halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Replace; and Each Independently represent single or double bonds, such that all valences are satisfied.

[0182] On one hand, a compound of formula (V) is provided: , Or a pharmaceutically acceptable salt or solvate thereof, wherein: Ring A is selected from single ring C7-10 Carbon rings, monocyclic 7- to 10-membered heterocyclic rings, and fused bicyclic C rings 8-12 Carbon rings and fused bicyclic 8- to 12-membered heterocyclic rings; X 1 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 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 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 Selected from C, C(R) 4 ) and N; X 5 Selected from C, C(R) 5 ) and N; X 6 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 Selected from C(R) 7 ), C(R 7 (R) 7a ) and N(R 7b ); X 8 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 Selected from C, C(R) 13a ) and N; X 14 Selected from C, C(R) 14a ) and N; R 7 Yes -L 7a -R 17 ;R 7b Yes -L 7b -R 17 ; L 7a Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; L 7b Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -C(O)- and -C(O)N(R) 12 )-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; R 9 Yes -L 19 -L 19a -R 19a ; L 19 Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl and 3- to 4-membered heteroynyl, wherein C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; L 19a Selected from -C(O)- and -N(R)- 12 )C(O)-; R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a The C(O) bonds are directly bonded, and R is in particular... 19a Optionally by one or more R 20 replace; R 1b R 2b R 3b R 6b and R 8b Independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 1 R 2 R 3 R 4 R 5 R 6 R 7a R 8 R 13a R 14a and R 17 Each time it appears, it is independently selected from hydrogen, halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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)R12 -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 12 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3- to 12-membered heterocyclic), wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl (3- to 12-membered heterocycle) optionally surrounded by one or more R 20 replace; R 13 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl; or R attached to the same nitrogen atom 12 and R 13 Formed optionally by one or more R 20 Replacement of 3- to 10-membered heterocycles; R 20 Each time it appears, it is independently selected from halogen, oxo, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ); where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -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 ); R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3- to 12-membered heterocycles) or two R 21 Together with the carbon atoms they are attached to, they form C 3-12 Carbon rings or 3- to 12-membered heterocycles, wherein C 3-12 The carbon ring or 3- to 12-membered heterocycles are each optionally selected independently from halogens, C 1-3 Alkyl, C 1-3 Substitution with haloalkyl groups and -OH groups; R 22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring), and -C 0-6 Alkyl groups (3- to 12-membered heterocycles); R 23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R atoms bonded to the same nitrogen atom 22 and R 23 Formation of 3- to 10-membered heterocycles; R 29 Each time it appears, it is independently selected from halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Substitution; and where two R atoms connected to the same atom 29 Optional linkage to form an oxo group; n29 is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13; and Each Independently represent single or double bonds, such that all valences are satisfied.

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

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

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

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

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

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

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

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

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

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

[0193] In embodiments of compounds of formulas IA, IB, and IIA, the compound is selected from: ; And n30 is 0, 1, or 2. In one implementation, n30 is 0. In another implementation, n30 is 1. In yet another implementation, n30 is 2.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[0212] In embodiments of compounds of formulas IA, IB, and IIA, the compound is selected from: And n30 is 0, 1, or 2. In one implementation, n30 is 0. In another implementation, n30 is 1. In yet another implementation, n30 is 2.

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

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

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

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

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

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

[0219] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has the following formula: ; X 6 Selected from C(R) 6 ), C(R 6 2. N and N(R) 6b ); X 7 Selected from C(R) 7 ) and N(R 7b ); X 8 Selected from C(R) 8 ) and C(R 8 )2; and L 7a It is a key; L 7b It is a key; All other variables are as described in equations I, IA, IB, II, IIA, V, or their implementation schemes.

[0220] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, the compound has a formula selected from the following: ;where R 12a Selected from hydrogen and unsubstituted methyl groups; and R 6 Selected from halogens and -CF3; wherein all other variables are as described in formulas I, IA, IB, II, IIA, V or their embodiments.

[0221] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from: All variables are as described in equations IA, IB, IIA, or their implementation schemes.

[0222] In embodiments of compounds of formula IA, IB, or IIA, the compound is selected from: ;where R 12a Selected from hydrogen and unsubstituted methyl groups; and R 6 Selected from halogens and -CF3, and R 17 Selected from All other variables are as described in equations IA, IB, IIA, or their implementation schemes.

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

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

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

[0226] In embodiments of compounds of formula I, II, or V, ring A is a partially unsaturated monocyclic 7-membered heterocycle. In embodiments of compounds of formula I, II, or V, ring A is a partially unsaturated monocyclic 8-membered heterocycle. In embodiments of compounds of formula I, II, or V, ring A is a partially unsaturated monocyclic 9-membered heterocycle. In embodiments of 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 fused bicyclic ring C. 8-12Carbon ring. In embodiments of the compound of formula V, ring A is a fused bicyclic carbon ring comprising 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 comprising 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 comprising 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 comprising a C8 carbon ring and a C6 carbon ring. In embodiments of the compound of formula V, ring A is a fused bicyclic 8- to 12-membered heterocycle. In embodiments of the compound of formula V, ring A is a fused bicyclic heterocycle comprising a 7-membered ring and a 5-membered ring. In embodiments of the compound of formula V, ring A is a fused bicyclic heterocycle comprising an 8-membered ring and a 5-membered ring. In embodiments of the compound of formula V, ring A is a fused bicyclic heterocycle comprising a 7-membered ring and a 6-membered ring. In embodiments of the compound of formula V, ring A is a fused bicyclic heterocycle comprising a 7-membered ring and a 7-membered ring. In embodiments of the compound of formula V, ring A is a fused bicyclic heterocycle comprising an 8-membered ring and a 6-membered ring. In embodiments of the compound of formula V, ring A is a fused bicyclic heterocycle comprising 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 For N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For N(R) 1b ).

[0230] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 1b Selected from C 3-12 Carbon rings and 3- to 12-membered heterocycles, of which C 3-12 Carbon rings and 3- to 12-membered heterocycles are optionally separated by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 1b To be optionally used by one or more R 20 Substituted phenyl. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 1b To be optionally used by one or more R 20 Substituted pyridinyl group.

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

[0232] In some implementations, for compounds of formula I, IA, IB, II, IIA, or V, R 2 Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 3-10 Carbon rings, 3- to 10-membered heterocycles, -OR 12 and -N(R) 12 (R) 13 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 3-10 Carbon rings and 3- to 10-membered heterocycles are optionally separated by one or more R 20 Replacement. In some implementations, R 2 Selected from hydrogen, -(C 0-3 alkylene)-O-(C 0-3 (alkylene)-R 20 C 1-3 Alkyl groups and 3- to 10-membered heterocycles, wherein each C 0-3 Alkylene, C 1-3 Alkyl groups and 3- to 10-membered heterocycles are optionally separated by one or more R groups. 20 Replacement. In some implementations, R 2 Selected from hydrogen, C 1-3 Alkyl, -OR 12and heterocyclic compounds ranging from 3 to 10, of which C 1-3 Alkyl groups and 3- to 10-membered heterocycles are optionally separated by one or more R groups. 20 Replacement. In some implementations, R 2 OR 12 In some implementations, R 2 -O(C) 1-3 Alkylene (4- to 10-membered heterocycles), wherein the 4- to 10-membered heterocycles are optionally selected independently by one or more halogens, C 1-3 Alkyl, C 1-3 Halogenated alkyl groups and =C(R) 21 Substituents of )2. In some embodiments, R 2 -O(C) 1-3 Alkylene (4- to 10-membered heterocycles), wherein the 4- to 10-membered heterocycles are optionally selected independently by one or more halogens, C 1-3 Alkyl, C 1-3 Halogenated alkyl groups and =C(R) 21 Substituents of )2, wherein R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-3 Alkyl group. In some embodiments, R 2 It is optionally controlled by one or more R 20 Substituted -OCH2 (hexahydro-1H-pyrrolizine). In some embodiments, R 2 It is optionally selected by one or more independently chosen from halogens, C 1-3 Alkyl, C 1-3 Halogenated alkyl groups and =C(R) 21 The substituent of )2 is -OCH2 (hexahydro-1H-pyrrolizine), wherein R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-3 alkyl.

[0233] In some implementations, for compounds of formula I, IA, IB, II, IIA, or V, R 2 Selected from In some implementations, R 2 Selected from , , , , and In some implementations, R 2 Selected from and In some implementations, R 2It is optionally controlled by one or more R 20 Replacement In some implementations, R 2 for Such as In some implementations, R 2 for In some implementations, R 2 for In some implementations, R 2 for In some implementations, R 2 for In some implementations, R 2 for In some implementations, R 2 for In some implementations, R 2 Selected from , , , , , and Such as .

[0234] In some implementations, for compounds of formula I, IA, IB, II, IIA, or V, R 2 It is selected independently by one, two, three or four halogens, oxo-, C 1-6 Alkyl, -OR 22 -N(R) 22 (R) 23 =C(R) 21 )2 and -OC(O)N(R 22 (R) 23 Substituents of ) where C 1-6 The alkyl group is optionally selected independently from one or more halogens, -CN, -OR. 22 -N(R) 22 (R) 23 ) and -OC(O)N(R 22 ) ( R 23 Substituents of ) are used. In some embodiments, R 2 Selected independently by one, two, three or four halogens, C 1-3 Alkyl, C 1-3 Halogenated alkyl groups and =C(R) 21 Substituents of )2, wherein R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-3Alkyl group. In some embodiments, R 2 Selected independently by one, two, three or four halogens, C 1-3 Alkyl, C 1-3 Substitution with haloalkyl groups, =CH2, =CHF, and =CF2. In some embodiments, R... 2 It is replaced by halogens (such as fluorine).

[0235] In some implementations, for compounds of formula I, IA, IB, II, IIA, or V, R 2b Selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 3-10 Carbon rings and 3- to 10-membered heterocycles, of which C 1-6 Alkyl, C 2-6 alkenyl, C 3-10 Carbon rings and 3- to 10-membered heterocycles are optionally separated by one or more R 20 Replacement. In some implementations, R 2b Selected from hydrogen, -(C 0-3 alkylene)-O-(C 0-3 (alkylene)-R 20 C 1-3 Alkyl groups and 3- to 10-membered heterocycles, wherein each C 0-3 Alkylene, C 1-3 Alkyl groups and 3- to 10-membered heterocycles are optionally separated by one or more R groups. 20 Replacement. In some implementations, R 2b Selected from hydrogen, C 1-3 Alkyl groups and 3- to 10-membered heterocycles, wherein C 1-3 Alkyl groups and 3- to 10-membered heterocycles are optionally separated by one or more R groups. 20 replace.

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

[0237] In some implementations, for compounds of formula I, IA, IB, II, IIA, or V, R 2b It is selected independently by one, two, three or four halogens, oxo-, C 1-6 Alkyl, -OR 22 -N(R) 22 (R) 23 =C(R) 21 )2 and -OC(O)N(R 22 (R) 23 Substituents of ) where C 1-6The alkyl group is optionally selected independently from one or more halogens, -CN, -OR. 22 -N(R) 22 (R) 23 ) and -OC(O)N(R 22 ) ( R 23 Substituents of ) are used. In some embodiments, R 2b Selected independently by one, two, three or four halogens, C 1-3 Alkyl, C 1-3 Halogenated alkyl groups and =C(R) 21 Substituents of )2, wherein R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-3 Alkyl group. In some embodiments, R 2b Selected independently by one, two, three or four halogens, C 1-3 Alkyl, C 1-3 Substitution with haloalkyl groups, =CH2, =CHF, and =CF2. In some embodiments, R... 2 It is replaced by halogens (such as fluorine).

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

[0239] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 3 Each time it appears, it is independently selected from hydrogen, halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, where C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl group is optionally surrounded by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 3 For -CN.

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

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

[0242] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 For C(R) 6 In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6 Each time it appears, it is independently selected from hydrogen and halogen. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6 To be optionally used by one or more R 20 Substituted methyl group. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6 A methyl group that is independently substituted with one or more halogens. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6 -CF3. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6 For -Cl. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 For N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 For N(R) 6b In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6b It is an unsubstituted cyclopropyl group. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 6b C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, where C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl group is optionally surrounded by one or more R 20 (e.g., CN, halogen, F or Cl) substitution.

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

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

[0245] In some implementations, for compounds of formula I, IA, IB, II, IIA, or V, R 17 Selected from C 6-12 Aryl and 5- to 12-membered heteroaryl groups, of which C 6-12 Aryl and 5- to 12-membered heteroaryl groups are each optionally bounded by one or more R groups. 20 Replacement. In some implementations, R 17 Selected from C 10 Aryl and 9-membered heteroaryl, of which C 10 The aryl and 9-membered heteroaryl groups are each optionally bounded by one or more R groups. 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 17 The group is selected from phenyl, pyridyl, naphthyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzothiaphenyl, indazole, and benzoxazolyl, wherein phenyl, pyridyl, naphthyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzothiaphenyl, indazole, and benzoxazolyl are optionally separated by one or more R 20 Replacement. In some implementations, R 17 Selected from naphthyl and benzothiophene, wherein naphthyl and benzothiophene are each optionally separated by one or more R 20 Replacement. In some implementations, R 17 Selected from C 3-10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, C 6-10 Aryl and 5- to 10-membered heteroaryl groups, of which C 3-10 Cycloalkyl, 3- to 10-membered heterocycloalkyl, C 6-10 Aryl and 5- to 10-membered heteroaryl groups are each optionally bounded by one or more R groups. 20 Replacement. In some implementations, R 17 Selected from double-ring C 4-10 Cycloalkyl, bicyclic 4- to 10-membered heterocyclic alkyl, bicyclic C 7-10 Aryl and bicyclic 7- to 10-membered heteroaryl groups, of which bicyclic C 4-10 Cycloalkyl, bicyclic 4- to 10-membered heterocyclic alkyl, bicyclic C 7-10 Aryl and bicyclic 7- to 10-membered heteroaryl groups are each optionally constituting one or more R groups. 20 Replacement. In some implementations, R 17 Selected from bridged double ring C 4-10 Cycloalkyl, bridged bicyclic 4- to 10-membered heterocyclic alkyl, bridged bicyclic C 7-10 Aryl and bridging bicyclic 7- to 10-member heteroaryl compounds, among which bridging bicyclic C 4-10 Cycloalkyl, bridged bicyclic 4- to 10-membered heterocyclic alkyl, bridged bicyclic C 7-10Aryl and bridging bicyclic 7- to 10-membered heteroaryl groups are each optionally constituting one or more R groups. 20 Replacement. In some implementations, R 17 Selected from fused bicyclic C 4-10 Cycloalkyl, fused bicyclic 4- to 10-membered heterocyclic alkyl, fused bicyclic C 7-10 Aryl and fused bicyclic 7- to 10-membered heteroaryl groups, of which the fused bicyclic C 4-10 Cycloalkyl, fused bicyclic 4- to 10-membered heterocyclic alkyl, fused bicyclic C 7-10 The aryl and fused bicyclic 7- to 10-membered heteroaryl groups are each optionally bounded by one or more R groups. 20 Replacement. In some implementations, R 17 Selected from C 6-10 Aryl and 5- to 10-membered heteroaryl groups, of which C 6-10 The aryl group and the 5- to 10-aryl group are each optionally surrounded by one, two, three, four, or five R groups. 20 Replacement. In some implementations, R 17 The group is selected from naphthyl, isoquinolinyl, indazole, benzothiazolyl, benzothiaphenyl, phenyl, and pyridyl, wherein naphthyl, isoquinolinyl, indazole, benzothiazolyl, benzothiaphenyl, phenyl, and pyridyl are each optionally separated by one or more R groups. 20 Replacement. In some implementations, R 17 Selected independently by one, two, three or four halogens, -CN, C 1-3 Alkyl, C 1-3 Haloalkyl, C 2-3 alkenyl, C 2-3 alkynyl group, -OR 22 -N(R) 22 (R) 23 ) and C 3-6 Cycloalkyl substituents. In some embodiments, R 17 Selected from C6 aryl and 6-membered heteroaryl groups, wherein the C6 aryl and 6-membered heteroaryl groups are each surrounded by one, two, three, four, or five R groups. 20 Replacement. In some implementations, R 17 Optionally by one or more R 20 Such as one, two, three, four, five, six or seven R 20 replace.

[0246] In some implementations, for compounds of formula I, IA, IB, II, IIA, or V, R 17 Selected from: ,in: Q 1 Q 3 and Q 5Independently selected from N and C(R) 1q ); Q 4 and Q 6 Independently selected from O, S, C(R) 1q )2 and N(R 1r ); Y 4 Y 5 Y 6 Y 9 and Y 10 Independently selected from C(R) 1q ) and N; Y 7 and Y 8 Independently selected from C(R) 1q ), C(R 1q 2. N and N(R) 1r ); Y 13 Selected from key, 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 Independently selected from C(O) and C(R) 1q ), N, C(R) 1q )2 and N(R 1r ); Y 16 Selected from C, N and C(R) 1q ); Each R 1q Independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Substitution; or two Rs bonded to the same carbon atom 1q The connection forms 3- to 10-membered heterocycles or C 3-10 Carbon rings, including 3- to 10-membered heterocycles and C 3-10 The carbon ring is optionally divided by one or more R 20 Substitution; or bonding to two adjacent R atoms 1q The connection forms 3- to 10-membered heterocycles or C 3-10 Carbon rings, including 3- to 10-membered heterocycles and C 3-10 The carbon ring is optionally divided by one or more R 20 Replace; or an R1q And an R 1r The links form ternary to decacyclic heterocycles, wherein the ternary to decacyclic heterocycles are optionally connected by one or more R... 20 replace; Each R 1r Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne groups, 3- to 10-membered heterocycles and C 3-10 Carbon ring, where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne groups, 3- to 10-membered heterocycles and C 3-10 The carbon ring is optionally divided by one or more R 20 Replace; and This indicates a single or double bond, such that all valences are satisfied.

[0247] In some implementation schemes, R 17 Selected from In some implementations, R 17 Selected from , In some implementations, R 17 Selected from In some implementations, R 17 Selected from .

[0248] In some implementations, for compounds of formula I, IA, IB, II, IIA, or V, R 17 Selected from: .

[0249] In some implementations, for compounds of formula I, IA, IB, II, IIA, or V, R 17 yes In some implementations, R 17 Selected from In some implementations, R 17 Selected from In some implementations, R 17 yes In some implementations, R17 yes In some implementations, R 17 yes In some implementations, R 17 yes In some implementations, R 17 yes In some implementations, R 17 yes .

[0250] In some implementations, for compounds of formula I, IA, IB, II, IIA, or V, R 17 yes In some implementations, R 17 Selected from In some implementations, R 17 Selected from In some implementations, R 17 yes In some implementations, R 17 yes In some implementations, R 17 yes In some implementations, R 17 Yes. In some implementations, R 17 yes In some implementations, R 17 yes In some implementations, R 17 yes .

[0251] In some implementation schemes, R 17 Selected from .

[0252] In some implementation schemes, R 17 Selected from In some implementations, R 17 Selected from In some implementations, R 17 yes In some implementations, R 17 yes In some implementations, R 17 Selected from .

[0253] In some implementations, for compounds of formula I, IA, IB, II, IIA, or V, R 17 Selected independently by one, two, three or four halogens, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -OR 22 -SR 22 and -N(R) 22 (R) 23 Substituents of ) where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group and C 3-6 The cycloalkyl group is optionally separated by one, two, or three independently selected from halogens, C... 1-6 Alkyl, C 1-6 Halogenated alkyl groups and -OR 22 Substituents are substituted. In some embodiments, R 17 Selected independently by one, two, three or four halogens, -CN, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, -OR 22 and -N(R) 22 (R) 23 Substituents of ) are used. In some embodiments, R 17 It is substituted by one, two, three, or four independent substituents selected from halogens, -CN, -CH3, -C≡CH, -OH, and -NH2. In some embodiments, R 17 Replaced by -F, -CN, and -NH2. In some implementations, R 17 It is replaced by -F, -C≡CH, and -OH. In some implementations, R 17 Replaced by -CF3, -CH3, and -NH2. In some implementations, R 17 Replaced by -CF3 and -NH2. In some implementations, R 17 Replaced by -CF3, -CH3, -F, and -NH2. In some implementations, R 17 Replaced by -CF3, -F, and -NH2. In some implementations, R 17It is substituted by one, two, three or four independent substituents selected from halogen, -CN, -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 For example, L is a bond. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 7b For key.

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

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

[0257] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For N; X 2 For C(R) 2 ); X 3 For N; X 4 For C; X5 For C; X 6 For C(R) 6 ); X 7 For C(R) 7 ); X 8 For C(R) 8 ); X 13 For C; X 14 C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For N; X 2 For C(R) 2 ); X 3 For N; X 4 For C; X 5 For C; X 6 C(Cl); X 7 For C(R) 7 ); X 8 For C(F); X 13 Let C be X; and X be X. 14 C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For N; X 2 For C(R) 2 ); X 3 For N; X 4 For C; X 5 For C; X 6 For N; X 7 For C(R) 7 ); X 8 For C(R) 8 ); X 13 Let C be X; and X be X. 14 C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For N; X 2 For C(R) 2 ); X 3 For N; X 4 For C; X 5 For C; X 6 For N; X 7 For C(R) 7 ); X 8 For C(F); X 13 Let C be X; and X be X. 14 C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For N; X 2 For C(R) 2 ); X 3 For N; X 4 For C; X 5 For CH; X6 C(H)2; X 7 For N(R) 7 b); X 8 For C(H)2, X 13 Let C be X; and X be X. 14 C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For N; X 2 For C(R) 2 ); X 3 For N; X 4 For C; X 5 For C(R) 5 ); X 6 For C(R) 6 )2;X 7 For N(R) 7 b); X 8 For C(R) 8 )2,X 13 Let C be X; and X be X. 14 C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For C(R) 1 In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For C(R) 1 2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For N(R) 1b In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For O. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 S. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 S(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 S(O)₂. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 1 For C(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 For C(R) 2 In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 For C(R) 22. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 For N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 For N(R) 2b In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 For O. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 S. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 S(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 S(O)₂. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 2 For C(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 For C(R) 3 In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 For C(R) 3 2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 For N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 For N(R) 3b In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 For O. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 S. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 S(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 S(O)₂. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 3 For C(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 4 C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 4 For C(R) 4 In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 4For N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 5 C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 5 For C(R) 5 In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 5 For N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 For C(R) 6 In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 For C(R) 6 2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 For N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 For N(R) 6b In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 For O. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 S. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 S(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 S(O)₂. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 6 For C(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 7 For C(R) 7 In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 7 For C(R) 7 (R) 7a In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 7 For N(R) 7b In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 For C(R) 8 In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 For C(R) 8 2. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8For N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 For N(R) 8b In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 For O. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 S. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 S(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 S(O)₂. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 8 For C(O). In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 13 C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 13 For C(R) 13a In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 13 For N. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 14 C. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 14 For C(R) 14a In embodiments of compounds of formula I, IA, IB, II, IIA, or V, X 14 For N. In embodiments of compounds of formula IA, IB, or IIA, X 9 For C(R) 9 In embodiments of compounds of formula IA, IB, or IIA, X 9 For C(R) 9 (R) 9a In embodiments of compounds of formula IA, IB, or IIA, X 9 For N(R) 9 In embodiments of compounds of formula IA, IB, or IIA, X 10 For C(R) 10 In embodiments of compounds of formula IA, IB, or IIA, X 10 For C(R) 10 2. In embodiments of compounds of formula IA, IB, or IIA, X 10 For N. In embodiments of compounds of formula IA, IB, or IIA, X 10 For N(R) 10bIn embodiments of compounds of formula IA, IB, or IIA, X 10 For O. In embodiments of compounds of formula IA, IB, or IIA, X 10 S. In embodiments of compounds of formula IA, IB, or IIA, X 10 S(O). In embodiments of compounds of formula IA, IB, or IIA, X 10 For S(O)2. In embodiments of compounds of formula IA, IB, or IIA, X 10 For C(O). In embodiments of compounds of formula IA, IB, or IIA, X 11 For C(R) 11 In embodiments of compounds of formula IA, IB, or IIA, X 11 For C(R) 11 2. In embodiments of compounds of formula IA, IB, or IIA, X 11 For N. In embodiments of compounds of formula IA, IB, or IIA, X 11 For N(R) 11b In embodiments of compounds of formula IA, IB, or IIA, X 11 For O. In embodiments of compounds of formula IA, IB, or IIA, X 11 S. In embodiments of compounds of formula IA, IB, or IIA, X 11 S(O). In embodiments of compounds of formula IA, IB, or IIA, X 11 For S(O)2. In embodiments of compounds of formula IA, IB, or IIA, X 11 For C(O). In embodiments of compounds of formula IA, IB, or IIA, X 12a For C(R) 12a In embodiments of compounds of formula IA, IB, or IIA, X 12a For C(R) 12a 2. In embodiments of compounds of formula IA, IB, or IIA, X 12a For N. In embodiments of compounds of formula IA, IB, or IIA, X 12a For N(R) 12b In embodiments of compounds of formula IA, IB, or IIA, X 12a For O. In embodiments of compounds of formula IA, IB, or IIA, X 12a S. In embodiments of compounds of formula IA, IB, or IIA, X 12a S(O). In embodiments of compounds of formula IA, IB, or IIA, X 12aFor S(O)2. In embodiments of compounds of formula IA, IB, or IIA, X 12a For C(O). In embodiments of compounds of formula IA, IB, or IIA, X 12b For C(R) 12a In embodiments of compounds of formula IA, IB, or IIA, X 12b For C(R) 12a 2. In embodiments of compounds of formula IA, IB, or IIA, X 12b For N. In embodiments of compounds of formula IA, IB, or IIA, X 12b For N(R) 12b In embodiments of compounds of formula IA, IB, or IIA, X 12b For O. In embodiments of compounds of formula IA, IB, or IIA, X 12b S. In embodiments of compounds of formula IA, IB, or IIA, X 12b S(O). In embodiments of compounds of formula IA, IB, or IIA, X 12b For S(O)2. In embodiments of compounds of formula IA, IB, or IIA, X 12b For C(O). In embodiments of compounds of formula IA, IB, or IIA, X 12c For C(R) 12a In embodiments of compounds of formula IA, IB, or IIA, X 12c For C(R) 12a 2. In embodiments of compounds of formula IA, IB, or IIA, X 12c For N. In embodiments of compounds of formula IA, IB, or IIA, X 12c For N(R) 12b In embodiments of compounds of formula IA, IB, or IIA, X 12c For O. In embodiments of compounds of formula IA, IB, or IIA, X 12c S. In embodiments of compounds of formula IA, IB, or IIA, X 12c S(O). In embodiments of compounds of formula IA, IB, or IIA, X 12c For S(O)2. In embodiments of compounds of formula IA, IB, or IIA, X 12c For C(O). In embodiments of compounds of formula IA, IB, or IIA, X 12d For C(R) 12a In embodiments of compounds of formula IA, IB, or IIA, X 12d For C(R) 12a2. In embodiments of compounds of formula IA, IB, or IIA, X 12d For N. In embodiments of compounds of formula IA, IB, or IIA, X 12d For N(R) 12b In embodiments of compounds of formula IA, IB, or IIA, X 12d For O. In embodiments of compounds of formula IA, IB, or IIA, X 12d S. In embodiments of compounds of formula IA, IB, or IIA, X 12d S(O). In embodiments of compounds of formula IA, IB, or IIA, X 12d For 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 It is an unsubstituted C1-2 alkylene group. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19 L is an unsubstituted methylene group. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19 For key.

[0259] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19 Selected from C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace.

[0260] In embodiments of compounds of formula I, IA, or IB, R 19 To be optionally used by one or more R 20 Replaced monocyclic C 3-8 Carbocyclic ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 Substituted monocyclic nonaromatic C 4-8 Carbocyclic ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 Substituted monocyclic nonaromatic C 4-6 Carbocyclic ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 Substituted monocyclic nonaromatic C 4-5 Carbocyclic ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted monocyclic non-aromatic C4 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 Substituted monocyclic non-aromatic C5 carbon ring. In embodiments of compounds of formulas I, IA, and IB, R 19 To be optionally used by one or more R 20 Substituted phenyl. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 Substituted monocyclic 3- to 8-membered heterocycles. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 Substituted monocyclic non-aromatic 4- to 5-membered heterocycles. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted monocyclic non-aromatic four-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20A substituted monocyclic non-aromatic 5-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 Selected from cyclopropyl, cyclobutyl, cyclopentyl, aziridinyl, aziridine, and pyrrolidinyl, wherein each group is optionally C-shaped. 1-3 Alkyl substitution. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 Selected from cyclopropyl, cyclobutyl, cyclopentyl, aziridinyl, aziridine, and pyrrolidinyl, wherein each group is optionally C-shaped. 3-4 Cycloalkyl substitution, wherein C 3-4 The cycloalkyl group is optionally substituted with a methyl group. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For optional use by C 1-3 Alkyl-substituted cyclobutyl. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 The cyclobutyl group is optionally substituted with a cyclopropyl group, wherein the cyclopropyl group is optionally substituted with a methyl group. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 Optionally cyclobutyl group substituted with cyclopropyl group, wherein the cyclopropyl group is substituted with methyl group. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For optional use by C 1-3 Alkyl-substituted cyclopentyl. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For being C 1-3 Alkyl-substituted cyclopentyl. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 It is a cyclopentyl group substituted with a methyl group.

[0261] In embodiments of compounds of formulas I, IA, and IB, R 19 To be optionally used by one or more R 20 Substituted monocyclic 5- to 6-membered heteroaryl groups. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 Substituted monocyclic non-aromatic 4- to 5-membered heterocycles. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 Selected from aziridine and pyrrolidinyl; wherein the aziridine and pyrrolidinyl are optionally separated by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 Optionally substituted by one or more substituents independently selected from the following: C 1-6 Alkyl, C2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3- to 12-membered heterocyclic rings); wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 The alkyl group (3- to 12-membered heterocycle) is optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -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(R22 (R) 23 In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 Optionally selected by one or more independently chosen from C 1-4 Alkyl and C 3-4 Substituents on the carbocyclic ring; where C 3-4 The carbon ring is optionally composed of one or more independently selected from halogens and C. 1-4 Alkyl substituents. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 Optionally substituted with an unsubstituted methyl group.

[0262] In embodiments of compounds of formula I, IA, or IB, R 19 To be optionally used by one or more R 20 A substituted monocyclic C3 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted monocyclic C4 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted monocyclic C5 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted monocyclic C6 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted monocyclic C7 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 It is optionally controlled by one or more R 20 The replaced monocyclic C8 carbon ring.

[0263] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 Replaced monocyclic C 3-8 Carbocyclic ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted monocyclic C3 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted monocyclic C4 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19For one or more R 20 A substituted monocyclic C5 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted monocyclic C6 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted monocyclic C7 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 The replaced monocyclic C8 carbon ring.

[0264] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted monocyclic 3-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted monocyclic four-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted monocyclic 5-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted monocyclic 6-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted monocyclic 7-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 Replaced monocyclic 8-membered heterocyclic rings.

[0265] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 Substituted monocyclic 3- to 8-membered heterocycles. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted monocyclic 3-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted monocyclic four-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R19 For one or more R 20 A substituted monocyclic 5-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted monocyclic 6-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted monocyclic 7-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 Replaced monocyclic 8-membered heterocyclic rings.

[0266] In embodiments of compounds of formula I, IA, or IB, R 19 To be optionally used by one or more R 20 A substituted non-aromatic monocyclic C3 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted non-aromatic monocyclic C4 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted non-aromatic monocyclic C5 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted non-aromatic monocyclic C6 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted non-aromatic monocyclic C7 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 The substituted non-aromatic monocyclic C8 carbon ring.

[0267] In embodiments of compounds of formula I, IA, or IB, R 19 For one or more R 20 Replaced non-aromatic monocyclic C 3-8 Carbocyclic ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 Replaced non-aromatic monocyclic C 4-8 Carbocyclic ring. In embodiments of compounds of formula I, IA, or IB, R 19 For one or more R 20Substituted non-aromatic monocyclic C3 carbon ring. In formula... I In embodiments of compounds of type I, II, III, IV, VI, VII, III, IV, VI, VII, III, IV, VI, VII, VI ... 19 For one or more R 20 A substituted non-aromatic monocyclic C4 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted non-aromatic monocyclic C5 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted non-aromatic monocyclic C6 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted non-aromatic monocyclic C7 carbon ring. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 The substituted non-aromatic monocyclic C8 carbon ring.

[0268] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted non-aromatic monocyclic 3-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted non-aromatic monocyclic four-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted non-aromatic monocyclic 5-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted non-aromatic monocyclic 6-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 A substituted non-aromatic monocyclic 7-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 To be optionally used by one or more R 20 The replaced non-aromatic monocyclic 8-membered heterocyclic ring.

[0269] In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20Substituted non-aromatic monocyclic 3- to 8-membered heterocycles. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted non-aromatic monocyclic 3-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted non-aromatic monocyclic four-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted non-aromatic monocyclic 5-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted non-aromatic monocyclic 6-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 A substituted non-aromatic monocyclic 7-membered heterocycle. In embodiments of compounds of formula I, IA, IB, II, or IIA, R 19 For one or more R 20 The replaced non-aromatic monocyclic 8-membered heterocyclic ring.

[0270] In embodiments of compounds of formula I, IA, IB, II, or IIA, -L 19 -R 19 -L 19a -R 19a Selected from: ,in: W 1 W 3 W 4 and W 5 Each occurrence is independently selected from N(R) 20b ), C(R 20a )2, C(O), O, S(O) and S(O)2; W 2 Selected from N and C(R) 20a ); 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; 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; The sum of n4 and n5 is selected from 0, 1, 2, 3, and 4; and R 20a R20b R 20c R 20d R 20e and R 20f Each time it appears, it is independently selected from hydrogen and R. 20 .

[0271] In the implementation plan, R 20a R 20c R 20d R 20e and R 20f Each time it appears, it is independently selected from hydrogen, halogen, -OH, -CN, C. 1-6 Alkyl and C 3-6 cycloalkyl, wherein C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally surrounded by one or more elements selected from halogen, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Substitution of cycloalkyl groups.

[0272] In the implementation plan, R 20b Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl and C 3-6 cycloalkyl, wherein C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally surrounded by one or more elements selected from halogen, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Substitution of cycloalkyl groups.

[0273] In the implementation plan, W 1 Independently selected from N(R) 20b ), C(R 20a 2. C(O), O, S(O) and S(O)2. In the implementation scheme, W 1 Independently for C(R) 20a 2. In the implementation plan, W 1 Independently for CH(R) 20a In the implementation plan, W 1 Independently C(H)2. In the implementation scheme, W 1 It is independently selected from C(O), S(O), and S(O)2. In the implementation scheme, W 1 It is C(O) independently.

[0274] In the implementation plan, W 2 Independently defined as N. In the implementation plan, W 2 Independently for C(R) 20a In the implementation plan, W2 Independently, it is CH.

[0275] In the implementation plan, W 3 Independently selected from N(R) 20b ), C(R 20a 2. C(O), O, S(O) and S(O)2. In the implementation scheme, W 3 Independently for C(R) 20a 2. In the implementation plan, W 3 Independently for CH(R) 20a In the implementation plan, W 3 Independently C(H)2. In the implementation scheme, W 3 It is independently selected from C(O), S(O), and S(O)2. In the implementation scheme, W 3 Independently C(O). In the implementation plan, W 3 It is O independently.

[0276] In the implementation plan, W 4 Independently selected from N(R) 20b ), C(R 20a 2. C(O), O, S(O) and S(O)2. In the implementation scheme, W 4 Independently for C(R) 20a 2. In the implementation plan, W 4 Independently for CH(R) 20a In the implementation plan, W 4 Independently C(H)2. In the implementation scheme, W 4 It is independently selected from C(O), S(O), and S(O)2. In the implementation scheme, W 4 It is C(O) independently.

[0277] In the implementation plan, W 5 Independently selected from N(R) 20b ), C(R 20a 2. C(O), O, S(O) and S(O)2. In the implementation scheme, W 5 Independently for C(R) 20a 2. In the implementation plan, W 5 Independently for CH(R) 20a In the implementation plan, W 5 Independently C(H)2. In the implementation scheme, W 5 It is independently selected from C(O), S(O), and S(O)2. In the implementation scheme, W 5 It is C(O) independently.

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

[0279] In the implementation, n4 is 0. In the implementation, n4 is 1. In the implementation, n4 is 2. In the implementation, n4 is 3. In the implementation, n4 is 4. In the implementation, n5 is 0. In the implementation, n5 is 1. In the implementation, n5 is 2. In the implementation, n5 is 3. In the implementation, n5 is 4. In the implementation, n4 is 1 and n5 is 1. In the implementation, n4 is 1 and n5 is 2. In the implementation, n4 is 1 and n5 is 3. In the implementation, n4 is 2 and n5 is 1. In the implementation, 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 Selected from: .

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

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

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

[0284] The embodiments described below, or combinations thereof, apply to compounds of formula I, IA, IB, II, IIA, or V, or their pharmaceutically acceptable salts or solvates. It should be understood that when a variable is described as an embodiment of a compound of formula I, IA, IB, II, IIA, V, or any other formula, it should be understood that the value of that variable can be combined with any compound selected from formula I, IA, IB, II, IIA, V, or any other compound formula (e.g., without number or label), which itself is also described as an embodiment of a compound of formula I, IA, IB, II, IIA, and / or V; and therefore is a subformula of formula I, IA, IB, II, IIA, and / or V.

[0285] In the implementation plan, R 20a Independently hydrogen. In the implementation scheme, R 20a Independently halogenated. In the implementation scheme, R 20a Independently -OH. In the implementation scheme, R 20a Independently designated as -CN. In the implementation plan, R... 20a Independently for unreplaced C 1-6 Alkyl group. In the implementation scheme, R 20a Independently for unreplaced C 3-6 Cycloalkyl.

[0286] In the implementation plan, R 20a Independently, it is an unsubstituted methyl group. In the embodiments, R 20a Independently, it is an unsubstituted ethyl group. In the embodiments, R 20a Independently, it is unsubstituted propyl. In the implementation scheme, R 20a Independently, it is an unsubstituted isopropyl group. In the embodiments, R 20a Independently, it is unsubstituted butyl. In the implementation, R 20a Independent of unsubstituted tert-butyl.

[0287] In the implementation plan, R 20a The methyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C.1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20a The ethyl group is independently selected from halogens, -OH, -CN, and C, optionally substituted with one, two, or three substituents. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20a The propyl group is optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20a The isopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20a The butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20a The tert-butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0288] In the implementation plan, R 20a Independently, it is an unsubstituted cyclopropyl group. In the embodiments, R 20a Independently, it is an unsubstituted cyclobutyl group. In the implementation, R 20a Independently, it is an unsubstituted cyclopentyl group.

[0289] In the implementation plan, R 20a The cyclopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20a Independently, arbitrarily, by a C 1-3 Alkyl-substituted cyclopropyl. In the embodiments, R20a Independently, it is a cyclopropyl group optionally substituted with a methyl group. In the embodiments, R 20a The cyclobutyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20a The cyclopentyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0290] In the implementation plan, R 20b Independently hydrogen. In the implementation scheme, R 20b Independently for unreplaced C 1-6 Alkyl group. In the implementation scheme, R 20b Independently for unreplaced C 3-6 Cycloalkyl.

[0291] In the implementation plan, R 20b The methyl group is unsubstituted. In the embodiments, R 20b It is an unsubstituted ethyl group. In the embodiments, R... 20b It is an unsubstituted propyl group. In the implementation scheme, R 20b It is an unsubstituted isopropyl group. In the embodiment, R 20b It is an unsubstituted butyl. In the implementation, R 20b It is unsubstituted tert-butyl.

[0292] In the implementation plan, R 20b The methyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20b The ethyl group is independently selected from halogens, -OH, -CN, and C, optionally substituted with one, two, or three substituents. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20b The propyl group is optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C3-6 Cycloalkyl. In the embodiment, R 20b The isopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20b The butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20b The tert-butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0293] In the implementation plan, R 20b Independently, it is an unsubstituted cyclopropyl group. In the embodiments, R 20b Independently, it is an unsubstituted cyclobutyl group. In the implementation, R 20b Independently, it is an unsubstituted cyclopentyl group.

[0294] In the implementation plan, R 20b The cyclopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20b Independently, arbitrarily, by a C 1-3 Alkyl-substituted cyclopropyl. In the embodiments, R 20b Independently, it is a cyclopropyl group optionally substituted with a methyl group. In the embodiments, R 20b The cyclobutyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20b The cyclopentyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0295] In the implementation plan, R 20c Independently hydrogen. In the implementation scheme, R 20c Independently halogenated. In the implementation scheme, R 20c Independently -OH. In the implementation scheme, R 20c Independently designated as -CN. In the implementation plan, R... 20c Independently for unreplaced C 1-6 Alkyl group. In the implementation scheme, R 20c Independently for unreplaced C 3-6 Cycloalkyl.

[0296] In the implementation plan, R 20c Independently, it is an unsubstituted methyl group. In the embodiments, R 20c Independently, it is an unsubstituted ethyl group. In the embodiments, R 20c Independently, it is unsubstituted propyl. In the implementation scheme, R 20c Independently, it is an unsubstituted isopropyl group. In the embodiments, R 20c Independently, it is unsubstituted butyl. In the implementation, R 20c Independent of unsubstituted tert-butyl.

[0297] In the implementation plan, R 20c The methyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20c The ethyl group is independently selected from halogens, -OH, -CN, and C, optionally substituted with one, two, or three substituents. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20c The propyl group is optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20c The isopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20cThe butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20c The tert-butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0298] In the implementation plan, R 20c Independently, it is an unsubstituted cyclopropyl group. In the embodiments, R 20c Independently, it is an unsubstituted cyclobutyl group. In the implementation, R 20c Independently, it is an unsubstituted cyclopentyl group.

[0299] In the implementation plan, R 20c The cyclopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20c Independently, arbitrarily, by a C 1-3 Alkyl-substituted cyclopropyl. In the embodiments, R 20c Independently, it is a cyclopropyl group optionally substituted with a methyl group. In the embodiments, R 20c The cyclobutyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20c The cyclopentyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0300] In the implementation plan, R 20d Independently hydrogen. In the implementation scheme, R 20d Independently halogenated. In the implementation scheme, R 20d Independently -OH. In the implementation scheme, R 20d Independently designated as -CN. In the implementation plan, R... 20dIndependently for unreplaced C 1-6 Alkyl group. In the implementation scheme, R 20d Independently for unreplaced C 3-6 Cycloalkyl.

[0301] In the implementation plan, R 20d Independently, it is an unsubstituted methyl group. In the embodiments, R 20d Independently, it is an unsubstituted ethyl group. In the embodiments, R 20d Independently, it is unsubstituted propyl. In the implementation scheme, R 20d Independently, it is an unsubstituted isopropyl group. In the embodiments, R 20d Independently, it is unsubstituted butyl. In the implementation, R 20d Independent of unsubstituted tert-butyl.

[0302] In the implementation plan, R 20d The methyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20d The ethyl group is independently selected from halogens, -OH, -CN, and C, optionally substituted with one, two, or three substituents. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20d The propyl group is optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20d The isopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20d The butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20d The tert-butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C.1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0303] In the implementation plan, R 20d Independently, it is an unsubstituted cyclopropyl group. In the embodiments, R 20d Independently, it is an unsubstituted cyclobutyl group. In the implementation, R 20d Independently, it is an unsubstituted cyclopentyl group.

[0304] In the implementation plan, R 20d The cyclopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20d Independently, arbitrarily, by a C 1-3 Alkyl-substituted cyclopropyl. In the embodiments, R 20d Independently, it is a cyclopropyl group optionally substituted with a methyl group. In the embodiments, R 20d The cyclobutyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20d The cyclopentyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0305] In the implementation plan, R 20e Independently hydrogen. In the implementation scheme, R 20e Independently halogenated. In the implementation scheme, R 20e Independently -OH. In the implementation scheme, R 20e Independently designated as -CN. In the implementation plan, R... 20e Independently for unreplaced C 1-6 Alkyl group. In the implementation scheme, R 20e Independently for unreplaced C 3-6 Cycloalkyl.

[0306] In the implementation plan, R 20e Independently, it is an unsubstituted methyl group. In the embodiments, R 20e Independently, it is an unsubstituted ethyl group. In the embodiments, R20e Independently, it is unsubstituted propyl. In the implementation scheme, R 20e Independently, it is an unsubstituted isopropyl group. In the embodiments, R 20e Independently, it is unsubstituted butyl. In the implementation, R 20e Independent of unsubstituted tert-butyl.

[0307] In the implementation plan, R 20e The methyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20e The ethyl group is independently selected from halogens, -OH, -CN, and C, optionally substituted with one, two, or three substituents. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20e The propyl group is optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20e The isopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20e The butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20e The tert-butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0308] In the implementation plan, R 20e Independently, it is an unsubstituted cyclopropyl group. In the embodiments, R 20e Independently, it is an unsubstituted cyclobutyl group. In the implementation, R 20e Independently, it is an unsubstituted cyclopentyl group.

[0309] In the implementation plan, R 20e The cyclopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20e Independently, arbitrarily, by a C 1-3 Alkyl-substituted cyclopropyl. In the embodiments, R 20e Independently, it is a cyclopropyl group optionally substituted with a methyl group. In the embodiments, R 20e The cyclobutyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20e The cyclopentyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0310] In the implementation plan, R 20f Independently hydrogen. In the implementation scheme, R 20f Independently halogenated. In the implementation scheme, R 20f Independently -OH. In the implementation scheme, R 20f Independently designated as -CN. In the implementation plan, R... 20f Independently for unreplaced C 1-6 Alkyl group. In the implementation scheme, R 20f Independently for unreplaced C 3-6 Cycloalkyl.

[0311] In the implementation plan, R 20f Independently, it is an unsubstituted methyl group. In the embodiments, R 20f Independently, it is an unsubstituted ethyl group. In the embodiments, R 20f Independently, it is unsubstituted propyl. In the implementation scheme, R 20f Independently, it is an unsubstituted isopropyl group. In the embodiments, R 20f Independently, it is unsubstituted butyl. In the implementation, R 20f Independent of unsubstituted tert-butyl.

[0312] In the implementation plan, R 20fThe methyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20f The ethyl group is independently selected from halogens, -OH, -CN, and C, optionally substituted with one, two, or three substituents. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20f The propyl group is optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20f The isopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20f The butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20f The tert-butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0313] In the implementation plan, R 20f Independently, it is an unsubstituted cyclopropyl group. In the embodiments, R 20f Independently, it is an unsubstituted cyclobutyl group. In the implementation, R 20f Independently, it is an unsubstituted cyclopentyl group.

[0314] In the implementation plan, R 20f The cyclopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20fIndependently, arbitrarily, by a C 1-3 Alkyl-substituted cyclopropyl. In the embodiments, R 20f Independently, it is a cyclopropyl group optionally substituted with a methyl group. In the embodiments, R 20f The cyclobutyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20f The cyclopentyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0315] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a Selected from C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a Selected from C 1-4 Alkylene, C 2-4imidene group, C 2-4 Alkyneyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a Selected from C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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-, wherein C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace.

[0316] In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a Selected from -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 In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a Selected from -C(O)-, -S(O)2-, and -S(O)-. In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a Selected from -C(O)- and -N(R)- 12 )C(O)-. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19a -N(R) 12 )C(O)-. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19a It is -N(H)C(O)-. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, L 19a It 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 Selected from C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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)(R12 )- and -P(O)(R 12 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a Selected from -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 In embodiments of compounds of formula I, IA, IB, II, or IIA, L 19a Selected from -C(O)-, -S(O)2-, -S(O)- and -P(O)(R 12 )-.

[0318] In embodiments of compounds of formula I, IA, II, IIA, or V, R 19a It is a 5-membered heteroaryl group having one or two cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, II, IIA, or V, R 19a Selected from pyrrole, imidazolyl, and pyrazolyl; wherein R 19a Through R 19a cyclic nitrogen atom and L 19a Direct bonding; and where R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a It is a non-aromatic 5- to 12-membered heterocycle containing three or four cyclic nitrogen atoms; wherein R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19aIt is a 5- to 12-membered heteroaryl group containing three or four cyclic nitrogen atoms; wherein R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a It is a 9- to 12-membered heteroaryl group containing three or four cyclic nitrogen atoms; wherein R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a It is a 5- to 6-membered heteroaryl group containing three or four cyclic nitrogen atoms; wherein R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a Selected from triazolyl and tetrazolyl; wherein R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a Selected from triazolyl and tetrazolyl; wherein R 19a Through R 19a cyclic nitrogen atom and L 19a Direct bonding; and where R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a Selected from triazolyl and imidazole; wherein R 19a Through R 19a cyclic nitrogen atom and L 19a Direct bonding; and where R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a Selected from 1,2,3-triazolyl and 1,2,4-triazolyl; wherein R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a Selected from 1,2,3-triazolyl and 1,2,4-triazolyl; wherein R 19a Through R 19a cyclic nitrogen atom and L 19a Direct bonding; and where R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19aOptionally substituted by one or more substituents independently selected from the following: halogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl and 3- to 6-membered heterokynyl; wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, and 3- to 6-membered heteroynyl groups are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -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 In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19aOptionally selected by one or more independently chosen from halogens, -CN and C 1-6 Alkyl substituents, wherein C 1-6 The alkyl group is optionally selected independently from one or more halogens, oxo groups, -CN groups, and -OR groups. 22 -SR 22 and -N(R) 22 (R) 23 The substituents of ) are substituted. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a 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 Optionally, it is selected by an R chosen from -F and -Cl. 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a Selected from ;where R 20g R 20h R 20i and R 20j Each time it appears, it is independently selected from hydrogen and R. 20 .

[0319] In the implementation plan, R 20g The methyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20g The ethyl group is independently selected from halogens, -OH, -CN, and C, optionally substituted with one, two, or three substituents. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20g The propyl group is optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20g The isopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R20g The butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20g The tert-butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0320] In the implementation plan, R 20g Independently, it is an unsubstituted cyclopropyl group. In the embodiments, R 20g Independently, it is an unsubstituted cyclobutyl group. In the implementation, R 20g Independently, it is an unsubstituted cyclopentyl group.

[0321] In the implementation plan, R 20g The cyclopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20g Independently, arbitrarily, by a C 1-3 Alkyl-substituted cyclopropyl. In the embodiments, R 20g Independently, it is a cyclopropyl group optionally substituted with a methyl group. In the embodiments, R 20g The cyclobutyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20g The cyclopentyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20g Independently halogenated. In the implementation scheme, R 20g Independently for F. In the implementation plan, R 20g Independently for Cl. In the implementation scheme, R 20g Independently for I. In the implementation plan, R 20g Independently, it is Br. In the implementation scheme, R 20gIndependently, it is an unsubstituted methyl group. In the embodiments, R 20g Independently, it is an unsubstituted ethyl group. In the embodiments, R 20g Independently, it is an unsubstituted isopropyl group. In the embodiments, R 20g Independently, it is unsubstituted tert-butyl. In the implementation, R 20g Independently for CN. In the implementation plan, R 20g Independently for CF3. In the implementation plan, R 20g Independently -CHF2. In the implementation scheme, R 20g Independently -CH2CN. In the implementation scheme, R 20g Independently -CH2OH. In the implementation scheme, R 20g Independently -CH2F. In the implementation scheme, R 20g Independently -CH2Cl. In the implementation scheme, R 20g Independently -CH2I. In the implementation scheme, R 20g Independently -CH2Br. In the implementation scheme, R 20g It is hydrogen independently.

[0322] In the implementation plan, R 20h The methyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20h The ethyl group is independently selected from halogens, -OH, -CN, and C, optionally substituted with one, two, or three substituents. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20h The propyl group is optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20h The isopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20h The butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C.1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20h The tert-butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0323] In the implementation plan, R 20h Independently, it is an unsubstituted cyclopropyl group. In the embodiments, R 20h Independently, it is an unsubstituted cyclobutyl group. In the implementation, R 20h Independently, it is an unsubstituted cyclopentyl group.

[0324] In the implementation plan, R 20h The cyclopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20h Independently, arbitrarily, by a C 1-3 Alkyl-substituted cyclopropyl. In the embodiments, R 20h Independently, it is a cyclopropyl group optionally substituted with a methyl group. In the embodiments, R 20h The cyclobutyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20h The cyclopentyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20h Independently halogenated. In the implementation scheme, R 20h Independently for F. In the implementation plan, R 20h Independently for Cl. In the implementation scheme, R 20h Independently for I. In the implementation plan, R 20h Independently, it is Br. In the implementation scheme, R 20h Independently, it is an unsubstituted methyl group. In the embodiments, R 20h Independently, it is an unsubstituted ethyl group. In the embodiments, R20h Independently, it is an unsubstituted isopropyl group. In the embodiments, R 20h Independently, it is unsubstituted tert-butyl. In the implementation, R 20h Independently for CN. In the implementation plan, R 20h Independently for CF3. In the implementation plan, R 20h Independently -CHF2. In the implementation scheme, R 20h Independently -CH2CN. In the implementation scheme, R 20h Independently -CH2OH. In the implementation scheme, R 20h Independently -CH2F. In the implementation scheme, R 20h Independently -CH2Cl. In the implementation scheme, R 20h Independently -CH2I. In the implementation scheme, R 20h Independently -CH2Br. In the implementation scheme, R 20h It is hydrogen independently.

[0325] In the implementation plan, R 20i The methyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20i The ethyl group is independently selected from halogens, -OH, -CN, and C, optionally substituted with one, two, or three substituents. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20i The propyl group is optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20i The isopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20i The butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R20i The tert-butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0326] In the implementation plan, R 20i Independently, it is an unsubstituted cyclopropyl group. In the embodiments, R 20i Independently, it is an unsubstituted cyclobutyl group. In the implementation, R 20i Independently, it is an unsubstituted cyclopentyl group.

[0327] In the implementation plan, R 20i The cyclopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20i Independently, arbitrarily, by a C 1-3 Alkyl-substituted cyclopropyl. In the embodiments, R 20i Independently, it is a cyclopropyl group optionally substituted with a methyl group. In the embodiments, R 20i The cyclobutyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20i The cyclopentyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20i Independently halogenated. In the implementation scheme, R 20i Independently for F. In the implementation plan, R 20i Independently for Cl. In the implementation scheme, R 20i Independently for I. In the implementation plan, R 20i Independently, it is Br. In the implementation scheme, R 20i Independently, it is an unsubstituted methyl group. In the embodiments, R 20i Independently, it is an unsubstituted ethyl group. In the embodiments, R 20i Independently, it is an unsubstituted isopropyl group. In the embodiments, R 20i Independently, it is unsubstituted tert-butyl. In the implementation, R20i Independently for CN. In the implementation plan, R 20i Independently for CF3. In the implementation plan, R 20i Independently -CHF2. In the implementation scheme, R 20i Independently -CH2CN. In the implementation scheme, R 20i Independently -CH2OH. In the implementation scheme, R 20i Independently -CH2F. In the implementation scheme, R 20i Independently -CH2Cl. In the implementation scheme, R 20i Independently -CH2I. In the implementation scheme, R 20i Independently -CH2Br. In the implementation scheme, R 20i It is hydrogen independently.

[0328] In the implementation plan, R 20j The methyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20j The ethyl group is independently selected from halogens, -OH, -CN, and C, optionally substituted with one, two, or three substituents. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20j The propyl group is optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20j The isopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20j The butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20j The tert-butyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C.1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl.

[0329] In the implementation plan, R 20j Independently, it is an unsubstituted cyclopropyl group. In the embodiments, R 20j Independently, it is an unsubstituted cyclobutyl group. In the implementation, R 20j Independently, it is an unsubstituted cyclopentyl group.

[0330] In the implementation plan, R 20j The cyclopropyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20j Independently, arbitrarily, by a C 1-3 Alkyl-substituted cyclopropyl. In the embodiments, R 20j Independently, it is a cyclopropyl group optionally substituted with a methyl group. In the embodiments, R 20j The cyclobutyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20j The cyclopentyl group is independently and optionally substituted with one, two, or three substituents, said substituents being independently selected from halogens, -OH, -CN, C. 1-3 Alkyl, C 1-3 Halogenated alkyl groups and C 3-6 Cycloalkyl. In the embodiment, R 20j Independently halogenated. In the implementation scheme, R 20j Independently for F. In the implementation plan, R 20j Independently for Cl. In the implementation scheme, R 20j Independently for I. In the implementation plan, R 20j Independently, it is Br. In the implementation scheme, R 20j Independently, it is an unsubstituted methyl group. In the embodiments, R 20j Independently, it is an unsubstituted ethyl group. In the embodiments, R 20j Independently, it is an unsubstituted isopropyl group. In the embodiments, R 20j Independently, it is unsubstituted tert-butyl. In the implementation, R 20j Independently for CN. In the implementation plan, R 20j Independently for CF3. In the implementation plan, R20j Independently -CHF2. In the implementation scheme, R 20j Independently -CH2CN. In the implementation scheme, R 20j Independently -CH2OH. In the implementation scheme, R 20j Independently -CH2F. In the implementation scheme, R 20j Independently -CH2Cl. In the implementation scheme, R 20j Independently -CH2I. In the implementation scheme, R 20j Independently -CH2Br. In the implementation scheme, R 20j It is hydrogen independently.

[0331] In the implementation schemes of formulas I, IA, IB, II, IIA, or V, R 19a Selected from .

[0332] In the implementation schemes of formulas I, IA, IB, II, IIA, or V, R 19a Selected from imidazole-1-yl and 1,2,4-triazol-1-yl, wherein imidazole-1-yl and 1,2,4-triazol-1-yl are each optionally separated by one or more R 20 Replacement. In embodiments of formulas I, IA, IB, II, IIA, or V, R 19a To be optionally used by one or more R 20 Substituted imidazole-1-yl. In embodiments of formula I, IA, IB, II, IIA, or V, R 19a To be optionally used by one or more R 20 Substituted 1,2,4-triazol-1-yl. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a Selected from imidazole-1-yl and 1,2,4-triazol-1-yl; wherein R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a Selected from imidazole-1-yl and 1,2,4-triazol-1-yl; wherein R 19a Through R 19a cyclic nitrogen atom and L 19a Direct bonding; and where R 19a Optionally by one or more R 20 Replacement. In embodiments of formulas I, IA, IB, II, IIA, or V, R 19a Selected from In the implementation schemes of formulas I, IA, IB, II, IIA, or V, R 19a Selected from Each of these is optionally controlled by one or more R 20k Replacement. In embodiments of formulas I, IA, IB, II, IIA, or V, R 19a Selected from Each of these is optionally controlled by one or more R 20k replace.

[0333] In the implementation schemes of formulas I, IA, IB, II, IIA, or V, R 19a Selected from Each of these is optionally controlled by one or more R 20k replace.

[0334] In the implementation schemes of formulas I, IA, IB, II, IIA, or V, R 19a Selected from Each of these is optionally controlled by one or more R 20k replace.

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

[0336] In embodiments of compounds of formula II or IIA, R 19a Selected from halogens, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Substitution. In embodiments of compounds of formula II or IIA, R 19a Selected from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl and 3- to 6-membered heteroynyl groups are optionally separated by one or more R groups. 20 replace.

[0337] In embodiments of compounds of formula II or IIA, R 19aSelected from C2-alkenyl and C2-ynyl, wherein the C2-alkenyl and C2-ynyl groups are optionally separated by one or more R groups. 20 Substitution. In embodiments of compounds of formula II or IIA, R 19a It is a -(3- to 12-membered heterocycle), wherein the -(3- to 12-membered heterocycle) is optionally bounded by one or more R 20 Substitution. In embodiments of compounds of formula II or IIA, R 19a It is a 5-membered heteroaryl group, wherein the 5-membered heteroaryl group is optionally surrounded by one or more R groups. 20 Substitution. In embodiments of compounds of formula II or IIA, R 19a It is a methyl group substituted with a halogen selected from Cl and F.

[0338] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a It is a 5-membered heteroaryl group containing one or more nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a Optionally by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a by one or more R 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a It is a 5-membered heteroaryl group containing three or four cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a by one or more R 20 replace.

[0339] In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a A 5-membered heterocycle comprising three or four cyclic nitrogen atoms, wherein the 5-membered heterocycle is optionally separated by one or more R atoms.20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a A 5-membered heterocycle containing three or four cyclic nitrogen atoms, wherein the 5-membered heterocycle is separated by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a A 6-membered heterocycle comprising three or four cyclic nitrogen atoms, wherein the 6-membered heterocycle is optionally separated by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IA, IB, II, IIA, or V, R 19a A 6-membered heterocycle containing three or four cyclic nitrogen atoms, wherein the 6-membered heterocycle is separated by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a A 7-membered heterocycle comprising three or four cyclic nitrogen atoms, wherein the 7-membered heterocycle is optionally separated by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a A 7-membered heterocycle containing three or four cyclic nitrogen atoms, wherein the 7-membered heterocycle is separated by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a An 8-membered heterocycle comprising three or four cyclic nitrogen atoms, wherein the 8-membered heterocycle is optionally separated by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a An 8-membered heterocycle containing three or four cyclic nitrogen atoms, wherein the 8-membered heterocycle is separated by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a A 9-membered heterocycle comprising three or four cyclic nitrogen atoms, wherein the 9-membered heterocycle is optionally separated by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a A 9-membered heterocycle containing three or four cyclic nitrogen atoms, wherein the 9-membered heterocycle is separated by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a A 10-membered heterocycle comprising three or four cyclic nitrogen atoms, wherein the 10-membered heterocycle is optionally separated by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a A 10-membered heterocycle containing three or four cyclic nitrogen atoms, wherein the 10-membered heterocycle is separated by one or more R atoms. 20Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a An 11-membered heterocycle comprising three or four cyclic nitrogen atoms, wherein the 11-membered heterocycle is optionally separated by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a An 11-membered heterocycle comprising three or four cyclic nitrogen atoms, wherein the 11-membered heterocycle is divided by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a A 12-membered heterocycle comprising three or four cyclic nitrogen atoms, wherein the 12-membered heterocycle is optionally separated by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a A 12-membered heterocycle containing three or four cyclic nitrogen atoms, wherein the 12-membered heterocycle is divided by one or more R atoms. 20 Substitution. In embodiments of compounds of formula I, IB, II, or IIA, R 19a It is a 5- to 12-membered heterocycle containing three or four cyclic nitrogen atoms, wherein the 12-membered heterocycle is separated by one or more R atoms. 20 replace.

[0340] In embodiments of compounds of formula II or IIA, -L 19a -R 19a Selected from ,in: R a Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, carboxyl, C 1-6 Alkoxycarbonyl, phenyl, C 2-7 Acylalkyl, 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-J3-(C(R) b )2) r ; R b Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C2-6 alkynyl group, C 3-6 cycloalkyl, C 2-7 Acylalkyl, C 2-7 Carboxylalkyl, phenyl, and phenyl groups optionally substituted with one or more of the following groups: halogen, C 1-6 Alkoxy, trifluoromethyl, amino, C 1-3 Alkylamino, C 2-6 Dialkylamino, nitro, azide, halomethyl, C 2-7 Alkoxymethyl, C 2-7 Alkyloxymethyl, C 1-6 Alkyl thio group, hydroxyl group, carboxyl group, C 2-7 Alkoxycarbonyl, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, C 1-6 Alkylamino or C 1-6 alkyl; R c Selected independently from -NR each time it appears. b R b and -OR b ; R d and R e Each is independently selected from -(C(R) b )2) r -NR b R b and -(C(R) b )2) r -OR b ; J 1 Each time it appears, it is independently selected from hydrogen, chlorine, fluorine, and bromine; J 2 Selected from C 1-6 Alkyl and hydrogen; M is independently selected from -N(R) each time it appears. b )-、-O-、-N[(C(R b )2) w -NR b R b ]- and -N[(C(R b )2) w -OR b ]-; J 3 It is selected independently from -N(R) each time it appears. b -, -O- and bonds; Het is independently selected from heterocycles each time it appears, optionally with R on carbon or nitrogen. b Mono- or di-substituted, and optionally with -CH2OR on carbon. bMonosubstituted; wherein 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, tetrazolium, piperazine, tetrahydrofuran, and tetrahydropyran; Each r is an independent integer from 1 to 4; Each w is an independent integer from 2 to 4; x is 0 or 1; y is an integer from 0 to 4; and Each z is an independent integer from 1 to 6; The sum of x + y is an integer from 2 to 4.

[0341] In embodiments of compounds of formula II or IIA, -L 19a -R 19a Selected from Each group is optionally bounded by one or more R groups, provided that the valence allows. 20 Replace; and R b Each time it appears, it is independently selected from hydrogen, hydroxyl, C. 1-6 Alkoxy and C 1-6 alkyl.

[0342] In embodiments of compounds of formula II or IIA: i. L 19 Selected from C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 Replace; and ii. -L 19a -R 19a Selected from ,in: R a Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, carboxyl, C 1-6 Alkoxycarbonyl, phenyl, C 2-7 Acylalkyl, 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-J3-(C(R) b )2) r ; R b Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, C 2-7 Acylalkyl, C 2-7 Carboxylalkyl, phenyl, and phenyl groups optionally substituted with one or more of the following groups: halogen, C 1-6 Alkoxy, trifluoromethyl, amino, C 1-3 Alkylamino, C 2-6 Dialkylamino, nitro, azide, halomethyl, C 2-7 Alkoxymethyl, C 2-7 Alkyloxymethyl, C 1-6 Alkyl thio group, hydroxyl group, carboxyl group, C 2-7 Alkoxycarbonyl, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, C 1-6 Alkylamino or C 1-6 alkyl; R c Selected independently from -NR each time it appears. b R b and -ORb ; R d and R e Each is independently selected from -(C(R) b )2) r -NR b R b and -(C(R) b )2) r -OR b ; J 1 Each time it appears, it is independently selected from hydrogen, chlorine, fluorine, and bromine; J 2 Selected from C 1-6 Alkyl and hydrogen; M is independently selected from -N(R) each time it appears. b )-、-O-、-N[(C(R b )2) w -NR b R b ]- and -N[(C(R b )2) w -OR b ]-; J 3 It is selected independently from -N(R) each time it appears. b -, -O- and bonds; Het is independently selected from heterocycles each time it appears, optionally with R on carbon or nitrogen. b Mono- or di-substituted, and optionally with -CH2OR on carbon. b Monosubstituted; wherein 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, tetrazolium, piperazine, tetrahydrofuran, and tetrahydropyran; Each r is an independent integer from 1 to 4; Each w is an independent integer from 2 to 4; x is 0 or 1; y is an integer from 0 to 4; and Each z is an independent integer from 1 to 6; The sum of x + y is an integer from 2 to 4.

[0343] In embodiments of compounds of formula II or IIA: i. L 19 Selected from C 1-4 Alkylene, C 2-4 imidene group, C 2-4Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 Replace; and ii. -L 19a -R 19a Selected from ,in: R a Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, carboxyl, C 1-6 Alkoxycarbonyl, phenyl, C 2-7 Acylalkyl, 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-J3-(C(R) b )2) r ; R b Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C2-6 alkynyl group, C 3-6 cycloalkyl, C 2-7 Acylalkyl, C 2-7 Carboxylalkyl, phenyl, and phenyl groups optionally substituted with one or more of the following groups: halogen, C 1-6 Alkoxy, trifluoromethyl, amino, C 1-3 Alkylamino, C 2-6 Dialkylamino, nitro, azide, halomethyl, C 2-7 Alkoxymethyl, C 2-7 Alkyloxymethyl, C 1-6 Alkyl thio group, hydroxyl group, carboxyl group, C 2-7 Alkoxycarbonyl, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, C 1-6 Alkylamino or C 1-6 alkyl; R c Selected independently from -NR each time it appears. b R b and -OR b ; R d and R e Each is independently selected from -(C(R) b )2) r -NR b R b and -(C(R) b )2) r -OR b ; J 1 Each time it appears, it is independently selected from hydrogen, chlorine, fluorine, and bromine; J 2 Selected from C 1-6 Alkyl and hydrogen; M is independently selected from -N(R) each time it appears. b )-、-O-、-N[(C(R b )2) w -NR b R b ]- and -N[(C(R b )2) w -OR b ]-; J 3 It is selected independently from -N(R) each time it appears. b -, -O- and bonds; Het is independently selected from heterocycles each time it appears, optionally with R on carbon or nitrogen. b Mono- or di-substituted, and optionally with -CH2OR on carbon. bMonosubstituted; wherein 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, tetrazolium, piperazine, tetrahydrofuran, and tetrahydropyran; Each r is an independent integer from 1 to 4; Each w is an independent integer from 2 to 4; x is 0 or 1; y is an integer from 0 to 4; and Each z is an independent integer from 1 to 6; The sum of x + y is an integer from 2 to 4.

[0344] In embodiments of compounds of formula II or IIA: i. L 19 Selected from C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 Replace; and ii. -L 19a -R 19a Selected from Each group is optionally bounded by one or more R groups, provided that the valence allows. 20 Replace; and R bEach time it appears, it is independently selected from hydrogen, hydroxyl, C. 1-6 Alkoxy and C 1-6 alkyl.

[0345] In embodiments of compounds of formula II or IIA, L 19 Selected from C 2-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 3- to 4-membered heteroalynyl, 3- to 4-membered heteroalynyl, -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 )O-, where C 2-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 3- to 4-membered heteroalkynyl and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace.

[0346] In embodiments of compounds of formula II or IIA: i. L 19 Selected from C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 Replace; and ii. -L 19a Selected from C 2-4 imidene group, C 2-4 Alynyl, 3- to 4-membered heteroalynyl, 3- to 4-membered heteroalynyl, -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 O-, where C 2-4 imidene group, C 2-4 The alkynyl, 3- to 4-membered heteroalkynyl and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 Replace; and iii. R 19a Selected from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 4-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(5- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(5- to 12-membered heterocyclic), -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 ), where C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 4-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(5- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(5- to 12-membered heterocycles) are optionally separated by one or more R 20 replace.

[0347] In embodiments of compounds of formula I, IA, IB, II, or IIA: i. L 19 Selected from C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace.

[0348] ii. X 12 It is -X 12a -; iii. R 19 It is by one or more R 20 Replaced monocyclic 3- to 8-membered heterocycles; and iv. R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a Optionally by one or more R 20 replace.

[0349] In embodiments of compounds of formula I, IA, IB, II, or IIA: i. L 19 It is optionally controlled by one or more R 20 Substituted C1 alkylene groups; ii. X 12 It is -X 12a -; iii. R 19 It is by one or more R 20 Replaced monocyclic 3- to 8-membered heterocycles; and iv. R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a Optionally by one or more R 20 replace.

[0350] In embodiments of compounds of formula I, IA, IB, II, or IIA: i. L 19 It is an unsubstituted C1 alkylene; ii. X 12 It is -X 12a -; iii. R 19 It is by one or more R 20 Replaced monocyclic 3- to 8-membered heterocycles; and iv. R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and R 19a Optionally by one or more R 20 replace.

[0351] In the implementation of formula II or IIA, R 19a A 3-membered heterocycle comprising a cyclic nitrogen atom, wherein the 3-membered heterocycle is optionally separated by one, two, or three R atoms. 20 Replacement. In embodiments of formula II or IIA, R 19a It is a 3-membered heterocycle containing a cyclic nitrogen atom, wherein the 3-membered heterocycle is optionally separated by C 1-6 Alkyl substitution, the C 1-6 The alkyl group is optionally substituted with one, two, or three halogens. In embodiments of formula II or IIA, R 19a It is a 3-membered heterocycle containing a cyclic nitrogen atom, wherein the 3-membered heterocycle is optionally separated by C 1-6 Alkyl substitution, wherein the C 1-6 The alkyl group is optionally substituted with one, two, or three F groups. In embodiments of formula II or IIA, R... 19a It is a 3-membered heterocycle containing a cyclic nitrogen atom, wherein the 3-membered heterocycle is optionally substituted with a methyl group, and the methyl group is optionally substituted with one, two or three halogens.

[0352] In the implementation of formula II or IIA, R 19a It is a 3-membered heterocycle containing a cyclic nitrogen atom, wherein the 3-membered heterocycle is optionally separated by C 3-5 Non-aromatic carbocyclic substitution, the C 3-5 The non-aromatic carbon ring is optionally substituted with one, two, or three halogens. In embodiments of formula II or IIA, R 19a It is a 3-membered heterocycle containing a cyclic nitrogen atom, wherein the 3-membered heterocycle is optionally separated by C 3-5 Non-aromatic carbocyclic substitution, the C 3-5 The non-aromatic carbon ring is optionally substituted with one, two, or three F. In embodiments of formula II or IIA, R 19aIt is a 3-membered heterocycle containing a cyclic nitrogen atom, wherein the 3-membered heterocycle is optionally substituted with a cyclopropyl group, which is optionally substituted with one, two, or three halogens. In embodiments of formula II or IIA, R 19a It is a 3-membered heterocycle containing a cyclic nitrogen atom, wherein the 3-membered heterocycle is optionally substituted with a cyclopropyl group, which is optionally substituted with one, two or three F atoms.

[0353] In the implementation of formula II or IIA, R 19a A 3-membered heterocycle comprising a cyclic nitrogen atom, wherein the 3-membered heterocycle is optionally surrounded by one or more atoms selected from C. 1-6 Alkyl and C 3-5 Substituents of non-aromatic carbocyclic rings. In embodiments of formula II or IIA, R 19a A 3-membered heterocycle comprising a cyclic nitrogen atom, wherein the 3-membered heterocycle is optionally surrounded by one or more atoms selected from C. 1-6 Alkyl and C 3-5 Substituent substitution of a non-aromatic carbocyclic ring, wherein the 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 It is a 3-membered heterocycle containing a cyclic nitrogen atom, wherein the 3-membered heterocycle is optionally substituted by one or more substituents selected from methyl and cyclopropyl, wherein the methyl and cyclopropyl groups are optionally substituted by halogens.

[0354] In the implementation of formula II or IIA, R 19a Selected from Each R 20 They are all chosen independently, and each one is different by choice.

[0355] In the implementation scheme of the above formula, R 19a Selected from Each R 20 They are all chosen independently, and each one is different by choice.

[0356] In the implementation scheme of the above formula, R 19a Selected from Each R 20 They are all chosen independently, and each one is different by choice.

[0357] In the implementation scheme of the above formula, R 19a Selected from , where each R 20 They are all chosen independently, and each one is different by choice.

[0358] In the implementation scheme of the above formula, R 19a Selected from , where each R 20 They are all chosen independently, and each one is different by choice.

[0359] In the implementation scheme of the above formula, R 19a Selected from: .

[0360] In the implementation scheme of the above formula, each R 20 Independently halogenated. In the implementation of the above formula, each R 20 Independently oxygenated. In the implementation of the above formula, each R 20 Independently for -CN. In the implementation of the above formula, each R 20 Independently for C 1-6 Alkyl group. In the embodiments of the above formula, each R 20 Independently for C 2-6 Alkenyl. In the embodiments of the above formula, each R 20 Independently for C 2-6 Alkynyl group. In the embodiments of the above formula, each R 20 Independently for C 3-12 Carbon ring. In the implementation scheme of the above formula, each R 20 Independently for C 2-11 Heterocyclic rings. In the implementation scheme of the above formula, each R 20 Independently for C 6-12 Aryl. In the embodiments of the above formula, each R 20 Independently for C1- 11 Heteroaryl. In the embodiments of the above formula, each R 20 Independently for -OR 22 In the implementation scheme of the above formula, each R 20 Independently for -SR 22 In the implementation scheme of the above formula, each R 20 Independently -N(R) 22 (R) 23 ).

[0361] In the implementation scheme of the above formula, each R 20 Independently -OH. In the implementation of the above formula, each R 20 Independently for -SH. In the implementation of the above formula, each R 20 Independently -NH2.

[0362] In the implementation plan, -L19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f It is an unsubstituted methyl group; and R 19a Selected from In the implementation plan, R 20f For unreplaced C 1-3 Alkyl; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it is substituted with one or more halogens, -CN, or unsubstituted C. 1-3 Halogenated alkyl substitution.

[0363] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f It is an unsubstituted methyl group; and R 19a Selected from In the implementation plan, R 20f For unreplaced C 1-3 Alkyl; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0364] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f It is an unsubstituted methyl group; and R 19a Selected from In the implementation plan, R20f For unreplaced C 1-3 Alkyl; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl and unsubstituted C 1-3 Halogenated alkyl substitution.

[0365] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f Selected from methyl-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl; and R 19a Selected from In the implementation plan, R 20f Selected from unsubstituted C 1-3 Alkyl and C 1-3 Alkyl-substituted C 3-4 Non-aromatic carbon ring; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0366] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f Selected from methyl-substituted cyclopropyl, cyclopropyl substituted with -CH2OCH3, cyclopropyl substituted with -CH2CN, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl; and R 19a Selected from In the implementation plan, R 20f Selected from unsubstituted C 1-3 Alkyl and C 1-3 Alkyl-substituted C 3-4 Non-aromatic carbon rings, in which C 1-3Alkyl groups are optionally C 1-3 Alkyl or CN substitution; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0367] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f Selected from methyl-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl; and R 19a Selected from In the implementation plan, R 20f Selected from unsubstituted C 1-3 Alkyl and C 1-3 Alkyl-substituted C 3-4 Non-aromatic carbon ring; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0368] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f Selected from methyl-substituted cyclopropyl, cyclopropyl substituted with -CH2OCH3, cyclopropyl substituted with -CH2CN, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl; and R 19a Selected from In the implementation plan, R 20f Selected from unsubstituted C 1-3 Alkyl and C 1-3 Alkyl-substituted C 3-4Non-aromatic carbon rings, in which C 1-3 Alkyl groups are optionally C 1-3 Alkyl or CN substitution; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0369] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f Selected from methyl-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl; and R 19a Selected from In the implementation plan, R 20f Selected from unsubstituted C 1-3 Alkyl and C 1-3 Alkyl-substituted C 3-4 Non-aromatic carbon ring; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0370] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f Selected from methyl-substituted cyclopropyl, cyclopropyl substituted with -CH2OCH3, cyclopropyl substituted with -CH2CN, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl; and R 19a Selected from In the implementation plan, R 20f Selected from unsubstituted C 1-3 Alkyl and C 1-3Alkyl-substituted C 3-4 Non-aromatic carbon rings, in which C 1-3 Alkyl groups are optionally C 1-3 Alkyl or CN substitution; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0371] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f Selected from methyl-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl; and R 19a Selected from In the implementation plan, R 20f Selected from unsubstituted C 1-3 Alkyl and C 1-3 Alkyl-substituted C 3-4 Non-aromatic carbon ring; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0372] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f Selected from methyl-substituted cyclopropyl, cyclopropyl substituted with -CH2OCH3, cyclopropyl substituted with -CH2CN, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl; and R 19a Selected from In the implementation plan, R 20f Selected from unsubstituted C 1-3Alkyl and C 1-3 Alkyl-substituted C 3-4 Non-aromatic carbon rings, in which C 1-3 Alkyl groups are optionally C 1-3 Alkyl or CN substitution; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0373] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f Selected from methyl-substituted cyclopropyl, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl; and R 19a Selected from In the implementation plan, R 20f Selected from unsubstituted C 1-3 Alkyl and C 1-3 Alkyl-substituted C 3-4 Non-aromatic carbon ring; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0374] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f Selected from methyl-substituted cyclopropyl, cyclopropyl substituted with -CH2OCH3, cyclopropyl substituted with -CH2CN, unsubstituted tert-butyl, unsubstituted isopropyl, and unsubstituted methyl; and R 19a Selected from In the implementation plan, R 20fSelected from unsubstituted C 1-3 Alkyl and C 1-3 Alkyl-substituted C 3-4 Non-aromatic carbon rings, in which C 1-3 Alkyl groups are optionally C 1-3 Alkyl or CN substitution; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0375] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 19a Selected from , In the implementation plan, R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0376] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 19a Selected from In the implementation plan, R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0377] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20 It is an unsubstituted methyl group; and R 19a Selected from In the implementation plan, R 20 Selected from unsubstituted C 1-3 Alkyl; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a It may be optionally replaced by one or more halogens.

[0378] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20 It is an unsubstituted methyl group; and R 19a Selected from In the implementation plan, R 20 Selected from unsubstituted C 1-3 Alkyl; and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally, it may be replaced by one or more halogens, -CN, or unsubstituted C. 1-3 Alkyl, unsubstituted C 1-3 Alkyl or unsubstituted C 1-3 Halogenated alkyl substitution.

[0379] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 19a Selected from In the implementation plan, R 19a Selected from unsubstituted cyclopentenyl, unsubstituted C 2-3 alkynyl group and C 2-3alkenyl, of which C 2-3 The alkenyl group is optionally substituted with one or more halogens, -CN, unsubstituted cyclopropyl, or -N(CH3)2. In the embodiments, R 19a Selected from unsubstituted C 4-6 Non-aromatic carbon ring, unsubstituted C 2-3 alkynyl group and C 2-3 alkenyl, of which C 2-3 The alkenyl group is optionally replaced by one or more halogens, -CN, or an unsubstituted C. 3-4 Non-aromatic carbon rings or -N(C) 1-3 Alkyl)2-substituted.

[0380] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f Selected from methyl-substituted cyclopropyl groups and unsubstituted methyl groups; and R 19a Selected from In the implementation plan, R 20f Selected from unsubstituted C 1-3 Alkyl and C 1-3 Alkyl-substituted C 3-4 Non-aromatic carbon ring; and R 19a Selected from unsubstituted cyclopentenyl, unsubstituted C 2-3 The alkynyl group and the C group optionally substituted with one or more halogens, -CN, unsubstituted cyclopropyl, or -N(CH3)2. 2-3 Alkenyl. In the embodiment, R 20f Selected from unsubstituted C 1-3 Alkyl and C 1-3 Alkyl-substituted C 3-4 Non-aromatic carbon ring; and R 19a Selected from unsubstituted C 4-6 Non-aromatic carbon ring, unsubstituted C 2-3 The alkynyl group and optionally the C group with one or more halogens, -CN, or unsubstituted C 3-4 Non-aromatic carbon rings or -N(C) 1-3 alkyl)2-substituted C 2-3 Alkenyl group.

[0381] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f Selected from methyl-substituted cyclopropyl groups and unsubstituted methyl groups; and R 19a Selected from In the implementation plan, R 20f Selected from unsubstituted C 1-3 Alkyl and C 1-3 Alkyl-substituted C 3-4 Non-aromatic carbon ring; and R 19a Selected from unsubstituted cyclopentenyl, unsubstituted C 2-3 The alkynyl group and the C group optionally substituted with one or more halogens, -CN, unsubstituted cyclopropyl, or -N(CH3) 2-3 Alkenyl. In the embodiment, R 20f Selected from unsubstituted C 1-3 Alkyl and C 1-3 Alkyl-substituted C 3-4 Non-aromatic carbon ring; and R 19a Selected from unsubstituted C 4-6 Non-aromatic carbon ring, unsubstituted C 2-3 The alkynyl group and optionally the C group with one or more halogens, -CN, or unsubstituted C 3-4 Non-aromatic carbon rings or -N(C) 1-3 alkyl)2-substituted C 2-3 Alkenyl group.

[0382] In the implementation plan, -L 19 -R 19 -L 19a -R 19a for In the implementation plan, R 20f It is an unsubstituted methyl group; and R 19a Selected from In the implementation plan, R 20f For unreplaced C 1-3 Alkyl; and R 19a Selected from unsubstituted cyclopentenyl, unsubstituted C 2-3 The alkynyl group and the C group optionally substituted with one or more halogens, -CN, unsubstituted cyclopropyl, or -N(CH3)2. 2-3 Alkenyl. In the embodiment, R 20f For unreplaced C 1-3 Alkyl, and R 19a Selected from unsubstituted C 4-6 Non-aromatic carbon ring, unsubstituted C 2-3 The alkynyl group and optionally the C group with one or more halogens, -CN, or unsubstituted C...

Claims

1. A compound having the following formula: Or a pharmaceutically acceptable salt or solvate thereof, wherein: X 1 Selected from N and C(R) 1 ); X 3 Selected from N and C(R) 3 ); X 5 It is C; X 6 Selected from C(R) 6 ) and N; X 8 Selected from C(R) 8 ) and N; X 10 It is C(R) 10 )2; X 11 It is C(R) 11 )2; X 12 Selected from -X 12a -、-X 12a -X 12b -、-X 12a -X 12b -X 12c -and-X 12a -X 12b -X 12c -X 12d -; where X 12a With X 5 Direct bonding; X 12a X 12b X 12c and X 12d Independently selected from O, C(R) 12a )2 and N(R 12b ); R 9 Yes -L 19 -R 19 -L 19a -R 19a ; L 19 Selected from key, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; R 19 Selected from monocyclic 3- to 8-membered heterocyclic rings and monocyclic C 3-8 Carbon rings, wherein the monocyclic 3- to 8-membered heterocyclic rings and monocyclic C 3-8 The carbon ring is optionally divided by one or more R 20 replace; L 19a Selected from -C(O)-, bond, C 1-4 Alkylene, C 2-4 imidene group, C 2-4 Alynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, 3- to 4-membered heteroalkynyl, -O-, -N(R) 12 )-、-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 )O-, where C 1-4 Alkylene, C 2-4 imidene group, C 2-4 The alkynyl, 2- to 4-membered heteroalkylene, 3- to 4-membered heteroalkenyl, and 3- to 4-membered heteroalkynyl groups are optionally separated by one or more R groups. 20 replace; R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a Optionally by one or more R 20 replace; Each R 12b Independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 1 R 2 R 3 R 6 R 8 R 10 R 11 R 12a and R 17 Each time it appears, it is independently selected from hydrogen, halogen, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 replace; R 12 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3- to 12-membered heterocyclic), wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl (3- to 12-membered heterocycle) optionally surrounded by one or more R 20 replace; R 13 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl; or R attached to the same nitrogen atom 12 and R 13 Formed optionally by one or more R 20 Replacement of 3- to 10-membered heterocycles; R 20 Each time it appears, it is independently selected from halogen, oxo, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ); where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -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 ); R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3- to 12-membered heterocycle), or two R groups 21 Together with the carbon atoms they are attached to, they form C 3-12 Carbon rings or 3- to 12-membered heterocycles, wherein the C 3-12 The carbon ring or 3- to 12-membered heterocycles are each optionally selected independently from halogens, C 1-3 Alkyl, C 1-3 Substitution with haloalkyl groups and -OH groups; R 22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl groups (3- to 12-membered heterocycles); R 23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R atoms bonded to the same nitrogen atom 22 and R 23 Formation of 3- to 10-membered heterocycles; and Each Independently represent single or double bonds, such that all valences are satisfied.

2. The compound according to claim 1, wherein R 19a It is a 5-membered heteroaryl group containing two, three, or four cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a cyclic nitrogen atom and L 19a Direct bonding, and where R 19a Optionally by one or more R 20 replace.

3. The compound according to any one of claims 1 to 2, wherein R 19a It is an imidazole group; where R 19a Through R 19a cyclic nitrogen atom and L 19a Direct bonding; and where R 19a Optionally by one or more R 20 replace.

4. The compound according to any one of claims 1 to 2, wherein R 19a It is a pyrazolyl group; where R 19a Through R 19a cyclic nitrogen atom and L 19a Direct bonding; and where R 19a Optionally by one or more R 20 replace.

5. The compound according to any one of claims 1 to 2, wherein R 19a It is a triazole group; where R 19a Through R 19a cyclic nitrogen atom and L 19a Direct bonding; and where R 19a Optionally by one or more R 20 replace.

6. The compound according to any one of claims 1 to 2, wherein R 19a It is 1,2,4-triazolyl; wherein R 19a Through R 19a cyclic nitrogen atom and L 19a Direct bonding; and where R 19a Optionally by one or more R 20 replace.

7. The compound according to any one of claims 1 to 6, wherein R 19a Optionally selected by one or more independently chosen from halogens, -CN and C 1-6 Alkyl substituents, wherein C 1-6 The alkyl group is optionally selected independently from one or more halogens, oxo groups, -CN groups, and -OR groups. 22 -SR 22 and -N(R) 22 (R) 23 Substituents of ) are used for substitution.

8. The compound according to any one of claims 1 to 6, wherein R 19a Optionally, it is selected by an R chosen from -F and -Cl. 20 replace.

9. The compound according to any one of claims 1 to 8, wherein L 19a Selected from -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 )-.

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

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

12. The compound according to any one of claims 1 to 11, wherein R 19 It is optionally controlled by one or more R 20 Replaced monocyclic C 3-8 Carbon ring.

13. The compound according to any one of claims 1 to 11, wherein R 19 It is optionally controlled by one or more R 20 Substituted monocyclic nonaromatic C 4-6 Carbon ring.

14. The compound according to any one of claims 1 to 11, wherein R 19 It is optionally controlled by one or more R 20 Replaced monocyclic 3- to 8-membered heterocyclic rings.

15. The compound according to any one of claims 1 to 11, wherein R 19 It is optionally controlled by one or more R 20 The replaced monocyclic non-aromatic 4- to 5-membered heterocycles.

16. The compound according to any one of claims 1 to 11, wherein R 19 Selected from aziridine and pyrrolidinyl; wherein the aziridine and pyrrolidinyl are optionally composed of one or more R 20 replace.

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

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

19. The compound according to any one of claims 1 to 17, wherein L 19 It is unreplaced C 1-2 Alkylene.

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

21. The compound according to any one of claims 1 to 20, wherein X 10 It is CH(R) 10 ).

22. The compound according to any one of claims 1 to 20, wherein X 10 It is CH2.

23. The compound according to any one of claims 1 to 21, wherein R 10 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 3-5 Carbon rings and 3- to 5-membered heterocycles, of which C 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 3-5 The carbon ring and 3- to 5-membered heterocycles are optionally separated by one or more R 20 replace.

24. The compound according to any one of claims 1 to 21, wherein R 10 Each time it appears, it is independently selected from hydrogen, 。 25. The compound according to any one of claims 1 to 24, wherein X 11 It is CH(R) 11 ).

26. The compound according to any one of claims 1 to 24, wherein X 11 It is CH2.

27. The compound according to any one of claims 1 to 25, wherein R 11 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 3-5 Carbon rings and 3- to 5-membered heterocycles, of which C 1-4 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group, C 3-5 The carbon ring and 3- to 5-membered heterocycles are optionally separated by one or more R 20 replace.

28. The compound according to any one of claims 1 to 27, wherein X 12 It is -X 12a - 29. The compound according to any one of claims 1 to 28, wherein X 12a It is O.

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

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

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

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

34. The compound according to any one of claims 1 to 32, wherein R 2 It is -O(C) 1-3 (alkylene)-(non-aromatic C) 3-5 (Carbon ring)-(C 1-3 Alkylene)-(non-aromatic 4- to 10-membered heterocycle), wherein the non-aromatic 4- to 10-membered heterocycle is optionally composed of one, two, or three independently selected from halogens, C 1-3 Alkyl, C 1-3 Haloalkyl and =C(R) 21 Substituents of )2.

35. The compound according to any one of claims 1 to 31, wherein R 2 Selected from 。 36. The compound according to any one of claims 1 to 31, wherein R 2 Selected from and .

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

38. The compound according to any one of claims 1 to 37, wherein X 6 It is C(R) 6 ).

39. The compound according to any one of claims 1 to 38, wherein R 6 Selected from hydrogen, halogens and C 1-3 Halogenated alkyl groups.

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

41. The compound according to any one of claims 1 to 38, wherein R 6 It is -CF3.

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

43. The compound according to any one of claims 1 to 42, wherein R 17 Selected from C 6-12 Carbon rings and 5- to 12-membered heterocycles, of which C 6-12 Carbon rings and 5- to 12-membered heterocycles are optionally separated by one or more R 20 replace.

44. The compound according to any one of claims 1 to 42, wherein R 17 The group is selected from phenyl, pyridyl, naphthyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzothiaphenyl, indazole, and benzoxazolyl, wherein phenyl, pyridyl, naphthyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzothiaphenyl, indazole, and benzoxazolyl are optionally separated by one or more R 20 replace.

45. The compound according to any one of claims 1 to 42, wherein R 17 Selected from: ,in: Q 1 Q 3 and Q 5 Independently selected from N and C(R) 1q ); Q 4 and Q 6 Independently selected from O, S, C(R) 1q )2 and N(R 1r ); Y 4 Y 5 Y 6 Y 9 and Y 10 Independently selected from C(R) 1q ) and N; Y 7 and Y 8 Independently selected from C(R) 1q ), C(R 1q 2. N and N(R) 1r ); Y 13 Selected from key, 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 Independently selected from C(O) and C(R) 1q ), N, C(R) 1q )2 and N(R 1r ); Y 16 Selected from C, N and C(R) 1q ); Each R 1q Independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ), where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) optionally separated by one or more R 20 Substitution; or two Rs bonded to the same carbon atom 1q The connection forms 3- to 10-membered heterocycles or C 3-10 Carbon rings, including 3- to 10-membered heterocycles and C 3-10 The carbon ring is optionally divided by one or more R 20 Substitution; or bonding to two adjacent R atoms 1q The connection forms 3- to 10-membered heterocycles or C 3-10 Carbon rings, including 3- to 10-membered heterocycles and C 3-10 The carbon ring is optionally divided by one or more R 20 Replace; or an R 1q And an R 1r The connection forms 3- to 10-membered heterocycles or C 3-10 Carbon rings, including 3- to 10-membered heterocycles and C 3-10 The carbon ring is optionally divided by one or more R 20 replace; Each R 1r Independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne groups, 3- to 10-membered heterocycles and C 3-10 Carbon ring, where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne groups, 3- to 10-membered heterocycles and C 3-10 The carbon ring is optionally divided by one or more R 20 Replace; and Each Independently represent single or double bonds, such that all valences are satisfied.

46. ​​The compound according to any one of claims 1 to 42, wherein R 17 Selected from .

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

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

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

50. A compound having a formula selected from the following: ; or its pharmaceutically acceptable salts or solvates, wherein: X 6 Selected from C(R) 6 ) and N; R 6 Selected from hydrogen, halogens, -CN, C 1-3 Alkyl, C 2-3 alkenyl and C 2-3 Alkyne group; wherein C 1-3 Alkyl, C 2-3 alkenyl and C 2-3 Each of the alkynyl groups is optionally surrounded by one, two, or three R groups. 20 replace; R 10 R 11 and R 12a Each is independently selected from hydrogen, halogen, -CN, C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group and C 3-6 Carbon ring; where C 1-3 Alkyl, C 2-3 alkenyl, C 2-3 alkynyl group and C 3-6 Each carbon ring is optionally separated by one, two, or three R 20 replace; R 12 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl-(3- to 12-membered heterocyclic), wherein C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl (3- to 12-membered heterocycle) optionally surrounded by one or more R 20 replace; R 8 It is halogen; R 9 Selected from ； R 20f Selected from C 1-6 Alkyl and C 3-6 Carbon ring; where C 1-6 Alkyl and C 3-6 Each carbon ring is optionally separated by one, two, or three R 20 replace; R 17 Selected from ,in: Q 3 is C(CN); Q 4 Selected from O and S; Y 4 Y 5 Y 6 Y 9 and Y 10 Independently selected from C(R) 1q ) and N; Y 14 、Y 15 、Y 17 和Y 18 is C(R 1q ); Each R 1q Independently selected from hydrogen, halogen, -CN, C 1-3 Alkyl, C 1-3 Haloalkyl, C 2-3 alkenyl, C 2-3 Alkynyl, 2- to 4-membered heteroalkyl, 2- to 4-membered heteroalkenyl, 2- to 4-membered heterokynyl, -C 0-6 Alkyl-(C 3-5 carbon ring), -C 0-6 Alkyl groups (3- to 5-membered heterocycles), -OH, -NH2, and -C(O)CH3; R 2 It is -O(C) 1-3 Alkylene (non-aromatic 4- to 10-membered heterocycle), wherein the non-aromatic 4- to 10-membered heterocycle is optionally selected independently by one or more halogens, C 1-3 Alkyl, C 1-3 Haloalkyl and =C(R) 21 Substituents of )2, wherein R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-3 Alkyl; and L 19a It is -N(R) 12 )C(O)-; R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally selected by one or more independently chosen from halogens, -CN, unsubstituted C 1-3 Alkyl and unsubstituted C 1-3 Substituents of haloalkyl groups; R 20 Each time it appears, it is independently selected from halogen, oxo, -CN, C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocyclic), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocyclic), -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 ); where C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkynyl, 2- to 6-membered heteroalkyl, 3- to 6-membered heteroalkenyl, 3- to 6-membered heterokynyl, -C 0-6 Alkyl-(C 3-12 (Carbocyclic), -(2- to 6-membered heteroalkyl)-(C 3-12 carbon ring), -C 0-6 Alkyl-(3- to 12-membered heterocycles) and -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycles) are optionally substituted by one or more substituents independently selected from the following: halogen, oxo, -CN, C. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, -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 ); R 21 Each time it appears, it is independently selected from hydrogen, halogen, and C. 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl group (3- to 12-membered heterocycle), or two R groups 21 Together with the carbon atoms they are attached to, they form C 3-12 Carbon rings or 3- to 12-membered heterocycles, wherein the C 3-12 The carbon ring or 3- to 12-membered heterocycles are each optionally selected independently from halogens, C 1-3 Alkyl, C 1-3 Substitution with haloalkyl groups and -OH groups; R 22 Each time it appears, it is independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl, -C 0-6 Alkyl-(C 3-12 (Carbon ring) and -C 0-6 Alkyl groups (3- to 12-membered heterocycles); R 23 Each time it appears, it is independently selected from hydrogen and C. 1-6 Alkyl groups; or R atoms bonded to the same nitrogen atom 22 and R 23 Formation of 3- to 10-membered heterocycles; and Each Independently represent single or double bonds, such that all valences are satisfied.

51. The compound according to claim 50, wherein... R 9 yes .

52. The compound according to claim 50, wherein... R 9 yes .

53. The compound according to any one of claims 50 to 52, wherein R 11 and R 12a Each is independently selected from hydrogen and -CH3; R 20f It is unreplaced C 1-3 alkyl; R 17 Selected from ; R 2 Selected from ;and R 19a It is a 5-membered heteroaryl group containing one or more cyclic nitrogen atoms, wherein the 5-membered heteroaryl group is determined by R 19a The cyclic nitrogen atom is directly bonded to -C(O)-, and R is located in the cyclic nitrogen atom. 19a Optionally selected by one or more independently chosen from halogens, -CN, unsubstituted C 1-3 Alkyl and unsubstituted C 1-3 Substitution of alkyl halogens.

54. The compound according to any one of claims 1 and 9 to 53, wherein R 19a Selected from .

55. The compound according to any one of claims 1 and 50, wherein the compound has the formula Or its pharmaceutically acceptable salts or solvates.

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

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

59. The method of claim 58, wherein the reduced Ras signaling output is demonstrated by one or more outputs selected from: (i) an increase in the steady-state level of GDP-bound modified proteins; (ii) a decrease in the steady-state level of GTP-bound modified proteins; (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 growth of tumor cells expressing Ras G12S mutant protein; and (vii) a decrease in Ras interactions with Ras pathway signaling proteins.

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

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

62. A method for treating cancer involving a subject containing a Ras mutant protein, the method comprising: The Ras mutant protein of the object is inhibited by applying the compound according to any one of claims 1 to 55 to the object, wherein the compound is characterized in that, upon contact with the Ras mutant protein, the Ras mutant protein exhibits a reduced Ras signaling output.

63. The method according to claim 61 or 62, wherein the cancer is a solid tumor or a hematologic 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 modulating the signal transduction output of a Ras protein, the method 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 modulating the signal transduction output of the Ras protein.

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

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

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