Complex cyclic compounds and their use

Abstract

The present disclosure provides compounds and pharmaceutically acceptable salts thereof, and methods of using them in the treatment of cancer or to inhibit cell growth. The compounds and methods have a wide range of uses as therapeutics, diagnostic methods, and research tools. In particular, the subject compositions and methods are useful for reducing the signaling output of oncogenic proteins such as Ras proteins. Cancer (e.g., tumors, neoplasms, metastases) is the second leading cause of death worldwide and is estimated to cause approximately 10 million deaths each year. Many types of cancer have mutations in one or more proteins involved in various signaling pathways, leading to uncontrolled growth of cancer cells.

Description

[Technical field]

[0001] cross reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 338,387, filed May 4, 2022, and U.S. Provisional Patent Application No. 63 / 491,723, filed March 22, 2023, each of which is incorporated by reference in its entirety.

[0002] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in XML format, which is incorporated by reference in its entirety. The XML copy created on May 2, 2023 is named 56690_747_601_SL.xml and is 13,992 bytes in size. [Background technology]

[0003] 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 percent (%) of tumors are known to harbor Rat sarcoma (Ras) mutations. In particular, mutations in the gene for the Kirsten Ras oncogene (K-Ras) are among the most frequent Ras mutations detected in human cancers, including lung adenocarcinoma (LUAD) and pancreatic ductal adenocarcinoma (PDAC).

[0004] Ras proteins have long been considered "undruggable," in part due to their high affinity for their substrate guanosine-5'-triphosphate (GTP) and / or their smooth surface without any obvious target regions. Specific G12C Ras gene mutations have been identified as druggable targets for which a number of G12C-specific inhibitors have been developed. However, such therapeutics remain of limited use due to drug resistance or relatively short duration of efficacy. In addition, it remains difficult to drug other mutant Ras molecules, including glycine to aspartate, glycine to valine, and glycine to serine at amino acid residues 12 or 13. Summary of the Invention

[0005] In view of the above, there remains a significant need for new designs of therapeutics and diagnostics 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 treating a variety of 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.

[0006] In one aspect, there is provided a compound of formula (I) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W is N, C(R 18 ), N(R 18b ), C(R 18 )(R18a ), C(O), S(O), or S(O) 2 and Z is N, C(R 8 ), N(R 8b ), C(R 8 )(R 8a ), C(O), S(O), or S(O) 2 and both W and Z are C(O), S(O), and S(O). 2 There is no selection from V and J are each independently C(R 17 ), C(R 17 )(R 16a ), C(R 16 ), C(R 16 )(R 16a ), N, N(R 17b ), and N(R 16b ), and exactly one of V and J is selected from C(R 17 ), C(R 17 )(R 16a ), or N(R 17b ) and Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), or S(O) 2 and U is N, C(R 2c ), C(R 2c )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 10 But -L 7 -R 7 and L 7 is a bond, -O-, -N(R 14 )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, C 1~4 an alkyl or 2-4 membered heteroalkyl linker, 1~4 The alkyl and 2-4 membered heteroalkyl linkers each have 1, 2, or 3 R 20a and optionally substituted with R 7 but, [ka] and W 1 and W 3 But independently, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 2 are independently bonded, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S(O), and S(O) 2 is selected from W 5 But N,C(R 1 ), and C(R 4 ), s1 is an integer from 1 to 6; s2 is an integer from 1 to 3; s3 is an integer from 1 to 3; Each R 1 are independently hydrogen, 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 6~12 Aryl, -CH 2 -C 6~12 Aryl, -CH 2 -C 1~11 Heteroaryl and C 1~11 heteroaryl; 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 one, two, or three R 20a and optionally substituted with Each R 4 are independently 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 ), 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 one, two, or three R 20a and optionally substituted with R 6 But -L 2 -R 5 and R 6 optionally capable of forming a covalent bond with a Ras amino acid; L 2 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 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-、-P(O)R 4d O-、-CR 4c R 4c CR 4c R 4c CR 4c R 4c -、-OCR 4c R 4c CR 4c R 4c -、-N(R 4d )CR 4c R 4c CR 4c R 4c -、-C(O)CR 4c R 4c CR 4c R 4c -、-SCR 4c R 4c CR 4c R 4c -、-S(O) 2 CR 4c R 4c CR 4c R 4c -、-S(O)CR 4c R 4c 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 CR 4c R 4c N(R 4d )-、-CR 4c R 4c CR 4c R 4c C(O)-、-CR 4c R 4c CR 4c R 4c S-、-CR 4c R 4c CR 4c R 4c S(O) 2 -、-CR 4cR 4c CR 4c R 4c S(O)- or -CR 4c R 4c CR 4c R 4c P(O)R 4d - and Each R 4c are independently 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 Selected from C1~6 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 independently selected from 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 1, 2, or 3 groups selected from Each R 4d are independently 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, C3~10 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 Selected from 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 and -CH 2 -C 2~9 Heterocycloalkyl is independently selected from 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(R14 )(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 1, 2, or 3 groups selected from R 5 But halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R12 )(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 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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 is one, two, or three R 20k and optionally substituted with R 8 and R 8a are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R20c and optionally substituted with R 8b are independently 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 ), 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 one, two, or three R 20c and optionally substituted with R 17 But -L 1 -R 19 and R 17b But -L 1b -R 19 and L 1 But, bond, C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -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 -,-OCON(R 14 )-, -N(R 14 )C(O)O-, N(R 1e ), C(O)N(R 1c ), S(O) 2 N(R 1c ), S(O)N(R 1c ), C(R 1f )(R 1g )O, C(R 1f )(R 1g )N(R 1c ), and C(R 1f )(R 1g ), and C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, and C 2 ~C 4 Alkynyl is one, two or three R 20i and optionally substituted with L 1b But, bond, C 1 ~C 4 Alkyl, C 2 ~C 4Alkenyl, C 2 ~C 4 Alkynyl, -C(O)-, -C(O)N(R 14 )-, C(O)N(R 1c ), C(R 1f )(R 1g )O, C(R 1f )(R 1g )N(R 1c ), and C(R 1f )(R 1g ), and C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, and C 2 ~C 4 Alkynyl is one, two or three R 20i and optionally substituted with R 1e , R 1f , and R 1g are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two or three R 20i or R 1f and R 1g are bonded to form a 4- to 7-membered heterocycloalkyl ring or a 4- to 7-membered cycloalkyl ring, and the 4- to 7-membered heterocycloalkyl ring or the 4- to 7-membered cycloalkyl ring is preferably 20i and optionally substituted with R 1c But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 heteroaryl; C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 Heteroaryl is one, two, or three R 20i and optionally substituted with R 19 But, C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 heteroaryl; C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with Each R 1i are independently halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R 20i and optionally substituted with R 16 and R 16a are independently 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 ), 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 one, two, or three R 20g and optionally substituted with R 16b are independently 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 1~9Heteroaryl, -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 ), 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 one, two, or three R 20g and optionally substituted with R 2 But halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12’ , -SR12’ , -N(R 12’’ )(R 13 ), -C(O)OR 12’ , -OC(O)N(R 12’ )(R 13 ), -N(R 14 )C(O)N(R 12’ )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12’ )(R 13 ), -C(O)C(O)N(R 12’ )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12’ )(R 13 )-, S(=O)(=NH)N(R 12’ )(R 13 ), -CH 2 C(O)N(R 12’ )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 2c are independently 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 2b are independently 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(R12’ )(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 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20dand optionally substituted with R 12b But 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; 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 one, two, or three R 20d and optionally substituted with X is C(R 3 ), C(R 3 )(R 3 ), N(R 3 ), or N, Each R 3 are independently 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 ), 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 one, two, or three R 20b and optionally substituted with Each R12 are independently 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; 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 one, two, or three R 20d and optionally substituted with Each R 12’ are independently 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 6~10Aryl, -C(R 12c ) 2 -C 1~9 Heteroaryl and C 1~9 heteroaryl; 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 one, two, or three R 20d and optionally substituted with Each R 12’’ But independently, 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; 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 one, two, or three R 20d and optionally substituted with Each R 12c are independently hydrogen and R 20m is selected from Each R 13 are independently 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, may contain one, two, or three R 20e C optionally substituted with 2~9 forming a heterocycloalkyl ring, Each R 14 are independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl; Each R 14a But independently, C 1~6 Alkyl and C 1~6 haloalkyl; Each R 15 But independently, C 1~6 Alkyl, 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; C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 Heteroaryl is one, two, or three R 20f and optionally substituted with R 18 and R 18a are independently 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)R15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 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 one, two, or three R 20h and optionally substituted with R 18b are independently 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 2S(O) 2 R 15 , and -CH 2 S(O) 2 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 one, two, or three R 20h and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , and R 20m each independently represents 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 )(R23 ), -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 and two R bonded to the same or adjacent atoms are selected from 20k is optionally combined to form C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl or C 1~9 can form a heteroaryl, 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 independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22, -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O) 2 R 25 , -C(O)R 25 , -S(O) 2 R 25 , -S(O) 2 N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with 1, 2, or 3 groups selected from Each R 21 However, independently, 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 However, independently, 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 independently, H and C 1~6 alkyl, Each R 24 independently, H and C 1~6alkyl, Each R 25 But independently, C 1~6 Alkyl, 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; [ka] indicates a single or double bond such that all valences are satisfied.

[0007] In embodiments, R 6 is capable of forming a covalent bond with a Ras amino acid side chain. 6 is capable of forming a covalent bond with a KRas amino acid. 6 is capable of forming a covalent bond with the 12th amino acid of the human KRas protein. 6 is capable of forming a covalent bond with the 12th amino acid of a mutant KRas protein selected from KRas G12D, KRas G12C, and KRas G12S. 6 is capable of forming a covalent bond with the 13th amino acid of the human KRas protein. 6 is capable of forming a covalent bond with the 13th amino acid of a mutant KRas protein selected from KRas G13D, KRas G13C, and KRas G13S.

[0008] In embodiments, R 6 teeth, [ka] Each R is selected from the group consisting of a are independently hydrogen, C 1~6 Alkyl, carboxy, C 1~6 Carboalkoxy, Phenyl, C 2~7Carboalkyl, R c -(C(R b ) 2 ) z -, R c -(C(R b ) 2 ) w -M-(C(R b ) 2 ) r -, (R d )(R e )CH-M-(C(R b ) 2 ) r - or Het-J 3 -(C(R b ) 2 ) r - and each R b are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, C 2~7 Carboalkyl, C 2~7 Carboxyalkyl, phenyl, or one or more halogens, C 1~6 Alkoxy, trifluoromethyl, amino, C 1~3 Alkylamino, C 2~6 Dialkylamino, nitro, azido, halomethyl, C 2~7 Alkoxymethyl, C 2~7 Alkanoyloxymethyl, C 1~6 Alkylthio, hydroxy, carboxyl, C 2~7 Carboalkoxy, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, C 1~6 Alkanoylamino or C 1~6 phenyl optionally substituted with alkyl; c are independently -NR b R b -OR b and R d and R e are each independently -(C(R b ) 2 ) r -NR b Rb Or -(C(R b ) 2 ) r -OR b and each J 1 are independently hydrogen, chlorine, fluorine, or bromine; J 2 is C 1~6 alkyl or hydrogen, and each M is independently -N(R b )-, -O-, -N[(C(R b ) 2 ) w -NR b R b ]- or -N[(C(R b ) 2 ) w -OR b ]-, and each J 3 are independently -N(R b )-, -O-, or a bond, and each Het is independently R on carbon or nitrogen. b and optionally mono- or disubstituted on carbon with -CH 2 OR b wherein the heterocycle is selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, piperazine, tetrahydrofuran, and tetrahydropyran; each r is independently 1 to 4; each w is independently 2 to 4; x is 0 to 1, y is 0 to 4, each z is independently 1 to 6, and the sum of x+y is 2 to 4.

[0009] In embodiments, R 6 teeth, [ka] wherein each R b are independently hydrogen, hydroxyl, C 1 ~C 6 Alkoxy and C 1 ~C 6alkyl.

[0010] In an embodiment, L 2 is a bond, -C(O)NH-, -NHC(O)-, or -C(O)-, R 5 is halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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 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 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 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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 is one, two, or three R 20k is optionally replaced by

[0011] In one aspect, there is provided a compound of formula (II) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W is N, C(R 18 ), N(R 18b ), C(R 18 )(R 18a ), C(O), S(O), or S(O) 2 and Z is N, C(R 8 ), N(R 8b ), C(R 8 )(R 8a ), C(O), S(O), or S(O)2 and both W and Z are C(O), S(O), and S(O). 2 There is no selection from V and J are each independently C(R 17 ), C(R 17 )(R 16a ), C(R 16 ), C(R 16 )(R 16a ), N, N(R 17b ), and N(R 16b ), and exactly one of V and J is selected from C(R 17 ), C(R 17 )(R 16a ), or N(R 17b ) and Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), U is N, C(R 2c ), C(R 2c )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 10 But -L 7 -R 7 and L 7 is a bond, -O-, -N(R 14 )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, C 1~4 an alkyl or 2-4 membered heteroalkyl linker, 1~4 The alkyl and 2-4 membered heteroalkyl linkers each have 1, 2, or 3 R 20a and optionally substituted with R 7 but, [ka] and W 1 and W 3 But independently, N(R1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 2 are independently bonded, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S(O), and S(O) 2 is selected from W 5 But N,C(R 1 ), and C(R 4 ), s1 is an integer from 1 to 6; s2 is an integer from 1 to 3; s3 is an integer from 1 to 3; Each R 1 are independently hydrogen, 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 -C6~12 Aryl, -CH 2 -C 1~11 Heteroaryl and C 1~11 heteroaryl; 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 one, two, or three R 20a and optionally substituted with Each R 4 are independently 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 )(R13 ), -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 ), 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 one, two, or three R 20a and optionally substituted with R 6 But -L 2 -R 5 and R 6 optionally capable of forming a covalent bond with a Ras amino acid; L 2 is -C(O)-, R 5 But, C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 heteroaryl; C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11Heteroaryl is one, two, or three R 20k and optionally substituted with R 8 and R 8a are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R 20c and optionally substituted with R 8b are independently 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(R12 )(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 one, two, or three R 20c and optionally substituted with R 17 But -L 1 -R 19 and R 17b But -L 1b -R 19 and L 1 But, bond, C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -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 -,-OCON(R 14 )-, -N(R 14 )C(O)O-, N(R 1e ), C(O)N(R 1c ), S(O) 2 N(R 1c ), S(O)N(R 1c ), C(R 1f )(R 1g )O, C(R 1f )(R 1g )N(R 1c ), and C(R 1f )(R 1g ), and C 1~C 4 Alkyl, C 2 ~C 4 Alkenyl, and C 2 ~C 4 Alkynyl is one, two or three R 20i and optionally substituted with L 1b But, bond, C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -C(O)-, -C(O)N(R 14 )-, C(O)N(R 1c ), C(R 1f )(R 1g )O, C(R 1f )(R 1g )N(R 1c ), and C(R 1f )(R 1g ), and C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, and C 2 ~C 4 Alkynyl is one, two or three R 20i and optionally substituted with R 1e , R 1f , and R 1g are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 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 ), 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 one, two or three R 20i or R 1f and R 1g are bonded to form a 4- to 7-membered heterocycloalkyl ring or a 4- to 7-membered cycloalkyl ring, and the 4- to 7-membered heterocycloalkyl ring or the 4- to 7-membered cycloalkyl ring is preferably 20i and optionally substituted with R1c But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 heteroaryl; C 1~6 Alkyl, 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 one, two, or three R 20i and optionally substituted with R 19 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 ), 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 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with Each R 1i are independently halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 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 ), 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 one, two, or three R 20i and optionally substituted with R 16 and R 16a are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R 20g and optionally substituted with R 16bare independently 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 ), 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 one, two, or three R 20g and optionally substituted with R 2 But halogen, -CN, C 1~6 Alkyl, C2~6 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 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 2c are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12 )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 2b are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12’ , -SR 12’ , -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 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the 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 one, two, or three R 20d and optionally substituted with R 12b But 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; 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 one, two, or three R 20d and optionally substituted with X is C(R 3 ), C(R 3 )(R 3 ), N(R 3 ), or N, Each R 3 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C2~6 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 ), and 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 one, two, or three R 20b and optionally substituted with Each R 12 are independently 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; 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 one, two, or three R 20d and optionally substituted with Each R 12’ are independently 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 2~9Heterocycloalkyl, -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; 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 one, two, or three R 20d and optionally substituted with Each R 12c are independently hydrogen and R 20m is selected from Each R 13 are independently 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, may contain one, two, or three R 20e C optionally substituted with 2~9 forming a heterocycloalkyl ring, Each R 14 are independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl; Each R 14aBut independently, C 1~6 Alkyl and C 1~6 haloalkyl; Each R 15 But independently, C 1~6 Alkyl, 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; C 1~6 Alkyl, 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 one, two, or three R 20f and optionally substituted with R 18 and R 18a are independently 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 )(R13 ), -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 ), 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 one, two, or three R 20h and optionally substituted with R 18b are independently 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 ), 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 one, two, or three R 20h and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , and R 20m each independently represents 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 ), -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 and two R bonded to the same or adjacent atoms are selected from 20k is optionally combined to form C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl or C 1~9 can form a heteroaryl, 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 is independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O) 2 R 25 , -C(O)R 25 , -S(O) 2 R 25 , -S(O) 2 N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with 1, 2, or 3 groups selected from Each R 21 However, independently, 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 However, independently, 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 independently, H and C 1~6 alkyl, Each R 24 independently, H and C 1~6 alkyl, Each R 25 But independently, C 1~6 Alkyl, 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; [ka] indicates a single or double bond such that all valences are satisfied.

[0012] In embodiments, R 19 is C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 heteroaryl; C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 Heteroaryl is one, two, three, four, five, six, or seven R 1i is optionally replaced by

[0013] In embodiments, R 6is capable of forming a covalent bond with a Ras amino acid. 6 is capable of forming a covalent bond with a KRas amino acid. 6 is capable of forming a covalent bond with the 12th amino acid of the human KRas protein. 6 is capable of forming a covalent bond with the 12th amino acid of a mutant KRas protein selected from KRas G12D, KRas G12C, and KRas G12S. 6 is capable of forming a covalent bond with the 13th amino acid of the human KRas protein. 6 is capable of forming a covalent bond with the 13th amino acid of a mutant KRas protein selected from KRas G13D, KRas G13C, and KRas G13S.

[0014] In embodiments, R 6 teeth, [ka] Each R is selected from the group consisting of a are independently hydrogen, C 1~6 Alkyl, carboxy, C 1~6 Carboalkoxy, Phenyl, C 2~7 Carboalkyl, R c -(C(R b ) 2 ) z -, R c -(C(R b ) 2 ) w -M-(C(R b ) 2 ) r -, (R d )(R e )CH-M-(C(R b ) 2 ) r - or Het-J 3 -(C(R b ) 2 ) r - and each R bare independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, C 2~7 Carboalkyl, C 2~7 Carboxyalkyl, phenyl, or one or more halogens, C 1~6 Alkoxy, trifluoromethyl, amino, C 1~3 Alkylamino, C 2~6 Dialkylamino, nitro, azido, halomethyl, C 2~7 Alkoxymethyl, C 2~7 Alkanoyloxymethyl, C 1~6 Alkylthio, hydroxy, carboxyl, C 2~7 Carboalkoxy, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, C 1~6 Alkanoylamino or C 1~6 phenyl optionally substituted with alkyl; c are independently -NR b R b -OR b and R d and R e are each independently (C(R b ) 2 ) r -NR b R b Or -(C(R b ) 2 ) r -OR b and each J 1 are independently hydrogen, chlorine, fluorine, or bromine; J 2 is C 1~6 alkyl or hydrogen, and each M is independently -N(R b )-, -O-, -N[(C(R b ) 2 ) w -NR b R b ]- or -N[(C(R b ) 2 ) w -OR b ]-, and each J3 are independently -N(R b )-, -O-, or a bond, and each Het is independently R on carbon or nitrogen. b and optionally mono- or disubstituted on carbon with -CH 2 OR b wherein the heterocycle is selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, piperazine, tetrahydrofuran, and tetrahydropyran; each r is independently 1 to 4; each w is independently 2 to 4; x is 0 to 1, y is 0 to 4, each z is independently 1 to 6, and the sum of x+y is 2 to 4.

[0015] In embodiments, R 5 can have 1, 2, or 3 R 20k and optionally substituted by a 5- or 6-membered partially unsaturated heterocycloalkyl or a 5- or 6-membered heteroaryl, the partially unsaturated 5- or 6-membered heterocycloalkyl or 5- or 6-membered heteroaryl containing 1, 2, or 3 ring nitrogen atoms and connected to L through the ring nitrogen. 2 is bonded to

[0016] In embodiments, R 6 teeth, [ka] It is.

[0017] In embodiments, R 6 is not capable of forming a covalent bond with the 12th amino acid of a human KRas protein selected from KRas wild type, KRas G12D, KRas G12C, KRas G12S, KRas G12V, KRas G13D, KRas G13C, KRas G13S, and KRas G13V. 6is not capable of forming a covalent bond with the 13th amino acid of a human KRas protein selected from KRas wild type, KRas G12D, KRas G12C, KRas G12S, KRas G12V, KRas G13D, KRas G13C, KRas G13S, and KRas G13V. 6 is not capable of forming a covalent bond with a KRas amino acid. 6 is not capable of forming a covalent bond with a Ras amino acid.

[0018] In an embodiment, L 2 is a bond, -C(O)NH-, -NHC(O)-, or -C(O)-, R 5 is halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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 12 , -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 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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 is one, two, or three R 20k is optionally replaced by

[0019] In an embodiment, L 2 is -C(O)-, and R 5 is one, two, or three R 20k C optionally substituted with 3~12 In embodiments, L is cycloalkyl. 2is -C(O)-, and R 5 is one, two or three R selected from halogen and CN; 20k is cyclopropyl optionally substituted with

[0020] In embodiments, R 6 teeth, [ka] In an embodiment, R 6 teeth, [ka] In an embodiment, R 6 teeth, [ka] In an embodiment, R 6 teeth, [ka] It is.

[0021] In an embodiment, L 2 is a bond, -C(O)NH-, -NHC(O)-, or -C(O)-, L 2 is R 5 is attached to a carbon atom of R 5 -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~12 Cycloalkyl, C 6~12 Aryl and C 1~11 heteroaryl; C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~12 Cycloalkyl, C 6~12 Aryl and C 1~11 Heteroaryl is one, two, or three R 20k is optionally replaced by

[0022] In an embodiment, L 2 is -C(O)-, L 2 is R 5 is attached to a carbon atom of R 5 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~12 Cycloalkyl, C 6~12 Aryl and C 1~11 heteroaryl; C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~12 Cycloalkyl, C 6~12 Aryl and C 1~11 Heteroaryl is one, two, or three R 20k is optionally replaced by

[0023] In an embodiment, L 2 is -C(O)-, L 2 is R 5 is attached to a carbon atom of R 5 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 cycloalkyl, and 5- to 6-membered heteroaryl; 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl and 5- to 6-membered heteroaryl can have 1, 2, or 3 R 20k is optionally replaced by

[0024] In an embodiment, L 2 is -C(O)-, R 5 is the expression: [ka] is a heteroaryl having the formula R 5a are independently O, S, CH, C(R 20k ), N, NH, or N(R 20k ) and R 5 is 0 to 3 independent R 20k Including, 0 to 4 R 5a are independently N, NH, or N(R 20k ).

[0025] In an embodiment, L 2 is -C(O)-, R 5 is the expression: [ka] is a heteroaryl having the formula R 5a are independently CH, C(R 20k ), N, NH, or N(R 20k ) and R 5 is 0 to 3 independent R 20k Including, 0 to 4 R 5a are independently N, NH, or N(R 20k ).

[0026] In an embodiment, L 2 is -C(O)-, R 5 teeth, [ka] and R 5a are independently CH, C(R 20k ), CH(R 20k ), C.H. 2 , C(R 20k ) 2 , N, NH, or N(R 20k ) and R 5 is 0 to 3 independent R 20k Including, 0 to 4 R 5a are independently N, NH, or N(R 20k ).

[0027] In an embodiment, L 2 is -C(O)-, and R 5 is C 2~6 Alkenyl and C 2~6 alkynyl, C 2~6 Alkenyl and C 2~6 Alkynyl is one, two, or three R 20k is optionally replaced by

[0028] In one aspect, there is provided a compound of formula (IV) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W is N, C(R 18 ), N(R 18b ), C(R 18 )(R 18a ), C(O), S(O), or S(O) 2 and Z is N, C(R 8 ), N(R 8b ), C(R 8 )(R 8a ), C(O), S(O), or S(O) 2 and both W and Z are C(O), S(O), and S(O). 2 There is no selection from V and J are each independently C(R 17 ), C(R 17 )(R 16a ), C(R 16 ), C(R 16 )(R 16a ), N, N(R 17b ), and N(R 16b ), and exactly one of V and J is selected from C(R 17 ), C(R 17 )(R 16a ), or N(R 17b ) and Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), U is N, C(R 2c ), C(R 2c )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 10 But -L 7 -R 7 and L 7 is a bond, -O-, -N(R 14 )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, C 1~4 an alkyl or 2-4 membered heteroalkyl linker, 1~4 The alkyl and 2-4 membered heteroalkyl linkers each have 1, 2, or 3 R 20a and optionally substituted with R 7 but, [ka] and W 1 and W 3 But independently, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 2 are independently bonded, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S(O), and S(O) 2 is selected from W 5 But N,C(R 1 ), and C(R 4 ), s1 is an integer of 1 to 6 and s2 is an integer of 2 to 3, or s1 is an integer of 2 to 6 and s2 is an integer of 1 to 3; s3 is an integer from 1 to 3; Each R 1 are independently hydrogen, 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; 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, -CH2 -C 6~12 Aryl, -CH 2 -C 1~11 Heteroaryl, and C 1~11 Heteroaryl is one, two, or three R 20a and optionally substituted with Each R 4 are independently 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)R15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 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 one, two, or three R 20a and optionally substituted with R 8 and R 8a are independently 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) 2R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R 20c 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, -C(O)OR 12 , -C(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R 20c and optionally substituted with R 17 But -L 1 -R 19 and R 17b But -L 1b -R 19 and L 1 But, bond, C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -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 -,-OCON(R 14 )-, -N(R 14 )C(O)O-, N(R 1e ), C(O)N(R 1c ), S(O) 2 N(R 1c ), S(O)N(R 1c ), C(R 1f )(R 1g )O, C(R 1f )(R 1g )N(R 1c ), and C(R 1f )(R1g ), and C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, and C 2 ~C 4 Alkynyl is one, two or three R 20i and optionally substituted with L 1b But, bond, C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -C(O)-, -C(O)N(R 14 )-, C(O)N(R 1c ), C(R 1f )(R 1g )O, C(R 1f )(R 1g )N(R 1c ), and C(R 1f )(R 1g ), and C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, and C 2 ~C 4 Alkynyl is selected from 1, 2, or 3 R 20i and optionally substituted with R 1e , R 1f , and R 1g are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 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 ), 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 one, two or three R 20i or R 1f and R 1g are bonded to form a 4- to 7-membered heterocycloalkyl ring or a 4- to 7-membered cycloalkyl ring, and the 4- to 7-membered heterocycloalkyl ring or the 4- to 7-membered cycloalkyl ring is preferably 20iand optionally substituted with R 1c But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 heteroaryl; C 1~6 Alkyl, 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 one, two, or three R 20i and optionally substituted with R 19 But, C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 heteroaryl; C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with Each R 1i are independently halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 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 ), 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 one, two, or three R 20i and optionally substituted with R 16 and R 16a are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 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 ), and 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 one, two, or three R 20g and optionally substituted with R 16b 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, -C(O)OR 12 , -C(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)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 ), 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 one, two, or three R 20g and optionally substituted with R 2 But halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12’ , -SR12’ , -N(R 12’’ )(R 13 ), -C(O)OR 12’ , -OC(O)N(R 12’ )(R 13 ), -N(R 14 )C(O)N(R 12’ )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12’ )(R 13 ), -C(O)C(O)N(R 12’ )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12’ )(R 13 )-, S(=O)(=NH)N(R 12’ )(R 13 ), -CH 2 C(O)N(R 12’ )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 2c are independently 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 2b are independently 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, -C(O)OR 12 , -C(O)R 15 , -C(O)N(R 12 )(R13 ), -C(O)C(O)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 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 12b But 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, -CH2 -C 6~10 Aryl, -CH 2 -C 1~9 Heteroaryl, and C 1~9 heteroaryl; 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 one, two, or three R 20d and optionally substituted with X is C(R 3 ), C(R 3 )(R 3 ), N(R 3 ), or N, Each R 3 are independently 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 ), 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 one, two, or three R 20b and optionally substituted with Each R 12 are independently 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 6~10Aryl, -CH 2 -C 1~9 Heteroaryl, and C 1~9 heteroaryl; 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 one, two, or three R 20d and optionally substituted with Each R 12’ are independently 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; 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 one, two, or three R 20d and optionally substituted with Each R 12’’ But independently, C 3~6 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; C 3~6 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 1~9Heteroaryl is one, two, or three R 20d and optionally substituted with Each R 12c are independently hydrogen and R 20m is selected from Each R 13 are independently 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, may contain one, two, or three R 20e C optionally substituted with 2~9 forming a heterocycloalkyl ring, Each R 14 are independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl; Each R 14a But independently, C 1~6 Alkyl and C 1~6 haloalkyl; Each R 15 But independently, C 1~6 Alkyl, 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; C 1~6 Alkyl, 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 one, two, or three R 20f and optionally substituted with R 18 and R 18a are independently 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 ), and 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 one, two, or three R 20h and optionally substituted with R 18b 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, -C(O)OR 12 , -C(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)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 ), 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 one, two, or three R 20h and optionally substituted with 1, 2, or 3 R 20h and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , and R 20meach independently represents 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 Selected from C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH 2 -C 3~10Cycloalkyl, 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 independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O) 2 R 25 , -C(O)R 25 , -S(O) 2 R 25 , -S(O) 2 N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with 1, 2, or 3 groups selected from Each R 21 However, independently, H, 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; Each R 22 However, independently, 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 independently, H and C 1~6 alkyl, Each R 24 independently, H and C 1~6 alkyl, Each R 25 But independently, C 1~6 Alkyl, 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; [ka] indicates a single or double bond such that all valences are satisfied.

[0029] In embodiments, Y is C(O). In embodiments, Y is N. In embodiments, Y is C(R 2 In an embodiment, Y is C(R 2 )(R 2c In an embodiment, Y is S(O). In an embodiment, Y is S(O). 2 In an embodiment, X is N. In an embodiment, X is C(R 3 In an embodiment, X is C(R 3 )(R 3 In an embodiment, X is N(R3 In an embodiment, U is N. In an embodiment, U is C(R 2c In an embodiment, U is C(R 2c )(R 2c In an embodiment, U is N(R 2b In an embodiment, U is S(O). In an embodiment, U is S(O). 2 In an embodiment, U is C(O). In an embodiment, W is N. In an embodiment, W is C(R 18 In an embodiment, W is N(R 18b In an embodiment, W is C(R 18 )(R 18a In an embodiment, W is C(O). In an embodiment, W is S(O). In an embodiment, W is S(O). 2 In an embodiment, Z is N. In an embodiment, Z is C(R 8 In an embodiment, Z is N(R 8b In an embodiment, Z is C(R 8 )(R 8a In an embodiment, Z is C(O). In an embodiment, Z is S(O). In an embodiment, Z is S(O). 2 In an embodiment, V is N(R 16b In an embodiment, V is N. In an embodiment, V is C(R 16 )(R 16a In an embodiment, V is C(R 16 In an embodiment, V is N(R 17b In an embodiment, V is C(R 17 )(R 16a In an embodiment, V is C(R 17 In an embodiment, J is N(R 16b In an embodiment, J is N. In an embodiment, J is C(R 16 )(R 16a In an embodiment, J is C(R 16 In an embodiment, J is N(R 17b In an embodiment, J is C(R 17)(R 16a In an embodiment, J is C(R 17 In an embodiment, L 7 is a bond. In embodiments, W 1 and W 3 are independently NH, CH 2 , C(O), S, O, S(O), and S(O) 2 In embodiments, W 1 and W 3 are independently 2 In an embodiment, W 2 are independently a bond, NH, or CH 2 , C(O), S, O, S(O), and S(O) 2 In embodiments, W 2 is a bond. In embodiments, W 2 is CH 2 In an embodiment, W 4 is CH 2 In an embodiment, W 5 is N. In embodiments, W 5 is CH. In an embodiment, s1 is 1. In an embodiment, s1 is 2. In an embodiment, s1 is 3. In an embodiment, s1 is 4. In an embodiment, s1 is 5. In an embodiment, s1 is 6. In an embodiment, s2 is 1. In an embodiment, s2 is 2. In an embodiment, s2 is 3. In an embodiment, s3 is 1. In an embodiment, s3 is 2. In an embodiment, s3 is 3. In an embodiment, L 1 is a bond, and L 1b is a bond. In embodiments, R 19 is a bicyclic C 4~12 Cycloalkyl, Bicyclic C 2~11 Heterocycloalkyl, Bicyclic C 7~12 Aryl and Bicyclic C 2~12 heteroaryl; C 4~12 Cycloalkyl, Bicyclic C 2~11 Heterocycloalkyl, Bicyclic C 7~12 Aryl and Bicyclic C 2~12 Heteroaryl is one, two, three, four, five, six, or seven R1i is optionally replaced by

[0030] In embodiments, R 19 is a bridged bicyclic C 4~12 Cycloalkyl, Bridged Bicyclic C 2~11 Heterocycloalkyl, Bridged Bicyclic C 7~12 Aryl and Bridged Bicyclic C 2~12 Heteroaryl, bridged bicyclic C 4~12 Cycloalkyl, Bridged Bicyclic C 2~11 Heterocycloalkyl, Bridged Bicyclic C 7~12 Aryl and Bridged Bicyclic C 2~12 Heteroaryl is one, two, three, four, five, six, or seven R 1i is optionally replaced by

[0031] In embodiments, R 19 is a fused bicyclic C 4~12 Cycloalkyl, fused bicyclic C 2~11 Heterocycloalkyl, Fused Bicyclic C 7~12 Aryl and Fused Bicyclic C 2~12 heteroaryl; 4~12 Cycloalkyl, fused bicyclic C 2~11 Heterocycloalkyl, Fused Bicyclic C 7~12 Aryl and Fused Bicyclic C 2~12 Heteroaryl is one, two, three, four, five, six, or seven R 1i is optionally replaced by

[0032] In embodiments, R 19 teeth, [ka] and Q 1 , Q 3 , and Q 5 are independently N and C(R 1d ), Q 4 and Q 6 are independently O, S, C(R 1a )(R 1b), and N(R 1c ), X 4 , X 5 , X 6 , X 9 , X 10 are independently 1a ) and N; X 13 is a bond, C(R 1a ), N, C(O), C(R 1a )(R 1b ), C(O)C(R 1a )(R 1b ), C(R 1a )(R 1b )C(R 1a )(R 1b ), C(R 1a )(R 1b )N(R 1c ), and N(R 1c ), X 14 , X 15 , X 17 , X 18 are independently C(O), C(R 1a ), N, C(R 1a )(R 1b ), and N(R 1c ), X 16 are independently C, N, and C(R 1a ), Each R 1a , R 1b , R 1d , and R 1h are each independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 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 ), 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 one, two, or three R 20i or R bonded to the same carbon 1a and R 1b is bonded to a 3- to 10-membered heterocycloalkyl ring or 3~10Forming a cycloalkyl ring, a 3- to 10-membered heterocycloalkyl ring or C 3~10 A cycloalkyl ring can contain one, two, or three R 20i or two R attached to adjacent atoms 1a is bonded to a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl ring, 5-12 membered heteroaryl ring, or C 3~10 Forming a cycloalkyl ring, a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl rings, 5-12 membered heteroaryl rings, and C 3~10 A cycloalkyl ring can contain one, two, or three R 20i or R 1h , and R bonded to adjacent atoms 1a , R 1b , R 1c , and R 1d one of which is bonded to a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl ring, 5-12 membered heteroaryl ring, or C 3~10 Forming a cycloalkyl ring, a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl ring, 5-12 membered heteroaryl ring, or C 3~10 A cycloalkyl ring can contain one, two, or three R 20i and optionally substituted with Each R 1c are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 heteroaryl; C 1~6 Alkyl, 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 one, two, or three R 20iis optionally replaced by

[0033] In embodiments, R 19 teeth, [ka] is selected from Q 1 , Q 3 , and Q 5 are independently N or C(R 1d ) and Q 4 and Q 6 are independently O, S, C(R 1a )(R 1b ), or N(R 1c ) and X 4 , X 5 , X 6 , X 9 , X 10 , and X 11 are independently 1a ) and N; X 7 and X 8 are independently 1a ), C(R 1a )(R 1b ), N, and N(R 1c ), Each R 1a , R 1b , R 1d , and R 1h are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R 20i or R bonded to the same carbon 1a and R 1bare joined to form a 4- to 7-membered heterocycloalkyl ring or a 4- to 7-membered cycloalkyl ring, and the 4- to 7-membered heterocycloalkyl ring or the 4- to 7-membered cycloalkyl ring is preferably joined to one, two, or three R 20i or two R attached to adjacent atoms 1a are combined to form a 4- to 7-membered heterocycloalkyl ring, a phenyl ring, a 5- to 6-membered heteroaryl ring, or a 4- to 7-membered cycloalkyl ring, and the 4- to 7-membered heterocycloalkyl ring, the phenyl ring, the 5- to 6-membered heteroaryl ring, or the 4- to 7-membered cycloalkyl ring is preferably joined to one, two, or three R 20i or R 1h , and R bonded to adjacent atoms 1a , R 1b , R 1c , and R 1d are joined to form a 4- to 7-membered heterocycloalkyl ring, a phenyl ring, a 5- to 6-membered heteroaryl ring, or a 4- to 7-membered cycloalkyl ring, and the 4- to 7-membered heterocycloalkyl ring, the phenyl ring, the 5- to 6-membered heteroaryl ring, or the 4- to 7-membered cycloalkyl ring is bound to one, two, or three R 20i and optionally substituted with Each R 1c are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 heteroaryl; C 1~6 Alkyl, 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 one, two, or three R 20i is optionally replaced by

[0034] In embodiments, R 19 teeth, [ka] [ka] [ka] is selected from.

[0035] In embodiments, R 2 -OR 12’ It is.

[0036] In embodiments, R 2 teeth, [ka] [ka] [ka] [ka] is selected from.

[0037] In one embodiment, the formula AL AB -B, wherein A is a monovalent form of a compound described herein; L AB is a covalent linker attached to A and B, B is a monovalent form of the decomposition promoter. In embodiments of the compounds described herein, the pro-degradation agent is selected from the group consisting of E3A, mdm2, APC, EDD1, SOCS / BC-box / eloBC / CUL5 / RING, LNXp80, CBX4, CBLL1, HACE1, HECTD1, HECTD2, HECTD3, HECTD4, HECW1, HECW2, HERC1, HERC2, HERC3, HERC4, HER5, HERC6, HUWE1, ITCH, NEDD4, NEDD4L, PPIL2, PRPF19, PIAS1, , PIAS2, PIAS3, PIAS4, RANBP2, RNF4, RBX1, SMURF1, SMURF2, STUB1, TOPORS, TRIP12, UBE3A, UBE3B, UBE3C, UBE3D, UBE4A, UBE4B, UBOX5, UBR5, VHL (von-Hippel-Lindau ubiquitin ligase), WWP1, WWP2, Parkin, MKRN1, CMA (chaperone-mediated autophagy), SCFb-TRCP (Skip-Cullin-F box (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.

[0038] In embodiments, the degradation promoter 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.

[0039] In an embodiment, 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, C 6~12Arylene or C 1~11 Heteroarylene, 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 have one, two, or three R 20j Optionally replaced by (-OC 1~6 Alkyl) z - and (-C 1~6 Alkyl-O) z -C 1~6 Alkyl is one, two, or three R 20j and optionally substituted with z is independently an integer from 0 to 10; Each R 12 are independently 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; C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH 2 -C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH 2 -C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH 2 -C 6~10Aryl, -CH 2 -C 1~9 Heteroaryl, and C 1~9 Heteroaryl is one, two, or three R 20d and optionally substituted with Each R 13 are independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl or R 12 and R 13 may contain, together with the nitrogen to which they are attached, one, two, or three R 20e C optionally substituted with 2~9 forming a heterocycloalkyl ring, Each R 14 are independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl; Each R 15 is independently 1~6 Alkyl, 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; C 1~6 Alkyl, 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 one, two, or three R 20f and optionally substituted with Each R 20d , R 20e , R 20f , and R 20j are each independently halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH 2 -C 3~10 Cycloalkyl, C 2~9Heterocycloalkyl, -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 Selected from 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 independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O) 2 R 25 , -C(O)R 25 , -S(O) 2 R 25 , -S(O) 2 N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with 1, 2, or 3 groups selected from Each R 21 are independently 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 are independently H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 heteroaryl; Each R 23 are independently H and C 1~6 alkyl, Each R 24 are independently H and C 1~6 alkyl, Each R 25 is independently 1~6 Alkyl, 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 selected from the group consisting of aryl, hetero ...

[0040] In an embodiment, L AB OC 2 Alkyl) z- and z is 1 to 10. In an embodiment, L AB is -(C 2 Alkyl-O-) z- and z is 1 to 10. In an embodiment, L AB is -(CH 2 ) zz1 L AB2 (CH 2 O) zz2- Wherein L AB2 is a bond, 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. AB is -(CH 2 ) zz1 (CH 2 O) zz2-In the formula, zz1 and zz2 are each independently an integer of 0 to 10. AB is a PEG linker. In an embodiment, B is [ka] is a monovalent form of a compound selected from:

[0041] In one aspect, there is provided a compound of formula (I-3), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W 2 But independently, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), S(O), and S(O) 2 is selected from s1 is an integer from 1 to 6; s2 is an integer of 0 to 3, Both s1 and s2 are not equal to 1, and both s1 and s2 are not equal to 2, All other variables in the formula (e.g., W, Z, V, J, Y, U, R 10 , L 7 , R 7 , W 1 , W 3 , W 5 , s3, R 1 , R 6 , L 2 , R 4, R 5 , R 2 , R 4c , R 4d , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 19 , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 ) is as described for formula (I) or an embodiment thereof.

[0042] In one aspect, there is provided a compound of formula (I-4), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, Each R 4are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkynyl, C 2~9 Heteroalkynyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), =C(R 21b ) 2 , -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 14 )C(O)R 12 , -(C 1~6 Alkyl)-S(O) 2 R 15 , -(C 1~6 Alkyl)-N(R 12 )(R13 ), and -(C 1~6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkynyl, C 2~9 Heteroalkynyl, C 6~10 Aryl and C 1~9 Heteroaryl is one, two, or three R 20a and optionally substituted with R 5 But halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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 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 14 )C(O)R 12 , -(C 1~6 Alkyl)-S(O) 2 R 15 , -(C 1~6 Alkyl)-N(R 12 )(R 13 ), and -(C 1~6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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 one, two, or three R 20k and optionally substituted with R 2 But halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 4~9Heterocycloalkyl, 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 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 4~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , and -(C 1~9 Heteroaryl)-R 12b C is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 4~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl is one, two, or three R 20d and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , and R 20m are independently 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(R 21b ) 2 , -C(O)OR 22 , -C(O)N(R22 )(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 and two R bonded to the same or adjacent atoms are selected from 20k are combined to form C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl or C 1~9 can form a heteroaryl, 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 independently selected from 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 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 1, 2, or 3 groups selected from [ka] indicates the position of attachment of the depicted chemical formula or atom to a substituent, further constituent of the molecule, or atom, R 21b independently, in each occurrence, 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 2~9heterocycloalkyl, each of which independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and -OH; [ka] represents a single or double bond such that all valences are satisfied; All other variables in the formula (e.g., W, Z, V, J, Y, U, R 10 , L 7 , R 7 , W 1 , W 3 , W 2 , W 4 , W 5 , s1, s2, s3, R 1 , R 6 , L 2 , R 4c , R 4d , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 19 , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 21 , R 22 , R 23 , R 24 , and R 25) is as described for formula (I-3) or an embodiment thereof.

[0043] In one aspect, there is provided a compound of formula (II-3), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W 2 But independently, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S(O), and S(O) 2 is selected from s1 is an integer from 1 to 6; s2 is an integer of 0 to 3, All other variables in the formula (e.g., W, Z, V, J, Y, U, R 10 , L 7 , L 2 , R 7 , R 5 , R 19 , R 2 , W 1 , W 3 , W 2 , W 5 , s3, R 1 , R 4 , R 6 , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 ) is as described for formula (II) or an embodiment thereof.

[0044] In one aspect, there is provided a compound of formula (II') or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W 2 But independently, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 4 But, C(R 1)(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S(O), and S(O) 2 is selected from s1 is an integer from 1 to 6; s2 is an integer of 0 to 3, s3 is an integer from 1 to 3; Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 10 But -L 7 -R 7 and R 7 but, [ka] and L 2 is -C(O)-, R 5 But, C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 heteroaryl; C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 Heteroaryl is one, two, or three R 20k and optionally substituted with R 19 is hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkynyl, C 2~9 Heteroalkynyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R12 )(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 14 )C(O)R 12 , -(C 1~6 Alkyl)-S(O) 2 R 15 , -(C 1~6 Alkyl)-N(R 12 )(R 13 ), and -(C 1~6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkynyl, C 2~9 Heteroalkynyl, C 6~10 Aryl and C 1~9Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with 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 ), -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 , -CH2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , and -(C 1~9 Heteroaryl)-R 12b C is selected from 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with [ka] indicates the position of attachment of the depicted chemical formula or atom to a substituent, further constituent of the molecule, or atom, [ka] represents a single or double bond such that all valences are satisfied; All other variables in the formula (e.g., W, Z, V, J, U, L 7 , W 1 , W 3 , W 2 , W 5 , R 1 , R 4 , R 6 , R 8 , R 8a , R 8b , R 17 , R 17b , L 1, L 1b , R 1e , R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 ) is as described for formula (I-4) or an embodiment thereof.

[0045] In one aspect, there is provided a compound of formula (II″) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W 2 But independently, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O)2 is selected from W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S(O), and S(O) 2 is selected from s1 is an integer from 1 to 6; s2 is an integer of 0 to 3, s3 is an integer from 1 to 3; Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 10 But -L 7 -R 7 and R 7 but, [ka] and L 2 is -C(O)-, R 5 But, C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 heteroaryl; C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 Heteroaryl is one, two, or three R 20k and optionally substituted with R 19 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkynyl, C 2~9 Heteroalkynyl, C 6~10Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -(C 1~6 alkyl)-C(O)N(R 12 )(R 13 ), -(C 1~6 Alkyl)-N(R 14 )C(O)R 12 , -(C 1~6 Alkyl)-S(O) 2 R 15 , -(C 1~6 Alkyl)-N(R 12 )(R 13 ), and -(C 1~6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10Cycloalkynyl, C 2~9 Heteroalkynyl, C 6~10 Aryl and C 1~9 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with R 2 But 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)R15 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , and -(C 1~9 Heteroaryl)-R 12b C is selected from 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with [ka] indicates the position of attachment of the depicted chemical formula or atom to a substituent, further constituent of the molecule, or atom, [ka] represents a single or double bond such that all valences are satisfied; All other variables in the formula (e.g., W, Z, V, J, U, L 7 , W 1 , W 3 , W 2 , W 5 , R 1 , R 4 , R 6 , R 8 , R8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 ) is as described for formula (I-4) or an embodiment thereof.

[0046] In one aspect, there is provided a compound of formula (IV-3), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W 2 But independently, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1)(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), and C(R 4 )(R 4 ), s1 is an integer from 1 to 6; s2 is an integer of 0 to 3, s1+s2 is not equal to 2 or 4, R 19 But, C 2~11 Heterocycloalkyl and C 2~12 heteroaryl; C 2~11 Heterocycloalkyl and C 2~12 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with 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)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 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with All other variables in the formula (e.g., W, Z, V, J, Y, U, R 10 , L 7 , R 7 , W 1 , W 3 , W 2 , W 5 , s3, R 1 , R 6 , L 2 , R 4 , R 5 , R 4c , R 4d , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 22 , R 23 , R 24 , and R 25 ) is as described for formula (IV) or an embodiment thereof.

[0047] In one aspect, there is provided a compound of formula (IV-4), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 10 But -L 7 -R 7 and R 7 but, [ka] and W 2 But independently, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), or C(R 4 )(R 4 ), s1 is an integer of 1 to 6, and s2 is an integer selected from 2 to 3, or s1 is an integer of 2 to 6, and s2 is an integer of 1 to 3; s1+s2 is not equal to 2 or 4, R 19 But, C 2~11 Heterocycloalkyl and C 2~12 heteroaryl; C 2~11 Heterocycloalkyl and C 2~12Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with R 2 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 4~9 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 , -CH2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 4~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with [ka] represents a single or double bond such that all valences are satisfied; All other variables in the formula (e.g., W, Z, V, J, U, L 7 , W 1 , W 3 , W 5 , s3, R 1 , R 4 , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 ) is as described for formula (I-4) or an embodiment thereof.

[0048] When applied to a compound according to any of the formulae provided herein, in some embodiments, s1 is 1 and s2 is 0, 2, or 3. In some embodiments, s1 is 2 and s2 is 0, 1, or 3. In some embodiments, s1 is 2 and s2 is 1 or 3. In some embodiments, s1 is 3 and s2 is 0-3. In some embodiments, s1 is 4 and s2 is 0-3. In some embodiments, s1 is 5 and s2 is 0-3. In some embodiments, s1 is 1 and s2 is 1 and s3 is 1, 2, or 3. In some embodiments, s2 is 1 or 2. In some embodiments, s2 is 3. In some embodiments, s1 is 2 and s2 is 1 and s3 is 1. In some embodiments, s2 is 1, 2, or 3 and s3 is 1, 2, or 3. In some embodiments, s2 is 1 and s3 is 1, 2, or 3.

[0049] In one aspect, a pharmaceutical composition is provided comprising a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof, and a pharma- ceutically acceptable excipient.

[0050] 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.

[0051] In one aspect, a method is provided for treating cancer in a subject containing a Ras mutant protein, comprising modifying the subject's Ras mutant protein by administering to the subject a compound that is characterized in that, upon contact with the Ras mutant protein, the compound covalently modifies the Ras mutant protein at a residue corresponding to residue 12 of SEQ ID NO:1, such that the modified Ras mutant protein exhibits reduced Ras signaling output.

[0052] In embodiments, the cancer is a solid tumor. In embodiments, the cancer is a hematological cancer.

[0053] In one aspect, a method of modulating the signaling 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 signaling output of the Ras protein.

[0054] 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.

[0055] In embodiments, the method includes administering an additional agent. In embodiments, the additional agent is selected from the group consisting of (1) an inhibitor of MEK (e.g., MEK1, MEK2) or a mutant thereof (e.g., trametinib, cobimetinib, binimetinib, selumetinib, refametinib), (2) an inhibitor of epidermal growth factor receptor (EGFR) and / or a mutant thereof (e.g., afatinib, erlotinib, gefitinib, lapatinib, cetuximab, panitumumab, osimertinib, olmutinib, EGF-816), (3) an immunotherapeutic agent (e.g., any of the agents disclosed herein). (4) taxanes (e.g., paclitaxel, docetaxel); (5) antimetabolites (e.g., antifolates such as methotrexate, pyrimidine analogs such as raltitrexed, 5-fluorouracil (5-FU), ribonucleoside and deoxyribonucleoside analogs, purine and adenosine analogs such as capecitabine and gemcitabine, mercaptopurine, thioguanine, cladribine and pentostatin, cytarabine (arabinose), C), fludarabine), (6) inhibitors of FGFR1 and / or FGFR2 and / or FGFR3 and / or mutants thereof (e.g., nintedanib), (7) mitotic kinase inhibitors (e.g., CDK4 / 6 inhibitors, e.g., palbociclib, ribociclib, abemaciclib, etc.), (8) antiangiogenic agents (e.g., anti-VEGF antibodies, e.g., bevacizumab, etc.), (9) topoisomerase inhibitors (e.g., epipodophyllotoxins, e.g., etoposide and etopophos, teniposide, amsacrine, topotecan, irinotecan, mitoxantrone), (10) platinum-containing compounds (e.g., cisplatin, oxaliplatin, latinib, carboplatin), (11) inhibitors of ALK and / or its mutants (e.g., crizotinib, alectinib, entrectinib, brigatinib), (12) inhibitors of c-MET and / or its mutants (e.g., K252a, SU11274, PHA665752, PF2341066), (13) inhibitors of BCR-ABL and / or its mutants (e.g., imatinib, dasatinib, nilotinib), (14) inhibitors of ErbB2 (Her2) and / or its mutants (e.g., afatinib, lapatinib, trastuzumab, pertuzumab), (15) inhibitors of AXL and / or its mutants (e.g., R428,amuvatinib, XL-880), (16) inhibitors of NTRK1 and / or mutants thereof (e.g., merestinib), (17) inhibitors of RET and / or mutants thereof (e.g., BLU-667, lenvatinib), (18) inhibitors of A-Raf and / or B-Raf and / or C-Raf and / or mutants thereof (RAF-709, LY-3009120), (19) inhibitors of ERK and / or mutants thereof (e.g., ulixertinib), (20) MDM2 inhibitors (e.g., HDM-201, NVP-CGM097, RG-71 12, MK-8242, RG-7388, SAR405838, AMG-232, DS-3032, RG-7775, APG-115), (21) mTOR inhibitors (e.g., rapamycin, temsirolimus, everolimus, ridaforolimus), (22) BET inhibitors (e.g., I-BET 151, I-BET 762, OTX-015, TEN-010, CPI-203, CPI-0610, olionon, RVX-208, ABBC-744, LY294002, AZD5153, MT-1, MS645), (23) IGF1 / 2 and / or IGF1-R inhibitors (e.g., zentuzumab, MEDI-573), (24) CDK9 inhibitors (e.g., DRB, flavopiridol, CR8, AZD 5438, purvalanol B B), AT7519, dinaciclib, SNS-032), (25) farnesyltransferase inhibitors (e.g., tipifarnib), (26) SHIP pathway inhibitors, including SHIP2 inhibitors and SHIP1 inhibitors, (27) SRC inhibitors (e.g., dasatinib), (28) JAK inhibitors (e.g., tofacitinib), (29) PARP inhibitors (e.g., olaparib, rucaparib, niraparib, (30) BTK inhibitors (e.g., ibrutinib, acalabrutinib, zanubrutinib), (31) ROS1 inhibitors (e.g., entrectinib), (32) SHP2 inhibitors (e.g., 6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine), and SHP1 inhibitors, or (33) Src, FLT3, HDAC, VEGFR, PDGFR, LCK,Inhibitors of Bcr-Abl or AKT, or (34) inhibitors of KrasG12C mutants (e.g., AMG510, MRTX849, and any covalent inhibitors that bind to cysteine ​​residue 12 of Kras, the structures of which are known) (see, e.g., US20180334454, US20190144444, US20150239900, US102 46424, US20180086753, WO2018143315, WO2018206539, WO20191107519, WO2019141250, WO2019150305, US9862701, US 20170197945, US20180086753, US10144724, US20190055211, US20190092767, US20180127396, US20180273523, US102 80172, US20180319775, US20180273515, US20180282307, US20180282308, WO2019051291, WO2019213526, WO20192135 16, WO2019217691, WO2019241157, WO2019217307, WO2020047192, WO2017087528, WO2018218070, WO2018218069, WO20 18218071, WO2020027083, WO2020027084, WO2019215203, WO2019155399, WO2020035031, WO2014160200, WO2018195349, WO2018112240, WO2019204442, WO2019204449, WO2019104505, WO2016179558, WO2016176338, or related patents and applications. G12C inhibitors), (35) SHC inhibitors (e.g., PP2, AID371185), (36) GAB inhibitors (e.g., GAB-0001), (37) GRB inhibitors, (38) PI-3 kinase inhibitors (e.g., idelalisib, copanlisib, duvelisib, alpelisib, taselisib, perifosine, buparlisib, umbralisib, NVP-BEZ235-AN), (39) MARPK inhibitors, (40) CDK4 / 6 (e.g., palbociclib, ribociclib,abemaciclib), or (41) MAPK inhibitors (e.g., VX-745, VX-702, RO-4402257, SCIO-469, BIRB-796, SD-0006, PH-797804, AMG-548, LY2228820, SB-681323, GW-856553, RWJ67657, BCT-197), or (42) SHP2 inhibitors (e.g., 6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine, RMC-4630, ERAS-601, [ka] or SHP1 inhibitors, (43) checkpoint immune blockers (e.g., anti-PD-1 and / or anti-PD-L1 antibodies, including but not limited to nivolumab, pembrolizumab, cemiplimab, and durvalumab, anti-CLTA-4 antibodies, including ipilimumab).

[0056] In embodiments, the additional agent is RMC-4630, ERAS-601, [ka] The present invention includes an inhibitor of SHP2 selected from the group consisting of:

[0057] In embodiments, the additional agent is [ka] RMC-5845, and BI-1701963.

[0058] In embodiments, the additional agent comprises an EGFR inhibitor selected from afatinib, erlotinib, gefitinib, lapatinib, cetuximab panitumumab, osimertinib, olmutinib, and EGF-816. In embodiments, the additional agent comprises a MEK inhibitor selected from trametinib, cobimetinib, binimetinib, selumetinib, refametinib, and AZD6244. In embodiments, the additional agent comprises an ERK inhibitor selected from ulixertinib, MK-8353, LTT462, AZD0364, SCH772984, BIX02189, LY3214996, and lavoxertinib. In embodiments, the additional agent comprises a CDK4 / 6 inhibitor selected from palbociclib, ribociclib, and abemaciclib. In embodiments, the additional agent comprises an inhibitor of BRAF selected from sorafenib, vemurafenib, dabrafenib, encorafenib, regorafenib, and GDC-879.

[0059] In one aspect, there is provided a compound of formula (I) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W is N, C(R 18 ), N(R 18b ), C(R 18 )(R 18a ), C(O), S(O), or S(O) 2 and Z is N, C(R 8 ), N(R 8b ), C(R 8 )(R 8a ), C(O), S(O), or S(O) 2 and both W and Z are C(O), S(O), and S(O). 2 There is no selection from V and J are each independently C(R 17 ), C(R 17 )(R 16a ), C(R 16 ), C(R 16 )(R 16a ), N, N(R17b ), and N(R 16b ), and exactly one of V and J is selected from C(R 17 ), C(R 17 )(R 16a ), or N(R 17b ) and Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), or S(O) 2 and U is N, C(R 2c ), C(R 2c )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 10 But -L 7 -R 7 and L 7 is a bond, -O-, -N(R 14 )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, C 1~4 an alkyl or 2-4 membered heteroalkyl linker, 1~4 The alkyl and 2-4 membered heteroalkyl linkers each have 1, 2, or 3 R 20a and optionally substituted with R 7 but, [ka] and Each W 1 And each W 3 But independently, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from Each W 2But independently, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), S(O), and S(O) 2 is selected from W 5 But N,C(R 1 ), and C(R 4 ), s1 is 1 and s2 is 0, 2, or 3; s1 is 2 and s2 is 0, 1, or 3; s1 is 3 and s2 is 0 to 3; s1 is 4 and s2 is 0 to 3; s1 is 5 and s2 is 0 to 3; or s1 is 6 and s2 is 0 to 3; s3 is an integer from 1 to 3; Each R 1 are independently hydrogen, 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; C 1~6 Alkyl, C 2~6Alkenyl, 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 one, two, or three R 20a and optionally substituted with Each R 4 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R 20a and optionally substituted with R 6 But -L 2 -R 5 and R 6 optionally capable of forming a covalent bond with a Ras amino acid; L 2 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 R4c -、-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-、-P(O)R 4d O-、-CR 4c R 4c CR 4c R 4c CR 4c R 4c -、-OCR 4c R 4c CR 4c R 4c -、-N(R 4d )CR 4c R 4c CR 4c R 4c-, -C(O)CR 4c R 4c CR 4c R 4c -,-SCR 4c R 4c CR 4c R 4c -, -S(O) 2 CR 4c R 4c CR 4c R 4c -,-S(O)CR 4c R 4c 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 CR 4c R 4c N(R 4d )-, -CR 4c R 4c CR 4c R 4c C(O)-, -CR 4c R 4c CR 4c R 4c S-, -CR 4c R 4c CR 4c R 4c S(O) 2 -, -CR 4c R 4c CR 4c R 4c S(O)- or -CR 4c R 4c CR 4c R 4c P(O)R 4d - and Each R 4c are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C1~6 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 Selected from 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 and -CH 2 -C 2~9 Heterocycloalkyl is independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6Haloalkoxy, -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 1, 2, or 3 groups selected from Each R 4d are independently 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(R14 )(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 Selected from 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 and -CH 2 -C 2~9 Heterocycloalkyl is independently selected from 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)R14a and optionally substituted with 1, 2, or 3 groups selected from R 5 But halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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 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 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 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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 is one, two, or three R 20k and optionally substituted with R 8 and R 8a are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R 20c and optionally substituted with R 8b are independently 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 ), 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 one, two, or three R 20c and optionally substituted with R 17 But -L 1 -R 19 and R 17b But -L 1b -R 19 and L 1 But, bond, C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -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 -,-OCON(R 14 )-, -N(R 14 )C(O)O-, N(R 1e ), C(O)N(R 1c ), S(O) 2 N(R 1c ), S(O)N(R 1c ), C(R 1f )(R 1g )O, C(R 1f )(R 1g )N(R 1c ), and C(R 1f )(R 1g ), and C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, and C 2 ~C 4 Alkynyl is one, two or three R 20i and optionally substituted with L 1b But, bond, C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -C(O)-, -C(O)N(R 14 )-, C(O)N(R 1c ), C(R 1f )(R 1g )O, C(R 1f )(R 1g )N(R 1c ), and C(R 1f )(R 1g ), and C 1 ~C 4 Alkyl, C 2 ~C4 Alkenyl, and C 2 ~C 4 Alkynyl is one, two or three R 20i and optionally substituted with R 1e , R 1f , and R 1g are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two or three R 20i or R 1f and R 1g are bonded to form a 4- to 7-membered heterocycloalkyl ring or a 4- to 7-membered cycloalkyl ring, and the 4- to 7-membered heterocycloalkyl ring or the 4- to 7-membered cycloalkyl ring is preferably 20i and optionally substituted with R 1c But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 heteroaryl; C 1~6 Alkyl, 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 one, two, or three R 20i and optionally substituted with R 19 But, C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 heteroaryl; C 3~12Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with Each R 1i are independently halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R 20i and optionally substituted with R 16 and R 16a are independently 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 ), 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 one, two, or three R 20g and optionally substituted with R 16b are independently 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 ), 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 one, two, or three R 20g and optionally substituted with R 2 But 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)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 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 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R2c are independently 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), -(C 1 ~C6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 2b are independently 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’ )(R13 ), -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 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 12b But 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, -CH2 -C 1~9 Heteroaryl and C 1~9 heteroaryl; 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 one, two, or three R 20d and optionally substituted with X is C(R 3 ), C(R 3 )(R 3 ), N(R 3 ), or N, Each R 3 are independently 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)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 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 ), 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 one, two, or three R 20b and optionally substituted with Each R 12 are independently 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 -C1~9 Heteroaryl and C 1~9 heteroaryl; 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 one, two, or three R 20d and optionally substituted with Each R 12’ are independently 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; 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 -C2~9 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 one, two, or three R 20d and optionally substituted with Each R 12’’ But independently, 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; 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 one, two, or three R 20dand optionally substituted with Each R 12c are independently hydrogen and R 20m is selected from Each R 13 are independently 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, may contain one, two, or three R 20e C optionally substituted with 2~9 forming a heterocycloalkyl ring, Each R 14 are independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl; Each R 14a But independently, C 1~6 Alkyl and C 1~6 haloalkyl; Each R 15 But independently, C 1~6 Alkyl, 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; C 1~6 Alkyl, 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 one, two, or three R 20f and optionally substituted with R 18 and R 18a are independently 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 ), 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 one, two, or three R20h and optionally substituted with R 18b are independently 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 ), 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 one, two, or three R 20h and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , and R 20m each independently represents 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 and two R bonded to the same or adjacent atoms are selected from 20k is optionally combined to form C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl or C 1~9 can form a heteroaryl, 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 independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O) 2 R25 , -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 1, 2, or 3 groups selected from Each R 21 However, independently, 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 However, independently, 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 independently, H and C 1~6 alkyl, Each R 24 independently, H and C 1~6 alkyl, Each R 25 But independently, C 1~6 Alkyl, 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; [ka] indicates a single or double bond such that all valences are satisfied.

[0060] A compound of formula (II) or a pharma- ceutically acceptable salt or solvate thereof, [ka] During the ceremony, W is N, C(R 18 ), N(R 18b ), C(R 18 )(R 18a ), C(O), S(O), or S(O) 2 and Z is N, C(R 8 ), N(R 8b ), C(R 8 )(R 8a ), C(O), S(O), or S(O) 2 and both W and Z are C(O), S(O), and S(O). 2 There is no selection from V and J are each independently C(R 17 ), C(R 17 )(R 16a ), C(R 16 ), C(R 16 )(R 16a ), N, N(R 17b ), and N(R 16b ), and exactly one of V and J is selected from C(R 17 ), C(R 17 )(R 16a ), or N(R 17b ) and Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), U is N, C(R 2c ), C(R 2c )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R10 But -L 7 -R 7 and L 7 is a bond, -O-, -N(R 14 )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, C 1~4 an alkyl or 2-4 membered heteroalkyl linker, 1~4 The alkyl and 2-4 membered heteroalkyl linkers each have 1, 2, or 3 R 20a and optionally substituted with R 7 but, [ka] and W 1 and W 3 But independently, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 2 are independently bonded, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S(O), and S(O) 2 is selected from W 5 But N,C(R1 ), and C(R 4 ), s1 is an integer from 1 to 6; s2 is an integer from 1 to 3; s3 is an integer from 1 to 3; Each R 1 are independently hydrogen, 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; 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 one, two, or three R 20a and optionally substituted with Each R 4 are independently 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 ), 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 C1~9 Heteroaryl is one, two, or three R 20a and optionally substituted with R 6 But -L 2 -R 5 and R 6 optionally capable of forming a covalent bond with a Ras amino acid; L 2 is -C(O)-, R 5 But, C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 heteroaryl; C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 Heteroaryl is one, two, or three R 20k and optionally substituted with R 8 and R 8a are independently 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 ), 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 one, two, or three R 20c and optionally substituted with R 8b are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -C(O)R 15 , -S(O)R 15 , -OC(O)R15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R 20c and optionally substituted with R 17 But -L 1 -R 19 and R 17b But -L 1b -R 19 and L 1 But, bond, C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -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 -,-OCON(R 14 )-, -N(R 14 )C(O)O-, N(R 1e ), C(O)N(R 1c ), S(O) 2 N(R 1c ), S(O)N(R 1c ), C(R 1f )(R 1g )O, C(R 1f )(R 1g )N(R 1c ), and C(R 1f )(R 1g ), and C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, and C 2 ~C 4 Alkynyl is one, two or three R 20i and optionally substituted with L 1b But, bond, C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -C(O)-, -C(O)N(R 14 )-, C(O)N(R 1c ), C(R 1f )(R 1g )O, C(R 1f )(R 1g )N(R 1c ), and C(R 1f )(R 1g ), and C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, and C 2 ~C 4 Alkynyl is one, two or three R 20iand optionally substituted with R 1e , R 1f , and R 1g are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH2 S(O) 2 N(R 12 )(R 13 ), 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 one, two or three R 20i or R 1f and R 1g are bonded to form a 4- to 7-membered heterocycloalkyl ring or a 4- to 7-membered cycloalkyl ring, and the 4- to 7-membered heterocycloalkyl ring or the 4- to 7-membered cycloalkyl ring is preferably 20i and optionally substituted with R 1c But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 heteroaryl; C 1~6 Alkyl, 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 one, two, or three R 20i and optionally substituted with R 19 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(R12 )(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 ), 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 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with Each R 1iare independently halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 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), 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 one, two, or three R 20i and optionally substituted with R 16 and R 16a are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R 20g and optionally substituted with R 16b are independently 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 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 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 one, two, or three R 20g and optionally substituted with R 2 But 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)R15 , -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 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 2c are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -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 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 2b are independently 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 2S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 12b But 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; 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 and C 1~9 Heteroaryl is one, two, or three R 20d and optionally substituted with X is C(R 3 ), C(R 3 )(R 3 ), N(R 3 ), or N, Each R 3 are independently 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)R15 , -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 ), 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 one, two, or three R 20b and optionally substituted with Each R 12 are independently 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; 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 one, two, or three R 20d and optionally substituted with Each R 12’ are independently 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; C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -C(R 12c ) 2 -C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -C(R 12c ) 2 -C 2~9 Heterocycloalkyl, C 6~10 Aryl, -C(R 12c ) 2 -C 6~10 Aryl, -C(R 12c ) 2 -C 1~9 Heteroaryl and C1~9 Heteroaryl is one, two, or three R 20d and optionally substituted with Each R 12c are independently hydrogen and R 20m is selected from Each R 13 are independently 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, may contain one, two, or three R 20e C optionally substituted with 2~9 forming a heterocycloalkyl ring, Each R 14 are independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl; Each R 14a But independently, C 1~6 Alkyl and C 1~6 haloalkyl; Each R 15 But independently, C 1~6 Alkyl, 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; C 1~6 Alkyl, 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 one, two, or three R 20f and optionally substituted with R 18 and R 18a are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 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 ), and 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 one, two, or three R 20h and optionally substituted with R 18b are independently 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 ), 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 1~9Heteroaryl is one, two, or three R 20h and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , and R 20m are independently 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 and two R bonded to the same or adjacent atoms are selected from 20k is optionally combined to form C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl or C 1~9 can form a heteroaryl, 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 independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25, -N(R 24 )S(O) 2 R 25 , -C(O)R 25 , -S(O) 2 R 25 , -S(O) 2 N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with 1, 2, or 3 groups selected from Each R 21 However, independently, 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 However, independently, 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 independently, H and C 1~6 alkyl, Each R 24 independently, H and C 1~6 alkyl, Each R 25 But independently, C 1~6 Alkyl, 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; [ka] represents a single or double bond such that all valences are satisfied, or a pharma- ceutically acceptable salt or solvate thereof.

[0061] In an embodiment, L 2 is -C(O)-. In embodiments, R 5 Each of them has 1, 2, or 3 R 20k and optionally substituted by L, wherein the partially unsaturated 5- or 6-membered heterocycloalkyl or 5- or 6-membered heteroaryl contains 1, 2, or 3 ring nitrogen atoms, each of which is connected through a ring nitrogen to L. 2 In an embodiment, R 5 can have 1, 2, or 3 R 20k and wherein the 5-membered heteroaryl contains 1, 2, or 3 ring nitrogen atoms and the 5-membered heteroaryl is bonded to L through a ring nitrogen. 2 is bonded to

[0062] In an embodiment, L 2 is -C(O)-, and R 5 can have 1, 2, or 3 R 20k C optionally substituted with 3~12 In embodiments, L is cycloalkyl. 2 is -C(O)-, and R 5 is one, two or three R selected from halogen and CN; 20k In embodiments, L is cyclopropyl optionally substituted with 2 is -C(O)-, and R 5 is C 2~6 alkenyl, C 2~6 Alkenyl is one, two, or three R 20k In embodiments, L 2 is -C(O)-, and R 5 is C 2~6 Alkynyl, C 2~6 Alkynyl is one, two, or three R 20kis optionally replaced by

[0063] In embodiments, Y is C(O). In embodiments, Y is C(R 2 In an embodiment, X is N. In an embodiment, X is C(R 3 In an embodiment, U is N. In an embodiment, U is N(R 2b In an embodiment, W is C(R 18 In an embodiment, W is CH. In an embodiment, W is C(O). In an embodiment, Z is N. In an embodiment, Z is C(R 8 In an embodiment, Z is C(Cl). In an embodiment, Z is N(R 8b In an embodiment, Z is N(cyclopropyl). In an embodiment, V is C(R 17 In an embodiment, J is C(R 16 In an embodiment, J is C(F). In an embodiment, L 7 is a bond. In embodiments, W 1 is C(R 4 ) 2 In an embodiment, W 1 are independently 2 and CH(CH 3 In embodiments, W 1 are independently 2 and CH(CH 2 In embodiments, W 1 is CH 2 In an embodiment, W 3 is CH 2 In an embodiment, W 2 is C(R 4 ) 2 In an embodiment, W 2 are independently 2 , CH(CH 2 CN), CH(CHF 2 ), CH(CH 2 CH 3 ), and CH(CH 3 In embodiments, W 2is CH 2 In an embodiment, W 2 are independently CH(CH 2 CH 3 ) and CH(CH 3 In embodiments, W 4 is CH 2 It is.

[0064] In the embodiment, W 5 is N. In embodiments, W 5 is CH. In an embodiment, s1 is 2. In an embodiment, s1 is 3. In an embodiment, s1 is 4. In an embodiment, s2 is 1. In an embodiment, s2 is 2. In an embodiment, s3 is 1.

[0065] When applied to a compound according to any of the formulae provided herein, in some embodiments, s1 is 1 and s2 is 0, 2, or 3. In some embodiments, s1 is 2 and s2 is 0, 1, or 3. In some embodiments, s1 is 2 and s2 is 1 or 3. In some embodiments, s1 is 3 and s2 is 0-3. In some embodiments, s1 is 4 and s2 is 0-3. In some embodiments, s1 is 5 and s2 is 0-3. In some embodiments, s1 is 1 and s2 is 1 and s3 is 1, 2, or 3. In some embodiments, s2 is 1 or 2. In some embodiments, s2 is 3. In some embodiments, s1 is 2 and s2 is 1 and s3 is 1. In some embodiments, s2 is 1, 2, or 3 and s3 is 1, 2, or 3. In some embodiments, s2 is 1 and s3 is 1, 2, or 3.

[0066] In embodiments, R 7 teeth, [ka] wherein R 1 and R 4Substituents may be attached to any of the spirocyclic rings.

[0067] In embodiments, R 7 teeth, [ka] wherein R 1 and R 4 Substituents may be attached to any of the spirocyclic rings.

[0068] In embodiments, R 7 teeth, [ka] is selected from.

[0069] In embodiments, R 7 teeth, [ka] and In the formula, R 1 and R 4 Substituents may be attached to any of the spirocyclic rings.

[0070] In embodiments, R 17 -L 1 -R 19 Or -L 1b -R 19 And L 1 is a bond, and L 1b is a bond.

[0071] In embodiments, R 19 teeth, [ka] and Q 1 , Q 3 , and Q 5 are independently N and C(R 1d ), Q 4 and Q 6are independently O, S, C(R 1a )(R 1b ), and N(R 1c ), X 4 , X 5 , X 6 , X 9 , X 10 are independently 1a ) and N; X 13 is a bond, C(R 1a ), N, C(O), C(R 1a )(R 1b ), C(O)C(R 1a )(R 1b ), C(R 1a )(R 1b )C(R 1a )(R 1b ), C(R 1a )(R 1b )N(R 1c ), and N(R 1c ), X 14 , X 15 , X 17 , X 18 are independently C(O), C(R 1a ), N, C(R 1a )(R 1b ), and N(R 1c ), X 16 is C, N, and C(R 1a ), Each R 1a , R 1b , R 1d , and R 1h are each independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 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 ), 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 one, two, or three R 20i or R bonded to the same carbon 1a and R 1bis bonded to a 3- to 10-membered heterocycloalkyl ring or 3~10 Forming a cycloalkyl ring, a 3- to 10-membered heterocycloalkyl ring or C 3~10 A cycloalkyl ring can contain one, two, or three R 20i or two R attached to adjacent atoms 1a is bonded to a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl ring, 5-12 membered heteroaryl ring, or C 3~10 Forming a cycloalkyl ring, a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl rings, 5-12 membered heteroaryl rings, and C 3~10 A cycloalkyl ring can contain one, two, or three R 20i or R 1h , and R attached to adjacent atoms 1a , R 1b , R 1c , and R 1d one of which is bonded to a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl ring, 5-12 membered heteroaryl ring, or C 3~10 Forming a cycloalkyl ring, a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl ring, 5-12 membered heteroaryl ring, or C 3~10 A cycloalkyl ring can contain one, two, or three R 20i and optionally substituted with Each R 1c are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 heteroaryl; C 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 one, two, or three R 20i is optionally replaced by

[0072] In embodiments, R 19 teeth, [ka] [ka] [ka] is selected from.

[0073] In embodiments, R 19 teeth, [ka] is selected from.

[0074] In embodiments, R 19 teeth, [ka] is selected from.

[0075] In embodiments, R 2 teeth, [ka] [ka] [ka] is selected from.

[0076] In embodiments, R 2 teeth, [ka] is selected from.

[0077] In one aspect, a pharmaceutical composition is provided comprising a compound described herein, or a pharma- ceutically acceptable salt or solvate thereof, and a pharma- ceutically acceptable excipient.

[0078] 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.

[0079] In embodiments, the cancer is a solid tumor or a hematological cancer.

[0080] 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.

[0081] In an embodiment, the method includes administering an additional agent.

[0082] In embodiments, the additional agent is: (1) an inhibitor of MEK, (2) an inhibitor of epidermal growth factor receptor (EGFR) and / or its variants, (3) an immunotherapeutic agent, (4) a taxane, (5) an antimetabolite, (6) an inhibitor of FGFR1 and / or FGFR2 and / or FGFR3 and / or its variants, (7) a mitotic kinase inhibitor, (8) an antiangiogenic drug, (9) a topoisomerase inhibitor, (10) a platinum-containing compound, (12) c-MET and / or its variants, (13) inhibitors of BCR-ABL and / or mutants thereof, (14) inhibitors of ErbB2 (Her2) and / or mutants thereof, (15) inhibitors of AXL and / or mutants thereof, (16) inhibitors of NTRK1 and / or mutants thereof, (17) inhibitors of RET and / or mutants thereof, (18) inhibitors of A-Raf and / or B-Raf and / or C-Raf and / or mutants thereof, (19) inhibitors of ERK and / or mutants thereof, (20) MDM2 inhibitors, (21) mTOR inhibitors, (23) IGF1 / 2 and / or IGF1-R inhibitors, (24) CDK9 inhibitors, (25) farnesyltransferase inhibitors, (26) SHIP pathway inhibitors, (27) SRC inhibitors, (28) JAK inhibitors, (29) PARP inhibitors, (31) ROS1 inhibitors, (32) SHP pathway inhibitors, or (33) Src, FLT3, HDAC, VEGFR, PDGFR, LC K, Bcr-Abl, or AKT inhibitors, (34) inhibitors of KrasG12C mutants, (35) SHC inhibitors (e.g., PP2, AID371185), (36) GAB inhibitors, (38) PI-3 kinase inhibitors, (39) MARPK inhibitors, (40) CDK4 / 6 inhibitors, (41) MAPK inhibitors, (42) SHP2 inhibitors, (43) checkpoint immune blockers, (44) or SOS1 inhibitors, or (45) SOS2 inhibitors.

[0083] Incorporation 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]

[0084] 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.

[0085] [Figure 1] From top to bottom, it depicts a sequence alignment of various wild-type Ras proteins, including K-Ras, H-Ras, N-Ras, RalA, and RalB. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0086] 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 that are within the skill of those in the art. See, e.g., Sambrook and Green, Molecular Cloning: A Laboratory Manual, 4 th Edition (2012), the series Current Protocols in Molecular Biology (FMAusubel, et al. eds.), the series Methods In Enzymology (Academic Press, Inc.), PCR 2:A Practical Approach (MJ MacPherson, BD Hames and GRTaylor 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 Please refer to the R.I. Freshney, ed. (2010).

[0087] 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 in this specification, 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 in this specification are incorporated by reference. When referring to a URL or other such identifier or address, it is understood that such identifiers may vary and specific information on the Internet may come and go, but equivalent information may be found by searching the Internet. Reference thereto is evidence that such information is available and publicly disseminated.

[0088] 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 claimed subject matter. In this application, the use of the singular includes the plural unless specifically stated otherwise. 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 specifically stated otherwise. Furthermore, the use of the term "including," as well as other forms such as "include," "includes," and "included," is not limiting.

[0089] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0090] Standard definitions of chemical terms are given in Carey and Sundberg's "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, and pharmacology are used.

[0091] Unless specific definitions are provided, the nomenclature employed 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, and 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 foregoing 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.

[0092] 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, as such 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.

[0093] As used herein, C 1 ~C x is C 1 ~C 2 , C 1 ~C 3 …C 1 ~C x Includes: C 1 ~C xrefers to the number of carbon atoms that make up the moiety it designates (excluding optional substituents).

[0094] 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 Alkyl" or a similar designation. 1 ~C 6 "Alkyl" indicates that there are 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).

[0095] "Alkoxy" refers to the group "-O-alkyl" where alkyl is as defined herein.

[0096] The term "alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms and containing at least one carbon-carbon double bond. Non-limiting examples of alkenyl groups include CH=CH 2 , -C(CH 3 )=CH 2 , -CH=CHCH 3 , -CH=C(CH 3 ) 2, and -C(CH 3 )=CHCH 3 In some embodiments, an alkenyl group can have 2 to 6 carbons. An alkenyl group can be substituted or unsubstituted. Depending on the structure, an alkenyl group can be a monoradical or a diradical (an alkenylene group).

[0097] The term "alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms and containing at least one carbon-carbon triple bond. Non-limiting examples of alkynyl groups include -C≡CH, -C≡CCH 3 , -C≡CCH 2 CH 3 , and -C≡CCH 2 CH 2 CH 3 In some embodiments, an alkynyl group 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 (i.e., an alkynylene group).

[0098] "Amino" is -NH 2 Refers to the base.

[0099] The term "alkylamine" or "alkylamino" refers to -N(alkyl) x H y "Dialkylamino" refers to the -N(alkyl) 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.

[0100] The term "aromatic" refers to a planar ring having a delocalized π-electron system containing 4n+2 π-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.

[0101] 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 and aromatic, 2) the bond to the remainder of the compound is directly attached 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 attached (e.g., fused) to a 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, the aryl radical is a monocyclic, bicyclic, or tricyclic ring system. In an embodiment, the aryl is a monocyclic ring. In an embodiment, the aryl is a fused ring polycyclic ring system. In embodiments, an aryl is a bridged ring polycyclic system. In some embodiments, an aryl is a "fused ring aryl" in which an aryl ring is fused to a cycloalkyl or heterocycloalkyl ring.

[0102] "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 a 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 may 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] These include, but are not limited to:

[0103] 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 and 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 from 3 to 10 ring atoms. Depending on the structure, a cycloalkyl group can be a monoradical or a diradical (ie, a cycloalkylene group).

[0104] 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 to an aromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur, or an aromatic ring directly bonded (e.g., fused) to an aromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur of the aryl ring system. 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, a heteroaryl ring is a "fused ring heteroaryl" in which the heteroaryl ring is fused to 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, a heteroaryl group can be monovalent or divalent (i.e., a heteroarylene group).

[0105] A "heterocycloalkyl" or "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) 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 directly bonded to a ring of the ring system that is a saturated or partially unsaturated non-aromatic ring containing one or more heteroatoms, or to a non-aromatic ring that is directly bonded (e.g., fused) to a saturated or partially unsaturated non-aromatic ring containing one or more heteroatoms of the ring system. Heterocycloalkyls can be saturated or partially unsaturated. The term heterocycloalkyl also includes all ring forms of carbohydrates, including, but not limited to, monosaccharides, disaccharides, and oligosaccharides. In some embodiments, the heterocycloalkyl ring is a spirocyclic heterocycloalkyl ring. In embodiments, the heterocycloalkyl is a monocyclic ring. In embodiments, the heterocycloalkyl is a fused 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).

[0106] The term "halo" or alternatively "halogen" means fluoro, chloro, bromo, and iodo.

[0107] The abbreviations "Fmoc", "Ac", "Bn", "PMB", "Tr", "Ts", "Boc", and "Cbz" are used in accordance with their common meaning well understood in the chemical art to denote monovalent chemical substituents: fluorenylmethyloxycarbonyl, acetyl, benzyl, p-methoxybenzyl, trityl or triphenylmethyl, tosyl, tert-butyloxycarbonyl, and carbobenzyloxy.

[0108] The term "haloalkyl" refers to an alkyl group that is substituted with one or more halogens. The halogens can be the same or different. Non-limiting examples of haloalkyl include -CH 2 Cl, -CF 3 , -CHF 2 , -CH 2 CF 3 , -CF 2 CF 3 etc.

[0109] 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 ) 2etc.

[0110] The term "heteroalkyl" refers to an alkyl radical 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 can be placed 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, examples include, but are not limited to, -CH 2 -NH-OCH 3 and -CH 2 -O-Si(CH 3 ) 3Up to two heteroatoms can be consecutive, such as: Excluding the number of heteroatoms, a "heteroalkyl" can have 1 to 6 carbon atoms.

[0111] The term "oxo" refers to the radical =O.

[0112] The term "bond" or "single bond" refers to a chemical bond between two atoms or two moieties when the atoms joined by the bond are considered part of a larger substructure.

[0113] The term "moiety" refers to a specific segment or functional group of a molecule. A chemical moiety is a chemical entity that is often embedded within or attached to a molecule for recognition.

[0114] The suffix "-di-yl" is understood to mean that the substituent or linker is a divalent substituent or linker.

[0115] 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 through a ring carbon), and heterocycloalkyl.

[0116] "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.

[0117] The term “optionally substituted” or “substituted” means that, unless otherwise specified, the group being referred to is individually and independently an 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 ) and their protected derivatives. By way of example, optional substituents include L s R s Each L s are independently a bond, -O-, -C(=O)-, -S-, -S(=O)-, -S(=O) 2 -, -NH-, -NHC(O)-, -C(O)NH-, S(=O) 2 NH-, -NHS(=O) 2 , -OC(O)NH-, -NHC(O)O-, -(C 1 ~C 6 alkyl)- or -(C 2 ~C 6 alkenyl), and each R s are independently 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.

[0118] "Pharmaceutically acceptable salts" include both acid and base addition salts. A pharmaceutically acceptable salt of any one of the compounds described herein is intended to encompass any and all pharmaceutically suitable salt forms. Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0119] "Pharmaceutically acceptable acid addition salts" refer to salts formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphorous acid, and the like, which retain the biological effectiveness and properties of the free base, and which 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, including, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, 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, and the like. Also contemplated are amino acid salts such as arginate, gluconate, and galacturonate (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.

[0120] "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, and the like. See Berge et al., supra.

[0121] 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 contain modified amino acids and may be interrupted by non-amino acids. These terms also encompass modified amino acid polymers, e.g., disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component. As used herein, the term "amino acid" refers to any natural and / or unnatural or synthetic amino acid, including glycine and both D or L optical isomers, as well as amino acid analogs and peptidomimetics.

[0122] 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 can have any three-dimensional structure and can perform any function, known or unknown. The following are non-limiting examples of polynucleotides: 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), short 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 contain one or more modified nucleotides, such as methylated nucleotides and nucleotide analogs, e.g., 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. A polynucleotide may be further modified after polymerization, such as by conjugation with a label component or other conjugation target.

[0123] As used herein, "expression" refers to the process by which a polynucleotide is transcribed from a DNA template (such as into mRNA or other RNA 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 the "gene product." If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in a eukaryotic cell.

[0124] The terms "subject," "individual," and "patient" are used interchangeably herein to refer to a vertebrate, preferably a mammal, more preferably a human. 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.

[0125] 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 when administered 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.

[0126] As used herein, "treatment" or "treating" or "alleviating" or "ameliorating" are used interchangeably. These terms refer to an approach to obtain a beneficial or desired outcome, 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 during treatment. For prophylactic benefit, the composition may be administered to a subject at risk of developing a particular disease, condition, or symptom, or to a subject who reports one or more of the physiological symptoms of a disease, even if the disease, condition, or symptom may not yet be manifest. Typically, prophylactic benefit includes reducing the incidence and / or worsening of one or more diseases, conditions, or symptoms during treatment (e.g., between treated and untreated populations, or between treated and untreated states of a subject).

[0127] 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 condition being treated, the subject's weight and age, the severity of the condition, the mode of administration, etc., which can be easily 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. A component may be described herein as having at least an effective amount, or having at least an effective amount, such as those associated with a particular goal or purpose, such as any described herein. The term "effective amount" also applies to a dose that provides an image for detection by an appropriate imaging method. The specific dose may vary depending on one or more of the particular agent selected, the administration regimen to be followed, whether 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.

[0128] The term "in vivo" refers to events that take place inside a subject's body.

[0129] 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 can include preparing cells outside of a subject's body for the purpose of introducing the prepared cells into the same or a different subject's body.

[0130] 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 employed. An in vitro assay includes cell-free assays, in which no intact cells are employed.

[0131] The term "Ras" or "RAS" refers to proteins of the Rat Sarcoma (Ras) superfamily of small GTPases, such as 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, such as the group consisting of KRAS, HRAS, NRAS, RALA, RALB, and any combination thereof. The terms "mutated Ras" and "Ras mutant" as 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 present at any position in Ras.In some embodiments, the mutations may be present at positions 12, 13, 62, 92, 95, or any combination thereof of Ras of SEQ ID NO:2 when optimally aligned. In some embodiments, the mutant Ras may contain about or at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, or more than 50 mutations. In some embodiments, the mutant Ras may contain up to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 mutations. In some embodiments, the mutant Ras is about or up to about 500, 400, 300, 250, 240, 233, 230, 220, 219, 210, 208, 206, 204, 200, 195, 190, 189, 188, 187, 186, 185, 180, 175, 174, 173, 172, 171, 170, 169, 168, 167, 166, 165, 160, 155, 150, 125, 100, 90, 80, 70, 60, 50, or less than 50 amino acids in length. In some embodiments, the mutant amino acid is a proteogenic amino acid, a naturally occurring 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 mutated Ras can be further modified, such as by conjugation with a detectable label. In some embodiments, the mutated Ras is a full-length or truncated polypeptide. For example, the mutated Ras can be a truncated polypeptide comprising residues 1-169 or residues 11-183 (e.g., residues 11-183 of mutated RALA or mutated RALB).

[0132] As used herein, the term "corresponding to" or "corresponds to" applied to an amino acid residue in a polypeptide sequence refers to the correspondence of such amino acid to a reference sequence when optimally aligned (e.g., taking into account gaps, insertions, and mismatches). For example, a serine residue in a Ras G12S mutant refers to the serine corresponding to residue 12 of SEQ ID NO:1, which may serve as a reference sequence. Modified Ras mutant proteins disclosed herein may include truncations at the C-terminus or at the N-terminus preceding the serine residue. The serine residue in such an N-terminal truncation modified mutant is still considered to correspond to position 12 of SEQ ID NO:1. In addition, an aspartic acid residue at position 12 of SEQ ID NO:1 finds the corresponding residue in SEQ ID NOs:3 and 5. As used herein, a "prodrug" is intended to refer to a compound that can be converted under physiological conditions or by solvation to a biologically active compound described herein. The term "prodrug" refers to a precursor of a biologically active compound that is pharma- ceutically acceptable. A prodrug may be inactive when administered to a subject, but is converted to an active compound in vivo, for example, by hydrolysis. A prodrug compound may provide advantages of solubility, tissue compatibility, and / or delayed release in a mammalian organism (see, for example, Bundgard, H., Design of Prodrug (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 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 entirety. A "prodrug" may be any covalently bonded carrier that releases an active compound in vivo when such a prodrug is administered to a mammalian subject.Prodrugs of the active compounds described herein can be prepared by modifying functional groups present in the active compound such that the modifications are cleaved, either in routine manipulation or in vivo, to the parent active compound.

[0133] The term "leaving group" is used herein in accordance with its meaning well understood in the chemical arts to refer to an atom or group of atoms that separates from the remainder of a molecule, taking with it the electron pair that was the bond between the leaving group and the remainder of the molecule.

[0134] "Degradation-promoting agent" refers to 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 ubiquitin ligase protein to form a protein complex capable of conjugating the ubiquitin protein to a target protein. In embodiments, the degradation-promoting agent is capable of binding to an E3 ubiquitin ligase protein or a protein complex comprising an E3 ubiquitin ligase protein. In embodiments, the degradation-promoting agent is capable of binding to an E2 ubiquitin conjugating enzyme. In embodiments, the degradation-promoting agent is capable of binding to a protein complex comprising an E2 ubiquitin conjugating enzyme and an E3 ubiquitin ligase protein.

[0135] [ka] refers to a substituent, a further component of a molecule, or to a depicted chemical formula or the position of attachment of an atom (e.g., the position of the bond to another atom). [ka] can equally be located at the end of a bond or overlap a bond. [ka] and dashed bonds [ka] are used interchangeably herein to indicate where a bond break or bond occurs.

[0136] compound In one aspect, there is provided a compound of formula (I) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W is N, C(R 18 ), N(R 18b ), C(R 18 )(R 18a ), C(O), S(O), or S(O) 2 and Z is N, C(R 8 ), N(R 8b ), C(R 8 )(R 8a ), C(O), S(O), or S(O) 2 and both W and Z are C(O), S(O), and S(O). 2 There is no selection from V and J are each independently C(R 17 ), C(R 17 )(R 16a ), C(R 16 ), C(R 16 )(R 16a ), N, N(R 17b ), and N(R 16b ), and exactly one of V and J is selected from C(R 17 ), C(R 17 )(R 16a ), or N(R 17b ) and Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), or S(O) 2 and U is N, C(R 2c ), C(R 2c )(R 2c ), N(R 2b ), S(O), S(O)2 or C(O), R 10 But -L 7 -R 7 and L 7 is a bond, -O-, -N(R 14 )-, -C(O)-, -S-, -S(O) 2 -, -S(O)-, C 1~4 an alkyl or 2-4 membered heteroalkyl linker, 1~4 The alkyl and 2-4 membered heteroalkyl linkers each have 1, 2, or 3 R 20a and optionally substituted with R 7 but, [ka] and W 1 and W 3 But independently, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 2 are independently bonded, N(R 1 ), N(R 4 ), C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S, O, S(O), and S(O) 2 is selected from W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S(O), and S(O) 2is selected from W 5 But N,C(R 1 ), and C(R 4 ), s1 is an integer from 1 to 6; s2 is an integer from 1 to 3; s3 is an integer from 1 to 3; Each R 1 are independently hydrogen, 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; 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 one, two, or three R 20a and optionally substituted with Each R 4 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9Heterocycloalkyl, C 6~10 Aryl and C 1~9 Heteroaryl is one, two, or three R 20a and optionally substituted with R 6 But -L 2 -R 5 and R 6 optionally capable of forming a covalent bond with a Ras amino acid; L 2 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 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-、-P(O)R 4d O-、-CR 4c R 4c CR 4c R 4c CR 4c R 4c -、-OCR 4c R 4c CR 4c R 4c -、-N(R 4d )CR 4c R 4c CR 4c R 4c -、-C(O)CR 4c R 4c CR 4c R 4c -、-SCR 4c R 4c CR 4c R 4c -、-S(O) 2 CR 4c R 4c CR 4c R 4c -、-S(O)CR 4c R 4c 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-、-CR4c R 4c CR 4c R 4c N(R 4d )-, -CR 4c R 4c CR 4c R 4c C(O)-, -CR 4c R 4c CR 4c R 4c S-, -CR 4c R 4c CR 4c R 4c S(O) 2 -, -CR 4c R 4c CR 4c R 4c S(O)- or -CR 4c R 4c CR 4c R 4c P(O)R 4d - and Each R 4c are independently 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 )(R14 ), -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 Selected from 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 and -CH 2 -C 2~9 Heterocycloalkyl is independently selected from 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 1, 2, or 3 groups selected from Each R 4d are independently 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 Selected from 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 and -CH 2 -C 2~9 Heterocycloalkyl is independently selected from halogen, oxo, -CN, C 1~6Alkyl, 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 1, 2, or 3 groups selected from R 5 But halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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(R12 )(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 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 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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 -C6~12 Aryl, -CH 2 -C 1~11 Heteroaryl, C 1~11 Heteroaryl is one, two, or three R 20k and optionally substituted with R 8 and R 8a are independently 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)R15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 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 one, two, or three R 20c and optionally substituted with R 8b are independently 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 2S(O) 2 R 15 , and -CH 2 S(O) 2 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 one, two, or three R 20c and optionally substituted with R 17 But -L 1 -R 19 and R 17b But -L 1b -R 19 and L 1 But, bond, C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -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 -,-OCON(R 14 )-, -N(R 14 )C(O)O-, N(R 1e ), C(O)N(R 1c ), S(O) 2 N(R 1c ), S(O)N(R 1c ), C(R 1f )(R 1g )O, C(R 1f )(R 1g)N(R 1c ), and C(R 1f )(R 1g ), and C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, and C 2 ~C 4 Alkynyl is one, two or three R 20i and optionally substituted with L 1b But, bond, C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -C(O)-, -C(O)N(R 14 )-, C(O)N(R 1c ), C(R 1f )(R 1g )O, C(R 1f )(R 1g )N(R 1c ), and C(R 1f )(R 1g ), and C 1 ~C 4 Alkyl, C 2 ~C 4 Alkenyl, and C 2 ~C 4 Alkynyl is one, two or three R 20i and optionally substituted with R 1e , R 1f , and R 1g are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 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 ), 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 one, two or three R 20i or R 1f and R 1gare bonded to form a 4- to 7-membered heterocycloalkyl ring or a 4- to 7-membered cycloalkyl ring, and the 4- to 7-membered heterocycloalkyl ring or the 4- to 7-membered cycloalkyl ring is preferably 20i and optionally substituted with R 1c But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 heteroaryl; C 1~6 Alkyl, 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 one, two, or three R 20i and optionally substituted with R 19 But, C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 heteroaryl; C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with Each R 1i are independently halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R12 )(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 ), 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 one, two, or three R 20i and optionally substituted with R 16 and R 16aare independently 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 ), and C 1~6 Alkyl, C2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 Heteroaryl is one, two, or three R 20g and optionally substituted with R 16b are independently 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 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 Heteroaryl is one, two, or three R 20g and optionally substituted with R 2 But 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)R15 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 2c are independently 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 , -CH 2 S(O) 2 N(R 12 )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9Heterocycloalkyl, C 6~10 Aryl and C 1~9 Heteroaryl is one, two, or three R 20d and optionally substituted with R 2b are independently 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 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 12b But 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; 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 1~9Heteroaryl is one, two, or three R 20d and optionally substituted with X is C(R 3 ), C(R 3 )(R 3 ), N(R 3 ), or N, Each R 3 are independently 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 ), 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 one, two, or three R 20b and optionally substituted with Each R 12 are independently 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; 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 one, two, or three R20d and optionally substituted with Each R 12’ are independently 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; 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 one, two, or three R 20d and optionally substituted with Each R 12’’ But independently, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -C(R 12c ) 2 -C 3~10Cycloalkyl, 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; 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 one, two, or three R 20d and optionally substituted with Each R 12c are independently hydrogen and R 20m is selected from Each R 13 are independently 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, may contain one, two, or three R 20e C optionally substituted with 2~9 forming a heterocycloalkyl ring, Each R 14 are independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl; Each R 14a But independently, C 1~6 Alkyl and C 1~6 haloalkyl; Each R 15 But independently, C 1~6 Alkyl, 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; C 1~6 Alkyl, 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 one, two, or three R 20f and optionally substituted with R 18 and R 18a are independently 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 ), 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 one, two, or three R 20h and optionally substituted with R 18b are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -C(O)R 15 , -S(O)R 15 , -OC(O)R15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two, or three R 20h and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , and R 20m are independently 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 -C2~9 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 and two R bonded to the same or adjacent atoms are selected from 20k is optionally combined to form C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl or C 1~9 can form a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH 2 -C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2 -C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH 2 -C 6~10 Aryl, -CH 2 -C 1~9 Heteroaryl, and C 1~9 Heteroaryl is independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O) 2 R 25 , -C(O)R 25 , -S(O) 2 R 25 , -S(O) 2 N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with 1, 2, or 3 groups selected from Each R 21 However, independently, 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 22 However, independently, 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 independently, H and C 1~6 alkyl, Each R 24 independently, H and C 1~6 alkyl, Each R 25 But independently, C 1~6 Alkyl, 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; [ka] indicates the position of attachment of the depicted chemical formula or atom to a substituent, further constituent of the molecule, or atom, [ka] indicates a single or double bond such that all valences are satisfied.

[0137] In one aspect, there is provided a compound of formula (II) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W, Z, V, J, U, R 10 , L 7 , W 1 , W 3, W 2 , W 4 , W 5 , s1, s2, s3, R 1 , R 4 , R 6 , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , 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); Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 7 but, [ka] and L 2 is -C(O)-, R 5 But, C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 heteroaryl; C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 Heteroaryl is one, two, or three R 20k and optionally substituted with R 19 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 R15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with R 2 But halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12’ , -SR 12’ , -N(R 12’ )(R 13 ), -C(O)OR 12’ , -OC(O)N(R 12’ )(R 13 ), -N(R 14 )C(O)N(R 12’ )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12’ )(R 13 ), -C(O)C(O)N(R 12’ )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12’ )(R 13 )-, S(=O)(=NH)N(R 12’ )(R 13 ), -CH 2 C(O)N(R 12’ )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20dand optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0138] In one aspect, there is provided a compound of formula (IV) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W, Z, V, J, U, R 10 , L 7 , W 1 , W 3 , W 2 , W 4 , W 5 , s3, R 1 , R 4 , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 19 , R 1i , R 16 , R 16a , R 16b , R 2 , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R20h , R 20i , 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); Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 7 but, [ka] and s1 is an integer of 1 to 6 and s2 is an integer of 2 to 3, or s1 is an integer of 2 to 6 and s2 is an integer of 1 to 3; Each R 12’’ But independently, C 3~6 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; C 3~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -C(R 12c ) 2 -C 3~10 Cycloalkyl, C2~9 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 one, two, or three R 20d and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0139] In one aspect, there is provided a compound of formula (I') or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W, Z, V, J, Y, U, R 10 , L 7 , R 7 , W 1 , W 3 , W 2 , W 4 , W 5 , s1, s2, s3, R 1 , R 6 , L 2 , R 4c , R 4d , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 19 , R 1i , R 16 , R 16a , R 16b , R 2c , R2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 21 , R 22 , R 23 , R 24 , and R 25 is as described for formula (I), including embodiments of compounds of formula (I); Each R 4 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkynyl, C 2~9 Heteroalkynyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), =C(R 21b ) 2 , -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 14 )C(O)R 12 , -(C 1~6 Alkyl)-S(O) 2 R 15 , -(C 1~6 Alkyl)-N(R 12 )(R 13 ), and -(C 1~6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkynyl, C 2~9 Heteroalkynyl, C 6~10 Aryl and C 1~9 Heteroaryl is one, two, or three R 20a and optionally substituted with R 5 But halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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 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 14 )C(O)R 12 , -(C 1~6 Alkyl)-S(O) 2 R 15 , -(C 1~6 Alkyl)-N(R 12 )(R 13 ), and -(C 1~6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~12 Cycloalkyl, -CH 2 -C 3~12 Cycloalkyl, C 1~11Heterocycloalkyl, -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 one, two, or three R 20k and optionally substituted with R 2 But halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 4~9 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 ), -CH2 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 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 4~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , and -(C 1~9 Heteroaryl)-R 12b C is selected from 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 4~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl is one, two, or three R 20d and optionally substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , and R 20m are independently halogen, oxo, -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(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 and two R bonded to the same or adjacent atoms are selected from 20k are combined to form C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl or C 1~9 can form a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C3~10 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 independently selected from halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O) 2 R 25 , -C(O)R 25 , -S(O) 2 R 25 , -S(O) 2 N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with 1, 2, or 3 groups selected from [ka] indicates the position of attachment of the depicted chemical formula or atom to a substituent, further constituent of the molecule, or atom, R 21b independently, in each occurrence, 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 independently represents a halogen, C 1~3 Alkyl, C 1~3 optionally substituted with 1, 2, or 3 substituents selected from haloalkyl, and -OH; [ka] indicates a single or double bond such that all valences are satisfied.

[0140] In one aspect, there is provided a compound of formula (II') or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W, Z, V, J, U, L 7 , W 1 , W 3 , W 2 , W 4 , W 5 , s1, s2, s3, R 1 , R 4 , R 6 , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e, R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 10 But -L 7 -R 7 and R 7 but, [ka] and L 2 is -C(O)-, R 5 But, C 3~12Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 heteroaryl; C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 Heteroaryl is one, two, or three R 20k and optionally substituted with R 19 is hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkynyl, C 2~9 Heteroalkynyl, 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 ), -(C 1~6alkyl)-C(O)N(R 12 )(R 13 ), -(C 1~6 Alkyl)-N(R 14 )C(O)R 12 , -(C 1~6 Alkyl)-S(O) 2 R 15 , -(C 1~6 Alkyl)-N(R 12 )(R 13 ), and -(C 1~6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkynyl, C 2~9 Heteroalkynyl, C 6~10 Aryl and C 1~9 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with 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 ), -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)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 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 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , and -(C 1~9 Heteroaryl)-R 12b C is selected from 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with [ka] indicates the position of attachment of the depicted chemical formula or atom to a substituent, further constituent of the molecule, or atom, [ka] indicates a single or double bond such that all valences are satisfied.

[0141] In one aspect, there is provided a compound of formula (II″) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W, Z, V, J, U, L 7 , W 1 , W 3 , W 2 , W 4 , W 5 , s1, s2, s3, R 1 , R 4 , R 6 , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b, R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 10 But -L 7 -R 7 and R 7 but, [ka] and L 2 is -C(O)-, R 5 But, C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 heteroaryl; C 3~12 Cycloalkyl, C 1~11 Heterocycloalkyl, C 6~12 Aryl and C 1~11 Heteroaryl is one, two, or three R 20k and optionally substituted with R 19 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkynyl, C 2~9 Heteroalkynyl, C 6~10Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -(C 1~6 alkyl)-C(O)N(R 12 )(R 13 ), -(C 1~6 Alkyl)-N(R 14 )C(O)R 12 , -(C 1~6 Alkyl)-S(O) 2 R 15 , -(C 1~6 Alkyl)-N(R 12 )(R 13 ), and -(C 1~6 Alkyl)-S(O) 2 N(R 12 )(R 13 ), and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10Cycloalkynyl, C 2~9 Heteroalkynyl, C 6~10 Aryl and C 1~9 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with R 2 But 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)R15 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , and -(C 1~9 Heteroaryl)-R 12b C is selected from 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with [ka] indicates the position of attachment of the depicted chemical formula or atom to a substituent, further constituent of the molecule, or atom, [ka] indicates a single or double bond such that all valences are satisfied.

[0142] In one aspect, there is provided a compound of formula (IV') or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W, Z, V, J, U, L7 , W 1 , W 3 , W 2 , W 5 , s3, R 1 , R 4 , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 10But -L 7 -R 7 and R 7 but, [ka] and W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), or C(R 4 )(R 4 ), s1 is an integer of 1 to 6, and s2 is an integer selected from 2 to 3, or s1 is an integer of 2 to 6, and s2 is an integer of 1 to 3; R 19 But, C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 heteroaryl; C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with R 2 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 4~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12’’’ , -SR 12’ , -N(R 12’’’’ )(R 13 ), -C(O)OR 12’ , -OC(O)N(R 12’ )(R 13 ), -N(R 14 )C(O)N(R 12’ )(R 13 ), -N(R14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12’ )(R 13 ), -C(O)C(O)N(R 12’ )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12’ )(R 13 )-, S(=O)(=NH)N(R 12’ )(R 13 ), -CH 2 C(O)N(R 12’ )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 4~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9Heterocycloalkyl, C 6~10 Aryl and C 1~9 Heteroaryl is one, two, or three R 20d and optionally substituted with Each R 12’’’ are independently hydrogen, C 2~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -C(R 12c ) 2 -C 4~10 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; C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -C(R 12c ) 2 -C 4~10 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 one, two, or three R 20d and optionally substituted with Each R 12’’’’ But independently, 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; 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 one, two, or three R 20d and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0143] In one aspect, there is provided a compound of formula (IV') or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W, Z, V, J, U, L 7, W 1 , W 3 , W 2 , W 5 , s3, R 1 , R 4 , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), R 10 But -L7 -R 7 and R 7 but, [ka] and W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), or C(R 4 )(R 4 ), s1 is an integer of 1 to 6, and s2 is an integer selected from 2 to 3, or s1 is an integer of 2 to 6, and s2 is an integer of 1 to 3; s1, s2, and s3 are not all 2, R 19 But, C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 heteroaryl; C 3~12 Cycloalkyl, C 2~11 Heterocycloalkyl, C 6~12 Aryl and C 2~12 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with R 2 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 4~9 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 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 4~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 Heteroaryl is one, two, or three R 20d and optionally substituted with Each R 12’’’ are independently hydrogen, C 2~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -C(R 12c ) 2 -C 4~10 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; C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -C(R 12c ) 2 -C 4~10 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 one, two, or three R 20d and optionally substituted with Each R 12’’’’ But independently, C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 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; 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 one, two, or three R 20d and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0144] In one aspect, there is provided a compound of formula (Ia) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W, Z, V, J, U, R 10 , L 7 , R 7 , W 1 , W 3 , W 2 , W 5 , s1, s2, s3, R 1 , R 4 , R 6 , L 2 , R 5 , R 4c , R 4d , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); Y is N,C(R2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), and C(R 4 )(R 4 ), 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 ), -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(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 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , and -(C 1~9 Heteroaryl)-R 12b C is selected from 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 19 But, C 2~11 Heterocycloalkyl and C 2~12 heteroaryl; C 2~11 Heterocycloalkyl and C 2~12 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0145] In one aspect, there is provided a compound of formula (Ib) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W, Z, V, J, U, R 10 , L 7 , R 7 , W 1 , W 3 , W 2 , W 4 , W 5 , s1, s2, s3, R 1 , R 4 , R 6 , L 2 , R 5 , R 4c , R 4d , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R20h , R 20i , R 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); Y is N,C(R 2 ), C(R 2 )(R 2c ), N(R 2b ), S(O), S(O) 2 or C(O), 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 ), -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 R15 , -S(O) 2 N(R 12’ )(R 13 )-, S(=O)(=NH)N(R 12’ )(R 13 ), -CH 2 C(O)N(R 12’ )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , or -(C 1~9 Heteroaryl)-R 12b and the C 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with R 19 but, [ka] and Q 1 , Q 3 , and Q 5 independently, N and C(R 1d), Q 4 and Q 6 However, independently, O, S, C(R 1a )(R 1b ), and N(R 1c ), X 4 , X 5 , X 6 , X 9 , X 10 But independently, C(R 1a ) or N; X 13 is the bond, C(R 1a ), N, C(O), C(R 1a )(R 1b ), C(O)C(R 1a )(R 1b ), C(R 1a )(R 1b )C(R 1a )(R 1b ), C(R 1a )(R 1b )N(R 1c ), and N(R 1c ), X 14 , X 15 , X 17 , X 18 However, independently, C(O), C(R 1a ), N, C(R 1a )(R 1b ), and N(R 1c ), X 16 are independently C, N, and C(R 1a ), Each R 1a , R 1b , R 1d , and R 1h are each independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O) 2 R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2 R 15 , -S(O) 2 N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH 2 C(O)N(R 12 )(R 13 ), -CH 2 N(R 14 )C(O)R 15 , -CH 2 S(O) 2 R 15 , and -CH 2 S(O) 2 N(R 12 )(R 13 ), 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 one, two or three R 20ior R bonded to the same carbon 1a and R 1b is bonded to a 3- to 10-membered heterocycloalkyl ring or 3~10 Forming a cycloalkyl ring, a 3- to 10-membered heterocycloalkyl ring or C 3~10 The cycloalkyl ring may contain one, two or three R 20i or two R attached to adjacent atoms 1a is bonded to a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl ring, 5-12 membered heteroaryl ring, or C 3~10 Forming a cycloalkyl ring, a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl rings, 5-12 membered heteroaryl rings, and C 3~10 The cycloalkyl ring may contain one, two or three R 20i or R 1h , and R bonded to adjacent atoms 1a , R 1b , R 1c , and R 1d one of which is bonded to a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl ring, 5-12 membered heteroaryl ring, or C 3~10 Forming a cycloalkyl ring, a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl ring, 5-12 membered heteroaryl ring, or C 3~10 The cycloalkyl ring may contain 1, 2, or 3 R 20i and optionally substituted with Each R 1c are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 heteroaryl; C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl and C 1~9 Heteroaryl is one, two, or three R 20i and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0146] In one aspect, there is provided a compound of formula (IVa) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, W, Z, V, J, U, Y, L 7 , R 7 , W 1 , W 3 , W 2 , W 5 , R 1 , R 4 , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a , R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (IV'), including embodiments of compounds of formula (IV'); R 10 But -L 7 -R 7 and W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S(O), and S(O) 2 is selected from s1 is an integer from 1 to 6; s2 is an integer from 1 to 3; s3 is an integer from 1 to 3; 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(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 , -CH 2 S(O) 2 N(R 12’ )(R 13 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , and -(C 1~9 Heteroaryl)-R 12b C is selected from 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 one, two, or three R 20d and optionally substituted with Each R 12’’’ are independently 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; 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 one, two, or three R 20d and optionally substituted with Each R 12’’’’ are independently 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; 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 one, two, or three R 20d and optionally substituted with R 19 but, [ka] and Q 3 But, C(R 1d ), and Q 4 But S, X 13 But, C(R 1a ) and X 14 and X 15 But independently, C(R 1a ) and X 16 But C, Each R 1a, R 1d , and R 1h are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 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(R12 )(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 one, two, or three R 20i and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0147] A compound of formula (IVa) or a pharma- ceutically acceptable salt or solvate thereof, [ka] During the ceremony, W, Z, V, J, U, Y, L 7 , R 7 , W 1 , W 3 , W 2 , W 5 , R 1 , R 4 , R 8 , R 8a , R 8b , R 17 , R 17b , L 1 , L 1b , R 1e , R 1f , R 1g , R 1c , R 1i , R 16 , R 16a , R 16b , R 2c , R 2b , R 12b , X, R 3 , R 12 , R 12’ , R 12’’ , R 12c , R 13 , R 14 , R 14a, R 15 , R 18 , R 18a , R 18b , R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (IV'), including embodiments of compounds of formula (IV'); R 10 But -L 7 -R 7 and W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), C(O), S(O), and S(O) 2 is selected from s1 is an integer from 1 to 6; s2 is an integer from 1 to 3; s3 is an integer from 1 to 3; s1, s2, and s3 are not all 2, 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(R12’ )(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 ), -(C 1 ~C 6 Alkyl)-R 12b , -(C 2~6 alkenyl)-R 12b , -(C 2~6 alkynyl)-R 12b , -(C 3~10 Cycloalkyl)-R 12b , -(C 2~9 Heterocycloalkyl)-R 12b , -(C 6~10 Aryl)-R 12b , and -(C 1~9 Heteroaryl)-R 12bC is selected from 1~6 Alkyl, 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 one, two, or three R 20d and optionally substituted with Each R 12’’’ are independently 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; 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 one, two, or three R 20dand optionally substituted with Each R 12’’’’ are independently 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; 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 one, two, or three R 20d and optionally substituted with R 19 but, [ka] and Q 3 But, C(R 1d ), and Q 4 But S, X 13 But, C(R 1a ) and X 14 and X 15 But independently, C(R 1a ) and X 16 But C, Each R 1a , R 1d , and R 1h are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 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 ), 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 one, two, or three R 20i and optionally substituted with [ka] represents a single or double bond such that all valences are satisfied, or a pharma- ceutically acceptable salt or solvate thereof.

[0148] In one aspect, there is provided a compound of formula (Ic), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, s1, s2, s3, R 1 , R 4 , R 6 , R 4c , R 4d , R 17 , L 1b , R 1e , R 1f , R 1g , R 1c , R 19 , R 1i , R 16a , R 16b , R 2c , R 2b , R 12b , R 3 , R 12 , R 12’ , R 12’’, R 12c , 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 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); W is C(R 18 ) or C(O), and Z is N, C(R 8 ), or N(R 8b ) and V is C(R 17 ), and J is C(R 16 ) and Y is C(R 2 ), U is N, X is N, R 10 But -L 7 -R 7 and L 7 is a bond, R 7 but, [ka] and W 1 , W 2 , and W 3 But independently, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), and O; W 4 But, C(R 1 )(R 1 ), C(R1 )(R 4 ), and C(R 4 )(R 4 ), W 5 is selected from N and CH; L 2 is selected from -C(O)-; R 5 But 1, 2, or 3 R 20k and optionally substituted with R 5 L 2 When directly bonded to the C(O) of L 2 But R 5 is directly bonded to the N atom of R 8 are independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -OR 12 , -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 and C 2~9 Heterocycloalkyl is one, two, or three R 20c and optionally substituted with R 8b But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl and C 2~9 heterocycloalkyl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl and C 2~9 Heterocycloalkyl is one, two, or three R 20cand optionally substituted with L 1 is a bond, R 16 are independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -OR 12 , -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 and C 2~9 Heterocycloalkyl is one, two, or three R 20g and optionally substituted with R 2 But, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -OR 12’ , -SR 12’ , and -N(R 12’’ )(R 13 ), and the C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl and C 2~9 Heterocycloalkyl is one, two, or three R 20d and optionally substituted with R 18 are independently hydrogen, halogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl and C 2~9 heterocycloalkyl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C3~10 Cycloalkyl and C 2~9 Heterocycloalkyl is one, two, or three R 20h and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0149] In one aspect, there is provided a compound of formula (Id) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, s1, s2, s3, R 1 , R 4 , R 6 , R 17 , R 12b , R 3 , R 12 , R 12’’ , R 12c , 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 20k , R 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); W is CH and Z is N or C(R 8 ) and V is C(R 17 ), and J is C(R 16 ) and Y is C(R 2 ), U is N, X is N, R10 But -L 7 -R 7 and L 7 is a bond, R 7 but, [ka] and W 1 , W 2 , and W 3 But independently, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), and O; W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), and C(R 4 )(R 4 ), and W 5 is selected from N and CH; L 2 is -C(O)-, and R 5 But 1, 2, or 3 R 20k and R 5 But, L 2 When directly bonded to the C(O) of L 2 But R 5 is directly bonded to the N atom of R 8 is independently selected from hydrogen and halogen; L 1 is a bond, and R 19 But, C 6~12 Aryl and C 2~12 heteroaryl; C 6~12 Aryl and C 2~12 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and each R 1iare independently halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -OR 12 , -N(R 12 )(R 13 ), and C 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Alkynyl is selected from 1, 2, or 3 R 20i and optionally substituted with R 16 is independently selected from hydrogen and halogen; R 2 But -OR 12’ And each R 12’ However, independently, -C(R 12c ) 2 -C 2~9 heterocycloalkyl; —C(R 12c ) 2 -C 2~9 Heterocycloalkyl is one, two, or three R 20d and optionally substituted with [ka] indicates a single or double bond such that all valences are satisfied.

[0150] In one aspect, there is provided a compound of formula (Id) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, s1, s2, s3, R 1 , R 4 , R 6 , R 17 , R 12b , R 3 , R 12 , R 12’’ , R 12c , 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 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); W is CH and Z is N or C(R 8 ) and V is C(R 17 ), and J is C(R 16 ) and Y is C(R 2 ), U is N, X is N, R 10 But -L 7 -R 7 and L 7 is a bond, R 7 but, [ka] and W 1 , W 2 , and W 3 But independently, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), and O; W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), and C(R 4 )(R 4 ), and W 5 is selected from N and CH; L 2 is -C(O)-, and R 5 But 1, 2, or 3 R20k and R 5 But, L 2 When directly bonded to the C(O) of L 2 But R 5 is directly bonded to the N atom of R 8 is independently selected from hydrogen and halogen; L 1 is a bond, and R 19 But, C 6~12 Aryl and C 2~12 heteroaryl; C 6~12 Aryl and C 2~12 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and each R 1i are independently halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -OR 12 , -N(R 12 )(R 13 ), and C 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Alkynyl is selected from 1, 2, or 3 R 20i and optionally substituted with R 16 is independently selected from hydrogen and halogen; R 2 But -OR 12’ And each R 12’ However, independently, -C(R 12c ) 2 -C 2~9 heterocycloalkyl; —C(R 12c ) 2 -C 2~9 Heterocycloalkyl is one, two, or three R 20d and optionally substituted with Each R 20k are independently halogen, -CN, -CH 2 -CN, C 1~6Alkyl, and C 3~10 cycloalkyl, C 1~6 Alkyl and C 3~10 Cycloalkyl is independently 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 1, 2, or 3 groups selected from [ka] indicates a single or double bond such that all valences are satisfied.

[0151] In one aspect, there is provided a compound of formula (Id) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, s1, s2, s3, R1 , R 4 , R 6 , R 17 , R 12b , R 3 , R 12 , R 12’’ , R 12c , 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 20m , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); W is CH and Z is N or C(R 8 ) and V is C(R 17 ), and J is C(R 16 ) and Y is C(R 2 ), U is N, X is N, R 10 But -L 7 -R 7 and L 7 is a bond, R 7 but, [ka] and W 1 , W 2 , and W 3 But independently, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), and O; W 4But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), and C(R 4 )(R 4 ), and W 5 is selected from N and CH; L 2 is -C(O)-, and R 5 But 1, 2, or 3 R 20k and R 5 But, L 2 When directly bonded to the C(O) of L 2 But R 5 is directly bonded to the N atom of R 8 is independently selected from hydrogen and halogen; L 1 is a bond, and R 19 But, C 6~12 Aryl and C 2~12 heteroaryl; C 6~12 Aryl and C 2~12 Heteroaryl is 1, 2, 3, 4, 5, 6, or 7 R 1i and each R 1i are independently halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, -OR 12 , -N(R 12 )(R 13 ), and C 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Alkynyl is selected from 1, 2, or 3 R 20i and optionally substituted with R 16 is independently selected from hydrogen and halogen; R 2 But -OR 12’ And each R 12’ However, independently, -C(R 12c )2 -C 2~9 heterocycloalkyl; —C(R 12c ) 2 -C 2~9 Heterocycloalkyl is one, two, or three R 20d and optionally substituted with Each R 20k are independently halogen, -CN, -CH 2 -CN, C 1~3 Alkyl, and C 3~4 cycloalkyl, C 1~3 Alkyl and C 3~4 Cycloalkyl is independently 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 1, 2, or 3 groups selected from [ka] indicates a single or double bond such that all valences are satisfied.

[0152] In one aspect, there is provided a compound of formula (Ie) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, s1, s2, s3, R 1 , R 4 , R 6 , R 12 , R 13 , R 14 , R 14a , R 15 , R 20a , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); W is CH and Z is N or C(R 8 ) and V is C(R 17 ), and J is C(R 16 ) and Y is C(R 2 ), U is N, X is N, R 10 But -L 7 -R 7 and L 7 is a bond, R 7 but, [ka] and W 1 , W 2 , and W 3 But independently, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), and O; W4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), and C(R 4 )(R 4 ), and W 5 is selected from N and CH; L 2 is -C(O)-, R 5 but, [ka] is selected from R 8 is independently selected from hydrogen and halogen; R 17 but, [ka] Selected from R 16 is independently selected from hydrogen and halogen; R 2 but, [ka] is selected from [ka] indicates a single or double bond such that all valences are satisfied.

[0153] In one aspect, there is provided a compound of formula (If), or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, s1, s2, s3, R 1 , R 4 , R 6 , R 12 , R 13 , R 14 , R 14a , R 15 , R 20a , R 21 , R 21b , R 22, R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); W is CH and Z is N or C(R 8 ) and V is C(R 17 ), and J is C(R 16 ) and Y is C(R 2 ), U is N, X is N, R 10 But -L 7 -R 7 and L 7 is a bond, R 7 but, [ka] and W 1 , W 2 , and W 3 But independently, C(R 1 )(R 1 ), C(R 1 )(R 4 ), C(R 4 )(R 4 ), and O; W 4 But, C(R 1 )(R 1 ), C(R 1 )(R 4 ), and C(R 4 )(R 4 ), and W 5 is selected from N and CH; L 2 is -C(O)-, R 5 but, [ka] is selected from R 8 is independently selected from hydrogen and halogen; R 17 but, [ka] Selected from R 16 is independently selected from hydrogen and halogen; R 2 but, [ka] is selected from [ka] indicates a single or double bond such that all valences are satisfied.

[0154] In one aspect, there is provided a compound of formula (Ig) or a pharma- ceutically acceptable salt or solvate thereof: [ka] During the ceremony, R 1 , R 4 , R 6 , R 12 , R 13 , R 14 , R 14a , R 15 , R 20a , R 20c , R 21 , R 21b , R 22 , R 23 , R 24 , and R 25 is as described for formula (I'), including embodiments of compounds of formula (I'); W is CH or C(O) and Z is N, C(R 8 ), or N(R 8b ) and V is C(R 17 ), and J is C(R 16 ) and Y is C(R 2 ), U is N, X is N, R 10 But -L 7 -R 7 and L 7 is a bond, R 7 but, [ka] [ka] is selected from L 2 is -C(O)-, and R 5 but, [ka] is selected from R 8 is independently selected from hydrogen or halogen; R 8b But, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl and C 2~9 heterocycloalkyl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl and C 2~9 Heterocycloalkyl is one, two, or three R 20c and optionally substituted with R 17 but, [ka] Selected from R 16 is independently selected from hydrogen and halogen; R 2 but, [ka] is selected from [ka] indicates a single or double bond such that all valences are satisfied.

[0155] In an embodiment of formula (Ig), [(R 1 )0~6 and (R 4 ) 0~6 ] is R 4 is equal to R 4 is halogen, methyl, and -CH 2 In an embodiment of formula (Ig), [(R 1 ) 0~6 and (R 4 ) 0~6 ] is [(R 1 ) 0 and (R 4 ) 0 ] (i.e., R 1 or R 4 In an embodiment of formula (Ig), [(R 1 ) 0~6 and (R 4 ) 0~6 ] is two R 4 Equal to each R 4 are independently halogen, methyl, and -CH 2 CN is selected.

[0156] In embodiments of formula (I), (I-3), (I-4), (II-3), (I'), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (II), (II'), (II''), (IV-3), (IV-4), (IV), (IV'), or (IVa), the compound is [ka] R 10 is as described herein, including any aspect or embodiment.

[0157] In an embodiment of formula (I), (I-3), (I-4), (II-3), (I'), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ii), (Ij), (Ik), (Im), (In), (Io), (Ip), (Iq), (Ir), (II), (II'), or (II''): R 7 teeth, [ka] and At least one W 3 and / or W 4 is C(R 1 )(R 1 ), C(R 1 )(R 4 ), or C(R 4 )(R 4 ) and R 1 and R 4 is as described for formula (I'), including embodiments of compounds of formula (I), (I-3), (I-4), (II-3), (I'), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ii), (Ij), (Ik), (Im), (In), (Io), (Ip), (Iq), (Ir), (II), (II'), or (II''); W 3 Or W 4 At least one of i)R 1 is not hydrogen, or ii) W 3 Or W 4 1 R 4 is not hydrogen.

[0158] In an embodiment of formula (I), (I-3), (I-4), (II-3), (I'), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ii), (Ij), (Ik), (Im), (In), (Io), (Ip), (Iq), (Ir), (II), (II'), or (II''): R 7 teeth, [ka] and At least one W 3 and / or W 4 is C(R 1 )(R 1 ), C(R 1 )(R 4 ), or C(R 4 )(R 4 ) and R 1 and R4 is as described for formula (I'), including embodiments of compounds of formula (I), (I-3), (I-4), (II-3), (I'), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ii), (Ij), (Ik), (Im), (In), (Io), (Ip), (Iq), (Ir), (II), (II'), or (II''). In an embodiment, R 1 and R 4 is hydrogen.

[0159] In an embodiment of formula (I), (I-3), (I-4), (II-3), (I'), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ii), (Ij), (Ik), (Im), (In), (Io), (Ip), (Iq), (Ir), (II), (II'), or (II''): R 7 teeth, [ka] and R 1 and R 4 is as described for formula (I'), including embodiments of compounds of formula (I), (I-3), (I-4), (II-3), (I'), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ii), (Ij), (Ik), (Im), (In), (Io), (Ip), (Iq), (Ir), (II), (II'), or (II''); At least one R shown in the formula above 1 or R 4 is not hydrogen, s3a is 0, 1, or 2; s3b is 0, 1, or 2; and the sum of s3a and s3b is 0, 1, or 2.

[0160] In an embodiment of formula (IV-3), (IV-4), (IV), (IVa), or (IV'), R 7 teeth, [ka] and At least one W...

Claims

1. Formula: 【Chemical 801】 A compound having, or a pharmaceutically acceptable salt or solvate thereof, During the ceremony, Z is N or C (R 8), R 10 is -L 7 -R 7, L7 is a bond, -O-, -N(R14)-, -C(O)-, -S-, -S(O)2-, -S(O)-, C1-4 alkyl, or a 2-4 membered heteroalkyl linker, and the C1-4 alkyl and 2-4 membered heteroalkyl linkers are each optionally substituted with 1, 2, or 3 R20a. R 7, 【Chemical 802】 And, W1 and W3 are independently selected from N(R1), N(R4), C(R1)(R1), C(R1)(R4), C(R4)(R4), C(O), S, O, S(O), and S(O)2. W2 is independently selected from combination, N(R1), N(R4), C(R1)(R1), C(R1)(R4), C(R4)(R4), C(O), S, O, S(O), and S(O)2. W4 is selected from C(R1)(R1), C(R1)(R4), C(R4)(R4), S(O), and S(O)2. W5 is selected from N, C(R1), and C(R4), s1 is an integer from 1 to 6, s2 is an integer between 1 and 3, s3 is an integer between 1 and 3, Each R1 is independently selected from hydrogen, 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, C6-12 aryl, -CH2-C6-12 aryl, -CH2-C1-11 heteroaryl, and C1-11 heteroaryl, and C1-11 heteroaryl, 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, C 6-12 aryls, -CH2-C 6-12 aryls, -CH2-C 1-11 heteroaryls, and C 1-11 heteroaryls are optionally substituted with 1, 2, or 3 R20a. Each R4 independently consists of hydrogen, halogen, -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)R 15, -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) are selected from C1-6 alkyl, C2-6 Alkenyls, C2-6 alkynyls, C3-10 cycloalkyls, C2-9 heterocycloalkyls, C6-10 aryls, and C1-9 heteroaryls are optionally substituted with 1, 2, or 3 R20a atoms. R6 is -L2-R5, and R6 can optionally form a covalent bond with the Ras amino acid. L2 is -C(O)-, R5 is selected from C3-12 cycloalkyl, C1-11 heterocycloalkyl, C6-12 aryl, and C1-11 heteroaryl, and the C3-12 cycloalkyl, C1-11 heterocycloalkyl, C6-12 aryl, and C1-11 heteroaryl are optionally substituted with 1, 2, or 3 R20k. R8 is hydrogen, halogen, -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)N(R12)(R13), -N(R14)C(O)OR15, -N(R14)S(O)2R15, -C(O)R15, -S(O)R15, -OC(O)R15 -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) are selected from 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 1, 2, or 3 R20c groups. R 17 is -L 1 -R 19, L1 is bonded to C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, -O-, -N(R14)-, -C(O)-, -N(R14)C(O)-, -C(O)N(R14)-, -S-, -S(O)2-, -S(O)-, -S(O)2N(R14)-, -S(O)N(R14)-, -N(R14)S(O)-, -N(R14)S(O)2-, -OCON(R14)-, -N(R14)C(O)O-, N(R1e), C(O)N(R1c), S(O)2N(R1c ), S(O)N(R 1c), C(R 1f)(R 1g)O, C(R 1f)(R 1g)N(R 1c), and C(R 1f)(R 1g), wherein the C1-C4 alkyl, C2-C4 alkenyl, and C2-C4 alkynyl are optionally substituted with 1, 2, or 3 R 20i. R1e, R1f, and R1g are independently hydrogen, halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, 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)C(O)OR15, -N(R14)S(O)2R15, -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 2S(O)2N(R12)(R13 ) are selected from and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with 1, 2, or 3 R20i, or R1f and R1g are bonded to form a 4-7 membered heterocycloalkyl ring or a 4-7 membered cycloalkyl ring, and the 4-7 membered heterocycloalkyl ring or 4-7 membered cycloalkyl ring is optionally substituted with 1, 2, or 3 R20i, R1c is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl, and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with 1, 2, or 3 R20i. R 19 is selected from C3-12 cycloalkyl, C2-11 heterocycloalkyl, C6-12 aryl, and C2-12 heteroaryl, and the C3-12 cycloalkyl, C2-11 heterocycloalkyl, C6-12 aryl, and C2-12 heteroaryl are optionally substituted with 1, 2, 3, 4, 5, 6, or 7 R 1i. Each R 1i independently comprises halogen, oxo, -CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 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)2R 15, -C(O)R 15, -S(O)R Selected from 15, -OC(O)R 15, -C(O)N(R 12)(R 13), -C(O)C(O)N(R 12)(R 13), -N(R 14)C(O)R 15, -S(O)2R 15, -S(O)2N(R 12)(R 13)-, S(=O)(=NH)N(R 12)(R 13), -CH2C(O)N(R 12)(R 13), -CH2N(R 14)C(O)R 15, -CH2S(O)2R 15, and -CH2S(O)2N(R 12)(R 13), C1-6 Alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with 1, 2, or 3 R20i. R 16 is hydrogen, halogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 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)2R 15, -C(O)R 15, -S(O)R 15, -OC(O)R 15, -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) are selected from C1-6 alkyl, C2-6 Alkenyls, C2-6 alkynyls, C3-10 cycloalkyls, C2-9 heterocycloalkyls, C6-10 aryls, and C1-9 heteroaryls are optionally substituted with 1, 2, or 3 R 20 g. R2 is a halogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 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)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 ), -(C 1 to C 6 alkyl)-R 12b, -(C2-6 alkenyl)-R 12b, -(C2-6 alkynyl)-R 12b, -(C3-10 cycloalkyl)-R 12b, -(C2-9 heterocycloalkyl)-R 12b, -(C6-10 aryl)-R 12b, or -(C1-9 heteroaryl)-R 12b, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with 1, 2, or 3 R 20d. R 12b is selected from hydrogen, 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, and C1-9 heteroaryl, and C1-9 heteroaryl, 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, -CH 2 -C1-9 heteroaryls, and C1-9 heteroaryls are optionally substituted with 1, 2, or 3 R20d, Each R12 is independently selected from hydrogen, 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, and C1-9 heteroaryl, and C1-9 heteroaryl, 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, and C1-9 heteroaryl are optionally substituted with 1, 2, or 3 R20d. Each R12' is independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, -C(R12c)2-C3-10 cycloalkyl, C2-9 heterocycloalkyl, -C(R12c)2-C2-9 heterocycloalkyl, C6-10 aryl, -C(R12c)2-C6-10 aryl, -C(R12c)2-C1-9 heteroaryl, and C1-9 heteroaryl, and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, -C(R12c)2-C3-10 cycloalkyl, C2-9 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 are optionally substituted with 1, 2, or 3 R 20d. Each R12c is independently selected from hydrogen and R20m. 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 1, 2, or 3 R20e. Each R14 is independently selected from hydrogen, C1-6 alkyl, and C1-6 haloalkyl. Each R 15 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl, and C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with 1, 2, or 3 R 20f. R 18 is hydrogen, halogen, -CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 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)2R 15, -C(O)R 15, -S(O)R 15, -OC(O)R 15, -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) are selected from C1-6 alkyl, C2-6 Alkenyls, C2-6 alkynyls, C3-10 cycloalkyls, C2-9 heterocycloalkyls, C6-10 aryls, and C1-9 heteroaryls are optionally substituted with 1, 2, or 3 R20h groups. Each of R 20a, R 20c, R 20d, R 20e, R 20f, R 20g, R 20h, R 20i, R 20k, and R 20m independently comprises 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) 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 Two R20k atoms, selected from and bonded to the same or adjacent atoms, can be optionally bonded to form C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, or C1-9 heteroaryl, and 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, and C1-9 heteroaryl can independently form halogen, oxo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R23), -OC(O)N(R22)(R23), -N(R24)C(O)N(R22)(R23), -N(R24)C(O)OR25, -N(R24)C(O)R25, -N(R24)S(O)2R25, -C(O)R25, -S(O)2R25, -S(O)2N(R22)(R23), and -OC(O)R25 are optionally substituted with one, two, or three groups selected from: Each R 21 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 R 22 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 R 23 is independently selected from H and C 1-6 alkyl groups. Each R 24 is independently selected from H and C 1-6 alkyl groups. Each R 25 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl. 【Chemical 803】 A compound, or a pharmaceutically acceptable salt or solvate thereof, exhibiting single or double bonds such that all valencies are satisfied.

2. The compound according to Claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R 5 is a 5 or 6-membered partially unsaturated heterocycloalkyl or 5 or 6-membered heteroaryl, each optionally substituted with 1, 2, or 3 R 20k, and the partially unsaturated 5 or 6-membered heterocycloalkyl or 5 or 6-membered heteroaryl comprises 1, 2, or 3 ring nitrogen atoms, each bonded to L 2 through the ring nitrogen.

3. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R5 is a five-membered heteroaryl compound optionally substituted with one, two, or three R20k atoms, the five-membered heteroaryl compound comprises one, two, or three ring nitrogen atoms, and the five-membered heteroaryl compound is bonded to L2 through the ring nitrogen atoms.

4. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is C(R 8).

5. The compound according to claim 3, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is C(R 8).

6. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R 8 is selected from hydrogen and halogens.

7. The compound according to claim 5, or a pharmaceutically acceptable salt or solvate thereof, wherein R 8 is selected from hydrogen and halogens.

8. The compound according to claim 5, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is C(Cl).

9. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein Z is N.

10. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein L7 is a bond.

11. The compound according to claim 7, or a pharmaceutically acceptable salt or solvate thereof, wherein L7 is a bond.

12. R 7 is, 【Chemical 804】 A compound according to claim 1, selected from, wherein the R1 and R4 substituents can be bonded to either spirocyclic ring, or a pharmaceutically acceptable salt or solvate thereof.

13. R 7 is, 【Chemical 805】 A compound according to claim 11, selected from, wherein the R1 and R4 substituents can be bonded to either spirocyclic ring, or a pharmaceutically acceptable salt or solvate thereof.

14. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein L1 is a bond.

15. The compound according to claim 13, or a pharmaceutically acceptable salt or solvate thereof, wherein L1 is a bond.

16. R 19 is, 【Chemical 806】 And, Q1, Q3, and Q5 are independently selected from N and C(R1d), Q4 and Q6 are independently selected from O, S, C(R1a)(R1b), and N(R1c), X4, X5, X6, X9, and X10 are independently selected from C(R1a) and N. X 13 is selected from the following: bond, C(R 1a), N, C(O), C(R 1a)(R 1b), C(O)C(R 1a)(R 1b), C(R 1a)(R 1b)C(R 1a)(R 1b), C(R 1a)(R 1b)N(R 1c), and N(R 1c). X14, X15, X17, and X18 are independently selected from C(O), C(R1a), N, C(R1a)(R1b), and N(R1c). X 16 is selected from C, N, and C(R 1a), Each of R1a, R1b, R1d, and R1h is independently hydrogen, halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, 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)N(R12)(R13), -N(R14)C(O)OR15, -N(R14)S(O)2R15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2R 15 , -S(O) 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) Selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with 1, 2, or 3 R 20i, or R 1a and R 1b bonded to the same carbon are bonded to form a 3-10 heterocycloalkyl ring or a C3-10 cycloalkyl ring, and the 3-10 heterocycloalkyl ring or C3-10 cycloalkyl ring is optionally substituted with 1, 2, or 3 R 20i, or two R 1a bonded to adjacent atoms are bonded to form a 3-10 membered heterocycloalkyl ring, a C6-10 aryl ring, a 5-12 membered heteroaryl ring, or a C3-10 A cycloalkyl ring is formed, and the 3-10 membered heterocycloalkyl ring, C6-10 aryl ring, 5-12 membered heteroaryl ring, or C3-10 cycloalkyl ring has 1, 2, or 3 RR 1h is optionally substituted with 20i, or one of R 1a, R 1b, R 1c, and R 1d bonded to an adjacent atom is bonded to form a 3-10 membered heterocycloalkyl ring, a C 6-10 aryl ring, a 5-12 membered heteroaryl ring, or a C 3-10 cycloalkyl ring, and the 3-10 membered heterocycloalkyl ring, C 6-10 aryl ring, 5-12 membered heteroaryl ring, and C 3-10 cycloalkyl ring are optionally substituted with 1, 2, or 3 R 20i. Each R1c is independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl, and the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with 1, 2, or 3 R20i, the compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

17. R 19 is, 【Chemical 807】 And, Q1, Q3, and Q5 are independently selected from N and C(R1d), Q4 and Q6 are independently selected from O, S, C(R1a)(R1b), and N(R1c), X4, X5, X6, X9, and X10 are independently selected from C(R1a) and N. X 13 is selected from the following: bond, C(R 1a), N, C(O), C(R 1a)(R 1b), C(O)C(R 1a)(R 1b), C(R 1a)(R 1b)C(R 1a)(R 1b), C(R 1a)(R 1b)N(R 1c), and N(R 1c). X14, X15, X17, and X18 are independently selected from C(O), C(R1a), N, C(R1a)(R1b), and N(R1c). X 16 is selected from C, N, and C(R 1a), Each of R1a, R1b, R1d, and R1h is independently hydrogen, halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, 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)N(R12)(R13), -N(R14)C(O)OR15, -N(R14)S(O)2R15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O) 2R 15 , -S(O) 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) Selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with 1, 2, or 3 R 20i, or R 1a and R 1b bonded to the same carbon are bonded to form a 3-10 heterocycloalkyl ring or a C3-10 cycloalkyl ring, and the 3-10 heterocycloalkyl ring or C3-10 cycloalkyl ring is optionally substituted with 1, 2, or 3 R 20i, or two R 1a bonded to adjacent atoms are bonded to form a 3-10 membered heterocycloalkyl ring, a C6-10 aryl ring, a 5-12 membered heteroaryl ring, or a C3-10 A cycloalkyl ring is formed, and the 3-10 membered heterocycloalkyl ring, C6-10 aryl ring, 5-12 membered heteroaryl ring, or C3-10 cycloalkyl ring has 1, 2, or 3 RR 1h is optionally substituted with 20i, or one of R 1a, R 1b, R 1c, and R 1d bonded to an adjacent atom is bonded to form a 3-10 membered heterocycloalkyl ring, a C 6-10 aryl ring, a 5-12 membered heteroaryl ring, or a C 3-10 cycloalkyl ring, and the 3-10 membered heterocycloalkyl ring, C 6-10 aryl ring, 5-12 membered heteroaryl ring, and C 3-10 cycloalkyl ring are optionally substituted with 1, 2, or 3 R 20i. Each R1c is independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl, and the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl are optionally substituted with 1, 2, or 3 R20i, the compound according to claim 15, or a pharmaceutically acceptable salt or solvate thereof.

18. R 19 is, 【Chemical 808】 【Chemical 809】 【Chemical 810】 A compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, selected from the above.

19. R 19 is, 【Chemical 811】 【Chemical 812】 【Chemical 813】 A compound according to claim 15, or a pharmaceutically acceptable salt or solvate thereof, selected from the above.

20. R2 is 【Chemical Formula 814】 【Chemical 815】 【Chemical Formula 816】 【Chemical 817】 A compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, selected from the above.

21. R2 is 【Chemical 818】 【Chemical 819】 【Chemical 820】 【Chemical 821】 A compound according to claim 19, or a pharmaceutically acceptable salt or solvate thereof, selected from the above.

22. R 5 is, 【Chemical 822】 A compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, selected from the above.

23. R 5 is, 【Chemical 823】 A compound according to claim 21, or a pharmaceutically acceptable salt or solvate thereof, selected from the above. 【Request Item 24】 【Chemistry 824】 【Chemical 825】 【Chemical 826】 【Chemical 827】 【Chemical 828】 A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from the above. 【Request Item 25】 【Chemistry 829】 【Chemical 830】 【Chemical 831】 A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from the above. 【Request Item 26】 【Chemistry 832】 A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from the above.

27. ​​Formula 【Chemical 833】 A compound having, or a pharmaceutically acceptable salt or solvate thereof.

28. Formula 【Chemical 834】 A compound having, or a pharmaceutically acceptable salt or solvate thereof.

29. Formula 【Chemical 835】 A compound having, or a pharmaceutically acceptable salt or solvate thereof.

30. Formula 【Chemical 836】 A compound having, or a pharmaceutically acceptable salt or solvate thereof.

31. Formula 【Chemical 837】 A compound having, or a pharmaceutically acceptable salt or solvate thereof.

32. Formula 【Chemical 838】 A compound having, or a pharmaceutically acceptable salt or solvate thereof.

33. A pharmaceutical composition comprising a compound according to any one of claims 1 to 32, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

34. A composition for treating cancer in a person requiring cancer treatment, comprising a compound according to any one of claims 1 to 32, or a pharmaceutically acceptable salt or solvate thereof.

35. A composition for inhibiting cell growth, comprising a compound according to any one of claims 1 to 32, or a pharmaceutically acceptable salt or solvate thereof.

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