Heterocyclic compounds and uses thereof

Abstract

The present disclosure provides compounds and their pharmaceutically acceptable salts, as well as methods for their use.The compounds and methods have a wide range of applications as therapeutic, diagnostic, and research tools.In particular, the subject compositions and methods are useful for reducing the signaling output of specific oncogenic proteins.In one aspect, a pharmaceutical composition is provided comprising a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.In one aspect, a method for treating cancer in a subject in need thereof is provided, comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof.

Description

[Background technology]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 395,649, filed August 5, 2022, which is incorporated herein 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 herein by reference in its entirety. The XML copy was created on August 2, 2023, is named 56690_756_601_SL.xml, and is 13,992 bytes in size.

[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 each year. Many types of cancer harbor mutations in one or more proteins involved in various signaling pathways, leading to the uncontrolled proliferation of cancer cells. In some cases, approximately 25–30 percent (%) of tumors are known to harbor Ras (rat sarcoma) mutations. In particular, mutations in K-Ras (Kirsten Ras oncogene) are one of 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 lacking any obvious target region. The specific G12C Ras gene mutation has been identified as a druggable target, with numerous G12C-specific inhibitors being developed. However, because the G12C mutation in Ras exhibits a much lower prevalence than other known Ras mutations, such as G12D and G12V, such therapeutics remain of limited use. Drug resistance and lack of durability pose further limitations to these therapeutics. Summary of the Invention [Means for solving the problem]

[0005] In light of the above, there remains a significant need for novel designs of therapeutic and diagnostic methods that can specifically target Ras, including wild-type Ras, Ras mutants, and / or related proteins, and reduce Ras signaling output. Of particular interest are Ras inhibitors for the treatment of Ras-related diseases (e.g., cancer), including pan-Ras inhibitors capable of inhibiting two or more Ras 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 may be 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 applicable to the diagnosis, prognosis, and / or treatment of a variety of diseases.

[0006] In one aspect, there is provided a compound of formula (A) or a pharmaceutically acceptable salt or solvate thereof: [ka] During the ceremony, W 1 is N(R 1) or N, R 1 is hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20a may be substituted with W 2 is C(R 2 ), N(R 2 ), C(R 2 )2, C(O), S(O), S(O)2, or N; Each R 2 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12a , -SR 12a , -N(R 12a )(R 13 ), -N=(R 15 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 )-, -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and 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 can be one, two, or three R 20b may be substituted with W 3 is C(R 3 ), N(R 3 ), C(R 3 )2, C(O), S(O), S(O)2, or N; Each R 3 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20c may be substituted with W 4 is C(R 4 ), C, or N, R 4 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15, -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20d may be substituted with W 5 is C(R 5 ), C, or N, R 5 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)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)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20e may be substituted with W 6 is C(R 6 ), N(R 6 ), C(R 6 )2, C(O), S(O), S(O)2, or N; Each R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12, -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20f may be substituted with W 7 is C(R 7a ), C, or N, R 7a is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with R 7 -L 7 -R17 and L 7 is a bond, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, a 2-4 membered heteroalkylene linker, -O-, -N(R 7d )-, -C(O)-, -S-, -S(O)2-, -S(O)-, -P(O)R 7d -, CR 7c R 7c , -OCR 7c R 7c -, -N(R 7d )CR 7c R 7c -, -C(O)CR 7c R 7c -,-SCR 7c R 7c -, -S(O)2CR 7c R 7c -, -S(O)CR 7c R 7c -, -P(O)R 7d CR 7c R 7c -, -CR 7c R 7c CR 7c R 7c , -CR 7c R 7c O-, -CR 7c R 7c N(R 7d )-, -CR 7c R 7c C(O)-, -CR 7c R 7c S-, -CR 7c R 7c S(O)2-, -CR 7c R 7c S(O)-, -CR 7c R 7c P(O)R 7d -, -N(R 7d )C(O)-, -N(R 7d )S(O)2-, -N(R 7d )S(O)-, -N(R 7d )P(O)R 7d -, -C(O)N(R 7d )-, -S(O)2N(R 7d )-, -S(O)N(R 7d )-, -P(O)R7d N(R 7d )-, -OC(O)-, -OS(O)2-, -OS(O)-, -OP(O)R 7d -, -C(O)O-, -S(O)2O-, -S(O)O-, or -P(O)R 7d O-, and the C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 2-4 membered heteroalkylene linker is one, two, or three R 20g may be substituted with Each R 7c 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with Each R 7d 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)R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with R 17 is C 3~10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; 3~10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6~10 Aryl and 5- to 10-membered heteroaryl are each independently one or more R 20q or L 7 is a bond and R 7a and R 17 together with the carbon to which they are attached, C 3~10 forming a cycloalkyl or a 3- to 10-membered heterocycloalkyl, 3~10 Cycloalkyl and 3- to 10-membered heterocycloalkyl may be one or more R 20q may be substituted with W 8 is C(R 8 ), N(R 8 ), C(R 8 )2, C(O), S(O), S(O)2, or N; Each R 8 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20h may be substituted with W 9 is C(R 9 ), C, or N, R 9 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20i may be substituted with W 10 is C(R10 ), C, or N, R 10 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and 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 can be one, two, or three R 20j may be substituted with each Z 1 are independently, C(R z1 ), N(R z1 ), C(R z1 )2, C(O), S(O), S(O)2, O, S, or N; z1n is 0, 1, 2, or 3. If z1n is 0, then Z 2 is W 5 is directly bonded to Each R z1 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z1 may be substituted with each Z 9 are independently, C(R z9 ), N(R z9 ), C(R z9 )2, C(O), S(O), S(O)2, O, S, or N; z9n is 0, 1, 2, or 3. If z9n is 0, then Z 3 is W 4 is directly bonded to Each R z9 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z9 may be substituted with The sum of z1n and z9n is 2 or 3, Z 2 is C(R z2 ), C, or N, R z2 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 , -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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z2 may be substituted with Z 3 is C(R z3 ), C, or N, R z3 is 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R20z3 may be substituted with Z 4 is a bond, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c , or Z 4a Z 4b Z 4c Z 4d wherein Z 4a is Z 2 and wherein Z 4 If is a bond, Z 2 is Z 5 directly bonded to Z 4a , Z 4b , Z 4c , and Z 4d are independently, C(R z4 ), N(R z4 ), C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S, or N, however, i) z9n is 0 and Z 4 But Z 4a Z 4b If (1)Z 4b is C(R z4 ), C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S, or N, or (2) Z 4b is N(R z4 ) and Z 4a is C(O), S(O), or S(O)2, or (3)Z 4b is N(R z4 ) and Z 5 is C(O), S(O), or S(O)2, or (4)Z 4b is N(R z4 ) and Z 3 is C(R z3 ) or C, and ii) One R z4 , R z5, R z6 , R 20z4 , R 20z5 , R 20z6 , or R 20z are independently -C(O)R 12 and -N(H)C(O)R 12 wherein one R 12 is C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl, and C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with Each R z4 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)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can have one, two, or three R 20z4 or two R bonded to the same carbon z4 can be combined to form one, two, or three R 20z4 C optionally substituted with 2~6 forming an alkenyl, Z 5 is C(R z5 ), N(R z5 ), C(R z5 )2, C(O), S(O), S(O)2, S(O)(NR z5 ), O, S, or N, Each R z5 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12, -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can have one, two, or three R 20z5 or two R bonded to the same carbon z5 can be combined to form one, two, or three R 20z5 C optionally substituted with 2~6 forming an alkenyl, Z 6 is C(R z6 ), N(R z6 ), C(R z6)2, C(O), S(O), S(O)2, S(O)(NR z6 ), O, S, or N, Each R z6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can have one, two, or three R 20z6 or two R bonded to the same carbon z6 can be combined to form one, two, or three R 20z6 C optionally substituted with 2~6 forming an alkenyl, Additionally, the compound may include one of the following: (1) Two Rs bonded to the same carbon atom z4 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (2) Two or more Rs bonded to adjacent atoms z4 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z may be substituted with (3) Two Rs bonded to the same carbon atom z5 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (4) One or two Rs attached to one atom z4 and one or two R attached to adjacent atoms. z5 is bonded to form a monocyclic C3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z may be substituted with (5) One or two Rs attached to one atom z4 and one or two R attached to the second atom. z5 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (6) Two Rs bonded to the same carbon atom z6 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (7) One or two Rs attached to one atom z5 and one or two R attached to adjacent atoms. z6 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z or (8) One or two Rs attached to one atom z4 and one or two R attached to the second atom. z6 is bonded to form a monocyclic C 3~7cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with Each R 12 are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 heteroaryl, and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with Each R 12a 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-C6~10 Aryl, -C(R 12c )2-C 1~9 Heteroaryl, and C 1~9 heteroaryl, and 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 can be one, two, or three R 20l may be substituted with Each R 12c are independently hydrogen and R 20lc 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, can be one, two, or three R 20m 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 are 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 1~9heteroaryl, 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 can be one, two, or three R 20o may be substituted with Each R 20z1 , R 20z2 , R 20z3 , R 20z4 , R 20z5 , R 20z6 , and R 20z9 are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z may be substituted with Each R 20z are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20zz may be substituted with Two Rs attached to the same carbon atom 20z is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20zz or Two or more R attached to two adjacent atoms 20z is bonded to form a monocyclic C 3~7 may form a cycloalkyl, a monocyclic 3- to 7-membered heterocycloalkyl, a phenyl, or a monocyclic 5- to 6-membered heteroaryl, 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20zz may be substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e, R 20f , R 20g , R 20h , R 20i , R 20j , R 20lc , R 20l , R 20m , R 20o , R 20q , and R 20zz are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, C 1~9 Heteroaryl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 21 , -N(R 24 )S(O)2R 25 , -C(O)R 21 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), -OCH2C(O)OR 22 , =NR 21 , and -OC(O)R 25 and two R bonded to adjacent atoms are selected from20q is combined with C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, or C 1~9 may form a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl is a group containing halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O)2R 25 , -C(O)R 25 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently selected from Each R 21 are independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl; Each R 22 are independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl; Each R 23 are independently hydrogen and C 1~6 alkyl, Each R 24 are independently hydrogen and C 1~6 alkyl, Each R 25 are 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; and [ka] indicates a single or double bond where all valences are satisfied.

[0007] In one aspect, there is provided a compound of formula (A) or a pharmaceutically acceptable salt or solvate thereof: [ka] During the ceremony, W 1 is N(R 1 ) or N, R 1 is hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20a may be substituted with W 2 is C(R 2 ), N(R2 ), C(R 2 )2, C(O), S(O), S(O)2, or N; Each R 2 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 12a , -SR 12a , -N(R 12a )(R 13 ), -N=(R 15 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 )-, -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and C 1~6Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20b may be substituted with W 3 is C(R 3 ), N(R 3 ), C(R 3 )2, C(O), S(O), S(O)2, or N; Each R 3 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20c may be substituted with W 4 is C(R 4 ), C, or N, R 4 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)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(R12 )(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 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20d may be substituted with W 5 is C(R 5 ), C, or N, R 5 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20e may be substituted with W 6 is C(R 6 ), N(R 6 ), C(R 6 )2, C(O), S(O), S(O)2, or N; Each R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12, -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20f may be substituted with W 7 is C(R 7a ), C, or N, R 7a is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20gmay be substituted with R 7 -L 7 -R 17 and L 7 is a bond, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, a 2-4 membered heteroalkylene linker, -O-, -N(R 7d )-, -C(O)-, -S-, -S(O)2-, -S(O)-, -P(O)R 7d -, CR 7c R 7c , -OCR 7c R 7c -, -N(R 7d )CR 7c R 7c -, -C(O)CR 7c R 7c -,-SCR 7c R 7c -, -S(O)2CR 7c R 7c -, -S(O)CR 7c R 7c -, -P(O)R 7d CR 7c R 7c -, -CR 7c R 7c CR 7c R 7c , -CR 7c R 7c O-, -CR 7c R 7c N(R 7d )-, -CR 7c R 7c C(O)-, -CR 7c R 7c S-, -CR 7c R 7c S(O)2-, -CR 7c R 7c S(O)-, -CR 7c R 7c P(O)R 7d -, -N(R 7d )C(O)-, -N(R 7d )S(O)2-, -N(R 7d )S(O)-, -N(R 7d )P(O)R 7d -, -C(O)N(R 7d)-, -S(O)2N(R 7d )-, -S(O)N(R 7d )-, -P(O)R 7d N(R 7d )-, -OC(O)-, -OS(O)2-, -OS(O)-, -OP(O)R 7d -, -C(O)O-, -S(O)2O-, -S(O)O-, or -P(O)R 7d O-, and the C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 2-4 membered heteroalkylene linker is one, two, or three R 20g may be substituted with Each R 7c 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with Each R 7d 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)R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15, and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with R 17 is C 3~10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; 3~10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6~10 Aryl and 5- to 10-membered heteroaryl are each independently one or more R 20q or L 7 is a bond and R 7a and R 17 together with the carbon to which they are attached, C 3~10 forming a cycloalkyl or a 3- to 10-membered heterocycloalkyl, 3~10 Cycloalkyl and 3- to 10-membered heterocycloalkyl may be one or more R 20q may be substituted with W 8 is C(R 8 ), N(R 8 ), C(R 8 )2, C(O), S(O), S(O)2, or N; Each R 8 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12, -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20h may be substituted with W 9 is C(R 9 ), C, or N, R 9 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20imay be substituted with W 10 is C(R 10 ), C, or N, R 10 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and 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 can be one, two, or three R 20j may be substituted with each Z 1 are independently, C(R z1 ), N(R z1 ), C(R z1 )2, C(O), S(O), S(O)2, O, S, or N; z1n is 0, 1, 2, or 3. If z1n is 0, then Z 2 is W 5 is directly bonded to Each R z1 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)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)2R15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z1 may be substituted with each Z 9 are independently, C(R z9 ), N(R z9 ), C(R z9 )2, C(O), S(O), S(O)2, O, S, or N; z9n is 0, 1, 2, or 3. If z9n is 0, then Z 3 is W 4 is directly bonded to Each R z9 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(R12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z9 may be substituted with The sum of z1n and z9n is 2 or 3, Z 2 is C(R z2 ), C, or N, R z2 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z2 may be substituted with Z 3 is C(R z3 ), C, or N, Rz3 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z3 may be substituted with Z 4 is a bond, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c , or Z 4a Z 4b Z 4c Z 4d wherein Z 4a is Z 2 and wherein Z 4 If is a bond, Z 2 is Z 5 directly bonded to Z 4a , Z 4b , Z 4c , and Z 4d are independently, C(R z4 ), N(R z4 ), C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S, or N, however, i) z9n is 0 and Z 4 But Z 4a Z 4b If (1)Z 4b is C(R z4 ), C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S, or N, or (2) Z 4b is N(R z4 ) and Z 4a is C(O), S(O), or S(O)2, or (3)Z 4b is N(R z4 ) and Z 5 is C(O), S(O), or S(O)2, or (4)Z 4b is N(R z4 ) and Z 3 is C(R z3) or C, and ii) R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 , R 20z , R 20zz or R z4 , R z5 , R z6 , R 20z , and R 20zz wherein one of the bonds of the two substituents selected from is E, and E is a moiety capable of covalently binding to a Ras mutant protein at an amino acid corresponding to G12D or G12S in the human K-Ras mutant G12D or G12S protein, respectively; Each R z4 are independently E, hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can have one, two, or three R 20z4 or two R bonded to the same carbon z4 can be combined to form one, two, or three R 20z4 C optionally substituted with 2~6 forming an alkenyl, Z 5 is C(R z5 ), N(R z5 ), C(R z5 )2, C(O), S(O), S(O)2, S(O)(NR z5 ), O, S, or N, Each R z5 are independently E, hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can have one, two, or three R 20z5 or two R bonded to the same carbon z5 can be combined to form one, two, or three R 20z5 C optionally substituted with 2~6 forming an alkenyl, Z 6 is C(R z6 ), N(R z6 ), C(R z6 )2, C(O), S(O), S(O)2, S(O)(NR z6), O, S, or N, Each R z6 are independently E, hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and 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 can have one, two, or three R 20z6 or two R bonded to the same carbon z6 can be combined to form one, two, or three R 20z6 C optionally substituted with 2~6 forming an alkenyl, Additionally, the compound may include one of the following: (1) Two Rs bonded to the same carbon atom z4 is bonded to E, monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (2) Two or more Rs bonded to adjacent atoms z4 is bonded to E, monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z may be substituted with (3) Two Rs bonded to the same carbon atom z5 is bonded to E, monocyclic C 3~7 cycloalkyl, or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (4) One or two Rs attached to one atom z4 and one or two R attached to adjacent atoms. z5 is bonded to E, monocyclic C 3~7cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z may be substituted with (5) One or two Rs attached to one atom z4 and one or two R attached to the second atom. z5 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (6) Two Rs bonded to the same carbon atom z6 is bonded to E, monocyclic C 3~7 cycloalkyl, or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (7) One or two Rs attached to one atom z5 and one or two R attached to adjacent atoms. z6 is bonded to E, monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z or (8) One or two Rs attached to one atom z4 and one or two R attached to the second atom. z6 is bonded to form a monocyclic C 3~7cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with Each R 12 are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 heteroaryl, and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with Each R 12a 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-C6~10 Aryl, -C(R 12c )2-C 1~9 Heteroaryl, and C 1~9 heteroaryl, and 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 can be one, two, or three R 20l may be substituted with Each R 12c are independently hydrogen and R 20lc 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, can be one, two, or three R 20m 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 are 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 1~9heteroaryl, 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 can be one, two, or three R 20o may be substituted with Each R 20z1 , R 20z2 , R 20z3 , and R 20z9 are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z may be substituted with Each R 20z4 , R 20z5 , and R 20z6 are independently E, halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z may be substituted with Each R 20z are independently E, halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20zz may be substituted with Two Rs attached to the same carbon atom 20z is bonded to E, monocyclic C 3~7 cycloalkyl, or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20zz or Two or more R attached to two adjacent atoms 20z is bonded to E, monocyclic C 3~7 may form a cycloalkyl, a monocyclic 3- to 7-membered heterocycloalkyl, a phenyl, or a monocyclic 5- to 6-membered heteroaryl, 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R20zz may be substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20lc , R 20l , R 20lz , R 20m , R 20o , and R 20q are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, C 1~9 Heteroaryl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 21 , -N(R 24 )S(O)2R 25 , -C(O)R 21 , -S(O)2R 25 , -S(O)2N(R 22 )(R23 ), -OCH2C(O)OR 22 , =NR 21 , and -OC(O)R 25 and two R bonded to adjacent atoms are selected from 20q is combined with C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, or C 1~9 may form a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl is a group containing halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O)2R 25 , -C(O)R 25 , -S(O)2R 25, -S(O)2N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently selected from Each R 20zz are independently E, halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, C 1~9 Heteroaryl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 21 , -N(R 24 )S(O)2R 25 , -C(O)R 21 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), -OCH2C(O)OR 22 , =NR 21 , and -OC(O)R 25 and two R bonded to adjacent atoms are selected from 20q is combined with C 3~10 Cycloalkyl, C2~9 Heterocycloalkyl, C 6~10 Aryl, or C 1~9 may form a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl is a group containing halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O)2R 25 , -C(O)R 25 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), and -OC(O)R 25 and each R 21 are independently hydrogen, C 1~6 Alkyl, C1~6 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 hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl; Each R 23 are independently hydrogen and C 1~6 alkyl, Each R 24 are independently hydrogen and C 1~6 alkyl, Each R 25 are 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; and [ka] indicates a single or double bond where all valences are satisfied.

[0008] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, one R z4, R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 , or R 20z are independently -C(O)R 12 or -N(H)C(O)R 12 where one R 12 is C 1~9 Heteroaryl, C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with.

[0009] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 , or R 20z are independently --C(O)R 12 or -N(H)C(O)R 12 where one R 12 is C 2~9 Heterocycloalkyl, C 2~9 Heterocycloalkyl can have one, two, or three R 20l may be substituted with.

[0010] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, one R z4 are independently, 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, 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 can be one, two, or three R 20z4 and one R 20z4 is -C(O)R 12 and -N(H)C(O)R 12 wherein one R 12 is C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl, and C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with.

[0011] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, one R z5 are 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, C 1~9 heteroaryl, 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 can be one, two, or three R 20z5 and one R 20z5 is -C(O)R 12 and -N(H)C(O)R 12 wherein one R 12 is C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl, and C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with.

[0012] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, one R z6 are 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, C 1~9 heteroaryl, 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 can be one, two, or three R 20z6 and one R 20z6 is -C(O)R 12 and -N(H)C(O)R 12 wherein one R 12 is C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl, and C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with.

[0013] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, one R z4 are 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, C 1~9 heteroaryl, 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 can be one, two, or three R 20z4 wherein one R 20z4 is 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, 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 can be one, two, or three R 20z and one R 20z is -C(O)R 12 and -N(H)C(O)R 12 wherein one R 12 is C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl, and C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with.

[0014] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, one R z5 are 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, C 1~9 heteroaryl, and C 1~6Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20z5 wherein one R 20z5 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 heteroaryl, 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 can be one, two, or three R 20z and one R 20z is -C(O)R 12 and -N(H)C(O)R 12 wherein one R 12 is C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl, and C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with.

[0015] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, one R z6 are 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, C 1~9 heteroaryl, 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 can be one, two, or three R 20z6 wherein one R 20z6 is C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 heteroaryl, 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 can be one, two, or three R 20z and one R 20z is -C(O)R 12 and -N(H)C(O)R 12 wherein one R 12 is C 3~10 Cycloalkyl, C2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl, and C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with.

[0016] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, two or more R z4 , R z5 , or R z6 can be combined to form one, two, or three R 20z and forming a ring substituted with one R 20z is -C(O)R 12 and -N(H)C(O)R 12 wherein one R 12 is C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl, and C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with.

[0017] In one aspect, there is provided a compound of formula (A) or a pharmaceutically acceptable salt or solvate thereof: [ka] During the ceremony, W 1is N(R 1 ) or N, R 1 is hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20a may be substituted with W 2 is C(R 2 ), N(R 2 ), C(R 2)2, C(O), S(O), S(O)2, or N; Each R 2 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12a , -SR 12a , -N(R 12a )(R 13 ), -N=(R 15 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 )-, -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20b may be substituted with W 3 is C(R 3 ), N(R 3 ), C(R 3 )2, C(O), S(O), S(O)2, or N; Each R 3 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20c may be substituted with W 4 is C(R 4 ), C, or N, R 4 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20d may be substituted with W 5 is C(R 5 ), C, or N, R 5 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15, -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20e may be substituted with W 6 is C(R 6 ), N(R 6 ), C(R 6 )2, C(O), S(O), S(O)2, or N; Each R 6 are independently 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 )(R13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20f may be substituted with W 7 is C(R 7a ), C, or N, R 7a is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with R7 -L 7 -R 17 and L 7 is a bond, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, a 2-4 membered heteroalkylene linker, -O-, -N(R 7d )-, -C(O)-, -S-, -S(O)2-, -S(O)-, -P(O)R 7d -, CR 7c R 7c , -OCR 7c R 7c -, -N(R 7d )CR 7c R 7c -, -C(O)CR 7c R 7c -,-SCR 7c R 7c -, -S(O)2CR 7c R 7c -, -S(O)CR 7c R 7c -, -P(O)R 7d CR 7c R 7c -, -CR 7c R 7c CR 7c R 7c , -CR 7c R 7c O-, -CR 7c R 7c N(R 7d )-, -CR 7c R 7c C(O)-, -CR 7c R 7c S-, -CR 7c R 7c S(O)2-, -CR 7c R 7c S(O)-, -CR 7c R 7c P(O)R 7d -, -N(R 7d )C(O)-, -N(R 7d )S(O)2-, -N(R 7d )S(O)-, -N(R 7d )P(O)R 7d -, -C(O)N(R 7d )-, -S(O)2N(R 7d)-, -S(O)N(R 7d )-, -P(O)R 7d N(R 7d )-, -OC(O)-, -OS(O)2-, -OS(O)-, -OP(O)R 7d -, -C(O)O-, -S(O)2O-, -S(O)O-, or -P(O)R 7d O-, and the C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 2-4 membered heteroalkylene linker is one, two, or three R 20g may be substituted with Each R 7c 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with Each R 7d 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)R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15, and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with R 17 is C 3~10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; 3~10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6~10 Aryl and 5- to 10-membered heteroaryl are each independently one or more R 20q or L 7 is a bond and R 7a and R 17 together with the carbon to which they are attached, C 3~10 forming a cycloalkyl or a 3- to 10-membered heterocycloalkyl, 3~10 Cycloalkyl and 3- to 10-membered heterocycloalkyl may be one or more R 20q may be substituted with W 8 is C(R 8 ), N(R 8 ), C(R 8 )2, C(O), S(O), S(O)2, or N; Each R 8 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12, -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20h may be substituted with W 9 is C(R 9 ), C, or N, R 9 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20imay be substituted with W 10 is C(R 10 ), C, or N, R 10 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and 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 can be one, two, or three R 20j may be substituted with each Z 1 are independently, C(R z1 ), N(R z1 ), C(R z1 )2, C(O), S(O), S(O)2, O, S, or N; z1n is 0, 1, 2, or 3. If z1n is 0, then Z 2 is W 5 is directly bonded to Each R z1 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)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)2R15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z1 may be substituted with each Z 9 are independently, C(R z9 ), N(R z9 ), C(R z9 )2, C(O), S(O), S(O)2, O, S, or N; z9n is 0, 1, 2, or 3. If z9n is 0, then Z 3 is W 4 is directly bonded to Each R z9 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(R12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z9 may be substituted with The sum of z1n and z9n is 2 or 3, Z 2 is C(R z2 ), C, or N, R z2 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z2 may be substituted with Z 3 is C(R z3 ), C, or N, Rz3 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z3 may be substituted with Z 4 is a bond, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c , or Z 4a Z 4b Z 4c Z 4d wherein Z 4a is Z 2 and wherein Z 4 If is a bond, Z 2 is Z 5 directly bonded to Z 4a , Z 4b , Z 4c , and Z 4d are independently, C(R z4 ), N(R z4 ), C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S, or N, However, z9n is 0 and Z 4 Z 4a Z 4b If (1)Z 4b is C(R z4 ), C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S, or N, or (2) Z 4b is N(R z4 ) and Z 4a is C(O), S(O), or S(O)2, or (3)Z 4b is N(R z4 ) and Z 5 is C(O), S(O), or S(O)2, or (4)Z 4b is N(R z4 ) and Z 3 is C(R z3 ) or C, and Each R z4 are independently, -L z1 -L z2 -L z3 -R 12 , hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can have one, two, or three R 20z4 or two R bonded to the same carbon z4 can be combined to form one, two, or three R 20z4 C optionally substituted with 2~6 forming an alkenyl, Z 5 is C(R z5 ), N(R z5 ), C(R z5 )2, C(O), S(O), S(O)2, S(O)(NR z5 ), O, S, or N, Each R z5 are independently, -L z1 -L z2 -L z3 -R 12 , hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can have one, two, or three R 20z5 or two R bonded to the same carbon z5 can be combined to form one, two, or three R 20z5 C optionally substituted with 2~6 forming an alkenyl, Z 6 is C(R z6 ), N(R z6 ), C(R z6 )2, C(O), S(O), S(O)2, S(O)(NR z6 ), O, S, or N, Each R z6 are independently, -L z1 -L z2 -L z3 -R 12 , hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10Aryl, 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)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can have one, two, or three R 20z6 or two R bonded to the same carbon z6 can be combined to form one, two, or three R 20z6 C optionally substituted with2~6 forming an alkenyl, Additionally, the compound may include one of the following: (1) Two Rs bonded to the same carbon atom z4 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (2) Two or more Rs bonded to adjacent atoms z4 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z may be substituted with (3) Two Rs bonded to the same carbon atom z5 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (4) One or two Rs attached to one atom z4 and one or two R attached to adjacent atoms. z5 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z may be substituted with (5) One or two Rs attached to one atom z4and one or two R attached to the second atom. z5 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (6) Two Rs bonded to the same carbon atom z6 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (7) One or two Rs attached to one atom z5 and one or two R attached to adjacent atoms. z6 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z or (8) One or two Rs attached to one atom z4 and one or two R attached to the second atom. z6 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with Each R 12 are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 heteroaryl, and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with Each R 12a 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, and 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(R12c )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 can be one, two, or three R 20l may be substituted with Each R 12c are independently hydrogen and R 20lc 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, can be one, two, or three R 20m 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 are 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, 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 can be one, two, or three R 20o may be substituted with Each R 20z1 , R 20z2 , R 20z3 , R20z4 , R 20z5 , R 20z6 , and R 20z9 are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z may be substituted with Each R 20z are independently, -L z3 -R 12 , halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15, and -CH2S(O)2N(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 can be one, two, or three R 20zz may be substituted with Two Rs attached to the same carbon atom 20z is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20zz or Two or more R attached to two adjacent atoms 20z is bonded to form a monocyclic C 3~7 may form a cycloalkyl, a monocyclic 3- to 7-membered heterocycloalkyl, a phenyl, or a monocyclic 5- to 6-membered heteroaryl, 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20zz may be substituted with L z1 is a bond, C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, C 3~10 Cycloalkylene, C 2~9 Heterocycloalkylene, C 6~10 arylene, and C 1~9 heteroarylene, 1~6 Alkyl, C 2~6 Alkenylene, C 2~6 Alkynylene, C 3~10 Cycloalkylene, C 2~9Heterocycloalkylene, C 6~10 Arylene, and C 1~9 Heteroarylene is a heteroaryl group consisting of one or two R 30z may be substituted with R 30z are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and C1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20z may be substituted with L z2 is a bond, C 1~6 Alkylene, C 2~6 Alkenylene, C 2~6 Alkynylene, C 3~10 Cycloalkylene, C 2~9 Heterocycloalkylene, C 6~10 Arylene, and C 1~9 heteroarylene, 1~6 Alkyl, C 2~6 Alkenylene, C 2~6 Alkynylene, C 3~10 Cycloalkylene, C 2~9 Heterocycloalkylene, C 6~10 Arylene, and C 1~9 Heteroarylene is a heteroaryl group consisting of one or two R 31z may be substituted with R 31z are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20zz may be substituted with L z3 -R 12 teeth, i.-C(O)R 12 or -N(H)C(O)R 12 wherein L z3 -R 12 R 12 is a 5-membered heteroaryl containing two or more ring nitrogen atoms, and the 5-membered heteroaryl is R 12 is directly bonded to C(O) through the ring nitrogen atom of R 12 is one or more R 20l -C(O)R 12 or -N(H)C(O)R 12 , and ii.-C(O)R 12 or -N(H)C(O)R 12 wherein L z3 -R 12 R 12 is a 3-membered heterocycloalkyl containing one or more ring nitrogen atoms, where R 12 is one or more R 20l -C(O)R 12 or -N(H)C(O)R 12 , selected from R 20l are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, C 1~9 Heteroaryl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 21 , -N(R 24 )S(O)2R 25 , -C(O)R 21 , -S(O)2R 25 , -S(O)2N(R 22 )(R23 ), -OCH2C(O)OR 22 , =NR 21 , and -OC(O)R 25 and two R bonded to adjacent atoms are selected from 20q is combined with C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, or C 1~9 may form a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl is a group containing halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O)2R 25 , -C(O)R 25 , -S(O)2R 25, -S(O)2N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently selected from Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20l , R 20lc , R 20m , R 20o , R 20q , and R 20zz are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, C 1~9 Heteroaryl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 21 , -N(R 24 )S(O)2R25 , -C(O)R 21 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), -OCH2C(O)OR 22 , =NR 21 , and -OC(O)R 25 and two R bonded to adjacent atoms are selected from 20q is combined with C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, or C 1~9 may form a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl is a group containing halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25, -N(R 24 )S(O)2R 25 , -C(O)R 25 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently selected from Each R 21 are independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl; Each R 22 are independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl; Each R 23 are independently hydrogen and C 1~6 alkyl, Each R 24 are independently hydrogen and C 1~6 alkyl, Each R 25 are 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; and [ka] indicates a single or double bond where all valences are satisfied.

[0018] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, L z1 is a bond, C 1~6 Alkylene, C 3~10 Cycloalkylene, and C 2~9 heterocycloalkylene, 1~6 Alkylene, C 3~10 Cycloalkylene, and C 2~9 Heterocycloalkylene can be one or two R 30z may be substituted with R 30z are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z may be substituted with L z2 is a bond, C 1~6 Alkylene, C 3~10 Cycloalkylene, and C 2~9 heterocycloalkylene, 1~6 Alkylene, C 3~10 Cycloalkylene, and C 2~9 Heterocycloalkylene can be one or two R 31z may be substituted with R 31z are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(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)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20zz may be substituted with L z3 -R 12 teeth, i.-C(O)R 12 or -N(H)C(O)R 12 wherein L z3 -R 12R 12 is a 5-membered heteroaryl containing two or more ring nitrogen atoms, and the 5-membered heteroaryl is R 12 is directly bonded to C(O) through the ring nitrogen atom of R 12 is one or more R 20l -C(O)R 12 or -N(H)C(O)R 12 , and ii.-C(O)R 12 or -N(H)C(O)R 12 wherein L z3 -R 12 R 12 is a 3-membered heterocycloalkyl containing one or more ring nitrogen atoms, where R 12 is one or more R 20l -C(O)R 12 or -N(H)C(O)R 12 , selected from R 20l are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, C 1~9 Heteroaryl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 21 , -N(R 24 )S(O)2R 25 , -C(O)R 21 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), -OCH2C(O)OR 22 , =NR 21 , and -OC(O)R 25 and two R bonded to adjacent atoms are selected from 20q is combined with C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, or C 1~9 may form a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl is a group containing 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(R22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O)2R 25 , -C(O)R 25 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently selected from:

[0019] In an embodiment of the compound of Formula (A), or a pharmaceutically acceptable salt or solvate thereof, has the formula: [ka]

[0020] In an embodiment of the compound of Formula (A), or a pharmaceutically acceptable salt or solvate thereof, has the formula: [ka]

[0021] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, [ka] teeth, [ka] is.

[0022] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, [ka] teeth, [ka] is.

[0023] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, two R z5 are joined to form a monocyclic 4-membered heterocycloalkyl, which 4-membered heterocycloalkyl is selected from one, two, or three R 20z is replaced by

[0024] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, [ka] teeth, [ka] wherein one R shown in each formula above is selected from 20z is -C(O)R 12 or -N(H)C(O)R12 is.

[0025] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, one or two R z4 and one or two R attached to adjacent atoms. z5 are linked to form a monocyclic 5- to 6-membered heteroaryl, and the monocyclic 5- to 6-membered heteroaryl is one, two, or three R 20z may be substituted with.

[0026] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, [ka] teeth [ka] wherein one R 20z is -C(O)R 12 or -N(H)C(O)R 12 is.

[0027] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, z1n is 1, 2, or 3; and z9n is 1, 2, or 3. In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, W 1 is N. In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, W 2 is C(R 2 In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, W 3 is N. In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, W 4is C. In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, W 5 is C. In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, W 5 is C(R 5 In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, W 6 is C(R 6 In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, R 6 is hydrogen, halogen, -CN, C 1~6 Alkyl, and -OR 12 C 1~6 Alkyl can be one, two, or three R 20fIn embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, R 6 is halogen. In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, W 7 is C. In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, W 8 is C(R 8 In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, R 8 is hydrogen, halogen, -CN, C 1~6 Alkyl, and -OR 12 C 1~6 Alkyl can be one, two, or three R 20h In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, R8 is halogen. In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, W 9 is C. In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, W 10 is C. In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, [ka] teeth, [ka] is selected from.

[0028] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, L 7is a bond. In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, R 17 is selected from naphthalenyl and benzothiophenyl, each of which is selected from one, two, or three R 20q In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, R 17 is substituted with one, two, or three substituents independently selected from halogen, —CN, —CH 3 , —C≡CH, —OH, and —NH 2 .

[0029] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, R 17 teeth, [ka] is selected from.

[0030] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, R 17 teeth, [ka] [ka] is selected from.

[0031] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, R 2 are independently -OR 12a is.

[0032] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, R 2 are, independently, [ka] [ka] is selected from.

[0033] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, R 2 are, independently, [ka] is.

[0034] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, Z 4 is Z 4a In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or pharmaceutically acceptable salts or solvates thereof, Z 4 is Z 4a Z 4b is.

[0035] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, each R z4 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -N(H)C(O)R 12 , -S(O)2R 15 , and -S(O)N(R 12 )(R 13)-, and C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20z4 or two R bonded to the same carbon z4 can be combined to form one, two, or three R 20z4 C optionally substituted with 2~6 In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, each R z4 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , and -S(O)R 15 C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20z4 or two R bonded to the same carbon z4 can be combined to form one, two, or three R 20z4 C optionally substituted with 2~6In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, each R z5 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -N(H)C(O)R 12 , -S(O)2R 15 , and -S(O)N(R 12 )(R 13 )-, and C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20z5 or two R bonded to the same carbon z5 can be combined to form one, two, or three R 20z5 C optionally substituted with 2~6 In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, each Rz5 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , and -S(O)R 15 C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20z5 or two R bonded to the same carbon z5 can be combined to form one, two, or three R 20z5 C optionally substituted with 2~6 In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, each R z6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -N(H)C(O)R 12 , -S(O)2R 15, and -S(O)N(R 12 )(R 13 )-, and C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20z6 or two R bonded to the same carbon z6 can be combined to form one, two, or three R 20z6 C optionally substituted with 2~6 In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, each R z6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , and -S(O)R 15 C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20z6 or two R bonded to the same carbon z6 can be combined to form one, two, or three R 20z6 C optionally substituted with 2~6In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, each R 20z are independently hydrogen, halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -N(H)C(O)R 12 , -S(O)2R 15 , and -S(O)N(R 12 )(R 13 )-, and C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl is one, two, or three R 20zz or two R bonded to the same carbon 20z can be combined to form one, two or three R 20zz C optionally substituted with 2~6 In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, each R20z are independently hydrogen, halogen, oxo, -CN, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , and -S(O)R 15 C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20zz or two R bonded to the same carbon 20z can be combined to form one, two, or three R 20zz C optionally substituted with 2~6 Forms alkenyl.

[0036] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 , or R 20z are independently -C(O)R 12 and -N(H)C(O)R 12 and -C(O)R 12 or -N(H)C(O)R 12 R 12 teeth, [ka] is selected from.

[0037] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 , or R 20z are independently -C(O)R 12 and -N(H)C(O)R 12 and -C(O)R 12 or -N(H)C(O)R 12 R 12 teeth, [ka] is selected from.

[0038] In embodiments of the compounds of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B, or a pharmaceutically acceptable salt or solvate thereof, one R z4 , R z5 , R z6 , R 20z4 , R 20z5 , R 20z6 , or R 20z are independently C(O)R 12 and -N(H)C(O)R 12 and -C(O)R 12 or -N(H)C(O)R 12 R 12 teeth, [ka] is selected from.

[0039] In one aspect, a pharmaceutical composition is provided comprising a compound described herein (e.g., a compound of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

[0040] 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 (e.g., a compound of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B), or a pharmaceutically acceptable salt or solvate thereof.

[0041] 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, upon contact with the Ras mutant protein, covalently modifies the Ras mutant protein at a residue corresponding to residue 12 of SEQ ID NO: 1, and the modified Ras mutant protein is characterized in that it exhibits reduced Ras signaling output.

[0042] In embodiments, the cancer is a solid tumor. In embodiments, the cancer is a hematological cancer.

[0043] 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 (e.g., a compound of Formula (A), A-1, A-2, A-2a, A-2b, A-3, A-3a, A-3b, A-4, A-4a, A-4b, A-5, A-5a, A-5b, A-5c, A-5d, A-6, A-6a, A-6b, A-6c, A-6d, A-6e, A-6f, and / or B) or a pharmaceutically acceptable salt or solvate thereof, thereby modulating the signaling output of the Ras protein.

[0044] In an embodiment, the method includes administering an additional agent.

[0045] In one aspect, there is provided a compound of formula (A) or a pharmaceutically acceptable salt or solvate thereof: [ka] During the ceremony, W 1 is N(R 1 ) or N, R 1 is hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 15 , -S(O)2N(R12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20a may be substituted with W 2 is C(R 2 ), N(R 2 ), C(R 2 )2, C(O), S(O), S(O)2, or N; Each R 2 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12a , -SR 12a , -N(R 12a )(R 13 ), -N=(R 15 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)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)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20b may be substituted with W 3 is C(R 3 ), N(R 3 ), C(R 3 )2, C(O), S(O), S(O)2, or N; Each R 3 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12)(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20c may be substituted with W 4 is C(R 4 ), C, or N, R 4 is 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20d may be substituted with W 5 is C(R 5 ), C, or N, R 5 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20e may be substituted with W 6 is C(R 6 ), N(R 6 ), C(R 6 )2, C(O), S(O), S(O)2, or N; Each R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20f may be substituted with W 7 is C(R 7a ), C, or N, R 7a 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with R 7 -L 7 -R 17 and L 7 is a bond, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, a 2-4 membered heteroalkylene linker, -O-, -N(R 7d ), -C(O)-, -S-, -S(O)2-, -S(O)-, -P(O)R 7d -, CR 7c R 7c , -OCR 7c R 7c -, -N(R 7d )CR 7c R 7c -, -C(O)CR 7c R 7c -,-SCR 7c R 7c -, -S(O)2CR 7c R 7c -, -S(O)CR 7c R 7c -, -P(O)R 7d CR 7c R7c -, -CR 7c R 7c CR 7c R 7c , -CR 7c R 7c O-, -CR 7c R 7c N(R 7d )-, -CR 7c R 7c C(O)-, -CR 7c R 7c S-, -CR 7c R 7c S(O)2-, -CR 7c R 7c S(O)-, -CR 7c R 7c P(O)R 7d -, -N(R 7d )C(O)-, -N(R 7d )S(O)2-, -N(R 7d )S(O)-, -N(R 7d )P(O)R 7d -, -C(O)N(R 7d )-, -S(O)2N(R 7d )-, -S(O)N(R 7d )-, -P(O)R 7d N(R 7d )-, -OC(O)-, -OS(O)2-, -OS(O)-, -OP(O)R 7d -, -C(O)O-, -S(O)2O-, -S(O)O-, or -P(O)R 7d O—, and the C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, and 2-4 membered heteroalkylene linkers are selected from one, two, or three R 20g may be substituted with Each R 7c 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with Each R 7d are independently hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with R 17 is C 3~10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; 3~10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6~10 Aryl and 5- to 10-membered heteroaryl are each independently one or more R 20q may be substituted with W 8 is C(R 8), N(R 8 ), C(R 8 )2, C(O), S(O), S(O)2, or N; Each R 8 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and 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 can be one, two, or three R 20h may be substituted with W 9 is C(R 9 ), C, or N, R 9 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20i may be substituted with W 10 is C(R 10 ), C, or N, R 10 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)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)2R15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20j may be substituted with each Z 1 are independently, C(R z1 ), N(R z1 ), C(R z1 )2, C(O), S(O), S(O)2, O, S, or N; z1n is 0, 1, 2, 3, or 4. If z1n is 0, then Z 2 is W 5 is directly bonded to Each R z1 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(R12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z1 may be substituted with Z 2 is C(R z2 ), C, or N, R z2 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z2 may be substituted with Z 3 is C(R z3 ), C, or N, R z3 is 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R20z3 may be substituted with Z 4 is a bond, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c , Z 4a Z 4b Z 4c Z 4d , or Z 4a Z 4b Z 4c Z 4d Z 4e wherein Z 4a is Z 2 and wherein Z 4 If is a bond, Z 2 is Z 5 is directly bonded to Z 4a , Z 4b , Z 4c , Z 4d , and Z 4e are independently, C(R z4 ), N(R z4 ), C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S, or N, However, z9n is 0 and Z 4 Z 4a Z 4b If (1)Z 4b is C(R z4 ), C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S, or N, or (2) Z 4b is N(R z4 ) and Z 4a is C(O), S(O), or S(O)2, or (3)Z 4b is N(R z4 ) and Z 5 is C(O), S(O), or S(O)2, or (4)Z 4b is N(R z4 ) and Z 3 is C(Rz3 ) or C, Each R z4 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)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and 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 can have one, two, or three R 20z4 or two R bonded to the same carbon z4 can be combined to form one, two, or three R 20z4 C optionally substituted with 2~6 forming an alkenyl, Z 5 is C(R z5 ), N(R z5 ), C(R z5 )2, C(O), S(O), S(O)2, S(O)(NR z5 ), O, S, or N, Each R z5 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15, -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can have one, two, or three R 20z5 or two R bonded to the same carbon z5 can be combined to form one, two, or three R 20z5 C optionally substituted with 2~6 forming an alkenyl, Z 6 is C(R z6 ), N(R z6 ), C(R z6 )2, C(O), S(O), S(O)2, S(O)(NR z6 ), O, S, or N, Each R z6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can have one, two, or three R 20z6 or two R bonded to the same carbon z6 can be combined to form one, two, or three R 20z6 C optionally substituted with 2~6 forming an alkenyl, Additionally, the compound may include one of the following: (1) Two Rs bonded to the same carbon atom z4 is bonded to form a monocyclic C 3~7cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (2) Two or more Rs bonded to adjacent atoms z4 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z may be substituted with (3) Two Rs bonded to the same carbon atom z5 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (4) One or two Rs attached to one atom z4 and one or two R attached to adjacent atoms. z5 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z may be substituted with (5) One or two Rs attached to one atom z4 and one or two R attached to the second atom. z5 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (6) Two Rs bonded to the same carbon atom z6 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (7) One or two Rs attached to one atom z5 and one or two R attached to adjacent atoms. z6 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z or (8) One or two Rs attached to one atom z4 and one or two R attached to the second atom. z6 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with Two Rs attached to the same carbon atom 20z is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20zz or Two or more R attached to two adjacent atoms 20zis bonded to form a monocyclic C 3~7 may form a cycloalkyl, a monocyclic 3- to 7-membered heterocycloalkyl, a phenyl, or a monocyclic 5- to 6-membered heteroaryl, 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20zz may be substituted with each Z 9 are independently, C(R z9 ), N(R z9 ), C(R z9 )2, C(O), S(O), S(O)2, O, S, or N; z9n is 0, 1, 2, 3, or 4. If z9n is 0, then Z 3 is W 4 is directly bonded to Each R z9 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14)C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z9 may be substituted with The sum of z1n and z9n is 2, 3, or 4, Each R 12 are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 heteroaryl, and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with Each R 12a 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, and 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 can be one, two, or three R 20l may be substituted with Each R 12c are independently hydrogen and R 20lc is selected from Each R 13 are independently hydrogen, C 1~6 Alkyl, and C 1~6 haloalkyl, or R12 and R 13 together with the nitrogen to which they are attached, can be one, two, or three R 20m 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 are 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, 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 can be one, two, or three R 20o may be substituted with Each R 20z1 , R 20z2 , R 20z3 , R 20z4 , R 20z5 , R 20z6 , and R 20z9 are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z may be substituted with Each R 20z are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12, -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20zz may be substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R20i , R 20j , R 20l , R 20lc , R 20m , R 20o , R 20q , and R 20zz are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, C 1~9 Heteroaryl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 21 , -N(R 24 )S(O)2R 25 , -C(O)R 21 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), -OCH2C(O)OR 22 , =NR 21 , and -OC(O)R 25 and two R bonded to adjacent atoms are selected from 20q is combined with C 3~10 Cycloalkyl, C 2~9Heterocycloalkyl, C 6~10 Aryl, or C 1~9 may form a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl is a group containing halogen, oxo, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O)2R 25 , -C(O)R 25 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently selected from Each R 21 are independently hydrogen, C 1~6 Alkyl, C1~6 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 hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl; Each R 23 are independently hydrogen and C 1~6 alkyl, Each R 24 are independently hydrogen and C 1~6 alkyl, Each R 25 are 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; and [ka] indicates a single or double bond where all valences are satisfied.

[0046] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka]

[0047] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] is selected from.

[0048] In some embodiments, two R z5 is bonded to form a monocyclic C 3~7 cycloalkyl, or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z In embodiments, two R z5 are joined to form a monocyclic 4-membered heterocycloalkyl, which 4-membered heterocycloalkyl is selected from one, two, or three R 20z is replaced by

[0049] In an embodiment, [ka] teeth, [ka] [ka] In an embodiment, [ka] teeth, [ka] is selected from.

[0050] In embodiments, one or two R z4 and one or two R attached to adjacent atoms. z5 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z In embodiments, one or two R z4 and one or two R attached to adjacent atoms. z5 are linked to form a monocyclic 5- to 6-membered heteroaryl, and the monocyclic 5- to 6-membered heteroaryl is one, two, or three R 20z In embodiments, one or two R z4 and one or two R attached to adjacent atoms z5 The monocyclic 5- to 6-membered heteroaryl formed by the bonding of R is triazolyl, pyrazolyl, imidazolyl, pyrrolyl, furanyl, thienyl, oxazolyl, isoxazolyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, each of which is selected from the group consisting of one, two, or three R 20z In embodiments, one or two R z4 and one or two R attached to adjacent atoms z5 The monocyclic 5- to 6-membered heteroaryl formed by the bonding of 20z and optionally substituted pyrazolyl.

[0051] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] is selected from.

[0052] In an embodiment, z1n is 1, 2 or 3, and z9n is 1, 2 or 3. In an embodiment, z1n is 0. In an embodiment, z9n is 0.

[0053] In an embodiment, W 1 is N. In an embodiment, W 1 is N(R 1 )

[0054] In an embodiment, W 2 is C(R 2 In an embodiment, W 2 is N(R 2 In an embodiment, W 2 is C(O).

[0055] In an embodiment, W 3 is N. In an embodiment, W 3 is C(R 3 )

[0056] In an embodiment, W 4 is C.

[0057] In an embodiment, W 5 is C. In an embodiment, W 5 is C(R 5 )

[0058] In an embodiment, W 6 is C(R 6In an embodiment, W 6 is N(R 6 In an embodiment, R 6 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 3~6 Cycloalkyl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -C(O)R 15 , -C(O)N(R 12 )(R 13 ), -S(O)R 15 , and -S(O)N(R 12 )(R 13 ) and C 1~6 Alkyl, and C 3~6 Cycloalkyl can have one, two, or three R 20f In some embodiments, R 6 is hydrogen, halogen, -CN, C 1~6 Alkyl, and -OR 12 C 1~6 Alkyl can be one, two, or three R 20f In embodiments, R 6 is a halogen. In an embodiment, W 6 is N.

[0059] In an embodiment, W 7 is C. In an embodiment, W 7 is C(R 7a In an embodiment, W 7 is N.

[0060] In an embodiment, W 8 is C(R 8 In an embodiment, R 8 is hydrogen, halogen, -CN, C 1~6 Alkyl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12, -C(O)R 15 , -C(O)N(R 12 )(R 13 ), -S(O)R 15 , and -S(O)N(R 12 )(R 13 ) and C 1~6 Alkyl can be one, two, or three R 20h In embodiments, R 8 is hydrogen, halogen, -CN, C 1~6 Alkyl, and -OR 12 C 1~6 Alkyl can be one, two, or three R 20h In embodiments, R 8 is a halogen. In an embodiment, W 8 is N.

[0061] In an embodiment, W 9 is C.

[0062] In an embodiment, W 10 is C.

[0063] In an embodiment, [ka] teeth, [ka] is selected from.

[0064] In an embodiment, L 7 is a bond.

[0065] In embodiments, R 17 is C 6~10 aryl and 5- to 10-membered heteroaryl, each of which is selected from one, two, or three R 20q In embodiments, R 17 is C 10aryl and 9-membered heteroaryl, each of which is selected from one, two, or three R 20q In embodiments, R 17 is selected from naphthalenyl and benzothiophenyl, each of which is selected from one, two, or three R 20q In embodiments, R 17 is halogen, -CN, C 1~3 Alkyl, C 2~3 Alkenyl, C 2~3 Alkynyl, -OR 21 , and -N(R 22 )(R 23 In embodiments, R 17 is substituted with one, two, or three substituents independently selected from halogen, —CN, —CH, —C≡CH, —OH, and —NH. In embodiments, R 17 is substituted with -F, -CN, and -NH. In embodiments, R 17 teeth, [ka] is selected from.

[0066] In embodiments, R 17 teeth, [ka] is selected from Q 1 , Q 3 , and Q 5 are independently N and C(R 1d ) and Q 4 and Q 6 are independently O, S, C(R 1a )(R 1b ), and N(R 1c ) and X 4 , X 5 , X 6 , X 9 , X10 are independently, C(R 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 ) and 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 ) and X 16 are independently determined by C, N, and C(R 1a ) and 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 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can have one, two, or three R 20q or R attached to the same carbon 1a and R 1b are bonded to form a 3- to 10-membered heterocycloalkyl ring or C 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 20q or two R bonded to adjacent atoms 1a are bonded to form a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl ring, 5- to 12-membered heteroaryl ring, or C 3~10Forming a cycloalkyl ring, 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl ring, 5- to 12-membered heteroaryl ring, or C 3~10 A cycloalkyl ring can contain one, two, or three R 20q or R 1h , and R attached to adjacent atoms 1a , R 1b , R 1c , and R 1d one of which is bonded to form a 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl ring, 5- to 12-membered heteroaryl ring, or C 3~10 Forming a cycloalkyl ring, 3- to 10-membered heterocycloalkyl ring, C 6~10 Aryl rings, 5- to 12-membered heteroaryl rings, and C 3~10 A cycloalkyl ring can contain one, two, or three R 20q and 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, 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 can be one, two, or three R 20q may be substituted with.

[0067] In embodiments, R 17 teeth, [ka] [ka] is selected from.

[0068] In embodiments, R 2 are independently -OR 12a is.

[0069] In embodiments, R 2 are, independently, [ka] [ka] In embodiments, R 2 are, independently, [ka] is.

[0070] In an embodiment, Z 4 is a bond, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c , Z 4a Z 4b Z 4c Z 4d , or Z 4a Z 4b Z 4c Z 4d Z 4e In an embodiment, Z 4 is Z 4a In an embodiment, Z 4 is Z 4a Z 4b In an embodiment, Z 4 is Z 4a Z 4b Z 4c In an embodiment, Z 4 is Z 4a Z 4b Z 4c Z 4d In an embodiment, Z 4 is Z 4a Z 4b Z4c Z 4d Z 4e is.

[0071] In embodiments, each R z4 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , and -S(O)N(R 12 )(R 13 )-, and C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20z4 or two R bonded to the same carbon z4 can be combined to form one, two, or three R 20z4 C optionally substituted with 2~6 In embodiments, each R z4 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15, and -S(O)R 15 C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20z4 or two R bonded to the same carbon z4 can be combined to form one, two, or three R 20z4 C optionally substituted with 2~6 Forms alkenyl.

[0072] In embodiments, each R z5 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , and -S(O)N(R 12 )(R 13 )-, and C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20z5 or two R bonded to the same carbon z5 can be combined to form one, two, or three R 20z5 C optionally substituted with 2~6In embodiments, each R z5 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , and -S(O)R 15 C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20z5 or two R bonded to the same carbon z5 can be combined to form one, two, or three R 20z5 C optionally substituted with 2~6 Forms alkenyl.

[0073] In embodiments, each R z6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , and -S(O)N(R 12 )(R 13 )-, and C 1~6Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20z6 or two R bonded to the same carbon z6 can be combined to form one, two, or three R 20z6 C optionally substituted with 2~6 Forms alkenyl.

[0074] In embodiments, each R z6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , and -S(O)R 15 C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20z6 or two R bonded to the same carbon z6 can be combined to form one, two, or three R 20z6 C optionally substituted with 2~6 Forms alkenyl.

[0075] In embodiments, each R 20z are independently hydrogen, halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , and -S(O)N(R 12 )(R 13 )-, and C 1~6 Alkyl, C 2~6 Alkenyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20zz or two R bonded to the same carbon 20z can be combined to form one, two, or three R 20zz C optionally substituted with 2~6 In embodiments, each R 20z are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -OR 12 , -N(R 12 )(R 13 ), -N(R 14 )S(O)2R 15 , and -S(O)R 15 C 1~6 Alkyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryl can have one, two, or three R 20zz or two R bonded to the same carbon 20z can be combined to form one, two, or three R 20zz C optionally substituted with 2~6 In embodiments, each R 20zare independently oxo.

[0076] In one aspect, 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, Compounds are provided in which B is a monovalent form of a degradation promoter.

[0077] In embodiments, 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, P IAS4, 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 (chaperon-mediated autophagy) autophage), 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) is capable of binding to a protein selected from ubiquitin ligase, XIAP, IAP, KEAP1, DCAF15, RNF114, DCAF16, AhR, SOCS2, KLHL12, UBR2, SPOP, KLHL3, KLHL20, KLHDC2, SPSB1, SPSB2, SPSB4, SOCS6, FBXO4, FBXO31, BTRC, FBW7, CDC20, PML, TRIM21, TRIM24, TRIM33, GID4, avadomide, iberdomide, and CC-885. In embodiments, the degradation-promoting agent is capable of binding to a protein selected from UBE2A, UBE2B, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2DR, UBE2E1, UBE2E2, UBE2E3, UBE2F, UBE2G1, UBE2G2, UBE2H, UBE2I, UBE2J1, UBE2J2, UBE2K, UBE2L3, UBE2L6, UBE2L1, UBE2L2, UBE2L4, UBE2M, UBE2N, UBE2O, UBE2Q1, UBE2Q2, UBE2R1, UBE2R2, UBE2S, UBE2T, UBE2U, UBE2V1, UBE2V2, UBE2W, UBE2Z, ATG3, BIRC6, and UFC1. 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)2N(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 1~6Alkyl-O) z -, 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, 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 be one, two, or three R 20n and optionally substituted with (-OC 1~6 alkyl) z - and (-C 1~6 Alkyl-O) z -Each C 1~6 Alkyl can be one, two, or three R 20n may be 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, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 heteroaryl, and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with 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, can be one, two, or three R 20m 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 are 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, 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 can be one, two, or three R 20o may be substituted with Each R 20l , R 20m , R 20n , and R 20o are each independently a halogen, -CN, or C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, C 1~9 Heteroaryl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O)2R 25 , -C(O)R 25 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), -OCH2C(O)OR 22 , and -OC(O)R 25 C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl is a group containing halogen, oxo, -CN, C1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O)2R 25 , -C(O)R 25 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently 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 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 23 are independently H and C 1~6 alkyl, Each R 24 are independently H and C 1~6 alkyl; Each R 25 are 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.

[0078] In an embodiment, L AB is -(O-C2 alkyl) z - and z is an integer from 1 to 10. In an embodiment, L AB is -(C2 alkyl-O-) z - and z is an integer from 1 to 10. In an embodiment, L AB is -(CH2) zz1 L AB2 (CH2O) zz2 - in which L AB2 is a bond, 5- or 6-membered heterocycloalkylene or heteroarylene, phenylene, -(C2-C4)alkynylene, -SO2-, or -NH-, and zz1 and zz2 are independently integers of 0-10.

[0079] In an embodiment, L AB is -(CH2) zz1 (CH2O) zz2 -, wherein zz1 and zz2 are each independently an integer of 0 to 10. In an embodiment, L AB is a PEG linker. In embodiments, B is [ka] is a monovalent form of a compound selected from

[0080] In one aspect, there is provided a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

[0081] 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 pharmaceutically acceptable salt or solvate thereof.

[0082] 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 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, thereby causing the modified Ras mutant protein to exhibit reduced Ras signaling output.

[0083] In embodiments, the cancer is a solid tumor or a hematological cancer.

[0084] 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 pharmaceutically acceptable salt or solvate thereof, thereby modulating the signaling output of the Ras protein.

[0085] In one aspect, a method of inhibiting cell growth is provided, comprising administering an effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, to a cell expressing a Ras protein, thereby inhibiting growth of the cell.

[0086] In embodiments, the method includes administering an additional agent, which in embodiments includes (1) an inhibitor of MEK, (2) an inhibitor of epidermal growth factor receptor (EGFR) and / or a mutant thereof, (3) an immunotherapeutic agent, (4) a taxane, (5) an antimetabolite, (6) an inhibitor of FGFR1 and / or FGFR2 and / or FGFR3 and / or a mutant thereof, (7) a mitotic kinase inhibitor, (8) an anti-angiogenic agent, (9) a topoisomerase inhibitor, (10) a platinum-containing compound, (11) a c-MET and / or or an inhibitor of a mutant thereof, (13) an inhibitor of BCR-ABL and / or a mutant thereof, (14) an inhibitor of ErbB2 (Her2) and / or a mutant thereof, (15) an inhibitor of AXL and / or a mutant thereof, (16) an inhibitor of NTRK1 and / or a mutant thereof, (17) an inhibitor of RET and / or a mutant thereof, (18) an inhibitor of A-Raf and / or B-Raf and / or C-Raf and / or a mutant thereof, (19) an inhibitor of E Inhibitors of RK and / or its mutants, (20) MDM2 inhibitors, (21) inhibitors of mTOR, (23) inhibitors of IGF1 / 2 and / or IGF1-R, (24) inhibitors of CDK9, (25) inhibitors of farnesyltransferase, (26) inhibitors of the SHIP pathway, (27) inhibitors of SRC, (28) inhibitors of JAK, (29) PARP inhibitors, (31) ROS1 inhibitors, (32) inhibitors of the SHP pathway, or (33) inhibitors of Src, FLT3, HDAC, V In some embodiments, the additional agent is selected from the group consisting of an inhibitor of EGFR, PDGFR, LCK, Bcr-Abl, or AKT, an inhibitor of KrasG12C mutant, an SHC inhibitor (e.g., PP2, AID371185), an inhibitor of GAB, an inhibitor of PI-3 kinase, an inhibitor of MARPK, an inhibitor of CDK4 / 6, an inhibitor of MAPK, an inhibitor of MAPK, an inhibitor of SHP2, an inhibitor of SHP2, an inhibitor of SOS1, or an inhibitor of SOS2. [ka] In embodiments, the additional agent comprises an inhibitor of SHP2 selected from RMC-5845, BI-1701963, [ka] In embodiments, the additional agent comprises an SOS inhibitor selected from afatinib, erlotinib, gefitinib, lapatinib, cetuximab, panitumumab, osimertinib, olmutinib, and EGF-816. In embodiments, the additional agent comprises an 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 a BRAF inhibitor selected from sorafenib, vemurafenib, dabrafenib, encorafenib, regorafenib, and GDC-879.

[0087] 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.

[0088] 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. [Brief explanation of the drawings]

[0089] [Figure 1]Figure 1 shows a sequence alignment of various wild-type Ras proteins, including, from top to bottom, K-Ras, H-Ras, N-Ras, RalA, and RalB. DETAILED DESCRIPTION OF THE INVENTION

[0090] 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 one of ordinary skill in the art. See, e.g., Sambrook and Green, Molecular Cloning: A Laboratory Manual, 4 th See, for example, Current Protocols in Molecular Biology series (eds. F.M.A.usubel et al.), Methods in Enzymology series (Academic Press, Inc.), PCR 2: A Practical Approach (eds. M.J. MacPherson, B.D. Hames, and G.R. Taylor (1995)), Harlow and Lane (1988) Antibodies, A Laboratory Manual, and Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6th Edition (ed. R.I. Freshney (2010)).

[0091] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood to which the claimed subject matter belongs. In the event that there are multiple definitions for terms in this specification, the definitions in this section shall prevail. All patents, patent applications, publications, and published nucleotide and amino acid sequences (e.g., sequences available in GenBank or other databases) mentioned herein are incorporated by reference. When referring to a URL or other such identifier or address, it should be understood that such identifiers may change and specific information on the Internet may come and go, but that equivalent information may be found by searching the Internet. Reference thereto attests to the availability and public dissemination of such information.

[0092] 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. As used herein, the use of the singular includes the plural unless expressly 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 dictates otherwise. As used herein, the use of "or" means "and / or" unless expressly stated otherwise. Furthermore, the use of the term "including," as well as other forms such as "include," "includes," and "included," is not limiting.

[0093] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0094] Definitions of standard chemical terms include, but are not limited to, Carey and Sundberg "Advanced Organic Chemistry 4 th" Ed." 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.

[0095] Unless specific definitions are provided, the nomenclature utilized in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are art-recognized. Standard techniques can be used for chemical synthesis, chemical analysis, pharmaceutical preparation, formulation, and 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-specific 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.

[0096] 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.

[0097] As used herein, C1-C x are C1~C2, C1~C3...C1~C x Includes C1~C x indicates the number of carbon atoms that make up the moiety it designates (excluding optional substituents).

[0098] 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 to 18, 1 to 12, 1 to 10, 1 to 8, or 1 to 6 carbon atoms. (Whenever appearing herein, a numerical range such as "1 to 6" refers to each integer within the given range; for example, "1 to 6 carbon atoms" means that the alkyl group can consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 6 carbon atoms, although this definition also encompasses appearances of the term "alkyl" where no numerical range is specified.) The alkyl groups of the compounds described herein may be designated as "C1-C6 alkyl" or similar designations. As just one example, "C1-C6 alkyl" refers to 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, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, and hexyl. Alkyl groups can be substituted or unsubstituted. Depending on the structure, alkyl groups can be monoradicals or diradicals (i.e., alkylene groups).

[0099] "Alkoxy" refers to the group "-O-alkyl", where alkyl is as defined herein.

[0100] 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=CH2, -C(CH3)=CH2, -CH=CHCH3, -CH=C(CH3)2, and -C(CH3)=CHCH3. 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 (i.e., an alkenylene group).

[0101] 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≡CCH3, -C≡CCH2CH3, and -C≡CCH2CH2CH3. 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).

[0102] "Amino" refers to the group -NH2.

[0103] The term "alkylamine" or "alkylamino" refers to an -N(alkyl) x H y "Dialkylamino" refers to the group -N(alkyl)2, 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 the group -N(alkyl)2, where alkyl is as defined herein.

[0104] The term "aromatic" refers to a planar ring having a delocalized electron system containing π4n+2π electrons, where n is an integer. An aromatic ring can be formed from five, six, seven, eight, nine, or more than nine atoms. An aromatic can be optionally substituted. The term "aromatic" includes both aryl groups (e.g., phenyl, naphthalenyl) and heteroaryl groups (e.g., pyridinyl, quinolinyl).

[0105] As used herein, the term "aryl" refers to a monocyclic aromatic ring (e.g., phenyl) or a polycyclic ring system (e.g., bicyclic or tricyclic) in which each of the atoms forming the ring is a carbon atom, where 1) at least one ring is a carbocyclic aromatic ring, 2) the bond to the rest of the compound is directly attached to a 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 in the polycyclic ring system. The aryl ring can be formed from five, six, seven, eight, nine, or more than nine carbon atoms. The aryl group can be optionally substituted. Examples of aryl groups include, but are not limited to, phenyl and naphthalenyl. Depending on the structure, the aryl group can be a monoradical or a diradical (i.e., an arylene group). As used herein, the aryl group is a monocyclic, bicyclic, or tricyclic ring system. In embodiments, the aryl is a monocyclic ring. In embodiments, the aryl is a fused-ring polycyclic system. In embodiments, the aryl is a bridged-ring polycyclic system. In some embodiments, the aryl is a "fused-ring aryl" in which the aryl ring is fused to a cycloalkyl or heterocycloalkyl ring. In embodiments, the aryl is a "fused bicyclic" aryl in which the two rings of the aryl group share one bond.

[0106] "Carboxy" refers to -CO2H. In some embodiments, the carboxy moiety can be replaced with a "carboxylic acid bioisostere," which refers to a functional group or moiety that exhibits similar physical and / or chemical properties to a carboxylic acid moiety. A carboxylic acid bioisostere has similar biological properties to a carboxylic acid group. A compound having a carboxylic acid moiety can have its carboxylic acid moiety replaced with a carboxylic acid bioisostere and have similar physical and / or biological properties compared to the carboxylic acid-containing compound. For example, in one embodiment, a carboxylic acid bioisostere will ionize 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:

[0107] The term "cycloalkyl" refers to a monocyclic carbocyclic saturated or partially unsaturated non-aromatic ring or a polycyclic carbocyclic (i.e., containing no heteroatoms) ring system (e.g., bicyclic or tricyclic) in which 1) at least one ring is a carbocyclic saturated or partially unsaturated non-aromatic ring system, 2) the bond to the remainder of the compound is directly 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 within the polycyclic ring 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, cycloalkyl groups include groups having 3 to 10 ring atoms. Depending on the structure, cycloalkyl groups can be monoradicals or diradicals (i.e., cycloalkylene groups). In embodiments, cycloalkyls are "fused bicyclic" cycloalkyls, in which the two rings of the cycloalkyl group share one bond.

[0108] 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 to an aromatic ring directly bonded (e.g., fused) to an aromatic ring of the aryl ring system containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur. As used herein, a heteroaryl group 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 embodiments, a heteroaryl is a monocyclic ring. In embodiments, a heteroaryl is a fused-ring polycyclic system. In embodiments, a heteroaryl is a bridged-ring polycyclic 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). In embodiments, the heteroaryl is a "fused bicyclic" heteroaryl in which the two rings of the heteroaryl group share one bond.

[0109] 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 a saturated or partially unsaturated non-aromatic ring containing one or more heteroatoms, and 2) the bond to the remainder of the compound is directly bonded to a ring in 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 ring, spiro ring) to a saturated or partially unsaturated non-aromatic ring containing one or more heteroatoms in the ring system. Heterocycloalkyls can be saturated or partially unsaturated. The term heterocycloalkyl also includes carbohydrates of all ring forms, 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 specified, a heterocycloalkyl has 2 to 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) comprising the heterocycloalkyl (i.e., the skeletal atoms of the heterocycloalkyl ring). Depending on the structure, a heterocycloalkyl group can be a monoradical or a diradical (i.e., a heterocycloalkylene group). In embodiments, the heterocycloalkyl is a "fused bicyclic" heterocycloalkyl, in which the two rings of the heterocycloalkyl group share one bond.

[0110] The term "halo" or alternatively "halogen" means fluoro, chloro, bromo and iodo.

[0111] The abbreviations "Fmoc," "Ac," "Bn," "PMB," "Tr," "Ts," "Boc," and "Cbz" are used according to their ordinary meaning, as is well understood in the chemical arts, to refer to monovalent chemical substituents, which are fluorenylmethyloxycarbonyl, acetyl, benzyl, p-methoxybenzyl, trityl or triphenylmethyl, tosyl, tert-butyloxycarbonyl, and carbobenzyloxy, respectively. The term "monovalent" is used herein according to its meaning, as is well understood in the chemical arts, to refer to the ability of a substituent to form one covalent bond with another substituent or compound capable of forming a covalent bond. In a related manner, the term "divalent" refers to a substituent or compound capable of forming two covalent bonds, e.g., a linker capable of covalently linking two monovalent substituents or compounds.

[0112] The term "haloalkyl" refers to an alkyl group substituted with one or more halogens. The halogens can be the same or different. Non-limiting examples of haloalkyls include -CH2Cl, -CF3, -CHF2, -CH2CF3, -CF2CF3, and the like.

[0113] The terms "fluoroalkyl" and "fluoroalkoxy" include alkyl and alkoxy groups, respectively, substituted with one or more fluorine atoms. Non-limiting examples of fluoroalkyl include -CF, -CHF, -CHF, -CHCF, -CFCF, -CFCF, -CF(CH), and the like. Non-limiting examples of fluoroalkoxy groups include -OCF, -OCHF, -OCHF, -OCHCF, -OCFCF, -OCFCF, -OCF(CH), and the like.

[0114] The term "heteroalkyl" refers to an alkyl group in which one or more skeletal atoms are selected from atoms other than carbon, such as oxygen, nitrogen, sulfur, phosphorus, silicon, or combinations thereof. The heteroatoms can be located at any interior position of the heteroalkyl group. Examples include, but are not limited to, -CH2-O-CH3, -CH2-CH2-O-CH3, -CH2-NH-CH3, -CH2-CH2-NH-CH3, -CH2-N(CH3)-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH2-S(O)-CH3, -CH2-CH2-S(O)-CH3, -CH2-NH-OCH3, -CH2-O-Si(CH3)3, -CH2-CH=N-OCH3, and -CH=CH-N(CH3)-CH3. Additionally, up to two heteroatoms may be consecutive, such as, for example, -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. A "heteroalkyl" may have 1 to 6 carbon atoms, excluding the number of heteroatoms.

[0115] The term "heteroalkylene linker" refers to a divalent alkyl group in which one or more skeletal atoms are selected from atoms other than carbon, such as oxygen, nitrogen, sulfur, phosphorus, silicon, or combinations thereof. In some embodiments, the heteroatoms can be located at any interior position of the heteroalkyl group. In some embodiments, the heteroatoms can be located at one or both terminal positions of the heteroalkylene linker (i.e., positions directly attached to a portion of the molecule other than the heteroalkylene linker). Examples include, but are not limited to, -CH2-O-CH2-, -CH2-CH2-O-CH2-, -CH2-NH-CH2-, -CH2-CH2-NH-CH2-, -CH2-N(CH3)-CH2-, -CH2-CH2-N(CH3)-CH2-, -CH2-S-CH2-CH2-, -CH2-CH2-S(O)-CH2-, -CH2-CH2-S(O)-CH2-, -CH2-NH-O-CH2-, -CH2-O-Si(CH3)2-, -CH2-CH=NO-CH2-, and -CH=CH-N(CH3)-CH2-. Examples are -CH2-O-, -CH2-CH2-O-, -CH2-NH-, -CH2-CH2-NH-, -CH2-N(CH3)-, -CH2-CH2-N(CH3)-, -CH2-S-, -CH2-CH2-S-, -C H2-CH2-S(O)-, -CH2-CH2-S(O)2-, -CH2-S(O)-, -CH2-S(O)2-, -CH2-CH2-CH2-S(O)-, -CH2-CH2-CH2-S(O)2-, -CH2-CH2-C These include, but are not limited to, H2-O-, -CH2-CH2-CH2-O-, -CH2-CH2-CH2-S-, -CH2-CH2-CH2-S-, -CH2-CH2-CH2-NH-, -CH2-CH2-CH2-NH-, -CH2-CH2-CH2-N(CH3)-, -CH2-CH2-CH2-N(CH3)-, -CH2-NH-O-, -O-Si(CH3)2-, -CH2-CH=NO-, and -CH=CH-N(CH3)-.Examples are -O-CH2-, -O-CH2-CH2-, -NH-CH2-, -NH-CH2-CH2-, -N(CH3)-CH2-, -N(CH3)-CH2-CH2-, -S-CH2-, -S-CH2-CH2-, -S (O)-CH2-CH2-, -S(O)2-CH2-CH2-, -S(O)-CH2-, -S(O)2-CH2-, -S(O)-CH2-CH2-CH2-, -S(O)2-CH2-CH2-CH2-, -O-CH2-CH2 These heteroatoms include, but are not limited to, -CH-, -O-CH-CH-CH-, -S-CH-CH-CH-, -S-CH-CH-CH-, -NH-CH-CH-CH-, -NH-CH-CH-CH-, -N(CH)-CH-CH-CH-, -N(CH)-CH-CH-CH-, -O-NH-CH-, -Si(CH)-O-, -ON=CH-CH-, and -N(CH)-CH=CH-. Additionally, up to two heteroatoms may be consecutive, such as, for example, -CH-NH-O- and -O-Si(CH)-. Examples include, but are not limited to, -P(O)(CH3)-CH2-, -P(O)(CH3)-CH2-CH2-, -P(O)(CH3)-CH2-CH2-, -CH2-P(O)(CH3)-, -CH2-CH2-P(O)(CH3)-, -CH2-CH2-P(O)(CH3)-, and -CH2-CH2-CH2-P(O)(CH3)-. Additionally, up to two heteroatoms may be consecutive, such as, for example, -CH2-NH-O- and -O-Si(CH3)2-. A "heteroalkylene linker" may have 2 to 4 main chain atoms, unless otherwise specified.

[0116] The term "oxo" refers to the group =O.

[0117] 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 structure.

[0118] The term "moiety" refers to a specific segment or functional group of a molecule. A chemical moiety is a chemical entity that is often recognized as embedded within or attached to a molecule.

[0119] It is understood that the suffix "-di-yl" means that the substituent or linker is a divalent substituent or linker.

[0120] As used herein, the substituent "R" appearing alone and without a numerical designation refers to a substituent selected from among alkyl, haloalkyl, heteroalkyl, alkenyl, cycloalkyl, aryl, heteroaryl (bonded via a ring carbon), and heterocycloalkyl.

[0121] "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes cases where the event or circumstance occurs and cases where it does not occur.

[0122] The terms "optionally substituted," "optionally substituted," or "substituted," unless otherwise specified, mean that the referenced group can be substituted with one or more additional groups individually and independently selected from alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, -OH, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, arylsulfone, -CN, alkyne, C1-C6 alkylalkyne, halo, acyl, acyloxy, -COH, -CO2-alkyl, nitro, haloalkyl, fluoroalkyl, and amino, including mono- and di-substituted amino groups (e.g., -NH2, -NHR, -NR2), and protected derivatives thereof. By way of example, optional substituents are L s R s wherein each L sis independently selected from a bond, —O—, —C(═O)—, —S—, —S(═O)—, —S(═O)2-, —NH—, —NHC(O)—, —C(O)NH-, S(═O)2NH-, —NHS(═O)2, —OC(O)NH-, —NHC(O)O—, —(C1-C6 alkyl)-, or —(C2-C6 alkenyl)-; and each R s are independently selected from H, (C1-C6 alkyl), (C3-C8 cycloalkyl), aryl, heteroaryl, heterocycloalkyl, and C1-C6 heteroalkyl. Protecting groups that may form the protective derivatives of the above substituents can be found in references such as Greene and Wuts, above.

[0123] "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.

[0124] "Pharmaceutically acceptable acid addition salts" refer to those salts which retain the biological effectiveness and properties of the free base, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphorous acid, etc. Also included are salts formed with organic acids such as, for example, aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxyalkanoic acids, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, and 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, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, 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. Amino acid salts such as arginate, gluconate, and galacturonate are also contemplated (see, e.g., Berge SM et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science, 66:1-19 (1997)). Acid addition salts of basic compounds are, in some embodiments, prepared by contacting the free base form with a sufficient amount of the desired acid to produce the salt, according to methods and techniques familiar to those skilled in the art.

[0125] "Pharmaceutically acceptable base addition salts" refer to those salts that retain the biological effectiveness and characteristics of the free acid 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, in some embodiments, formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, N,N-dibenzylethylenediamine, chloroprocaine, hydrabamine, choline, betaine, ethylenediamine, ethylenedianiline, N-methylglucamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, etc. See Berge et al., supra.

[0126] 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. The terms also encompass modified amino acid polymers, such as 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 either natural and / or unnatural or synthetic amino acids, including glycine and both D- and L-optical isomers, as well as amino acid analogs and peptidomimetics.

[0127] The terms "polynucleotide," "nucleotide," "nucleotide sequence," "nucleic acid," and "oligonucleotide" are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides may have any three-dimensional structure and may perform any function, known or unknown. The following are non-limiting examples of polynucleotides: coding or non-coding regions of a gene or gene fragment, loci determined 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 acids (PNAs), morpholinos and locked nucleic acids (LNAs), glycol nucleic acids (GNAs), threose nucleic acids (TNAs), 2'-fluoro, 2'-OMe, and phosphorothiolated DNA. If present, modifications to the nucleotide structure may be imparted before or after assembly of the polymer. The sequence of nucleotides may be interrupted by non-nucleotide components. Polynucleotides may be further modified after polymerization, such as by conjugation with a labeling component or another binding target.

[0128] As used herein, "expression" refers to the process by which a polynucleotide is transcribed from a DNA template (such as into mRNA or other RNA transcripts) and / or the process by which the transcribed mRNA is subsequently translated into a peptide, polypeptide, or protein. The transcript and the encoded polypeptide may be collectively referred to as a "gene product." If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in a eukaryotic cell.

[0129] As used herein, the terms "subject," "individual," and "patient" are used interchangeably 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 encompassed are tissues, cells, and their progeny of biological entities obtained in vivo or cultured in vitro.

[0130] 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 onset of a disease, symptom, disorder, or condition, and generally counteracting a disease, symptom, disorder, or pathological condition.

[0131] As used herein, "treatment" or "treating," or "alleviating" or "ameliorating" are used interchangeably. These terms refer to an approach to obtaining a beneficial or desired result, including, but not limited to, therapeutic benefit and / or prophylactic benefit. Therapeutic benefit refers to any therapeutically relevant improvement in or effect on one or more diseases, conditions, or symptoms under treatment. For prophylactic benefit, the compositions can be administered to subjects at risk of developing a particular disease, condition, or symptom, or to subjects who report one or more physiological symptoms of a disease, even though 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 under treatment (e.g., between a treated and an untreated population, or between a treated and an untreated state of a subject).

[0132] The term "effective amount" or "therapeutically effective amount" refers to an amount of an agent sufficient to produce a beneficial or desired result. A 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., and can be readily determined by one of ordinary skill in the art. An effective amount of an active agent may be administered in a single dose or multiple doses. A component may be described herein as having at least an effective amount, or at least an effective amount, such as those associated with a particular goal or objective, such as any described herein. The term "effective amount" also applies to a dose that will provide 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 or not it is co-administered with other compounds, the timing of administration, the tissue to be imaged, and the bodily delivery system by which the agent is delivered.

[0133] The term "in vivo" refers to events that take place inside a subject's body.

[0134] The term "ex vivo" refers to an event that initially occurs outside a subject's body for later application in vivo within the subject's body. For example, ex vivo preparation can involve preparing cells outside a subject's body with the intent of introducing the prepared cells into the same or a different subject.

[0135] The term "in vitro" refers to an event that occurs outside a subject's body. For example, an in vitro assay includes any assay that is performed outside 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 that do not use intact cells.

[0136] The term "Ras" or "RAS" refers to a protein in the Rat sarcoplasmic reticulum (Ras) superfamily of small GTPases, such as in the Ras subfamily. The Ras superfamily includes, but is not limited to, the Ras subfamily, Rho subfamily, Rab subfamily, Rap subfamily, Arf subfamily, Ran subfamily, Rheb subfamily, RGK subfamily, Rit subfamily, Miro subfamily, and an unclassified subfamily. In some embodiments, the Ras protein is selected from the group consisting of KRAS (also interchangeably referred to herein as K-Ras, K-ras, or Kras), HRAS (or H-Ras), NRAS (or N-Ras), MRAS (or M-Ras), ERAS (or E-Ras), RRAS2 (or R-Ras2), RALA (or RalA), RALB (or RalB), RIT1, and any combination thereof, such as KRAS, HRAS, NRAS, RALA, RALB, and any combination thereof. The terms "mutant 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 induced mutation, a naturally occurring mutation, or a non-naturally occurring mutation. In some embodiments, the mutation can be a substitution (e.g., a substituted amino acid), an insertion (e.g., an addition of one or more amino acids), or a deletion (e.g., a removal of one or more amino acids). In some embodiments, the two or more mutations can be consecutive, non-consecutive, or a combination thereof. In some embodiments, the mutation can be at any position in Ras.In some embodiments, the mutations may be present at positions 12, 13, 62, 92, 95, 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 amino acids in length, or less than 50 amino acids. In some embodiments, the mutated amino acid is a proteinogenic 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 nonpolar side chain, a hydrophobic side chain, a hydrophilic side chain, an aliphatic side chain, an aromatic side chain, a cyclic side chain, an acyclic side chain, a basic side chain, or an acidic side chain. In some embodiments, the mutation comprises a reactive moiety. In some embodiments, the replacement amino acid comprises a reactive moiety. In some embodiments, the mutant Ras can be further modified, such as by conjugation with a detectable label. In some embodiments, the mutant Ras is a full-length polypeptide or a truncated polypeptide. For example, the mutant Ras can be a truncated polypeptide comprising residues 1-169 or residues 11-183 (e.g., residues 11-183 of mutant RALA or mutant RALB).

[0137] As used herein, when applied to an amino acid residue in a polypeptide sequence, the term "corresponding to" or "corresponding to" refers to the correspondence of that amino acid relative to a reference sequence when optimally aligned (e.g., the alignment may be a primary sequence alignment or a three-dimensional structural alignment of a folded protein, taking into account gaps, insertions, and mismatches). For example, a serine residue in a Ras G12S mutant refers to the serine corresponding to residue 12 of SEQ ID NO:4, which can serve as a reference sequence. For example, an aspartic acid residue in a Ras G12D mutant refers to the aspartic acid corresponding to residue 12 of SEQ ID NO:2, which can serve as a reference sequence. Where an amino acid in a mutant Ras protein corresponds to an amino acid position in a wild-type Ras protein, it is understood that the amino acid in the mutant Ras protein may be a different amino acid (e.g., G12D, in which the wild-type G at position 12 is replaced with aspartic acid at position 12 of SEQ ID NO:1), but the mutant amino acid is at the position corresponding to the wild-type amino acid (e.g., in SEQ ID NO:1). In embodiments, the modified Ras mutant proteins disclosed herein may include truncations at the C-terminus or at the N-terminus before the serine residue. The serine residue in such N-terminal truncated modified mutants is still considered to correspond to position 12 of SEQ ID NO:1. In addition, the serine residue at position 12 of SEQ ID NO:4 is found in the corresponding residues in SEQ ID NOs:6 and 8. 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 pharmaceutically acceptable precursor of a biologically active compound. A prodrug may be inactive when administered to a subject but is converted in vivo, for example, by hydrolysis, to an active compound.Prodrug compounds may offer advantages of solubility, tissue compatibility, and / or delayed release in mammalian organisms (see, e.g., Bundgard, H., Design of Prodrugs (1985), pp. 7-9, 21-24 (Elsevier, Amsterdam)). A discussion of prodrugs is provided in Higuchi, T., et al., "Prodrugs 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 entireties. A "prodrug" may be any covalently bonded carrier that releases the active compound in vivo when such prodrug is administered to a mammalian subject. Prodrugs of the active compounds described herein can be prepared by modifying functional groups present in the active compound in such a way that the modifications are cleaved, either by routine manipulation or in vivo, to the parent active compound.

[0138] 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 rest of a molecule, taking with it the pair of electrons that was used in the bond between the leaving group and the rest of the molecule.

[0139] A "degradation-promoting agent" refers to a compound capable of binding to a ubiquitin ligase protein (e.g., an E3 ubiquitin ligase protein) or a protein capable of binding to a ubiquitin ligase protein to form a protein complex capable of binding 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 enzyme that binds to E2 ubiquitin. In embodiments, the degradation-promoting agent is capable of binding to a protein complex comprising an enzyme that binds to E2 ubiquitin and an E3 ubiquitin ligase protein.

[0140] Across a bond or a bond or dashed bond [ka] [ka] The symbol at the end of the atom indicates the location of a bond scission or addition to a substituent, further component or atom of a molecule (e.g., the location of a bond to another atom). For example, [ka] represent a single or double bond, a single bond, a double bond, and a triple bond, respectively, in the formula: [ka] is as defined immediately above.

[0141] compound In one embodiment, there is provided a compound of formula (A) below, or a pharmaceutically acceptable salt or solvate thereof: [ka] During the ceremony, W 1 is N(R 1 ) or N, R 1 is hydrogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20a may be substituted with W 2 is C(R 2 ), N(R 2 ), C(R 2)2, C(O), S(O), S(O)2, or N; Each R 2 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12a , -SR 12a , -N(R 12a )(R 13 ), -N=(R 15 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) and C 1~6 Alkyl, C 2~6 Alkenyl, C2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl can be one, two, or three R 20b may be substituted with W 3 is C(R 3 ), N(R 3 ), C(R 3 )2, C(O), S(O), S(O)2, or N; Each R 3 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20c may be substituted with W 4 is C(R 4 ), C, or N, R 4 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20d may be substituted with W 5 is C(R 5 ), C, or N, R 5 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15, -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20e may be substituted with W 6 is C(R 6 ), N(R 6 ), C(R 6 )2, C(O), S(O), S(O)2, or N; Each R 6 are independently 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 )(R13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20f may be substituted with W 7 is C(R 7a ), C, or N, R 7a is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with R7 -L 7 -R 17 and L 7 is a bond, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, a 2-4 membered heteroalkylene linker, -O-, -N(R 7d ), -C(O)-, -S-, -S(O)2-, -S(O)-, -P(O)R 7d -, CR 7c R 7c , -OCR 7c R 7c -, -N(R 7d )CR 7c R 7c -, -C(O)CR 7c R 7c -,-SCR 7c R 7c -, -S(O)2CR 7c R 7c -, -S(O)CR 7c R 7c -, -P(O)R 7d CR 7c R 7c -, -CR 7c R 7c CR 7c R 7c , -CR 7c R 7c O-, -CR 7c R 7c N(R 7d )-, -CR 7c R 7c C(O)-, -CR 7c R 7c S-, -CR 7c R 7c S(O)2-, -CR 7c R 7c S(O)-, -CR 7c R 7c P(O)R 7d -, -N(R 7d )C(O)-, -N(R 7d )S(O)2-, -N(R 7d )S(O)-, -N(R 7d )P(O)R 7d -, -C(O)N(R 7d )-, -S(O)2N(R 7d)-, -S(O)N(R 7d )-, -P(O)R 7d N(R 7d )-, -OC(O)-, -OS(O)2-, -OS(O)-, -OP(O)R 7d -, -C(O)O-, -S(O)2O-, -S(O)O-, or -P(O)R 7d O—, and the C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, and 2-4 membered heteroalkylene linkers are selected from one, two, or three R 20g may be substituted with Each R 7c 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with Each R 7d 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)R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15, and -CH2S(O)2N(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 can be one, two, or three R 20g may be substituted with R 17 is C 3~10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6~10 aryl, and 5- to 10-membered heteroaryl; 3~10 Cycloalkyl, 3-10 membered heterocycloalkyl, C 6~10 Aryl and 5- to 10-membered heteroaryl are each independently one or more R 20q may be substituted with W 8 is C(R 8 ), N(R 8 ), C(R 8 )2, C(O), S(O), S(O)2, or N; Each R 8 are independently 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20h may be substituted with W 9 is C(R 9 ), C, or N, R 9 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20i may be substituted with W 10 is C(R 10 ), C, or N, R 10 is hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20j may be substituted with each Z 1 are independently, C(R z1), N(R z1 ), C(R z1 )2, C(O), S(O), S(O)2, O, S, or N; z1n is 0, 1, 2, 3, or 4. If z1n is 0, then Z 2 is W 5 is directly bonded to Each R z1 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15, and -CH2S(O)2N(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 can be one, two, or three R 20z1 may be substituted with Z 2 is C(R z2 ), C, or N, R z2 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z2 may be substituted with Z 3 is C(R z3 ), C, or N, R z3 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z3 may be substituted with Z 4 is a bond, Z 4a , Z 4a Z 4b , Z 4a Z 4b Z 4c , Z 4a Z 4b Z 4c Z 4d , or Z 4a Z 4b Z 4c Z 4d Z 4e wherein Z 4a is Z 2 and wherein Z 4 If is a bond, Z 2 is Z 5 is directly bonded to Z 4a , Z 4b , Z 4c , Z 4d , and Z 4e are independently, C(Rz4 ), N(R z4 ), C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S, or N, However, z9n is 0 and Z 4 Z 4a Z 4b If (1)Z 4b is C(R z4 ), C(R z4 )2, C(O), S(O), S(O)2, S(O)(NR z4 ), O, S, or N, or (2) Z 4b is N(R z4 ) and Z 4a is C(O), S(O), or S(O)2, or (3)Z 4b is N(R z4 ) and Z 5 is C(O), S(O), or S(O)2, or (4)Z 4b is N(R z4 ) and Z 3 is C(R z3 ) or C, Each R z4 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)2R 15 , -C(O)R12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can have one, two, or three R 20z4 or two R bonded to the same carbon z4 can be combined to form one, two, or three R 20z4 C optionally substituted with 2~6 forming an alkenyl, Z 5 is C(R z5 ), N(R z5 ), C(R z5 )2, C(O), S(O), S(O)2, S(O)(NR z5 ), O, S, or N, Each R z5 are independently 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)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can have one, two, or three R 20z5 or two R bonded to the same carbon z5 can be combined to form one, two, or three R20z5 C optionally substituted with 2~6 forming an alkenyl, Z 6 is C(R z6 ), N(R z6 ), C(R z6 )2, C(O), S(O), S(O)2, S(O)(NR z6 ), O, S, or N, Each R z6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15, -CH2S(O)2R 15 , and -CH2S(O)2N(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 can have one, two, or three R 20z6 or two R bonded to the same carbon z6 can be combined to form one, two, or three R 20z6 C optionally substituted with 2~6 forming an alkenyl, Additionally, the compound may include one of the following: (1) Two Rs bonded to the same carbon atom z4 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (2) Two or more Rs bonded to adjacent atoms z4 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z may be substituted with (3) Two Rs bonded to the same carbon atom z5 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R20z may be substituted with (4) One or two Rs attached to one atom z4 and one or two R attached to adjacent atoms. z5 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z may be substituted with (5) One or two Rs attached to one atom z4 and one or two R attached to the second atom. z5 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (6) Two Rs bonded to the same carbon atom z6 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with (7) One or two Rs attached to one atom z5 and one or two R attached to adjacent atoms. z6 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z or (8) One or two Rs attached to one atom z4 and one or two R attached to the second atom. z6 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z may be substituted with Two Rs attached to the same carbon atom 20z is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20zz or Two or more R attached to two adjacent atoms 20z is bonded to form a monocyclic C 3~7 may form a cycloalkyl, a monocyclic 3- to 7-membered heterocycloalkyl, a phenyl, or a monocyclic 5- to 6-membered heteroaryl, 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20zz may be substituted with each Z 9 are independently, C(R z9 ), N(R z9 ), C(R z9 )2, C(O), S(O), S(O)2, O, S, or N; z9n is 0, 1, 2, 3, or 4. If z9n is 0, then Z 3 is W 4 is directly bonded to Each R z9 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)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20z9 may be substituted with The sum of z1n and z9n is 2, 3, or 4, Each R12 are independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 heteroaryl, and C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl can be one, two, or three R 20l may be substituted with Each R 12a 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, and 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 can be one, two, or three R 20l may be substituted with Each R 12c are independently hydrogen and R 20lc 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, can be one, two, or three R 20m 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 are 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, 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 can be one, two, or three R 20o may be substituted with Each R 20z1 , R 20z2 , R 20z3 , R 20z4 , R 20z5 , R 20z6 , and R 20z9 are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15, and -CH2S(O)2N(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 can be one, two, or three R 20z may be substituted with Each R 20z are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 12 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 12 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R12 )(R 13 ), -CHN(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(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 can be one, two, or three R 20zz may be substituted with Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , R 20l , R 20lc , R 20m , R 20o , R 20q , and R 20zz are independently halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, C 1~9 Heteroaryl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 , -C(O)N(R 22 )(R 23), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 21 , -N(R 24 )S(O)2R 25 , -C(O)R 21 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), -OCH2C(O)OR 22 , =NR 21 , and -OC(O)R 25 and two R bonded to adjacent atoms are selected from 20q is combined with C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, or C 1~9 may form a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, -CH2-C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, -CH2-C 1~9 Heteroaryl, and C 1~9 Heteroaryl is a group containing 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(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 25 , -N(R 24 )S(O)2R 25 , -C(O)R 25 , -S(O)2R 25 , -S(O)2N(R 22 )(R 23 ), and -OC(O)R 25 and optionally substituted with one, two, or three groups independently selected from Each R 21 are independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl; Each R 22 are independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 heteroaryl; Each R 23 are independently hydrogen and C 1~6 alkyl, Each R 24 are independently hydrogen and C 1~6 alkyl, Each R 25are 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; and [ka] indicates a single or double bond where all valences are satisfied.

[0142] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka]

[0143] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka] In embodiments, the compound has the formula: [ka]

[0144] In an embodiment, [ka] or any embodiment thereof (e.g., sub-formula): [ka] In an embodiment, [ka] or any embodiment thereof (e.g., sub-formula): [ka] is selected from.

[0145] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] is selected from.

[0146] In some embodiments, two R z5 is bonded to form a monocyclic C 3~7 cycloalkyl, or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z In embodiments, two R z5 are joined to form a monocyclic 4-membered heterocycloalkyl, which 4-membered heterocycloalkyl is selected from one, two, or three R 20z is replaced by In an embodiment, [ka] teeth, [ka] [ka] In an embodiment, [ka] teeth, [ka] is selected from.

[0147] In embodiments, one or two R z4 and one or two R attached to adjacent atoms. z5 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z In embodiments, one or two R z4 and one or two R attached to adjacent atoms. z5 are linked to form a monocyclic 5- to 6-membered heteroaryl, and the monocyclic 5- to 6-membered heteroaryl is one, two, or three R 20z In embodiments, one or two R z4 and one or two R attached to adjacent atoms z5 The monocyclic 5- to 6-membered heteroaryl formed by the bonding of R is triazolyl, pyrazolyl, imidazolyl, pyrrolyl, furanyl, thienyl, oxazolyl, isoxazolyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, each of which is selected from the group consisting of one, two, or three R 20z In embodiments, one or two R z4 and one or two R attached to adjacent atoms z5The monocyclic 5- to 6-membered heteroaryl formed by the bonding of 20z and optionally substituted pyrazolyl.

[0148] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] is selected from.

[0149] In an embodiment, z1n is 1, 2 or 3, and z9n is 1, 2 or 3. In an embodiment, z1n is 0. In an embodiment, z9n is 0.

[0150] In an embodiment, W 1 is N. In an embodiment, W 1 is N(R 1 )

[0151] In an embodiment, W 2 is C(R 2 In an embodiment, W 2 is N(R 2 In an embodiment, W 2 is C(O).

[0152] In an embodiment, W 3 is N. In an embodiment, W 3 is C(R 3 )

[0153] In an embodiment, W 3 is N. In an embodiment, W 3is O. In an embodiment, W 3 is S. In an embodiment, W 3 is C(O). In an embodiment, W 3 is S(O). In an embodiment, W 3 is S(O). In an embodiment, W 3 is C(R 3 In an embodiment, W 3 is C(R 3 )(R 3a In an embodiment, R 3 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -C(O)R 15 , -C(O)N(R 12 )(R 13 ), -S(O)R 15 , and -S(O)N(R 12 )(R 13 )-, and C 1~6 Alkyl can be one, two, or three R 20c In embodiments, R 3 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, and -OR 12 C 1~6 Alkyl can be one, two, or three R 20c In embodiments, R 3 is hydrogen.

[0154] In embodiments, R 3 are independently hydrogen. In embodiments, R 3 is independently halogen. In an embodiment, R 3 is independently -CN. In an embodiment, R 3 are independently -OR 12 In an embodiment, R 3 are independently, -SR 12 In an embodiment, R3 are independently -N(R 12 )(R 13 In an embodiment, R 3 are independently -C(O)OR 12 In an embodiment, R 3 are independently -OC(O)N(R 12 )(R 13 In an embodiment, R 3 are independently -N(R 14 )C(O)N(R 12 )(R 13 In an embodiment, R 3 are independently -N(R 14 )C(O)OR 15 In an embodiment, R 3 are independently -N(R 14 )S(O)2R 15 In an embodiment, R 3 are independently -C(O)R 15 In an embodiment, R 3 are independently -S(O)R 15 In an embodiment, R 3 are independently -OC(O)R 15 In an embodiment, R 3 are independently -C(O)N(R 12 )(R 13 In an embodiment, R 3 are independently -C(O)C(O)N(R 12 )(R 13 In an embodiment, R 3 are independently -N(R 14 )C(O)R 15 In an embodiment, R 3 are independently -S(O)R 15 In an embodiment, R 3 are independently -S(O)N(R 12 )(R 13 In an embodiment, R 3 are independently -S(=O)(=NH)N(R 12 )(R 13 In an embodiment, R 3 are independently -CH2C(O)N(R12 )(R 13 In an embodiment, R 3 are independently -CH2N(R 14 )C(O)R 15 In an embodiment, R 3 are independently -CH2S(O)2R 15 In an embodiment, R 3 are independently -CH2S(O)2N(R 12 )(R 13 )

[0155] In an embodiment of the compound, R 3 are independently one or two R 20c In a further embodiment of the compound, R 3 is independently methyl. In some embodiments of the compound, R 3 independently, one, two, or three R 20c In an embodiment of the compound, R 3 is independently ethyl. In some embodiments of the compound, R 3 independently, one, two, or three R 20c In an embodiment of the compound, R 3 is independently propyl.

[0156] In embodiments, R 3 is independently -CN. In an embodiment, R 3 independently, one, two, or three R 20b C optionally substituted with 1~6 In embodiments, R 3 independently, one, two, or three R 20b C optionally substituted with 2~6 In embodiments, R is an alkenyl. 3 independently, one, two, or three R 20a C optionally substituted with 2~6 In embodiments, R is alkynyl. 3 independently, one, two, or three R 20bC optionally substituted with 3~10 In embodiments, R 3 independently, one, two, or three R 20b C optionally substituted with 2~9 In embodiments, R is heterocycloalkyl. 3 independently, one, two, or three R 20b C optionally substituted with 6~10 In embodiments, R 3 independently, one, two, or three R 20b C optionally substituted with 1~9 In embodiments, R 3 are independently -OR 12 In an embodiment, R 3 are independently -C(O)OR 12 In an embodiment, R 3 are independently -OC(O)N(R 12 )(R 13 In an embodiment, R 3 are independently -C(O)R 15 In an embodiment, R 3 is independently halogen. In an embodiment, R 3 are independently -N(R 12 )(R 13 In an embodiment, R 3 are independently -NH2.

[0157] In an embodiment, W 4 is C.

[0158] In an embodiment, W 5 is C. In an embodiment, W 5 is C(R 5 )

[0159] In an embodiment, W 6 is C(R 6 In an embodiment, W 6 is N(R 6 In an embodiment, R 6 are independently hydrogen, halogen, -CN, C1~6 Alkyl, C 3~6 Cycloalkyl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -C(O)R 15 , -C(O)N(R 12 )(R 13 ), -S(O)R 15 , and -S(O)N(R 12 )(R 13 ) and C 1~6 Alkyl, and C 3~6 Cycloalkyl can have one, two, or three R 20f In embodiments, R 6 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, and -OR 12 C 1~6 Alkyl can be one, two, or three R 20f In embodiments, R 6 is a halogen. In an embodiment, W 6 is N.

[0160] In embodiments, R 6 is independently hydrogen. 6 is independently halogen. In an embodiment, R 6 is independently -CN. In an embodiment, R 6 are independently -OR 12 In an embodiment, R 6 are independently, -SR 12 In an embodiment, R 6 are independently -N(R 12 )(R 13 In an embodiment, R 6 are independently -C(O)OR 12 In an embodiment, R 6 are independently -OC(O)N(R 12 )(R 13 In an embodiment, R 6are independently -N(R 14 )C(O)N(R 12 )(R 13 In an embodiment, R 6 are independently -N(R 14 )C(O)OR 15 In an embodiment, R 6 are independently -N(R 14 )S(O)2R 15 In an embodiment, R 6 are independently -C(O)R 15 In an embodiment, R 6 are independently -S(O)R 15 In an embodiment, R 6 are independently -OC(O)R 15 In an embodiment, R 6 are independently -C(O)N(R 12 )(R 13 In an embodiment, R 6 are independently -C(O)C(O)N(R 12 )(R 13 In an embodiment, R 6 are independently -N(R 14 )C(O)R 15 In an embodiment, R 6 are independently -S(O)R 15 In an embodiment, R 6 are independently -S(O)N(R 12 )(R 13 In an embodiment, R 6 are independently -S(=O)(=NH)N(R 12 )(R 13 In an embodiment, R 6 are independently -CH2C(O)N(R 12 )(R 13 In an embodiment, R 6 are independently -CH2N(R 14 )C(O)R 15 In an embodiment, R 6 are independently -CH2S(O)2R 15 In an embodiment, R 6 are independently -CH2S(O)2N(R12 )(R 13 )

[0161] In selected embodiments of the compound, R 6 independently, one, two, or three R 20f C optionally substituted with 1~6 In some embodiments, R 6 independently, one, two, or three R 20f C optionally substituted with 2~6 In some embodiments, R is alkenyl. 6 independently, one, two, or three R 20f C optionally substituted with 2~6 In some embodiments, R is alkynyl. 6 independently, one, two, or three R 20f C optionally substituted with 3~10 In some embodiments, R 6 independently, one, two, or three R 20f C optionally substituted with 2~9 In some embodiments, R 6 independently, one, two, or three R 20f C optionally substituted with 6~10 In some embodiments, R 6 independently, one, two, or three R 20f C optionally substituted with 1~9 In a further embodiment, R 6 are independently hydrogen.

[0162] In an embodiment of the compound, R 6 are independently one or two R 20f In a further embodiment of the compound, R 6 is independently methyl. In some embodiments of the compound, R 6 independently, one, two, or three R 20f In an embodiment of the compound, R 6is independently ethyl. In some embodiments of the compound, R 6 independently, one, two, or three R 20f In an embodiment of the compound, R 6 is independently propyl.

[0163] In an embodiment, W 7 is C. In an embodiment, W 7 is C(R 7a In an embodiment, W 7 is N.

[0164] In embodiments, R 7a is hydrogen. In embodiments, R 7a is halogen. In embodiments, R 7a is -CN. In embodiments, R 7a -OR 12 In an embodiment, R 7a -SR 12 In an embodiment, R 7a is -N(R 12 )(R 13 In an embodiment, R 7a is -C(O)OR 12 In an embodiment, R 7a is -OC(O)N(R 12 )(R 13 In an embodiment, R 7a is -N(R 14 )C(O)N(R 12 )(R 13 In an embodiment, R 7a is -N(R 14 )C(O)OR 15 In an embodiment, R 7a is -N(R 14 )S(O)2R 15 In an embodiment, R 7a is -C(O)R 15 In an embodiment, R 7a is -S(O)R 15 In an embodiment, R 7a is -OC(O)R15 In an embodiment, R 7a is -C(O)N(R 12 )(R 13 In an embodiment, R 7a is -C(O)C(O)N(R 12 )(R 13 In an embodiment, R 7a is -N(R 14 )C(O)R 15 In an embodiment, R 7a is -S(O)2R 15 In an embodiment, R 7a is -S(O)2N(R 12 )(R 13 In an embodiment, R 7a is -S(=O)(=NH)N(R 12 )(R 13 In an embodiment, R 7a is -CH2C(O)N(R 12 )(R 13 In an embodiment, R 7a is -CH2N(R 14 )C(O)R 15 In an embodiment, R 7a is -CH2S(O)2R 15 In an embodiment, R 7a is -CH2S(O)2N(R 12 )(R 13 )

[0165] In selected embodiments of the compound, R 7a independently, one, two, or three R 20g C optionally substituted with 1~6 In embodiments, R 7a independently, one, two, or three R 20g C optionally substituted with 2~6 In embodiments, R is an alkenyl. 7a independently, one, two, or three R 20g C optionally substituted with 2~6 In embodiments, R is alkynyl. 7a independently, one, two, or three R 20gC optionally substituted with 3~10 In embodiments, R 7a independently, one, two, or three R 20g C optionally substituted with 2~9 In embodiments, R is heterocycloalkyl. 7a independently, one, two, or three R 20g C optionally substituted with 6~10 In embodiments, R 7a independently, one, two, or three R 20g C optionally substituted with 1~9 In a further embodiment, R 7a are independently hydrogen.

[0166] In an embodiment of the compound, R 7a are independently one or two R 20g In a further embodiment of the compound, R 7a is independently methyl. In some embodiments of the compound, R 7a independently, one, two, or three R 20g In an embodiment of the compound, R 7a is independently ethyl. In some embodiments of the compound, R 7a independently, one, two, or three R 20g In an embodiment of the compound, R 7a is independently propyl.

[0167] In an embodiment, W 8 are independently, C(R 8 In an embodiment, R 8 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -C(O)R 15 , -C(O)N(R 12 )(R13 ), -S(O)R 15 , and -S(O)N(R 12 )(R 13 ) and C 1~6 Alkyl can be one, two, or three R 20h In embodiments, R 8 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, and -OR 12 C 1~6 Alkyl can be one, two, or three R 20h In embodiments, R 8 is independently a halogen. In an embodiment, W 8 are independently N.

[0168] In embodiments, R 8 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -C(O)R 15 , -C(O)N(R 12 )(R 13 ), -S(O)R 15 , and -S(O)N(R 12 )(R 13 )-, and C 1~6 Alkyl can be one, two, or three R 20h In embodiments, R 8 are independently hydrogen, halogen, -CN, C 1~6 Alkyl, and -OR 12 C 1~6 Alkyl can be one, two, or three R 20h In embodiments, R 8a are independently hydrogen, halogen, -CN, C 1~6 Alkyl, -OR 12 , -SR 12 , -N(R 12 )(R13 ), -C(O)OR 12 , -C(O)R 15 , -C(O)N(R 12 )(R 13 ), -S(O)R 15 , and -S(O)N(R 12 )(R 13 )-, and C 1~6 Alkyl can be one, two, or three R 20h In embodiments, R 8a are independently hydrogen, halogen, -CN, C 1~6 Alkyl, and -OR 12 C 1~6 Alkyl can be one, two, or three R 20h In embodiments, W 8 are independently N(R 8b In an embodiment, R 8b are independently hydrogen.

[0169] In embodiments, R 8 are independently hydrogen. In embodiments, R 8 is independently halogen. In an embodiment, R 8 is independently -CN. In an embodiment, R 8 are independently, C 1~6 In embodiments, R 8 are independently, C 2~6 In embodiments, R is an alkenyl. 8 are independently, C 2~6 In embodiments, R is alkynyl. 8 are independently, C 3~10 In embodiments, R 8 are independently, C 2~9 In embodiments, R is heterocycloalkyl. 8 are independently, C 6~10 In embodiments, R 8 are independently, C 1~9 It is heteroaryl.

[0170] In embodiments, R8 independently, one, two, or three R 20h C optionally substituted with 1~6 In embodiments, R 8 independently, one, two, or three R 20h C optionally substituted with 2~6 In embodiments, R is an alkenyl. 8 independently, one, two, or three R 20h C optionally substituted with 2~6 In embodiments, R is alkynyl. 8 independently, one, two, or three R 20h C optionally substituted with 3~10 In embodiments, R 8 independently, one, two, or three R 20h C optionally substituted with 2~9 In embodiments, R is heterocycloalkyl. 8 independently, one, two, or three R 20h C optionally substituted with 6~10 In embodiments, R 8 independently, one, two, or three R 20h C optionally substituted with 1~9 It is heteroaryl.

[0171] In embodiments, R 8 are independently -OR 12 In an embodiment, R 8 are independently, -SR 12 In an embodiment, R 8 are independently -N(R 12 )(R 13 In an embodiment, R 8 are independently -C(O)OR 12 In an embodiment, R 8 are independently -OC(O)N(R 12 )(R 13 In an embodiment, R 8 are independently -N(R 14 )C(O)N(R 12 )(R 13In an embodiment, R 8 are independently -N(R 14 )C(O)OR 15 In an embodiment, R 8 are independently -N(R 14 )S(O)2R 15 In an embodiment, R 8 are independently -C(O)R 15 In an embodiment, R 8 are independently -S(O)R 15 In an embodiment, R 8 are independently -OC(O)R 15 In an embodiment, R 8 are independently -C(O)N(R 12 )(R 13 In an embodiment, R 8 are independently -C(O)C(O)N(R 12 )(R 13 In an embodiment, R 8 are independently -N(R 14 )C(O)R 15 In an embodiment, R 8 are independently -S(O)R 15 In an embodiment, R 8 are independently -S(O)N(R 12 )(R 13 In an embodiment, R 8 are independently S(=O)(=NH)N(R 12 )(R 13 In an embodiment, R 8 are independently -CH2C(O)N(R 12 )(R 13 In an embodiment, R 8 are independently -CH2N(R 14 )C(O)R 15 In an embodiment, R 8 are independently -CH2S(O)2R 15 In an embodiment, R 8 are independently -CH2S(O)2N(R 12 )(R 13 )

[0172] In an embodiment, W 9 is C. In an embodiment, W 10 is C.

[0173] In an embodiment, [ka] teeth, [ka] is selected from.

[0174] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] is selected from.

[0175] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] is selected from.

[0176] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] is selected from.

[0177] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] is selected from.

[0178] In an embodiment, [ka] teeth, [ka] is selected from.

[0179] In an embodiment, [ka] teeth, [ka] is selected from.

[0180] In an embodiment, [ka] teeth, [ka] and is selected from.

[0181] In an embodiment, [ka] teeth, [ka] is selected from.

[0182] In an embodiment, [ka] teeth, [ka] is selected from.

[0183] In an embodiment, [ka] teeth, [ka] is selected from.

[0184] In an embodiment, [ka] teeth, [ka] is selected from.

[0185] In an embodiment, [ka] teeth, [ka] is selected from.

[0186] In an embodiment, [ka] teeth, [ka] is selected from.

[0187] In an embodiment, [ka] teeth, [ka] is selected from.

[0188] In an embodiment, [ka] teeth, [ka] is selected from.

[0189] In an embodiment, [ka] teeth, [ka] is selected from.

[0190] In an embodiment, [ka] teeth, [ka] is selected from.

[0191] In an embodiment, [ka] teeth, [ka] is selected from.

[0192] In an embodiment, [ka] teeth, [ka] is selected from.

[0193] In an embodiment, [ka] teeth, [ka] [ka] is selected from.

[0194] In an embodiment, [ka] teeth, [ka] is selected from.

[0195] In an embodiment, [ka] teeth, [ka] is selected from.

[0196] In an embodiment, [ka] teeth, [ka] [ka] is selected from.

[0197] In an embodiment, [ka] teeth, [ka] is selected from.

[0198] In an embodiment, [ka] teeth, [ka] is selected from.

[0199] In an embodiment, [ka] teeth, [ka] is selected from.

[0200] In an embodiment, [ka] teeth, [ka] is selected from.

[0201] In an embodiment, [ka] teeth, [ka] is selected from.

[0202] In an embodiment, [ka] teeth, [ka] is selected from.

[0203] In an embodiment, [ka] teeth, [ka] is selected from.

[0204] In an embodiment, [ka] teeth, [ka] is selected from.

[0205] In an embodiment, [ka] teeth, [ka] is selected from.

[0206] In an embodiment, [ka] teeth, [ka] is selected from.

[0207] In an embodiment, [ka] teeth, [ka] is selected from.

[0208] In an embodiment, [ka] teeth, [ka] is selected from.

[0209] In an embodiment, [ka] teeth, [ka] is selected from.

[0210] In an embodiment, [ka] teeth, [ka] is selected from.

[0211] In an embodiment, [ka] teeth, [ka] is selected from.

[0212] In an embodiment, [ka] teeth, [ka] is selected from.

[0213] In an embodiment, [ka] teeth, [ka] is selected from.

[0214] In an embodiment, [ka] teeth, [ka] is selected from.

[0215] In an embodiment, [ka] teeth, [ka] [ka] is selected from.

[0216] In an embodiment, [ka] teeth, [ka] is selected from.

[0217] In an embodiment, [ka] teeth, [ka] is selected from.

[0218] In an embodiment, [ka] teeth, [ka] [ka] is selected from.

[0219] In an embodiment, [ka] teeth, [ka] is selected from.

[0220] In an embodiment, [ka] teeth, [ka] is selected from.

[0221] In an embodiment, [ka] teeth, [ka] is selected from.

[0222] In an embodiment, [ka] teeth, [ka] is selected from.

[0223] In an embodiment, [ka] teeth, [ka] In an embodiment, [ka] teeth, [ka] [ka] In an embodiment, [ka] teeth, [ka] [ka] is selected from.

[0224] In an embodiment, Z 4a Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 4a Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3-membered heterocycloalkyl optionally substituted with 4a Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 4-membered heterocycloalkyl optionally substituted with 4a Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5-membered heterocycloalkyl optionally substituted with 4a Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heterocycloalkyl optionally substituted with 4a Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 7-membered heterocycloalkyl optionally substituted with 4aTwo R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In embodiments, Z forms an azetidine which may be substituted with 4a Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 4a Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted piperidine. 4a Two R's z4 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In one embodiment, Z forms a cycloalkyl. 4a Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C cycloalkyl optionally substituted with 4a Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C4 cycloalkyl optionally substituted with 4a Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C5 cycloalkyl optionally substituted with 4a Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C6 cycloalkyl optionally substituted with 4a Two R's z4 can be combined to form one, two, or three R 20z Forms a monocyclic C7 cycloalkyl optionally substituted with

[0225] In an embodiment, Z 4b Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 4b Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3-membered heterocycloalkyl optionally substituted with 4b Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 4-membered heterocycloalkyl optionally substituted with 4b Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5-membered heterocycloalkyl optionally substituted with 4b Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heterocycloalkyl optionally substituted with 4b Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 7-membered heterocycloalkyl optionally substituted with 4b Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In embodiments, Z forms an azetidine which may be substituted with 4b Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 4b Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted piperidine.4b Two R's z4 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In one embodiment, Z forms a cycloalkyl. 4b Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C cycloalkyl optionally substituted with 4b Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C4 cycloalkyl optionally substituted with 4b Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C5 cycloalkyl optionally substituted with 4b Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C6 cycloalkyl optionally substituted with 4b Two R's z4 can be combined to form one, two, or three R 20z Forms a monocyclic C7 cycloalkyl optionally substituted with

[0226] In an embodiment, Z 4c Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 4c Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3-membered heterocycloalkyl optionally substituted with 4c Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 4-membered heterocycloalkyl optionally substituted with 4c Two R's z4 can be combined to form one, two, or three R20z In one embodiment, Z forms a monocyclic 5-membered heterocycloalkyl optionally substituted with 4c Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heterocycloalkyl optionally substituted with 4c Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 7-membered heterocycloalkyl optionally substituted with 4c Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In embodiments, Z forms an azetidine which may be substituted with 4c Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 4c Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted piperidine. 4c Two R's z4 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In one embodiment, Z forms a cycloalkyl. 4c Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C cycloalkyl optionally substituted with 4c Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C4 cycloalkyl optionally substituted with 4c Two R's z4 can be combined to form one, two, or three R 20zIn one embodiment, Z forms a monocyclic C5 cycloalkyl optionally substituted with 4c Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C6 cycloalkyl optionally substituted with 4c Two R's z4 can be combined to form one, two, or three R 20z Forms a monocyclic C7 cycloalkyl optionally substituted with

[0227] In an embodiment, Z 4d Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 4d Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3-membered heterocycloalkyl optionally substituted with 4d Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 4-membered heterocycloalkyl optionally substituted with 4d Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5-membered heterocycloalkyl optionally substituted with 4d Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heterocycloalkyl optionally substituted with 4d Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 7-membered heterocycloalkyl optionally substituted with 4d Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20zIn embodiments, Z forms an azetidine which may be substituted with 4d Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 4d Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted piperidine. 4d Two R's z4 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In one embodiment, Z forms a cycloalkyl. 4d Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C cycloalkyl optionally substituted with 4d Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C4 cycloalkyl optionally substituted with 4d Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C5 cycloalkyl optionally substituted with 4d Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C6 cycloalkyl optionally substituted with 4d Two R's z4 can be combined to form one, two, or three R 20z Forms a monocyclic C7 cycloalkyl optionally substituted with

[0228] In an embodiment, Z 4e Two R's z4 can be combined to form one, two, or three R 20zIn one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 4e Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3-membered heterocycloalkyl optionally substituted with 4e Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 4-membered heterocycloalkyl optionally substituted with 4e Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5-membered heterocycloalkyl optionally substituted with 4e Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heterocycloalkyl optionally substituted with 4e Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 7-membered heterocycloalkyl optionally substituted with 4e Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In embodiments, Z forms an azetidine which may be substituted with 4e Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 4e Two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted piperidine. 4e Two R's z4 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with3~7 In one embodiment, Z forms a cycloalkyl. 4e Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C cycloalkyl optionally substituted with 4e Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C4 cycloalkyl optionally substituted with 4e Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C5 cycloalkyl optionally substituted with 4e Two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C6 cycloalkyl optionally substituted with 4e Two R's z4 can be combined to form one, two, or three R 20z Forms a monocyclic C7 cycloalkyl optionally substituted with

[0229] In an embodiment, Z 5 Two R's z5 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 5 Two R's z5 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3-membered heterocycloalkyl optionally substituted with 5 Two R's z5 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 4-membered heterocycloalkyl optionally substituted with 5 Two R's z5 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5-membered heterocycloalkyl optionally substituted with 5 Two R'sz5 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heterocycloalkyl optionally substituted with 5 Two R's z5 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 7-membered heterocycloalkyl optionally substituted with 5 Two R's z5 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In embodiments, Z forms an azetidine which may be substituted with 5 Two R's z5 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 5 Two R's z5 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted piperidine. 5 Two R's z5 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In one embodiment, Z forms a cycloalkyl. 5 Two R's z5 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C cycloalkyl optionally substituted with 5 Two R's z5 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C4 cycloalkyl optionally substituted with 5 Two R's z5 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C5 cycloalkyl optionally substituted with 5 Two R's z5can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C6 cycloalkyl optionally substituted with 5 Two R's z5 can be combined to form one, two, or three R 20z Forms a monocyclic C7 cycloalkyl optionally substituted with

[0230] In an embodiment, Z 6 Two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 6 Two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3-membered heterocycloalkyl optionally substituted with 6 Two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 4-membered heterocycloalkyl optionally substituted with 6 Two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5-membered heterocycloalkyl optionally substituted with 6 Two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heterocycloalkyl optionally substituted with 6 Two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 7-membered heterocycloalkyl optionally substituted with 6 Two R's z6 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In embodiments, Z forms an azetidine which may be substituted with 6 Two R's z6 can be combined to form one, two, or three R 20z(For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 6 Two R's z6 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted piperidine. 6 Two R's z6 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In one embodiment, Z forms a cycloalkyl. 6 Two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C cycloalkyl optionally substituted with 6 Two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C4 cycloalkyl optionally substituted with 6 Two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C5 cycloalkyl optionally substituted with 6 Two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic C6 cycloalkyl optionally substituted with 6 Two R's z6 can be combined to form one, two, or three R 20z Forms a monocyclic C7 cycloalkyl optionally substituted with

[0231] In an embodiment, Z 4a One or two R's z4 and Z 4b One or two R's z4 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z may be substituted with.

[0232] In an embodiment, Z 4a One or two R's z4 and Z 4b One or two R's z4 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In one embodiment, Z forms a cycloalkyl. 4a One or two R's z4 and Z 4b One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 4a One or two R's z4 and Z 4b One or two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 4a One or two R's z4 and Z 4b One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4a One or two R's z4 and Z 4b One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5- to 6-membered heteroaryl optionally substituted with 4a One or two R's z4 and Z 4b One or two R's z4 can be combined to form one, two, or three R 20zIn one embodiment, Z forms a monocyclic 5-membered heteroaryl optionally substituted with 4a One or two R's z4 and Z 4b One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heteroaryl optionally substituted with 4a One or two R's z4 and Z 4b One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4a One or two R's z4 and Z 4b One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4a One or two R's z4 and Z 4b One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4a One or two R's z4 and Z 4b One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4a One or two R's z4 and Z 4b One or two R's z4 can be combined to form one, two, or three R 20z to form an optionally substituted pyrimidine.

[0233] In an embodiment, Z 4b One or two R's z4 and Z 4c One or two R's z4 can be combined to form one, two, or three R 20zMonocyclic C optionally substituted with 3~7 In one embodiment, Z forms a cycloalkyl. 4b One or two R's z4 and Z 4c One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 4b One or two R's z4 and Z 4c One or two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 4b One or two R's z4 and Z 4c One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4b One or two R's z4 and Z 4c One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5- to 6-membered heteroaryl optionally substituted with 4b One or two R's z4 and Z 4c One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5-membered heteroaryl optionally substituted with 4b One or two R's z4 and Z 4c One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heteroaryl optionally substituted with 4b One or two R's z4 and Z 4c One or two R'sz4 can be combined to form one, two, or three R 20z In an embodiment, Z 4b One or two R's z4 and Z 4c One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4b One or two R's z4 and Z 4c One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4b One or two R's z4 and Z 4c One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4b One or two R's z4 and Z 4c One or two R's z4 can be combined to form one, two, or three R 20z to form an optionally substituted pyrimidine.

[0234] In an embodiment, Z 4c One or two R's z4 and Z 4d One or two R's z4 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In one embodiment, Z forms a cycloalkyl. 4c One or two R's z4 and Z 4d One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 4c One or two R's z4 and Z4d One or two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 4c One or two R's z4 and Z 4d One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4c One or two R's z4 and Z 4d One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5- to 6-membered heteroaryl optionally substituted with 4c One or two R's z4 and Z 4d One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5-membered heteroaryl optionally substituted with 4c One or two R's z4 and Z 4d One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heteroaryl optionally substituted with 4c One or two R's z4 and Z 4d One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4c One or two R's z4 and Z 4d One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4c One or two R's z4and Z 4d One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4c One or two R's z4 and Z 4d One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4c One or two R's z4 and Z 4d One or two R's z4 can be combined to form one, two, or three R 20z to form an optionally substituted pyrimidine.

[0235] In an embodiment, Z 4d One or two R's z4 and Z 4e One or two R's z4 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In one embodiment, Z forms a cycloalkyl. 4d One or two R's z4 and Z 4e One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 4d One or two R's z4 and Z 4e One or two R's z4 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 4d One or two R's z4 and Z 4e One or two R's z4 can be combined to form one, two, or three R 20zIn an embodiment, Z 4d One or two R's z4 and Z 4e One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5- to 6-membered heteroaryl optionally substituted with 4d One or two R's z4 and Z 4e One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5-membered heteroaryl optionally substituted with 4d One or two R's z4 and Z 4e One or two R's z4 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heteroaryl optionally substituted with 4d One or two R's z4 and Z 4e One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4d One or two R's z4 and Z 4e One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4d One or two R's z4 and Z 4e One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z 4d One or two R's z4 and Z 4e One or two R's z4 can be combined to form one, two, or three R 20z In an embodiment, Z4d One or two R's z4 and Z 4e One or two R's z4 can be combined to form one, two, or three R 20z to form an optionally substituted pyrimidine.

[0236] In an embodiment, Z 4e One or two R's z4 and Z 5 One or two R's z5 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In one embodiment, Z forms a cycloalkyl. 4e One or two R's z4 and Z 5 One or two R's z5 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 4e One or two R's z4 and Z 5 One or two R's z5 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 4e One or two R's z4 and Z 5 One or two R's z5 can be combined to form one, two, or three R 20z In an embodiment, Z 4e One or two R's z4 and Z 5 One or two R's z5 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5- to 6-membered heteroaryl optionally substituted with 4e One or two R's z4 and Z 5 One or two R's z5can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5-membered heteroaryl optionally substituted with 4e One or two R's z4 and Z 5 One or two R's z5 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heteroaryl optionally substituted with 4e One or two R's z4 and Z 5 One or two R's z5 can be combined to form one, two, or three R 20z In an embodiment, Z 4e One or two R's z4 and Z 5 One or two R's z5 can be combined to form one, two, or three R 20z In an embodiment, Z 4e One or two R's z4 and Z 5 One or two R's z5 can be combined to form one, two, or three R 20z In an embodiment, Z 4e One or two R's z4 and Z 5 One or two R's z5 can be combined to form one, two, or three R 20z In an embodiment, Z 4e One or two R's z4 and Z 5 One or two R's z5 can be combined to form one, two, or three R 20z to form an optionally substituted pyrimidine.

[0237] In an embodiment, Z 5 One or two R's z5 and Z 6 One or two R's z6can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In one embodiment, Z forms a cycloalkyl. 5 One or two R's z5 and Z 6 One or two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with 5 One or two R's z5 and Z 6 One or two R's z6 can be combined to form one, two, or three R 20z (For example, R on N of the ring 20z In one embodiment, Z forms an optionally substituted pyrrolidine. 5 One or two R's z5 and Z 6 One or two R's z6 can be combined to form one, two, or three R 20z In an embodiment, Z 5 One or two R's z5 and Z 6 One or two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5- to 6-membered heteroaryl optionally substituted with 5 One or two R's z5 and Z 6 One or two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 5-membered heteroaryl optionally substituted with 5 One or two R's z5 and Z 6 One or two R's z6 can be combined to form one, two, or three R 20z In one embodiment, Z forms a monocyclic 6-membered heteroaryl optionally substituted with 5 One or two R's z5and Z 6 One or two R's z6 can be combined to form one, two, or three R 20z In an embodiment, Z 5 One or two R's z5 and Z 6 One or two R's z6 can be combined to form one, two, or three R 20z In an embodiment, Z 5 One or two R's z5 and Z 6 One or two R's z6 can be combined to form one, two, or three R 20z In an embodiment, Z 5 One or two R's z5 and Z 6 One or two R's z6 can be combined to form one, two, or three R 20z In an embodiment, Z 5 One or two R's z5 and Z 6 One or two R's z6 can be combined to form one, two, or three R 20z to form an optionally substituted pyrimidine.

[0238] In some embodiments, two R z4 is bonded to form a monocyclic C 3~7 cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and 3~7 Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl may have one, two, or three R 20z In embodiments, two R z4 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In one embodiment, two R bonded to the same carbon atom form a cycloalkyl. z4can be combined to form one, two, or three R 20z and forming a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with

[0239] In embodiments, two or more R z4 is bonded to form a monocyclic C 3~7 cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, or monocyclic 5- to 6-membered heteroaryl, and 3~7 Cycloalkyl, monocyclic 3- to 7-membered heterocycloalkyl, phenyl, and monocyclic 5- to 6-membered heteroaryl may have one, two, or three R 20z In embodiments, two or more R z4 can be combined to form one, two, or three R 20z Monocyclic C optionally substituted with 3~7 In embodiments, two or more R attached to adjacent atoms form a cycloalkyl. z4 can be combined to form one, two, or three R 20z In one embodiment, two or more R bonded to adjacent atoms form a monocyclic 3- to 7-membered heterocycloalkyl optionally substituted with z4 can be combined to form one, two, or three R 20z In embodiments, two or more R bonded to adjacent atoms form a phenyl optionally substituted with z4 can be combined to form one, two, or three R 20z and forming a monocyclic 5- to 6-membered heteroaryl which may be substituted by the following:

[0240] In some embodiments, two R z5 is bonded to form a monocyclic C 3~7 cycloalkyl, or monocyclic 3- to 7-mem...

Claims

1. A compound of the following formula (A), or a pharmaceutically acceptable salt or solvate thereof, 【Chemical 605】 During the ceremony, W １ N is, W ２ is C(R ２ ) and R ２ It is -OR12a, W ３ N is, W ４ C is, W ５ C is, W ６ is C(R ６ ), N(R ６ ), C(R ６ ), ２ C(O), S(O), S(O ２ ), or N, and Each R ６ These are, independently, hydrogen, halogen, -CN, and C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Ariel, C １～９ heteroaryl, -OR １２ , -SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)N(R １２ ) (Caution 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 ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)R １５ , -S(O) ２ R １５ , -S(O) ２ N(R) １２ ) (Caution １３ ), -S(=O)(=NH)N(R １２ ) (Caution １３ ), -CH ２ C(O)N(R) １２ ) (Caution １３ ), -CH ２ N(R) １４ ) C(O)R １５ ien-CH ２ S(O) ２ R １５ , and -CH ２ S(O) ２ N(R) １２ ) (Caution １３ ) is selected from C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ A heteroaryl has one, two, or three R ２０ｆ It may also be replaced with W ７ C is, R ７ is, -L ７ -R １７ And, L ７ It is a combination, R １７ C ３～１０ Cycloalkyl, 3-10 member heterocycloalkyl, C ６～１０ Selected from aryls and 5- to 10-membered heteroaryls, C ３～１０ Cycloalkyl, 3-10 member heterocycloalkyl, C ６～１０ Aryls and 5- to 10-membered heteroaryls contain one or more R ２０ｑ It may also be replaced with W ８ is C(R ８ ) and R ８ It is a halogen, W ９ C is, W １０ C is, Each Z １ is independently C(R ｚ１ ), N(R ｚ１ ), C(R ｚ１ ), ２ C(O), S(O), S(O ２ ), O, S, or N, and z1n is 0, 1, 2, or 3, and when z1n is 0, Z ２ is directly connected to W ５ and Each R ｚ１ These are, independently, hydrogen, halogen, -CN, and C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Ariel, C １～９ heteroaryl, -OR １２ , -SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)N(R １２ ) (Caution 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 ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)R １５ , -S(O) ２ R １５ , -S(O) ２ N(R) １２ ) (Caution １３ ), -S(=O)(=NH)N(R １２ ) (Caution １３ ), -CH ２ C(O)N(R) １２ ) (Caution １３ ), -CH ２ N(R) １４ ) C(O)R １５ ien-CH ２ S(O) ２ R １５ , and -CH ２ S(O) ２ N(R) １２ ) (Caution １３ ) is selected from C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ A heteroaryl has one, two, or three R ２０ｚ１ It may also be replaced with Each Z ９ Independently, C(R) ｚ９ ), N (R ｚ９ ), C (R ｚ９ ) ２ , C(O), S(O), S(O) ２ , O, S, or N, z9n is 0, 1, 2, or 3, and if z9n is 0, Z ３ is, W ４ Directly coupled, Each R ｚ９ These are, independently, hydrogen, halogen, -CN, and C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Ariel, C １～９ heteroaryl, -OR １２ , -SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)N(R １２ ) (Caution 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 ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)R １５ , -S(O) ２ R １５ , -S(O) ２ N(R) １２ ) (Caution １３ ), -S(=O)(=NH)N(R １２ ) (Caution １３ ), -CH ２ C(O)N(R) １２ ) (Caution １３ ), -CH ２ N(R) １４ ) C(O)R １５ ien-CH ２ S(O) ２ R １５ , and -CH ２ S(O) ２ N(R) １２ ) (Caution １３ ) is selected from C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ A heteroaryl has one, two, or three R ２０ｚ９ It may also be replaced with The sum of z1n and z9n is 2 or 3. Z ２ is C(R ｚ２ ), C, or N, R ｚ２ is hydrogen, halogen, -CN, C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Ariel, C １～９ heteroaryl, -OR １２ , -SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)N(R １２ ) (Caution 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 ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)R １５ , -S(O) ２ R １５ , -S(O) ２ N(R) １２ ) (Caution １３ ), -S(=O)(=NH)N(R １２ ) (Caution １３ ), -CH ２ C(O)N(R) １２ ) (Caution １３ ), -CH ２ N(R) １４ ) C(O)R １５ ien-CH ２ S(O) ２ R １５ , and -CH ２ S(O) ２ N(R) １２ ) (Caution １３ ) is selected from C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ A heteroaryl has one, two, or three R ２０ｚ２ It may also be replaced with Z ３ is C(R ｚ３ ), C, or N, R ｚ３ is hydrogen, halogen, -CN, C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Ariel, C １～９ heteroaryl, -OR １２ , -SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)N(R １２ ) (Caution 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 ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)R １５ , -S(O) ２ R １５ , -S(O) ２ N(R) １２ ) (Caution １３ ), -S(=O)(=NH)N(R １２ ) (Caution １３ ), -CH ２ C(O)N(R) １２ ) (Caution １３ ), -CH ２ N(R) １４ ) C(O)R １５ ien-CH ２ S(O) ２ R １５ , and -CH ２ S(O) ２ N(R) １２ ) (Caution １３ ) is selected from C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ A heteroaryl has one, two, or three R ２０ｚ３ It may also be replaced with Z ４ is a bond, Z ４ａ Z ４ａ Z ４ｂ Z ４ａ Z ４ｂ Z ４ｃ , or Z ４ａ Z ４ｂ Z ４ｃ Z ４ｄ And in the formula, Z ４ａ is, Z ２ It is directly coupled, and in the formula, Z ４ If Z is a bond, ２ is, Z ５ Directly connect, Z ４ａ Z ４ｂ Z ４ｃ , and Z ４ｄ Independently, C(R) ｚ４ ), N (R ｚ４ ), C (R ｚ４ ) ２ , C(O), S(O), S(O) ２ , S(O)(NR ｚ４ ), O, S, or N, however, i) z9n is 0, and Z ４ However, Z ４ａ Z ４ｂ If so, (1) Z ４ｂ is C(R ｚ４ ), C (R ｚ４ ) ２ , C(O), S(O), S(O) ２ , S(O)(NR ｚ４ (2) Z ４ｂ N(R) ｚ４ ) and also Z ４ａ is C(O), S(O), or S(O) ２ (3) Z ４ｂ N(R) ｚ４ ) and also Z ５ is C(O), S(O), or S(O) ２ (4) Z ４ｂ N(R) ｚ４ ) and also Z ３ is C(R ｚ３ ) or C, and ii) R ｚ４ , R ｚ５ , R ｚ６ , R ２０ｚ４ , R ２０ｚ５ , R ２０ｚ６ , R ２０ｚ , or R ２０ｚｚ Only one of them is E, and E is a region that can covalently bind to the Ras mutant protein at the amino acid corresponding to G12D or G12S in the human K-Ras mutant G12D or G12S protein, Each R ｚ４ These are independently E, hydrogen, halogen, -CN, and C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Ariel, C １～９ heteroaryl, -OR １２ , -SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)N(R １２ ) (Caution 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 ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)R １２ , -S(O) ２ R １５ , -S(O) ２ N(R) １２ ) (Caution １３ ), -S(=O)(=NH)N(R １２ ) (Caution １３ ), -CH ２ C(O)N(R) １２ ) (Caution １３ ), -CH ２ N(R) １４ ) C(O)R １５ ien-CH ２ S(O) ２ R １５ , and -CH ２ S(O) ２ N(R) １２ ) (Caution １３ ) is selected from C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ A heteroaryl has one, two, or three R atoms. ２０ｚ４ It may be substituted with, or two R bonded to the same carbon ｚ４ These combine to form one, two, or three R ２０ｚ４ C may be replaced with ２～６ Forming alkenyls, Z ５ is C(R ｚ５ ), N (R ｚ５ ), C (R ｚ５ ) ２ , C(O), S(O), S(O) ２ , S(O)(NR ｚ５ ), O, S, or N, Each R ｚ５ These are independently E, hydrogen, halogen, -CN, and C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Ariel, C １～９ heteroaryl, -OR １２ , -SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)N(R １２ ) (Caution 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 ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)R １２ , -S(O) ２ R １５ , -S(O) ２ N(R) １２ ) (Caution １３ ), -S(=O)(=NH)N(R １２ ) (Caution １３ ), -CH ２ C(O)N(R) １２ ) (Caution １３ ), -CH ２ N(R) １４ ) C(O)R １５ ien-CH ２ S(O) ２ R １５ , and -CH ２ S(O) ２ N(R) １２ ) (Caution １３ ) is selected from C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ A heteroaryl has one, two, or three R atoms. ２０ｚ５ It may be substituted with, or two R bonded to the same carbon ｚ５ These combine to form one, two, or three R ２０ｚ５ C may be replaced with ２～６ Forming alkenyls, Z ６ is C(R ｚ６ ), N (R ｚ６ ), C (R ｚ６ ) ２ , C(O), S(O), S(O) ２ , S(O)(NR ｚ６ ), O, S, or N, Each R ｚ６ These are independently E, hydrogen, halogen, -CN, and C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Ariel, C １～９ heteroaryl, -OR １２ , -SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)N(R １２ ) (Caution 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 ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)R １２ , -S(O) ２ R １５ , -S(O) ２ N(R) １２ ) (Caution １３ ), -S(=O)(=NH)N(R １２ ) (Caution １３ ), -CH ２ C(O)N(R) １２ ) (Caution １３ ), -CH ２ N(R) １４ ) C(O)R １５ ien-CH ２ S(O) ２ R １５ , and -CH ２ S(O) ２ N(R) １２ ) (Caution １３ ) is selected from C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ A heteroaryl has one, two, or three R atoms. ２０ｚ６ It may be substituted with, or two R bonded to the same carbon ｚ６ These combine to form one, two, or three R ２０ｚ６ C may be replaced with ２～６ Forming alkenyls, Furthermore, the compound may contain one of the following: (1) Two R atoms bonded to the same carbon atom ｚ４ It combines to form a monocyclic C ３～７ It forms a cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C ３～７ Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl groups have one, two, or three R groups. ２０ｚ It may also be replaced with (2) Two or more R atoms bonded to adjacent atoms ｚ４ It combines to form a monocyclic C ３～７ These form cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl, or monocyclic 5-6 membered heteroaryl, and monocyclic C ３～７ Cycloalkyls, monocyclic 3- to 7-membered heterocycloalkyls, phenyls, and monocyclic 5- to 6-membered heteroaryls have one, two, or three R groups. ２０ｚ It may also be replaced with (3) Two R atoms bonded to the same carbon atom ｚ５ It combines to form a monocyclic C ３～７ It forms a cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C ３～７ Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl groups have one, two, or three R groups. ２０ｚ It may also be replaced with (4) One or two R atoms bonded to one atom ｚ４ , and one or two R atoms bonded to adjacent atoms ｚ５ It combines to form a monocyclic C ３～７ These form cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl, or monocyclic 5-6 membered heteroaryl, and monocyclic C ３～７ Cycloalkyls, monocyclic 3- to 7-membered heterocycloalkyls, phenyls, and monocyclic 5- to 6-membered heteroaryls have one, two, or three R groups. ２０ｚ It may also be replaced with (5) One or two R atoms bonded to one atom ｚ４ , and one or two R atoms bonded to the second atom ｚ５ It combines to form a monocyclic C ３～７ It forms a cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C ３～７ Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl groups have one, two, or three R groups. ２０ｚ It may also be replaced with (6) Two R atoms bonded to the same carbon atom ｚ６ It combines to form a monocyclic C ３～７ It forms a cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C ３～７ Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl groups have one, two, or three R groups. ２０ｚ It may also be replaced with (7) One or two R atoms bonded to one atom ｚ５ , and one or two R atoms bonded to adjacent atoms ｚ６ It combines to form a monocyclic C ３～７ These form cycloalkyl, monocyclic 3-7 membered heterocycloalkyl, phenyl, or monocyclic 5-6 membered heteroaryl, and monocyclic C ３～７ Cycloalkyls, monocyclic 3- to 7-membered heterocycloalkyls, phenyls, and monocyclic 5- to 6-membered heteroaryls have one, two, or three R groups. ２０ｚ It may be replaced with, or (8) One or two R atoms bonded to one atom ｚ４ , and one or two R atoms bonded to the second atom ｚ６ It combines to form a monocyclic C ３～７ It forms a cycloalkyl or monocyclic 3- to 7-membered heterocycloalkyl, and monocyclic C ３～７ Cycloalkyl and monocyclic 3- to 7-membered heterocycloalkyl groups have one, two, or three R groups. ２０ｚ It may also be replaced with Each R １２ These are, independently, hydrogen and C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, -CH ２ -C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, -CH ２ -C ２～９ Heterocycloalkyl, C ６～１０ Ariel, -CH ２ -C ６～１０ Ariel, -CH ２ -C １～９ Heteroaryls, and C １～９ Selected from heteroaryls, C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, -CH ２ -C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, -CH ２ -C ２～９ Heterocycloalkyl, C ６～１０ Ariel, -CH ２ -C ６～１０ Ariel, -CH ２ -C １～９ Heteroaryls, and C １～９ A heteroaryl has one, two, or three R ２０ｌ It may also be replaced with R １２ａ Independently, -C(R １２ｃ ) ２ -C ２～９ It is a heterocycloalkyl, -C(R １２ｃ ) ２ -C ２～９ Heterocycloalkyl groups have one, two, or three R atoms. ２０ｌ It may also be replaced with Each R １２ｃ Independently, hydrogen and R ２０ｌｃ Selected from, Each R １３ These are, independently, hydrogen and C １～６ Alkyl and C １～６ Selected from haloalkyls, or R １２ and R １３ Together with the nitrogen atoms to which they are bound, they form one, two, or three R atoms. ２０ｍ C may be replaced with ２～９ Forming a heterocycloalkyl ring, Each R １４ These are, independently, hydrogen and C １～６ Alkyl and C １～６ Selected from haloalkyl groups, Each R １５ Independently, C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ Selected from heteroaryls, C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ A heteroaryl has one, two, or three R ２０ｏ It may also be replaced with Each R ２０ｚ１ , R ２０ｚ２ , R ２０ｚ３ , and R ２０ｚ９ These are, independently, halogen, oxo, -CN, and C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Ariel, C １～９ heteroaryl, -OR １２ , -SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)N(R １２ ) (Caution 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 ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)R １２ , -S(O) ２ R １５ , -S(O) ２ N(R) １２ ) (Caution １３ ), -S(=O)(=NH)N(R １２ ) (Caution １３ ), -CH ２ C(O)N(R) １２ ) (Caution １３ ), -CH ２ N(R) １４ ) C(O)R １５ ien-CH ２ S(O) ２ R １５ , and -CH ２ S(O) ２ N(R) １２ ) (Caution １３ ) is selected from C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ A heteroaryl has one, two, or three R ２０ｚ It may also be replaced with Each R ２０ｚ４ , R ２０ｚ５ , and R ２０ｚ６ These are independently E, halogen, oxo, -CN, and C. １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Ariel, C １～９ heteroaryl, -OR １２ , -SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)N(R １２ ) (Caution 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 ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)R １２ , -S(O) ２ R １５ , -S(O) ２ N(R) １２ ) (Caution １３ ), -S(=O)(=NH)N(R １２ ) (Caution １３ ), -CH ２ C(O)N(R) １２ ) (Caution １３ ), -CH ２ N(R) １４ ) C(O)R １５ ien-CH ２ S(O) ２ R １５ , and -CH ２ S(O) ２ N(R) １２ ) (Caution １３ ) is selected from C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ A heteroaryl has one, two, or three R ２０ｚ It may also be replaced with Each R ２０ｚ These are independently E, halogen, oxo, -CN, and C. １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Ariel, C １～９ heteroaryl, -OR １２ , -SR １２ , -N(R １２ ) (Caution １３ ), -C(O)OR １２ , -OC(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)N(R １２ ) (Caution 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 ) (Caution １３ ), -C(O)C(O)N(R １２ ) (Caution １３ ), -N(R １４ ) C(O)R １２ , -S(O) ２ R １５ , -S(O) ２ N(R) １２ ) (Caution １３ ), -S(=O)(=NH)N(R １２ ) (Caution １３ ), -CH ２ C(O)N(R) １２ ) (Caution １３ ), -CH ２ N(R) １４ ) C(O)R １５ ien-CH ２ S(O) ２ R １５ , and -CH ２ S(O) ２ N(R) １２ ) (Caution １３ ) is selected from C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ A heteroaryl has one, two, or three R ２０ｚｚ It may also be replaced with Two Rs bonded to the same carbon atom ２０ｚ may combine to form a monocyclic C ３～７ cycloalkyl or a monocyclic 3- to 7-membered heterocycloalkyl, and the monocyclic C ３～７ cycloalkyl and the monocyclic 3- to 7-membered heterocycloalkyl may be substituted with one, two, or three Rs ２０ｚｚ or Two or more R atoms bonded to two adjacent atoms ２０ｚ It combines to form a monocyclic C ３～７ It may form a cycloalkyl, a monocyclic 3- to 7-membered heterocycloalkyl, a phenyl, or a monocyclic 5- to 6-membered heteroaryl, C ３～７ Cycloalkyls, monocyclic 3- to 7-membered heterocycloalkyls, phenyls, and monocyclic 5- to 6-membered heteroaryls have one, two, or three R groups. ２０ｚｚ It may also be replaced with Each R ２０ｆ , R ２０ｌｃ , R ２０ｌ , R ２０ｍ , R ２０ｏ , and R ２０ｑ is, 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[[ID=३३]] ２ -C ６～１０ aryl, -CH ２ -C １～９ heteroaryl, C １～９ heteroaryl, -OR ２１ , -SR ２１ , -N(R[[ID=4७]] ２２ )(R ２３ ), -C(O)OR ２２ , -C(O)N(R ２２ )(R<0000�32> ), -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[[ID=8१]]<0000९45> )R ２５ , -C(O)R ２１ , -S(O ２ )R ２５ , -S(O ２ )N(R ２２ )(R<000०952> ), -OCH ２ C(O)OR ２２ , =NR ２１ , and -OC(O)R ２５ selected from, two Rs attached to adjacent atoms ２０ｑ are bonded to form C ３～１０ cycloalkyl, C ２～９ heterocycloalkyl, C ６～１０ aryl, or C １～９ heteroaryl, and C １～６ alkyl, C ２～６ alkenyl, C<000096​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ ２ N(R) ２２ ) (Caution ２３ ), and -OC(O)R ２５ It may be replaced by one, two, or three bases independently selected from, Each R ２０ｚｚ These are independently E, halogen, oxo, -CN, and C. １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, -CH ２ -C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, -CH ２ -C ２～９ Heterocycloalkyl, C ６～１０ Ariel, -CH ２ -C ６～１０ Ariel, -CH ２ -C １～９ Heteroaryl, C １～９ heteroaryl, -OR ２１ , -SR ２１ , -N(R ２２ ) (Caution ２３ ), -C(O)OR ２２ , -C(O)N(R ２２ ) (Caution ２３ ), -C(O)C(O)N(R ２２ ) (Caution ２３ ), -OC(O)N(R ２２ ) (Caution ２３ ), -N(R ２４ ) C(O)N(R ２２ ) (Caution 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 ) (Caution ２３ ), -OCH ２ C(O)OR ２２ , = NR ２１ , and -OC(O)R ２５ Selected from, C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, -CH ２ -C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, -CH ２ -C ２～９ Heterocycloalkyl, C ６～１０ Ariel, -CH ２ -C ６～１０ Ariel, -CH ２ -C １～９ Heteroaryls, and C １～９ Heteroaryls include halogens, oxo, -CN, and C. １～６ Alkyl, C １～６ Haloalkyl, C １～６ Alkoxy, C １～６ Haloalkoxy, -OR ２１ , -SR ２１ , -N(R ２２ ) (Caution ２３ ), -C(O)OR ２２ , -C(O)N(R ２２ ) (Caution ２３ ), -C(O)C(O)N(R ２２ ) (Caution ２３ ), -OC(O)N(R ２２ ) (Caution ２３ ), -N(R ２４ ) C(O)N(R ２２ ) (Caution 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 ) (Caution ２３ ), and -OC(O)R ２５ It may be replaced by one, two, or three bases independently selected from, Each R ２１ These are, independently, hydrogen and C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ Selected from heteroaryls, Each R ２２ These are, independently, hydrogen and C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ Selected from heteroaryls, Each R ２３ These are, independently, hydrogen and C １～６ Selected from alkyl groups, Each R ２４ These are, independently, hydrogen and C １～６ Selected from alkyl groups, Each R ２５ Independently, C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C ３～１０ Cycloalkyl, C ２～９ Heterocycloalkyl, C ６～１０ Aryl, and C １～９ Selected from heteroaryls, and 【Chemical 606】 A compound is one that exhibits single or double bonds such that all valencies are satisfied.

2. The compound of formula (A) is formula (A-1): 【Chemical 605-1】 The compound described in claim 1, or a pharmaceutically acceptable salt or solvate thereof. 【Request Item 3】 【Chemistry 611】 teeth, 【Chemical 612】 The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof. 【Request Item 4】 【Chemical 611-1】 teeth, 【Chemical 612-1】 The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof. 【Request Item 5】 【Chemical 611-2】 teeth, 【Chemical 612-2】 The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

6. W ６ is C(R ６ The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof.

7. R ６ is hydrogen, halogen, -CN, C １～６ Alkyl and -OR １２ It is selected from C １～６ Alkyl groups consist of one, two, or three R groups. ２０ｆ The compound according to claim 6, or a pharmaceutically acceptable salt or solvate thereof, which may be substituted with.

8. R ６ The compound according to claim 6, or a pharmaceutically acceptable salt or solvate thereof, wherein is a halogen.

9. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein W6 is N.

10. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R 17 is a 5- to 10-membered heteroaryl which may be substituted with one, two, three, four, five, six or seven R 20q.

11. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R 17 is a C 6-10 aryl which may be substituted with one, two, three, four, five, six or seven R 20q.

12. R １７ These are halogen, -CN, and -CH ３ -C≡CH, -OH, and -NH ２ The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, substituted with one, two, or three substituents independently selected from the above.

13. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, which is covalently bonded to the Kras G12D mutant.

14. The compound according to claim 1, or a pharmaceutically acceptable salt or solvate thereof, which is covalently bonded to the Kras G12S mutant.

15. A pharmaceutical composition comprising a compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

16. Use of a compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a pharmaceutical for the treatment of cancer.

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