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 signalling output of certain oncogenic proteins.

Description

[0001] Cross-references

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 395,649, filed on August 5, 2022, which is incorporated herein by reference in its entirety.

[0003] Sequence Listing

[0004] This application contains a sequence listing submitted electronically in XML format and hereby incorporated by reference in its entirety. The XML copy was created on August 2, 2023, is named 56690_756_601_SL.xml, and is 13,992 bytes in size. Background Art

[0005] Cancer (e.g., tumors, neoplasms, metastases) is the second leading cause of death worldwide, accounting for an estimated 10 million deaths per year. Many types of cancer are marked by mutations in one or more proteins that are involved in various signaling pathways, leading to uncontrolled growth of cancer cells. In some cases, about 25% to 30% of tumors are known to contain rat sarcoma (Ras) mutations. In particular, mutations in the Kirsten Ras oncogene (K-Ras) are one of the most common Ras mutations detected in human cancers, including lung adenocarcinoma (LUAD) and pancreatic ductal adenocarcinoma (PDAC).

[0006] Ras proteins have long been considered "undruggable", in part due to the high affinity for their substrate guanosine-5'-triphosphate (GTP) and / or their smooth surface without any obvious targeting areas. The specific G12C Ras gene mutation has been identified as a druggable target, against which a number of G12C-specific inhibitors have been developed. However, the application of such therapies remains limited, as 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 limit such therapies. Summary of the invention

[0007] In view of the foregoing, there is still a considerable need for new designs of therapeutic agents and diagnostic agents that can specifically target Ras (including wild-type Ras, mutants and / or related proteins of Ras) to reduce Ras signaling output. Of particular interest are Ras inhibitors, including pan-Ras inhibitors that can inhibit two or more Ras mutants and / or wild-type Ras, and mutation-selective inhibitors targeting mutant Ras proteins such as Ras G12D, G12C, G12S, G13D and / or G12V, for the treatment of Ras-related diseases (e.g., cancer). Such compositions and methods can be particularly useful for the treatment of a variety of diseases, including but not limited to cancer and neoplasia conditions. The present disclosure meets these needs and provides additional advantages that are suitable for the diagnosis, prognosis and / or treatment of a variety of diseases.

[0008] In one aspect, provided is a compound of formula (A), or a pharmaceutically acceptable salt or solvate thereof:

[0009]

[0010] in:

[0011] W 1 is N(R 1 ) or N;

[0012] R 1 Selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20a replace;

[0013] W 2 is C(R 2 )、N(R 2 )、C(R 2 ) 2 、C(O), S(O), S(O) 2 or N;

[0014] Each R 2 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12a 、-SR 12a 、-N(R 12a )(R 13 ),-N=(R 15 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )-、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20b replace;

[0015] W 3 is C(R 3 )、N(R 3 )、C(R 3 ) 2 、C(O),S(O),S(O) 2 or N;

[0016] Each R 3 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20c replace;

[0017] W 4 is C(R4 ), C or N;

[0018] R 4 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20d replace;

[0019] W 5 is C(R 5 ), C or N;

[0020] R 5 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20e replace;

[0021] W 6 is C(R 6 )、N(R 6 )、C(R 6 ) 2 、C(O),S(O),S(O) 2 or N;

[0022] Each R 6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20f replace;

[0023] W 7 is C(R 7a ), C or N;

[0024] R 7a Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace;

[0025] R 7 Yes-L 7 -R 17 ;

[0026] L 7 Yes key, C 1 -C 4 Alkyl, C 2 -C 4Alkenyl, C 2 -C 4 Alkynyl, 2-4 membered heteroalkyl linker, -O-, -N(R 7d )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, -P(O)R 7d -, CR 7c R 7c -, -OCR 7c R 7c -, -N(R 7d )CR 7c R 7c -, -C(O)CR 7c R 7c -, -SCR 7c R 7c -, -S(O) 2 CR 7c R 7c -, -S(O)CR 7c R 7c -, -P(O)R 7d CR 7c R 7c -, -CR 7c R 7c CR 7c R 7c , -CR 7c R 7c O-, -CR 7c R 7c N(R 7d )-, -CR 7c R 7c C(O)-, -CR 7c R 7c S-, -CR 7c R 7c S(O) 2 -, -CR 7c R 7c S(O)-, -CR 7c R 7c P(O)R 7d -, -N(R 7d )C(O)-, -N(R 7d )S(O) 2 -, -N(R 7d )S(O)-, -N(R 7d )P(O)R 7d -, -C(O)N(R 7d )-, -S(O) 2 N(R 7d )-, -S(O)N(R 7d)-、-P(O)R 7d N(R 7d )-、-OC(O)-、-OS(O) 2 -、-OS(O)-、-OP(O)R 7d -、-C(O)O-、-S(O) 2 O-, -S(O)O-, or -P(O)R 7d O-; wherein said C 1 -C 4 Alkyl, C 2 -C 4 Alkenyl, C 2 -C 4 Alkynyl, 2-4 membered heteroalkylene linker is optionally substituted by one, two or three R 20g replace;

[0027] Each R 7c are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace;

[0028] Each R 7d are independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace;

[0029] R 17 Selected from C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl, wherein C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl are optionally substituted by one or more R 20q Replace; or L 7 is a key and R 7a and R 17 Together with the carbon to which they are attached, they form C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl are optionally substituted with one or more R 20q replace;

[0030] W 8 is C(R 8 )、N(R 8 )、C(R 8 ) 2 、C(O), S(O), S(O) 2 or N;

[0031] Each R 8 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20h replace;

[0032] W 9 is C(R9 ), C or N;

[0033] R 9 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20i replace;

[0034] W 10 is C(R 10 ), C or N;

[0035] R 10 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20j replace;

[0036] Each Z 1 Independently C(R z1 )、N(R z1 )、C(R z1 ) 2 、C(O),S(O),S(O) 2 , O, S or N;

[0037] z1n is 0, 1, 2, or 3; if z1n is 0, then Z 2 Direct bonding to W 5 ;

[0038] Each R z1 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14)S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z1 replace;

[0039] Each Z 9 Independently C(R z9 )、N(R z9 )、C(R z9 ) 2 、C(O),S(O),S(O) 2 , O, S or N;

[0040] z9n is 0, 1, 2, or 3; if z9n is 0, then Z 3 Direct bonding to W 4 ;

[0041] Each R z9are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z9 replace;

[0042] The sum of z1n and z9n is 2 or 3;

[0043] Z 2 is C(R z2 ), C or N;

[0044] R z2 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z2 replace;

[0045] Z 3 is C(R z3 ), C or N;

[0046] R z3 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z3 replace;

[0047] Z 4 Yes key, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c or Z 4a Z 4b Z 4c Z 4d ; where Z 4a Direct Bonding to Z 2 ; and if Z 4 is a key, then Z 2 Direct Bonding to Z 5 ;

[0048] Z 4a , Z 4b , Z 4c and Z 4d Independently C(R z4 )、N(R z4 )、C(R z4 ) 2 、C(O), S(O), S(O) 2、S(O)(NR z4 ), O, S or N;

[0049] The conditions are:

[0050] i) If z9n is 0 and Z 4 It's Z 4a Z 4b ; then (1) Z 4b is C(R z4 )、C(R z4 ) 2 、C(O),S(O),S(O) 2 、S(O)(NR z4 ), O, S or N, (2) Z 4b is N(R z4 ) and Z 4a is C(O), S(O) or S(O) 2 ; (3) Z 4b is N(R z4 ) and Z 5 is C(O), S(O) or S(O) 2 ; or (4) Z 4b is N(R z4 ) and Z 3 is C(R z3 ) or C; and

[0051] ii) One R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 or R 20z Independently selected from -C(O)R 12 and -N(H)C(O)R 12 ; One of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace;

[0052] Each R z4 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 alkenyl;

[0053] Z 5 is C(R z5 )、N(R z5 )、C(R z5 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z5 ), O, S or N;

[0054] Each R z5 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12)(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 Alkenyl; Z 6 is C(R z6 )、N(R z6 )、C(R z6 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z6 ), O, S or N;

[0055] Each R z6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 alkenyl; and further wherein the compound optionally comprises one of:

[0056] (1) Two R bonded to the same carbon atom z4 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0057] (2) Two or more R bonded to adjacent atoms z4 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace;

[0058] (3) Two R bonded to the same carbon atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0059] (4) One or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace;

[0060] (5) One or two R bonded to an atom z4 and one or two R bonded to a second atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0061] (6) Two R bonded to the same carbon atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0062] (7) One or two R bonded to an atom z5 and one or two R bonded to adjacent atoms z6 Connect to form a single ring C 3-7Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; or

[0063] (8) One or two R bonded to an atom z4 and one or two R bonded to a second atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0064] Each R 12 are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace;

[0065] Each R 12a are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-10 Cycloalkyl, -C(R 12c ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c ) 2 -C 6-10 Aryl, -C(R 12c ) 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c ) 2 -C 6-10 Aryl, -C(R 12c ) 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace;

[0066] Each R 12c are independently selected from hydrogen and R 20lc ;

[0067] Each R 13 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 haloalkyl; or R 12 and R 13 Together with the nitrogen to which they are attached, they form a 20m Substituted C 2-9 heterocycloalkyl ring;

[0068] Each R 14 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl;

[0069] Each R 15 Independently selected from C1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20o replace;

[0070] Each R 20z1 , R 20z2 , R 20z3 , R 20z4 , R 20z5 , R 20z6 and R 20z9 are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z replace;

[0071] Each R 20z are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20zz replace;

[0072] Two R bonded to the same carbon atom 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20zz replace; or

[0073] Two or more R bonded to two adjacent atoms 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20zz replace;

[0074] Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20lc , R 20l , R 20m , R 20o , R 20q and R 20zz are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O) 2 R 25 、-C(O)R 21 、-S(O) 2 R 25 、-S(O) 2 N(R22 )(R 23 ),-OCH 2 C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O) 2 R 25 、-C(O)R 25 、-S(O)2 R 25 、-S(O) 2 N(R 22 )(R 23 ) and -OC(O)R 25 ;

[0075] Each R 21 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl;

[0076] Each R 22 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl;

[0077] Each R 23 are independently selected from hydrogen and C 1-6 alkyl;

[0078] Each R 24 are independently selected from hydrogen and C 1-6 alkyl;

[0079] Each R 25 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; and represents a single or double bond such that all valences are satisfied.

[0080] In one aspect, provided is a compound of formula (A), or a pharmaceutically acceptable salt or solvate thereof:

[0081]

[0082] in:

[0083] W 1 is N(R 1) or N;

[0084] R 1 Selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20a replace;

[0085] W 2 is C(R 2 )、N(R 2 )、C(R2 ) 2 、C(O),S(O),S(O) 2 or N;

[0086] Each R 2 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12a 、-SR 12a 、-N(R 12a )(R 13 ),-N=(R 15 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )-、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20b replace;

[0087] W 3 is C(R 3 )、N(R 3 )、C(R 3 ) 2 、C(O),S(O),S(O) 2 or N;

[0088] Each R 3 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20c replace;

[0089] W 4 is C(R 4 ), C or N;

[0090] R 4 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20d replace;

[0091] W 5 is C(R 5 ), C or N;

[0092] R 5 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13)、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20e replace;

[0093] W 6 is C(R 6 )、N(R 6 )、C(R 6 ) 2、C(O), S(O), S(O) 2 or N;

[0094] Each R 6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20f replace;

[0095] W 7 is C(R 7a ), C or N;

[0096] R 7a Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace;

[0097] R 7 Yes-L 7 -R 17 ;

[0098] L 7 Yes key, C 1 -C 4 Alkyl, C 2 -C 4 Alkenyl, C 2 -C 4 Alkynyl, 2-4 membered heteroalkylene linker, -O-, -N(R 7d )-、-C(O)-、-S-、-S(O) 2 -、-S(O)-、-P(O)R 7d -, CR 7c R 7c , -OCR 7c R 7c -、-N(R 7d )CR 7c R 7c -、-C(O)CR 7c R 7c -、-SCR 7c R 7c -、-S(O) 2 CR 7c R 7c -、-S(O)CR 7c R 7c -、-P(O)R 7d CR 7c R 7c -、-CR 7c R7c CR 7c R 7c , -CR 7c R 7c O-、-CR 7c R 7c N(R 7d )-、-CR 7c R 7c C(O)-、-CR 7c R 7c S-、-CR 7c R 7c S(O) 2 -、-CR 7c R 7c S(O)-、-CR 7c R 7c P(O)R 7d -、-N(R 7d )C(O)-、-N(R 7d )S(O) 2 -、-N(R 7d )S(O)-、-N(R 7d )P(O)R 7d -、-C(O)N(R 7d )-、-S(O) 2 N(R 7d )-、-S(O)N(R 7d )-、-P(O)R 7d N(R 7d )-、-OC(O)-、-OS(O) 2 -、-OS(O)-、-OP(O)R 7d -、-C(O)O-、-S(O) 2 O-, -S(O)O-, or -P(O)R 7d O-; wherein said C 1 -C 4 Alkyl, C 2 -C 4 Alkenyl, C 2 -C 4 Alkynyl, 2-4 membered heteroalkylene linker is optionally substituted by one, two or three R 20g replace;

[0099] Each R 7c are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace;

[0100] Each R7d are independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20g replace;

[0101] R 17 Selected from C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl, wherein C 3-10Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl are optionally substituted by one or more R 20q Replace; or L 7 is a key and R 7a and R 17 Together with the carbon to which they are attached, they form C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl are optionally substituted with one or more R 20q replace;

[0102] W 8 is C(R 8 )、N(R 8 )、C(R 8 ) 2 、C(O), S(O), S(O) 2 or N;

[0103] Each R 8 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20h replace;

[0104] W 9 is C(R 9 ), C or N;

[0105] R 9 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20i replace;

[0106] W 10 is C(R 10 ), C or N;

[0107] R 10 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20j replace;

[0108] Each Z 1 Independently C(R z1 )、N(R z1 )、C(R z1 ) 2 、C(O),S(O),S(O)2 , O, S or N;

[0109] z1n is 0, 1, 2, or 3; if z1n is 0, then Z 2 Direct bonding to W 5 ;

[0110] Each R z1 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z1 replace;

[0111] Each Z 9 Independently C(R z9 )、N(R z9 )、C(R z9 ) 2 、C(O),S(O),S(O) 2 , O, S or N;

[0112] z9n is 0, 1, 2, or 3; if z9n is 0, then Z 3 Direct bonding to W 4 ;

[0113] Each R z9 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12)(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z9 replace;

[0114] The sum of z1n and z9n is 2 or 3;

[0115] Z 2 is C(R z2 ), C or N;

[0116] R z2 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z2 replace;

[0117] Z 3 is C(R z3 ), C or N;

[0118] R z3 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9The heteroaryl group is optionally substituted by one, two or three R 20z3 replace;

[0119] Z 4 Yes key, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c or Z 4a Z 4b Z 4c Z 4d ; where Z 4a Direct Bonding to Z 2 ; and if Z 4 is a key, then Z 2 Direct Bonding to Z 5 ;

[0120] Z 4a , Z 4b , Z 4c and Z 4d Independently C(R z4 )、N(R z4 )、C(R z4 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z4 ), O, S or N;

[0121] The conditions are:

[0122] i) If z9n is 0 and Z 4 It's Z 4a Z 4b ; then (1) Z 4b is C(R z4 )、C(R z4 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z4 ), O, S or N, (2) Z 4b is N(R z4 ) and Z 4a is C(O), S(O) or S(O) 2 ; (3) Z 4b is N(R z4 ) and Z 5 is C(O), S(O) or S(O) 2 ; or (4) Z 4b is N(R z4 ) and Z 3 is C(R z3 ) or C; and

[0123] ii) R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 , R 20z , R 20zz One or a combination of R z4 , R z5 , R z6 , R 20z and R 20zz One of the two substituents in the formula (A) is E, wherein E is capable of binding to the human K-Ras mutant G12D or G12S protein, respectively.

[0124] The part covalently bound to the Ras mutant protein at the amino acid corresponding to G12D or G12S: each R z4 are independently selected from E, hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 Alkenyl; Z 5 is C(R z5 )、N(R z5 )、C(R z5 ) 2 、C(O),S(O),S(O) 2 、S(O)(NR z5 ), O, S or N;

[0125] Each R z5 are independently selected from E, hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 Alkenyl; Z 6 is C(R z6 )、N(R z6 )、C(R z6 ) 2 、C(O), S(O), S(O) 2 、S(O)(NRz6 ), O, S or N;

[0126] Each R z6 are independently selected from E, hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 alkenyl; and further wherein the compound optionally comprises one of:

[0127] (1) Two R bonded to the same carbon atom z4 Connect to form E, single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0128] (2) Two or more R bonded to adjacent atoms z4 Connect to form E, single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace;

[0129] (3) Two R bonded to the same carbon atom z5 Connect to form E, single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0130] (4) One or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 Connect to form E, single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace;

[0131] (5) One or two R bonded to an atom z4 and one or two R bonded to a second atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0132] (6) Two R bonded to the same carbon atom z6 Connect to form E, single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0133] (7) One or two R bonded to an atom z5 and one or two R bonded to adjacent atoms z6 Connect to form E, single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; or

[0134] (8) One or two R bonded to an atom z4 and one or two R bonded to a second atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0135] Each R 12 are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace;

[0136] Each R 12a are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c ) 2 -C 6-10 Aryl, -C(R 12c ) 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c ) 2 -C 6-10 Aryl, -C(R 12c ) 2 -C 1-9 Heteroaryl and C1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace;

[0137] Each R 12c are independently selected from hydrogen and R 20lc ;

[0138] Each R 13 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 haloalkyl; or R 12 and R 13 Together with the nitrogen to which they are attached, they form a 20m Substituted C 2-9 heterocycloalkyl ring;

[0139] Each R 14 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl;

[0140] Each R 15 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20o replace;

[0141] Each R 20z1 , R 20z2 , R 20z3 and R 20z9 are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z replace;

[0142] Each R 20z4 , R 20z5 and R 20z6 are independently selected from E, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z replace;

[0143] Each R 20z are independently selected from E, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20zz replace;

[0144] Two R bonded to the same carbon atom 20z Optionally linked to form E, monocyclic C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20zz replace; or

[0145] Two or more R bonded to two adjacent atoms 20z Optionally linked to form E, monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20zz replace;

[0146] Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20lc , R 20l , R 20lz , R 20m , R 20o and R 20q are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2-C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O) 2 R 25 、-C(O)R 21 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ),-OCH 2 C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O) 2 R 25 、-C(O)R 25 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ) and -OC(O)R 25 ;

[0147] Each R 20zz are independently selected from E, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O) 2 R 25 、-C(O)R 21 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ),-OCH 2 C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O) 2 R 25 、-C(O)R 25 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ) and -OC(O)R 25 ; Each R 21 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl;

[0148] Each R 22 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl;

[0149] Each R 23 are independently selected from hydrogen and C 1-6 alkyl;

[0150] Each R 24are independently selected from hydrogen and C 1-6 alkyl;

[0151] Each R 25 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; and

[0152] represents a single or double bond such that all valences are satisfied.

[0153] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 or R 20z independently -C(O)R 12 or -N(H)C(O)R 12 ; One of the R 12 It is C 1-9 Heteroaryl, wherein C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace.

[0154] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 or R 20z Independently - C(O)R 12 or -N(H)C(O)R 12 ; One of the R 12 Selected from C2-9 Heterocycloalkyl; wherein C 2-9 The heterocycloalkyl group is optionally substituted by one, two or three R 20l replace.

[0155] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, one R z4 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z4 Replace, and an R 20z4 Selected from -C(O)R 12 and -N(H)C(O)R 12 ; One of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace.

[0156] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, one R z5 Independently selected from C 1-6 Alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z5 Replace; and an R 20z5 Selected from -C(O)R 12 and -N(H)C(O)R 12 ; One of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace.

[0157] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, one R z6 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z6 Replace; and an R 20z6 Selected from -C(O)R 12and -N(H)C(O)R 12 ; One of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace.

[0158] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, one R z4 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z4 Replace; one of the R 20z4 Selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z Replace; and an R 20z Selected from -C(O)R12 and -N(H)C(O)R 12 ; One of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace.

[0159] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, one R z5 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z5 Replace; one of the R 20z5 Selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z Replace; and an R 20zSelected from -C(O)R 12 and -N(H)C(O)R 12 ; One of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace.

[0160] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, one R z6 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z6 Replace; one of the R 20z6 Selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z Replace; and an R20z Selected from -C(O)R 12 and -N(H)C(O)R 12 ; One of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl; wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace.

[0161] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, two or more R z4 , R z5 or R z6 Connect to form one, two or three R 20z substituted ring; and an R 20z Selected from -C(O)R 12 and -N(H)C(O)R 12 ; One of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl; wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace.

[0162] In one aspect, provided is a compound of formula (A) or a pharmaceutically acceptable salt or solvate thereof:

[0163]

[0164] in:

[0165] W 1 is N(R 1 ) or N;

[0166] R 1 Selected from hydrogen, -CN, C1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20a replace;

[0167] W 2 is C(R 2 )、N(R 2 )、C(R 2 ) 2 、C(O),S(O),S(O) 2 or N;

[0168] Each R 2 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12a 、-SR 12a 、-N(R 12a )(R 13 ),-N=(R 15 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )-、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20b replace;

[0169] W 3 is C(R 3 )、N(R 3 )、C(R 3 ) 2 、C(O), S(O), S(O) 2 or N;

[0170] Each R 3 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20c replace;

[0171] W 4 is C(R 4 ), C or N;

[0172] R 4 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20d replace;

[0173] W 5 is C(R 5 ), C or N;

[0174] R 5 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20e replace;

[0175] W 6 is C(R 6 )、N(R 6 )、C(R 6 ) 2 、C(O), S(O), S(O) 2 or N;

[0176] Each R 6are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20f replace;

[0177] W 7 is C(R 7a ), C or N;

[0178] R 7a Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace;

[0179] R 7 Yes-L 7 -R 17 ;

[0180] L 7 Yes key, C 1 -C 4 Alkyl, C 2 -C 4 Alkenyl, C 2 -C 4 Alkynyl, 2-4 membered heteroalkylene linker, -O-, -N(R 7d )-、-C(O)-、-S-、-S(O) 2 -、-S(O)-、-P(O)R 7d -, CR 7c R 7c , -OCR 7c R 7c -、-N(R 7d )CR 7c R 7c -、-C(O)CR 7c R 7c -、-SCR 7c R 7c -、-S(O) 2 CR 7c R 7c -、-S(O)CR 7c R 7c -、-P(O)R 7d CR 7c R 7c -、-CR 7c R 7c CR 7c R 7c , -CR 7c R7c O-、-CR 7c R 7c N(R 7d )-、-CR 7c R 7c C(O)-、-CR 7c R 7c S-、-CR 7c R 7c S(O) 2 -、-CR 7c R 7c S(O)-、-CR 7c R 7c P(O)R 7d -、-N(R 7d )C(O)-、-N(R 7d )S(O) 2 -、-N(R 7d )S(O)-、-N(R 7d )P(O)R 7d -、-C(O)N(R 7d )-、-S(O) 2 N(R 7d )-、-S(O)N(R 7d )-、-P(O)R 7d N(R 7d )-、-OC(O)-、-OS(O) 2 -、-OS(O)-、-OP(O)R 7d -、-C(O)O-、-S(O) 2 O-, -S(O)O-, or -P(O)R 7d O-; wherein said C 1 -C 4 Alkyl, C 2 -C 4 Alkenyl, C 2 -C 4 Alkynyl, 2-4 membered heteroalkylene linker is optionally substituted by one, two or three R 20g replace;

[0181] Each R 7c are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12)(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20g replace;

[0182] Each R 7d are independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace;

[0183] R 17 Selected from C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl, wherein C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl are optionally substituted by one or more R 20qReplace; or L 7 is a key, and R 7a and R 17 Together with the carbon to which they are attached, they form C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl are optionally substituted with one or more R 20q replace;

[0184] W 8 is C(R 8 )、N(R 8 )、C(R 8 ) 2 、C(O),S(O),S(O) 2 or N;

[0185] Each R 8 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20h replace;

[0186] W 9 is C(R 9 ), C or N;

[0187] R 9 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20i replace;

[0188] W 10 is C(R 10 ), C or N;

[0189] R 10 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20j replace;

[0190] Each Z 1 Independently C(R z1 )、N(R z1 )、C(R z1 ) 2 、C(O),S(O),S(O) 2 , O, S or N;

[0191] z1n is 0, 1, 2, or 3; if z1n is 0, then Z 2 Direct bonding to W 5 ;

[0192] Each R z1 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O)2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z1 replace;

[0193] Each Z 9 Independently C(R z9 )、N(R z9 )、C(R z9 ) 2 、C(O),S(O),S(O) 2 , O, S or N;

[0194] z9n is 0, 1, 2, or 3; if z9n is 0, then Z 3 Direct bonding to W 4 ;

[0195] Each R z9 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z9 replace;

[0196] The sum of z1n and z9n is 2 or 3;

[0197] Z 2 is C(R z2 ), C or N;

[0198] R z2 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z2 replace;

[0199] Z 3 is C(R z3 ), C or N;

[0200] R z3 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R20z3 replace;

[0201] Z 4 Yes key, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c or Z 4a Z 4b Z 4c Z 4d ; where Z 4a Direct Bonding to Z 2 ; and if Z 4 is a key, then Z 2 Direct Bonding to Z 5 ;

[0202] Z 4a , Z 4b , Z 4c and Z 4d Independently C(R z4 )、N(R z4 )、C(R z4 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z4 ), O, S or N;

[0203] The condition is that if z9n is 0 and Z 4 It's Z 4a Z 4b ; then (1) Z 4b is C(R z4 )、C(R z4 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z4 ), O, S or N, (2) Z 4b is N(R z4 ) and Z 4a is C(O), S(O) or S(O) 2 ; (3) Z 4b is N(R z4 ) and Z 5 is C(O), S(O) or S(O) 2 ; or (4) Z 4b is N(R z4 ) and Z 3 is C(R z3 ) or C; and

[0204] Each R z4 Independently selected from -Lz1 -L z2 -L z3 -R 12 , hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 alkenyl;

[0205] Z 5 is C(R z5 )、N(R z5 )、C(R z5 ) 2 、C(O),S(O),S(O) 2 、S(O)(NR z5 ), O, S or N;

[0206] Each R z5 Independently selected from -L z1 -L z2 -L z3 -R 12 , hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13)、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 alkenyl;

[0207] Z 6 is C(R z6 )、N(R z6 )、C(R z6 ) 2 、C(O),S(O),S(O) 2 、S(O)(NR z6 ), O, S or N;

[0208] Each R z6 Independently selected from -L z1 -L z2 -L z3 -R 12 , hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9The heteroaryl group is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 alkenyl;

[0209] And further wherein the compound optionally comprises one of the following:

[0210] (1) Two R bonded to the same carbon atom z4 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0211] (2) Two or more R bonded to adjacent atoms z4 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace;

[0212] (3) Two R bonded to the same carbon atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0213] (4) One or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace;

[0214] (5) One or two R bonded to an atom z4 and one or two R bonded to a second atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0215] (6) Two R bonded to the same carbon atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0216] (7) One or two R bonded to an atom z5 and one or two R bonded to adjacent atoms z6 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; or

[0217] (8) One or two R bonded to an atom z4 and one or two R bonded to a second atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0218] Each R 12 are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace;

[0219] Each R 12a are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c ) 2 -C 6-10 Aryl, -C(R 12c ) 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c ) 2 -C 6-10 Aryl, -C(R 12c ) 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace;

[0220] Each R 12c are independently selected from hydrogen and R 20lc ;

[0221] Each R 13 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 haloalkyl; or R 12 and R 13 Together with the nitrogen to which they are attached, they form a 20m Substituted C 2-9 heterocycloalkyl ring;

[0222] Each R 14 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl;

[0223] Each R 15 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20o replace;

[0224] Each R 20z1 , R 20z2 , R 20z3 , R 20z4 , R 20z5 , R 20z6 and R 20z9 are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z replace;

[0225] Each R 20z Independently selected from -L z3 -R 12 , halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20zz replace;

[0226] Two R bonded to the same carbon atom 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20zz replace; or

[0227] Two or more R bonded to two adjacent atoms 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20zz replace;

[0228] L z1 Select from key, C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 3-10 Cycloalkylene, C 2-9 Heterocycloalkylene, C 6-10 Arylene and C 1-9 Heteroarylene; wherein C 1-6 Alkyl, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 3-10 Cycloalkylene, C 2-9 Heterocycloalkylene, C 6-10 Arylene and C 1-9 The heteroarylene group is optionally substituted by one or two R 30z replace;

[0229] R 30z are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z replace;

[0230] L z2 Select from key, C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 3-10 Cycloalkylene, C 2-9 Heterocycloalkylene, C 6-10 Arylene and C 1-9 Heteroarylene; wherein C 1-6 Alkyl, C 2-6 Alkenylene, C2-6 Alkynylidene, C 3-10 Cycloalkylene, C 2-9 Heterocycloalkylene, C 6-10 Arylene and C 1-9 The heteroarylene group is optionally substituted by one or two R 31z replace;

[0231] R 31z are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20zz replace;

[0232] L z3 -R 12 Selected from:

[0233] i.-C(O)R 12 or -N(H)C(O)R 12 ; where L z3 -R 12 R 12 is a 5-membered heteroaryl group containing two or more ring nitrogen atoms, wherein the 5-membered heteroaryl group is 12 The ring nitrogen atom is directly bonded to C(O) and wherein R 12 Optionally one or more R 20l Replacement; and

[0234] ii.-C(O)R 12 or -N(H)C(O)R 12 ; where L z3 -R 12 R 12 is a 3-membered heterocycloalkyl group containing one or more ring nitrogen atoms, wherein R 12 Optionally one or more R 20l replace;

[0235] R 20l are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O) 2 R 25 、-C(O)R 21 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ),-OCH 2 C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O) 2 R 25 、-C(O)R 25 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ) and -OC(O)R 25 ; Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20l , R 20lc , R 20m , R 20o , R 20q and R 20zz are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O) 2 R 25 、-C(O)R 21 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ),-OCH 2 C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O) 2 R 25 、-C(O)R 25 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ) and -OC(O)R 25 ;

[0236] Each R 21 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl;

[0237] Each R 22 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl;

[0238] Each R 23 are independently selected from hydrogen and C 1-6 alkyl;

[0239] Each R 24 are independently selected from hydrogen and C 1-6 alkyl;

[0240] Each R 25 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; and

[0241] represents a single or double bond such that all valences are satisfied.

[0242] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, wherein:

[0243] L z1 Select from key, C 1-6 Alkylene, C 3-10 Cycloalkylene and C 2-9 Heterocycloalkylene; wherein C 1-6 Alkylene, C 3-10 Cycloalkylene and C 2-9 The heterocycloalkylene group is optionally substituted by one or two R 30z replace;

[0244] R 30z are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z replace;

[0245] L z2Select from key, C 1-6 Alkylene, C 3-10 Cycloalkylene and C 2-9 Heterocycloalkylene; wherein C 1-6 Alkylene, C 3-10 Cycloalkylene and C 2-9 The heterocycloalkylene group is optionally substituted by one or two R 31z replace;

[0246] R 31z are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20zz replace;

[0247] L z3 -R 12 Selected from:

[0248] i.-C(O)R 12 or -N(H)C(O)R 12 ; where L z3 -R 12 R 12 is a 5-membered heteroaryl group containing two or more ring nitrogen atoms, wherein the 5-membered heteroaryl group is 12 The ring nitrogen atom is directly bonded to C(O) and wherein R 12 Optionally one or more R 20l Replacement; and

[0249] ii.-C(O)R 12 or -N(H)C(O)R 12 ; where L z3 -R 12 R 12 is a 3-membered heterocycloalkyl group containing one or more ring nitrogen atoms, wherein R 12 Optionally one or more R 20l replace;

[0250] R 20l are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10Aryl, -CH 2 -C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O) 2 R 25 、-C(O)R 21 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ),-OCH 2 C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O) 2 R 25 、-C(O)R 25 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ) and -OC(O)R 25 .

[0251] In an embodiment of the compound of formula (A), or a pharmaceutically acceptable salt or solvate thereof, it has the formula:

[0252]

[0253] In an embodiment of the compound of formula (A), or a pharmaceutically acceptable salt or solvate thereof, it has the formula:

[0254]

[0255] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, wherein

[0256] yes

[0257] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, wherein yes

[0258] In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, two R bonded to the same carbon atom z5 to form a monocyclic 4-membered heterocycloalkyl group, wherein the 4-membered heterocycloalkyl group is surrounded by one, two or three R 20z replace.

[0259] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, Selected from

[0260]

[0261] In each of the above formulas, one R 20z Yes-C(O)R 12 or -N(H)C(O)R 12 .

[0262] In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, one or two R bonded to one atomz4 and one or two R bonded to adjacent atoms z5 to form a monocyclic 5-6 membered heteroaryl, wherein the monocyclic 5-6 membered heteroaryl is optionally substituted by one, two or three R 20z replace.

[0263] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, yes Wherein one R shown in the above formula 20z Yes-C(O)R 12 or -N(H)C(O)R 12 .

[0264] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, z1n is 1, 2 or 3, and z9n is 1, 2 or 3. In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, W 1 is N. In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, W 2 is C(R 2). In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, W 3 is N. In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, W 4 is C. In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, W 5 is C. In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, W 5 is C(R 5 ). In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, W 6 is C(R 6 ). In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, R 6 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl and -OR12 , where C 1-6 The alkyl group is optionally substituted by one, two or three R 20f In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, R 6 In the embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B or their pharmaceutically acceptable salts or solvates, W 7 is C. In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, W 8 is C(R 8 ). In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, R 8 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl and -OR 12 , where C 1-6 The alkyl group is optionally substituted by one, two or three R 20h In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, R 8In the embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B or their pharmaceutically acceptable salts or solvates, W 9 is C. In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, W 10 is C. In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, Selected from

[0265] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, L 7 In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, R 17 is selected from naphthyl and benzothienyl, each of which is optionally substituted by one, two or three R 20qIn embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, R 17 Substituted by one, two or three substituents independently selected from halogen, -CN, -CH 3 , -C≡CH, -OH and -NH 2 .

[0266] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, R 17 Selected from

[0267] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, R 17 Selected from:

[0268]

[0269]

[0270] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, R 2 Independently is -OR 12a .

[0271] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, R 2 Independently selected from

[0272]

[0273] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, R 2 Independently

[0274] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, Z 4 It's Z 4a In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, Z 4 It's Z 4a Z 4b .

[0275] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, each R z4 are independently selected from hydrogen, halogen, -CN, C1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-N(H)C(O)R 12 、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 )-, where C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, each R z4 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 and -S(O) 2 R 15 , where C 1-6 Alkyl, C 3-10Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, each R z5 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-N(H)C(O)R 12 、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 )-, where C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, each R z5 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 and -S(O) 2 R 15 , where C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, each R z6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12)(R 13 )、-N(H)C(O)R 12 、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 )-, where C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, each R z6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 and -S(O) 2 R 15 , where C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, each R 20z are independently selected from hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-N(H)C(O)R 12 、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 )-, where C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20zz or two R bonded to the same carbon 20z connected to form a 20zz Substituted C 2-6 In embodiments of the compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, each R 20z are independently selected from hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 and -S(O) 2 R 15 , where C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20zz or two R bonded to the same carbon 20z connected to form a 20zz Substituted C 2-6 Alkenyl.

[0276] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 or R 20z Independently selected from -C(O)R 12 and -N(H)C(O)R 12 ; and -C(O)R 12 or -N(H)C(O)R 12 R 12 Selected from

[0277] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 or R20z Independently selected from -C(O)R 12 and -N(H)C(O)R 12 ; and -C(O)R 12 or -N(H)C(O)R 12 R 12 Selected from

[0278] In embodiments of compounds of formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B, or pharmaceutically acceptable salts or solvates thereof, one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 or R 20z Independently selected from -C(O)R 12 and -N(H)C(O)R 12 ; and -C(O)R 12 or -N(H)C(O)R 12 R 12 Selected from

[0279] In one aspect, a pharmaceutical composition is provided, comprising a compound described herein (e.g., a compound of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B) or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable excipient.

[0280] In one aspect, a method of treating cancer in a subject in need thereof is provided, comprising administering to the subject a therapeutically effective amount of a compound described herein (e.g., a compound of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B) or a pharmaceutically acceptable salt or solvate thereof.

[0281] In one aspect, a method for treating cancer in a subject comprising a Ras mutant protein is provided, the method comprising: modifying the Ras mutant protein of the subject by administering a compound to the subject, wherein the compound is characterized in that when contacting the Ras mutant protein, the Ras mutant protein is covalently modified at the residue corresponding to residue 12 of SEQ ID No: 1, such that the modified Ras mutant protein exhibits reduced Ras signaling output.

[0282] In embodiments, the cancer is a solid tumor.In embodiments, the cancer is a hematological cancer.

[0283] In one aspect, a method for regulating the signaling output of a Ras protein is provided, the method comprising contacting the Ras protein with an effective amount of a compound described herein (e.g., a compound of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f and / or B) or a pharmaceutically acceptable salt or solvate thereof, thereby regulating the signaling output of the Ras protein.

[0284] In embodiments, the method comprises administering an additional agent.

[0285] In one aspect, provided is a compound of formula (A) or a pharmaceutically acceptable salt or solvate thereof:

[0286]

[0287] in:

[0288] W 1 is N(R 1 ) or N;

[0289] R 1 Selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20a replace;

[0290] W 2 is C(R 2 )、N(R 2 )、C(R 2 ) 2 、C(O), S(O), S(O) 2 or N;

[0291] Each R 2 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12a 、-SR 12a 、-N(R 12a )(R 13 ),-N=(R 15)、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20b replace;

[0292] W 3 is C(R 3 )、N(R 3 )、C(R 3 ) 2、C(O), S(O), S(O) 2 or N;

[0293] Each R 3 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20c replace;

[0294] W 4 is C(R 4 ), C or N;

[0295] R 4 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20d replace;

[0296] W 5 is C(R 5 ), C or N;

[0297] R 5 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20e replace;

[0298] W 6 is C(R 6 )、N(R 6 )、C(R 6 ) 2 、C(O),S(O),S(O) 2 or N;

[0299] Each R 6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13)、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20f replace;

[0300] W 7 is C(R 7a ), C or N;

[0301] R 7a Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9The heteroaryl group is optionally substituted by one, two or three R 20g replace;

[0302] R 7 Yes-L 7 -R 17 ;

[0303] L 7 Yes key, C 1 -C 4 Alkyl, C 2 -C 4 Alkenyl, C 2 -C 4 Alkynyl, 2-4 membered heteroalkylene linker, -O-, -N(R 7d )、-C(O)-、-S-、-S(O) 2 -、-S(O)-、-P(O)R 7d -, CR 7c R 7c , -OCR 7c R 7c -、-N(R 7d )CR 7c R 7c -、-C(O)CR 7c R 7c -、-SCR 7c R 7c -、-S(O) 2 CR 7c R 7c -、-S(O)CR 7c R 7c -、-P(O)R 7d CR 7c R 7c -、-CR 7c R 7c CR 7c R 7c , -CR 7c R 7c O-、-CR 7c R 7c N(R 7d )-、-CR 7c R 7c C(O)-、-CR 7c R 7c S-、-CR 7c R 7c S(O) 2 -、-CR 7c R 7c S(O)-、-CR 7c R 7c P(O)R 7d-、-N(R 7d )C(O)-、-N(R 7d )S(O) 2 -、-N(R 7d )S(O)-、-N(R 7d )P(O)R 7d -、-C(O)N(R 7d )-、-S(O) 2 N(R 7d )-、-S(O)N(R 7d )-、-P(O)R 7d N(R 7d )-、-OC(O)-、-OS(O) 2 -、-OS(O)-、-OP(O)R 7d -、-C(O)O-、-S(O) 2 O-, -S(O)O-, or -P(O)R 7d O-; wherein said C 1 -C 4 Alkyl, C 2 -C 4 Alkenyl, C 2 -C 4 Alkynyl and 2-4 membered heteroalkylene linkers are optionally substituted by one, two or three R 20g replace;

[0304] Each R 7c are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20g replace;

[0305] Each R 7d are independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace;

[0306] R 17 Selected from C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl, wherein C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl are optionally substituted by one or more R 20q replace;

[0307] W 8 is C(R 8 )、N(R 8 )、C(R 8 ) 2 、C(O), S(O), S(O) 2 or N;

[0308] Each R 8 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R20h replace;

[0309] W 9 is C(R 9 ), C or N;

[0310] R 9 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20i replace;

[0311] W 10 is C(R 10 ), C or N;

[0312] R 10 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13)、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20j replace;

[0313] Each Z 1 Independently C(R z1 )、N(R z1 )、C(R z1 ) 2 、C(O), S(O), S(O) 2 , O, S or N;

[0314] z1n is 0, 1, 2, 3 or 4; if z1n is 0, then Z 2 Direct bonding to W 5 ; Each R z1 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z1 replace;

[0315] Z 2 is C(R z2 ), C or N;

[0316] R z2 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z2 replace;

[0317] Z 3is C(R z3 ), C or N;

[0318] R z3 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z3 replace;

[0319] Z 4 Yes key, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c , Z 4a Z 4b Z 4c Z 4d or Z 4a Z 4b Z 4c Z 4d Z 4e ; where Z 4a Direct Bonding to Z 2 ; and if Z 4 is a key, then Z 2 Direct Bonding to Z 5 ;

[0320] Z 4a , Z 4b , Z 4c , Z 4d and Z 4e Independently C(R z4 )、N(R z4 )、C(R z4 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z4 ), O, S or N;

[0321] The condition is that if z9n is 0 and Z 4 It's Z 4a Z 4b ; then (1) Z 4b is C(R z4 )、C(R z4 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z4 ), O, S or N, (2) Z 4b is N(R z4 ) and Z 4ais C(O), S(O) or S(O) 2 ; (3) Z 4b is N(R z4 ) and Z 5 is C(O), S(O) or S(O) 2 ; or (4) Z 4b is N(R z4 ) and Z 3 is C(R z3 ) or C;

[0322] Each R z4 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 Alkenyl; Z 5 is C(R z5 )、N(R z5 )、C(R z5 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z5 ), O, S or N;

[0323] Each R z5 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 Alkenyl; Z 6 is C(R z6 )、N(R z6 )、C(R z6 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z6 ), O, S or N;

[0324] Each R z6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9The heteroaryl group is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 alkenyl; and further wherein the compound optionally comprises one of:

[0325] (1) Two R bonded to the same carbon atom z4 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0326] (2) Two or more R bonded to adjacent atoms z4 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace;

[0327] (3) Two R bonded to the same carbon atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0328] (4) One or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace;

[0329] (5) One or two R bonded to an atom z4 and one or two R bonded to a second atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R20z replace;

[0330] (6) Two R bonded to the same carbon atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0331] (7) One or two R bonded to an atom z5 and one or two R bonded to adjacent atoms z6 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; or

[0332] (8) One or two R bonded to an atom z4 and one or two R bonded to a second atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0333] Two R bonded to the same carbon atom 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20zz replace; or

[0334] Two or more R bonded to two adjacent atoms 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20zz replace;

[0335] Each Z 9 Independently C(R z9 )、N(R z9 )、C(R z9 )2 、C(O),S(O),S(O) 2 , O, S or N;

[0336] z9n is 0, 1, 2, 3, or 4; if z9n is 0, then Z 3 Direct bonding to W 4 ; Each R z9 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O)2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z9 replace;

[0337] where the sum of z1n and z9n is 2, 3 or 4;

[0338] Each R 12 are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace;

[0339] Each R 12a are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-10 Cycloalkyl, -C(R 12c ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c ) 2 -C 6-10 Aryl, -C(R 12c ) 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c ) 2 -C 6-10 Aryl, -C(R 12c ) 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace;

[0340] Each R 12c are independently selected from hydrogen and R 20lc ;

[0341] Each R 13 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 haloalkyl; or R 12 and R 13 Together with the nitrogen to which they are attached, they form a 20m Substituted C 2-9 heterocycloalkyl ring;

[0342] Each R 14 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl;

[0343] Each R 15 Independently selected from C1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20o replace;

[0344] Each R 20z1 , R 20z2 , R 20z3 , R 20z4 , R 20z5 , R 20z6 and R 20z9 are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z replace;

[0345] Each R 20z are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20zz replace;

[0346] Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20l , R 20lc , R 20m , R 20o , R 20q and R 20zz are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O) 2 R 25 、-C(O)R 21 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ),-OCH 2 C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O) 2 R 25 、-C(O)R 25 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ) and -OC(O)R 25 ;

[0347] Each R 21 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl;

[0348] Each R 22are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl;

[0349] Each R 23 are independently selected from hydrogen and C 1-6 alkyl;

[0350] Each R 24 are independently selected from hydrogen and C 1-6 alkyl;

[0351] Each R 25 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; and

[0352] represents a single or double bond such that all valences are satisfied.

[0353] In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula:

[0354] In an implementation scheme, yes In an implementation scheme, yes In an implementation scheme, Selected from In an implementation scheme, Selected from In an implementation scheme, Selected from

[0355] In an embodiment, two R bonded to the same carbon atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z In an embodiment, two R bonded to the same carbon atom z5 to form a monocyclic 4-membered heterocycloalkyl group, wherein the 4-membered heterocycloalkyl group is surrounded by one, two or three R 20z replace.

[0356] In an implementation scheme, Selected from

[0357] In an implementation scheme, Selected from

[0358]

[0359] In an embodiment, one or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z In an embodiment, one or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 to form a monocyclic 5-6 membered heteroaryl, wherein the monocyclic 5-6 membered heteroaryl is optionally substituted by one, two or three R 20z In an embodiment, one or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 The monocyclic 5-6 membered heteroaryl formed by connecting is triazolyl, pyrazolyl, imidazolyl, pyrrolyl, furanyl, thienyl, oxazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazinyl; each of which is optionally substituted by one, two or three R 20z In an embodiment, one or two R bonded to an atom z4and one or two R bonded to adjacent atoms z5 The monocyclic 5-6 membered heteroaryl formed by connecting 20z Substituted pyrazolyl.

[0360] In an implementation scheme, Selected from In an implementation scheme, Selected from

[0361] In an embodiment, z1n is 1, 2 or 3 and z9n is 1, 2 or 3. In an embodiment, z1n is 0. In an embodiment, z9n is 0.

[0362] In an embodiment, W 1 is N. In an embodiment, W 1 is N(R 1 ).

[0363] In an embodiment, W 2 is C(R 2 ). In an embodiment, W 2 is N(R 2 ). In an embodiment, W 2 It is C(O).

[0364] In an embodiment, W 3 is N. In an embodiment, W 3 is C(R 3 ).

[0365] In an embodiment, W 4 It is C.

[0366] In an embodiment, W 5 is C. In an embodiment, W 5 is C(R 5 ).

[0367] In an embodiment, W 6 is C(R 6 ). In an embodiment, W 6 is N(R 6 ). In an embodiment, R 6 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 3-6 Cycloalkyl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12、-C(O)R 15 、-C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted by one, two or three R 20f In an embodiment, R 6 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl and -OR 12 , where C 1-6 The alkyl group is optionally substituted by one, two or three R 20f In an embodiment, R 6 is halogen. In an embodiment, W 6 It is N.

[0368] In an embodiment, W 7 is C. In an embodiment, W 7 is C(R 7a ). In an embodiment, W 7 It is N.

[0369] In an embodiment, W 8 is C(R 8 ). In an embodiment, R 8 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-C(O)R 15 、-C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 ), where C 1-6 The alkyl group is optionally substituted by one, two or three R 20h In an embodiment, R 8 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl and -OR 12 , where C 1-6 The alkyl group is optionally substituted by one, two or three R 20hIn an embodiment, R 8 is halogen. In an embodiment, W 8 It is N.

[0370] In an embodiment, W 9 It is C.

[0371] In an embodiment, W 10 It is C.

[0372] In an implementation scheme, Selected from

[0373] In an embodiment, L 7 is the key.

[0374] In an embodiment, R 17 Selected from C 6-10 Aryl and 5-10 membered heteroaryl, each of which is optionally substituted by one, two or three R 20q In an embodiment, R 17 Selected from C 10 Aryl and 9-membered heteroaryl, each of which is optionally substituted by one, two or three R 20q In an embodiment, R 17 is selected from naphthyl and benzothienyl, each of which is optionally substituted by one, two or three R 20q In an embodiment, R 17 Substituted by one, two or three substituents independently selected from halogen, -CN, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, -OR 21 and -N(R 22 )(R 23 ). In an embodiment, R 17 Substituted by one, two or three substituents independently selected from halogen, -CN, -CH 3 , -C≡CH, -OH and -NH 2 In an embodiment, R 17 By -F, -CN and -NH 2 In an embodiment, R 17 Selected from

[0375] In an embodiment, R 17 Selected from

[0376] Q 1 , Q3 and Q 5 are independently selected from N and C(R 1d );

[0377] Q 4 and Q 6 independently selected from O, S, C(R 1a )(R 1b ) and N(R 1c );

[0378] X 4 , X 5 , X 6 , X 9 , X 10 Independently selected from C(R 1a ) and N;

[0379] X 13 Select from bonds, C(R 1a )、N、C(O)、C(R 1a )(R 1b )、C(O)C(R 1a )(R 1b )、C(R 1a )(R 1b )C(R 1a )(R 1b )、C(R 1a )(R 1b )N(R 1c ) and N(R 1c );

[0380] X 14 , X 15 , X 17 , X 18 independently selected from C(O), C(R 1a )、N、C(R 1a )(R 1b ) and N(R 1c );X 16 are independently selected from C, N and C(R 1a );

[0381] Each R 1a , R 1b , R 1d and R 1h are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20q substituted; or R bonded to the same carbon 1aand R 1b Connected to form a 3-10 membered heterocycloalkyl ring or C 3-10 Cycloalkyl ring, wherein the 3-10 membered heterocycloalkyl ring or C 3-10 The cycloalkyl ring is optionally substituted by one, two or three R 20q or two R bonded to adjacent atoms 1a connected to form a 3-10 membered heterocycloalkyl ring, C 6-10 Aryl ring, 5-12 membered heteroaryl ring or C 3-10 Cycloalkyl ring, wherein the 3-10 membered heterocycloalkyl ring, C 6-10 Aryl ring, 5-12 membered heteroaryl ring or C 3-10 The cycloalkyl ring is optionally substituted by one, two or three R 20q Replace; or R 1h R bonded to adjacent atoms 1a , R 1b , R 1c and R 1d to form a 3-10 membered heterocycloalkyl ring, C 6-10 Aryl ring, 5-12 membered heteroaryl ring or C 3-10 Cycloalkyl ring, wherein the 3-10 membered heterocycloalkyl ring, C 6-10 Aryl ring, 5-12 membered heteroaryl ring and C 3-10 The cycloalkyl ring is optionally substituted by one, two or three R 20q Replace; and each R 1c are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20q replace.

[0382] In an embodiment, R 17 Selected from:

[0383]

[0384] In an embodiment, R 2Independently is -OR 12a .

[0385] In an embodiment, R 2 Independently selected from

[0386] In an embodiment, R 2 Independently

[0387] In an embodiment, Z 4 Yes key, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c , Z 4a Z 4b Z 4c Z 4d or Z 4a Z 4b Z 4c Z 4d Z 4e In an embodiment, Z 4 It's Z 4a In an embodiment, Z 4 It's Z 4a Z 4b In an embodiment, Z 4 It's Z 4a Z 4b Z 4c In an embodiment, Z 4 It's Z 4a Z 4b Z 4c Z 4d In an embodiment, Z 4 It's Z 4a Z 4b Z 4c Z 4d Z 4e .

[0388] In an embodiment, each R z4 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O)2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 )-, where C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 In an embodiment, each R z4 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 and -S(O) 2 R 15 , where C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 Alkenyl.

[0389] In an embodiment, each R z5 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 )-, where C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 In an embodiment, each R z5 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 and -S(O) 2 R 15 , where C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 Alkenyl.

[0390] In an embodiment, each Rz6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 )-, where C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 Alkenyl.

[0391] In an embodiment, each R z6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 and -S(O) 2 R 15 , where C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z6or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 Alkenyl.

[0392] In an embodiment, each R 20z are independently selected from hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 )-, where C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20zz or two R bonded to the same carbon 20z connected to form a 20zz Substituted C 2-6 In an embodiment, each R 20z are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O) 2 R 15 and -S(O) 2 R 15 , where C1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20zz or two R bonded to the same carbon 20z connected to form a 20zz Substituted C 2-6 In an embodiment, each R 20z is independently oxo.

[0393] In one aspect, there is provided a AB -B, wherein

[0394] A is a monovalent form of a compound described herein;

[0395] L AB is a covalent linker bonded to A and B; and

[0396] B is the monovalent form of the degradation enhancer.

[0397] In an embodiment, the degradation enhancer is capable of binding to a protein selected from the group consisting of 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 (Skip-Cullin-F box (β-TRCP) ubiquitin complex), b-TRCP (b-transducing repeat-containing protein), cIAP1 (apoptosis inhibitory protein 1), APC / C (anaphase-promoting complex / cyclin), 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. In embodiments, the degradation enhancer is capable of binding to a protein selected from the group consisting of: 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. AB Yes-L AB1 -L AB2 -L AB3 -L AB4 -L AB5 -;

[0398] L AB1 , L AB2 , L AB3 , L AB4 and L AB5 are independently a bond, -O-, -N(R 14 )-、-C(O)-、-N(R 14 )C(O)-、-C(O)N(R 14 )-、-S-、-S(O) 2 -、-S(O)-、-S(O) 2 N(R 14 )-、-S(O)N(R 14 )-、-N(R 14 )S(O)-、-N(R 14 )S(O) 2 -、C 1-6 Alkylene, (-OC 1-6 alkyl) z -、(-C1-6 Alkyl-O) z -、C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Halogenated alkylene, C 3-12 Cycloalkylene, C 1-11 Heterocycloalkylene, C 6-12 Arylene or C 1-11 Heteroarylene, wherein C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 1-6 Halogenated alkylene, C 3-12 Cycloalkylene, C 1-11 Heterocycloalkylene, C 6-12 Arylene or C 1-11 The heteroarylene group is optionally substituted by one, two or three R 20n Replacement; where (-OC 1-6 alkyl) z - and (-C 1-6 Alkyl-O) z - Each C 1-6 The alkyl groups are optionally substituted by one, two or three R 20n replace;

[0399] z is independently an integer from 0 to 10;

[0400] Each R 12 are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace;

[0401] Each R 13 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 haloalkyl; or R 12 and R 13 Together with the nitrogen to which they are attached, they form a 20m Substituted C 2-9 heterocycloalkyl ring;

[0402] Each R 14 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl;

[0403] Each R 15 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20o replace;

[0404] Each R 20l , R 20m , R 20n and R 20o are independently selected from halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10Aryl, -CH 2 -C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O) 2 R 25 、-C(O)R 25 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ),-OCH 2 C(O)OR 22 and -OC(O)R 25 , where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O) 2 R 25 、-C(O)R 25 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ) and -OC(O)R 25 ;

[0405] Each R 21 Independently selected from H, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl;

[0406] Each R 22 Independently selected from H, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl;

[0407] Each R 23 Independently selected from H and C 1-6 alkyl;

[0408] Each R 24 Independently selected from H and C1-6 Alkyl; and

[0409] Each R 25 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl.

[0410] In an embodiment, L AB Yes-(OC 2 alkyl) z - and z is an integer from 1 to 10. In an embodiment, L AB Yes-(C 2 Alkyl-O-) z - and z is an integer from 1 to 10. In an embodiment, L AB Yes-(CH 2 ) zz1 L AB2 (CH 2 O) zz2 -, where L AB2 is a bond, a 5-membered or 6-membered heterocycloalkylene or heteroarylene, a phenylene, -(C 2 -C 4 )Alkynylidene, -SO 2 - or -NH-; and zz1 and zz2 are independently an integer from 0 to 10.

[0411] In an embodiment, L AB Yes-(CH 2 ) zz1 (CH 2 O) zz2 -, wherein zz1 and zz2 are each independently an integer from 0 to 10. In an embodiment, L AB is a PEG linker. In an embodiment, B is a monovalent form of a compound selected from:

[0412] In one aspect, a pharmaceutical composition is provided, comprising a compound described herein or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable excipient.

[0413] In one aspect, provided is a method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof.

[0414] In one aspect, a method for treating cancer in a subject comprising a Ras mutant protein is provided, the method comprising: modifying the Ras mutant protein of the subject by administering a compound to the subject, wherein the compound is characterized in that when contacting the Ras mutant protein, the Ras mutant protein is covalently modified at the residue corresponding to residue 12 of SEQ ID No: 1, such that the modified Ras mutant protein exhibits reduced Ras signaling output.

[0415] In embodiments, the cancer is a solid tumor or a hematological cancer.

[0416] In one aspect, a method of modulating the signaling 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 signaling output of the Ras protein.

[0417] In one aspect, a method for inhibiting cell growth is provided, the method comprising administering an effective amount of a compound described herein or a pharmaceutically acceptable salt or solvate thereof to a cell expressing a Ras protein, thereby inhibiting the growth of the cell.

[0418] In an embodiment, the method comprises administering an additional agent. In an embodiment, the additional agent comprises (1) an inhibitor of MEK; (2) an inhibitor of epidermal growth factor receptor (EGFR) and / or its mutants; (3) an immunotherapeutic agent; (4) a taxane; (5) an antimetabolite; (6) an inhibitor of FGFR1 and / or FGFR2 and / or FGFR3 and / or its mutants; (7) a mitotic kinase inhibitor; (8) an anti-angiogenic drug; (9) a topoisomerase inhibitor; (10) a platinum-containing compound; (12) c-MET and / or its mutants (13) inhibitors of BCR-ABL and / or its mutants; (14) inhibitors of ErbB2 (Her2) and / or its mutants; (15) inhibitors of AXL and / or its mutants; (16) inhibitors of NTRK1 and / or its mutants; (17) inhibitors of RET and / or its mutants; (18) inhibitors of A-Raf and / or B-Raf and / or C-Raf and / or its mutants; (19) inhibitors of ERK and / or its mutants; (20) inhibitors of MDM2 preparations; (21) inhibitors of mTOR; (23) inhibitors of IGF1 / 2 and / or IGF1-R; (24) inhibitors of CDK9; (25) inhibitors of farnesyl transferase; (26) inhibitors of the SHIP pathway; (27) inhibitors of SRC; (28) inhibitors of JAK; (29) PARP inhibitors; (31) ROS1 inhibitors; (32) inhibitors of the SHP pathway; or (33) inhibitors of Src, FLT3, HDAC, VEGFR, PDGFR, LCK , Bcr-Abl or AKT inhibitors; (34) inhibitors of KrasG12C mutants; (35) SHC inhibitors (e.g., PP2, AID371185); (36) GAB inhibitors; (38) PI-3 kinase inhibitors; (39) MARPK inhibitors; (40) CDK4 / 6 inhibitors; (41) MAPK inhibitors; (42) SHP2 inhibitors; (43) checkpoint immune blockers; (44) SOS1 inhibitors; or (45) SOS2 inhibitors. In an embodiment, the additional agent includes an inhibitor of SHP2 selected from the following: RMC-4630, ERAS-601, In an embodiment, the additional agent comprises an inhibitor of SOS selected from the group consisting of RMC-5845, BI-1701963, In an embodiment, the additional agent comprises an inhibitor of EGFR selected from the group consisting of afatinib, erlotinib, gefitinib, lapatinib, cetuximab, panitumumab, osimertinib, olmutinib, and EGF-816. In an embodiment, the additional agent comprises an inhibitor of MEK selected from the group consisting of trametinib, cobimetinib, binimetinib, selumetinib, refametinib, and AZD6244. In an embodiment, the additional agent comprises an inhibitor of ERK selected from the group consisting of ulixertinib, MK-8353, LTT462, AZD0364, SCH772984, BIX02189, LY3214996, and ravoxertinib. In an embodiment, the additional agent comprises an inhibitor of CDK4 / 6 selected from the group consisting of palbociclib, ribociclib, and abemaciclib. In an embodiment, the additional agent comprises an inhibitor of BRAF selected from the group consisting of sorafenib, vemurafenib, dabrafenib, encorafenib, regorafenib, and GDC-879.

[0419] Incorporation by reference

[0420] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS

[0421] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the invention will be obtained by reference to the following detailed description and accompanying drawings which set forth illustrative embodiments in which the principles of the invention are utilized, in which:

[0422] Figure 1 The sequence alignment of various wild-type Ras proteins including K-Ras, H-Ras, N-Ras, RalA, and RalB is depicted from top to bottom. DETAILED DESCRIPTION

[0423] Unless otherwise indicated, the practice of some embodiments disclosed herein employs conventional techniques of immunology, biochemistry, chemistry, molecular biology, microbiology, cell biology, genomics, and recombinant DNA within the skill of the art. See, e.g., Sambrook and Green, Molecular Cloning: A Laboratory Manual, 4th edition (2012); Current Protocols in Molecular Biology series (ed. by FM Ausubel et al.); Methods In Enzymology series (Academic Press, Inc.); PCR 2: A Practical Approach (ed. by MJ MacPherson, BD Hames and GR Taylor (1995)); Harlow and Lane (1988) Antibodies, A Laboratory Manual; and Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6th edition (ed. by RI Freshney (2010)).

[0424] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood in the field of the claimed subject matter. If there are multiple definitions of this article term, then those definitions in this chapter and section shall prevail. All patents, patent applications, publications and disclosed nucleotide and amino acid sequences (such as sequences that can be obtained in GenBank or other databases) mentioned herein are incorporated herein by reference. When quoting URL or other such identifiers or addresses, it should be understood that such identifiers may change, and specific information on the Internet may change, but equivalent information can be found by searching the Internet. Its reference proves the availability and public dissemination of such information.

[0425] It should be understood that the foregoing general description and the following detailed description are merely exemplary and explanatory and do not limit any claimed subject matter. In the present application, unless otherwise specifically stated, the use of the singular includes the plural. It must be noted that, as used in the specification and the appended claims, the singular forms "a", "an", and "the" include plural indicators unless the context clearly specifies otherwise. In the present application, unless otherwise stated, the use of "or" means "and / or". In addition, the use of the term "including" and other forms, such as "include", "includes", and "included" is not restrictive.

[0426] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0427] Definitions of standard chemical terms may be found in the literature, including but not limited to Carey and Sundberg "Advanced Organic Chemistry 4th Edition" Vols. A (2000) and B (2001), Plenum Press, New York. Unless otherwise indicated, conventional methods of mass spectroscopy, NMR, HPLC, protein chemistry, biochemistry, recombinant DNA techniques, and pharmacology are used.

[0428] Unless specific definitions are provided, the nomenclature and laboratory procedures and techniques used in association with analytical chemistry, synthetic organic chemistry, and medical and pharmaceutical chemistry as described herein are those recognized in the art. Standard techniques can be used for chemical synthesis, chemical analysis, drug preparation, preparation and delivery, and the treatment of patients. Standard techniques can be used for recombinant DNA, oligonucleotide synthesis, and tissue culture and transformation (e.g., electroporation, liposome transfection). Reaction and purification techniques can, for example, use a test kit with manufacturer's instructions, or as generally implemented in the art, or as described herein. The aforementioned techniques and procedures can generally be carried out according to conventional methods and as described in various general and more specific references cited and discussed throughout this specification.

[0429] It should be understood that the methods and compositions described herein are not limited to the specific methods, protocols, cell lines, constructs and reagents described herein, and thus may vary. It should also be understood that the terminology used herein is only for the purpose of describing specific embodiments, and is not intended to limit the scope of the methods, compounds, compositions described herein.

[0430] As used herein, C 1 -C x Including C 1 -C 2, C 1 -C 3 …C 1 -C x . C 1 -C x It refers to the number of carbon atoms (excluding optional substituents) that make up the moiety to which it designates.

[0431] An "alkyl" group refers to a straight or branched hydrocarbon radical consisting only of carbon and hydrogen atoms, containing no unsaturation. In some embodiments, an "alkyl" group can have 1 to 18, 1 to 12, 1 to 10, 1 to 8, or 1 to 6 carbon atoms (whenever a numerical range such as "1 to 6" appears herein, it refers to each integer within the given range; for example, "1 to 6 carbon atoms" means that the alkyl group can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 6 carbon atoms, although this definition also covers the occurrence of the term "alkyl" where no numerical range is specified). The alkyl groups of the compounds described herein can be designated as "C 1 -C 6 "alkyl" or similar designations. For example only, "C 1 -C 6 "Alkyl" indicates that there are from one to six carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl and hexyl. The alkyl group may be substituted or unsubstituted. Depending on the structure, the alkyl group may be a monoradical or a diradical (i.e., an alkylene group).

[0432] "Alkoxy" means an "-O-alkyl" group where alkyl is as defined herein.

[0433] The term "alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms and containing at least one carbon-carbon double bond. Non-limiting examples of alkenyl groups include -CH=CH 2 、-C(CH 3 )=CH 2 、-CH=CHCH 3 、-CH=C(CH 3 ) 2 and –C(CH 3 )=CHCH 3 In some embodiments, an alkenyl group may have 2 to 6 carbons. An alkenyl group may be substituted or unsubstituted. Depending on the structure, an alkenyl group may be a monoradical or a diradical (i.e., an alkenylene group).

[0434] The term "alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms and containing at least one carbon-carbon triple bond. Non-limiting examples of alkynyl groups include -C≡CH, -C≡CCH 3 , –C≡CCH 2 CH 3 and –C≡CCH 2 CH 2 CH 3 In some embodiments, an alkynyl group may have 2 to 6 carbons. An alkynyl group may be substituted or unsubstituted. Depending on the structure, an alkynyl group may be a monoradical or a diradical (i.e., an alkynylene group).

[0435] "Amino" refers to -NH 2 Group.

[0436] The term "alkylamine" or "alkylamino" refers to an -N(alkyl) x H y wherein alkyl is as defined herein and x and y are selected from x=1, y=1 and x=2, y=0. When x=2, the alkyl groups together with the nitrogen to which they are attached may optionally form a cyclic ring system. "Dialkylamino" refers to -N(alkyl) 2 A group wherein alkyl is as defined herein.

[0437] The term "aromatic" refers to a planar ring having a delocalized π-electron system containing 4n+2π electrons, where n is an integer. The aromatic ring can be formed by five, six, seven, eight, nine or more than nine atoms. Aromatic compounds can be optionally substituted. The term "aromatic" includes aryl groups (e.g., phenyl, naphthyl) and heteroaryl groups (e.g., pyridyl, quinolyl).

[0438] As used herein, the term "aryl" refers to a monocyclic aromatic ring, wherein each atom forming the ring is a carbon atom (e.g., phenyl) or a polycyclic ring system (e.g., bicyclic or tricyclic), wherein 1) at least one ring is carbocyclic and aromatic, 2) the bonds of the remainder of the compound are directly bonded to the carbocyclic aromatic ring of the aryl ring system, and 3) the carbocyclic aromatic ring of the aryl ring system of 2) is not directly bonded (e.g., fused) to the heteroaryl ring in the polycyclic system. The aryl ring can be formed by five, six, seven, eight, nine, or more than nine carbon atoms. The aryl group can be optionally substituted. Examples of aryl groups include, but are not limited to, phenyl and naphthyl. Depending on the structure, the aryl group can be a monoradical or a diradical (i.e., an arylene group). As used herein, the aryl radical is a monocyclic, bicyclic, or tricyclic ring system. In an embodiment, the aryl is a monocyclic ring. In an embodiment, the aryl is a fused ring polycyclic ring system. In an embodiment, the aryl is a bridged ring polycyclic ring system. In some embodiments, aryl is a "fused ring aryl" in which the aryl ring is fused to a cycloalkyl or heterocycloalkyl ring. In embodiments, aryl is a "fused bicyclic" aryl in which the two rings of the aryl group share one bond.

[0439] "Carboxyl" refers to -CO 2 H. In some embodiments, the carboxyl moiety can be replaced with a "carboxylic acid bioisostere," which refers to a functional group or moiety that exhibits physical and / or chemical properties similar to those of a carboxylic acid moiety. Carboxylic acid bioisosteres have biological properties similar to those of the carboxylic acid group. Compounds having a carboxylic acid moiety can have a carboxylic acid moiety exchanged with a carboxylic acid bioisostere and have similar physical and / or biological properties when compared to compounds containing carboxylic acids. For example, in one embodiment, a carboxylic acid bioisostere will ionize at physiological pH to approximately the same extent as a carboxylic acid group. Examples of bioisosteres of carboxylic acids include, but are not limited to wait.

[0440] The term "cycloalkyl" refers to a monocyclic carbocyclic saturated or partially unsaturated non-aromatic ring or a polycyclic carbocyclic (i.e., excluding heteroatoms) ring system (e.g., bicyclic or tricyclic), wherein 1) at least one ring is a carbocyclic saturated or partially unsaturated non-aromatic ring, 2) the bond to the remainder of the compound is directly bonded to the carbocyclic saturated or partially unsaturated non-aromatic ring of the ring system, and 3) the carbocyclic saturated or partially unsaturated non-aromatic ring of the ring system of 2) is not directly bonded (e.g., fused or spiro) to the heterocycloalkyl ring in the polycyclic ring system. Cycloalkyl can be saturated or partially unsaturated. In some embodiments, the cycloalkyl ring is a spirocyclic cycloalkyl ring. In embodiments, the cycloalkyl is a monocyclic ring. In embodiments, the cycloalkyl is a fused polycyclic ring system. In embodiments, the cycloalkyl is a bridged polycyclic ring system. In embodiments, the cycloalkyl is a spirocyclic polycyclic ring system. In some embodiments, the cycloalkyl group includes a group having 3 to 10 ring atoms. Depending on the structure, the cycloalkyl group can be a monoradical or a diradical (i.e., a cycloalkylene group). In an embodiment, the cycloalkyl is a "fused bicyclic" cycloalkyl, wherein the two rings of the cycloalkyl group share one bond.

[0441] The term "heteroaryl" or alternatively "heteroaromatic" refers to a monocyclic aromatic group including one or more ring heteroatoms selected from nitrogen, oxygen and sulfur; or a polycyclic ring system (e.g., bicyclic or tricyclic) in which 1) at least one ring is aromatic and includes one or more heteroatoms selected from nitrogen, oxygen and sulfur, and 2) the bond to the remainder of the compound is directly bonded to an aromatic ring containing one or more heteroatoms selected from nitrogen, oxygen and sulfur, or directly bonded (e.g., fused) to an aromatic ring of an aromatic ring system containing one or more heteroatoms selected from nitrogen, oxygen and sulfur. As used herein, a heteroaryl radical can be a monocyclic, bicyclic or tricyclic ring system in which at least one ring in the ring system is fully unsaturated (i.e., aromatic) and includes heteroatoms. In embodiments, heteroaryl is a monocyclic ring. In embodiments, heteroaryl is a fused ring polycyclic ring system. In embodiments, heteroaryl is a bridged ring polycyclic ring system. In some embodiments, it is a "fused ring heteroaryl" in which the heteroaryl ring is fused to a cycloalkyl, aryl or heterocycloalkyl ring. N-containing "heteroaromatic" or "heteroaryl" moieties refer to aromatic groups in which at least one of the backbone atoms of the ring is a nitrogen atom. Depending on the structure, the heteroaryl group can be a monoradical or a diradical (i.e., a heteroarylene group). In an embodiment, the heteroaryl group is a "fused bicyclic" heteroaryl group, in which the two rings of the heteroaryl group share one bond.

[0442] A "heterocycloalkyl" group or a "heteroalicyclic" group refers to a cycloalkyl group in which at least one skeletal ring atom of a saturated or partially unsaturated non-aromatic ring is a heteroatom selected from nitrogen, oxygen, phosphorus and sulfur. Heterocycloalkyl refers to a monocyclic saturated or partially unsaturated non-aromatic ring or a polycyclic ring system (e.g., bicyclic or tricyclic) including one or more heteroatoms, wherein 1) at least one ring is a saturated or partially unsaturated non-aromatic ring and includes one or more heteroatoms, and 2) the bond to the remainder of the compound is directly bonded to the ring of the ring system, which is a saturated or partially unsaturated non-aromatic ring containing one or more heteroatoms, or a non-aromatic ring directly bonded (e.g., fused, spiro) to a saturated or partially unsaturated non-aromatic ring containing one or more heteroatoms of the ring system. Heterocycloalkyl can be saturated or partially unsaturated. The term heterocycloalkyl also includes all ring forms of carbohydrates, including but not limited to monosaccharides, disaccharides and oligosaccharides. In some embodiments, the heterocycloalkyl ring is a spirocyclic heterocycloalkyl ring. In embodiments, the heterocycloalkyl is a monocyclic ring. In embodiments, the heterocycloalkyl is a fused polycyclic ring system. In an embodiment, heterocycloalkyl is a bridged polycyclic ring system. In an embodiment, heterocycloalkyl is a spirocyclic polycyclic ring system. Unless otherwise indicated, heterocycloalkyl has 2 to 13 carbons in the ring or ring system. It should be understood that when referring to the number of carbon atoms in heterocycloalkyl, the number of carbon atoms in heterocycloalkyl is different from the total number (including heteroatoms) of the atoms (i.e., the skeleton atoms of the heterocycloalkyl ring) constituting the heterocycloalkyl. Depending on the structure, the heterocycloalkyl group can be a monoradical or a diradical (i.e., a heterocycloalkylene group). In an embodiment, heterocycloalkyl is a "fused bicyclic" heterocycloalkyl, in which the two rings of the heterocycloalkyl group share a bond.

[0443] The term "halo" or alternatively "halogen" refers to fluoro, chloro, bromo and iodo.

[0444] The abbreviations "Fmoc", "Ac", "Bn", "PMB", "Tr", "Ts", "Boc" and "Cbz" are used according to their common meanings well known in chemistry, and refer to the monovalent chemical substituents fluorenylmethoxycarbonyl, acetyl, benzyl, p-methoxybenzyl, trityl or triphenylmethyl, tosyl, tert-butoxycarbonyl and carbonylbenzyloxy, respectively. The term "monovalent" is used herein according to its well known meaning in chemistry, and refers to the ability of a substituent to form one covalent bond with another substituent or a compound capable of forming a covalent bond. In a related manner, the term "divalent" refers to a substituent or compound capable of forming two covalent bonds, such as a linker capable of covalently linking two monovalent substituents or compounds.

[0445] The term "haloalkyl" refers to an alkyl group substituted with one or more halogens. The halogens may be the same, or they may be different. Non-limiting examples of haloalkyl include -CH 2Cl, -CF 3 , -CHF 2 、-CH 2 CF 3 , -CF 2 CF 3 wait.

[0446] The terms "fluoroalkyl" and "fluoroalkoxy" include alkyl and alkoxy groups, respectively, substituted with one or more fluorine atoms. Non-limiting examples of fluoroalkyl groups include -CF 3 , -CHF 2 、-CH 2 F, -CH 2 CF 3 , -CF 2 CF 3 , -CF 2 CF 2 CF 3 、-CF(CH 3 ) 3 etc. Non-limiting examples of fluoroalkoxy groups include -OCF 3 、-OCHF 2 、-OCH 2 F, -OCH 2 CF 3 、-OCF 2 CF 3 、-OCF 2 CF 2 CF 3 、-OCF(CH 3 ) 2 wait.

[0447] The term "heteroalkyl" refers to an alkyl radical in which one or more backbone chain atoms are selected from atoms other than carbon, such as oxygen, nitrogen, sulfur, phosphorus, silicon, or a combination thereof. The heteroatom may be located at any interior position of the heteroalkyl group. Examples include, but are not limited to, -CH 2 -O-CH 3 、-CH 2 -CH 2 -O-CH 3 、-CH 2 -NH-CH 3 、-CH 2 -CH 2 -NH-CH 3 、-CH 2 -N(CH 3 )-CH 3 、-CH 2 -CH 2 -NH-CH 3 、-CH 2-CH 2 -N(CH 3 )-CH 3 、-CH 2 -S-CH 2 -CH 3 、-CH 2 -CH 2 -S(O)-CH 3 、-CH 2 -CH 2 -S(O) 2 -CH 3 、-CH 2 -NH-OCH 3 , –CH 2 -O-Si(CH 3 ) 3 、-CH 2 -CH=N-OCH 3 and -CH=CH-N(CH 3 )-CH 3 Furthermore, up to two heteroatoms may be consecutive, such as, for example, -CH 2 -NH-OCH 3 and -CH 2 -O-Si(CH 3 ) 3 Not including the number of heteroatoms, a "heteroalkyl" group may have from 1 to 6 carbon atoms.

[0448] The term "heteroalkylene linker" refers to a divalent alkyl radical in which one or more backbone chain atoms are selected from atoms other than carbon, such as oxygen, nitrogen, sulfur, phosphorus, silicon, or a combination thereof. In some embodiments, heteroatoms may be located at any interior position of the heteroalkyl group. In some embodiments, heteroatoms may be located at one or both terminal positions of the heteroalkylene linker (i.e., positions directly bonded to portions of the molecule other than the heteroalkylene linker). Examples include, but are not limited to, -CH 2 -O-CH 2 -、-CH 2 -CH 2 -O-CH 2 -、-CH 2 -NH-CH 2 -、-CH 2 -CH 2 -NH-CH 2 -、-CH 2 -N(CH 3 )-CH 2 -、-CH 2 -CH 2 -N(CH 3)-CH 2 -,-CH 2 -S-CH 2 -CH 2 -,-CH 2 -CH 2 -S(O)-CH 2 -,-CH 2 -CH 2 -S(O) 2 -CH 2 -,-CH 2 -NH-O-CH 2 -–CH 2 -O-Si(CH 3 ) 2 -,-CH 2 -CH=N-O-CH 2 -and-CH=CH-N(CH 3 )-CH 2 -.Examples include, but are not limited to, -CH 2 -O-,-CH 2 -CH 2 -O-,-CH 2 -NH-,-CH 2 -CH 2 -NH-,-CH 2 -N(CH 3 )-,-CH 2 -CH 2 -N(CH 3 )-,-CH 2 -S-,-CH 2 -CH 2 -S-,-CH 2 -CH 2 -S(O)-,-CH 2 -CH 2 -S(O) 2 -,-CH 2 -S(O)-,-CH 2 -S(O) 2 -,-CH 2 -CH 2 -CH 2 -S(O)-,-CH 2 -CH 2 -CH 2 -S(O) 2 -,-CH 2 -CH 2 -CH 2 -O-,-CH 2 -CH 2 -CH2 -O-, -CH 2 -CH 2 -CH 2 -S-, -CH 2 -CH 2 -CH 2 -S-, -CH 2 -CH 2 -CH 2 -NH-, -CH 2 -CH 2 -CH 2 -NH-, -CH 2 -CH 2 -CH 2 -N(CH 3 )-, -CH 2 -CH 2 -CH 2 -N(CH 3 )-, -CH 2 -NH-O-, -O-Si(CH 3 ) 2 -, -CH 2 -CH=N-O- and -CH=CH-N(CH 3 )-. Examples include, but are not limited to, -O-CH 2 -, -O-CH 2 -CH 2 -, -NH-CH 2 -, -NH-CH 2 -CH 2 -, -N(CH 3 )-CH 2 -, -N(CH 3 )-CH 2 -CH 2 -, -S-CH 2 -, -S-CH 2 -CH 2 -, -S(O)-CH 2 -CH 2 -, -S(O) 2 -CH 2 -CH 2 -, -S(O)-CH 2 -, -S(O) 2 -CH 2 -, -S(O)-CH 2 -CH 2 -CH 2 -, -S(O) 2 -CH 2 -CH 2-CH 2 -、-O-CH 2 -CH 2 -CH 2 -、-O-CH 2 -CH 2 -CH 2 -、-S-CH 2 -CH 2 -CH 2 -、-S-CH 2 -CH 2 -CH 2 -、-NH-CH 2 -CH 2 -CH 2 -、-NH-CH 2 -CH 2 -CH 2 -、-N(CH 3 )-CH 2 -CH 2 -CH 2 -、-N(CH 3 )-CH 2 -CH 2 -CH 2 -、-O-NH-CH 2 -、-Si(CH 3 ) 2 -O-, -ON=CH-CH 2 - and -N(CH 3 )-CH=CH-. In addition, up to two heteroatoms may be consecutive, such as, for example, -CH 2 -NH-O- and -O-Si(CH 3 ) 2 -. Examples include, but are not limited to, -P(O)(CH 3 )-CH 2 -、-P(O)(CH 3 )-CH 2 -CH 2 -、-P(O)(CH 3 )-CH 2 -CH 2 -CH 2 -、-CH 2 -P(O)(CH 3 )-、-CH 2 -CH 2 -P(O)(CH 3 )- and -CH 2 -CH 2 -CH 2 -P(O)(CH3 )-. In addition, up to two heteroatoms may be consecutive, such as, for example, -CH 2 -NH-O- and -O-Si(CH 3 ) 2 Unless otherwise specified, a "heteroalkylene linker" may have 2 to 4 backbone atoms.

[0449] The term "oxo" refers to the =0 radical.

[0450] The term "bond" or "single bond" refers to a chemical bond between two atoms, or between two moieties when the atoms joined by the bond are considered as parts of a larger substructure.

[0451] The term "moiety" refers to a specific segment or functional group of a molecule. A chemical moiety is often considered to be a chemical entity embedded in or attached to a molecule.

[0452] The suffix "-diyl" will be understood to mean that the substituent or linker is a divalent substituent or linker.

[0453] As used herein, a substituent "R" appearing alone and without a numerical designation refers to a substituent selected from alkyl, haloalkyl, heteroalkyl, alkenyl, cycloalkyl, aryl, heteroaryl (bonded through a ring carbon), and heterocycloalkyl.

[0454] “Optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances when the event or circumstance occurs and instances when it does not occur.

[0455] Unless otherwise specified, the term "optionally substituted" or "substituted" means that the referenced group may be substituted by one or more additional groups individually and independently selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, -OH, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, arylsulfone, -CN, alkyne, C 1 -C 6 Alkylalkyne, halide, acyl, acyloxy, -CO 2 H, -CO 2 -alkyl, nitro, haloalkyl, fluoroalkyl and amino (including mono- and di-substituted amino groups (e.g. -NH 2 , -NHR, -NR 2 )), and protected derivatives thereof. For example, the optional substituent may be L s R s , where each L s are independently selected from a bond, -O-, -C(=O)-, -S-, -S(=O)-, -S(=O) 2-, -NH-, -NHC(O)-, -C(O)NH-, S(=O) 2 NH-, -NHS(=O) 2 , -OC(O)NH-, -NHC(O)O-, -(C 1 -C 6 Alkyl)- or -(C 2 -C 6 alkenyl)-; and each R s are independently selected from H, (C 1 -C 6 Alkyl), (C 3 -C 8 cycloalkyl), aryl, heteroaryl, heterocycloalkyl and C 1 -C 6 Heteroalkyl. Protecting groups that can form protected derivatives of the above substituents are found in sources such as Greene and Wuts, supra.

[0456] "Pharmaceutically acceptable salts" include both acid addition salts and base addition salts. A pharmaceutically acceptable salt of any of the compounds described herein is intended to encompass any and all pharmaceutically suitable salt forms. Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0457] "Pharmaceutically acceptable acid addition salts" refers to salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphorous acid, and the like. Also included are salts formed with organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxyalkanoic acids, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, and the like, and include, 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, and the like. Thus, exemplary salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, trifluoroacetates, propionates, octanoates, isobutyrates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, phthalates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, malates, tartrates, methanesulfonates, etc. Also contemplated are salts of amino acids such as arginates, gluconates, and galacturonates (see, e.g., Berge SM et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science, 66: 1-19 (1997)). In some embodiments, acid addition salts of basic compounds are prepared by contacting the free base form with a sufficient amount of the desired acid to produce the salt according to methods and techniques familiar to skilled artisans.

[0458] "Pharmaceutically acceptable base addition salts" refers to salts that retain the biological effectiveness and properties of the free acid and are not biologically or otherwise undesirable. These salts are prepared by adding an inorganic base or an organic base to the free acid. In some embodiments, pharmaceutically acceptable base addition salts are formed with 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 salts, potassium salts, lithium salts, ammonium salts, calcium salts, magnesium salts, iron salts, zinc salts, copper salts, manganese salts, aluminum salts, and the like. Salts derived from organic bases include, but are not limited to, salts of primary, secondary and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, N,N-dibenzylethylenediamine, chloroprocaine, hydrabamine, choline, betaine, ethylenediamine, ethylenediphenylamine, N-methylglucosamine, glucosamine, methylglucosamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, etc. See Berge et al. (supra).

[0459] The terms "polypeptide", "peptide" and "protein" are used interchangeably herein and refer to polymers of amino acids of any length. The polymer may be linear or branched, it may contain modified amino acids, and may be interrupted by non-amino acids. The term also encompasses amino acid polymers that have been modified (e.g., disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component). As used herein, the term "amino acid" refers to natural and / or non-natural or synthetic amino acids, including glycine and the D optical isomer or the L optical isomer, as well as amino acid analogs and peptide mimetics.

[0460] The terms "polynucleotide", "nucleotide", "nucleotide sequence", "nucleic acid" and "oligonucleotide" are used interchangeably. They refer to a polymeric form of any length of nucleotides or their analogs, either deoxyribonucleotides or ribonucleotides. A polynucleotide may have any three-dimensional structure and may perform any known or unknown function. The following are non-limiting examples of polynucleotides: coding or non-coding regions of a gene or gene fragment, loci / locus defined by linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, short interfering RNA (siRNA), short hairpin RNA (shRNA), micro RNA (miRNA), ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes and primers. Polynucleotides can include one or more modified nucleotides, such as methylated nucleotides and nucleotide analogs, such as peptide nucleic acids (PNA), morpholino oligonucleotides and locked nucleic acids (LNA), glycerol nucleic acids (GNA), threose nucleic acids (TNA), 2'-fluoro nucleic acids, 2'-OMe nucleic acids and thiophosphated DNA. If present, the modification of the nucleotide structure can be imparted before or after the assembly of the polymer. The sequence of nucleotides can be interrupted by non-nucleotide components. Polynucleotides can be further modified after polymerization, such as by conjugation with a labeling component or other conjugated targets.

[0461] As used herein, "expression" refers to the process by which a polynucleotide is transcribed from a DNA template (such as into mRNA or other RNA transcripts) and / or the process by which the transcribed mRNA is subsequently translated into a peptide, polypeptide, or protein. Transcripts and encoded polypeptides may be collectively referred to as "gene products." If the polynucleotide is derived from genomic DNA, expression may include splicing of mRNA in eukaryotic cells.

[0462] The terms "subject", "individual" and "patient" are used interchangeably herein and refer to vertebrates, preferably mammals, more preferably humans. Mammals include, but are not limited to, mice, monkeys, humans, farm animals, sports animals and pets. Tissues, cells and their progeny obtained in vivo or cultured in vitro of biological entities are also encompassed.

[0463] The terms "agent" or "therapeutic agent," "therapeutic capable agent," or "treatment agent" are used interchangeably and refer to a molecule or compound that confers some beneficial effect upon administration to a subject. Beneficial effects include enabling a diagnostic determination; ameliorating a disease, symptom, disorder, or pathological condition; reducing or preventing the onset of a disease, symptom, disorder, or condition; and generally combating a disease, symptom, disorder, or pathological condition.

[0464] As used herein, "treatment" or "treating", or "alleviate" or "improve" are used interchangeably. These terms refer to methods for obtaining beneficial or desired results, including, but not limited to, therapeutic benefit and / or prophylactic benefit. Therapeutic benefit means any therapeutically related improvement or effect on one or more diseases, conditions, or symptoms under treatment. For prophylactic benefit, the composition can be administered to a subject at risk of developing a particular disease, condition, or symptom, or to a subject reporting one or more physiological symptoms of a disease, even though the disease, condition, or symptom may not yet be manifested. Typically, a prophylactic benefit includes a reduction in the occurrence and / or worsening of one or more diseases, conditions, or symptoms under treatment (e.g., such as between a treated population and an untreated population, or between a treated state and an untreated state of a subject).

[0465] The term "effective amount" or "therapeutically effective amount" refers to an amount of a medicament sufficient to achieve a beneficial or desired result. The therapeutically effective amount may vary according to one or more of the following: the subject and disease condition being treated, the weight and age of the subject, the severity of the disease condition, the mode of administration, etc., which can be easily determined by a person of ordinary skill in the art. The effective amount of the active agent can be administered in a single dose or in multiple doses. A component may be described herein as having at least an effective amount or at least an effective amount, such as an amount associated with a specific goal or purpose such as any goal or purpose described herein. The term "effective amount" also applies to a dose that will provide a detection image by an appropriate imaging method. The specific dose may vary according to one or more of the following: the specific 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.

[0466] The term "in vivo" refers to events that occur in the body of a subject.

[0467] The term "ex vivo" refers to an event that first occurs outside of a subject's body for subsequent in vivo application into the subject's body. For example, ex vivo preparation may involve preparing cells outside of a subject's body for the purpose of introducing the prepared cells into the body of the same or a different subject.

[0468] The term "in vitro" refers to events that occur outside of a subject's body. For example, an in vitro assay encompasses any assay performed outside of a subject's body. In vitro assays encompass cell-based assays in which living or dead cells are employed. In vitro assays also encompass cell-free assays in which intact cells are not employed.

[0469] 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, the Rho subfamily, the Rab subfamily, the Rap subfamily, the Arf subfamily, the Ran subfamily, the Rheb subfamily, the RGK subfamily, the Rit subfamily, the Miro subfamily, and the unclassified subfamily. In some embodiments, the Ras protein is selected from KRAS (also used interchangeably herein as K-Ras, K-ras, 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 selected from KRAS, HRAS, NRAS, RALA, RALB, and any combination thereof. The terms "mutant Ras" and "Ras mutants" as used interchangeably herein refer to Ras proteins having one or more amino acid mutations, such as 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, such as selected from mutant KRAS, mutant HRAS, mutant NRAS, mutant RALA, mutant RALB, and any combination thereof. In some embodiments, the mutation may be an introduced mutation, a naturally occurring mutation, or a non-naturally occurring mutation. In some embodiments, the mutation may be a substitution (e.g., a substituted amino acid), an insertion (e.g., an addition of one or more amino acids), or a deletion (e.g., removal of one or more amino acids). In some embodiments, two or more mutations may be continuous, non-continuous, or a combination thereof. In some embodiments, the mutation may be present at any position of Ras. In some embodiments, when optimally aligned, the mutation may be present at position 12, 13, 62, 92, 95, or any combination thereof of Ras of SEQ ID No. 2. In some embodiments, the mutant Ras may comprise 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 comprise 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 length of the mutant Ras is about or up to 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 than 50 amino acids. In some embodiments, the mutated amino acid is a proteinogenic amino acid, a natural amino acid, a standard amino acid, a non-standard amino acid, an atypical amino acid, an essential amino acid, a non-essential amino acid, or an unnatural amino acid. In some embodiments, the mutated amino acid has a positively charged side chain, a negatively charged side chain, a polar uncharged side chain, a non-polar 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 comprises a reactive portion. In some embodiments, the substituted amino acid comprises a reactive portion. In some embodiments, the mutant Ras can be further modified, such as by conjugation with a detectable label. In some embodiments, the mutant Ras is a full-length or truncated polypeptide. For example, the mutant Ras can be a truncated polypeptide comprising residues 1-169 or residues 11-183 (e.g., residues 11-183 of mutant RALA or mutant RALB).

[0470] As used herein, the term "corresponding to" or "corresponds to" as applied to amino acid residues in a polypeptide sequence refers to the correspondence of such amino acids relative to a reference sequence when optimally aligned (e.g., taking into account gaps, insertions, and mismatches); wherein the alignment may be a primary sequence alignment of a folded protein or a three-dimensional structural alignment. For example, a serine residue in a Ras G12S mutant refers to a serine corresponding to residue 12 of SEQ ID No. 4, which may be used as a reference sequence. For example, an aspartic acid residue in a Ras G12D mutant refers to an aspartic acid corresponding to residue 12 of SEQ ID No. 2, which may be used as a reference sequence. When an amino acid of a mutant Ras protein corresponds to an amino acid position in a WT Ras protein, it will be understood that although the mutant Ras protein amino acid may be a different amino acid (e.g., G12D, wherein the wild-type G at position 12 is replaced by the aspartic acid at position 12 of SEQ ID. No. 1), the mutant amino acid is located at a position corresponding to the wild-type amino acid (e.g., of SEQ ID No. 1). In embodiments, the modified Ras mutant proteins disclosed herein may include a truncation at the C-terminus, or a truncation at the N-terminus before the serine residue. The serine residue in such N-terminally truncated modified mutants is still considered to correspond to position 12 of SEQ ID No. 1. In addition, the serine residue at position 12 of SEQ ID No. 4 finds a corresponding residue in SEQ ID No. 6 and 8. As used herein, "prodrug" means a compound that can be converted into a biologically active compound described herein under physiological conditions or by solvent decomposition. The term "prodrug" refers to a precursor of a pharmaceutically acceptable biologically active compound. The prodrug may be inactive when administered to a subject, but is converted into an active compound in vivo, for example, by hydrolysis. Prodrug compounds can provide advantages of solubility, tissue compatibility and / or delayed release in mammalian organisms (see, e.g., Bundgard, H., Design of Prodrugs (1985), pp. 7-9, 21-24 (Elsevier, Amsterdam)). A discussion of prodrugs is provided in Higuchi, T. et al., "Pro-drugs as Novel Delivery Systems," ACSSymposium Series, Vol. 14, and Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference in their entireties.A "prodrug" can be any covalently bonded carrier that releases the active compound in vivo when such prodrug is administered to a mammalian subject. As described herein, prodrugs of active compounds can be prepared by modifying functional groups present in the active compound in such a way that the modifications are cleaved to the parent active compound in routine manipulation or in vivo.

[0471] The term "leaving group" is used herein according to its well-known meaning in chemistry, and refers to an atom or group of atoms that breaks away from the rest of a molecule, taking with it a pair of electrons that was the bond between the leaving group and the rest of the molecule.

[0472] "Degradation enhancer" is a compound that can bind to a ubiquitin ligase protein (e.g., an E3 ubiquitin ligase protein), or a compound that can bind to a protein that can bind to a ubiquitin ligase protein to form a protein complex that can conjugate a ubiquitin protein to a target protein. In an embodiment, the degradation enhancer can bind to an E3 ubiquitin ligase protein or a protein complex comprising an E3 ubiquitin ligase protein. In an embodiment, the degradation enhancer can bind to an E2 ubiquitin conjugating enzyme. In an embodiment, the degradation enhancer can bind to a protein complex comprising an E2 ubiquitin conjugating enzyme and an E3 ubiquitin ligase protein.

[0473] Draw across or at the end of a key or dotted key Indicates the position where the chemical formula or atom is disconnected or connected to a substituent, another component of a molecule, or an atom (e.g., the position where it is bonded to another atom). For example, represent single or double bonds, single bonds, double bonds and triple bonds respectively, where As defined immediately above.

[0474] Compound

[0475] In one aspect, provided is a compound of formula (A) or a pharmaceutically acceptable salt or solvate thereof:

[0476]

[0477] in:

[0478] W 1 is N(R 1 ) or N;

[0479] R 1 Selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20a replace;

[0480] W 2 is C(R 2 )、N(R 2 )、C(R 2 ) 2 、C(O), S(O), S(O) 2 or N;

[0481] Each R 2 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12a 、-SR 12a 、-N(R 12a )(R 13 ),-N=(R 15 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20b replace;

[0482] W 3 is C(R 3 )、N(R 3 )、C(R 3 ) 2 、C(O), S(O), S(O) 2 or N;

[0483] Each R 3 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20c replace;

[0484] W 4 is C(R 4 ), C or N;

[0485] R 4 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13)、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20d replace;

[0486] W 5 is C(R 5 ), C or N;

[0487] R 5 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20e replace;

[0488] W 6 is C(R 6 )、N(R 6 )、C(R 6 ) 2 、C(O), S(O), S(O) 2 or N;

[0489] Each R 6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R20f replace;

[0490] W 7 is C(R 7a ), C or N;

[0491] R 7a Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace;

[0492] R 7 Yes-L 7 -R 17 ;

[0493] L 7 Yes key, C 1 -C 4 Alkyl, C 2 -C 4 Alkenyl, C 2 -C 4 Alkynyl, 2-4 membered heteroalkylene linker, -O-, -N(R 7d )、-C(O)-、-S-、-S(O) 2 -、-S(O)-、-P(O)R 7d -、CR 7c R 7c , -OCR 7c R 7c -、-N(R 7d )CR 7c R 7c -、-C(O)CR 7c R 7c -、-SCR 7c R 7c -、-S(O) 2 CR 7c R 7c -、-S(O)CR 7c R 7c -、-P(O)R 7d CR 7c R 7c -、-CR 7c R 7c CR 7c R 7c , -CR 7c R 7c O-、-CR 7c R 7c N(R 7d )-、-CR 7c R7c C(O)-、-CR 7c R 7c S-、-CR 7c R 7c S(O) 2 -、-CR 7c R 7c S(O)-、-CR 7c R 7c P(O)R 7d -、-N(R 7d )C(O)-、-N(R 7d )S(O) 2 -、-N(R 7d )S(O)-、-N(R 7d )P(O)R 7d -、-C(O)N(R 7d )-、-S(O) 2 N(R 7d )-、-S(O)N(R 7d )-、-P(O)R 7d N(R 7d )-、-OC(O)-、-OS(O) 2 -、-OS(O)-、-OP(O)R 7d -、-C(O)O-、-S(O) 2 O-, -S(O)O-, or -P(O)R 7d O-; among which C 1 -C 4 Alkyl, C 2 -C 4 Alkenyl, C 2 -C 4 Alkynyl and 2-4 membered heteroalkylene linkers are optionally substituted by one, two or three R 20g replace;

[0494] Each R 7c are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace;

[0495] Each R 7d are independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace;

[0496] R 17 Selected from C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl, wherein C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl are optionally substituted by one or more R 20q replace;

[0497] W 8 is C(R 8 )、N(R 8 )、C(R8 ) 2 、C(O), S(O), S(O) 2 or N;

[0498] Each R 8 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O)2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20h replace;

[0499] W 9 is C(R 9 ), C or N;

[0500] R 9 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12)(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20i replace;

[0501] W 10 is C(R 10 ), C or N;

[0502] R 10 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13)、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20j replace;

[0503] Each Z 1 Independently C(R z1 )、N(R z1 )、C(R z1 ) 2 、C(O), S(O), S(O) 2 , O, S or N;

[0504] z1n is 0, 1, 2, 3 or 4; if z1n is 0, then Z 2 Direct bonding to W 5 ; Each R z1 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z1 replace;

[0505] Z 2 is C(R z2 ), C or N;

[0506] R z2 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z2 replace;

[0507] Z 3 is C(R z3 ), C or N;

[0508] R z3 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z3 replace;

[0509] Z 4 Yes key, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c , Z 4a Z 4b Z 4c Z 4d or Z 4a Z 4b Z 4c Z 4d Z 4e ; where Z 4a Direct Bonding to Z 2 ; and if Z 4 is a key, then Z 2 Direct Bonding to Z 5 ;

[0510] Z 4a , Z 4b , Z 4c , Z 4d and Z 4e Independently C(R z4 )、N(R z4 )、C(R z4 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z4 ), O, S or N;

[0511] The condition is: if z9n is 0 and Z 4 It's Z 4a Z 4b ; then (1) Z4b is C(R z4 )、C(R z4 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z4 ), O, S or N, (2) Z 4b is N(R z4 ) and Z 4a is C(O), S(O) or S(O) 2 ; (3) Z 4b is N(R z4 ) and Z 5 is C(O), S(O) or S(O) 2 ; or (4) Z 4b is N(R z4 ) and Z 3 is C(R z3 ) or C;

[0512] Each R z4 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 Alkenyl; Z 5 is C(R z5 )、N(R z5 )、C(R z5 ) 2 、C(O), S(O), S(O) 2 、S(O)(NR z5 ), O, S or N;

[0513] Each R z5 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 Alkenyl; Z 6 is C(R z6 )、N(R z6 )、C(R z6 ) 2、C(O), S(O), S(O) 2 、S(O)(NR z6 ), O, S or N;

[0514] Each R z6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O)2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 alkenyl; and further wherein the compound optionally comprises one of:

[0515] (1) Two R bonded to the same carbon atom z4 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0516] (2) Two or more R bonded to adjacent atoms z4 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace;

[0517] (3) Two R bonded to the same carbon atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0518] (4) One or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace;

[0519] (5) One or two R bonded to an atom z4 and one or two R bonded to a second atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0520] (6) Two R bonded to the same carbon atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0521] (7) One or two R bonded to an atom z5 and one or two R bonded to adjacent atoms z6 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; or

[0522] (8) One or two R bonded to an atom z4 and one or two R bonded to a second atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0523] Two R bonded to the same carbon atom 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20zz replace; or

[0524] Two or more R bonded to two adjacent atoms 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the C3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20zz replace;

[0525] Each Z 9 Independently C(R z9 )、N(R z9 )、C(R z9 ) 2 、C(O), S(O), S(O) 2 , O, S or N;

[0526] z9n is 0, 1, 2, 3, or 4; if z9n is 0, then Z 3 Direct bonding to W 4 ; Each R z9 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13)、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z9 replace;

[0527] where the sum of z1n and z9n is 2, 3 or 4;

[0528] Each R 12 are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH2 -C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace;

[0529] Each R 12a are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c ) 2 -C 6-10 Aryl, -C(R 12c ) 2 -C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c ) 2 -C 6-10 Aryl, -C(R 12c ) 2 -C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace;

[0530] Each R 12c are independently selected from hydrogen and R 20lc ;

[0531] Each R 13 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 haloalkyl; or R 12 and R 13Together with the nitrogen to which they are attached, they form a 20m Substituted C 2-9 heterocycloalkyl ring;

[0532] Each R 14 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl;

[0533] Each R 15 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20o replace;

[0534] Each R 20z1 , R 20z2 , R 20z3 , R 20z4 , R 20z5 , R 20z6 and R 20z9 are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z replace;

[0535] Each R 20z are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O) 2 R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O) 2 R 15 、-S(O) 2 N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 ),-CH 2 C(O)N(R 12 )(R 13 ),-CH 2 N(R 14 )C(O)R 15 、-CH 2 S(O) 2 R 15 and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20zz replace;

[0536] Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i, R 20j , R 20l , R 20lc , R 20m , R 20o , R 20q and R 20zz are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O) 2 R 25 、-C(O)R 21 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ),-OCH 2 C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O) 2 R 25 、-C(O)R 25 、-S(O) 2 R 25 、-S(O) 2 N(R 22 )(R 23 ) and -OC(O)R 25 ;

[0537] Each R 21 are independently selected from hydrogen, C1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl;

[0538] Each R 22 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl;

[0539] Each R 23 are independently selected from hydrogen and C 1-6 alkyl;

[0540] Each R 24 are independently selected from hydrogen and C 1-6 alkyl;

[0541] Each R 25 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; and

[0542] represents a single or double bond such that all valences are satisfied.

[0543] In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula:

[0544] In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula: In an embodiment, the compound has the formula:

[0545] In an implementation scheme, or any embodiment thereof (eg, subformula) selected from In an implementation scheme, or any embodiment thereof (eg, subformula) selected from

[0546] In an implementation scheme, yes In an implementation scheme, yes In an implementation scheme, Selected from In an implementation scheme, Selected from In an implementation scheme, Selected from

[0547] In an embodiment, two R bonded to the same carbon atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z In an embodiment, two R bonded to the same carbon atom z5to form a monocyclic 4-membered heterocycloalkyl group, wherein the 4-membered heterocycloalkyl group is surrounded by one, two or three R 20z replace.

[0548] In an implementation scheme, Selected from In an implementation scheme, Selected from

[0549] In an embodiment, one or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z In an embodiment, one or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 to form a monocyclic 5-6 membered heteroaryl, wherein the monocyclic 5-6 membered heteroaryl is optionally substituted by one, two or three R 20z In an embodiment, one or two R z4 and one or two R bonded to adjacent atoms z5 The monocyclic 5-6 membered heteroaryl formed by connecting is triazolyl, pyrazolyl, imidazolyl, pyrrolyl, furanyl, thienyl, oxazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazinyl; each of which is optionally substituted by one, two or three R 20z In an embodiment, one or two R z4 and one or two R bonded to adjacent atoms z5 The monocyclic 5-6 membered heteroaryl formed by connecting 20z Substituted pyrazolyl.

[0550] In an implementation scheme, Selected from In an implementation scheme, Selected from

[0551] In an embodiment, z1n is 1, 2 or 3 and z9n is 1, 2 or 3. In an embodiment, z1n is 0. In an embodiment, z9n is 0.

[0552] In an embodiment, W 1 is N. In an embodiment, W 1 is N(R 1 ).

[0553] In an embodiment, W 2 is C(R 2 ). In an embodiment, W 2 is N(R 2 ). In an embodiment, W 2 It is C(O).

[0554] In an embodiment, W 3 is N. In an embodiment, W 3 is C(R 3 ).

[0555] In an embodiment, W 3 is N. In an embodiment, W 3 is O. In an embodiment, W 3 is S. In an embodiment, W 3 is C(O). In an embodiment, W 3 is S(O). In an embodiment, W 3 YesS(O) 2 In an embodiment, W 3 is C(R 3 ). In an embodiment, W 3 is C(R 3 )(R 3a ). In an embodiment, R 3 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-C(O)R 15 、-C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 )-, where C 1-6 The alkyl group is optionally substituted by one, two or three R 20c In an embodiment, R3 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl and -OR 12 , where C 1-6 The alkyl group is optionally substituted by one, two or three R 20c In an embodiment, R 3 It's hydrogen.

[0556] In an embodiment, R 3 are independently hydrogen. In an embodiment, R 3 are independently halogen. In an embodiment, R 3 are independently -CN. In an embodiment, R 3 Independently is -OR 12 In an embodiment, R 3 Independently -SR 12 In an embodiment, R 3 is independently -N(R 12 )(R 13 ). In an embodiment, R 3 is independently -C(O)OR 12 In an embodiment, R 3 are independently -OC(O)N(R 12 )(R 13 ). In an embodiment, R 3 is independently -N(R 14 )C(O)N(R 12 )(R 13 ). In an embodiment, R 3 is independently -N(R 14 )C(O)OR 15 In an embodiment, R 3 is independently -N(R 14 )S(O) 2 R 15 In an embodiment, R 3 independently -C(O)R 15 In an embodiment, R 3 Independently -S(O)R 15 In an embodiment, R 3 Independently -OC(O)R 15 In an embodiment, R 3 are independently -C(O)N(R 12 )(R 13 ). In an embodiment, R 3 are independently -C(O)C(O)N(R 12 )(R 13 ). In an embodiment, R 3is independently -N(R 14 )C(O)R 15 In an embodiment, R 3 Independently -S(O) 2 R 15 In an embodiment, R 3 Independently -S(O) 2 N(R 12 )(R 13 )-. In an embodiment, R 3 are independently -S(=O)(=NH)N(R 12 )(R 13 ). In an embodiment, R 3 Independently -CH 2 C(O)N(R 12 )(R 13 ). In an embodiment, R 3 Independently -CH 2 N(R 14 )C(O)R 15 In an embodiment, R 3 Independently -CH 2 S(O) 2 R 15 In an embodiment, R 3 Independently -CH 2 S(O) 2 N(R 12 )(R 13 ).

[0557] In embodiments of the compounds, R 3 are independently optionally replaced by one or two R 20c In further embodiments of the compound, R 3 In some embodiments of the compounds, R 3 is independently optionally replaced by one, two or three R 20c In the embodiment of the compound, R 3 In some embodiments of the compounds, R 3 is independently optionally replaced by one, two or three R 20c In the embodiment of the compound, R 3 is independently propyl.

[0558] In an embodiment, R 3 are independently -CN. In an embodiment, R 3 is independently optionally replaced by one, two or three R 20b Substituted C1-6 In an embodiment, R 3 is independently optionally replaced by one, two or three R 20b Substituted C 2-6 In an embodiment, R 3 is independently optionally replaced by one, two or three R 20a Substituted C 2-6 In one embodiment, R 3 is independently optionally replaced by one, two or three R 20b Substituted C 3-10 In one embodiment, R 3 is independently optionally replaced by one, two or three R 20b Substituted C 2-9 In one embodiment, R 3 is independently optionally replaced by one, two or three R 20b Substituted C 6-10 In an embodiment, R 3 is independently optionally replaced by one, two or three R 20b Substituted C 1-9 In one embodiment, R 3 Independently is -OR 12 In an embodiment, R 3 is independently -C(O)OR 12 In an embodiment, R 3 are independently -OC(O)N(R 12 )(R 13 ). In an embodiment, R 3 independently -C(O)R 15 In an embodiment, R 3 are independently halogen. In an embodiment, R 3 is independently -N(R 12 )(R 13 ). In an embodiment, R 3 Independently -NH 2 .

[0559] In an embodiment, W 4 It is C.

[0560] In an embodiment, W 5 is C. In an embodiment, W 5 is C(R 5 ).

[0561] In an embodiment, W 6 is C(R 6 ). In an embodiment, W 6is N(R 6 ). In an embodiment, R 6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 3-6 Cycloalkyl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-C(O)R 15 、-C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted by one, two or three R 20f In an embodiment, R 6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl and -OR 12 , where C 1-6 The alkyl group is optionally substituted by one, two or three R 20f In an embodiment, R 6 is halogen. In an embodiment, W 6 It is N.

[0562] In an embodiment, R 6 are independently hydrogen. In an embodiment, R 6 are independently halogen. In an embodiment, R 6 are independently -CN. In an embodiment, R 6 Independently is -OR 12 In an embodiment, R 6 Independently -SR 12 In an embodiment, R 6 is independently -N(R 12 )(R 13 ). In an embodiment, R 6 is independently -C(O)OR 12 In an embodiment, R 6 are independently -OC(O)N(R 12 )(R 13 ). In an embodiment, R 6 is independently -N(R 14 )C(O)N(R 12 )(R 13). In an embodiment, R 6 is independently -N(R 14 )C(O)OR 15 In an embodiment, R 6 is independently -N(R 14 )S(O) 2 R 15 In an embodiment, R 6 independently -C(O)R 15 In an embodiment, R 6 Independently -S(O)R 15 In an embodiment, R 6 Independently -OC(O)R 15 In an embodiment, R 6 are independently -C(O)N(R 12 )(R 13 ). In an embodiment, R 6 are independently -C(O)C(O)N(R 12 )(R 13 ). In an embodiment, R 6 is independently -N(R 14 )C(O)R 15 In an embodiment, R 6 Independently -S(O) 2 R 15 In an embodiment, R 6 Independently -S(O) 2 N(R 12 )(R 13 )-. In an embodiment, R 6 are independently -S(=O)(=NH)N(R 12 )(R 13 ). In an embodiment, R 6 Independently -CH 2 C(O)N(R 12 )(R 13 ). In an embodiment, R 6 Independently -CH 2 N(R 14 )C(O)R 15 In an embodiment, R 6 Independently -CH 2 S(O) 2 R 15 In an embodiment, R 6 Independently -CH 2 S(O) 2 N(R 12 )(R 13 ).

[0563] In selected embodiments of the compounds, R 6 is independently optionally replaced by one, two or three R 20f Substituted C 1-6 In some embodiments, R 6 is independently optionally replaced by one, two or three R 20f Substituted C 2-6 In some embodiments, R 6 is independently optionally replaced by one, two or three R 20f Substituted C 2-6 In some embodiments, R 6 is independently optionally replaced by one, two or three R 20f Substituted C 3-10 In some embodiments, R 6 is independently optionally replaced by one, two or three R 20f Substituted C 2-9 In some embodiments, R 6 is independently optionally replaced by one, two or three R 20f Substituted C 6-10 In some embodiments, R 6 is independently optionally replaced by one, two or three R 20f Substituted C 1-9 In another embodiment, R 6 are independently hydrogen.

[0564] In embodiments of the compounds, R 6 are independently optionally replaced by one or two R 20f In further embodiments of the compound, R 6 In some embodiments of the compounds, R 6 is independently optionally replaced by one, two or three R 20f In the embodiment of the compound, R 6 In some embodiments of the compounds, R 6 is independently optionally replaced by one, two or three R 20f In the embodiment of the compound, R 6 is independently propyl.

[0565] In an embodiment, W 7 is C. In an embodiment, W 7 is C(R 7a ). In an embodiment, W7 It is N.

[0566] In an embodiment, R 7a is hydrogen. In an embodiment, R 7a is halogen. In an embodiment, R 7a is -CN. In an embodiment, R 7a Yes-OR 12 In an embodiment, R 7a Yes-SR 12 In an embodiment, R 7a Yes-N(R 12 )(R 13 ). In an embodiment, R 7a Yes-C(O)OR 12 In an embodiment, R 7a Yes-OC(O)N(R 12 )(R 13 ). In an embodiment, R 7a Yes-N(R 14 )C(O)N(R 12 )(R 13 ). In an embodiment, R 7a Yes-N(R 14 )C(O)OR 15 In an embodiment, R 7a Yes-N(R 14 )S(O) 2 R 15 In an embodiment, R 7a Yes-C(O)R 15 In an embodiment, R 7a Yes-S(O)R 15 In an embodiment, R 7a Yes-OC(O)R 15 In an embodiment, R 7a Yes-C(O)N(R 12 )(R 13 ). In an embodiment, R 7a Yes -C(O)C(O)N(R 12 )(R 13 ). In an embodiment, R 7a Yes-N(R 14 )C(O)R 15 In an embodiment, R 7a Yes-S(O) 2 R 15 In an embodiment, R 7a Yes-S(O) 2 N(R 12 )(R13 )-. In an embodiment, R 7a is -S(=O)(=NH)N(R 12 )(R 13 ). In an embodiment, R 7a Yes-CH 2 C(O)N(R 12 )(R 13 ). In an embodiment, R 7a Yes-CH 2 N(R 14 )C(O)R 15 In an embodiment, R 7a Yes-CH 2 S(O) 2 R 15 In an embodiment, R 7a Yes-CH 2 S(O) 2 N(R 12 )(R 13 ).

[0567] In selected embodiments of the compounds, R 7a is independently optionally replaced by one, two or three R 20g Substituted C 1-6 In some embodiments, R 7a is independently optionally replaced by one, two or three R 20g Substituted C 2-6 In some embodiments, R 7a is independently optionally replaced by one, two or three R 20g Substituted C 2-6 In some embodiments, R 7a is independently optionally replaced by one, two or three R 20g Substituted C 3-10 In some embodiments, R 7a is independently optionally replaced by one, two or three R 20g Substituted C 2-9 In some embodiments, R 7a is independently optionally replaced by one, two or three R 20g Substituted C 6-10 In some embodiments, R 7a is independently optionally replaced by one, two or three R 20g Substituted C 1-9 In another embodiment, R 7a are independently hydrogen.

[0568] In embodiments of the compounds, R 7a are independently optionally replaced by one or two R 20g In further embodiments of the compound, R 7a In some embodiments of the compounds, R 7a is independently optionally replaced by one, two or three R 20g In the embodiment of the compound, R 7a In some embodiments of the compounds, R 7a is independently optionally replaced by one, two or three R 20g In the embodiment of the compound, R 7a is independently propyl.

[0569] In an embodiment, W 8 Independently C(R 8 ). In an embodiment, R 8 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-C(O)R 15 、-C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 ), where C 1-6 The alkyl group is optionally substituted by one, two or three R 20h In an embodiment, R 8 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl and -OR 12 , where C 1-6 The alkyl group is optionally substituted by one, two or three R 20h In an embodiment, R 8 is independently halogen. In an embodiment, W 8 Independently is N.

[0570] In an embodiment, R 8 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, -OR 12 、-SR 12 、-N(R 12 )(R13 )、-C(O)OR 12 、-C(O)R 15 、-C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 )-, where C 1-6 The alkyl group is optionally substituted by one, two or three R 20h In an embodiment, R 8 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl and -OR 12 , where C 1-6 The alkyl group is optionally substituted by one, two or three R 20h In an embodiment, R 8a are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-C(O)R 15 、-C(O)N(R 12 )(R 13 )、-S(O) 2 R 15 and -S(O) 2 N(R 12 )(R 13 )-, where C 1-6 The alkyl group is optionally substituted by one, two or three R 20h In an embodiment, R 8a are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl and -OR 12 , where C 1-6 The alkyl group is optionally substituted by one, two or three R 20h In an embodiment, W 8 Independently N(R 8b ). In an embodiment, R 8b are independently hydrogen.

[0571] In an embodiment, R 8 are independently hydrogen. In an embodiment, R 8 are independently halogen. In an embodiment, R 8 are independently -CN. In an embodiment, R 8 Independently C1-6 In an embodiment, R 8 Independently C 2-6 In an embodiment, R 8 Independently C 2-6 In one embodiment, R 8 Independently C 3-10 In one embodiment, R 8 Independently C 2-9 In one embodiment, R 8 Independently C 6-10 In an embodiment, R 8 Independently C 1-9 Heteroaryl.

[0572] In an embodiment, R 8 is independently optionally replaced by one, two or three R 20h Substituted C 1-6 In an embodiment, R 8 is independently optionally replaced by one, two or three R 20h Substituted C 2-6 In an embodiment, R 8 is independently optionally replaced by one, two or three R 20h Substituted C 2-6 In one embodiment, R 8 is independently optionally replaced by one, two or three R 20h Substituted C 3-10 In one embodiment, R 8 is independently optionally replaced by one, two or three R 20h Substituted C 2-9 In one embodiment, R 8 is independently optionally replaced by one, two or three R 20h Substituted C 6-10 In an embodiment, R 8 is independently optionally replaced by one, two or three R 20h Substituted C 1-9 Heteroaryl.

[0573] In an embodiment, R 8 Independently is -OR 12 In an embodiment, R 8 Independently -SR 12 In an embodiment, R 8 is independently -N(R 12 )(R 13 ). In an embodiment, R 8 is independently -C(O)OR12 In an embodiment, R 8 are independently -OC(O)N(R 12 )(R 13 ). In an embodiment, R 8 is independently -N(R 14 )C(O)N(R 12 )(R 13 ). In an embodiment, R 8 is independently -N(R 14 )C(O)OR 15 In an embodiment, R 8 is independently -N(R 14 )S(O) 2 R 15 In an embodiment, R 8 independently -C(O)R 15 In an embodiment, R 8 Independently -S(O)R 15 In an embodiment, R 8 Independently -OC(O)R 15 In an embodiment, R 8 are independently -C(O)N(R 12 )(R 13 ). In an embodiment, R 8 are independently -C(O)C(O)N(R 12 )(R 13 ). In an embodiment, R 8 is independently -N(R 14 )C(O)R 15 In an embodiment, R 8 Independently -S(O) 2 R 15 In an embodiment, R 8 Independently -S(O) 2 N(R 12 )(R 13 ). In an embodiment, R 8 are independently S(=O)(=NH)N(R 12 )(R 13 ). In an embodiment, R 8 Independently -CH 2 C(O)N(R 12 )(R 13 ). In an embodiment, R 8 Independently -CH 2 N(R 14 )C(O)R 15 In an embodiment, R8 Independently -CH 2 S(O) 2 R 15 In an embodiment, R 8 Independently -CH 2 S(O) 2 N(R 12 )(R 13 ).

[0574] In an embodiment, W 9 is C. In an embodiment, W 10 It is C.

[0575] In an implementation scheme, Selected from

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[0599]

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[0630] In an embodiment, Z 4a The two R's z4 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 4a The two R's z4 connected to form a 20z In one embodiment, Z 4a The two R's z4 connected to form a 20z substituted monocyclic 4-membered heterocycloalkyl. 4a The two R's z4 connected to form a 20z substituted monocyclic 5-membered heterocycloalkyl. 4a The two R's z4 connected to form a 20z substituted monocyclic 6-membered heterocycloalkyl. 4a The two R's z4 connected to form a 20z substituted monocyclic 7-membered heterocycloalkyl. 4a The two R's z4 connected to form a 20z Substituted azetidine (e.g., R 20z In an embodiment, Z 4a The two R's z4 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 4a The two R's z4 connected to form a 20z Substituted piperidine (e.g., R 20z In an embodiment, Z 4a The two R's z4 connected to form a 20z Substituted monocyclic C3-7 In one embodiment, Z 4a The two R's z4 connected to form a 20z Substituted monocyclic C 3 In one embodiment, Z 4a The two R's z4 connected to form a 20z Substituted monocyclic C 4 In one embodiment, Z 4a The two R's z4 connected to form a 20z Substituted monocyclic C 5 In one embodiment, Z 4a The two R's z4 connected to form a 20z Substituted monocyclic C 6 In one embodiment, Z 4a The two R's z4 connected to form a 20z Substituted monocyclic C 7 Cycloalkyl.

[0631] In an embodiment, Z 4b The two R's z4 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 4b The two R's z4 connected to form a 20z In one embodiment, Z 4b The two R's z4 connected to form a 20z substituted monocyclic 4-membered heterocycloalkyl. 4b The two R's z4 connected to form a 20z substituted monocyclic 5-membered heterocycloalkyl. 4b The two R's z4 connected to form a 20z substituted monocyclic 6-membered heterocycloalkyl. 4b The two R's z4 connected to form a 20z substituted monocyclic 7-membered heterocycloalkyl.4b The two R's z4 connected to form a 20z Substituted azetidine (e.g., R 20z In an embodiment, Z 4b The two R's z4 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 4b The two R's z4 connected to form a 20z Substituted piperidine (e.g., R 20z In an embodiment, Z 4b The two R's z4 connected to form a 20z Substituted monocyclic C 3-7 In one embodiment, Z 4b The two R's z4 connected to form a 20z Substituted monocyclic C 3 In one embodiment, Z 4b The two R's z4 connected to form a 20z Substituted monocyclic C 4 In one embodiment, Z 4b The two R's z4 connected to form a 20z Substituted monocyclic C 5 In one embodiment, Z 4b The two R's z4 connected to form a 20z Substituted monocyclic C 6 In one embodiment, Z 4b The two R's z4 connected to form a 20z Substituted monocyclic C 7 Cycloalkyl.

[0632] In an embodiment, Z 4c The two R's z4 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 4c The two R's z4connected to form a 20z In one embodiment, Z 4c The two R's z4 connected to form a 20z substituted monocyclic 4-membered heterocycloalkyl. 4c The two R's z4 connected to form a 20z substituted monocyclic 5-membered heterocycloalkyl. 4c The two R's z4 connected to form a 20z substituted monocyclic 6-membered heterocycloalkyl. 4c The two R's z4 connected to form a 20z substituted monocyclic 7-membered heterocycloalkyl. 4c The two R's z4 connected to form a 20z Substituted azetidine (e.g., R 20z In an embodiment, Z 4c The two R's z4 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 4c The two R's z4 connected to form a 20z Substituted piperidine (e.g., R 20z In an embodiment, Z 4c The two R's z4 connected to form a 20z Substituted monocyclic C 3-7 In one embodiment, Z 4c The two R's z4 connected to form a 20z Substituted monocyclic C 3 In one embodiment, Z 4c The two R's z4 connected to form a 20z Substituted monocyclic C 4 In one embodiment, Z 4c The two R's z4connected to form a 20z Substituted monocyclic C 5 In one embodiment, Z 4c The two R's z4 connected to form a 20z Substituted monocyclic C 6 In one embodiment, Z 4c The two R's z4 connected to form a 20z Substituted monocyclic C 7 Cycloalkyl.

[0633] In an embodiment, Z 4d The two R's z4 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 4d The two R's z4 connected to form a 20z In one embodiment, Z 4d The two R's z4 connected to form a 20z substituted monocyclic 4-membered heterocycloalkyl. 4d The two R's z4 connected to form a 20z substituted monocyclic 5-membered heterocycloalkyl. 4d The two R's z4 connected to form a 20z substituted monocyclic 6-membered heterocycloalkyl. 4d The two R's z4 connected to form a 20z substituted monocyclic 7-membered heterocycloalkyl. 4d The two R's z4 connected to form a 20z Substituted azetidine (e.g., R 20z In an embodiment, Z 4d The two R's z4 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 4d The two R's z4connected to form a 20z Substituted piperidine (e.g., R 20z In an embodiment, Z 4d The two R's z4 connected to form a 20z Substituted monocyclic C 3-7 In one embodiment, Z 4d The two R's z4 connected to form a 20z Substituted monocyclic C 3 In one embodiment, Z 4d The two R's z4 connected to form a 20z Substituted monocyclic C 4 In one embodiment, Z 4d The two R's z4 connected to form a 20z Substituted monocyclic C 5 In one embodiment, Z 4d The two R's z4 connected to form a 20z Substituted monocyclic C 6 In one embodiment, Z 4d The two R's z4 connected to form a 20z Substituted monocyclic C 7 Cycloalkyl.

[0634] In an embodiment, Z 4e The two R's z4 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 4e The two R's z4 connected to form a 20z In one embodiment, Z 4e The two R's z4 connected to form a 20z substituted monocyclic 4-membered heterocycloalkyl. 4e The two R's z4 connected to form a 20z substituted monocyclic 5-membered heterocycloalkyl. 4e The two R'sz4 connected to form a 20z substituted monocyclic 6-membered heterocycloalkyl. 4e The two R's z4 connected to form a 20z substituted monocyclic 7-membered heterocycloalkyl. 4e The two R's z4 connected to form a 20z Substituted azetidine (e.g., R 20z In an embodiment, Z 4e The two R's z4 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 4e The two R's z4 connected to form a 20z Substituted piperidine (e.g., R 20z In an embodiment, Z 4e The two R's z4 connected to form a 20z Substituted monocyclic C 3-7 In one embodiment, Z 4e The two R's z4 connected to form a 20z Substituted monocyclic C 3 In one embodiment, Z 4e The two R's z4 connected to form a 20z Substituted monocyclic C 4 In one embodiment, Z 4e The two R's z4 connected to form a 20z Substituted monocyclic C 5 In one embodiment, Z 4e The two R's z4 connected to form a 20z Substituted monocyclic C 6 In one embodiment, Z 4e The two R's z4 connected to form a 20z Substituted monocyclic C 7 Cycloalkyl.

[0635] In an embodiment, Z 5 The two R's z5 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 5 The two R's z5 connected to form a 20z In one embodiment, Z 5 The two R's z5 connected to form a 20z substituted monocyclic 4-membered heterocycloalkyl. 5 The two R's z5 connected to form a 20z substituted monocyclic 5-membered heterocycloalkyl. 5 The two R's z5 connected to form a 20z substituted monocyclic 6-membered heterocycloalkyl. 5 The two R's z5 connected to form a 20z substituted monocyclic 7-membered heterocycloalkyl. 5 The two R's z5 connected to form a 20z Substituted azetidine (e.g., R 20z In an embodiment, Z 5 The two R's z5 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 5 The two R's z5 connected to form a 20z Substituted piperidine (e.g., R 20z In an embodiment, Z 5 The two R's z5 connected to form a 20z Substituted monocyclic C 3-7 In one embodiment, Z 5 The two R's z5 connected to form a 20z Substituted monocyclic C 3In one embodiment, Z 5 The two R's z5 connected to form a 20z Substituted monocyclic C 4 In one embodiment, Z 5 The two R's z5 connected to form a 20z Substituted monocyclic C 5 In one embodiment, Z 5 The two R's z5 connected to form a 20z Substituted monocyclic C 6 In one embodiment, Z 5 The two R's z5 connected to form a 20z Substituted monocyclic C 7 Cycloalkyl.

[0636] In an embodiment, Z 6 The two R's z6 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 6 The two R's z6 connected to form a 20z In one embodiment, Z 6 The two R's z6 connected to form a 20z substituted monocyclic 4-membered heterocycloalkyl. 6 The two R's z6 connected to form a 20z substituted monocyclic 5-membered heterocycloalkyl. 6 The two R's z6 connected to form a 20z substituted monocyclic 6-membered heterocycloalkyl. 6 The two R's z6 connected to form a 20z substituted monocyclic 7-membered heterocycloalkyl. 6 The two R's z6 connected to form a 20z Substituted azetidine (e.g., R 20z In an embodiment, Z6 The two R's z6 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 6 The two R's z6 connected to form a 20z Substituted piperidine (e.g., R 20z In an embodiment, Z 6 The two R's z6 connected to form a 20z Substituted monocyclic C 3-7 In one embodiment, Z 6 The two R's z6 connected to form a 20z Substituted monocyclic C 3 In one embodiment, Z 6 The two R's z6 connected to form a 20z Substituted monocyclic C 4 In one embodiment, Z 6 The two R's z6 connected to form a 20z Substituted monocyclic C 5 In one embodiment, Z 6 The two R's z6 connected to form a 20z Substituted monocyclic C 6 In one embodiment, Z 6 The two R's z6 connected to form a 20z Substituted monocyclic C 7 Cycloalkyl.

[0637] In an embodiment, Z 4a One or two R z4 and Z 4b One or two R z4 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace.

[0638] In an embodiment, Z 4a One or two R z4 and Z 4b One or two R z4 connected to form a 20z Substituted monocyclic C 3-7 In one embodiment, Z 4a One or two R z4 and Z 4b One or two R z4 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 4a One or two R z4 and Z 4b One or two R z4 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 4a One or two R z4 and Z 4b One or two R z4 connected to form a 20z In one embodiment, Z 4a One or two R z4 and Z 4b One or two R z4 connected to form a 20z substituted monocyclic 5-6 membered heteroaryl. In an embodiment, Z 4a One or two R z4 and Z 4b One or two R z4 connected to form a 20z In one embodiment, Z 4a One or two R z4 and Z 4b One or two R z4 connected to form a 20z In one embodiment, Z 4a One or two R z4 and Z 4b One or two R z4 connected to form a 20z In one embodiment, Z 4a One or two Rz4 and Z 4b One or two R z4 connected to form a 20z In one embodiment, Z 4a One or two R z4 and Z 4b One or two R z4 connected to form a 20z In one embodiment, Z 4a One or two R z4 and Z 4b One or two R z4 connected to form a 20z In one embodiment, Z 4a One or two R z4 and Z 4b One or two R z4 connected to form a 20z Substituted pyrimidines.

[0639] In an embodiment, Z 4b One or two R z4 and Z 4c One or two R z4 connected to form a 20z Substituted monocyclic C 3-7 In one embodiment, Z 4b One or two R z4 and Z 4c One or two R z4 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 4b One or two R z4 and Z 4c One or two R z4 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 4b One or two R z4 and Z 4c One or two R z4 connected to form a 20z In one embodiment, Z 4b One or two R z4 and Z4c One or two R z4 connected to form a 20z substituted monocyclic 5-6 membered heteroaryl. In an embodiment, Z 4b One or two R z4 and Z 4c One or two R z4 connected to form a 20z In one embodiment, Z 4b One or two R z4 and Z 4c One or two R z4 connected to form a 20z In one embodiment, Z 4b One or two R z4 and Z 4c One or two R z4 connected to form a 20z In one embodiment, Z 4b One or two R z4 and Z 4c One or two R z4 connected to form a 20z In one embodiment, Z 4b One or two R z4 and Z 4c One or two R z4 connected to form a 20z In one embodiment, Z 4b One or two R z4 and Z 4c One or two R z4 connected to form a 20z In one embodiment, Z 4b One or two R z4 and Z 4c One or two R z4 connected to form a 20z Substituted pyrimidines.

[0640] In an embodiment, Z 4c One or two R z4 and Z 4d One or two R z4 connected to form a20z Substituted monocyclic C 3-7 In one embodiment, Z 4c One or two R z4 and Z 4d One or two R z4 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 4c One or two R z4 and Z 4d One or two R z4 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 4c One or two R z4 and Z 4d One or two R z4 connected to form a 20z In one embodiment, Z 4c One or two R z4 and Z 4d One or two R z4 connected to form a 20z substituted monocyclic 5-6 membered heteroaryl. In an embodiment, Z 4c One or two R z4 and Z 4d One or two R z4 connected to form a 20z In one embodiment, Z 4c One or two R z4 and Z 4d One or two R z4 connected to form a 20z In one embodiment, Z 4c One or two R z4 and Z 4d One or two R z4 connected to form a 20z In one embodiment, Z 4c One or two R z4 and Z 4d One or two R z4 connected to form a 20z In one embodiment, Z4c One or two R z4 and Z 4d One or two R z4 connected to form a 20z In one embodiment, Z 4c One or two R z4 and Z 4d One or two R z4 connected to form a 20z In one embodiment, Z 4c One or two R z4 and Z 4d One or two R z4 connected to form a 20z Substituted pyrimidines.

[0641] In an embodiment, Z 4d One or two R z4 and Z 4e One or two R z4 connected to form a 20z Substituted monocyclic C 3-7 In one embodiment, Z 4d One or two R z4 and Z 4e One or two R z4 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 4d One or two R z4 and Z 4e One or two R z4 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 4d One or two R z4 and Z 4e One or two R z4 connected to form a 20z In one embodiment, Z 4d One or two R z4 and Z 4e One or two R z4 connected to form a 20z substituted monocyclic 5-6 membered heteroaryl. In an embodiment, Z 4dOne or two R z4 and Z 4e One or two R z4 connected to form a 20z In one embodiment, Z 4d One or two R z4 and Z 4e One or two R z4 connected to form a 20z In one embodiment, Z 4d One or two R z4 and Z 4e One or two R z4 connected to form a 20z In one embodiment, Z 4d One or two R z4 and Z 4e One or two R z4 connected to form a 20z In one embodiment, Z 4d One or two R z4 and Z 4e One or two R z4 connected to form a 20z In one embodiment, Z 4d One or two R z4 and Z 4e One or two R z4 connected to form a 20z In one embodiment, Z 4d One or two R z4 and Z 4e One or two R z4 connected to form a 20z Substituted pyrimidines.

[0642] In an embodiment, Z 4e One or two R z4 and Z 5 One or two R z5 connected to form a 20z Substituted monocyclic C 3-7 In one embodiment, Z 4e One or two R z4 and Z 5 One or two Rz5 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 4e One or two R z4 and Z 5 One or two R z5 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 4e One or two R z4 and Z 5 One or two R z5 connected to form a 20z In one embodiment, Z 4e One or two R z4 and Z 5 One or two R z5 connected to form a 20z substituted monocyclic 5-6 membered heteroaryl. In an embodiment, Z 4e One or two R z4 and Z 5 One or two R z5 connected to form a 20z In one embodiment, Z 4e One or two R z4 and Z 5 One or two R z5 connected to form a 20z In one embodiment, Z 4e One or two R z4 and Z 5 One or two R z5 connected to form a 20z In one embodiment, Z 4e One or two R z4 and Z 5 One or two R z5 connected to form a 20z In one embodiment, Z 4e One or two R z4 and Z 5 One or two R z5 connected to form a 20zIn one embodiment, Z 4e One or two R z4 and Z 5 One or two R z5 connected to form a 20z In one embodiment, Z 4e One or two R z4 and Z 5 One or two R z5 connected to form a 20z Substituted pyrimidines.

[0643] In an embodiment, Z 5 One or two R z5 and Z 6 One or two R z6 connected to form a 20z Substituted monocyclic C 3-7 In one embodiment, Z 5 One or two R z5 and Z 6 One or two R z6 connected to form a 20z substituted monocyclic 3-7 membered heterocycloalkyl. 5 One or two R z5 and Z 6 One or two R z6 connected to form a 20z Substituted pyrrolidine (e.g., R 20z In an embodiment, Z 5 One or two R z5 and Z 6 One or two R z6 connected to form a 20z In one embodiment, Z 5 One or two R z5 and Z 6 One or two R z6 connected to form a 20z substituted monocyclic 5-6 membered heteroaryl. In an embodiment, Z 5 One or two R z5 and Z 6 One or two R z6 connected to form a 20zIn one embodiment, Z 5 One or two R z5 and Z 6 One or two R z6 connected to form a 20z In one embodiment, Z 5 One or two R z5 and Z 6 One or two R z6 connected to form a 20z In one embodiment, Z 5 One or two R z5 and Z 6 One or two R z6 connected to form a 20z In one embodiment, Z 5 One or two R z5 and Z 6 One or two R z6 connected to form a 20z In one embodiment, Z 5 One or two R z5 and Z 6 One or two R z6 connected to form a 20z In one embodiment, Z 5 One or two R z5 and Z 6 One or two R z6 connected to form a 20z Substituted pyrimidines.

[0644] In an embodiment, two R bonded to the same carbon atom z4 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z In an embodiment, two R bonded to the same carbon atom z4 connected to form a 20z Substituted monocyclic C 3-7 In an embodiment, two R bonded to the same carbon atom z4 connected to form a 20zSubstituted monocyclic 3-7 membered heterocycloalkyl.

[0645] In an embodiment, two or more R bonded to adjacent atoms z4 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z In an embodiment, two or more R bonded to adjacent atoms z4 connected to form a 20z Substituted monocyclic C 3-7 In an embodiment, two or more R bonded to adjacent atoms z4 connected to form a 20z In an embodiment, two or more R bonded to adjacent atoms are z4 connected to form a 20z In an embodiment, two or more R bonded to adjacent atoms z4 connected to form a 20z Substituted monocyclic 5-6 membered heteroaryl.

[0646] In an embodiment, two R bonded to the same carbon atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z In an embodiment, two R bonded to the same carbon atom z5 connected to form a 20z Substituted monocyclic C 3-7 In an embodiment, two R bonded to the same carbon atom z5 connected to form a 20z Substituted monocyclic 3-7 membered heterocycloalkyl.

[0647] In an embodiment, one or two R bonded to the atom z4 and one or two R bonded to adjacent atoms z5 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z In an embodiment, one or two R bonded to the atom z4 and one or two R bonded to adjacent atoms z5 connected to form a 20z Substituted monocyclic C 3-7 In an embodiment, one or two R bonded to the atom z4 and one or two R bonded to adjacent atoms z5 connected to form a 20z In an embodiment, one or two R bonded to the atom z4 and one or two R bonded to adjacent atoms z5 connected to form a 20z In an embodiment, one or two R bonded to the atom z4 and one or two R bonded to adjacent atoms z5 connected to form a 20z Substituted monocyclic 5-6 membered heteroaryl.

[0648] In an embodiment, one or two R bonded to an atom z4 and one or two R bonded to a second atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace;

[0649] In an embodiment, two R bonded to the same carbon atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z In an embodiment, one or two R bonded to an atom z4 and one or two R bonded to a second atom z5 connected to form a 20z Substituted monocyclic C 3-7 In an embodiment, one or two R bonded to an atom z4 and one or two R bonded to a second atom z5connected to form a 20z In one embodiment, one or two R bonded to one atom are z4 and one or two R bonded to a second atom z5 connected to form a 20z In an embodiment, one or two R bonded to an atom z4 and one or two R bonded to a second atom z5 connected to form a 20z Substituted monocyclic 5-6 membered heteroaryl.

[0650] In an embodiment, one or two R bonded to the atom z5 and one or two R bonded t...

Claims

1. A compound of formula (A), or a pharmaceutically acceptable salt or solvate thereof: in: W 1 is N(R 1 ) or N; R 1 Selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20a replace; W 2 is C(R 2 )、N(R 2 )、C(R 2 )2, C(O), S(O), S(O)2 or N; Each R 2 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12a 、-SR 12a 、-N(R 12a )(R 13 ),-N=(R 15 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )-、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20b replace; W 3 is C(R 3 )、N(R 3 )、C(R 3 )2, C(O), S(O), S(O)2 or N; Each R 3 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20c replace; W 4 is C(R 4 ), C or N; R 4 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20d replace; W 5 is C(R 5 ), C or N; R 5 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20e replace; W 6 is C(R 6 )、N(R 6 )、C(R 6 )2, C(O), S(O), S(O)2 or N; Each R 6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20f replace; W 7 is C(R 7a ), C or N; R 7a Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20g replace; R 7 Yes-L 7 -R 17 ; L 7 is a bond, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 2-4 membered heteroalkylene linker, -O-, -N(R 7d )-, -C(O)-, -S-, -S(O)2-, -S(O)-, -P(O)R 7d -、CR 7c R 7c , -OCR 7c R 7c -、-N(R 7d )CR 7c R 7c -、-C(O)CR 7c R 7c -、-SCR 7c R 7c -、-S(O)2CR 7c R 7c -、-S(O)CR 7c R 7c -、-P(O)R 7d CR 7c R 7c -、-CR 7c R 7c CR 7c R 7c , -CR 7c R 7c O-、-CR 7c R 7c N(R 7d )-、-CR 7c R 7c C(O)-、-CR 7c R 7c S-、-CR 7c R 7c S(O)2-、-CR 7c R 7c S(O)-、-CR 7c R 7c P(O)R 7d -、-N(R 7d )C(O)-、-N(R 7d )S(O)2-、-N(R 7d )S(O)-、-N(R 7d )P(O)R 7d -、-C(O)N(R 7d )-、-S(O)2N(R 7d )-、-S(O)N(R 7d )-、-P(O)R 7d N(R 7d )-, -OC(O)-, -OS(O)2-, -OS(O)-, -OP(O)R 7d -, -C(O)O-, -S(O)2O-, -S(O)O- or -P(O)R 7d O-; wherein the C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 2-4 membered heteroalkylene linker is optionally substituted by one, two or three R 20g replace; Each R 7c are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20g replace; Each R 7d are independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20g replace; R 17 Selected from C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl, wherein C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl are optionally substituted by one or more R 20q Replace; or L 7 is a key, and R 7a and R 17 Together with the carbon to which they are attached, they form C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl are optionally substituted with one or more R 20q replace; W 8 is C(R 8 )、N(R 8 )、C(R 8 )2, C(O), S(O), S(O)2 or N; Each R 8 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20h replace; W 9 is C(R 9 ), C or N; R 9 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20i replace; W 10 is C(R 10 ), C or N; R 10 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20j replace; Each Z 1 Independently C(R z1 )、N(R z1 )、C(R z1 )2, C(O), S(O), S(O)2, O, S or N; z1n is 0, 1, 2, or 3; if z1n is 0, then Z 2 Direct bonding to W 5 ; Each R z1 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z1 replace; Each Z 9 Independently C(R z9 )、N(R z9 )、C(R z9 )2, C(O), S(O), S(O)2, O, S or N; z9n is 0, 1, 2, or 3; if z9n is 0, then Z 3 Direct bonding to W 4 ; Each R z9 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z9 replace; The sum of z1n and z9n is 2 or 3; Z 2 is C(R z2 ), C or N; R z2 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z2 replace; Z 3 is C(R z3 ), C or N; R z3 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z3 replace; Z 4 Yes key, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c or Z 4a Z 4b Z 4c Z 4d ; where Z 4a Direct Bonding to Z 2 ; and if Z 4 is a key, then Z 2 Direct Bonding to Z 5 ; Z 4a , Z 4b , Z 4c and Z 4d Independently C(R z4 )、N(R z4 )、C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S or N; The conditions are: i) If z9n is 0 and Z 4 It's Z 4a Z 4b ; then (1) Z 4b is C(R z4 )、C(R z4 )2. C(O), S(O), S(O)2, S(O)(NR z4 ), O, S or N, (2) Z 4b is N(R z4 ) and Z 4a is C(O), S(O) or S(O)2; (3) Z 4b is N(R z4 ) and Z 5 is C(O), S(O) or S(O)2; or (4) Z 4b is N(R z4 ) and Z 3 is C(R z3 ) or C; and ii) One R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 or R 20z Independently selected from -C(O)R 12 and -N(H)C(O)R 12 ; wherein one of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, Two or Three R's 20l replace; Each R z4 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 alkenyl; Z 5 is C(R z5 ), N(R z5 ), C(R z5 )2, C(O), S(O), S(O)2, S(O)(NR z5 ), O, S or N; Each R z5 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 alkenyl; Z 6 is C(R z6 ), N(R z6 ), C(R z6 )2, C(O), S(O), S(O)2, S(O)(NR z6 ), O, S or N; Each R z6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 alkenyl; And further wherein the compound optionally comprises one of the following: (1) Two R bonded to the same carbon atom z4 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; (2) Two or more R bonded to adjacent atoms z4 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; (3) Two R bonded to the same carbon atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; (4) One or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; (5) One or two R bonded to an atom z4 and one or two R bonded to a second atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; (6) Two R bonded to the same carbon atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; (7) One or two R bonded to an atom z5 and one or two R bonded to adjacent atoms z6 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; or (8) One or two R bonded to an atom z4 and one or two R bonded to a second atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; Each R 12 are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace; Each R 12a are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c )2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c )2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c )2-C 6-10 Aryl, -C(R 12c )2-C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c )2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c )2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c )2-C 6-10 Aryl, -C(R 12c )2-C 1-9 Heteroaryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace; Each R 12c are independently selected from hydrogen and R 20lc ; Each R 13 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 haloalkyl; or R 12 and R 13 Together with the nitrogen to which they are attached, they form a 20m Substituted C 2-9 heterocycloalkyl ring; Each R 14 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl; Each R 15 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20o replace; Each R 20z1 , R 20z2 , R 20z3 , R 20z4 , R 20z5 , R 20z6 and R 20z9 are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z replace; Each R 20z are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20zz replace; Two R bonded to the same carbon atom 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20zz replace; or Two or more R bonded to two adjacent atoms 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20zz replace; Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20lc , R 20l , R 20m , R 20o , R 20q and R 20zz are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O)2R 25 、-C(O)R 21 、-S(O)2R 25 、-S(O)2N(R 22 )(R 23 )、-OCH2C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O)2R 25 、-C(O)R 25 、-S(O)2R 25 、-S(O)2N(R 22 )(R 23 ) and -OC(O)R 25 ; Each R 21 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; Each R 22 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; Each R 23 are independently selected from hydrogen and C 1-6 alkyl; Each R 24 are independently selected from hydrogen and C 1-6 alkyl; Each R 25 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; and represents a single or double bond such that all valences are satisfied.

2. A compound of formula (A), or a pharmaceutically acceptable salt or solvate thereof: in: W 1 is N(R 1 ) or N; R 1 Selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20a replace; W 2 is C(R 2 )、N(R 2 )、C(R 2 )2, C(O), S(O), S(O)2 or N; Each R 2 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12a 、-SR 12a 、-N(R 12a )(R 13 ),-N=(R 15 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )-、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20b replace; W 3 is C(R 3 )、N(R 3 )、C(R 3 )2, C(O), S(O), S(O)2 or N; Each R 3 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20c replace; W 4 is C(R 4 ), C or N; R 4 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20d replace; W 5 is C(R 5 ), C or N; R 5 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20e replace; W 6 is C(R 6 )、N(R 6 )、C(R 6 )2, C(O), S(O), S(O)2 or N; Each R 6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20f replace; W 7 is C(R 7a ), C or N; R 7a Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20g replace; R 7 Yes-L 7 -R 17 ; L 7 is a bond, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 2-4 membered heteroalkylene linker, -O-, -N(R 7d )-, -C(O)-, -S-, -S(O)2-, -S(O)-, -P(O)R 7d -、CR 7c R 7c , -OCR 7c R 7c -、-N(R 7d )CR 7c R 7c -、-C(O)CR 7c R 7c -、-SCR 7c R 7c -、-S(O)2CR 7c R 7c -、-S(O)CR 7c R 7c -、-P(O)R 7d CR 7c R 7c -、-CR 7c R 7c CR 7c R 7c , -CR 7c R 7c O-、-CR 7c R 7c N(R 7d )-、-CR 7c R 7c C(O)-、-CR 7c R 7c S-、-CR 7c R 7c S(O)2-、-CR 7c R 7c S(O)-、-CR 7c R 7c P(O)R 7d -、-N(R 7d )C(O)-、-N(R 7d )S(O)2-、-N(R 7d )S(O)-、-N(R 7d )P(O)R 7d -、-C(O)N(R 7d )-、-S(O)2N(R 7d )-、-S(O)N(R 7d )-、-P(O)R 7d N(R 7d )-, -OC(O)-, -OS(O)2-, -OS(O)-, -OP(O)R 7d -, -C(O)O-, -S(O)2O-, -S(O)O- or -P(O)R 7d O-; wherein the C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 2-4 membered heteroalkylene linker is optionally substituted by one, two or three R 20g replace; Each R 7c are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20g replace; Each R 7d are independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace; R 17 Selected from C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl, wherein C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl are optionally substituted by one or more R 20q Replace; or L 7 is a key, and R 7a and R 17 Together with the carbon to which they are attached, they form C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl are optionally substituted with one or more R 20q replace; W 8 is C(R 8 )、N(R 8 )、C(R 8 )2, C(O), S(O), S(O)2 or N; Each R 8 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20h replace; W 9 is C(R 9 ), C or N; R 9 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20i replace; W 10 is C(R 10 ), C or N; R 10 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20j replace; Each Z 1 Independently C(R z1 )、N(R z1 )、C(R z1 )2, C(O), S(O), S(O)2, O, S or N; z1n is 0, 1, 2, or 3; if z1n is 0, then Z 2 Direct bonding to W 5 ; Each R z1 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z1 replace; Each Z 9 Independently C(R z9 )、N(R z9 )、C(R z9 )2, C(O), S(O), S(O)2, O, S or N; z9n is 0, 1, 2, or 3; if z9n is 0, then Z 3 Direct bonding to W 4 ; Each R z9 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z9 replace; The sum of z1n and z9n is 2 or 3; Z 2 is C(R z2 ), C or N; R z2 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z2 replace; Z 3 is C(R z3 ), C or N; R z3 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z3 replace; Z 4 Yes key, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c or Z 4a Z 4b Z 4c Z 4d ; where Z 4a Direct Bonding to Z 2 ; and if Z 4 is a key, then Z 2 Direct Bonding to Z 5 ; Z 4a , Z 4b , Z 4c and Z 4d Independently C(R z4 )、N(R z4 )、C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S or N; The conditions are: i) If z9n is 0 and Z 4 It's Z 4a Z 4b ; then (1) Z 4b is C(R z4 )、C(R z4 )2. C(O), S(O), S(O)2, S(O)(NR z4 ), O, S or N, (2) Z 4b is N(R z4 ) and Z 4a is C(O), S(O) or S(O)2; (3) Z 4b is N(R z4 ) and Z 5 is C(O), S(O) or S(O)2; or (4) Z 4b is N(R z4 ) and Z 3 is C(R z3 ) or C; and ii) R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 , R 20z or R 20zz Only one of them is E, wherein E is a moiety capable of covalently binding to the Ras mutant protein at the amino acid corresponding to G12D or G12S of the human K-Ras mutant G12D or G12S protein, respectively: Each R z4 are independently selected from E, hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 alkenyl; Z 5 is C(R z5 ), N(R z5 ), C(R z5 )2, C(O), S(O), S(O)2, S(O)(NR z5 ), O, S or N; Each R z5 are independently selected from E, hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 alkenyl; Z 6 is C(R z6 )、N(R z6 )、C(R z6 )2、C(O)、S(O)、S(O)2、S(O)(NR z6 )、O、S or N; Each R z6 are independently selected from E, hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 alkenyl; And further wherein the compound optionally comprises one of the following: (1) Two R bonded to the same carbon atom z4 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; (2) Two or more R bonded to adjacent atoms z4 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; (3) Two R bonded to the same carbon atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; (4) One or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; (5) One or two R bonded to an atom z4 and one or two R bonded to a second atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; (6) Two R bonded to the same carbon atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; (7) One or two R bonded to an atom z5 and one or two R bonded to adjacent atoms z6 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; or (8) One or two R bonded to an atom z4 and one or two R bonded to a second atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; Each R 12 are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace; Each R 12a are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c )2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c )2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c )2-C 6-10 Aryl, -C(R 12c )2-C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c )2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c )2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c )2-C 6-10 Aryl, -C(R 12c )2-C 1-9 Heteroaryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace; Each R 12c are independently selected from hydrogen and R 20lc ; Each R 13 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 haloalkyl; or R 12 and R 13 Together with the nitrogen to which they are attached, they form a 20m Substituted C 2-9 heterocycloalkyl ring; Each R 14 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl; Each R 15 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20o replace; Each R 20z1 , R 20z2 , R 20z3 and R 20z9 are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z replace; Each R 20z4 , R 20z5 and R 20z6 are independently selected from E, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z replace; Each R 20z are independently selected from E, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20zz replace; Two R bonded to the same carbon atom 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20zz replace; or Two or more R bonded to two adjacent atoms 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20zz replace; Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20lc , R 20l , R 20lz , R 20m , R 20o and R 20q are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O)2R 25 、-C(O)R 21 、-S(O)2R 25 、-S(O)2N(R 22 )(R 23 )、-OCH2C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O)2R 25 、-C(O)R 25 、-S(O)2R 25 、-S(O)2N(R 22 )(R 23 ) and -OC(O)R 25 ; Each R 20zz are independently selected from E, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O)2R 25 、-C(O)R 21 、-S(O)2R 25 、-S(O)2N(R 22 )(R 23 )、-OCH2C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O)2R 25 、-C(O)R 25 、-S(O)2R 25 、-S(O)2N(R 22 )(R 23 ) and -OC(O)R 25 ; Each R 21 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; Each R 22 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; Each R 23 are independently selected from hydrogen and C 1-6 alkyl; Each R 24 are independently selected from hydrogen and C 1-6 alkyl; Each R 25 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; and represents a single or double bond such that all valences are satisfied.

3. The compound according to one of claims 1-2, or a pharmaceutically acceptable salt or solvate thereof, wherein one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 or R 20z independently -C(O)R 12 or -N(H)C(O)R 12 ; wherein one of the R 12 It is C 1-9 Heteroaryl, wherein C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace.

4. The compound according to one of claims 1-2, or a pharmaceutically acceptable salt or solvate thereof, wherein one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 or R 20z Independently - C(O)R 12 or -N(H)C(O)R 12 ; wherein one of the R 12 Selected from C 2-9 Heterocycloalkyl; wherein C 2-9 The heterocycloalkyl group is optionally substituted by one, two or three R 20l replace.

5. The compound according to one of claims 1-2, or a pharmaceutically acceptable salt or solvate thereof, wherein one R z4 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z4 Replace and an R 20z4 Selected from -C(O)R 12 and -N(H)C(O)R 12 ; wherein one of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace.

6. The compound according to one of claims 1-2, or a pharmaceutically acceptable salt or solvate thereof, wherein one R z5 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z5 Replace; and an R 20z5 Selected from -C(O)R 12 and -N(H)C(O)R 12 ; wherein one of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace.

7. The compound according to one of claims 1-2, or a pharmaceutically acceptable salt or solvate thereof, wherein one R z6 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z6 Replace; and an R 20z6 Selected from -C(O)R 12 and -N(H)C(O)R 12 ; wherein one of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace.

8. The compound according to one of claims 1-2, or a pharmaceutically acceptable salt or solvate thereof, wherein one R z4 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z4 Replace; one of the R 20z4 Selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z substituted; and said R 20z One of -C(O)R 12 and -N(H)C(O)R 12 ; wherein one of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace.

9. The compound according to one of claims 1-2, or a pharmaceutically acceptable salt or solvate thereof, wherein one R z5 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z5 Replace; one of the R 20z5 Selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z substituted; and said R 20z One of -C(O)R 12 and -N(H)C(O)R 12 ; wherein one of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace.

10. The compound according to one of claims 1-2, or a pharmaceutically acceptable salt or solvate thereof, wherein one R z6 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z6 Replace; one of the R 20z6 Selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is replaced by one, two or three R 20z substituted; and said R 20z One of -C(O)R 12 and -N(H)C(O)R 12 ; wherein one of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl; wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace.

11. The compound according to one of claims 1-2, or a pharmaceutically acceptable salt or solvate thereof, wherein two or more R z4 , R z5 or R z6 Connect to form one, two or three R 20z substituted ring; and said R 20z One of -C(O)R 12 and -N(H)C(O)R 12 ; wherein one of the R 12 Selected from C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl; wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace.

12. A compound of formula (A), or a pharmaceutically acceptable salt or solvate thereof: in: W 1 is N(R 1 ) or N; R 1 Selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20a replace; W 2 is C(R 2 )、N(R 2 )、C(R 2 )2, C(O), S(O), S(O)2 or N; Each R 2 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12a 、-SR 12a 、-N(R 12a )(R 13 ),-N=(R 15 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )-、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20b replace; W 3 is C(R 3 )、N(R 3 )、C(R 3 )2, C(O), S(O), S(O)2 or N; Each R 3 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20c replace; W 4 is C(R 4 ), C or N; R 4 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20d replace; W 5 is C(R 5 ), C or N; R 5 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20e replace; W 6 is C(R 6 )、N(R 6 )、C(R 6 )2, C(O), S(O), S(O)2 or N; Each R 6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20f replace; W 7 is C(R 7a ), C or N; R 7a Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20g replace; R 7 Yes-L 7 -R 17 ; L 7 is a bond, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 2-4 membered heteroalkylene linker, -O-, -N(R 7d )-, -C(O)-, -S-, -S(O)2-, -S(O)-, -P(O)R 7d -、CR 7c R 7c , -OCR 7c R 7c -、-N(R 7d )CR 7c R 7c -、-C(O)CR 7c R 7c -、-SCR 7c R 7c -、-S(O)2CR 7c R 7c -、-S(O)CR 7c R 7c -、-P(O)R 7d CR 7c R 7c -、-CR 7c R 7c CR 7c R 7c , -CR 7c R 7c O-、-CR 7c R 7c N(R 7d )-、-CR 7c R 7c C(O)-、-CR 7c R 7c S-、-CR 7c R 7c S(O)2-、-CR 7c R 7c S(O)-、-CR 7c R 7c P(O)R 7d -、-N(R 7d )C(O)-、-N(R 7d )S(O)2-、-N(R 7d )S(O)-、-N(R 7d )P(O)R 7d -、-C(O)N(R 7d )-、-S(O)2N(R 7d )-、-S(O)N(R 7d )-、-P(O)R 7d N(R 7d )-, -OC(O)-, -OS(O)2-, -OS(O)-, -OP(O)R 7d -, -C(O)O-, -S(O)2O-, -S(O)O- or -P(O)R 7d O-; wherein the C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 2-4 membered heteroalkylene linker is optionally substituted by one, two or three R 20g replace; Each R 7c are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace; Each R 7d are independently selected from hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20g replace; R 17 Selected from C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl, wherein C 3-10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 Aryl and 5-10 membered heteroaryl are optionally substituted by one or more R 20q Replace; or L 7 is a key, and R 7a and R 17 Together with the carbon to which they are attached, they form C 3-10 Cycloalkyl or 3-10 membered heterocycloalkyl, wherein the C 3-10 Cycloalkyl and 3-10 membered heterocycloalkyl are optionally substituted with one or more R 20q replace; W 8 is C(R 8 )、N(R 8 )、C(R 8 )2, C(O), S(O), S(O)2 or N; Each R 8 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20h replace; W 9 is C(R 9 ), C or N; R 9 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20i replace; W 10 is C(R 10 ), C or N; R 10 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20j replace; Each Z 1 Independently C(R z1 )、N(R z1 )、C(R z1 )2, C(O), S(O), S(O)2, O, S or N; z1n is 0, 1, 2, or 3; if z1n is 0, then Z 2 Direct bonding to W 5 ; Each R z1 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z1 replace; Each Z 9 Independently C(R z9 )、N(R z9 )、C(R z9 )2, C(O), S(O), S(O)2, O, S or N; z9n is 0, 1, 2, or 3; if z9n is 0, then Z 3 Direct bonding to W 4 ; Each R z9 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z9 replace; The sum of z1n and z9n is 2 or 3; Z 2 is C(R z2 ), C or N; R z2 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z2 replace; Z 3 is C(R z3 ), C or N; R z3 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 15 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 15 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z3 replace; Z 4 Yes key, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c or Z 4a Z 4b Z 4c Z 4d ; where Z 4a Direct Bonding to Z 2 ; and if Z 4 is a key, then Z 2 Direct Bonding to Z 5 ; Z 4a , Z 4b , Z 4c and Z 4d Independently C(R z4 )、N(R z4 )、C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S or N; The condition is: if z9n is 0 and Z 4 It's Z 4a Z 4b ; then (1) Z 4b is C(R z4 )、C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S or N, (2) Z 4b is N(R z4 ) and Z 4a is C(O), S(O) or S(O)2; (3) Z 4b is N(R z4 ) and Z 5 is C(O), S(O) or S(O)2; or (4) Z 4b is N(R z4 ) and Z 3 is C(R z3 ) or C; and Each R z4 Independently selected from -L z1 -L z2 -L z3 -R 12 , hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 alkenyl; Z 5 is C(R z5 ), N(R z5 ), C(R z5 )2, C(O), S(O), S(O)2, S(O)(NR z5 ), O, S or N; Each R z5 Independently selected from -L z1 -L z2 -L z3 -R 12 , hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 alkenyl; Z 6 is C(R z6 )、N(R z6 )、C(R z6 )2、C(O)、S(O)、S(O)2、S(O)(NR z6 )、O、S or N; Each R z6 Independently selected from -L z1 -L z2 -L z3 -R 12 , hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 alkenyl; And further wherein the compound optionally comprises one of the following: (1) Two R bonded to the same carbon atom z4 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; (2) Two or more R bonded to adjacent atoms z4 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; (3) Two R bonded to the same carbon atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; (4) One or two R bonded to an atom z4 and one or two R bonded to adjacent atoms z5 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; (5) One or two R bonded to an atom z4 and one or two R bonded to a second atom z5 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; (6) Two R bonded to the same carbon atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; (7) One or two R bonded to an atom z5 and one or two R bonded to adjacent atoms z6 Connect to form a single ring C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20z replace; or (8) One or two R bonded to an atom z4 and one or two R bonded to a second atom z6 Connect to form a single ring C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20z replace; Each R 12 are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20l replace; Each R 12a are independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c )2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c )2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c )2-C 6-10 Aryl, -C(R 12c )2-C 1-9 Heteroaryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12c )2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12c )2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12c )2-C 6-10 Aryl, -C(R 12c )2-C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20l replace; Each R 12c are independently selected from hydrogen and R 20lc ; Each R 13 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 haloalkyl; or R 12 and R 13 Together with the nitrogen to which they are attached, they form a 20m Substituted C 2-9 heterocycloalkyl ring; Each R 14 are independently selected from hydrogen, C 1-6 Alkyl and C 1-6 Haloalkyl; Each R 15 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl, wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20o replace; Each R 20z1 , R 20z2 , R 20z3 , R 20z4 , R 20z5 , R 20z6 and R 20z9 are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z replace; Each R 20z Independently selected from -L z3 -R 12 , halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20zz replace; Two R bonded to the same carbon atom 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl or monocyclic 3-7 membered heterocycloalkyl, wherein the monocyclic C 3-7 Cycloalkyl and monocyclic 3-7 membered heterocycloalkyl are optionally substituted by one, two or three R 20zz replace; or Two or more R bonded to two adjacent atoms 20z Optionally linked to form a monocyclic C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl or monocyclic 5-6 membered heteroaryl, wherein the C 3-7 Cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl and monocyclic 5-6 membered heteroaryl are optionally substituted by one, two or three R 20zz replace; L z1 Select from key, C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 3-10 Cycloalkylene, C 2-9 Heterocycloalkylene, C 6-10 Arylene and C 1-9 Heteroarylene; wherein C 1-6 Alkyl, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 3-10 Cycloalkylene, C 2-9 Heterocycloalkylene, C 6-10 Arylene and C 1-9 The heteroarylene group is optionally substituted by one or two R 30z replace; R 30z are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z replace; L z2 Select from key, C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 3-10 Cycloalkylene, C 2-9 Heterocycloalkylene, C 6-10 Arylene and C 1-9 Heteroarylene; wherein C 1-6 Alkyl, C 2-6 Alkenylene, C 2-6 Alkynylidene, C 3-10 Cycloalkylene, C 2-9 Heterocycloalkylene, C 6-10 Arylene and C 1-9 The heteroarylene group is optionally substituted by one or two R 31z replace; R 31z are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20zz replace; L z3 -R 12 Selected from: i.-C(O)R 12 or -N(H)C(O)R 12 ; wherein one of the R 12 is a 5-membered heteroaryl group containing two or more ring nitrogen atoms, wherein the 5-membered heteroaryl group is 12 The ring nitrogen atom is directly bonded to C(O) and wherein R 12 Optionally one or more R 20l Replacement; and ii.-C(O)R 12 or -N(H)C(O)R 12 ; wherein one of the R 12 is a 3-membered heterocycloalkyl group containing one or more ring nitrogen atoms, wherein R 12 Optionally one or more R 20l replace; R 20l are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O)2R 25 、-C(O)R 21 、-S(O)2R 25 、-S(O)2N(R 22 )(R 23 )、-OCH2C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O)2R 25 、-C(O)R 25 、-S(O)2R 25 、-S(O)2N(R 22 )(R 23 ) and -OC(O)R 25 ; Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20l , R 20lc , R 20m , R 20o , R 20q and R 20zz are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O)2R 25 、-C(O)R 21 、-S(O)2R 25 、-S(O)2N(R 22 )(R 23 )、-OCH2C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O)2R 25 、-C(O)R 25 、-S(O)2R 25 、-S(O)2N(R 22 )(R 23 ) and -OC(O)R 25 ; Each R 21 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; Each R 22 are independently selected from hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; Each R 23 are independently selected from hydrogen and C 1-6 alkyl; Each R 24 are independently selected from hydrogen and C 1-6 alkyl; Each R 25 Independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 heteroaryl; and represents a single or double bond such that all valences are satisfied.

13. The compound according to claim 12, or a pharmaceutically acceptable salt or solvate thereof, wherein: L z1 Select from key, C 1-6 Alkylene, C 3-10 Cycloalkylene and C 2-9 Heterocycloalkylene; wherein C 1-6 Alkylene, C 3-10 Cycloalkylene and C 2-9 The heterocycloalkylene group is optionally substituted by one or two R 30z replace; R 30z are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z replace; L z2 Select from key, C 1-6 Alkylene, C 3-10 Cycloalkylene and C 2-9 Heterocycloalkylene; wherein C 1-6 Alkylene, C 3-10 Cycloalkylene and C 2-9 The heterocycloalkylene group is optionally substituted by one or two R 31z replace; R 31z are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl, -OR 12 、-SR 12 、-N(R 12 )(R 13 )、-C(O)OR 12 、-OC(O)N(R 12 )(R 13 )、-N(R 14 )C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)OR 15 、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-C(O)C(O)N(R 12 )(R 13 )、-N(R 14 )C(O)R 12 、-S(O)2R 15 、-S(O)2N(R 12 )(R 13 )、-S(=O)(=NH)N(R 12 )(R 13 )、-CH2C(O)N(R 12 )(R 13 )、-CH2N(R 14 )C(O)R 15 、-CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20zz replace; L z3 -R 12 Selected from: i.-C(O)R 12 or -N(H)C(O)R 12 ; wherein one of the R 12 is a 5-membered heteroaryl group containing two or more ring nitrogen atoms, wherein the 5-membered heteroaryl group is 12 The ring nitrogen atom is directly bonded to C(O) and wherein R 12 Optionally one or more R 20l Replacement; and ii.-C(O)R 12 or -N(H)C(O)R 12 ; wherein one of the R 12 is a 3-membered heterocycloalkyl group containing one or more ring nitrogen atoms, wherein R 12 Optionally one or more R 20l replace; R 20l are independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl, C 1-9 Heteroaryl, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 21 、-N(R 24 )S(O)2R 25 、-C(O)R 21 、-S(O)2R 25 、-S(O)2N(R 22 )(R 23 )、-OCH2C(O)OR 22 , =NR 21 and -OC(O)R 25 ; Two R bonded to adjacent atoms 20q Optionally linked to form C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or C 1-9 Heteroaryl; wherein C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -CH2-C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH2-C 2-9 Heterocycloalkyl, C 6-10 Aryl, -CH2-C 6-10 Aryl, -CH2-C 1-9 Heteroaryl and C 1-9 The heteroaryl group is optionally substituted with one, two or three groups independently selected from halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 、-SR 21 、-N(R 22 )(R 23 )、-C(O)OR 22 、-C(O)N(R 22 )(R 23 )、-C(O)C(O)N(R 22 )(R 23 )、-OC(O)N(R 22 )(R 23 )、-N(R 24 )C(O)N(R 22 )(R 23 )、-N(R 24 )C(O)OR 25 、-N(R 24 )C(O)R 25 、-N(R 24 )S(O)2R 25 、-C(O)R 25 、-S(O)2R 25 、-S(O)2N(R 22 )(R 23 ) and -OC(O)R 25 .

14. A compound according to one of claims 12-13, or a pharmaceutically acceptable salt or solvate thereof, having the formula:

15. A compound according to one of claims 12-13, or a pharmaceutically acceptable salt or solvate thereof, having the formula:

16. A compound according to any one of claims 1 to 15, or a pharmaceutically acceptable salt or solvate thereof, wherein yes 17. A compound according to any one of claims 1 to 15, or a pharmaceutically acceptable salt or solvate thereof, wherein yes 18. A compound according to any one of claims 1 to 15, or a pharmaceutically acceptable salt or solvate thereof, wherein two R bonded to the same carbon atom z5 to form a monocyclic 4-membered heterocycloalkyl group, wherein the 4-membered heterocycloalkyl group is surrounded by one, two or three R 20z replace.

19. The compound according to claim 18, or a pharmaceutically acceptable salt or solvate thereof, wherein Selected from Wherein the one R shown in each of the above formulas is 20z Yes-C(O)R 12 or -N(H)C(O)R 12 .

20. The compound according to any one of claims 1 to 15, or a pharmaceutically acceptable salt or solvate thereof, wherein one or two R bonded to one atom z4 and one or two R bonded to adjacent atoms z5 to form a monocyclic 5-6 membered heteroaryl, wherein the monocyclic 5-6 membered heteroaryl is optionally substituted by one, two or three R 20z replace.

21. The compound according to claim 20, or a pharmaceutically acceptable salt or solvate thereof, wherein yes Wherein one R shown in the above formula 20z Yes-C(O)R 12 or -N(H)C(O)R 12 .

22. The compound according to one of claims 1-21, or a pharmaceutically acceptable salt or solvate thereof, wherein z1n is 1, 2 or 3, and z9n is 1, 2 or 3.

23. A compound according to any one of claims 1 to 22, or a pharmaceutically acceptable salt or solvate thereof, wherein W 1 It is N.

24. A compound according to any one of claims 1 to 23, or a pharmaceutically acceptable salt or solvate thereof, wherein W 2 is C(R 2 ).

25. A compound according to any one of claims 1 to 24, or a pharmaceutically acceptable salt or solvate thereof, wherein W 3 It is N.

26. A compound according to any one of claims 1 to 25, or a pharmaceutically acceptable salt or solvate thereof, wherein W 4 It is C.

27. A compound according to any one of claims 1 to 26, or a pharmaceutically acceptable salt or solvate thereof, wherein W 5 It is C.

28. A compound according to any one of claims 1 to 26, or a pharmaceutically acceptable salt or solvate thereof, wherein W 5 is C(R 5 ).

29. A compound according to any one of claims 1 to 28, or a pharmaceutically acceptable salt or solvate thereof, wherein W 6 is C(R 6 ).

30. The compound according to claim 29, or a pharmaceutically acceptable salt or solvate thereof, wherein R 6 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl and -OR 12 , where C 1-6 The alkyl group is optionally substituted by one, two or three R 20f replace.

31. The compound according to claim 29, or a pharmaceutically acceptable salt or solvate thereof, wherein R 6 It's a halogen.

32. A compound according to any one of claims 1 to 31, or a pharmaceutically acceptable salt or solvate thereof, wherein W 7 It is C.

33. A compound according to any one of claims 1 to 32, or a pharmaceutically acceptable salt or solvate thereof, wherein W 8 is C(R 8 ).

34. The compound according to claim 33, or a pharmaceutically acceptable salt or solvate thereof, wherein R 8 Selected from hydrogen, halogen, -CN, C 1-6 Alkyl and -OR 12 , where C 1-6 The alkyl group is optionally substituted by one, two or three R 20h replace.

35. The compound according to claim 33, or a pharmaceutically acceptable salt or solvate thereof, wherein R 8 It's a halogen.

36. A compound according to any one of claims 1 to 35, or a pharmaceutically acceptable salt or solvate thereof, wherein W 9 It is C.

37. A compound according to any one of claims 1 to 36, or a pharmaceutically acceptable salt or solvate thereof, wherein 10 It is C.

38. A compound according to any one of claims 1-22, or a pharmaceutically acceptable salt or solvate thereof, wherein Selected from 39. A compound according to any one of claims 1 to 38, or a pharmaceutically acceptable salt or solvate thereof, wherein L 7 is the key.

40. The compound according to claim 39, or a pharmaceutically acceptable salt or solvate thereof, wherein R 17 is selected from naphthyl and benzothienyl, each of which is optionally substituted by one, two or three R 20q replace.

41. The compound according to claim 39, or a pharmaceutically acceptable salt or solvate thereof, wherein R 17 Substituted with one, two or three substituents independently selected from halogen, -CN, -CH3, -C≡CH, -OH and -NH2.

42. A compound according to any one of claims 1-39, or a pharmaceutically acceptable salt or solvate thereof, wherein R 17 Selected from 43. A compound according to any one of claims 1-39, or a pharmaceutically acceptable salt or solvate thereof, wherein R 17 Selected from:

44. A compound according to any one of claims 1 to 43, or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 Independently is -OR 12a .

45. A compound according to any one of claims 1 to 43, or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 Independently selected from 46. ​​The compound according to claim 45, or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 Independently 47. A compound according to one of claims 1-46, or a pharmaceutically acceptable salt or solvate thereof, wherein Z 4 It's Z 4a .

48. A compound according to one of claims 1-46, or a pharmaceutically acceptable salt or solvate thereof, wherein Z 4 It's Z 4a Z 4b .

49. A compound according to any one of claims 1-48, or a pharmaceutically acceptable salt or solvate thereof, wherein each R z4 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-N(H)C(O)R 12 、-S(O)2R 15 and -S(O)2N(R 12 )(R 13 )-, where C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 Alkenyl.

50. A compound according to any one of claims 1-48, or a pharmaceutically acceptable salt or solvate thereof, wherein each R z4 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O)2R 15 and -S(O)2R 15 , where C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z4 or two R bonded to the same carbon z4 connected to form a 20z4 Substituted C 2-6 Alkenyl.

51. A compound according to any one of claims 1-50, or a pharmaceutically acceptable salt or solvate thereof, wherein each R z5 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-N(H)C(O)R 12 、-S(O)2R 15 and -S(O)2N(R 12 )(R 13 )-, where C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 Alkenyl.

52. A compound according to any one of claims 1-50, or a pharmaceutically acceptable salt or solvate thereof, wherein each R z5 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O)2R 15 and -S(O)2R 15 , where C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20z5 or two R bonded to the same carbon z5 connected to form a 20z5 Substituted C 2-6 Alkenyl.

53. A compound according to any one of claims 1-52, or a pharmaceutically acceptable salt or solvate thereof, wherein each R z6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-N(H)C(O)R 12 、-S(O)2R 15 and -S(O)2N(R 12 )(R 13 )-, where C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 Alkenyl.

54. A compound according to any one of claims 1-52, or a pharmaceutically acceptable salt or solvate thereof, wherein each R z6 are independently selected from hydrogen, halogen, -CN, C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O)2R 15 and -S(O)2R 15 , where C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20z6 or two R bonded to the same carbon z6 connected to form a 20z6 Substituted C 2-6 Alkenyl.

55. A compound according to any one of claims 1-54, or a pharmaceutically acceptable salt or solvate thereof, wherein each R 20z are independently selected from hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O)2R 15 、-C(O)R 12 、-S(O)R 15 、-OC(O)R 15 、-C(O)N(R 12 )(R 13 )、-N(H)C(O)R 12 、-S(O)2R 15 and -S(O)2N(R 12 )(R 13 )-, where C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is optionally substituted by one, two or three R 20zz or two R bonded to the same carbon 20z connected to form a 20zz Substituted C 2-6 Alkenyl.

56. A compound according to any one of claims 1-54, or a pharmaceutically acceptable salt or solvate thereof, wherein each R 20z are independently selected from hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 1-9 Heteroaryl, -OR 12 、-N(R 12 )(R 13 )、-N(R 14 )S(O)2R 15 and -S(O)2R 15 , where C 1-6 Alkyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl and C 1-9 The heteroaryl group is optionally substituted by one, two or three R 20zz or two R bonded to the same carbon 20z connected to form a 20zz Substituted C 2-6 Alkenyl.

57. A compound according to any one of claims 1 and 3-56, or a pharmaceutically acceptable salt or solvate thereof, wherein one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 or R 20z Independently selected from -C(O)R 12 and -N(H)C(O)R 12 ; and the one R 12 Selected from 58. A compound according to any one of claims 1 and 3-56, or a pharmaceutically acceptable salt or solvate thereof, wherein one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 or R 20z Independently selected from -C(O)R 12 and -N(H)C(O)R 12 ; and the one R 12 Selected from 59. A compound according to any one of claims 1 and 3-56, or a pharmaceutically acceptable salt or solvate thereof, wherein one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 or R 20z Independently selected from -C(O)R 12 and -N(H)C(O)R 12 ; and the one R 12 Selected from 60. A pharmaceutical composition comprising a compound according to any one of claims 1 to 59 or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

61. A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1-59, or a pharmaceutically acceptable salt or solvate thereof.

62. A method of treating cancer in a subject comprising a Ras mutant protein, the method comprising: The Ras mutant protein of the subject is modified by administering a compound to the subject, wherein the compound is characterized in that when contacting the Ras mutant protein, the Ras mutant protein is covalently modified at the residue corresponding to residue 12 of SEQ ID No: 1, so that the modified Ras mutant protein exhibits reduced Ras signaling output.

63. The method of any one of claims 61-62, wherein the cancer is a solid tumor.

64. The method of any one of claims 61-62, wherein the cancer is a hematological cancer.

65. A method of modulating the signaling output of a Ras protein, comprising contacting a Ras protein with an effective amount of a compound according to any one of claims 1 to 59, or a pharmaceutically acceptable salt or solvate thereof, thereby modulating the signaling output of the Ras protein.

66. The method of any one of claims 61-65, comprising administering an additional agent.

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