Heterocyclic compounds and uses thereof

Abstract

The present disclosure provides compounds and their pharma- ceutically acceptable salts, as well as methods of use thereof.The compounds and methods have a wide range of applications as therapeutic, diagnostic, and research tools.The subject compounds and methods are useful for reducing the signaling output of oncogenic proteins.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 319,253, filed March 11, 2022, U.S. Provisional Patent Application No. 63 / 319,256, filed March 11, 2022, U.S. Provisional Patent Application No. 63 / 322,630, filed March 22, 2022, U.S. Provisional Patent Application No. 63 / 322,631, filed March 22, 2022, U.S. Provisional Patent Application No. 63 / 415,955, filed October 13, 2022, and U.S. Provisional Patent Application No. 63 / 415,956, filed October 13, 2022, each of which is incorporated by reference in its entirety herein. [Background technology]

[0002] Cancer (e.g., tumors, neoplasms, metastases) is the second leading cause of death worldwide and is estimated to be responsible for approximately 10 million deaths annually. Many types of cancer harbor mutations in one or more proteins involved in various signaling pathways, leading to uncontrolled proliferation of cancer cells. In some cases, approximately 25–30% (%) of tumors are known to harbor Rat sarcoma (Ras) mutations. In particular, mutations in the gene for the Kirsten Ras oncogene (K-Ras) are one of the most frequent Ras mutations detected in human cancers, including lung adenocarcinoma (LUAD) and pancreatic ductal adenocarcinoma (PDAC).

[0003] Ras proteins have long been considered "undruggable" due to their high affinity for the substrate guanosine-5'-triphosphate (GTP) and the lack of target regions and smooth surface. The specific G12C Ras gene mutation has been identified as a druggable target for which a number of G12C-specific inhibitors have been developed. However, such therapeutics are still of limited use, as the G12C mutation in Ras shows a much lower prevalence compared to other known Ras mutations, including G12D and G12V. Summary of the Invention

[0004] In view of the above, there remains a significant need for new designs of therapeutic and diagnostic agents that can specifically target Ras, including wild-type Ras, mutants and / or associated proteins of Ras, and reduce Ras signaling output. Of particular interest are inhibitors for the treatment of Ras-related diseases (e.g., cancer), including pan-Ras inhibitors that can inhibit two or more Ras mutants and / or wild-type Ras, as well as mutant-selective inhibitors that target mutant Ras proteins such as Ras G12D, G12C, G12S, G13D, and / or G12V. Such compositions and methods are particularly useful for the treatment of various diseases, including but not limited to cancer and neoplastic conditions. The present disclosure addresses these needs and provides additional advantages that are applicable to the diagnosis, prognosis, and / or treatment of a variety of diseases.

[0005] In one embodiment, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, Z 1 , Z 2 , Z 3 , and Z 4 are N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, O, and C(O), Z 1 , Z 2 , Z 3 , and Z 4At least one of N(R 4 ), N(R 11d ), C(R 4 ), C(R 11d ), C(R 4 )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), or C(O), W 1 is C(R 1 ), C, or N; R 1 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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 ), -CH2 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, and C 2-6 Alkynyl is one, two, or three R 20a and optionally substituted with W 2 is N(R 2a ), N, C(R 2 ), C(R 2 )(R 2a)、 S(O) 2 or S(O), R 2 is 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 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 a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with R 2a is 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 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 a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with W 3 is N(R 3b ), N, C(R 3 ), C(R 3 )(R 3a)、 C(O), S(O) 2 or S(O), R 3 and R 3a is hydrogen, halogen, -CN, C 1-6Alkyl, 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, C2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with R 3b is 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 , C.H. 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 a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with W 4 is N or N(R 3c ) and R 3c is 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 2-6Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with W 5 is C(R 5 ), C, or N; R 5 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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, and C 2-6 Alkynyl is one, two, or three R 20d and optionally substituted with W 6 is N(R 6b ), N, C(R 6 ), C(R 6 )(R 6a)、 C(O), S(O), or S(O) 2 and R 6 and R 6a is 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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with R 6b is 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 ), in the formula, 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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with W 7 is N(R 7 ), C(R 7 ), or C(R 7 )(R 7a ) and R 7a and each R 7c is 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 a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7d is hydrogen, -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 , -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 a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7 -L 7 -R 17 and L 7 is a bond, -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)R7d -, -C(O)O-, -S(O) 2 O-, -S(O)O-, or -P(O)R 7d O-, R 17 is 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 a heteroaryl group consisting of one, two, or three R 20g and optionally substituted with W 8 is C(R 8 ), C(R 8 )(R 8a ), N, N(R 8b)、 C(O), S(O), or S(O) 2 and R 8 and R 8a is 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)R15 , -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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted with R 8b is 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)R15 , -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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted from W 9 is C(R 9 ), C, or N; W 10 is C(R 9 ), C, or N; Each R 9 is 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 2-9Heterocycloalkyl, 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 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20i and optionally substituted with R 4 -L 4 -R 4a and L 4 is a bond, -O-, -N(R 4d )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, -P(O)R 4d -, CR 4c R 4c , -OCR 4c R 4c -, -N(R 4d )CR 4c R 4c -, -C(O)CR 4c R 4c -,-SCR 4c R 4c -, -S(O) 2 CR 4c R 4c -,-S(O)CR 4c R 4c -, -P(O)R 4d CR 4c R 4c -, -CR 4c R4c CR 4c R 4c , -CR 4c R 4c O-, -CR 4c R 4c N(R 4d )-, -CR 4c R 4c C(O)-, -CR 4c R 4c S-, -CR 4c R 4c S(O) 2 -, -CR 4c R 4c S(O)-, -CR 4c R 4c P(O)R 4d -, -N(R 4d )C(O)-, -N(R 4d )S(O) 2 -, -N(R 4d )S(O)-, -N(R 4d )P(O)R 4d -, -C(O)N(R 4d )-, -S(O) 2 N(R 4d )-, -S(O)N(R 4d )-, -P(O)R 4d N(R 4d )-, -OC(O)-, -OS(O) 2 -, -OS(O)-, -OP(O)R 4d -, -C(O)O-, -S(O) 2 O-, -S(O)O-, or -P(O)R 4d O-, Each R4c is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14 , -OC(O)R 14a , -N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14a , and -N(R 14 )S(O) 2 R 14 are independently selected from, 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, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R 4d is hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14, and -OC(O)R 14a are independently selected from, 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, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R 4a is C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9heteroaryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is one, two, three, or four R 4b and optionally substituted with Each R4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one or more R 20j and optionally substituted with Each R 11c is hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20k and optionally substituted with Each R 11d is halogen, oxo, -CN, C 1-6Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20k and optionally substituted with Each R 12 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12b ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12b ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12b ) 2 -C 6-10 Aryl, -C(R 12b ) 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(R12b ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12b ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12b ) 2 -C 6-10 Aryl, -C(R 12b ) 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20l and optionally substituted with R 12a is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12b ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12b ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12b ) 2 -C 6-10 Aryl, -C(R 12b ) 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 12b ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12b ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12b ) 2 -C6-10 Aryl, -C(R 12b ) 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20l and optionally substituted with Each R 12b is hydrogen and R 20l are independently selected from Each R 13 is 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, can be one, two, or three R 20l C optionally substituted with 2-9 forming a heterocycloalkyl ring, Each R 14 is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 14a is C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 15 is 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 a heteroaryl group consisting of one, two, or three R 20m and optionally substituted with Each R 20a , R 20b, R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20k , R 20l , and R 20m is 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 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 2C(O)OR 22 , and -OC(O)R 25 are each independently selected from 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 is 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 25and optionally substituted with one, two, or three groups independently selected from Each R 21 , 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; Each R 22 , 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; Each R 23 H and C 1-6 alkyl, Each R 24 H and C 1-6 alkyl, Each R 25 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; [ka] indicates a single or double bond such that all valences are satisfied.

[0006] In another aspect, there is provided a compound of formula (II) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, Z 1 , Z 2 , and Z 3 are N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, O, and C(O); Z 4 is N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d)、 and O; In the formula, Z 1 , Z 2 , and Z 3 At least one of N(R 4 ), N(R 11d ), C(R 4 ), C(R 11d ), C(R 4 )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d)、 or C(O) or Z 4 is N(R 4 ), N(R 11d ), C(R 4 ), C(R 11d), C(R 4 )(R 11c)、 C(R 4 )(R 4 ), or C(R 11c )(R 11d) and W 1 is C(R 1 ), C, or N; R 1 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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, and C 2-6 Alkynyl is one, two, or three R 20a and optionally substituted with W 2 is N(R 2a ), N, C(R 2 ), C(R 2 )(R 2a)、 C(O), S(O) 2 or S(O), R 2 is 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 a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with R 2a is 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 a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with W 3 is N(R 3b ), N, C(R 3 ), C(R 3 )(R 3a)、 C(O), S(O) 2 or S(O), R 3 and R 3a is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9Heterocycloalkyl, 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 6-10Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with R 3b is 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 , C.H. 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 1-9Heteroaryl is a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with W 4 is N or N(R 3c ) and R 3c is 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, C6-10 Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with W 5 is C(R 5 ), C, or N; R 5 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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, and C 2-6 Alkynyl is one, two, or three R 20d and optionally substituted with W 6 is N(R 6b ), N, C(R 6 ), C(R 6 )(R 6a ), C(O), S(O), or S(O) 2 and Each R 6 and R 6a is 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) 2N(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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with R 6b is 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 )(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 ), in the formula, 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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with W 7 is N(R 7 ), C(R 7 ), or C(R 7 )(R 7a ) and R 7a and each R 7c is 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 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 a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7d is 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 a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7 -L 7 -R 17 and L 7 is a bond, -O-, -N(R 7d )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, -P(O)R 7d -, CR 7c R 7c , -OCR7c R 7c -、-N(R 7d )CR 7c R 7c -、-C(O)CR 7c R 7c -、-SCR 7c R 7c -,-ONLY) 2 CR 7c R 7c -、-S(O)CR 7c R 7c -,-PUT 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 ONLY) 2 -、-CR 7c R 7c S(O)-、-CR 7c R 7c PUT 7d -、-N(R 7d )C(O)-、-N(R 7d )ONLY) 2 -、-N(R 7d )S(O)-、-N(R 7d )PUT 7d -、-C(O)N(R 7d )-,-ONLY) 2 N(R 7d )-、-S(O)N(R 7d )-,-PUT 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-、または-P(O)R 7d O-であり、 R 17 is 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 a heteroaryl group consisting of one, two, or three R 20g and optionally substituted with W 8 is C(R 8 ), C(R 8 )(R 8a ), N, N(R 8b ), C(O), S(O), or S(O) 2 and R 8 and R 8a is 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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted with R 8b is 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(R12 )(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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted from W 9 is C(R 9 ), C, or N; W 10 is C(R 9 ), C, or N; Each R 9 is 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 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20i and optionally substituted with R 4 -L 4 -R 4a and L 4 is a bond, -O-, -N(R 4d )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, -P(O)R 4d -, CR 4c R 4c , -OCR 4c R 4c -, -N(R 4d )CR 4c R 4c -, -C(O)CR 4c R 4c -,-SCR 4c R 4c -, -S(O) 2 CR 4c R 4c -,-S(O)CR 4c R 4c -, -P(O)R 4d CR 4c R 4c -, -CR 4c R 4c CR 4c R 4c , -CR 4c R 4c O-, -CR 4c R4c N(R 4d )-, -CR 4c R 4c C(O)-, -CR 4c R 4c S-, -CR 4c R 4c S(O) 2 -, -CR 4c R 4c S(O)-, -CR 4c R 4c P(O)R 4d -, -N(R 4d )C(O)-, -N(R 4d )S(O) 2 -, -N(R 4d )S(O)-, -N(R 4d )P(O)R 4d -, -C(O)N(R 4d )-, -S(O) 2 N(R 4d )-, -S(O)N(R 4d )-, -P(O)R 4d N(R 4d )-, -OC(O)-, -OS(O) 2 -, -OS(O)-, -OP(O)R 4d -, -C(O)O-, -S(O) 2 O-, -S(O)O-, or -P(O)R 4d O-, Each R4c is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14 , -OC(O)R 14a , -N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14a , and -N(R 14 )S(O) 2 R 14 are independently selected from, 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, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14)(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R 4d is hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14 , and -OC(O)R 14a are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R 4a is 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 6-10Aryl, and C 1-9 Heteroaryl is one, two, three, or four R 4b and optionally substituted with Each R4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one or more R 20j and optionally substituted with Each R 11c is hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20k and optionally substituted with Each R 11d is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20k and optionally substituted with Each R 12 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12b ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12b ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12b ) 2 -C 6-10 Aryl, -C(R 12b ) 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 12b ) 2 -C 3-10 Cycloalkyl, C 2-9Heterocycloalkyl, -C(R 12b ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12b ) 2 -C 6-10 Aryl, -C(R 12b ) 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20l and optionally substituted with Each R 12b is hydrogen and R 20l are independently selected from Each R 13 is 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, can be one, two, or three R 20l C optionally substituted with 2-9 forming a heterocycloalkyl ring, Each R 14 is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 14a is C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 15 is 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, C6-10 Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20m and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20k , R 20l , and R 20m is 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 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 are each independently selected from 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 is halogen, oxo, -CN, 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 R25 , -S(O) 2 N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently selected from Each R 21 , 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; Each R 22 , 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; Each R 23 H and C 1-6 alkyl, Each R 24 H and C 1-6 alkyl, Each R 25 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; [ka] indicates a single or double bond such that all valences are satisfied.

[0007] In some embodiments, a compound of formula (II), (IIa), (IIb), (IIc), (IId), (IIe), or (IIf), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z 1 , Z 2 , Z 3 , and Z 4 At least one of N(R 4 ), N(R 11d ), C(R 4 ), C(R 11d ), C(R 4 )(R 11c ), C(R 4 )(R 4 ), or C(R 11c )(R 11d ).

[0008] In some embodiments, W 4 is N. In some embodiments, W 4 is N(R 3c ).

[0009] In some embodiments, W 1 is C. In some embodiments, W 1 is C(R 1 In some embodiments, W 1 is N.

[0010] In some embodiments, W 5 is C. In some embodiments, W 5 is C(R 5 In some embodiments, W 5 is N.

[0011] In some embodiments, W 2 is C(R 2 In some embodiments, W 2 is C(R 2 )(R 2a In some embodiments, W 2 is N. In some embodiments, W 2 is N(R 2a).

[0012] In some embodiments, W 3 is N. In some embodiments, W 3 is N(R 3b In some embodiments, W 3 is C(R 3 In some embodiments, W 3 is C(R 3 )(R 3a In some embodiments, W 3 is C(O).

[0013] In some embodiments, W 6 is C(R 6 In some embodiments, W 6 is C(R 6 )(R 6a In some embodiments, W 6 is N. In some embodiments, W 6 is N(R 6b In some embodiments, W 6 is C(O).

[0014] In some embodiments, W 7 is C(R 7 In some embodiments, W 7 is C(R 7 )(R 7a In some embodiments, W 7 is N(R 7 ).

[0015] In some embodiments, W 8 is C(R 8 In some embodiments, W 8 is C(R 8 )(R 8a In some embodiments, W 8 is N. In some embodiments, W 8 is N(R 8b In some embodiments, W8 is C(O).

[0016] In some embodiments, W 9 is C. In some embodiments, W 9 is N.

[0017] In some embodiments, W 10 is C. In some embodiments, W 10 is N.

[0018] In some embodiments, the compound of formula (I) has the structure of formula (Ia), or a pharma- ceutically acceptable salt or solvate thereof. [ka]

[0019] In some embodiments, the compound of formula (I) has the structure of formula (Ib), or a pharma- ceutically acceptable salt or solvate thereof. [ka]

[0020] In some embodiments, the compound of formula (I) has the structure of formula (Ic), or a pharma- ceutically acceptable salt or solvate thereof. [ka]

[0021] In some embodiments, the compound of formula (I) has the structure of formula (Id), or a pharma- ceutically acceptable salt or solvate thereof. [ka]

[0022] In some embodiments, the compound of formula (I) has the structure of formula (Ie), or a pharma- ceutically acceptable salt or solvate thereof. [ka]

[0023] In some embodiments, the compound of formula (I) has the structure of formula (If): or a pharma- ceutically acceptable salt or solvate thereof. [ka]

[0024] In some embodiments, R 2 is 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 12 , and -N(R 12 )(R 13 ), and 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 a heteroaryl group consisting of one, two, or three R 20b In some embodiments, R 2 -OR 12a , -SR 12 , -N(R 12 )(R 13 ), and one, two, or three R 20b C optionally substituted with 1-6 In some embodiments, R 2 teeth, [ka] [ka] is selected from.

[0025] In some embodiments, R 3 is 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 )-, C 1-6 Alkyl can be one, two, or three R 20c In some embodiments, R 3 is hydrogen, halogen, -CN, C 1-6 Alkyl, and -OR 12 are independently selected from, 1-6 Alkyl can be one, two, or three R 20c is optionally replaced by

[0026] In some embodiments, R 6 is 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 )-, C 1-6 Alkyl can be one, two, or three R 20eIn some embodiments, R 6 is hydrogen, halogen, -CN, C 1-6 Alkyl, and -OR 12 are independently selected from, 1-6 Alkyl can be one, two, or three R 20e is optionally replaced by

[0027] In some embodiments, R 17 1, 2, or 3 R 20g C optionally substituted with 3-10 In some embodiments, R 17 1, 2, or 3 R 20g C optionally substituted with 2-9 In some embodiments, R 17 1, 2, or 3 R 20g C optionally substituted with 6-10 In some embodiments, R 17 1, 2, or 3 R 20g C optionally substituted with 1-9 It is heteroaryl.

[0028] In some embodiments, L 7 is a bond, -O-, -N(R 7d )-, -C(O)-, or CR 7c R 7c In some embodiments, L 7 is a bond.

[0029] In some embodiments, R 17 teeth, [ka] [ka] is selected from.

[0030] In some embodiments, R 8is 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 Alkyl can be one, two, or three R 20h In some embodiments, R 8 is hydrogen, halogen, -CN, C 1-6 Alkyl, and -OR 12 where C 1-6 Alkyl can be one, two, or three R 20h is optionally replaced by

[0031] In some embodiments, Z 1 is O and Z 2 is C(R 11c )(R 11c ), and Z 3 is C(R 11c )(R 11c ), and Z 4 is N(R 4 In some embodiments, Z 1 is S and Z 2 is C(R 11c )(R 11c ), and Z 3 is C(R 11c )(R 11c ), and Z 4 is N(R 4 In some embodiments, Z 1 is N(R 11c ), and Z 2 is C(R 11c )(R 11c ), and Z 3 is C(R11c )(R 11c ), and Z 4 is N(R 4 In some embodiments, Z 1 is C(R 11c )(R 11c ), and Z 2 is C(R 11c )(R 11c ), and Z 3 is C(R 11c )(R 11c ), and Z 4 is N(R 4 In some embodiments, Z 1 is O and Z 2 is C(R 11c )(R 11c ), and Z 3 is C(O) and Z 4 is N(R 4 In some embodiments, Z 1 is O and Z 2 is C(R 11c )(R 11c ), and Z 3 is C(R 4 )(R 11c ), and Z 4 is N(R 11c In some embodiments, Z 1 is O and Z 2 is C(R 11c )(R 11c ), and Z 3 is C(R 11c )(R 11c ), and Z 4 is C(R 4 )(R 11c In some embodiments, Z 1 is O and Z 2 is C(R 11c )(R 11c ), and Z 3 is C(R 4 )(R 11c ), and Z 4 is C(R 11c )(R 11c In some embodiments, Z1 is O and Z 2 is C(R 11c )(R 11c ), and Z 3 is C(R 4 )(R 11c ), and Z 4 is O.

[0032] In some embodiments, each R 11c is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 heteroaryl, wherein C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20k In some embodiments, each R 11c is hydrogen and one, two, or three R 20k C optionally substituted with 1-6 In some embodiments, each R 11c is hydrogen.

[0033] In some embodiments, each R 4a 1, 2, 3 or 4 R 4b C optionally substituted with 3-10 In some embodiments, each R 4a can have one, two, three, or four R 4b C optionally substituted with 2-9 It is a heterocycloalkyl.

[0034] In some embodiments, each R 4a can have one, two, three, or four R 4b C optionally substituted with 6-10 In some embodiments, each R 4a can have one, two, three, or four R 4b C optionally substituted with 1-9 In some embodiments, each R 4a is C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl and one, two, three, or four R 4b C optionally substituted with 1-9 Heteroaryl is selected from the group consisting of aryl, hetero ...

[0035] In some embodiments, L 4 is a bond, -O-, -N(R 4d )-, -C(O)-, or CR 4c R 4c In some embodiments, L 4 is a bond.

[0036] In one embodiment, there is provided a compound of formula (A), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, Ring A is a 5- to 10-membered cycloalkyl or 5- to 10-membered heterocycloalkyl ring, and the 5- to 10-membered cycloalkyl and 5- to 10-membered heterocycloalkyl rings are each independently selected from one or more R 4 and one or more R 11c and optionally substituted with W 1 is C(R 1 ), C, or N; R 1 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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, and C 2-6 Alkynyl is one, two, or three R 20a and optionally substituted with W 2 is C(R 2 ) and; R 2 is 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(R12 )(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 a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with W 3 is N(R 3b ), N, C(R 3 ), C(R 3 )(R 3a ), or C(O), R 3 and R 3a is 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(R14 )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 a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with R 3b is 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 , C.H. 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 a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with W 5 is C(R 5 ), C, or N; R 5 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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, and C 2-6 Alkynyl is one, two, or three R 20d and optionally substituted with W 6 is N(R 6b ), N, C(R 6 ), C(R 6 )(R 6a ), C(O), S(O), or S(O) 2 and Each R 6 and R6a is 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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with R 6b is 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 ), in the formula, C 1-6 Alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with W 7 is N(R 7 ), C(R 7 ), or C(R 7 )(R 7a ) and R 7a and each R 7c is 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 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7d is 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 a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7 -L 7 -R 17 and L 7 is a bond, -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 CR7c 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-, R 17 teeth, [ka] is selected from Ring B is a 5- or 6-membered cycloalkyl ring, a 5- or 6-membered heterocycloalkyl ring, or a 5- or 6-membered heteroaryl ring, and the 5- or 6-membered cycloalkyl ring, the 5- or 6-membered heterocycloalkyl ring, and the 5- or 6-membered heteroaryl ring are optionally joined by one or more R 1c and optionally substituted with X 6 , X 7 , and X8 are independently C or C(R 1a ) and X 9 , X 10 , and X 11 are independently C(O), C(R 1a ), or C(R 1a )(R 1b ) and R 1a , R 1b , and R 1c are hydrogen, halogen, -CN, and 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, 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 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9 The heteroaryl is optionally substituted with 1, 2, or 3 R20g; W 8 is C(R 8 ), C(R 8 )(R 8a ), N, N(R 8b)、 C(O), S(O), or S(O) 2 and R 8 and R 8a is 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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted with R 8b is 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 , -SR12 , -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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted from W 9 is C(R 9 ), C, or N; W 10 is C(R 9 ), C, or N; Each R 9 is 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, -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 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20i and optionally substituted with R 4 -L 4 -R 4a and Each L 4 is a bond, --O-, -N(R 4d )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, -P(O)R 4d -, CR 4c R 4c , -OCR 4c R 4c -, -N(R 4d )CR 4c R 4c -, -C(O)CR 4c R 4c -,-SCR 4c R 4c -, -S(O) 2 CR 4c R 4c -,-S(O)CR4c R 4c -, -P(O)R 4d CR 4c R 4c -, -CR 4c R 4c CR 4c R 4c , -CR 4c R 4c O-, -CR 4c R 4c N(R 4d )-, -CR 4c R 4c C(O)-, -CR 4c R 4c S-, -CR 4c R 4c S(O) 2 -, -CR 4c R 4c S(O)-, -CR 4c R 4c P(O)R 4d -, -N(R 4d )C(O)-, -N(R 4d )S(O) 2 -, -N(R 4d )S(O)-, -N(R 4d )P(O)R 4d -, -C(O)N(R 4d )-, -S(O) 2 N(R 4d )-, -S(O)N(R 4d )-, -P(O)R 4d N(R 4d )-, -OC(O)-, -OS(O) 2 -, -OS(O)-, -OP(O)R 4d -, -C(O)O-, -S(O) 2 O-, -S(O)O-, and -P(O)R 4d O-, Each R4c is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14 , -OC(O)R 14a , -N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14a , and -N(R 14 )S(O) 2 R 14 are independently selected from, 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, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R 4d is hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14 , and -OC(O)R 14a are independently selected from, 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, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R4a is C 2-9 heterocycloalkyl, wherein C 2-9 Heterocycloalkyl can have one, two, three, or four R 4b and optionally substituted with Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ) and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl is a heteroaryl group consisting of one or more R 20j and optionally substituted with Each R 11c is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-12 Aryl, -CH 2 -C 6-12 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-12 Aryl, -CH 2 -C 6-12 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20k and optionally substituted with Each R 12 is 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 a heteroaryl group consisting of one, two, or three R 20l and optionally substituted with Each R 12c is hydrogen and R 20l are independently selected from Each R 13 is 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, can be one, two, or three R 20l C optionally substituted with 2-9 forming a heterocycloalkyl ring, Each R 14 is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 14a is C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 15 is 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 a heteroaryl group consisting of one, two, or three R 20m and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20k , R 20l , and R 20m is 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 -C6-10 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 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 are each independently selected from 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 is halogen, oxo, -CN, C 1-6 Haloalkyl, C1-6 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 and optionally substituted with one, two, or three groups independently selected from Each R 21 , 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; Each R 22 , 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 C1-9 heteroaryl; Each R 23 H and C 1-6 alkyl, Each R 24 H and C 1-6 alkyl, Each R 25 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; [ka] indicates a single or double bond such that all valences are satisfied.

[0037] In one embodiment, there is provided a compound of formula (B): or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, Ring A is a 5- to 10-membered cycloalkyl or 5- to 10-membered heterocycloalkyl ring, and the 5- to 10-membered cycloalkyl and 5- to 10-membered heterocycloalkyl rings are each independently selected from one or more R 4 and optionally substituted with one or more R 11c and optionally substituted with W 1 is C(R 1 ), C, or N; R 1 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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, and C 2-6 Alkynyl is one, two, or three R 20a and optionally substituted with W 2 is C(R 2 ) and; R 2 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10Cycloalkyl, C 2-9 Heterocycloalkyl, 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, and C 1-9Heteroaryl is a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with W 3 is N(R 3b ), N, C(R 3 ), C(R 3 )(R 3a ), or C(O), R 3 and R 3a is 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 a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with R 3b is 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(R14 )C(O)R 15 , C.H. 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 a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with W 5 is C(R 5 ), C, or N; R 5 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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, and C 2-6 Alkynyl is one, two, or three R 20d and optionally substituted with W 6 is N(R 6b ), N, C(R 6 ), C(R 6 )(R 6a)、 C(O), S(O), or S(O) 2 and Each R 6 and R 6a is 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(R14 )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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with R 6b is 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 ), in the formula, 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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with W 7 is N(R 7 ), C(R 7 ), or C(R 7 )(R 7a ) and R 7a and each R 7c is 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, C6-10 Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7d is 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 C1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7 -L 7 -R 17 and L 7 is a bond, -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-, R 17 teeth, [ka] is selected from Ring B is a 5- or 6-membered cycloalkyl ring, a 5- or 6-membered heterocycloalkyl ring, a 5- or 6-membered heteroaryl ring, or a 6-membered aryl ring, and the 5- or 6-membered cycloalkyl ring, the 5- or 6-membered heterocycloalkyl ring, the 5- or 6-membered heteroaryl ring, and the 6-membered aryl ring are optionally joined by one or more R 1c and optionally substituted with X 6 , X 7 , and X 8 are independently C or C(R 1a ) and X 9 , X 10 , and X 11 are independently C(O), C(R 1a)、 or C(R 1a )(R 1b ) and R 1a , R 1b , and R 1c are hydrogen, halogen, -CN, and 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, 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 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, C 1-9The heteroaryl is optionally substituted with 1, 2, or 3 R20g; W 8 is C(R 8 ), C(R 8 )(R 8a ), N, N(R 8b)、 C(O), S(O), or S(O) 2 and R 8 and R 8a is 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 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20h and optionally substituted with R 8b is 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 ), -CH2 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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted from W 9 is C(R 9 ), C, or N; W 10 is C(R 9 ), C, or N; Each R 9 is 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 -C2-9 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20i and optionally substituted with R 4 -L 4 -R 4a and Each L 4 is a bond, --O-, -N(R 4d )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, -P(O)R 4d -, CR 4c R 4c , -OCR 4c R 4c -, -N(R 4d )CR 4c R 4c -, -C(O)CR 4c R 4c -,-SCR 4c R 4c -, -S(O) 2 CR 4c R 4c -,-S(O)CR 4c R 4c -, -P(O)R 4d CR 4c R 4c -, -CR 4c R 4c CR 4c R 4c , -CR 4c R 4c O-, -CR 4c R 4c N(R 4d )-, -CR 4c R 4c C(O)-, -CR 4c R 4c S-, -CR 4c R 4c S(O) 2 -, -CR 4c R 4c S(O)-, -CR 4c R 4cP(O)R 4d -, -N(R 4d )C(O)-, -N(R 4d )S(O) 2 -, -N(R 4d )S(O)-, -N(R 4d )P(O)R 4d -, -C(O)N(R 4d )-, -S(O) 2 N(R 4d )-, -S(O)N(R 4d )-, -P(O)R 4d N(R 4d )-, -OC(O)-, -OS(O) 2 -, -OS(O)-, -OP(O)R 4d -, -C(O)O-, -S(O) 2 O-, -S(O)O-, and -P(O)R 4d O-, Each R4c is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14, -OC(O)R 14a , -N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14a , and -N(R 14 )S(O) 2 R 14 are independently selected from, 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, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O)2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R 4d is hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14 , and -OC(O)R 14a are independently selected from, 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, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R 4a is 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 one, two, three, or four R 4b and optionally substituted with Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11Heterocycloalkyl, 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ) and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C2-11 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl is a heteroaryl group consisting of one or more R 20j and optionally substituted with Each R 11c is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-12 Aryl, -CH 2 -C 6-12 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-12 Aryl, -CH 2 -C 6-12 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20k and optionally substituted with Each R 12 is 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 a heteroaryl group consisting of one, two, or three R 20l and optionally substituted with Each R 12c is hydrogen and R 20l are independently selected from Each R 13 is 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, can be one, two, or three R 20l C optionally substituted with 2-9 forming a heterocycloalkyl ring, Each R 14 is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 14a is C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 15 is 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, 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 a heteroaryl group consisting of one, two, or three R 20m and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20k , R 20l , and R 20m is 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(R22 )(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 are each independently selected from 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 is halogen, oxo, -CN, 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(R24 )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 and optionally substituted with one, two, or three groups independently selected from Each R 21 , 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; Each R 22 , 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; Each R 23 H and C 1-6 alkyl, Each R 24 H and C 1-6 alkyl, Each R 25 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; [ka] indicates a single or double bond such that all valences are satisfied.

[0038] In one embodiment, there is provided a compound of formula (C), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, Ring A is a 5- to 10-membered cycloalkyl or 5- to 10-membered heterocycloalkyl ring, and the 5- to 10-membered cycloalkyl and 5- to 10-membered heterocycloalkyl rings are each independently selected from the group consisting of at least one R 4 and the 5- to 10-membered cycloalkyl and 5- to 10-membered heterocycloalkyl rings are substituted with one or more R 11c and optionally substituted with W 1 is C(R 1 ), C, or N; R 1 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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)R15 , -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, and C 2-6 Alkynyl is one, two, or three R 20a and optionally substituted with W 2 is C(R 2 ) and; R 2 is 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 a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with W 3 is N(R 3b ), N, C(R 3 ), C(R 3 )(R 3a ), or C(O), R 3 and R 3ais 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 1-6Alkyl, 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 a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with R 3b is 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 , C.H. 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, C2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with W 5 is C(R 5 ), C, or N; R 5 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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 , -CH2 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, and C 2-6 Alkynyl is one, two, or three R 20d and optionally substituted with W 6 is N(R 6b ), N, C(R 6 ), C(R 6 )(R 6a)、 C(O), S(O), or S(O) 2 and Each R 6 and R 6a is 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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with R 6b is 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 ), in the formula, 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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with W 7 is N(R 7 ), C(R 7 ), or C(R 7 )(R 7a ) and R 7a and each R 7c is 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 a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7d is hydrogen, -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 , -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 a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7 -L 7 -R 17 and L 7 is a bond, -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)R7d -, -C(O)O-, -S(O) 2 O-, -S(O)O-, or -P(O)R 7d O-, R 17 is C 2-9 Heterocycloalkyl and C 1-9 heteroaryl; C 2-9 Heterocycloalkyl and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20g and optionally substituted with W 8 is C(R 8 ), C(R 8 )(R 8a ), N, N(R 8b)、 C(O), S(O), or S(O) 2 and R 8 and R 8a is 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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted with R 8b is 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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted from W 9 is C(R 9 ), C, or N; W 10 is C(R 9 ), C, or N; Each R 9 is 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 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20i and optionally substituted with R 4 -L 4 -R 4a and L 4 is a bond, -O-, -N(R 4d )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, -P(O)R 4d -, CR 4c R 4c , -OCR 4c R 4c -, -N(R 4d )CR 4c R 4c -, -C(O)CR 4c R 4c -,-SCR 4c R 4c -, -S(O) 2 CR 4c R 4c -,-S(O)CR 4c R 4c -, -P(O)R 4d CR 4c R 4c -, -CR 4c R 4c CR 4c R 4c , -CR 4c R 4c O-, -CR 4c R4c N(R 4d )-, -CR 4c R 4c C(O)-, -CR 4c R 4c S-, -CR 4c R 4c S(O) 2 -, -CR 4c R 4c S(O)-, -CR 4c R 4c P(O)R 4d -, -N(R 4d )C(O)-, -N(R 4d )S(O) 2 -, -N(R 4d )S(O)-, -N(R 4d )P(O)R 4d -, -C(O)N(R 4d )-, -S(O) 2 N(R 4d )-, -S(O)N(R 4d )-, -P(O)R 4d N(R 4d )-, -OC(O)-, -OS(O) 2 -, -OS(O)-, -OP(O)R 4d -, -C(O)O-, -S(O) 2 O-, -S(O)O-, or -P(O)R 4d O-, Each R4c is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14 , -OC(O)R 14a , -N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14a , and -N(R 14 )S(O) 2 R 14 are independently selected from, 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, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14)(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R 4d is hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14 , and -OC(O)R 14a are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from R4a is C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, and C 6-10 aryl, wherein C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, and C 6-10 The aryl is optionally substituted with one, two, three, or four R; Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13) and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl is a heteroaryl group consisting of one or more R 20j and optionally substituted with Each R 11c is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-12 Aryl, -CH 2 -C 6-12 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-12 Aryl, -CH 2 -C 6-12 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20k and optionally substituted with Each R 12 is 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 a heteroaryl group consisting of one, two, or three R 20l and optionally substituted with Each R 12c is hydrogen and R 20l are independently selected from Each R 13 is 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, can be one, two, or three R 20l C optionally substituted with 2-9 forming a heterocycloalkyl ring, Each R 14 is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 14a is C1-6 Alkyl, and C 1-6 haloalkyl; Each R 15 is 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 a heteroaryl group consisting of one, two, or three R 20m and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20k , R 20l , and R 20m is 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(R22 )(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 are each independently selected from 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 is halogen, oxo, -CN, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR22 , -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 and optionally substituted with one, two, or three groups independently selected from Each R 21 , 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; Each R 22 , 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; Each R 23 H and C 1-6 alkyl, Each R 24H and C 1-6 alkyl, Each R 25 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; [ka] indicates a single or double bond such that all valences are satisfied.

[0039] In some embodiments, the compound of formula (A), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (A-1): [ka] During the ceremony, Z 1 , Z 3 , and Z 5 are N(R 4 ), N(R 11c ), N(H), N, C(R 4 ), C(R 11c ), C(H), C(R 4 )(H), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(H), CH 2 , S, O, and C(O); Z 2 and Z 4 are bonds, N(R 4 ), N(R 11c ), N(H), N, C(R 4 ), C(R 11c ), C(H), C(R 4 )(H), C(R 4)(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(H), CH 2 , S, O, and C(O); In the formula, Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 At least one of N(R 4 ), C(R 4 ), C(R 4 )(H), C(R 4 )(R 11c)、 or C(R 4 )(R 4 ).

[0040] In some embodiments, the compound of formula (B), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (B-1): [ka] During the ceremony, Z 1 , Z 3 , and Z 5 are N(R 4 ), N(R 11c ), N(H), N, C(R 4 ), C(R 11c ), C(H), C(R 4 )(H), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(H), CH 2 , S, O, and C(O); Z 2 and Z 4 are bonds, N(R 4 ), N(R 11c ), N(H), N, C(R 4 ), C(R11c ), C(H), C(R 4 )(H), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(H), CH 2 , S, O, and C(O).

[0041] In some embodiments, the compound of formula (C), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (C-1): [ka] During the ceremony, Z 1 , Z 3 , and Z 5 are N(R 4 ), N(R 11c ), N(H), N, C(R 4 ), C(R 11c ), C(H), C(R 4 )(H), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(H), CH 2 , S, O, and C(O); Z 2 and Z 4 are bonds, N(R 4 ), N(R 11c ), N(H), N, C(R 4 ), C(R 11c ), C(H), C(R 4 )(H), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(H), CH 2, S, O, and C(O); In the formula, Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 At least one of N(R 4 ), C(R 4 ), C(R 4 )(H), C(R 4 )(R 11c)、 or C(R 4 )(R 4 ).

[0042] In some embodiments, W 1 is C. In some embodiments, W 1 is C(R 1 In some embodiments, W 1 is N. In some embodiments, W 5 is C. In some embodiments, W 5 is C(R 5 In some embodiments, W 5 is N. In some embodiments, W 2 is C(R 2 In some embodiments, W 2 is C(R 2 )(R 2a In some embodiments, W 2 is N. In some embodiments, W 2 is N(R 2a In some embodiments, W 3 is N. In some embodiments, W 3 is N(R 3b In some embodiments, W 3 is C(R 3 In some embodiments, W 3 is C(R 3 )(R 3a In some embodiments, W 3 is C(O). In some embodiments, W 6 is C(R 6In some embodiments, W 6 is C(R 6 )(R 6a In some embodiments, W 6 is N. In some embodiments, W 6 is N(R 6b In some embodiments, W 6 is C(O). In some embodiments, W 7 is C(R 7 In some embodiments, W 7 is C(R 7 )(R 7a In some embodiments, W 7 is N(R 7 In some embodiments, W 8 is C(R 8 In some embodiments, W 8 is C(R 8 )(R 8a In some embodiments, W 8 is N. In some embodiments, W 8 is N(R 8b In some embodiments, W 8 is C(O). In some embodiments, W 9 is C. In some embodiments, W 9 is N. In some embodiments, W 10 is C. In some embodiments, W 10 is N.

[0043] In some embodiments, the compound of formula (A-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (A-1a): [ka]

[0044] In some embodiments, the compound of formula (A-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (A-1b): [ka]

[0045] In some embodiments, the compound of formula (A-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (A-1c): [ka]

[0046] In some embodiments, the compound of formula (A-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (A-1d): [ka]

[0047] In some embodiments, the compound of formula (A-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (A-1e): [ka]

[0048] In some embodiments, the compound of formula (A-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (A-1f): [ka]

[0049] In some embodiments of a compound of Formula (A), (A-1), (A-1a), (A-1b), (A-1c), (A-1d), (A-1e), or (A-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 teeth, [ka] It is.

[0050] In some embodiments of a compound of Formula (A), (A-1), (A-1a), (A-1b), (A-1c), (A-1d), (A-1e), or (A-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 teeth, [ka] It is.

[0051] In some embodiments of a compound of Formula (A), (A-1), (A-1a), (A-1b), (A-1c), (A-1d), (A-1e), or (A-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 teeth, [ka] It is.

[0052] In some embodiments of a compound of Formula (A), (A-1), (A-1a), (A-1b), (A-1c), (A-1d), (A-1e), or (A-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 teeth, [ka] It is.

[0053] In some embodiments of a compound of Formula (A), (A-1), (A-1a), (A-1b), (A-1c), (A-1d), (A-1e), or (A-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 1a are hydrogen, halogen, and C, respectively. 1-6 Alkyl, and -OR 12 are independently selected from C 1-6 Alkyl can be one, two, or three R 20g is optionally replaced by

[0054] In some embodiments of the compound of Formula (A), (A-1), (A-1a), (A-1b), (A-1c), (A-1d), (A-1e), or (A-1f), or a pharma- ceutically acceptable salt or solvate thereof, ring B is selected from the group consisting of one or more R 1c is a 5- or 6-membered heteroaryl ring optionally substituted with

[0055] In some embodiments of a compound of Formula (A), (A-1), (A-1a), (A-1b), (A-1c), (A-1d), (A-1e), or (A-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 teeth, [ka] [ka] is selected from.

[0056] In some embodiments, the compound of formula (B-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (B-1a): [ka]

[0057] In some embodiments, the compound of formula (B-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (B-1b): [ka]

[0058] In some embodiments, the compound of formula (B-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (B-1c): [ka]

[0059] In some embodiments, the compound of formula (B-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (B-1d): [ka]

[0060] In some embodiments, the compound of formula (B-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (B-1e): [ka]

[0061] In some embodiments, the compound of formula (B-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (B-1f): [ka]

[0062] In some embodiments of a compound of Formula (B), (B-1), (B-1a), (B-1b), (B-1c), (B-1d), (B-1e), or (B-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 teeth, [ka] It is.

[0063] In some embodiments of a compound of Formula (B), (B-1), (B-1a), (B-1b), (B-1c), (B-1d), (B-1e), or (B-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 teeth, [ka] It is.

[0064] In some embodiments of a compound of Formula (B), (B-1), (B-1a), (B-1b), (B-1c), (B-1d), (B-1e), or (B-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 teeth, [ka] It is.

[0065] In some embodiments of a compound of Formula (B), (B-1), (B-1a), (B-1b), (B-1c), (B-1d), (B-1e), or (B-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 teeth, [ka] It is.

[0066] In some embodiments of a compound of Formula (B), (B-1), (B-1a), (B-1b), (B-1c), (B-1d), (B-1e), or (B-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 1a are hydrogen, halogen, and C, respectively. 1-6 Alkyl, and -OR 12 are independently selected from C 1-6 Alkyl can be one, two, or three R 20g is optionally replaced by

[0067] In some embodiments of a compound of Formula (B), (B-1), (B-1a), (B-1b), (B-1c), (B-1d), (B-1e), or (B-1f), or a pharma- ceutically acceptable salt or solvate thereof, ring B is selected from the group consisting of one or more R 1c In some embodiments of a compound of Formula (B), (B-1), (B-1a), (B-1b), (B-1c), (B-1d), (B-1e), or (B-1f), or a pharma- ceutically acceptable salt or solvate thereof, ring B is substituted with one or more R 1cis a 6-membered aryl ring optionally substituted with

[0068] In some embodiments of a compound of Formula (B), (B-1), (B-1a), (B-1b), (B-1c), (B-1d), (B-1e), or (B-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 teeth, [ka] [ka] is selected from.

[0069] In some embodiments, the compound of formula (C-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (C-1a): [ka]

[0070] In some embodiments, the compound of formula (C-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (C-1b): [ka]

[0071] In some embodiments, the compound of formula (C-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (C-1c): [ka]

[0072] In some embodiments, the compound of formula (C-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (C-1d): [ka]

[0073] In some embodiments, the compound of formula (C-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (C-1e): [ka]

[0074] In some embodiments, the compound of formula (C-1), or a pharma- ceutically acceptable salt or solvate thereof, has the structure of formula (C-1f): [ka]

[0075] In some embodiments of a compound of Formula (C), (C-1), (C-1a), (C-1b), (C-1c), (C-1d), (C-1e), or (C-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 1, 2, or 3 R 20g C optionally substituted with 2-9 In some embodiments of a compound of Formula (C), (C-1), (C-1a), (C-1b), (C-1c), (C-1d), (C-1e), or (C-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 1, 2, or 3 R 20g C optionally substituted with 1-9 It is heteroaryl.

[0076] In some embodiments of a compound of Formula (C), (C-1), (C-1a), (C-1b), (C-1c), (C-1d), (C-1e), or (C-1f), or a pharma- ceutically acceptable salt or solvate thereof, R 17 teeth, [ka] is selected from.

[0077] In some embodiments, L7 is a bond, -O-, -N(R 7d )-, -C(O)-, or CR 7c R 7c In some embodiments, L 7 is a bond.

[0078] In some embodiments, R 2 is 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 , and -N(H)(R 12 ), and 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 a heteroaryl group consisting of one, two, or three R 20b is optionally replaced by

[0079] In some embodiments, R 2 -OR 12 , -SR 12 , -N(H)(R 12 ), and one, two, or three R 20b C optionally substituted with 1-6 is selected from alkyl.

[0080] In some embodiments, R 2 teeth, [ka] [ka] is selected from.

[0081] In some embodiments, R 3 is 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 )-, C 1-6 Alkyl can be one, two, or three R 20c In some embodiments, R 3 is hydrogen, halogen, -CN, C 1-6 Alkyl, and -OR 12 are independently selected from, 1-6 Alkyl can be one, two, or three R 20c is optionally replaced by

[0082] In some embodiments, R 6 is 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 )-, C 1-6 Alkyl can be one, two, or three R 20e In some embodiments, R 6 is hydrogen, halogen, -CN, C 1-6 Alkyl, and -OR12 are independently selected from, 1-6 Alkyl can be one, two, or three R 20e is optionally replaced by

[0083] In some embodiments, R 8 is 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 Alkyl can be one, two, or three R 20h In some embodiments, R 8 is hydrogen, halogen, -CN, C 1-6 Alkyl, and -OR 12 where C 1-6 Alkyl can be one, two, or three R 20h is optionally replaced by

[0084] In some embodiments, Z 1 is O and Z 2 is CH 2 and Z 3 is CH 2 and Z 4 is CH 2 and Z 5 is N(R 4 In some embodiments, Z 1 is S and Z 2 is CH 2 and Z 3 is CH 2 and Z 4 is CH 2 and Z5 is N(R 4 In some embodiments, Z 1 is N(H) and Z 2 is CH 2 and Z 3 is CH 2 and Z 4 is CH 2 and Z 5 is N(R 4 In some embodiments, Z 1 CH 2 and Z 2 CH 2 and Z 3 CH 2 and Z 4 CH 2 and Z 5 is N(R 4 In some embodiments, Z 1 is O and Z 2 CH 2 and Z 3 CH 2 and Z 4 is C(R 4 )(H), and Z 5 is O. In some embodiments, Z 1 is O and Z 2 CH 2 and Z 3 is C(R 4 )(H), and Z 4 CH 2 and Z 5 is O. In some embodiments, Z 1 is O and Z 2 is C(R 4 )(H), and Z 3 CH 2 and Z 4 CH 2 and Z 5 is O. In some embodiments, Z 1 is O and Z 2 CH 2 and Z 3 CH 2 and Z 4 CH 2and Z 5 is C(R 4 )(H). In some embodiments, Z 1 is O and Z 2 is CH 2 and Z 3 is CH 2 and Z 4 is C(R 4 )(H), and Z 5 is CH 2 In some embodiments, Z 1 is O and Z 2 is CH 2 and Z 3 is C(R 4 )(H), and Z 4 is CH 2 and Z 5 is CH 2 In some embodiments, Z 1 is O and Z 2 is C(R 4 )(H), and Z 3 is CH 2 and Z 4 is CH 2 and Z 5 is CH 2 In some embodiments, Z 1 is O and Z 2 is a bond, and Z 3 CH 2 and Z 4 is a bond, and Z 5 is C(R 4 )(H). In some embodiments, Z 1 is O and Z 2 is a bond, and Z 3 is C(R 4 )(H), and Z 4 is a bond, and Z 5 CH 2 In some embodiments, Z 1 is N(H) and Z 2 is a bond, and Z 3 CH 2 and Z 4 is a bond, and Z 5 is C(R4 )(H). In some embodiments, Z 1 is N(H) and Z 2 is a bond, and Z 3 is C(R 4 )(H), and Z 4 is a bond, and Z 5 is CH 2 In some embodiments, Z 1 is N(R 11c ), and Z 2 is a bond, and Z 3 is CH 2 and Z 4 is a bond, and Z 5 is C(R 4 )(H). In some embodiments, Z 1 is N(R 11c ), and Z 2 is a bond, and Z 3 is C(R 4 )(H), and Z 4 is a bond, and Z 5 is CH 2 In some embodiments, Z 1 is O and Z 2 is a bond, and Z 3 CH 2 and Z 4 is a bond, and Z 5 is N(R 4 ).

[0085] In some embodiments, R 4a can have one, two, three, or four R 4b C optionally substituted with 3-10 In some embodiments, R 4a can have one, two, three, or four R 4b C optionally substituted with 2-9 In some embodiments, R 4a can have one, two, three, or four R 4b C optionally substituted with 6-10 In some embodiments, R 4acan have one, two, three, or four R 4b C optionally substituted with 1-9 In some embodiments, R 4a is C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl or one, two, three, or four R 4b C optionally substituted with 1-9 It is heteroaryl.

[0086] In some embodiments, L 4 is a bond, -O-, -N(R 4d )-, -C(O)-, or CR 4c R 4c In some embodiments, L 4 is a bond.

[0087] In one aspect, the formula AL AB -B, wherein A is a monovalent compound from those described herein; L AB is a covalent linker connecting A and B; and B is a monovalent from a degradation enhancer.

[0088] In some embodiments, the degradation promoter is 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, PIAS5, PIAS6, PIAS7, PIAS8, PIAS9, PIAS10, PIAS11, PIAS12, PIAS13, PIAS14, PIAS15, PIAS16, PIAS17, PIAS18, PIAS19 ...9, PIAS19, PIAS19, PIAS20, PIAS21, PIAS22, PIAS23, PIAS24, PIAS25, PIAS26, PIAS27, PIAS28, PIAS29, PIAS30, PIAS31, PIAS32, PIAS33, PIAS34, PIAS35, PIAS36, PIAS37, PIAS38, PIAS39, PIAS40, PIAS41, PIAS4 2, 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 (beta-TRCP) ubiquitin complex), b-TRCP (b-transducing repeat-containing protein), cIAP1 (cellular inhibitor of apoptosis protein 1), APC / C (anaphase-promoting complex / cyclosome), CRBN (cereblon), CUL4-RBX1-DDB1-CRBN (CRL4 CRBN ) ubiquitin ligase, XIAP, IAP, KEAP1, DCAF15, RNF114, DCAF16, AhR, SOCS2, KLHL12, UBR2, SPOP, KLHL3, KLHL20, KLHDC2, SPSB1, SPSB2, SPSB4, SOCS6, FBXO4, FBXO31, BTRC, FBW7, CDC20, PML, TRIM21, TRIM24, TRIM33, GID4, avadomide, iberdomide, and CC-885.

[0089] In some embodiments, the degradation promoting agent is capable of binding to a protein selected from UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2DR, UBE2E1, UBE2E2, UBE2E3, UBE2F, UBE2G1, UBE2G2, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2K, UBE2L3, UBE2L6, UBE2L1, UBE2L2, UBE2L4, UBE2M, UBE2N, UBE2O, UBE2Q1, UBE2Q2, UBE2R1, UBE2R2, UBE2S, UBE2T, UBE2U, UBE2V1, UBE2V2, UBE2W, UBE2Z, ATG3, BIRC6, and UFC1.

[0090] In some embodiments, L AB -L AB1 -L AB2 -L AB3 -L AB4 -L AB5 - and 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 -, (-C 1-6 Alkyl-O) z -, C 2-6 Alkenylene, C 2-6 Alkynylene, C 1-6 Haloalkylene, C 3-12 Cycloalkylene, C 1-11 Heterocycloalkylene, C6-12 Arylene, or C 1-11 heteroarylene, where C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 1-6 Haloalkylene, C 3-12 Cycloalkylene, C 1-11 Heterocycloalkylene, C 6-12 Arylene, or C 1-11 Heteroarylene can contain one, two, or three R 20n where (-OC 1-6 Alkyl) z - and (-C 1-6 Alkyl-O) z -C 1-6 Alkyl can be one, two, or three R 20n and optionally substituted with z is independently an integer from 0 to 10; Each R 12 is 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 6-10Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20l and optionally substituted with Each R 13 is 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, can be one, two, or three R 20l C optionally substituted with 2-9 forming a heterocycloalkyl ring, Each R 14 is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 15 is 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 a heteroaryl group consisting of one, two, or three R 20m and optionally substituted with Each R 20l , R 20m , and R 20n is halogen, -CN, 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, 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 are each independently selected from 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 is 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 and optionally substituted with one, two, or three groups independently selected from Each R 21 , 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; Each R 22 , H, C 1-6Alkyl, 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 H and C 1-6 alkyl, Each R 24 H and C 1-6 alkyl, Each R 25 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl.

[0091] In some embodiments, L AB Ha-(OC 2 Alkyl) z and z is an integer from 1 to 10.

[0092] In some embodiments, L AB Ha-(C 2 Alkyl-O-) z and z is an integer from 1 to 10.

[0093] In some embodiments, L AB is -(CH 2 ) zz1 L AB2 (CH 2 O) zz2 - where L AB2 is a bond, a 5- or 6-membered heterocycloalkylene or heteroarylene, phenylene, -(C 2 -C 4 ) Alkynylene, -SO 2- or -NH-, and zz1 and zz2 are independently an integer of 0 to 10.

[0094] In some embodiments, L AB is -(CH 2 ) zz1 (CH 2 O) zz2 -, where zz1 and zz2 are each independently an integer from 0 to 10.

[0095] In some embodiments, L AB is a PEG linker.

[0096] In some embodiments, B is [ka] is a monovalent form of a compound selected from:

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

[0098] In one aspect, provided is a method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof.

[0099] In one aspect, a method of treating cancer in a subject containing a Ras mutant protein is provided, the method comprising inhibiting a Ras mutant protein in the subject by administering to the subject a compound characterized in that, upon contact with the Ras mutant protein, the Ras mutant protein exhibits reduced Ras signaling output.

[0100] In some embodiments, the cancer is a solid tumor. In some embodiments, the cancer is a hematological cancer.

[0101] In some embodiments of the methods described herein, the compound is a compound described herein.

[0102] In one embodiment, a method of modulating the signal output of a Ras protein is provided, comprising contacting the Ras protein with an effective amount of a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof, thereby modulating the signal output of the Ras protein.

[0103] In one aspect, a method of inhibiting cell growth is provided, comprising administering an effective amount of a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof, to a cell expressing a Ras protein, thereby inhibiting growth of the cell.

[0104] In some embodiments of the methods described herein, the methods comprise administering an additional agent.

[0105] In some embodiments, the additional agent is: (1) an inhibitor of MEK, (2) an inhibitor of epidermal growth factor receptor (EGFR) and / or a mutant thereof, (3) an immunotherapeutic agent, (4) a taxane, (5) an antimetabolite, (6) an inhibitor of FGFR1 and / or FGFR2 and / or FGFR3 and / or a mutant thereof, (7) a mitotic phase kinase inhibitor, (8) an antiangiogenic drug, (9) a topoisomerase inhibitor, (10) a platinum-containing compound, (12) an inhibitor of c-MET and / or a mutant thereof, (13) an inhibitor of BCR-ABL and / or a mutant thereof, (14) an inhibitor of ErbB2 (Her2) and / or a mutant thereof, (15) an inhibitor of AXL and / or a mutant thereof, (16) an inhibitor of NTRK1 and / or a mutant thereof, (17) an inhibitor of RET and / or a mutant thereof, (18) an inhibitor of A-Raf and / or B-Raf and / or C-Raf and / or a mutant thereof, (19) an inhibitor of ERK and / or inhibitors of its mutants, (20) MDM2 inhibitors, (21) inhibitors of mTOR, (23) inhibitors of IGF1 / 2 and / or IGF1-R, (24) inhibitors of CDK9, (25) inhibitors of farnesyltransferase, (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, VEG (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.

[0106] In some embodiments, the additional agent is RMC-4630, ERAS-601, [ka] The present invention includes an inhibitor of SHP2 selected from the group consisting of:

[0107] In some embodiments, the additional agent is [ka] RMC-5845, and BI-1701963.

[0108] In some embodiments, the additional agent comprises an inhibitor of EGFR selected from afatinib, erlotinib, gefitinib, lapatinib, cetuximab, panitumumab, osimertinib, olmutinib, and EGF-816. In some embodiments, the additional agent comprises an inhibitor of MEK selected from trametinib, cobimetinib, binimetinib, selumetinib, refametinib, and AZD6244. In some embodiments, the additional agent comprises an inhibitor of ERK selected from ulixertinib, MK-8353, LTT462, AZD0364, SCH772984, BIX02189, LY3214996, and ravoxertinib. In some embodiments, the additional agent comprises an inhibitor of CDK4 / 6 selected from palbociclib, ribociclib, and abemaciclib. In some embodiments, the additional agent comprises an inhibitor of BRAF selected from sorafenib, vemurafenib, dabrafenib, encorafenib, regorafenib, and GDC-879.

[0109] (Incorporated by reference) All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. [Brief description of the drawings]

[0110] 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 present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings.

[0111] [Figure 1] FIG. 1 shows a top-to-bottom sequence alignment of various wild-type Ras proteins, including K-Ras, H-Ras, N-Ras, RalA, and RalB. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0112] The practice of some embodiments disclosed herein will employ, unless otherwise indicated, conventional techniques of immunology, biochemistry, chemistry, molecular biology, microbiology, cell biology, genomics and recombinant DNA, which are within the skill of those in the art. See, e.g., Sambrook and Green, Molecular Cloning: A Laboratory Manual, 4 th Edition (2012), Series Current Protocols in Molecular Biology (FM Ausubel, et al. eds.); Series Methods In Enzymology (Academic Press, Inc.), PCR 2: A Practical Approach (MJ MacPherson, BD Hames and GR Taylor eds. (1995)), Harlow and Lane, eds. (1988) Antibodies, A Laboratory Manual, and Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications,6 th Edition (R.I. Freshney, ed. (2010)).

[0113] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the claimed subject matter belongs. In the event of multiple definitions for terms herein, the definitions in this section prevail. All patents, patent applications, publications, and published nucleotide and amino acid sequences (e.g., sequences available in GenBank or other databases) mentioned herein are incorporated by reference. When referring to a URL or other identifier or address, it is understood that such identifiers may change and that particular information on the Internet may come and go, but that equivalent information may be found by searching the Internet. Reference thereto evidences that such information is available and publicly disseminated.

[0114] It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not intended to limit any of the subject matter claimed. In this application, the use of the singular includes the plural unless otherwise specified. It should be noted that as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly indicates otherwise. In this application, the use of "or" means "and / or" unless otherwise specified. Furthermore, the use of the term "including," as well as other forms such as "include," "includes," "included," and the like, is not limiting.

[0115] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0116] Definitions of standard chemical terms include, but are not limited to, those set forth in Carey and Sundberg “Advanced Organic Chemistry 4 thEd." Vols. A(2000) and B(2001), Plenum Press, New York. Unless otherwise indicated, conventional methods of mass spectrometry, NMR, HPLC, protein chemistry, biochemistry, recombinant DNA techniques, pharmacology and the like are used.

[0117] Unless specific definitions are provided, the nomenclature utilized in connection with analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein, as well as the laboratory procedures and techniques thereof, are art-recognized. Standard techniques can be used for chemical synthesis, chemical analysis, pharmaceutical preparation, formulation, delivery, and patient treatment. Standard techniques can be used for recombinant DNA, oligonucleotide synthesis, tissue culture, and transformation (electroporation, lipofection, etc.). Reactions and purification techniques can be performed, for example, using manufacturer's specification kits or as commonly accomplished in the art, or as described herein. The aforementioned techniques and procedures can generally be performed in a conventional manner and as described in various general and more specific references cited and discussed throughout this specification.

[0118] It is understood that the methods and compositions described herein are not limited to the particular methodology, protocols, cell lines, constructs, and reagents described herein, and may vary. It is also understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the methods, compounds, and compositions described herein.

[0119] As used herein, C 1 ~C x is C 1 ~C 2 , C 1 ~C 3 … C 1 ~C x Includes: C 1 ~C xindicates the number of carbon atoms that make up the moiety it designates (excluding optional substituents).

[0120] An "alkyl" group refers to a straight or branched hydrocarbon chain group consisting solely of carbon and hydrogen atoms and containing no unsaturation. In some embodiments, an "alkyl" group can have 1-18, 1-12, 1-10, 1-8, or 1-6 carbon atoms (wherever it appears herein, a numerical range such as "1-6" refers to each integer within the given range, e.g., "1-6 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 includes occurrences of the term "alkyl" where no numerical range is specified). The alkyl groups of the compounds described herein are referred to as "C 1 -C 6 As merely an example, "C 1 -C 6 "Alkyl" refers to the presence of 1 to 6 carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, iso-pentyl, neo-pentyl, and hexyl. Alkyl groups can be substituted or unsubstituted. Depending on the structure, alkyl groups can be monoradicals or diradicals (i.e., alkylene groups).

[0121] "Alkoxy" refers to the group "-O-alkyl" where alkyl is as defined herein.

[0122] The term "alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, linear or branched, 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(CH3 ) 2 and -C(CH 3 )=CHCH 3 In some embodiments, the alkenyl group may have 2 to 6 carbons. The alkenyl group may be substituted or unsubstituted. Depending on the structure, the alkenyl group may be a monoradical or a diradical (alkenylene group).

[0123] The term "alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, linear or branched, 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および -C≡CCH 2 CH 2 CH 3 In some embodiments, an alkynyl group can have 2 to 6 carbons. An alkynyl group can be substituted or unsubstituted. Depending on the structure, an alkynyl group can be a monoradical or a diradical (alkynylene group).

[0124] "Amino" is -NH 2 Refers to the base.

[0125] The term "alkylamine" or "alkylamino" refers to -N(alkyl) x H y "Dialkylamino" refers to the group, where alkyl is as defined herein, and x and y are selected from the group: x=1, y=1 and x=2, y=0. When x=2, the alkyl groups, together with the nitrogen to which they are attached, can optionally form a cyclic ring system. "Dialkylamino" refers to -N(alkyl) 2 refers to the group, where alkyl is as defined herein.

[0126] The term "aromatic" refers to a planar ring having a delocalized-electron system containing 4n+2 electrons, where n is an integer. An aromatic ring may be formed from 5, 6, 7, 8, 9, or more than 9 atoms. An aromatic may be optionally substituted. The term "aromatic" includes both aryl (e.g., phenyl, naphthalenyl) and heteroaryl (e.g., pyridinyl, quinolinyl) groups.

[0127] As used herein, the term "aryl" refers to a monocyclic aromatic ring (e.g., phenyl) in which each of the atoms forming the ring is a carbon atom, or a polycyclic ring system (e.g., bicyclic or tricyclic) in which 1) at least one ring is carbocyclic aromatic, 2) the bond to the rest of the compound is directly bonded to the carbocyclic aromatic ring of the aryl ring system, and 3) the carbocyclic aromatic ring of the aryl ring system in 2) is not directly bonded (e.g., fused) to the heteroaryl ring of the polycyclic ring system. The aryl ring may be formed from 5, 6, 7, 8, 9, or more than 9 atoms. The aryl group may be optionally substituted. Examples of aryl groups include, but are not limited to, phenyl and naphthalenyl. Depending on the structure, the aryl group may be a monoradical or a diradical (i.e., an arylene group). As used herein, an aryl radical is a monocyclic, bicyclic, or tricyclic ring system. In embodiments, the aryl is a monocyclic ring. In embodiments, the aryl is a fused ring polycyclic ring system. In embodiments, the aryl is a bridged ring polycyclic ring system. In some embodiments, the aryl is a "fused ring aryl" in which the aryl ring is fused with a cycloalkyl or heterocycloalkyl ring. In embodiments, the aryl is a "fused bicyclic" aryl in which the two rings of the aryl group share one bond.

[0128] "Carboxy" is -CO 2H. In some embodiments, the carboxy moiety may be replaced with a "carboxylic acid bioisostere," which refers to a functional group or moiety that exhibits similar physical and / or chemical properties as the carboxylic acid moiety. A carboxylic acid bioisostere has similar biological properties as a carboxylic acid group. A compound having a carboxylic acid moiety may have the carboxylic acid residue replaced with a carboxylic acid bioisostere and have similar physical and / or biological properties compared to the carboxylic acid-containing compound. For example, in one embodiment, a carboxylic acid bioisostere ionizes to approximately the same extent as a carboxylic acid group at physiological pH. Examples of carboxylic acid bioisosteres include: [ka] Examples include, but are not limited to, the following:

[0129] The term "cycloalkyl" refers to a monocyclic carbocyclic saturated or partially unsaturated non-aromatic ring or a polycyclic carbocyclic (i.e., does not contain heteroatoms) ring system (e.g., bicyclic or tricyclic) in which 1) at least one ring is carbocyclic saturated or partially unsaturated non-aromatic, 2) the bond to the remainder of the compound is directly attached to a carbocyclic saturated or partially unsaturated non-aromatic ring of the ring system, and 3) the carbocyclic saturated or partially unsaturated non-aromatic ring of 2) is not directly attached (e.g., fused or spiro) to a heterocycloalkyl ring of the polycyclic system. A cycloalkyl can be saturated or partially unsaturated. In some embodiments, a cycloalkyl ring is a spirocyclic cycloalkyl ring. In embodiments, a cycloalkyl is a monocyclic ring. In embodiments, a cycloalkyl is a fused ring polycyclic ring system. In embodiments, a cycloalkyl is a bridged ring polycyclic ring system. In embodiments, a cycloalkyl is a spirocyclic polycyclic ring system. In some embodiments, a cycloalkyl group includes groups having 3 to 10 ring atoms. Depending on the structure, a cycloalkyl group can be a monoradical or a diradical (i.e., a cycloalkylene group). In embodiments, the cycloalkyl is a fused bicyclic cycloalkyl, in which the two rings of the cycloalkyl group share one bond.

[0130] The term "heteroaryl" or alternatively "heteroaromatic" refers to a monocyclic aryl group containing 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 contains one or more heteroatoms selected from nitrogen, oxygen, and sulfur, and 2) the bond to the remainder of the compound is directly bonded (e.g., fused) to an aromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur, or an aryl 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 of the rings in the ring system is fully unsaturated (i.e., aromatic) and contains a heteroatom. In an embodiment, the heteroaryl is a monocyclic ring. In an embodiment, the heteroaryl is a fused ring polycyclic ring system. In an embodiment, the heteroaryl is a bridged ring polycyclic ring system. In some embodiments, the heteroaryl ring is a "fused ring heteroaryl" fused with a cycloalkyl, aryl, or heterocycloalkyl ring. An N-containing "heteroaromatic" or "heteroaryl" moiety refers to an aromatic group in which at least one of the skeletal atoms of the ring is a nitrogen atom. Depending on the structure, the heteroaryl group can be monovalent or divalent (i.e., a heteroarylene group). In some embodiments, the heteroaryl is a "fused bicyclic" heteroaryl in which the two rings of the heteroaryl group share one bond.

[0131] 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 containing one or more heteroatoms, or a polycyclic ring system (e.g., bicyclic or tricyclic) directly bonded to a non-aromatic ring in which 1) at least one ring is saturated or partially unsaturated non-aromatic and contains one or more heteroatoms, and 2) the bond to the remainder of the compound is a saturated or partially unsaturated non-aromatic ring containing one or more heteroatoms, the ring of the ring system being directly bonded (e.g., fused ring, spiro ring) to a saturated or partially unsaturated non-aromatic ring containing one or more heteroatoms in the ring system. Heterocycloalkyl may be saturated or partially unsaturated. The term heterocycloalkyl includes, but is not limited to, all ring forms of carbohydrates, including 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 ring polycyclic ring system. In embodiments, the heterocycloalkyl is a bridged ring polycyclic ring system. In embodiments, the heterocycloalkyl is a spirocyclic polycyclic ring system. Unless otherwise noted, the heterocycloalkyl has 2-13 carbons in the ring or ring system. When referring to the number of carbon atoms in a heterocycloalkyl, it is understood that the number of carbon atoms in the heterocycloalkyl is not the same as the total number of atoms (including heteroatoms) that make up the heterocycloalkyl (i.e., the skeletal atoms of the heterocycloalkyl ring). Depending on the structure, the heterocycloalkyl group can be a monoradical or a diradical (i.e., a heterocycloalkylene group). In embodiments, the heterocycloalkyl is a "fused bicyclic" heterocycloalkyl, in which the two rings of the heterocycloalkyl group share one bond.

[0132] The term "halo" or alternatively "halogen" means fluoro, chloro, bromo and iodo.

[0133] The abbreviations "Fmoc", "Ac", "Bn", "PMB", "Tr", "Ts", "Boc", and "Cbz" are used according to their common meaning well understood in the chemical arts to refer to monovalent chemical substituents such as fluorenylmethyloxycarbonyl, acetyl, benzyl, p-methoxybenzyl, trityl or triphenylmethyl, tosyl, tert-butyloxycarbonyl, and carbobenzyloxy. The term "monovalent" is used herein according to its common meaning well understood in chemistry to refer to the ability of a substituent to form one covalent bond with another substituent or compound capable of forming a covalent bond. In a related manner, the term "bivalent" refers to a substituent or compound capable of forming two covalent bonds, e.g., a linker capable of covalently linking two monovalent substituents or compounds.

[0134] The term "haloalkyl" refers to an alkyl group that is substituted with one or more halogens. The halogens may be the same or they may be different. Non-limiting examples of haloalkyl include -CH 2 Cl, -CF 3 , -CHF 2 , -CH 2 CF 3 , -CF 2 CF 3 etc.

[0135] The terms "fluoroalkyl" and "fluoroalkoxy" include alkyl and alkoxy groups, respectively, that are substituted with one or more fluorine atoms. A non-limiting example of a fluoroalkyl is -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 A non-limiting example of a fluoroalkoxy group is -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 etc.

[0136] The term "heteroalkyl" refers to an alkyl group in which one or more skeletal atoms are selected from atoms other than carbon, such as oxygen, nitrogen, sulfur, phosphorus, silicon, or combinations thereof. The heteroatom may be located at any interior position of the heteroalkyl group. Examples include -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 In addition, -CH 2 -NH-OCH 3 and -CH 2 -O-Si(CH 3 ) 3 Up to two heteroatoms may be consecutive, such as: "Heteroalkyl" may have 1 to 6 carbon atoms, excluding the number of heteroatoms.

[0137] The term "heteroalkylene linker" refers to a divalent alkyl radical in which one or more backbone atoms are selected from atoms other than carbon, such as oxygen, nitrogen, sulfur, phosphorus, silicon, or combinations thereof. In some embodiments, the heteroatoms may be located at any interior position of the heteroalkyl group. In some embodiments, the heteroatoms may be located at one or both terminal positions of the heteroalkylene linker (i.e., positions directly attached to a portion of the molecule other than the heteroalkylene linker). Examples include -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-CH2 -, -CH 2 -O-Si(CH 3 ) 2 -, -CH 2 -CH=NO-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 -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 -NH-O-, -O-Si(CH 3 ) 2 -, -CH 2 -CH=NO- 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-CH2 -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 In addition, up to two heteroatoms may be, for example, -CH 2 -NH-O- and -O-Si(CH 3 ) 2 For example, -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)(CH 3 In addition, up to two heteroatoms may be, for example, -CH 2 -NH-O- and -O-Si(CH 3 ) 2They may be consecutive, such as -. A "heteroalkylene linker" may have 2 to 4 main chain atoms, unless otherwise specified.

[0138] The term "oxo" refers to the =O radical.

[0139] The term "bond", or "single bond", refers to a chemical bond between two atoms, or a chemical joining of two moieties when the atoms joined by the bond are considered part of a larger substructure.

[0140] The term "residue" refers to a specific segment or functional group of a molecule. A chemical moiety is a chemical entity that is often recognized as embedded within or appended to a molecule.

[0141] It is understood that the suffix "-di-yl" means that the substituent or linker is a divalent substituent or linker.

[0142] As used herein, the substituent "R" appearing alone and without a number designation refers to a substituent selected from alkyl, haloalkyl, heteroalkyl, alkenyl, cycloalkyl, aryl, heteroaryl (bonded via a ring carbon), and heterocycloalkyl.

[0143] "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and the description includes cases where the event or circumstance occurs and cases where it does not occur.

[0144] The term “optionally substituted” or “substituted” means, unless otherwise specified, that the group being referred to is alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, —OH, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, arylsulfone, —CN, alkyne, C 1 -C6 Alkyl alkyne, halo, acyl, acyloxy, -CO 2 H, -CO 2 -Alkyl, nitro, haloalkyl, fluoroalkyl, and mono- and di-substituted amino groups (e.g., -NH 2 , -NHR, -N(R) 2 ), as well as protective derivatives thereof. By way of example, optional substituents include L s R s where each L s is 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 is H, (C 1 -C 6 Alkyl), (C 3 -C 8 cycloalkyl), aryl, heteroaryl, heterocycloalkyl, and C 1 -C 6 The protecting groups that may form the protective derivatives of the above substituents can be found in references such as Greene and Wuts, above.

[0145] "Pharmaceutically acceptable salt" includes both acid and base addition salts.The pharmaceutically acceptable salt of any one of the compounds described herein is intended to include any and all pharmaceutically suitable salt forms.The preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0146] "Pharmaceutically acceptable acid addition salts" refers to salts 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, which retain the biological effectiveness and properties of the free base and are not biologically or otherwise undesirable. 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. Examples include 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 sulfate, disulfate, hydrogen sulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, trifluoroacetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, toluenesulfonate, phenylacetate, citrate, lactate, malate, tartrate, methanesulfonate, etc. Amino acid salts such as arginate, gluconate, and galacturonate are also contemplated (see, e.g., Berge SM et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science, 66:1-19 (1997)). Acid addition salts of basic compounds are prepared in some embodiments by contacting the free base form with a sufficient amount of the desired acid to produce the salt according to methods and techniques familiar to those of ordinary skill in the art.

[0147] "Pharmaceutically acceptable base addition salts" refer to salts that retain the biological effectiveness and properties of the free acids and are not biologically or otherwise undesirable. These salts are prepared by adding an inorganic or organic base to the free acid. Pharmaceutically acceptable base addition salts are formed in some embodiments with metals or amines, such as alkali and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, 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, ethylenedianiline, N-methylglucamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, etc. See Berge et al., supra.

[0148] The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymers may be linear or branched, may comprise modified amino acids, and may be interrupted by non-amino acids. The terms also contemplate amino acid polymers that have been modified, such as by disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or conjugation with a labeling component. As used herein, the term "amino acid" refers to either natural and / or unnatural or synthetic amino acids, and includes glycine and both D or L optical isomers, as well as amino acid analogs and peptidomimetics.

[0149] The terms "polynucleotide", "nucleotide", "nucleotide sequence", "nucleic acid" and "oligonucleotide" are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides may have any three-dimensional structure and may perform any function, known or unknown. Non-limiting examples of polynucleotides are: coding or non-coding regions of a gene or gene fragment, locus(es) defined from linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, small interfering RNA (siRNA), small hairpin RNA (shRNA), microRNA (miRNA), ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers. A polynucleotide may include one or more modified nucleotides, such as methylated nucleotides and nucleotide analogs, such as peptide nucleic acid (PNA), morpholino and locked nucleic acid (LNA), glycol nucleic acid (GNA), threose nucleic acid (TNA), 2'-fluoro, 2'-OMe, and phosphorothiolated DNA. If present, modifications to the nucleotide structure may be added before or after assembly of the polymer. The sequence of nucleotides may be interrupted by non-nucleotide components. Polynucleotides may be further modified after polymerization, such as by conjugation with a labeling component or other conjugation target.

[0150] As used herein, "expression" refers to the process by which a polynucleotide is transcribed from a DNA template (such as into an mRNA or other RNA transcript) and / or the process by which the transcribed mRNA is subsequently translated into a peptide, polypeptide, or protein. The transcript and the encoded polypeptide may be collectively referred to as a "gene product." If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in a eukaryotic cell.

[0151] As used herein, the terms "subject," "individual," and "patient" are used interchangeably to refer to vertebrates, preferably mammals, more preferably humans. Mammals include, but are not limited to, murines, simians, humans, farm animals, sport animals, and pets. Also included are tissues, cells, and their progeny of biological entities obtained in vivo or cultured in vitro.

[0152] The terms "drug" or "therapeutic agent", "therapeutic agent" or "treatment agent" are used interchangeably and refer to a molecule or compound that provides 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 occurrence of a disease, symptom, disorder, or condition, and generally counteracting a disease, symptom, disorder, or pathological condition.

[0153] As used herein, "treatment" or "treating", or "alleviating" or "ameliorating" are used interchangeably. "Ameliorate" is used interchangeably. These terms refer to an approach to obtain beneficial or desired results, including but not limited to therapeutic benefit and / or prophylactic benefit. By therapeutic benefit is meant any therapeutically relevant improvement in or effect on one or more diseases, conditions, or symptoms under treatment. For prophylactic benefit, the composition can be administered to subjects at risk of developing a particular disease, condition, or symptom, or to subjects who report one or more physiological symptoms of a disease, even if the disease, condition, or symptom has not yet manifested. Typically, prophylactic benefit includes reducing the incidence and / or worsening of one or more diseases, conditions, or symptoms under treatment (e.g., between treated and untreated populations, or between treated and untreated states of a subject).

[0154] The term "effective amount" or "therapeutically effective amount" refers to an amount of an agent sufficient to produce a beneficial or desired result. The therapeutically effective amount may vary depending on one or more of the subject and disease state being treated, the weight and age of the subject, the severity of the disease state, the method of administration, and the like, which can be readily determined by one of ordinary skill in the art. An effective amount of an active agent may be administered in a single dose or multiple doses. Ingredients may be described herein as having at least an effective amount, or at least an effective amount, as related to a particular purpose or goal as described herein. The term "effective amount" also applies to a dose that provides an image for detection by an appropriate imaging method. The specific dosage may vary depending on one or more of the particular agent selected, the administration regimen to be followed, whether or not it is administered in combination with other compounds, the timing of administration, the tissue to be imaged, and the physical delivery system in which the agent is delivered.

[0155] The term "in vivo" refers to events that take place inside a subject's body.

[0156] The term "ex vivo" refers to an event that initially occurs outside of a subject's body for subsequent application in vivo within the subject's body. For example, ex vivo preparation may involve preparing cells outside of a subject's body with the intent of introducing the prepared cells into the same or a different subject.

[0157] The term "in vitro" refers to an event that occurs outside of a subject's body. For example, an in vitro assay includes any assay that is performed outside of a subject's body. An in vitro assay includes cell-based assays in which live or dead cells are used. An in vitro assay includes cell-free assays that do not use intact cells.

[0158] The term "Ras" or "RAS" refers to a small GTPase, such as a protein of the Rat sarcoma (Ras) superfamily, including 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 the group consisting of 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, and KRAS, HRAS, NRAS, RALA, RALB, and any combination thereof. The terms "mutant Ras" and "Ras mutant", used interchangeably herein, refer to a Ras protein having one or more amino acid mutations, such as with respect to a common reference sequence, such as a wild-type (WT) sequence. In some embodiments, the mutant Ras is selected from mutant KRAS, mutant HRAS, mutant NRAS, mutant MRAS, mutant ERAS, mutant RRAS2, mutant RALA, mutant RALB, mutant RIT1, and any combination thereof, such as mutant KRAS, mutant HRAS, mutant NRAS, mutant RALA, mutant RALB, and any combination thereof. In some embodiments, the mutation can be an introduced mutation, a naturally occurring mutation, or a non-naturally occurring mutation. In some embodiments, the mutation can be a substitution (e.g., a substituted amino acid), an insertion (e.g., an addition of one or more amino acids), or a deletion (e.g., a removal of one or more amino acids). In some embodiments, the two or more mutations can be consecutive, non-consecutive, or a combination thereof. In some embodiments, the mutation can be at any position in Ras.In some embodiments, the mutations may be present at positions 12, 13, 62, 92, 95, 96, or any combination thereof of Ras of SEQ ID NO:2 when optimally aligned. In some embodiments, the mutant Ras may contain about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, or more than 50 mutations. In some embodiments, the mutant Ras may contain up to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 mutations. In some embodiments, the mutant Ras is less than 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 50 amino acids in length. 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, a non-canonical amino acid, an essential amino acid, a non-essential amino acid, or a non-naturally occurring 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, a cyclic side chain, a basic side chain, or an acidic side chain. In some embodiments, the mutation comprises a reactive moiety. In some embodiments, the substituted amino acid comprises a reactive moiety. 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).

[0159] As used herein, the term "corresponding to" or "responds to" when applied to amino acid residues in a polypeptide sequence refers to the correspondence of such amino acids to a reference sequence when optimally aligned (e.g., the alignment may be a primary sequence alignment or a three-dimensional structural alignment of a folded protein, taking into account gaps, insertions, and mismatches). 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 serve 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 serve as a reference sequence. When an amino acid of a mutant Ras protein corresponds to an amino acid position of a wild-type Ras protein, it will be understood that the amino acid of the mutant Ras protein may be a different amino acid (e.g., G12D at position 12, where the wild-type G at position 12 of SEQ ID NO:1 is replaced with an aspartic acid), but the mutant amino acid is at the 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 truncations at the C-terminus or truncations at the N-terminus before the serine residue. The serine residue in such N-terminal truncated modified mutants is still considered to correspond to position 12 of SEQ ID NO: 1. Furthermore, the aspartic acid residue at position 12 of SEQ ID NO: 2 finds the corresponding residue in SEQ ID NO: 6 and 8.

[0160] As used herein, prodrug is intended to refer to a compound that can be converted under physiological conditions or by solvation into a biologically active compound as described herein.The term prodrug refers to a precursor of a pharmaceutically acceptable biologically active compound.Prodrugs may be inactive when administered to a subject, but are converted to active compounds in vivo, for example, by hydrolysis. Prodrug compounds may offer advantages of solubility, tissue compatibility, and / or delayed release in the mammalian organism (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,” ACS Symposium Series, Vol. 14, and in 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” may be any covalently bonded carrier that releases the active compound in vivo when such prodrug is administered to a mammalian subject. Prodrugs of the active compounds described herein may be prepared by modifying functional groups present in the active compound such that the modifications are cleaved to the parent active compound either in routine manipulation or in vivo.

[0161] The term "leaving group" is used herein in accordance with its well-understood meaning in chemistry to refer to an atom or group of atoms that separates from the rest of a molecule, taking with it the electron pair that used to be the bond between the leaving group and the rest of the molecule.

[0162] A "degradation promoter" is a compound capable of binding to a ubiquitin ligase protein (e.g., an E3 ubiquitin ligase protein) or a compound capable of binding to a protein capable of binding to a ubiquitin ligase protein, forming a protein complex capable of binding the ubiquitin protein to a target protein. In embodiments, the degradation promoter is capable of binding to an E3 ubiquitin ligase protein or a protein complex comprising an E3 ubiquitin ligase protein. In embodiments, the degradation promoter is capable of binding to an E2 ubiquitin conjugating enzyme. In embodiments, the degradation promoter is capable of binding to a protein complex comprising an E2 ubiquitin conjugating enzyme and an E3 ubiquitin ligase protein.

[0163] compound In some embodiments, there is provided a compound of formula (I), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, Z 1 , Z 2 , Z 3 , and Z 4 are N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, O, and C(O), Z 1 , Z 2 , Z 3 , and Z 4 At least one of N(R 4 ), N(R 11d ), C(R 4 ), C(R 11d), C(R 4 )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), or C(O), W 1 is C(R 1 ), C, or N; R 1 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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 R15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl is one, two, or three R 20a and optionally substituted with W 2 is N(R 2a ), N, C(R 2 ), C(R 2 )(R 2a)、 S(O) 2 or S(O), R 2 is 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 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 a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with R 2a is 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 a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with W 3 is N(R 3b ), N, C(R 3 ), C(R 3 )(R 3a)、 C(O), S(O) 2 or S(O), R 3 and R 3a is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9Heterocycloalkyl, 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 6-10Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with R 3b is 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 , C.H. 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 1-9Heteroaryl is a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with W 4 is N or N(R 3c ) and R 3c is 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, C6-10 Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with W 5 is C(R 5 ), C, or N; R 5 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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, and C 2-6 Alkynyl is one, two, or three R 20d and optionally substituted with W 6 is N(R 6b ), N, C(R 6 ), C(R 6 )(R 6a)、 C(O), S(O), or S(O) 2 and R 6 and R 6a is 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) 2N(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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with R 6b is 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 )(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 ), in the formula, 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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with W 7 is N(R 7 ), C(R 7 ), or C(R 7 )(R 7a ) and R 7a and each R 7c is 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 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 a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7d is 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 a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7 -L 7 -R 17 and L 7 is a bond, -O-, -N(R 7d )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, -P(O)R 7d -, CR 7c R 7c , -OCR7c R 7c -、-N(R 7d )CR 7c R 7c -、-C(O)CR 7c R 7c -、-SCR 7c R 7c -,-ONLY) 2 CR 7c R 7c -、-S(O)CR 7c R 7c -,-PUT 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 ONLY) 2 -、-CR 7c R 7c S(O)-、-CR 7c R 7c PUT 7d -、-N(R 7d )C(O)-、-N(R 7d )ONLY) 2 -、-N(R 7d )S(O)-、-N(R 7d )PUT 7d -、-C(O)N(R 7d )-,-ONLY) 2 N(R 7d )-、-S(O)N(R 7d )-,-PUT 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-、または-P(O)R 7d O-であり、 R 17 is 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 a heteroaryl group consisting of one, two, or three R 20g and optionally substituted with W 8 is C(R 8 ), C(R 8 )(R 8a ), N, N(R 8b)、 C(O), S(O), or S(O) 2 and R 8 and R 8a is 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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted with R 8b is 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(R12 )(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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted from W 9 is C(R 9 ), C, or N; W 10 is C(R 9 ), C, or N; Each R 9 is 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 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20i and optionally substituted with R 4 -L 4 -R 4a and L 4 is a bond, -O-, -N(R 4d )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, -P(O)R 4d -, -CR 4c R 4c -,-OCR 4c R 4c -, -N(R 4d )CR 4c R 4c -, -C(O)CR 4c R 4c -,-SCR 4c R 4c -, -S(O) 2 CR 4c R 4c -,-S(O)CR 4c R 4c -, -P(O)R 4d CR 4c R 4c -, -CR 4c R 4c CR 4c R 4c , -CR 4c R 4c O-, -CR 4c R4c N(R 4d )-, -CR 4c R 4c C(O)-, -CR 4c R 4c S-, -CR 4c R 4c S(O) 2 -, -CR 4c R 4c S(O)-, -CR 4c R 4c P(O)R 4d -, -N(R 4d )C(O)-, -N(R 4d )S(O) 2 -, -N(R 4d )S(O)-, -N(R 4d )P(O)R 4d -, -C(O)N(R 4d )-, -S(O) 2 N(R 4d )-, -S(O)N(R 4d )-, -P(O)R 4d N(R 4d )-, -OC(O)-, -OS(O) 2 -, -OS(O)-, -OP(O)R 4d -, -C(O)O-, -S(O) 2 O-, -S(O)O-, or -P(O)R 4d O-, Each R4c is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14 , -OC(O)R 14a , -N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14a , and -N(R 14 )S(O) 2 R 14 are independently selected from, 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, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14)(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R 4d is hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14 , and -OC(O)R 14a are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C2-6 Alkynyl, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R 4a is 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 6-10Aryl, and C 1-9 Heteroaryl is one, two, three, or four R 4b and optionally substituted with Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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, -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is one or more R 20j and optionally substituted with Each R 11c is hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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)R15 , -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 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20k and optionally substituted with Each R 11d is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20k and optionally substituted with Each R 12 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12b ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12b ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12b ) 2 -C 6-10 Aryl, -C(R 12b ) 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 12b ) 2 -C 3-10 Cycloalkyl, C 2-9Heterocycloalkyl, -C(R 12b ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12b ) 2 -C 6-10 Aryl, -C(R 12b ) 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20l and optionally substituted with R 12a is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12b ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12b ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12b ) 2 -C 6-10 Aryl, -C(R 12b ) 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 12b ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12b ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12b ) 2 -C 6-10 Aryl, -C(R 12b ) 2 -C 1-9Heteroaryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20l and optionally substituted with Each R 12b is hydrogen and R 20l are independently selected from Each R 13 is 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, can be one, two, or three R 20l C optionally substituted with 2-9 forming a heterocycloalkyl ring, Each R 14 is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 14a is C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 15 is 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 a heteroaryl group consisting of one, two, or three R 20m and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R20g , R 20h , R 20i , R 20j , R 20k , R 20l , and R 20m is 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 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 are each independently selected from1-6 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 is halogen, oxo, -CN, 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 and optionally substituted with one, two, or three groups independently selected from Each R21 is H, C 1-6 Alkyl, C 1-6 Haloalkyl, C2-6 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 , 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; Each R 23 H and C 1-6 alkyl, Each R 24 H and C 1-6 alkyl, Each R 25 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; [ka] indicates a single or double bond such that all valences are satisfied.

[0164] In some embodiments, the compound of formula (I) has the structure of formula (Ia): or a pharma- ceutically acceptable salt or solvate thereof. [ka] In the formula, Z 1 , Z 2 , Z 3 , Z 4 , R2 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 4b , R 11c , R 11d , R 12 , R 12a , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20e , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 includes embodiments of compounds of formula (I) and is as described for formula (I); [ka] indicates a single or double bond that fills all valences.

[0165] In some embodiments, the compound of formula (I) has the structure of formula (Ib): or a pharma- ceutically acceptable salt or solvate thereof. [ka] In the formula, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 3 , R 6 , R 7c , R 7d , L 7 , R17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 4b , R 11c , R 11d , R 12 , R 12a , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20c , R 20e , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 includes embodiments of compounds of formula (I) and is as described for formula (I); [ka] indicates a single or double bond that fills all valences.

[0166] In some embodiments, the compound of formula (I) has the structure of formula (Ic): or a pharma- ceutically acceptable salt or solvate thereof. [ka] In the formula, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R4d , R 4a , R 4b , R 11c , R 11d , R 12 , R 12a , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20e , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 includes embodiments of compounds of formula (I) and is as described for formula (I); [ka] indicates a single or double bond that fills all valences.

[0167] In some embodiments, the compound of formula (I) has the structure of formula (Id): or a pharma- ceutically acceptable salt or solvate thereof. [ka] In the formula, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 4b , R 11c , R 11d , R 12 , R 12a , R12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (I), including embodiments of compounds of formula (I); [ka] indicates a single or double bond that fills all valences.

[0168] In some embodiments, the compound of formula (I) has the structure of formula (Ie): [ka] In the formula, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 4b , R 11c , R 11d , R 12 , R 12a , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20f , R 20g , R20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (I), including embodiments of compounds of formula (I); [ka] indicates a single or double bond that fills all valences.

[0169] In some embodiments, the compound of formula (I) has the structure of formula (If): or a pharma- ceutically acceptable salt or solvate thereof. [ka] In the formula, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 3 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 4b , R 11c , R 11d , R 12 , R 12a , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20c , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R22 , R 23 , R 24 , and R 25 includes embodiments of compounds of formula (I) and is as described for formula (I); [ka] indicates a single or double bond that fills all valences.

[0170] In some embodiments, there is provided a compound of formula (II), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, Z 1 , Z 2 , and Z 3 are N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, O, and C(O); Z 4 is N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, and O; In the formula, Z1 , Z 2 , and Z 3 At least one of N(R 4 ), N(R 11d ), C(R 4 ), C(R 11d ), C(R 4 )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d)、 or C(O) or Z 4 is N(R 4 ), N(R 11d ), C(R 4 ), C(R 11d ), C(R 4 )(R 11c)、 C(R 4 )(R 4 ), or C(R 11c )(R 11d) and W 1 is C(R 1 ), C, or N; R 1 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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, and C 2-6 Alkynyl is one, two, or three R 20a and optionally substituted with W 2 is N(R 2a ), N, C(R 2 ), C(R 2 )(R 2a)、 C(O), S(O) 2 or S(O), R 2 is 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 a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with R 2a is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10Aryl, 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 1-9Heteroaryl is a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with W 3 is N(R 3b ), N, C(R 3 ), C(R 3 )(R 3a)、 C(O), S(O) 2 or S(O), R 3 and R 3a is 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 a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with R 3b is 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 )(R13 ), -CH 2 N(R 14 )C(O)R 15 , C.H. 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 a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with W 4 is N or N(R 3c ) and R 3c is 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 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 a heteroaryl group consisting of one, two, or three R 20c and optionally substituted with W 5 is C(R 5 ), C, or N; R 5 is hydrogen, halogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -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, and C 2-6 Alkynyl is one, two, or three R 20d and optionally substituted with W 6 is N(R 6b ), N, C(R 6 ), C(R 6 )(R 6a)、 C(O), S(O), or S(O) 2 and Each R 6 and R 6a is 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 )(R13 ), -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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with R 6b is 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, C1-9 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 ), in the formula, 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 a heteroaryl group consisting of one, two, or three R 20e and optionally substituted with W 7 is N(R 7 ), C(R 7 ), or C(R 7 )(R 7a ) and R 7a and each R 7c is 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 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 a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7d is 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, C2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20f and optionally substituted with R 7 -L 7 -R 17 and L 7 is a bond, -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-, R 17 is 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 a heteroaryl group consisting of one, two, or three R 20g and optionally substituted with W 8 is C(R 8 ), C(R 8 )(R 8a ), N, N(R 8b)、 C(O), S(O), or S(O) 2 and R 8 and R 8a is 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)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 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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted with R 8b is hydrogen, -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 , -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 a heteroaryl group consisting of one, two, or three R 20h and optionally substituted with W 9 is C(R 9 ), C, or N; W 10 is C(R9 ), C, or N; Each R 9 is 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 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20i and optionally substituted with R 4 -L 4 -R 4a and L 4 is a bond, -O-, -N(R 4d )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, -P(O)R 4d -, CR 4c R 4c , -OCR 4c R 4c -, -N(R 4d )CR 4c R4c -,-C(O)CR 4c R 4c -,-SCR 4c R 4c -,-S(O) 2 CR 4c R 4c -,-S(O)CR 4c R 4c -,-P(O)R 4d CR 4c R 4c -,-CR 4c R 4c CR 4c R 4c ,-CR 4c R 4c O-,-CR 4c R 4c N(R 4d )-,-CR 4c R 4c C(O)-,-CR 4c R 4c S-,-CR 4c R 4c S(O) 2 -,-CR 4c R 4c S(O)-,-CR 4c R 4c P(O)R 4d -,-N(R 4d )C(O)-,-N(R 4d )S(O) 2 -,-N(R 4d )S(O)-,-N(R 4d )P(O)R 4d -,-C(O)N(R 4d )-,-S(O) 2 N(R 4d )-,-S(O)N(R 4d )-,-P(O)R 4d N(R 4d )-,-OC(O)-,-OS(O) 2 -,-OS(O)-,-OP(O)R 4d -,-C(O)O-,-S(O) 2 O-,-S(O)O-,-or-P(O)R 4d O-and, each R4c is hydrogen, halogen, -CN, C 1-6 alkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14 , -OC(O)R 14a , -N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14a , and -N(R 14 )S(O) 2 R 14 are independently selected from, 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, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R 4d is hydrogen, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 Cycloalkyl, -CH 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -CH 2 -C 2-9 Heterocycloalkyl, -OR 14 , -SR 14 , -C(O)OR 14 , -C(O)N(R 14)(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -C(O)R 14a , -S(O) 2 R 14 , -S(O) 2 N(R 14 )(R 14 ), -OCH 2 C(O)OR 14 , and -OC(O)R 14a are independently selected from, 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, and -CH 2 -C 2-9 Heterocycloalkyl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, -OR 14 , -SR 14 , -N(R 14 )(R 14 ), -C(O)OR 14 , -C(O)N(R 14 )(R 14 ), -C(O)C(O)N(R 14 )(R 14 ), -OC(O)N(R 14 )(R 14 ), -N(R 14 )C(O)N(R 14 )(R 14 ), -N(R 14 )C(O)OR 14 , -N(R 14 )C(O)R 14 , -N(R 14 )S(O) 2 R 14 , -C(O)R 14a , -S(O) 2 R14 , -S(O) 2 N(R 14 )(R 14 ), and -OC(O)R 14a and optionally substituted with one, two, or three groups independently selected from Each R 4a is 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 one, two, three, or four R 4b and optionally substituted with Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ) and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, C 1-9 Heteroaryl is a heteroaryl group consisting of one or more R 20j and optionally substituted with Each R 11c is hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20k and optionally substituted with Each R 11d is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20k and optionally substituted with Each R 12 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, -C(R 12b ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12b ) 2 -C 2-9 Heterocycloalkyl, C 6-10Aryl, -C(R 12b ) 2 -C 6-10 Aryl, -C(R 12b ) 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 12b ) 2 -C 3-10 Cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12b ) 2 -C 2-9 Heterocycloalkyl, C 6-10 Aryl, -C(R 12b ) 2 -C 6-10 Aryl, -C(R 12b ) 2 -C 1-9 Heteroaryl, and C 1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20l and optionally substituted with Each R 12b is hydrogen and R 20l are independently selected from Each R 13 is 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, can be one, two, or three R 20l C optionally substituted with 2-9 forming a heterocycloalkyl ring, Each R 14 is hydrogen, C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 14a is C 1-6 Alkyl, and C 1-6 haloalkyl; Each R 15 is 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 a heteroaryl group consisting of one, two, or three R 20m and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20k , R 20l , and R 20m is 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 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 are each independently selected from 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 is halogen, oxo, -CN, 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 and optionally substituted with one, two, or three groups independently selected from Each R 21 , 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; Each R 22 , 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; Each R 23 H and C 1-6 alkyl, Each R 24 H and C 1-6 alkyl, Each R25 is C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-6 Cycloalkyl, C 2-9 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 heteroaryl; [ka] indicates a single or double bond such that all valences are satisfied.

[0171] In some embodiments, a compound of formula (II), (IIa), (IIb), (IIc), (IId), (IIe), or (IIf), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z 1 , Z 2 , Z 3 , and Z 4 At least one of N(R 4 ), N(R 11d ), C(R 4 ), C(R 11d ), C(R 4 )(R 11c ), C(R 4 )(R 4 ), or C(R 11c )(R 11d ).

[0172] In some embodiments, the compound of formula (II) has the structure of formula (IIa): or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8, R 4 , L 4 , R 4c , R 4d , R 4a , R 4b , R 11c , R 11d , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20e , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (II), including embodiments of compounds of formula (II); [ka] indicates a single or double bond that fills all valences.

[0173] In some embodiments, the compound of formula (II) has the structure of formula (IIb): or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 3 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R4b , R 11c , R 11d , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20c , R 20e , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (II), including embodiments of compounds of formula (II); [ka] indicates a single or double bond that fills all valences.

[0174] In some embodiments, the compound of formula (II) has the structure of formula (IIc), or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 4b , R 11c , R 11d , R 12 , R 12b , R13 , R 14 , R 14a , R 15 , R 20b , R 20e , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (II), including embodiments of compounds of formula (II); [ka] indicates a single or double bond that fills all valences.

[0175] In some embodiments, the compound of formula (II) has the structure of formula (IId): or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 4b , R 11c , R 11d , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20f , R 20g , R20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (II), including embodiments of compounds of formula (II); [ka] indicates a single or double bond that fills all valences.

[0176] In some embodiments, the compound of formula (II) has the structure of formula (IIe), or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 4b , R 11c , R 11d , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R24 , and R 25 is as described for formula (II), including embodiments of compounds of formula (II); [ka] indicates a single or double bond that fills all valences.

[0177] In some embodiments, the compound of formula (II) has the structure of formula (IIf), or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 3 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 4b , R 11c , R 11d , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20c , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (II), including embodiments of compounds of formula (II); [ka] indicates a single or double bond that fills all valences.

[0178] In some embodiments, a compound of formula (II), (IIa), (IIb), (IIc), (IId), (IIe), or (IIf), or a pharma- ceutically acceptable salt or solvate thereof, wherein Z 1 , Z 2 , Z 3 , and Z 4 At least one of N(R 4 ), N(R 11d ), C(R 4 ), C(R 11d ), C(R 4 )(R 11c ), C(R 4 )(R 4 ), or C(R 11c )(R 11d ).

[0179] The individual embodiments of the present specification below, or combinations thereof (e.g., 1 The embodiment of Z 2 , Z 3 or Z 4 ) applies to a compound of formula (I), (II), (III), (IV), (XVI), (XVII), (Ia), (IIa), (IIIa), (IVa), (XVIa), (XVIIa), (Ib), (IIb), (IIIb), (IVb), (XVIb), (XVIIb), (Ic), (IIc), (IIIc), (IVc), (XVIc), (XVIIc), (Id), (IId), (IIId), (IVd), (XVId), (XVIId), (Ie), (IIe), (IIIe), (IVe), (XVIe), (XVIIe), (If), (IIf), (IIIf), (IVf), (XVIf), or (XVIIf), or a pharma- ceutically acceptable salt or solvate thereof. In the above formula embodiment, Z 1 is N(R 4 In the above formula embodiment, Z 1 is N(R 11cIn the above formula embodiment, Z 1 is N(R 11d In the above formula embodiment, Z 1 is N. In the above formula embodiment, Z 1 is C(R 4 In the above formula embodiment, Z 1 is C(R 11c In the above formula embodiment, Z 1 is C(R 11d In the above formula embodiment, Z 1 is C(R 4 )(R 11c In the above formula embodiment, Z 1 is C(R 11c )(R 11c In the above formula embodiment, Z 1 is C(R 4 )(R 4 In the above formula embodiment, Z 1 is C(R 11c )(R 11d In the above formula embodiment, Z 1 is S. In the above formula embodiment, Z 1 is O. In the above formula embodiment, Z 1 is C(O). In the above formula embodiment, Z 2 is N(R 4 In the above formula embodiment, Z 2 is N(R 11c In the above formula embodiment, Z 2 is N(R 11d In the above formula embodiment, Z 2 is N. In the above formula embodiment, Z 2 is C(R 4 In the above formula embodiment, Z 2 is C(R 11c In the above formula embodiment, Z 2 is C(R 11d In the above formula embodiment, Z 2 is C(R 4 )(R 11c In the above formula embodiment, Z2 is C(R 11c )(R 11c In the above formula embodiment, Z 2 is C(R 4 )(R 4 In the above formula embodiment, Z 2 is C(R 11c )(R 11d In the above formula embodiment, Z 2 is S. In the above formula embodiment, Z 2 is O. In the above formula embodiment, Z 2 is C(O). In the above formula embodiment, Z 3 is N(R 4 In the above formula embodiment, Z 3 is N(R 11c In the above formula embodiment, Z 3 is N(R 11d In the above formula embodiment, Z 3 is N. In the above formula embodiment, Z 3 is C(R 4 In the above formula embodiment, Z 3 is C(R 11c In the above formula embodiment, Z 3 is C(R 11d In the above formula embodiment, Z 3 is C(R 4 )(R 11c In the above formula embodiment, Z 3 is C(R 11c )(R 11c In the above formula embodiment, Z 3 is C(R 4 )(R 4 In the above formula embodiment, Z 3 is C(R 11c )(R 11d In the above formula embodiment, Z 3 is S. In the above formula embodiment, Z 3 is O. In the above formula embodiment, Z 3 is C(O). In the above formula embodiment, Z 4 is N(R4 In the above formula embodiment, Z 4 is N(R 11c In the above formula embodiment, Z 4 is N(R 11d In the above formula embodiment, Z 4 is N. In the above formula embodiment, Z 4 is C(R 4 In the above formula embodiment, Z 4 is C(R 11c In the above formula embodiment, Z 4 is C(R 11d In the above formula embodiment, Z 4 is C(R 4 )(R 11c In the above formula embodiment, Z 4 is C(R 11c )(R 11c In the above formula embodiment, Z 4 is C(R 4 )(R 4 In the above formula embodiment, Z 4 is C(R 11c )(R 11d In the above formula embodiment, Z 4 is S. In the above formula embodiment, Z 4 is O. In the above formula embodiment, Z 4 is C(O).

[0180] In one embodiment, there is provided a compound of formula (III): [ka] During the ceremony, Z 1 , Z 2 , and Z 3 are N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, O, and C(O); Z 4 is N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, and O; In the formula, Z 1 , Z 2 , Z 3 , and Z 4 At least one of N(R 4 ), N(R 11d)、 C(R 4 ), C(R 11d ), C(R 4 )(R 11c)、 C(R 4 )(R 4 ), or C(R 11c )(R 11d ) and W 1 , R 1 , W 2 , R 2 , R 2a , W 3 , R 3 , R 3a , R 3b , W 4 , R 3c , W 5 , R 5 , W 6 , R 6 , R 6a , R 6b , W 7 , R7a , R 7c , R 7d , R 7 , L 7 , R 17 , W 8 , R 8 , R 8a , R8 b , W 9 , W 10 , R 9 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (II), including embodiments of compounds of formula (II); Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl can be one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0181] In some embodiments, the compound of formula (III) has the structure of formula (IIIa): or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , and Z 3 are N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, O, and C(O); Z 4 is N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, and O; In the formula, Z 1 , Z 2 , Z 3 , and Z 4 At least one of N(R 4 ), N(R 11d)、 C(R 4 ), C(R 11d ), C(R 4)(R 11c)、 C(R 4 )(R 4 ), or C(R 11c )(R 11d ) and R 2 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20e , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described in Formula (IIa), including embodiments of compounds of Formula (IIa). Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl can be one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0182] In some embodiments, the compound of formula (III) has the structure of formula (IIIb): [ka] During the ceremony, Z 1 , Z 2 , and Z 3 are N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, O, and C(O); Z 4 is N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, and O; In the formula, Z 1 , Z 2 , Z 3 , and Z 4 At least one of N(R 4 ), N(R 11d)、 C(R 4 ), C(R 11d ), C(R 4 )(R 11c)、 C(R 4 )(R4 ), or C(R 11c )(R 11d ) and R 2 , R 3 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20c , R 20e , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described in formula (IIb), including embodiments of compounds of formula (IIb); Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl can be one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0183] In some embodiments, the compound of formula (III) has the structure of formula (IIIc): [ka] During the ceremony, Z 1 , Z 2 , and Z 3 are N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, O, and C(O); Z 4 is N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, and O; In the formula, Z 1 , Z 2 , Z 3 , and Z 4 At least one of N(R 4 ), N(R 11d)、 C(R 4 ), C(R 11d ), C(R 4 )(R 11c)、 C(R 4 )(R4 ), or C(R 11c )(R 11d ) and R 2 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20e , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described in Formula (IIc), including embodiments of compounds of Formula (IIc). Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl can be one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0184] In some embodiments, the compound of formula (III) has the structure of formula (IIId): [ka] During the ceremony, Z 1 , Z 2 , and Z 3 are N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, O, and C(O); Z 4 is N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, and O; In the formula, Z 1 , Z 2 , Z 3 , and Z 4 At least one of N(R 4 ), N(R 11d)、 C(R 4 ), C(R 11d ), C(R 4 )(R 11c)、 C(R 4 )(R 4 ), or C(R 11c)(R 11d ) and R 2 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (IId), including embodiments of compounds of formula (IId). Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl can be one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0185] In some embodiments, the compound of formula (III) has the structure of formula (IIIe): [ka] During the ceremony, Z 1 , Z 2 , and Z 3 are N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, O, and C(O); Z 4 is N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, and O; In the formula, Z 1 , Z 2 , Z 3 , and Z 4 At least one of N(R 4 ), N(R 11d)、 C(R 4 ), C(R 11d ), C(R 4 )(R 11c)、 C(R 4 )(R 4 ), or C(R 11c )(R 11d ) and R 2 , R 7c, R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (IIe), including embodiments of compounds of formula (IIe). Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl can be one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0186] In some embodiments, the compound of formula (III) has the structure of formula (IIIf): [ka] During the ceremony, Z 1 , Z 2 , and Z 3 are N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, O, and C(O); Z 4 is N(R 4 ), N(R 11c ), N(R 11d ), N, C(R 4 ), C(R 11c ), C(R 11d ), C(R 4 )(R 11c ), C(R 11c )(R 11c ), C(R 4 )(R 4 ), C(R 11c )(R 11d ), S, and O; In the formula, Z 1 , Z 2 , Z 3 , and Z 4 At least one of N(R 4 ), N(R 11d)、 C(R 4 ), C(R 11d ), C(R 4 )(R 11c)、 C(R 4 )(R 4 ), or C(R 11c )(R 11d ) and R 2 , R 3 , R 7c , R 7d , L 7 , R 17 , R8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20c , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described in formula (IIf), including embodiments of compounds of formula (IIf). Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl can be one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0187] In one embodiment, there is provided a compound of formula (IV), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, Z 1 , Z 2 , Z 3, Z 4 , W 1 , R 1 , W 2 , R 2 , R 2a , W 3 , R 3 , R 3a , R 3b , W 4 , R 3c , W 5 , R 5 , W 6 , R 6 , R 6a , R 6b , W 7 , R 7a , R 7c , R 7d , R 7 , L 7 , R 17 , W 8 , R 8 , R 8a , R 8b , W 9 , W 10 , R 9 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12a , R 12b , R 13 , R 14 , R 14a , R 15 , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described in formula (I), including embodiments of compounds of formula (I). Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl can be one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0188] In some embodiments, the compound of formula (IV) has the structure of formula (IVa): or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12a , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20e , R 20f , R 20g , R 20h , R 20j , R 20k, R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (Ia), including embodiments of compounds of formula (Ia). Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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(R14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl can be one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0189] In some embodiments, the compound of formula (IV) has the structure of formula (IVb): [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 3 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12a , R 12b , R13 , R 14 , R 14a , R 15 , R 20b , R 20c , R 20e , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described in formula (Ib), including embodiments of compounds of formula (Ib). Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0190] In some embodiments, the compound of formula (IV) has the structure of formula (IVc), or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 6 , R 7c , R 7d , L 7 , R 17 , R8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12a , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20e , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described in formula (Ic), including embodiments of compounds of formula (Ic). Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0191] In some embodiments, the compound of formula (IV) has the structure of formula (IVd), or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z1 , Z 2 , Z 3 , Z 4 , R 2 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12a , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (Id), including embodiments of compounds of formula (Id). Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0192] In some embodiments, the compound of formula (IV) has the structure of formula (IVe): [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12a , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (Ie), including embodiments of compounds of formula (Ie). Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0193] In some embodiments, the compound of formula (IV) has the structure of formula (IVf): [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 2 , R 3 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 11c , R 11d , R 12 , R 12a , R 12b , R 13 , R 14 , R 14a , R 15 , R 20b , R 20c , R 20f , R 20g , R 20h , R 20j , R 20k , R 20l , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 is as described in formula (If), including embodiments of compounds of formula (If). Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12Cycloalkyl, C 2-11 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is one or more R 20j and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0194] In one embodiment, there is provided a compound of formula (XVI): or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 Z 4 , W 1 , R 1 , W 2 , R 2a , W 3 , R 3 , R 3a , R 3b , W 4 , R 3c , W 5 , R 5 , W 6 , R 6 , R 6a , R6 b , W 7 , R 7a , R 7c , R 7d , R 7 , L 7 , R 17 , W 8 , R 8 , R 8a , R 8b , W 9 , W 10 , R 9 , R 4 , L 4 , R 4c , R 4d , R 4a , R 12 , R12b , R 13 , R 14 , R 14a , R 15 , R 21 , R 22 , R 23 , R 24 , and R 25 includes embodiments of compounds of formula (III) and are as described in formula (III). R 2 is 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 ), -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 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 a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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(R 21b ) 2 , -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 12 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is one or more R 20j and optionally substituted with Each R 11c is hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C1-11 Heteroaryl, C 1-11 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 ), -(C 1-6 alkyl)-C(O)N(R 12 )(R 13 ), -(C 1-6 Alkyl)-N(R 12 )(R 13 ), -(C 1-6 Alkyl)-OC(O)R 12 , -(C 1-6 Alkyl)-N(R 14 )C(O)R 12 , -(C 1-6 Alkyl)-S(O) 2 R 15 , and -(C 1-6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), where C 1-6Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is one, two, three, four, or five R 20k and optionally substituted with Each R 11d is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 ), -(C 1-6 alkyl)-C(O)N(R 12 )(R 13 ), -(C 1-6 Alkyl)-OC(O)R 12 , -(C 1-6 Alkyl)-N(R 14 )C(O)R 12 , -(C 1-6 Alkyl)-N(R 12 )(R 13 ), -(C 1-6 Alkyl)-S(O) 2 R 15 , and -(C 1-6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11Heteroaryl is one, two, three, four, or five R 20k and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20k , R 20l , and R 20m is 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 ), =NR 21 , =C(R 21b ) 2 , -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 , and -OC(O)R 25 are independently selected from, 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 is halogen, oxo, -CN, 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 is 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 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 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently selected from R 21b represents hydrogen, halogen, C in each occurrence. 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 or two R 21b together with the carbon atom to which they are attached, C 3-10 Cycloalkyl or C 2-9 heterocycloalkyl, each of which is selected from halogen, C 1-3 Alkyl, C 1-3 optionally substituted with 1, 2, or 3 substituents optionally substituted from haloalkyl, and -OH; [ka] indicates a single or double bond such that all valences are satisfied.

[0195] In some embodiments, the compound of formula (XVI) has the structure of formula (XVIa), or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 21 , R 22 , R 23 , R 24 , and R 25 is as described in formula (IIIa), including embodiments of compounds of formula (IIIa); R 2 is 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 ), -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 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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(R 21b ) 2 , -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 12 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C6-10 Aryl, and C 1-9 Heteroaryl is one or more R 20j and optionally substituted with Each R 11c is hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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(R12 )(R 13 ), -(C 1-6 alkyl)-C(O)N(R 12 )(R 13 ), -(C 1-6 Alkyl)-N(R 12 )(R 13 ), -(C 1-6 Alkyl)-OC(O)R 12 , -(C 1-6 Alkyl)-N(R 14 )C(O)R 12 , -(C 1-6 Alkyl)-S(O) 2 R 15 , and -(C 1-6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is one, two, three, four, or five R 20k and optionally substituted with Each R 11d is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 ), -(C 1-6 alkyl)-C(O)N(R 12 )(R 13 ), -(C 1-6 Alkyl)-N(R 12 )(R 13 ), -(C 1-6 Alkyl)-OC(O)R 12 , -(C 1-6 Alkyl)-N(R 14 )C(O)R 12 , -(C 1-6 Alkyl)-S(O) 2 R 15 , and -(C 1-6Alkyl)-S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is one, two, three, four, or five R 20k and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20k , R 20l , and R 20m is 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 , -SR21 , -N(R 22 )(R 23 ), =NR 21 , =C(R 21b ) 2 , -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 , 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 Heteroaryl is halogen, oxo, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6Haloalkoxy, -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 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently selected from R 21b is independently selected at each occurrence from hydrogen, halogen, 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, or two R 21b together with the carbon atom to which they are attached, C 3-10 Cycloalkyl or C 2-9 heterocycloalkyl, each of which is selected from the group consisting of halogen, C 1-3 Alkyl, C 1-3 optionally substituted with 1, 2 or 3 substituents independently selected from haloalkyl, and -OH; [ka] indicates a single or double bond where all valences are satisfied.

[0196] In some embodiments, the compound of formula (XVI) has the structure of formula (XVIb), or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 3 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (IIIb), including embodiments of compounds of formula (IIIb); R 2 is 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 ), -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 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with Each R 4b is halogen, oxo, -CN, C 1-6Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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(R 21b ) 2 , -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 12 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 )2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is one or more R 20j and optionally substituted with Each R 11c is hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 ), -(C 1-6 alkyl)-C(O)N(R 12 )(R 13 ), -(C 1-6 Alkyl)-N(R 12 )(R 13 ), -(C 1-6 Alkyl)-OC(O)R 12 , -(C 1-6 Alkyl)-N(R 14 )C(O)R 12 , -(C 1-6 Alkyl)-S(O) 2 R 15 , and -(C 1-6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is one, two, three, four, or five R 20k and optionally substituted with Each R 11d is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 ), -(C 1-6 alkyl)-C(O)N(R 12 )(R 13 ), -(C 1-6 Alkyl)-N(R 12 )(R 13 ), -(C 1-6 Alkyl)-OC(O)R12 , -(C 1-6 Alkyl)-N(R 14 )C(O)R 12 , -(C 1-6 Alkyl)-S(O) 2 R 15 , and -(C 1-6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is one, two, three, four, or five R 20k and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20k , R 20l , and R 20m is 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, C6-10 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 ), =NR 21 , =C(R 21b ) 2 , -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 , 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 -C1-9 Heteroaryl, and C 1-9 Heteroaryl is 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 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 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently selected from R 21b is independently selected at each occurrence from hydrogen, halogen, 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, or two R 21b together with the carbon atom to which they are attached, C 3-10 Cycloalkyl or C2-9 heterocycloalkyl, each of which is selected from the group consisting of halogen, C 1-3 Alkyl, C 1-3 optionally substituted with 1, 2 or 3 substituents independently selected from haloalkyl, and -OH; [ka] indicates a single or double bond where all valences are satisfied.

[0197] In some embodiments, the compound of formula (XVI) has the structure of formula (XVIc), or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 6 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 21 , R 22 , R 23 , R 24 , and R 25 is as described in formula (IIIc), including embodiments of compounds of formula (IIIc); R 2 is halogen, -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 ), -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 C1-9 Heteroaryl is a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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(R 21b ) 2 , -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 12 , -CH 2 S(O)2 R 15 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is one or more R 20j and optionally substituted with Each R 11c is hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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)R15 , -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 ), -(C 1-6 alkyl)-C(O)N(R 12 )(R 13 ), -(C 1-6 Alkyl)-N(R 12 )(R 13 ), -(C 1-6 Alkyl)-OC(O)R 12 , -(C 1-6 Alkyl)-N(R 14 )C(O)R 12 , -(C 1-6 Alkyl)-S(O) 2 R 15 , and -(C 1-6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is one, two, three, four, or five R 20kand optionally substituted with Each R 11d is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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 ), -(C 1-6 alkyl)-C(O)N(R12 )(R 13 ), -(C 1-6 Alkyl)-N(R 12 )(R 13 ), -(C 1-6 Alkyl)-OC(O)R 12 , -(C 1-6 Alkyl)-N(R 14 )C(O)R 12 , -(C 1-6 Alkyl)-S(O) 2 R 15 , and -(C 1-6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), where C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, and C 1-11 Heteroaryl is one, two, three, four, or five R 20k and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20k , R 20l , and R 20m is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10Cycloalkyl, -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 ), =NR 21 , =C(R 21b ) 2 , -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 , 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 2-9Heterocycloalkyl, -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 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 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 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently selected from R 21b is independently selected at each occurrence from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 2-9Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl, or two R 21b together with the carbon atom to which they are attached, C 3-10 Cycloalkyl or C 2-9 heterocycloalkyl, each of which is selected from the group consisting of halogen, C 1-3 Alkyl, C 1-3 optionally substituted with 1, 2 or 3 substituents independently selected from haloalkyl, and -OH; [ka] indicates a single or double bond where all valences are satisfied.

[0198] In some embodiments, the compound of formula (XVI) has the structure of formula (XVId), or a pharma- ceutically acceptable salt or solvate thereof. [ka] During the ceremony, Z 1 , Z 2 , Z 3 , Z 4 , R 7c , R 7d , L 7 , R 17 , R 8 , R 4 , L 4 , R 4c , R 4d , R 4a , R 4b , R 12 , R 12b , R 13 , R 14 , R 14a , R 15 , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (IIId), including embodiments of compounds of formula (IIId); R 2is 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 ), -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 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 a heteroaryl group consisting of one, two, or three R 20b and optionally substituted with Each R 4b is halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 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(R 21b ) 2 , -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 ), -CH2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 12 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 are independently selected from, 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, C 2-11 Heterocycloalkyl, C 6-10 Aryl, and C 1-9 Heteroaryl is one or more R 20j and optionally substituted with Each R 11c is hydrogen, halogen, oxo, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 3-12 Cycloalkyl, -CH 2 -C 3-12 Cycloalkyl, C 1-11 Heterocycloalkyl, -CH 2 -C 1-11 Heterocycloalkyl, C 6-10 Aryl, -CH 2 -C 6-10 Aryl, -CH 2 -C 1-11 Heteroaryl, C 1-11 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...

Claims

1. Formula: 【Chemistry 1】 A compound having, or a pharmaceutically acceptable salt or solvate thereof, During the ceremony, R2 is -OR 12a, halogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, C1-9 heteroaryl, -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 Selected from -C(O)N(R12)(R13), -C(O)C(O)N(R12)(R13), -N(R14)C(O)R15, -S(O)2R15, -S(O)2N(R12)(R13)-, S(=O)(=NH)N(R12)(R13), -CH2C(O)N(R12)(R13), -CH2N(R14)C(O)R15, -CH2S(O)2R15, and -CH2S(O)2N(R12)(R13), where C1-6 alkyl, C2-6 alkenyl, C 2-6 alkynyls, C3-10 cycloalkyls, C2-9 heterocycloalkyls, C6-10 aryls, and C1-9 heteroaryls are optionally substituted with one, two, or three R20b groups. R6 is a halogen, hydrogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, C1-9 heteroaryl, -OR12, -SR12, -N(R12)(R13), -C(O)OR12, -OC(O)N(R12)(R13), -N(R14)C(O)N(R12)(R13), -N(R14)C(O)OR15, -N(R14)S(O)2R15, -C(O)R15, -S(O)R15, -OC(O)R15 Selected from -C(O)N(R12)(R13), -C(O)C(O)N(R12)(R13), -N(R14)C(O)R15, -S(O)2R15, -S(O)2N(R12)(R13)-, S(=O)(=NH)N(R12)(R13), -CH2C(O)N(R12)(R13), -CH2N(R14)C(O)R15, -CH2S(O)2R15, and -CH2S(O)2N(R12)(R13), where C1-6 alkyl, C2-6 alkenyl, C 2-6 alkynyls, C3-10 cycloalkyls, C2-9 heterocycloalkyls, C6-10 aryls, and C1-9 heteroaryls are optionally substituted with one, two, or three R20e groups. R17 【Chemistry 2】 Selected from, R8 is a halogen, hydrogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, C1-9 heteroaryl, -OR12, -SR12, -N(R12)(R13), -C(O)OR12, -OC(O)N(R12)(R13), -N(R14)C(O)N(R12)(R13), -N(R14)C(O)OR15, -N(R14)S(O)2R15, -C(O)R15, -S(O)R15, -OC(O)R15 Selected from -C(O)N(R12)(R13), -C(O)C(O)N(R12)(R13), -N(R14)C(O)R15, -S(O)2R15, -S(O)2N(R12)(R13), -S(=O)(=NH)N(R12)(R13), -CH2C(O)N(R12)(R13), -CH2N(R14)C(O)R15, -CH2S(O)2R15, and -CH2S(O)2N(R12)(R13), where C1-6 alkyl, C2-6 alkenyl, C 2-6 alkynyls, C3-10 cycloalkyls, C2-9 heterocycloalkyls, C6-10 aryls, and C1-9 heteroaryls are optionally substituted with one, two, or three R20h groups. R4 is -L4 -R4a, L 4 が、CR 4c R 4c 、 coupling、-O-、-N(R 4d )-、-C(O)-、--、-S----、-S---------------------------- -、-C(O)CR 4c R 4c -、-SCR 4c R 4c -、-S(O) 2CR 4c R 4# -、-SO)CR 4#R -- 4c 、-CR 4c R 4c O-、-ER 4A N(R 4d )-、-OC(O)-、-OS(O) 2 -、-OS(O)-、-OP(O)RR--、-C(O)--、-OO-------OO-、-------------------- Each R 4c is hydrogen, halogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-10 cycloalkyl, -CH2-C3-10 cycloalkyl, C2-9 heterocycloalkyl, -CH2-C2-9 heterocycloalkyl, -OR 14, -SR 14, -C(O)OR 14, -C(O)N(R 14)(R 14), -C(O)C(O)N(R 14)(R 14), -OC(O)N(R 14)(R 14), -C(O)R 14a, -S(O)2R 14, -S(O)2 Independently selected from N(R 14)(R 14), -OCH2C(O)OR 14, -OC(O)R 14a, -N(R 14)(R 14), -N(R 14)C(O)N(R 14)(R 14), -N(R 14)C(O)OR 14, -N(R 14)C(O)R 14a, and -N(R 14)S(O)2R 14, where C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, -CH2-C3-10 cycloalkyl, C2-9 heterocycloalkyl, and -CH2-C2-9 Heterocycloalkyls include halogens, oxo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, -OR 14, -SR 14, -N(R 14)(R 14), -C(O)OR 14, -C(O)N(R 14)(R 14), -C(O)C(O)N(R 14)(R 14), -OC(O)N(R 14)(R 14), -N(R 14)C(O)N(R 14)(R 14), -N(R 14)C(O)OR 14, -N(R 14)C(O)R 14, -N(R 14)S(O)2R 14 , -C(O)R 14a, -S(O) 2R 14, -S(O) 2N(R 14)(R 14), and -OC(O)R 14a are optionally substituted with one, two, or three groups independently selected from these. Each R 4d is hydrogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-10 cycloalkyl, -CH2-C3-10 cycloalkyl, C2-9 heterocycloalkyl, -CH2-C2-9 heterocycloalkyl, -OR 14, -SR 14, -C(O)OR 14, -C(O)N(R 14)(R 14), -C(O)C(O)N(R 14)(R 14), -OC(O)N(R 14)(R 14), -C(O)R 14a, -S(O)2R 14, -S(O)2 N(R 14)(R 14), -OCH2C(O)OR 14, and -OC(O)R 14a are independently selected, where C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, -CH2-C3-10 cycloalkyl, C2-9 heterocycloalkyl, and -CH2-C2-9 heterocycloalkyl are halogen, oxo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, -OR 14, -SR 14, -N(R 14)(R 14), -C(O)OR 14, -C(O)N(R 14)(R 14) ), -C(O)C(O)N(R 14)(R 14), -OC(O)N(R 14)(R 14), -N(R 14)C(O)N(R 14)(R 14), -N(R 14)C(O)OR 14, -N(R 14)C(O)R 14, -N(R 14)S(O)2R 14, -C(O)R 14a, -S(O)2R 14, -S(O)2N(R 14)(R 14), and -OC(O)R 14a are optionally substituted with one, two, or three groups independently selected from these. Each R 4a is independently selected from C1-9 heteroaryl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, and C6-10 aryl, where C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with one, two, three, or four R 4b. Each R 4b is -N(R 12)(R 13), halogen, oxo, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 cycloalkyl, C2-11 heterocycloalkyl, C6-10 aryl, C1-9 heteroaryl, -OR 12, -SR 12, -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) 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), and -P(=O)(R 12 ) 2 independently selected, where C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 cycloalkyl, C2-11 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with one or more R20j, Each R 11c is a C 2-6 alkenyl, C 2-6 alkynyl, hydrogen, halogen, oxo, -CN, C 1-6 alkyl, C 1-6 haloalkyl, C 3-12 cycloalkyl, -CH 2-C 3-12 cycloalkyl, C 1-11 heterocycloalkyl, -CH 2-C 1-11 heterocycloalkyl, C 6-10 aryl, -CH 2-C 6-10 aryl, -CH 2-C 1-11 heteroaryl, C 1-11 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, -CH2S(O)2R 15, and -CH2S(O)2N(R 12)(R 13) are independently selected, where C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-12 cycloalkyl, -CH2-C3-12 cycloalkyl, C1-11 heterocycloalkyl, -CH2-C1-11 heterocycloalkyl, C6-10 aryl, -CH2-C6-10 aryl, -CH2-C1-11 heteroaryl, and C1-11 heteroaryl are optionally substituted with one, two, or three R 20k. Each R12 is independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, -C(R12b)2 -C3-10 cycloalkyl, C2-9 heterocycloalkyl, -C(R12b)2 -C2-9 heterocycloalkyl, C6-10 aryl, -C(R12b)2 -C6-10 aryl, -C(R12b)2 -C1-9 heteroaryl, and C1-9 heteroaryl, where C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, -C(R12b)2 -C3-10 cycloalkyl, and C2-9 Heterocycloalkyl, -C(R 12b) 2-C 2-9 heterocycloalkyl, C 6-10 aryl, -C(R 12b) 2-C 6-10 aryl, -C(R 12b) 2-C 1-9 heteroaryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three R 20l. R 12a is selected from -C(R 12b) 2 -C 2-9 heterocycloalkyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -C(R 12b) 2 -C 3-10 cycloalkyl, C 2-9 heterocycloalkyl, C 6-10 aryl, -C(R 12b) 2 -C 6-10 aryl, -C(R 12b) 2 -C 1-9 heteroaryl, and C 1-9 heteroaryl, where C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, -C(R 12b) 2 -C 3-10 cycloalkyl, C 2-9 Heterocycloalkyl, -C(R 12b) 2-C 2-9 heterocycloalkyl, C 6-10 aryl, -C(R 12b) 2-C 6-10 aryl, -C(R 12b) 2-C 1-9 heteroaryl, and C 1-9 heteroaryl are optionally substituted with one, two, or three R 20l. Each R12b is independently selected from hydrogen and R20l. Each R13 is independently selected from hydrogen, C1-6 alkyl, and C1-6 haloalkyl, or R12 and R13, together with the nitrogen to which they are bonded, form a C2-9 heterocycloalkyl ring optionally substituted with one, two, or three R20l. Each R14 is independently selected from hydrogen, C1-6 alkyl, and C1-6 haloalkyl. Each R 14a is independently selected from C 1-6 alkyl and C 1-6 haloalkyl groups. Each R 15 is 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, 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 are optionally substituted with one, two, or three R 20m. Each of R 20b, R 20e, R 20h, R 20j, R 20k, R 20l, and R 20m is a halogen, oxo, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, -CH2-C3-10 cycloalkyl, C2-9 heterocycloalkyl, -CH2-C2-9 heterocycloalkyl, C6-10 aryl, -CH2-C6-10 aryl, -CH2-C1-9 heteroaryl, C1-9 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)2R 25, -C(O)R 25, -S(O)2R 25, -S(O)2N(R 22)(R 23), -OCH2C(O)OR 22, and -OC(O)R 25 independently selected, where C1-6 alkyl, C2-6 alkenyl, C 2-6 alkynyl, C3-10 cycloalkyl, -CH2-C3-10 cycloalkyl, C2-9 heterocycloalkyl, -CH2-C2-9 heterocycloalkyl, C6-10 aryl, -CH2-C6-10 aryl, -CH2-C1-9 heteroaryl, and C1-9 heteroaryl are halogens, oxo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, -OR21, -SR21, -N(R22)(R23), -C(O)OR22, -C(O)N(R22)(R23), -C(O)C(O)N(R22)(R23) ), -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)R25, -S(O)2R25, -S(O)2N(R22)(R23), and -OC(O)R25 are optionally substituted with one, two, or three groups independently selected from these. Each R21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl. Each R22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl. Each R23 is independently selected from H and C1-6 alkyl groups. Each R24 is independently selected from H and C1-6 alkyl groups. Compounds, or pharmaceutically acceptable salts or solvates thereof, in which each R 25 is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl.

2. R 17 is, 【Transformation 3】 The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

3. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R 6 is selected from hydrogen, halogen, -CN, C1-6 alkyl, and -OR 12, and the C1-6 alkyl is optionally substituted with one, two, or three R 20e.

4. The compound according to claim 2, or a pharmaceutically acceptable salt or solvate thereof, wherein R 6 is selected from hydrogen, halogen, -CN, C1-6 alkyl, and -OR 12, and the C1-6 alkyl is optionally substituted with one, two, or three R 20e.

5. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R 8 is selected from hydrogen, halogen, -CN, C1-6 alkyl, and -OR 12, and the C1-6 alkyl is optionally substituted with one, two, or three R 20h.

6. The compound according to claim 2, or a pharmaceutically acceptable salt or solvate thereof, wherein R 8 is selected from hydrogen, halogen, -CN, C1-6 alkyl, and -OR 12, and the C1-6 alkyl is optionally substituted with one, two, or three R 20h.

7. The compound according to claim 4, or a pharmaceutically acceptable salt or solvate thereof, wherein R 8 is selected from hydrogen, halogen, -CN, C1-6 alkyl, and -OR 12, and the C1-6 alkyl is optionally substituted with one, two, or three R 20h.

8. Formula: 【Chemistry 4】 The compound according to claim 7, or a pharmaceutically acceptable salt or solvate thereof, having the above.

9. Formula: 【Transformation 5】 The compound according to claim 6, or a pharmaceutically acceptable salt or solvate thereof, having the above.

10. Each R11c is independently selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, -CH2-C3-12 cycloalkyl, C1-11 heterocycloalkyl, -CH2-C1-11 heterocycloalkyl, C6-10 aryl, -CH2-C6-10 aryl, -CH2-C1-11 heteroaryl, and C1-11 heteroaryl, and C1-11 alkyl, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, -CH2-C3-12 cycloalkyl, C1-11 heterocycloalkyl, -CH2-C1-11 heterocycloalkyl, C6-10 aryl, -CH2-C6-10 aryl, -CH2 A compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, wherein the C1-11 heteroaryl and the C1-11 heteroaryl are optionally substituted with one, two, or three R20k groups.

11. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, wherein R 11c is independently selected from hydrogen and C 1-6 alkyl groups optionally substituted with one, two, or three R 20k.

12. The compound according to any one of claims 1 to 9, wherein R 11c is hydrogen, or a pharmaceutically acceptable salt or solvate thereof.

13. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, wherein L 4 is a bond, -O-, -N(R 4d)-, -C(O)-, or CR 4c R 4c.

14. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4a is a C 3-10 cycloalkyl group optionally substituted with one, two, three, or four R 4b groups.

15. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4a is a C2-9 heterocycloalkyl group optionally substituted with one, two, three, or four R 4b groups.

16. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4a is a C 6-10 aryl optionally substituted with one, two, three, or four R 4b.

17. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4a is a C 1-9 heteroaryl in which R 4a is optionally substituted with one, two, three, or four R 4b.

18. The compound according to any one of claims 1 to 9, wherein R 2 is -OR 12a, or a pharmaceutically acceptable salt or solvate thereof.

19. The compound according to claim 18, or a pharmaceutically acceptable salt or solvate thereof, wherein R 12a is independently a -C(R 12b)2-C2-9 heterocycloalkyl group substituted with one, two, or three R 20l groups.

20. R2 is 【Transformation 6】 【Transformation 7】 【Transformation 8】 A compound according to any one of claims 1 to 9, selected from, or a pharmaceutically acceptable salt or solvate thereof.

21. R2 is 【Chemistry 9】 【Chemistry 10】 【Chemistry 11】 A compound according to claim 17, or a pharmaceutically acceptable salt or solvate thereof, selected from the above.

22. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is 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, -OR 12a, -SR 12, and -N(R 12)(R 13), and 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 are optionally substituted with one, two, or three R 20b.

23. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4a is a monocyclic six-membered heteroaryl in which R 4a is optionally substituted with one, two, three, or four R 4b.

24. The compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or solvate thereof, wherein R 6 is independently selected from halogens and -CF 3.

25. The compound according to any one of claims 1 to 9, wherein R 8 is a halogen, or a pharmaceutically acceptable salt or solvate thereof.

26. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4a is a six-membered heteroaryl comprising at least one nitrogen atom and optionally substituted with one, two, three, or four R 4b atoms.

27. ​​The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, wherein L 4 is CR 4c R 4c.

28. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, wherein R 4b is independently selected from halogens and -N(H)2.

29. R 4 is 【Chemistry 12】 The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof.

30. R2 is 【Chemistry 13】 【Chemistry 14】 【Chemistry 15】 【Chemistry 16】 Selected from, R 6 is independently selected from halogen and -CF 3. The compound according to claim 29, wherein R8 is a halogen, or a pharmaceutically acceptable salt or solvate thereof.

31. A pharmaceutical composition comprising a compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

32. A composition comprising a compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of cancer in a subject requiring cancer treatment.

33. Use of a compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt or solvate thereof, for the manufacture of a pharmaceutical for treating cancer in a person requiring cancer treatment.

34. A composition comprising the compound according to claim 30, or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of cancer in a subject requiring cancer treatment.

35. Use of the compound according to claim 30, or a pharmaceutically acceptable salt or solvate thereof, for the manufacture of a pharmaceutical for treating cancer in a person requiring cancer treatment.

36. A pharmaceutical composition comprising the compound described in claim 30, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

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