Heterocyclic compounds and their uses

Abstract

To provide heterocyclic compounds and their uses. [Solution] This disclosure provides compounds and pharmaceutically acceptable salts thereof, as well as methods for using them. The compounds and methods have various uses as therapeutic agents, diagnostic agents, and research tools. In particular, the compositions and methods of this disclosure are useful for reducing the signaling output of oncogenic proteins. In some embodiments, the treatment methods of this disclosure are combined with surgery, cell therapy, chemotherapy, radiation, and / or immunosuppressants. Furthermore, the compositions of this disclosure can be combined with other therapeutic agents, such as other anticancer agents, anti-allergic agents, anti-nausea agents (or antiemetics), analgesics, cytoprotective agents, immunostimulants, and combinations thereof.

Description

[Technical Field]

[0001] cross reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 072,056, filed on 28 August 2020, which is incorporated herein by whole reference. [Background technology]

[0002] background Cancer (e.g., tumors, neoplasms, metastases) is the second leading cause of death worldwide, estimated to cause approximately 10 million deaths annually. Many types of cancer are characterized by mutations in one or more proteins involved in various signaling pathways that lead to the unregulated growth of cancer cells. In some cases, it is known that about 25–30 percent (%) of tumors have rat sarcoma (Ras) mutations. In particular, mutations in the Kirsten Ras oncogene (K-Ras) gene are one of the most frequently detected Ras mutations in human cancers, including lung adenocarcinoma (LUAD) and pancreatic ductal adenocarcinoma (PDAC).

[0003] While Ras is known to be a carcinogenic driver, there are currently no clinically approved targeted therapies for Ras-mutated cancers. The Ras protein has long been considered "undruggable," partly due to its high affinity for its substrate, guanosine-5'-triphosphate (GTP), and / or its smooth surface lacking a clear targeting region. In recent years, certain G12C Ras gene mutations have been identified as potential drug targets. However, such therapeutic approaches remain limited because G12C mutations in Ras have a low prevalence compared to other known Ras mutations (e.g., about 3% in PDAC). [Overview of the project] [Means for solving the problem]

[0004] overview Considering the above, there is still a considerable need for the design of novel therapeutic and diagnostic agents that can specifically target Ras variants and / or Ras-related proteins to reduce Ras pathway signaling. Such compositions and methods may be particularly useful for treating a variety of diseases, including, but not limited to, cancer and neoplasms. This disclosure addresses these needs and provides additional advantages applicable to the diagnosis, prognosis, and treatment of a wide variety of diseases.

[0005] In one embodiment, the present disclosure relates to a compound of formula (I): [ka] (In the formula, [ka] R is absent, a 3-12 membered heterocycloalkyl ring, a 6-10 membered aryl ring, a 5-10 membered heteroaryl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring, 6-10 membered aryl ring, 5-10 membered heteroaryl ring, and 3-12 membered cycloalkyl ring have 1 or more R 10 It is replaced as needed; [ka] is absent, a 3-12 membered heterocycloalkyl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring and the 3-12 membered cycloalkyl ring have 1 or more R 11 It is replaced as needed; A is a bond, O, S, N(R) 1e ), or C(R 1f )(R 1g ) and; Q 1 is N or C(R 1d ) and; Q 2 is either S or O; X is either C or N; Y is C, S(O), S(O)2, C(O), or N; U is C, S(O), S(O)2, C(O), or N; Z is N or C(R 8 ); V and J are independently selected from N, C(R 5 ), and C(R 16 ), and one of V and J is C(R 5 ); W is N or C(R 18 ); L 1 and L 2 are selected independently from a bond, C1-C6 alkyl, -O-, -N(R 26 )-, -C(O)-, -N(R 26 )C(O)-, -C(O)N(R 26 )-, -S-, -S(O)2-, -S(O)-, -S(O)2N(R 26 ), -S(O)N(R 26 ), -N(R 26 )S(O)-, -N(R 26 )S(O)2-, -OCON(R 26 )-, -N(R 26 )C(O)O-, and -N(R 26 )C(O)N(R 26 ); R 1 is hydrogen, halogen, -CN, C 1~6 alkyl, C 1~6 haloalkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~6 cycloalkyl, C 2~9 heterocycloalkyl, C 1~9 heteroaryl, -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15, -N(R 14 )S(O)2R 15 , -C(O)R 15 , -S(O)R 15 , -OC(O)R 15 , -C(O)N(R 12 )(R 1 3 , -C(O)C(O)N(R 12 )(R 13 , -N(R 14 )C(O)R 15 , -S(O)2R 15 , -S(O)2N(R 12 )(R 13 ), S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 , -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) are selected from; C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~6 cycloalkyl, C 2~9 heterocycloalkyl, and C 1~9 heteroaryl may be optionally substituted with one, two, or three R 20a ; R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , and R 1g are hydrogen, halogen, -CN, C 1~6 alkyl, C 1~6 haloalkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~6 cycloalkyl, C 2~9 heterocycloalkyl, C 6~10 aryl, C 1~9 heteroaryl, -OR 12, -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R 12 )(R 13 ), -N(R 14 )(R 12 )(R 13 ), -N(R 14 )(R 15 ), -N(R 14 )(R 15 ), -C(O)R 15 ), -S(O)R 15 ), -OC(O)R 15 ), -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )(R 15 ), -S(O)2R 15 ), -S(O)2N(R 12 )(R 13 ), -S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )(R 15 ), -CH2S(O)2R 15 ), and -CH2S(O)2N(R 12 )(R 13 ) are each independently selected from C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~6 cycloalkyl, C 2~9 heterocycloalkyl, C 6~10 aryl, and C 1~9 heteroaryl, which are optionally substituted with one, two, or three R 20a ; or R 1a and R 1bThese rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1b and R 1c These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1f and R 1g These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; R 2 Halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20b It is replaced as needed; Each R 3 These are hydrogen, halogen, oxo, C1-C6 alkyl, C1-C6 haloalkyl, -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 , -OC(O)N (R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 Selected independently from; R 4 This refers to a group other than the electrophilic moiety that can form a covalent bond with hydrogen or the cysteine ​​residue at position 12 of the KRAS protein; R 5 teeth [ka] and; R 8 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20c It is replaced as needed; Each R 10 and each R 11 These include halogens, oxo, C1-C6 alkyl, C1-C6 haloalkyl, and -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; Each R 12 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20d It is replaced as needed; Each R 13 is hydrogen, C 1~6 Alkyl, and C 1~6 Selected independently of haloalkyl; or R 12 and R 13 These, together with the nitrogen they are bonded to, form one, two, or three R atoms. 20e C replaced as needed 2~9 Forming a heterocycloalkyl ring; Each R 14 is hydrogen, C 1~6 Alkyl, and C 1~6 Independently selected from haloalkyl groups; Each R 15 C is selected independently 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 It is a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20f And Substitutions are made as needed; R 16 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20g It is replaced as needed; R 18 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, 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 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20h It is replaced as needed; Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , and R20i Halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, 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 Each is independently selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9Heteroaryls 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 )(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 One selected independently from It is replaced as needed with one, two, or three groups; Each R 21 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 22 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 23 H and C 1~6 Selected independently of alkyl; Each R 24 H and C 1~6 Selected independently of alkyl; Each R 25 C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected from heteroaryls; Each R 26 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20i It is replaced as needed; n is 0, 1, or 2; [ka] (This indicates a single or double bond in which all valencies are satisfied.) The present invention provides a pharmaceutically acceptable salt or solvate thereof.

[0006] In some embodiments, the structure of formula (Ia) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0007] In some embodiments, the structure of formula (Ib) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0008] In some embodiments, V is C(R 16 Compounds of formula (I), (Ia), or (Ib), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, compounds of formula (I), (Ia), or (Ib), or pharmaceutically acceptable salts or solvates thereof, are provided, where V is C(H). In some embodiments, compounds of formula (I), (Ia), or (Ib), or pharmaceutically acceptable salts or solvates thereof, are provided, where V is N.

[0009] In some embodiments, the structure of formula (Ic) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0010] In some embodiments, the structure of formula (Id) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0011] In some embodiments, J is C(R 16A compound of formula (Ic) or (Id), or a pharmaceutically acceptable salt or solvate thereof, is provided, wherein J is C(H). In some embodiments, a compound of formula (Ic) or (Id), or a pharmaceutically acceptable salt or solvate thereof, is provided, wherein J is N.

[0012] In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), or (Id), or pharmaceutically acceptable salts or solvates thereof, are provided, where X is C. In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), or (Id), or pharmaceutically acceptable salts or solvates thereof, are provided, where X is N.

[0013] In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), or (Id), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is C. In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), or (Id), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is N. In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), or (Id), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is C(O).

[0014] In some embodiments, the structure of formula (Ie) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0015] In some embodiments, the structure of expression (If) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0016] In some embodiments, the structure of formula (Ig) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0017] In some embodiments, the structure of formula (Ih) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0018] In some embodiments, the structure of equation (Ii) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0019] In some embodiments, the structure of formula (Ij) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0020] In some embodiments, the structure of formula (Ik) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0021] In some embodiments, the structure of formula (Im) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0022] In some embodiments, the structure of formula (In): [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0023] In some embodiments, the structure of formula (Io) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0024] In some embodiments, V is C(R 16 Compounds of formula (I), (Ie), (If), (Ig), or (Ih), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, compounds of formula (I), (Ie), (If), (Ig), or (Ih), or pharmaceutically acceptable salts or solvates thereof, are provided, where V is C(H). In some embodiments, compounds of formula (I), (Ie), (If), (Ig), or (Ih), or pharmaceutically acceptable salts or solvates thereof, are provided, where V is N.

[0025] In some embodiments, J is C(R 16Compounds of formula (I), (Ii), (Ij), (Ik), or (Im), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, compounds of formula (I), (Ii), (Ij), (Ik), or (Im), or pharmaceutically acceptable salts or solvates thereof, are provided, where J is C(H). In some embodiments, compounds of formula (I), (Ii), (Ij), (Ik), or (Im), or pharmaceutically acceptable salts or solvates thereof, are provided, where J is N.

[0026] In some embodiments, W is C(R 18 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided, where W is N.

[0027] In some embodiments, Z is C(R 8 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided, where Z is N.

[0028] In another embodiment, the present disclosure relates to a compound of formula (II): [ka] (In the formula, [ka] R is absent, a 3-12 membered heterocycloalkyl ring, a 6-10 membered aryl ring, a 5-10 membered heteroaryl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring, 6-10 membered aryl ring, 5-10 membered heteroaryl ring, and 3-12 membered cycloalkyl ring have 1 or more R 10 It is replaced as needed; [ka] is absent, a 3-12 membered heterocycloalkyl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring and the 3-12 membered cycloalkyl ring have 1 or more R 11 It is replaced as needed; A is a bond, O, S, N(R) 1e ), or C(R 1f )(R 1g ) and; Q 1 is N or C(R 1d ) and; Q 2 is either S or O; X is either C or N; Y is C, C(O), or N; Z 1 is N or C(R 6 ) and; Z 2 is N(R 7 ) or C(R 8 )(R 9 ) and; Z 3 is non-existent, N(R) 17 ), or C(R 27 )(R 28 ) and; U is C, S(O), S(O)2, C(O), or N; L 1 and L 2 This is a bond, C1-C6 alkyl, -O-, -N(R26 )-, -C(O)-, -N(R 26 )C(O)-, -C(O)N(R 26 )-, -S-, -S(O)2-, -S(O)-, -S(O)2N(R 26 ), -S(O)N(R 26 ), -N(R 26 )S(O)-, -N(R 26 )S(O)2-,-OCON(R 26 )-,-N(R 26 )C(O)O-, and -N(R 26 )C(O)N(R 26 )- Selected independently of; R 1 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 1 4 )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 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , and R 1g Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(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 )(R13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) are independently selected from each, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; or R 1a and R 1b These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1b and R 1c These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1f and R 1gThese rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; R 2 Halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15, and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20b It is replaced as needed; Each R 3 These include hydrogen, halogens, oxo, C1-C6 alkyl, and C1-C6 haloalkyl. -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; R 4 This refers to a group other than the electrophilic moiety that can form a covalent bond with hydrogen or the cysteine ​​residue at position 12 of the KRAS protein; R 5 teeth [ka] and; R 6 is hydrogen and C 1~6 Selected from alkyl groups; R 7 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -C(O)OR 12 , -C(O)R 15,-S(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected from, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20c It is replaced as needed; R 8 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15-S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20c It is replaced as needed; R 9 is hydrogen and C 1~6 Selected from alkyl groups; Each R 10 and each R 11 These include halogens, oxo, C1-C6 alkyl, C1-C6 haloalkyl, and -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; Each R 12 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, and C 1~9 Heteroaryl is independently selected from, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Aryl, -CH2-C 6~10 Aryl, and C 1~9 Heteroaryl is optionally substituted with one, two, or three Rs 20d ; Each R 13 is independently selected from hydrogen, C 1~6 alkyl, and C 1~6 haloalkyl; or R 12 and R 13 together with the nitrogen to which they are attached form a C 20e heterocycloalkyl ring optionally substituted with one, two, or three Rs 2~9 ; Each R 14 is independently selected from hydrogen, C 1~6 alkyl, and C 1~6 haloalkyl; Each R 15 is independently selected C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~6 cycloalkyl, C 2~9 heterocycloalkyl, C 6~10 ​​​​​​​​​​​​​​​​​20f is optionally replaced as needed; R 16 is hydrogen, halogen, -CN, C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~6 cycloalkyl, C 2~9 heterocycloalkyl, C 6~10 aryl, C 1~9 heteroaryl, -OR 12 -SR 12 -N(R 12 )(R 13 )-C(O)OR 12 -OC(O)N(R 12 )(R 13 )-N(R 14 )C(O)N(R 12 )(R 13 )-N(R 14 )C(O)OR 15 -N(R 14 )S(O)2R 15 -C(O)R 15 -S(O)R 15 -OC(O)R 15 -C(O)N(R 12 )(R 13 )-C(O)C(O)N(R 12 )(R 13 )-N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-S(=O)(=NH)N(R 12 )(R 13 )-CH2C(O)N(R 12 )(R 13 )-CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 and -CH2S(O)2N(R 12 )(R 13 ) and is selected from C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~6Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryl is optionally substituted with one, two, or three R 20g ; R 17 is hydrogen, C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~6 cycloalkyl, C 2~9 heterocycloalkyl, C 6~10 aryl, C 1~9 heteroaryl, -C(O)OR 12 , -C(O)R 15 , -S(O)R 15 , -C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 ) - selected from, C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~6 cycloalkyl, C 2~9 heterocycloalkyl, C 6~10 aryl, and C 1~9 heteroaryl is optionally substituted with one, two, or three R 20k ; R 18 is hydrogen, halogen, -CN, C 1~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~6 cycloalkyl, C 2~9 heterocycloalkyl, C 6~10 aryl, C 1~9 heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 , -OC(O)N(R12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20h It is replaced as needed; Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , and R 20k Halogen, -CN, C 1~6Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, 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 Each is independently selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, 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 )(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 It is replaced as needed with one, two, or three elements selected independently from it; Each R 21 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 22 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C1~9 Selected independently from heteroaryls; Each R 23 H and C 1~6 Selected independently of alkyl; Each R 24 H and C 1~6 Selected independently of alkyl; Each R 25 C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected from heteroaryls; Each R 26 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20i It is replaced as needed; R 27 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20j as needed It has been replaced; R 28 is hydrogen and C 1~6 Selected from alkyl groups; n is 0, 1, or 2; [ka] (This indicates a single or double bond in which all valencies are satisfied.) The present invention provides a pharmaceutically acceptable salt or solvate thereof.

[0029] In some embodiments, the structure of formula (IIa) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0030] In some embodiments, the structure of formula (IIb) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0031] In some embodiments, Z 2 is C(R 8 )(R 9 A compound of formula (II), (IIa), or (IIb), or a pharmaceutically acceptable salt or solvate thereof, is provided. In some embodiments, R 9 Compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, where is hydrogen, are provided.

[0032] In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where X is C. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where X is N.

[0033] In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where Y is C. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where Y is N. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where Y is C(O).

[0034] In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is C. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is N. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is C(O).

[0035] In some embodiments, the structure of formula (IIc) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0036] In some embodiments, the structure of formula (IId) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0037] In some embodiments, the structure of formula (IIe) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0038] In some embodiments, the structure of the expression (IIf) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0039] In some embodiments, the structure of formula (IIg) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0040] In some embodiments, the structure of formula (IIh) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0041] In some embodiments, the structure of formula (IIi) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0042] In some embodiments, the structure of formula (IIj) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0043] In some embodiments, R 1 However, hydrogen, -N(R 12 )(R13 ), and one, two, or three R 20a C replaced as needed 1~6 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, selected from alkyl groups. In some embodiments, R 1 ga-N(R 12 )(R 13 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), and A pharmaceutically acceptable salt or solvate thereof is provided. In some embodiments, R 1 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein the integral is -NH2.

[0044] In some embodiments, R 1a , R 1b , and R 1c However, hydrogen, halogens, and one, two, or three R 20a C replaced as needed 1~6Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, each independently selected from alkyl groups. In some embodiments, R 1a , R 1b , and R 1c Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where each is hydrogen.

[0045] In some embodiments, Q 1 is C(R 1d Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 1d However, hydrogen and one, two, or three R 20a C replaced as needed 1~6Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, selected from alkyl groups, are provided. In some embodiments, Q 1 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where N is N.

[0046] In some embodiments, [ka] However, R is 1 or greater than 1. 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered heterocycloalkyl rings optionally substituted with . In some embodiments, [ka] R is selected from piperazinyl and piperidinyl, and piperazinyl and piperidinyl are present in 1 or more R values. 11Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, the R is a 3- to 12-membered heterocycloalkyl ring selected from spirocyclic heterocycloalkyl rings and fused heterocycloalkyl rings, and the spirocyclic heterocycloalkyl ring and fused heterocycloalkyl ring have 1 or more R 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, R is 1 or greater than 1. 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered cycloalkyl rings optionally substituted with . In some embodiments, [ka] However, R is 1 or greater than 1.11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where the cyclohexyl ring is optionally substituted with . In some embodiments, [ka] However, the R is a 3- to 12-membered cycloalkyl ring selected from a spirocyclic cycloalkyl ring and a fused cycloalkyl ring, and the spirocyclic cycloalkyl ring and the fused cycloalkyl ring are 1 or more R 11 The expressions (I), (Ia), and (Ib) are substituted as needed. Compounds of (I), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, [ka] Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, in which the element is absent.

[0047] In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered heterocycloalkyl rings optionally substituted with . In some embodiments, [ka] R is selected from piperazinyl and piperidinyl, and piperazinyl and piperidinyl are present in 1 or more R values. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are piperazinyl compounds substituted as needed. In some embodiments, [ka] However, the R is a 3- to 12-membered heterocycloalkyl ring selected from spirocyclic heterocycloalkyl rings and fused heterocycloalkyl rings, and the spirocyclic heterocycloalkyl ring and fused heterocycloalkyl ring have 1 or more R 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered cycloalkyl rings optionally substituted with . In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where the cyclohexyl ring is optionally substituted with . In some embodiments, [ka] However, the R is a 3- to 12-membered cycloalkyl ring selected from a spirocyclic cycloalkyl ring and a fused cycloalkyl ring, and the spirocyclic cycloalkyl ring and the fused cycloalkyl ring are 1 or more R 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] The expression (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (I Compounds of (o), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided.

[0048] In some embodiments, L 1 However, the bond, C1~C6 alkyl, -N(R 26 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, selected from - and -C(O)-. In some embodiments, L 1Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, in which L is a bond. In some embodiments, L 1 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein the base is C1-C6 alkyl.

[0049] In some embodiments, L 2 However, compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, selected from bond, C1-C6 alkyl, and -C(O)-. In some embodiments, L 2 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, in which L is a bond. In some embodiments, L 2Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein the base is C1-C6 alkyl.

[0050] In some embodiments, R 2 However, hydrogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , and -N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 One, two, or three heteroaryl R 20b Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, R 2 ga-OR 12 , -SR 12 , and C 1~6 Selected from alkyl groups, C 1~6 One alkyl group, Two or three R's 20bCompounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, R 2 ga-OR 12 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 12 However, C 1~6 Alkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Selected from heteroaryls, C 1~6 Alkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 One, two, or three heteroaryl R 20d Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, R 12 However, one, two, or three R20d C replaced as needed 1~6 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are alkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 12 However, one, two, or three R 20d C replaced as needed 2~9 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, R 12 However, one, two, or three R 20d -CH2-C substituted as needed 2~9 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, each R 20d However, halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O)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 Selected independently from C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryls are halogens, oxo, and 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 ), -S(O)2R 25 , and -S(O)2N(R 22 )(R 23Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are optionally substituted with one, two, or three groups independently selected from ). In some embodiments, each R 20d is halogen, C 1~6 Alkyl and -OR 21 Selected independently from C 1~6 Alkyl, halogen, oxo, C 1~6 Alkyl, -OR 21 , and -N(R 22 )(R 23 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are optionally substituted with one, two, or three groups independently selected from ). In some embodiments, R 2 but [ka] [ka] Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided.

[0051] In some embodiments, R 4 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where is hydrogen. In some embodiments, R 4 Provided are compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, which are groups other than the electrophilic moiety that can form a covalent bond with the cysteine ​​residue at position 12 of the KRAS protein.

[0052] In some embodiments, R 4 However, -H, -NH2, -OH, -NH(C 1~6 Alkyl), [ka] [ka] Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where m is 0, 1, 2, or 3, if present.

[0053] In another embodiment, compounds of formula (If), (Ig), (Ih), or (Ii): [ka] [ka] (In the formula, [ka] The rings are a 3-12 member heterocycloalkyl ring, a 6-10 member aryl ring, a 5-10 member heteroaryl ring, or a 3-12 member cycloalkyl ring, where the 3-12 member heterocycloalkyl ring, the 6-10 member aryl ring, the 5-10 member heteroaryl ring, and the 3-12 member cycloalkyl ring have 1 or more R 10 It is replaced as needed; [ka] is absent, a 3-12 membered heterocycloalkyl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring and the 3-12 membered cycloalkyl ring have 1 or more R 11 It is replaced as needed; Q 1 is N or C(R 1d ) and; Z is C(R 8 ) and; V is N and C(R 16 ) selected from; W is N or C(R 18 ) and; L 1 and L 2 This is a bond, C1-C6 alkyl, -O-, -N(R 26 )-, -C(O)-, -N(R 26 )C(O)-, -C(O)N(R 26 )-, -S-, -S(O)2-, -S(O)-, -S(O)2N(R 26 ), -S(O)N(R 26 ), -N(R 26 )S(O)-, -N(R 26 )S(O)2-,-OCON(R 26 )-,-N(R 26 )C(O)O-, and -N(R26 )C(O)N(R 26 )- Selected independently of; R 1 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinil, C3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; R 1a , R 1b , R 1c , and R 1d Hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15-CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) are independently selected from each, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; or R 1a and R 1b These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1b and R 1c These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; R 2 Halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -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 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20b It is replaced as needed; Each R 3 These are hydrogen, halogen, oxo, C1-C6 alkyl, C1-C6 haloalkyl, -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R13 Selected independently from; R 4 This refers to a group other than the electrophilic moiety that can form a covalent bond with hydrogen or the cysteine ​​residue at position 12 of the KRAS protein; R 8 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(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 1 2 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20c It is replaced as needed; Each R 10 and each R 11 These include halogens, oxo, C1-C6 alkyl, C1-C6 haloalkyl, and -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; Each R 12 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9Heteroaryls have one, two, or three R 20d It is replaced as needed; Each R 13 is hydrogen, C 1~6 Alkyl, and C 1~6 Selected independently of haloalkyl; or R 12 and R 13 These, together with the nitrogen they are bonded to, form one, two, or three R atoms. 20e C replaced as needed 2~9 Forming a heterocycloalkyl ring; Each R 14 is hydrogen, C 1~6 Alkyl, and C 1~6 Independently selected from haloalkyl groups; Each R 15 C is selected independently 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 It is a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20f It is replaced as needed; R 16 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, 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 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20g It is replaced as needed; R 18 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O) N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20h It is replaced as needed; Each R 20a , R 20b , R 20c , R 20d , R20e , R 20f , R 20g , R 20h , and R 20i Halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, 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 Each is independently selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, 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 )(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 It is replaced as needed with one, two, or three elements selected independently from it; Each R 21 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 22 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 23 H and C 1~6 Selected independently of alkyl; Each R 24 H and C 1~6 Selected independently of alkyl; Each R 25 C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected from heteroaryls; Each R 26 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20i It is replaced as needed; n is 0, 1, or 2; [ka] (This indicates a single or double bond in which all valencies are satisfied.) Alternatively, pharmaceutically acceptable salts or solvates thereof are provided.

[0054] In some embodiments, the compound of formula (If): [ka] Alternatively, pharmaceutically acceptable salts or solvates thereof are provided.

[0055] In some embodiments, the compound of formula (Ig): [ka] Alternatively, pharmaceutically acceptable salts or solvates thereof are provided.

[0056] In some embodiments, the compound of formula (Ih): [ka] Alternatively, pharmaceutically acceptable salts or solvates thereof are provided.

[0057] In some embodiments, the compound of formula (Ii): [ka] Alternatively, pharmaceutically acceptable salts or solvates thereof are provided.

[0058] In some embodiments, compounds of formula (Ik), (Im), (In), or (Io): [ka] [ka] (In the formula, [ka] The rings are a 3-12 member heterocycloalkyl ring, a 6-10 member aryl ring, a 5-10 member heteroaryl ring, or a 3-12 member cycloalkyl ring, where the 3-12 member heterocycloalkyl ring, the 6-10 member aryl ring, the 5-10 member heteroaryl ring, and the 3-12 member cycloalkyl ring have 1 or more R 10 It is replaced as needed; [ka] is absent, a 3-12 membered heterocycloalkyl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring and the 3-12 membered cycloalkyl ring have 1 or more R 11 It is replaced as needed; Q 1 is N or C(R 1d ) and; Z is N or C(R 8 ) and; J is N and C(R 16 ) selected from; W is N or C(R 18 ) and; L 1 and L 2 This is a bond, C1-C6 alkyl, -O-, -N(R 26 )-, -C(O)-, -N(R 26 )C(O)-, -C(O)N(R 26 )-, -S-, -S(O)2-, -S(O)-, -S(O)2N(R 26 ), -S(O)N(R 26 ), -N(R 26 )S(O)-, -N(R 26 )S(O)2-,-OCON(R 26 )-,-N(R 26 )C(O)O-, and -N(R 26 )C(O)N(R 26 )- Selected independently of; R 1 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 ) C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; R 1a , R 1b , R 1c, and R 1d Hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) are independently selected from each, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; or R 1a and R 1b These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1b and R 1c These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; R 2 Halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20b It is replaced as needed; Each R 3 These are hydrogen, halogen, oxo, C1-C6 alkyl, C1-C6 haloalkyl, -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 Selected independently from; R 4 This refers to a group other than the electrophilic moiety that can form a covalent bond with hydrogen or the cysteine ​​residue at position 12 of the KRAS protein; R 8 Hydrogen, halogen, -CN, C 1~6 Alkyl, C2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N (R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9Heteroaryls have one, two, or three R 20c It is replaced as needed; Each R 10 and each R 11 These include halogens, oxo, C1-C6 alkyl, C1-C6 haloalkyl, and -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; Each R 12 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20d It is replaced as needed; Each R 13 is hydrogen, C 1~6 Alkyl, and C 1~6 Selected independently of haloalkyl; or R 12 and R 13These, together with the nitrogen they are bonded to, form one, two, or three R atoms. 20e C replaced as needed 2~9 Forming a heterocycloalkyl ring; Each R 14 is hydrogen, C 1~6 Alkyl, and C 1~6 Independently selected from haloalkyl groups; Each R 15 C is selected independently 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 It is a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20f It is replaced as needed; R 16 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(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 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20g It is replaced as needed; R 18 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 a Reel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20h It is replaced as needed; Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , and R 20i Halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, 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 Each is independently selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, 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, -OR21 , -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 It is replaced as needed with one, two, or three elements selected independently from it; Each R 21 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 22 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 23 H and C 1~6Selected independently of alkyl; Each R 24 H and C 1~6 Selected independently of alkyl; Each R 25 C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected from heteroaryls; Each R 26 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20i Place as needed It has been replaced; n is 0, 1, or 2; [ka] (This indicates a single or double bond in which all valencies are satisfied.) Alternatively, pharmaceutically acceptable salts or solvates thereof are provided.

[0059] In some embodiments, the compound of formula (Ik): [ka] Alternatively, pharmaceutically acceptable salts or solvates thereof are provided.

[0060] In some embodiments, the compound of formula (Im): [ka] Alternatively, pharmaceutically acceptable salts or solvates thereof are provided.

[0061] In some embodiments, compounds of formula (In): [ka] Alternatively, pharmaceutically acceptable salts or solvates thereof are provided.

[0062] In some embodiments, the compound of formula (Io): [ka] Alternatively, pharmaceutically acceptable salts or solvates thereof are provided.

[0063] In some embodiments, V is C(R 16 Compounds of formula (If), (Ig), (Ih), or (Ii), or pharmaceutically acceptable salts or solvates thereof, are provided, where V is C(H). In some embodiments, compounds of formula (If), (Ig), (Ih), or (Ii), or pharmaceutically acceptable salts or solvates thereof, are provided, where V is N.

[0064] In some embodiments, J is C(R 16Compounds of formula (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided, where J is C(H). In some embodiments, compounds of formula (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof are provided, where J is N. A compound of (Io) or (Io), or a pharmaceutically acceptable salt or solvate thereof, is provided.

[0065] In some embodiments, Z is C(R 8 Compounds of formula (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, compounds of formula (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided, where Z is N.

[0066] In some embodiments, W is C(R 18 Compounds of formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, compounds of formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided, where W is N.

[0067] In some embodiments, the compound of formula (Ip): [ka] Alternatively, pharmaceutically acceptable salts or solvates thereof are provided.

[0068] In another embodiment, the present disclosure relates to a compound of formula (II): [ka] (In the formula, [ka] R is absent, a 3-12 membered heterocycloalkyl ring, a 6-10 membered aryl ring, a 5-10 membered heteroaryl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring, 6-10 membered aryl ring, 5-10 membered heteroaryl ring, and 3-12 membered cycloalkyl ring have 1 or more R 10 It is replaced as needed; [ka] is absent, a 3-12 membered heterocycloalkyl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring and the 3-12 membered cycloalkyl ring have 1 or more R 11 It is replaced as needed; A is a bond, O, S, N(R) 1e ), or C(R 1f )(R 1g ) and; Q 1 is N or C(R 1d ) and; Q 2 is either S or O; X is either C or N; Y is C, C(O), or N; Z 1 is N or C(R 6 ) and; Z 2 is N(R 7 ) or C(R 8 )(R 9 ) and; Z 3 is non-existent, N(R) 17 ), or C(R 27 )(R 28 ) and; U is C, S(O), S(O)2, C(O), or N; L 1 and L 2 This is a bond, C1-C6 alkyl, -O-, -N(R 26)-, -C(O)-, -N(R 26 )C(O)-, -C(O)N(R 26 )-, -S-, -S(O)2-, -S(O)-, -S(O)2N(R 26 ), -S(O)N(R 26 ), -N(R 26 )S(O)-, -N(R 26 )S(O)2-,-OCON(R 26 )-,-N(R 26 )C(O)O-, and -N(R 26 )C(O)N(R 26 )- Selected independently of; R 1 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12)(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , and R 1g Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(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 )(R13 ), -N(R 14 )C(O)R 15 -S(O)2R 1 5 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) are independently selected from each, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; or R 1a and R 1b These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1b and R 1c These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1f and R 1gThese rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; R 2 Halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15, and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20b It is replaced as needed; Each R 3 These are hydrogen, halogen, oxo, C1-C6 alkyl, C1-C6 haloalkyl, -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; R 4 This refers to a group other than the electrophilic moiety that can form a covalent bond with hydrogen or the cysteine ​​residue at position 12 of the KRAS protein; R 5 teeth [ka] and; R 6 is hydrogen and C 1~6 Selected from alkyl groups; R 7 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Hete Roaryl, -C(O)OR 12 , -C(O)R 15,-S(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected from, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20c It is replaced as needed; R 8 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15-S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20c It is replaced as needed; R 9 is hydrogen and C 1~6 Selected from alkyl groups; Each R 10 and each R 11 These include halogens, oxo, C1-C6 alkyl, C1-C6 haloalkyl, and -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; Each R 12 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20d It is replaced as needed; Each R 13 is hydrogen, C 1~6 Alkyl, and C 1~6 Selected independently of haloalkyl; or R 12 and R 13 These, together with the nitrogen they are bonded to, form one, two, or three R atoms. 20e C replaced as needed 2~9 Forming a heterocycloalkyl ring; Each R 14 is hydrogen, C 1~6 Alkyl, and C 1~6 Independently selected from haloalkyl groups; Each R 15 C is selected independently 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 It is a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R20f It is replaced as needed; R 16 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2 R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20g It is replaced as needed; R 17 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -C(O)OR 12 , -C(O)R 15 ,-S(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected from, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20k It is replaced as needed; R 18 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20h It is replaced as needed; Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , and R 20kHalogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, 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 Each is independently selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9Heteroaryls 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 )(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 It is replaced as needed with one, two, or three elements selected independently from it; Each R 21 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 22 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 23 H and C 1~6 Selected independently of alkyl; Each R 24 H and C 1~6 Selected independently of alkyl; Each R 25 C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected from heteroaryls; Each R 26 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20i It is replaced as needed; R 27 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, 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 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20j It is replaced as needed; R 28 is hydrogen and C 1~6 Selected from alkyl groups; n is 0, 1, or 2; [ka] (This indicates a single or double bond in which all valencies are satisfied.) The present invention provides a pharmaceutically acceptable salt or solvate thereof.

[0069] In some embodiments, the structure of formula (IIa) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0070] In some embodiments, the structure of formula (IIb) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0071] In some embodiments, Z 2 is C(R 8 )(R 9 A compound of formula (II), (IIa), or (IIb), or a pharmaceutically acceptable salt or solvate thereof, is provided. In some embodiments, R 9 Compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, where is hydrogen, are provided.

[0072] In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where X is C. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where X is N.

[0073] In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where Y is C. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where Y is N. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where Y is C(O).

[0074] In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is C. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is N. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is C(O).

[0075] In some embodiments, the structure of formula (IIc) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0076] In some embodiments, the structure of formula (IId) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0077] In some embodiments, the structure of formula (IIe) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0078] In some embodiments, the structure of the expression (IIf) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0079] In some embodiments, the structure of formula (IIg) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0080] In some embodiments, the structure of formula (IIh) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0081] In some embodiments, the structure of formula (IIi) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0082] In some embodiments, the structure of formula (IIj) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0083] In some embodiments, R 1 However, hydrogen, -N(R 12 )(R13 ), and one, two, or three R 20a C replaced as needed 1~6 Compounds of formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), selected from alkyl groups, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 1 ga-N(R 12 )(R 13 Compounds of formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 1 Compounds of formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein the integral is -NH2.

[0084] In some embodiments, R 1a , R 1b , and R 1c However, hydrogen, halogens, and one, two, or three R 20a C replaced as needed 1~6 Compounds of formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, each independently selected from alkyl groups. In some embodiments, R 1a , R1b , and R 1c Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), where each is hydrogen, or pharmaceutically acceptable salts or solvates thereof are provided.

[0085] In some embodiments, Q 1 is C(R 1d Compounds of formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 1d However, hydrogen and one, two, or three R 20a C replaced as needed 1~6 Compounds of formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), selected from alkyl groups, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, Q 1 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where N is N.

[0086] In some embodiments, [ka] However, R is 1 or greater than 1. 11Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered heterocycloalkyl rings optionally substituted with . In some embodiments, [ka] R is selected from piperazinyl and piperidinyl, and piperazinyl and piperidinyl are present in 1 or more R values. 11 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, the R is a 3- to 12-membered heterocycloalkyl ring selected from spirocyclic heterocycloalkyl rings and fused heterocycloalkyl rings, and the spirocyclic heterocycloalkyl ring and fused heterocycloalkyl ring have 1 or more R 11 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, R is 1 or greater than 1. 11Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered cycloalkyl rings optionally substituted with . In some embodiments, [ka] However, R is 1 or greater than 1. 11 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where the cyclohexyl ring is optionally substituted with . In some embodiments, [ka] However, the R is a 3- to 12-membered cycloalkyl ring selected from a spirocyclic cycloalkyl ring and a fused cycloalkyl ring, and the spirocyclic cycloalkyl ring and the fused cycloalkyl ring are 1 or more R 11 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, in which the element is absent.

[0087] In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered heterocycloalkyl rings optionally substituted with . In some embodiments, [ka] R is selected from piperazinyl and piperidinyl, and piperazinyl and piperidinyl are present in 1 or more R values. 10 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, R is 1 or greater than 1. 10Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are piperazinyl compounds as needed. In some embodiments, [ka] However, the R is a 3- to 12-membered heterocycloalkyl ring selected from spirocyclic heterocycloalkyl rings and fused heterocycloalkyl rings, and the spirocyclic heterocycloalkyl ring and fused heterocycloalkyl ring have 1 or more R 10 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered cycloalkyl rings substituted as needed. In terms of implementation methods, [ka] However, R is 1 or greater than 1. 10Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where the cyclohexyl ring is optionally substituted with . In some embodiments, [ka] However, the R is a 3- to 12-membered cycloalkyl ring selected from a spirocyclic cycloalkyl ring and a fused cycloalkyl ring, and the spirocyclic cycloalkyl ring and the fused cycloalkyl ring are 1 or more R 10 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitutions as necessary.

[0088] In some embodiments, L 1 However, the bond, C1~C6 alkyl, -N(R 26 Compounds of formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, selected from - and -C(O)-. In some embodiments, L 1 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, in which L is a bond. In some embodiments, L 1Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), where the parent molecule is C1-C6 alkyl, or pharmaceutically acceptable salts or solvates thereof are provided.

[0089] In some embodiments, L 2 However, compounds of formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, selected from bond, C1-C6 alkyl, and -C(O)-, are provided. 2 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, in which L is a bond. In some embodiments, L 2 is C1~C6 alkyl, formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (II Compounds of (f), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided.

[0090] In some embodiments, R 2 However, hydrogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR12 , and -N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 One, two, or three heteroaryl R 20b Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, R 2 ga-OR 12 , -SR 12 , and C 1~6 Selected from alkyl groups, C 1~6 One, two, or three alkyl groups 20b Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, R 2 ga-OR 12 Compounds of formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 12 However, C 1~6 Alkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10Aryl, and C 1~9 Selected from heteroaryls, C 1~6 Alkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 One, two, or three heteroaryl R 20d Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, R 12 However, one, two, or three R 20d C replaced as needed 1~6 Compounds of the formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are alkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 12 However, one, two, or three R 20d C replaced as needed 2~9 Compounds of the formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are heterocycloalkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 12 However, one, two, or three R 20d -CH2-C substituted as needed 2~9Compounds of the formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are heterocycloalkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, each R 20d However, halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, 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 Selected independently from C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryls are halogens, oxo, and C 1~6 Alkyl, C 1~6 Haloalkyl, C1~6 Alkoxy, C 1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 ,-C(O)N(R 22 )(R 23 ), -S(O)2R 25 , and -S(O)2N(R 22 )(R 23 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are optionally substituted with one, two, or three groups independently selected from ). In some embodiments, each R 20d is halogen, C 1~6 Alkyl and -OR 21 Selected independently from C 1~6 Alkyl, halogen, oxo, C 1~6 Alkyl, -OR 21 , and -N(R 22 )(R 23 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are optionally substituted with one, two, or three groups independently selected from ). In some embodiments, R 2 but [ka] [ka] [ka] Formulas selected from (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (II d) Compounds of (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided.

[0091] In some embodiments, R 8 is hydrogen, halogen, or C 1~6 Compounds of the formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are alkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 8 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), where (II) is hydrogen, or pharmaceutically acceptable salts or solvates thereof are provided.

[0092] In some embodiments, R 16 is hydrogen, halogen, or C 1~6 Compounds of the formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are alkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 16Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), where (II) is hydrogen, or pharmaceutically acceptable salts or solvates thereof are provided.

[0093] In some embodiments, R 18 is hydrogen, halogen, or C 1~6 Compounds of the formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are alkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 18 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), where (II) is hydrogen, or pharmaceutically acceptable salts or solvates thereof are provided.

[0094] In some embodiments, R 4 Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), where is hydrogen, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 4Provided are compounds of formula (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, which are groups other than the electrophilic moiety that can form a covalent bond with the cysteine ​​residue at position 12 of the KRAS protein.

[0095] In some embodiments, R 4 However, -H, -NH2, -OH, -NH(C 1~6 Alkyl), [ka] Compounds of formulas (If), (Ig), (Ih), (Ii), (Ik), (Im), (In), (Io), (Ip), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where m is 0, 1, 2, or 3 if present.

[0096] In another aspect, the Disclosure provides a pharmaceutical composition comprising a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient. In another aspect, the Disclosure provides a pharmaceutical composition comprising a compound of formula (Ip), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

[0097] In another aspect, the Disclosure provides a method for treating a cancer in a subject requiring treatment, comprising the step of administering a therapeutically effective amount of a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or a pharmaceutically acceptable salt or solvate thereof, to the subject. In another aspect, the Disclosure provides a method for treating a cancer in a subject requiring treatment, comprising administering a therapeutically effective amount of a compound of formula (Ip), or a pharmaceutically acceptable salt or solvate thereof. The present invention provides a method comprising the step of administering a substance to a target. In some embodiments, the cancer is a solid tumor. In some embodiments, the cancer is a blood cancer. In some embodiments, the method comprises the step of administering an additional drug or treatment. In some embodiments, the additional drug or treatment is selected from the group consisting of chemotherapeutic agents, radiopharmaceuticals, and immunomodulators.

[0098] In another aspect, the Disclosure provides a method for modulating the activity of a Ras protein, comprising the step of contacting the Ras protein with an effective amount of a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or a pharmaceutically acceptable salt or solvate thereof, thereby modulating the activity of the Ras protein. In another aspect, the Disclosure provides a method for modulating the activity of a Ras protein, comprising the step of contacting the Ras protein with an effective amount of a compound of formula (Ip), or a pharmaceutically acceptable salt or solvate thereof, thereby modulating the activity of the Ras protein. In some embodiments, the regulation includes inhibiting Ras protein activity. In some embodiments, the Ras protein is the K-Ras protein. In some embodiments, the Ras protein is the G12D or G12V variant K-Ras. In some embodiments, the method includes the step of administering an additional agent or treatment. In some embodiments, the additional agent or treatment is selected from the group consisting of chemotherapeutic agents, radiopharmaceuticals, and immunomodulators.

[0099] In another aspect, the disclosure provides a Ras protein to which a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or a pharmaceutically acceptable salt or solvate thereof, wherein the activity of the Ras protein is reduced compared to a Ras protein not bound to the compound. In another aspect, the disclosure provides a Ras protein to which a compound of formula (Ip), or a pharmaceutically acceptable salt or solvate thereof, is bound, wherein the activity of the Ras protein is reduced compared to a Ras protein not bound to the compound.

[0100] Embedding by reference All publications, patents, and patent applications referenced herein are incorporated by reference to the same extent as each individual publication, patent, or patent application is specifically and individually indicated as being incorporated by reference. [Modes for carrying out the invention]

[0101] Detailed explanation The implementation of some embodiments disclosed herein will, unless otherwise specified, utilize prior art in immunology, biochemistry, chemistry, molecular biology, microbiology, cell biology, genomics, and recombinant DNA within the scope of the skills possessed by those skilled in the art. For example, Sambrook and Green, Molecular Cloning: A Laboratory Manual, 4th edition (2012); current protocols in Molecular Biology series (edited by FMAusubel et al.); methods in enzymology series (Academic Press, Inc.); PCR 2: A Practical Approach (edited by MJ MacPherson, BD Hames, and GR Taylor (1995)); Harlow and See Lane (ed.) (1988) Antibodies, A Laboratory Manual, and Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6th edition (RIFreshney (ed.) (2010)).

[0102] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as that generally understood by those skilled in the art of the claimed subject matter. If there are multiple definitions of a term herein, the definition 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) referenced herein are incorporated by reference. Where URLs or other such identifiers or addresses are referenced, it is understood that such identifiers may change and specific information may circulate on the internet, but equivalent information can be found by searching the internet. References thereto demonstrate the availability and public dissemination of such information.

[0103] It should be understood that the above general description and the following detailed description are illustrative and descriptive only and do not limit the subject matter claimed. In this application, unless otherwise specified, the use of the singular includes the plural. It should be noted that, as used herein and in the appended claims, the singular “a,” “an,” and “the” include multiple referents unless the context clearly indicates otherwise. In this application, the use of “or” means “and / or” unless otherwise specified. Furthermore, the use of the term “including” and other forms such as “include,” “includes,” and “included” is not limited.

[0104] The section headings used herein are for structural purposes only and should not be construed as limiting the subject matter described herein.

[0105] Standard definitions of chemical terms, though not limited to these, can be found in references including Carey and Sundberg's "Advanced Organic Chemistry, 4th Edition," Volumes A (2000) and B (2001), Plenum Press, New York. Unless otherwise specified, these refer to conventional methods of mass spectrometry, NMR, HPLC, protein chemistry, biochemistry, recombinant DNA techniques, and pharmacology.

[0106] Unless otherwise specified, the nomenclature, experimental procedures, and techniques used in relation to analytical chemistry, synthetic organic chemistry, and pharmaceutical and medicinal chemistry described herein are recognized in the art. Standard techniques can be used for chemical synthesis, chemical analysis, pharmaceutical preparation, formulation, and delivery, as well as for patient treatment. Standard techniques (e.g., electroporation, lipofection) can be used for recombinant DNA, oligonucleotide synthesis, and tissue culture and transformation. Reaction and purification techniques can be carried out, for example, using kits specified by the manufacturer, or as commonly achieved in the art, or as described herein. The aforementioned techniques and procedures can generally be carried out in customary ways and as described in the various general and more specific references cited and discussed throughout this specification.

[0107] It should be understood that the methods and compositions described herein are not limited to, and are therefore subject to change, the specific methodologies, protocols, cell systems, constructs, and reagents described herein. The terms used herein are merely for the purpose of describing specific embodiments. It should also be understood that this specification is not intended to limit the scope of the methods, compounds, and compositions described herein.

[0108] When used in this specification, C1 to C x C1~C2, C1~C3...C1~C x Includes C1~C x This refers to the number of carbon atoms that make up the specified portion (excluding substituents as needed).

[0109] The “alkyl” group refers to a linear or branched hydrocarbon chain radical consisting only of carbon and hydrogen atoms and containing no unsaturation. In some embodiments, the “alkyl” group may have 1 to 6 carbon atoms (wherever it appears herein, numerical ranges such as “1 to 6” refer to each integer within a given range; for example, “1 to 6 carbon atoms” means that the alkyl group may consist of up to 6 carbon atoms, including 1, 2, 3, etc., but this definition also covers the existence of the term “alkyl” without a specified numerical range). Alkyl groups of compounds described herein may be designated as “C1 to C6 alkyl” or similar designations. As merely an example, “C1 to C6 alkyl” indicates that the alkyl chain contains 1 to 6 carbon atoms, 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 may be substituted or unsubstituted. Depending on the structure, the alkyl group can be a monoradical or a diradical (i.e., an alkylene group).

[0110] "Alkoxy" refers to an "-O-alkyl" group, where alkyl is as defined herein.

[0111] The term "alkenyl" refers to a linear or branched hydrocarbon radical group consisting only 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 may have 2 to 6 carbon atoms. Alkenyl groups can be substituted or unsubstituted. Depending on the structure, an alkenyl group can be a monoradical or a diradical (i.e., an alkenylene group).

[0112] The term "alkynyl" refers to a linear or branched hydrocarbon radical group consisting only 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 may have 2 to 6 carbon atoms. An alkynyl group may be substituted or unsubstituted. Depending on the structure, an alkynyl group may be a monoradical or a diradical (i.e., an alkynylene group).

[0113] "Amino" refers to the -NH2 group.

[0114] The terms "alkylamine" or "alkylamino" mean that alkyl is as defined herein, and x and y are selected from the group x=1,y=1 and x=2,y=0, -N(alkyl) x H y This refers to a group. When x=2, the alkyl groups, together with the nitrogen to which they are bonded, can optionally form a cyclic ring system. "Dialkylamino" refers to a -N(alkyl)2 group, where alkyl is as defined herein.

[0115] The term "aromatic" refers to a planar ring having a delocalized π-electron system containing 4n+2 π-electrons (where n is an integer). Aromatic rings can be formed from 5, 6, 7, 8, 9, or more than 9 atoms. Aromatics may be substituted as needed. The term "aromatic" includes both aryl groups (e.g., phenyl, naphthalenyl) and heteroaryl groups (e.g., pyridinyl, quinolinyl).

[0116] As used herein, the term "aryl" refers to an aromatic ring in which each of the ring-forming atoms is a carbon atom. An aryl ring may be formed by five, six, seven, eight, nine, or more than nine carbon atoms. The aryl group may be substituted as needed. Examples of aryl groups include, but are not limited to, phenyl and naphthalenyl. Depending on the structure, the aryl group may be a monoradical or a diradical (i.e., an arylene group).

[0117] "Carboxylate" refers to -CO2H. In some embodiments, the carboxyl portion may be replaced with a "carboxylic acid bioisostere," which refers to a functional group or portion that exhibits similar physical and / or chemical properties to the carboxylic acid portion. Carboxylic acid bioisosteres have similar biological properties to the carboxylic acid group. Compounds having a carboxylic acid portion can have similar physical and / or biological properties to carboxylic acid-containing compounds if the carboxylic acid portion is replaced with a carboxylic acid bioisostere. For example, in one embodiment, the carboxylic acid bioisostere ionizes at approximately the same physiological pH as the carboxylic acid group. Examples of carboxylic acid bioisosteres are not limited to these, but include: [ka] These are some examples.

[0118] The term "cycloalkyl" refers to a monocyclic or polycyclic non-aromatic radical in which each of the ring-forming atoms (i.e., skeletal atoms) is a carbon atom. Cycloalkyls can be saturated or partially unsaturated. In some embodiments, the cycloalkyl ring is fused with an aryl, heteroaryl, heterocycloalkyl, or second cycloalkyl ring. In some embodiments, the cycloalkyl ring is a spirocyclic cycloalkyl ring. In some embodiments, the cycloalkyl group contains 3 to 10 ring atoms. Depending on the structure, the cycloalkyl group can be a monoradical or a diradical (i.e., a cycloalkylene group).

[0119] The terms “heteroaryl” or, instead, “heteroaromatic” refer to an aryl group containing one or more ring heteroatoms selected from nitrogen, oxygen, and sulfur. As used herein, a heteroaryl radical is a monocyclic, bicyclic, or tricyclic ring system in which at least one of the rings of the ring system is completely unsaturated. The nitrogen-containing “heteroaromatic” or “heteroaryl” moiety refers to an aromatic group in which at least one of the ring skeletal atoms is a nitrogen atom. Depending on the structure, a heteroaryl group may be a monoradical or a diradical (i.e., a heteroarylene group).

[0120] A "heterocycloalkyl" or "heteroalicyclic" group refers to a cycloalkyl group in which at least one skeletal ring atom is a heteroatom selected from nitrogen, oxygen, and sulfur. Heterocycloalkyls can be saturated or partially unsaturated. In some embodiments, the heterocycloalkyl ring is condensed with an aryl, heteroaryl, cycloalkyl, or second heterocycloalkyl ring. The term heterocycloalkyl also includes, but is not limited to, all cyclic forms of carbohydrates, including monosaccharides, disaccharides, and oligosaccharides. In some embodiments, the heterocycloalkyl ring is a spirocyclic heterocycloalkyl ring. In some embodiments, the heterocycloalkyl ring is a bridged heterocycloalkyl ring. Unless otherwise specified, heterocycloalkyls have 2 to 10 carbon atoms in the ring. When referring to the number of carbon atoms in a heterocycloalkyl, it should be understood that the number of carbon atoms in a heterocycloalkyl is not the same as the total number of atoms (including heteroatoms) that make up the heterocycloalkyl (i.e., the skeletal atoms of the heterocycloalkyl ring). Depending on the structure, a heterocycloalkyl can be a monoradical or a diradical (i.e., a heterocycloalkylene group).

[0121] The term "halo" or, instead, "halogen" refers to fluoro, chloro, bromo, and iodine.

[0122] The term "haloalkyl" refers to an alkyl group that is substituted with one or more halogens. The halogens may be the same or different. Non-exclusive examples of haloalkyls include -CH2Cl, -CF3, -CHF2, -CH2CF3, and -CF2CF3.

[0123] The terms "fluoroalkyl" and "fluoroalkoxy" include alkyl and alkoxy groups that are substituted with one or more fluorine atoms, respectively. Non-limiting examples of fluoroalkyl groups include -CF3, -CHF2, -CH2F, -CH2CF3, -CF2CF3, -CF2CF2CF3, and -CF(CH3)3. Non-limiting examples of fluoroalkoxy groups include -OCF3, -OCHF2, -OCH2F, -OCH2CF3, -OCF2CF3, -OCF2CF2CF3, and -OCF(CH3)2.

[0124] The term "heteroalkyl" refers to an alkyl radical in which one or more atoms in the backbone chain are selected from atoms other than carbon, such as oxygen, nitrogen, sulfur, phosphorus, silicon, or combinations thereof. Heteroatoms(s) can be located at any internal position of the heteroalkyl group. Examples, but not limited to, include -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)2-CH3, -CH2-NH-OCH3, -CH2-O-Si(CH3)3, -CH2-CH=N-OCH3, and -CH=CH-N(CH3)-CH3. Furthermore, for example, up to two heteroatoms may be consecutive, such as -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. A "heteroalkyl" can have 1 to 6 carbon atoms, excluding the number of heteroatoms.

[0125] The term "oxo" refers to the O radical.

[0126] The terms "bond" or "single bond" refer to a chemical bond between two atoms, or between two parts when the atoms linked by the bond are considered part of a larger substructure.

[0127] The term "part" refers to a specific segment or functional group of a molecule. A chemical part is often a recognized chemical entity embedded in or attached to a molecule.

[0128] As used herein, the substituent "R" appearing alone without numerical specification refers to a substituent selected from alkyl, haloalkyl, heteroalkyl, alkenyl, cycloalkyl, aryl, heteroaryl (bonded via a ring carbon), and heterocycloalkyl.

[0129] "As needed" or "as required" means that the event or situation described below may or may not occur, and that the description includes both cases in which the event or situation occurs and cases in which it does not occur.

[0130] The terms "substituted as needed" or "substituted" mean that the group referred to may be substituted with one or more additional groups individually and independently selected from alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, -OH, alkoxy, aryloxy, alkylthio, arylthio, alkyl sulfoxide, aryl sulfoxide, alkyl sulfone, aryl sulfone, -CN, alkyne, C1-C6 alkylalkyne, halo, acyl, acyloxy, -CO2H, -CO2-alkyl, nitro, haloalkyl, fluoroalkyl, and amino (including monosubstituted and disubstituted amino groups (e.g., -NH2, -NHR, -N(R)2) and their protected derivatives). For example, substituents as needed may be L s R s (In the formula, each L sThe bonds are independently selected from -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)-; each R is independently selected from the bonds, -O-, -C(=O)-, -S-, -S(=O)-, -S(=O)2-, -NHS(=O)2, -OC(O)NH-, -NHC(O)O-, -(C1-C6 alkyl)-, or -(C2-C6 alkenyl)-; each R s The substituent can be H, (C1-C6 alkyl), (C3-C8 cycloalkyl), aryl, heteroaryl, heterocycloalkyl, and C1-C6 heteroalkyl (selected independently from these). Protecting groups that can form protected derivatives of the above substituents are found in the above-mentioned materials of Greene and Wuts, etc.

[0131] "Pharmacologically acceptable salts" include both acid addition salts and base addition salts. A pharmaceutically acceptable salt of any one of the heterocyclic compounds described herein is intended to encompass any and all pharmaceutically acceptable salt forms. Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0132] "Pharmacologically acceptable acid addition salts" refer to salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, and phosphorous acid, which retain the biological efficacy and properties of the free base and are not biologically or otherwise undesirable. Salts formed with organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanes, hydroxyalkanoates, alkanedioates, aromatic acids, and aliphatic and aromatic sulfonic acids are also included, 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, and salicylic acid. Therefore, exemplary salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, trifluoroacetates, propionates, caprylates, isobutyrates, oxalates, malons, succinates, suberates, sebacinates, fumarates, maleates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, phthalates, and benzenesulfates. Examples include nitrates, toluenesulfonates, phenylacetates, citrates, lactates, malates, tartrates, and methanesulfonates. Salts of amino acids, such as alginates, glucons, and galacturons, are also considered (see, for example, Berge SM et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science, 66:1-19 (1997)). In some embodiments, acid addition salts of basic compounds are prepared by contacting the free base form with a sufficient amount of the desired acid to produce the salt, according to methods and techniques well known to those skilled in the art.

[0133] A "pharmaceutically acceptable base addition salt" refers to a salt that retains the biological efficacy and properties of a free acid and is not biologically or otherwise undesirable. These salts are prepared by adding an inorganic or organic base to a free acid. In some embodiments, pharmaceutically acceptable base addition salts are formed with metals or amines such as alkalis and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, and aluminum salts. Salts derived from organic bases are not limited to these, but include 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, hydravamin, choline, betaine, ethylenediamine, ethylenedianiline, N-methylglucamine, glucosamine, methylglucamine, theobromine, purine, piperazine, piperidine, N-ethylpiperidine, and polyamine resins. See Berge et al. above.

[0134] 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, or may be interrupted by non-amino acids. These terms also encompass modified amino acid polymers; for example, any other operations such as disulfide bond formation, glycosylation, lipid modification, acetylation, phosphorylation, or conjugation with labeling components. Where used herein, the term “amino acid” refers to natural and / or unnatural or synthetic amino acids, including glycine and both D or L optical isomers, as well as amino acid analogs and peptide mimics.

[0135] The terms “polynucleotide,” “nucleotide,” “nucleotide sequence,” “nucleic acid,” and “oligonucleotide” are used interchangeably. These refer to polymeric forms of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or their analogues. Polynucleotides can have any three-dimensional structure and can perform any known or unknown function. The following are non-limiting examples of polynucleotides: coding or non-coding regions of genes or gene fragments, loci (plural) (singular) defined from linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, short interfering RNA (siRNA), short hairpin RNA (shRNA), microRNA (miRNA), ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers. Polynucleotides include one or more modified nucleotides, such as methylated nucleotides, as well as nucleotide analogs, such as peptide nucleic acids (PNA), morpholino and locked nucleic acids (LNA), glycol nucleic acids (GNA), and threose nucleic acids (TN). A) may include 2'-fluoro, 2'-OMe, and phosphorothiolated DNA. If present, modifications to the nucleotide structure may be conferred before or after polymer assembly. The nucleotide sequence may be interrupted by non-nucleotide components. Polynucleotides may be further modified after polymerization, such as by conjugation with labeling components or other conjugation targets.

[0136] As used herein, “prodrug” refers to a compound that can be converted to the biologically active compounds described herein under physiological conditions or by solvolysis. 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 can be converted to the active compound in vivo, for example, by hydrolysis. Prodrug compounds may offer advantages of solubility, histocompatibility, and / or delayed release in mammalian organisms (see, e.g., Bundgard, H., Design of Prodrugs (1985), pp. 7-9, 21-24 (Elsevier, Amsterdam)). The discussion of prodrugs is provided in Higuchi, T. et al., “Pro-drugs as Novel Delivery Systems,” ACSSymposium Series, Vol. 14, and in Bioreversible Carriers in Drug Design, edited by Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by whole reference. A “prodrug” can be any covalent carrier that releases an active compound in vivo when administered to a mammalian subject. Prodrugs of active compounds described herein can be prepared by modifying functional groups present in the active compound so that the modifications are cleaved either by conventional means or in vivo to become the parent active compound.

[0137] As used herein, “expression” refers to the process by which a polynucleotide is transcribed from a DNA template (into mRNA or other RNA transcripts, etc.), and / or the process by which the transcribed mRNA is subsequently translated into a peptide, polypeptide, or protein. Transcripts and encoded polypeptides may be collectively referred to as “gene products.” If the polynucleotide originates from genomic DNA, expression may include the splicing of mRNA in eukaryotic cells.

[0138] The terms “subject,” “individual,” and “patient” are used interchangeably herein to refer to vertebrates, preferably mammals, more preferably humans. Mammals include, but are not limited to, mice, monkeys, humans, livestock, sports animals, and pets. Tissues, cells, and their offspring of biological entities obtained in vivo or cultured in vitro are also included.

[0139] The terms “therapeutic agent,” “therapeutic drug,” or “treatment agent” are used interchangeably and refer to molecules or compounds that produce some beneficial effect when administered to a subject. Beneficial effects include enabling diagnostic determination; improving disease, symptoms, disorders, or pathological symptoms; reducing or preventing the onset of disease, symptoms, disorders, or symptoms; and generally, counteracting disease, symptoms, disorders, or pathological symptoms.

[0140] As used herein, “treatment,” “to treat,” “to alleviate,” and “to improve” are interchangeable. These terms refer to an approach to obtain beneficial or desired outcomes, including, but not limited to, therapeutic and / or preventive benefits. Therapeutic benefit means any therapeutically related improvement or effect on one or more diseases, symptoms, or signs during treatment. For preventive benefits, The composition may be administered to subjects at risk of developing a particular disease, symptom, or sign, or to subjects who may not yet have a disease, symptom, or sign, but who report one or more of the physiological signs of the disease. Typically, the prophylactic benefit includes reducing the incidence and / or exacerbation of one or more diseases, symptoms, or signs during treatment (e.g., between a treated population and an untreated population, or between a treated state and an untreated state in a single subject).

[0141] The terms “effective dose” or “therapeutic effective dose” refer to the amount of drug sufficient to produce a beneficial or desired result. The therapeutic effective dose may vary depending on one or more of the following: the subject and disease symptoms being treated, the subject’s weight and age, the severity of the disease symptoms, the mode of administration, etc., which can be readily determined by those skilled in the art. An effective dose of the activator may be administered in a single dose or multiple doses. Components may be described herein as having at least an effective dose, or at least an effective dose relating to a specific target or purpose, such as any of those described herein. The term “effective dose” also applies to doses that provide an image for detection by appropriate imaging methods. Specific doses may vary depending on one or more of the following: the specific drug selected, the dosing regimen to be followed, whether it is administered in combination with other compounds, the timing of administration, the tissue being imaged, and the physical delivery system to which it is carried.

[0142] An "antigen" is a part or molecule that contains an epitope and therefore specifically binds to an antibody.

[0143] An "antigen-binding unit" can be a full-length antibody, its structural variant, its functional variant, or a whole or fragment (or multiple fragments) of a combination thereof. Full-length antibodies can be, for example, monoclonal antibodies, recombinant antibodies, chimeric antibodies, deimmunized antibodies, humanized antibodies, and human antibodies. Examples of full-length antibody fragments include, but are not limited to, variable heavy chains (VH), variable light chains (VL), and heavy chains (VHH or V) found in camelids such as camels, llamas, and alpacas. H Examples include heavy chains (V-NAR domains) found in sharks, single-domain antibodies containing a single antigen-binding domain (sdAb, i.e., "nanobodies"), Fv, Fd, Fab, Fab', F(ab')2, and "r IgG" (or half-antibodies). Examples of modified antibody fragments, though not limited to these, include scFv, di-scFv or bi(s)scFv, scFv-Fc, scFv-zipper, scFab, Fab2, Fab3, diabody, single-stranded diabody, tandem diabody (Tandab's), tandem di-scFv, tandem tri-scFv, minibody (e.g., (VH-VL-CH3)2, (scFv-CH3)2, ((scFv)2-CH3+CH3), ((scFv)2-CH3) or (scFv-CH3-scFv)2), and multibody (e.g., triabody or tetrabody).

[0144] The terms “antibody (singular)” and “antibody (plural)” encompass any antigen-binding unit, including, but not limited to, monoclonal antibodies, human antibodies, humanized antibodies, camelized antibodies, chimeric antibodies, and any other epitope-binding fragments.

[0145] The term "in vivo" refers to events that occur within the body of a subject.

[0146] The term "ex vivo" refers to the initial events that occur outside the body of a subject for the purpose of subsequent in vivo administration into the subject's body. For example, ex vivo preparation may include preparing cells outside the body of a subject for the purpose of introducing the prepared cells into the body of the same or a different subject.

[0147] The term "in vitro" refers to events that occur outside the body of the subject. For example, in vitro An assay encompasses any assay performed outside the body of the subject. An in vitro assay encompasses cell-based assays that use live or dead cells. An in vitro assay also encompasses cell-free assays that do not use intact cells.

[0148] The term “Ras” or “RAS” refers to the rat sarcoma (Ras) superfamily of small GTPases, such as the Ras subfamily. The Ras superfamily includes, but is not limited to, the Ras subfamily, 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 used interchangeably herein as K-Ras, K-ras, and 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, e.g., KRAS, HRAS, NRAS, RALA, RALB, and any combination thereof.

[0149] The terms “mutant Ras” and “Ras mutant,” when used interchangeably herein, refer to a Ras protein having one or more amino acid mutations with respect to a common reference sequence, such as a wild-type (WT) sequence. In some embodiments, mutant Ras is selected from mutant KRAS, mutant HRAS, mutant NRAS, mutant MRAS, mutant ERAS, mutant RRAS2, mutant RALA, mutant RALB, mutant RIT1, and any combination thereof, e.g., mutant KRAS, mutant HRAS, mutant NRAS, mutant RALA, mutant RALB, and any combination thereof. In some embodiments, the mutation may be an introduced mutation, a naturally occurring mutation, or a mutation that does not exist naturally. In some embodiments, the mutation may be a substitution (e.g., a substituted amino acid), an insertion (e.g., the addition of one or more amino acids), or a deletion (e.g., the removal of one or more amino acids). In some embodiments, two or more mutations may be consecutive, discontinuous, or a combination thereof. In some embodiments, the mutation may be located at any position in Ras. In some embodiments, mutations may be located at position 12, 13, 62, 92, 95, or any combination thereof, relative to the optimally aligned sequence number 1 of Ras. In some embodiments, the mutant Ras may contain approximately or at least 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 approximately 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 may have an amino acid length of approximately or up to approximately 500, 400, 300, 250, 240, 233, 230, 220, 219, 210, 208, 206, 204, 200, 195, 190, 189, 188, 187, 186, 185, 180, 175, 174, 173, 172, 171, 170, 169, 168, 167, 166, 165, 160, 155, 150, 125, 100, 90, 80, 70, 60, 50, or less than 50. In some embodiments, the mutant amino acid may be a protein constituent amino acid, a native 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-native 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 includes a reactive moiety. In some embodiments, the substituted amino acids constitute a reactive moiety. In some embodiments, mutant Ras can be further modified, such as by conjugation with a detectable label. In some embodiments, mutant Ras is a full-length or truncated polypeptide. For example, mutant Ras may be a truncated polypeptide comprising residues 1-169 or residues 11-183 (e.g., residues 11-183 of mutant RALA or mutant RALB). compound

[0150] Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or their pharmaceutically acceptable salts or solvates, are Ras modifiers (including Ras inhibitors) and have a wide range of applications in therapeutic, diagnostic, and other biomedical research.

[0151] In some embodiments, the compound of formula (I): [ka] (In the formula, [ka] R is absent, a 3-12 membered heterocycloalkyl ring, a 6-10 membered aryl ring, a 5-10 membered heteroaryl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring, 6-10 membered aryl ring, 5-10 membered heteroaryl ring, and 3-12 membered cycloalkyl ring have 1 or more R 10 It is replaced as needed; [ka] is absent, a 3-12 membered heterocycloalkyl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring and the 3-12 membered cycloalkyl ring have 1 or more R 11 It is replaced as needed; A is a bond, O, S, N(R) 1e ), or C(R 1f )(R 1g ) and; Q 1 is N or C(R 1d ) and; Q 2 is either S or O; X is either C or N; Y is C, S(O), S(O)2, C(O), or N; U is C, S(O), S(O)2, C(O), or N; Z is N or C(R 8 ) and; V and J are N, C(R 5 ), and C(R 16 ) is selected independently from, and one of V and J is C(R 5 ) and; W is N or C(R 18 ) and; L 1 and L 2This is a bond, C1-C6 alkyl, -O-, -N(R 26 )-, -C(O)-, -N(R 26 )C(O)-, -C(O)N(R 26 )-, -S-, -S(O)2-, -S(O)-, -S(O)2N(R 26 ), -S(O)N(R 26 ), -N(R 26 )S(O)-, -N(R 26 )S(O)2-,-OCON(R 26 )-,-N(R 26 )C(O)O-, and -N(R 26 )C(O)N(R 26 )- Selected independently of; R 1 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(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 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , and R 1g Hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) are independently selected from each, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; or R 1a and R 1b These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1b and R 1c These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1f and R 1gThese rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; R 2 Halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15, and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20b It is replaced as needed; Each R 3 These are hydrogen, halogen, oxo, C1-C6 alkyl, C1-C6 haloalkyl, -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 Selected independently from; R 4 This refers to a group other than the electrophilic moiety that can form a covalent bond with hydrogen or the cysteine ​​residue at position 12 of the KRAS protein; R 5 teeth [ka] and; R 8 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20c It is replaced as needed; Each R 10 and each R 11 These include halogens, oxo, C1-C6 alkyl, C1-C6 haloalkyl, and -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; Each R 12 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C6 ~10 Aryl, and C 1~9 Selected independently from heteroaryls, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20d It is replaced as needed; Each R 13 is hydrogen, C 1~6 Alkyl, and C 1~6 Selected independently of haloalkyl; or R 12 and R 13 These, together with the nitrogen they are bonded to, form one, two, or three R atoms. 20e C replaced as needed 2~9 Forming a heterocycloalkyl ring; Each R 14 is hydrogen, C 1~6 Alkyl, and C 1~6 Independently selected from haloalkyl groups; Each R 15 C is selected independently 1~6 Alkyl, C 2~6Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 It is a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20f It is replaced as needed; R 16 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13)-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20g It is replaced as needed; R 18 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(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(R14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20h It is replaced as needed; Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , and R 20i Halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, C 1~9 Heteroaryl, -OR 21 , -SR 2 1 , -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 ), -OCH2C(O)OR 22 , and -OC(O)R 25 Each is independently selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, 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 )(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 It is replaced as needed with one, two, or three elements selected independently from it; Each R 21 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 22 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 23 H and C 1~6 Selected independently of alkyl; Each R 24 H and C 1~6 Selected independently of alkyl; Each R 25 C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9Selected from heteroaryls; Each R 26 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20i It is replaced as needed; n is 0, 1, or 2; [ka] (This indicates a single or double bond in which all valencies are satisfied.) Alternatively, pharmaceutically acceptable salts or solvates thereof are provided.

[0152] In some embodiments, the structure of formula (Ia) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0153] In some embodiments, the structure of formula (Ib) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0154] In some embodiments, V is C(R 16Compounds of formula (I), (Ia), or (Ib), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, compounds of formula (I), (Ia), or (Ib), or pharmaceutically acceptable salts or solvates thereof, are provided, where V is C(H). In some embodiments, compounds of formula (I), (Ia), or (Ib), or pharmaceutically acceptable salts or solvates thereof, are provided, where V is N.

[0155] In some embodiments, the structure of formula (Ic) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0156] In some embodiments, the structure of formula (Id) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0157] In some embodiments, J is C(R 16 A compound of formula (Ic) or (Id), or a pharmaceutically acceptable salt or solvate thereof, is provided, wherein J is C(H). In some embodiments, a compound of formula (Ic) or (Id), or a pharmaceutically acceptable salt or solvate thereof, is provided, wherein J is N.

[0158] In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), or (Id), or pharmaceutically acceptable salts or solvates thereof, are provided, where X is C. In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), or (Id), or pharmaceutically acceptable salts or solvates thereof, are provided, where X is N. To be served.

[0159] In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), or (Id), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is C. In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), or (Id), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is N. In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), or (Id), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is C(O).

[0160] In some embodiments, the structure of formula (Ie) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0161] In some embodiments, the structure of expression (If) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0162] In some embodiments, the structure of formula (Ig) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0163] In some embodiments, the structure of formula (Ih) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0164] In some embodiments, the structure of equation (Ii) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0165] In some embodiments, the structure of formula (Ij) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0166] In some embodiments, the structure of formula (Ik) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0167] In some embodiments, the structure of formula (Im) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0168] In some embodiments, the structure of formula (In): [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0169] In some embodiments, the structure of formula (Io) is: [ka] A compound of formula (I) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0170] In some embodiments, V is C(R 16 Compounds of formula (I), (Ie), (If), (Ig), (Ih), or (Ii), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, compounds of formula (I), (Ie), (If), (Ig), (Ih), or (Ii), or pharmaceutically acceptable salts or solvates thereof, are provided, where V is C(H). In some embodiments, compounds of formula (I), (Ie), (If), (Ig), or (Ih), or pharmaceutically acceptable salts or solvates thereof, are provided, where V is N.

[0171] In some embodiments, J is C(R 16 Compounds of formula (I), (Ij), (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, compounds of formula (I), (Ij), (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided, where J is C(H). In some embodiments, compounds of formula (I), (Ii), (Ij), (Ik), or (Im), or pharmaceutically acceptable salts or solvates thereof, are provided, where J is N.

[0172] In some embodiments, W is C(R 18Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided, where W is N.

[0173] In some embodiments, Z is C(R 8 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), or (Io), or pharmaceutically acceptable salts or solvates thereof, are provided, where Z is N.

[0174] In another embodiment, the present disclosure relates to a compound of formula (II): [ka] (In the formula, [ka] R is absent, a 3-12 membered heterocycloalkyl ring, a 6-10 membered aryl ring, a 5-10 membered heteroaryl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring, 6-10 membered aryl ring, 5-10 membered heteroaryl ring, and 3-12 membered cycloalkyl ring have 1 or more R 10 It is replaced as needed; [ka] is absent, a 3-12 membered heterocycloalkyl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring and the 3-12 membered cycloalkyl ring have 1 or more R 11 It is replaced as needed; A is a bond, O, S, N(R) 1e ), or C(R 1f )(R 1g ) and; Q 1 is N or C(R 1d ) and; Q 2 is either S or O; X is either C or N; Y is C, C(O), or N; Z 1 is N or C(R 6 ) and; Z 2 is N(R 7 ) or C(R 8 )(R 9 ) and; Z 3 is non-existent, N(R) 17 ), or C(R 27 )(R 28 ) and; U is C, S(O), S(O)2, C(O), or N; L 1 and L 2 This is a bond, C1-C6 alkyl, -O-, -N(R 26 )-, -C(O)-, -N(R 26 )C(O)-, -C(O)N(R 26 )-, -S-, -S(O)2-, -S(O)-, -S(O)2N(R 26 ), -S(O)N(R 26 ), -N(R 26 )S(O)-, -N(R 26 )S(O)2-,-OCON(R 26 )-,-N(R 26 )C(O)O-, and -N(R 26 )C(O)N(R 26 )- Selected independently of; R1 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 1~9 Heteroaryl, -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 1 4 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , and R 1g Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15, and -CH2S(O)2N(R 12 )(R 13 ) are independently selected from each, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; or R 1a and R 1b These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1b and R 1c These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1f and R 1g These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; R 2 Halogen, -CN, C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20b It is replaced as needed; Each R 3 These include hydrogen, halogens, oxo, C1-C6 alkyl, and C1-C6 haloalkyl. -OR 12, -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; R 4 This refers to a group other than the electrophilic moiety that can form a covalent bond with hydrogen or the cysteine ​​residue at position 12 of the KRAS protein; R 5 teeth [ka] and; R 6 is hydrogen and C 1~6 Selected from alkyl groups; R 7 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -C(O)OR 12 , -C(O)R 15 ,-S(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected from, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R20c It is replaced as needed; R 8 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20c It is replaced as needed; R 9 is hydrogen and C 1~6 Selected from alkyl groups; Each R 10 and each R 11 These include halogens, oxo, C1-C6 alkyl, C1-C6 haloalkyl, and -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; Each R 12 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20d It is replaced as needed; Each R 13 is hydrogen, C 1~6 Alkyl, and C 1~6 Selected independently of haloalkyl; or R 12 and R 13 These, together with the nitrogen they are bonded to, form one, two, or three R atoms. 20e C replaced as needed 2~9 Forming a heterocycloalkyl ring; Each R 14 is hydrogen, C 1~6 Alkyl, and C 1~6 Independently selected from haloalkyl groups; Each R 15 C is selected independently 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 It is a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20f It is replaced as needed; R 16 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20g It is replaced as needed; R 17 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -C(O)OR 12 , -C(O)R 15 ,-S(O)R15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected from, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20k It is replaced as needed; R 18 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(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 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20h It is replaced as needed; Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , R 20i , R 20j , and R 20k Halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, C 1~9 Heteroaryl, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 ,-C(O)N(R 22 )(R23 ), -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 Each is independently selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, 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 )(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 It is replaced as needed with one, two, or three elements selected independently from it; Each R 21 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 22 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 23 H and C 1~6 Selected independently of alkyl; Each R 24 H and C 1~6 Selected independently of alkyl; Each R 25 C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected from heteroaryls; Each R 26 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20i It is replaced as needed; R 27 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(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)R15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20j as needed It has been replaced; R 28 is hydrogen and C 1~6 Selected from alkyl groups; n is 0, 1, or 2; [ka] (This indicates a single or double bond in which all valencies are satisfied.) The present invention provides a pharmaceutically acceptable salt or solvate thereof.

[0175] In some embodiments, Q 1 If N is Q 2 A compound of formula (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, is provided, wherein Q is S. In some embodiments, Q 1 If N is Q 2 A compound of formula (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, is provided, wherein Q is O. In some embodiments, 1 is C(R 1d ) and Q2 A compound of formula (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, is provided, wherein Q is S. In some embodiments, Q 1 is C(R 1d ) and Q 2 A compound of formula (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, is provided, wherein the compound is O.

[0176] In some embodiments, the structure of formula (IIa) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0177] In some embodiments, the structure of formula (IIb) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0178] In some embodiments, Z 2 is C(R 8 )(R 9 A compound of formula (II), (IIa), or (IIb), or a pharmaceutically acceptable salt or solvate thereof, is provided. In some embodiments, R 9 Compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, where is hydrogen, are provided.

[0179] In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where X is C. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where X is N.

[0180] In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where Y is C. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where Y is N. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where Y is C(O).

[0181] In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is C. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is N. In some embodiments, compounds of formula (II), (IIa), or (IIb), or pharmaceutically acceptable salts or solvates thereof, are provided, where U is C(O).

[0182] In some embodiments, the structure of formula (IIc) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0183] In some embodiments, the structure of formula (IId) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0184] In some embodiments, the structure of formula (IIe) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0185] In some embodiments, the structure of the expression (IIf) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0186] In some embodiments, the structure of formula (IIg) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0187] In some embodiments, the structure of formula (IIh) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0188] In some embodiments, the structure of formula (IIi) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0189] In some embodiments, the structure of formula (IIj) is: [ka] A compound of formula (II) having the same as a pharmaceutically acceptable salt or solvate is provided.

[0190] In some embodiments, R 1 However, hydrogen, -N(R 12 )(R13 ), and one, two, or three R 20a C replaced as needed 1~6 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, selected from alkyl groups. In some embodiments, R 1 ga-N(R 12 )(R 13 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 1 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where R is -NH2. In some embodiments, R 1 However, one, two, or three R 20a C replaced as needed 1~6 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are alkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R1 is non-substituted C 1~6 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are alkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 1 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, where is -CH3, are provided. In that embodiment, R 1 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein (I) is hydrogen.

[0191] In some embodiments, R 1 ga-N(R 14 )C(O)R 15 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 1 -N(H)C(O)R 15 And R15 However, one, two, or three R 20f C replaced as needed 1~9 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are heteroaryl compounds, or pharmaceutically acceptable salts or solvates thereof.

[0192] In some embodiments, R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , and R 1g However, hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14)C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) are independently selected from each, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 A heteroaryl group has one, two, or three R 20a Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary.

[0193] In some embodiments, R 1a , R 1b , and R 1c However, hydrogen, halogens, and one, two, or three R 20a C replaced as needed 1~6Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, each independently selected from alkyl groups. In some embodiments, R 1a , R 1b , and R 1c However, hydrogen and one, two, or three R 20a C replaced as needed 1~6 Formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa) are independently selected from alkyl groups. Compounds of (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 1a , R 1b , and R 1c Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where each is hydrogen.

[0194] In some embodiments, R 1a and R 1b is hydrogen, R 1c -N(H)C(O)R 15Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 1a and R 1b is hydrogen, R 1c -N(H)C(O)R 15 And R 15 However, one, two, or three R 20f C replaced as needed 1~9 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, R 1a and R 1c is hydrogen, R 1b -N(H)C(O)R 15 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 1a and R 1c is hydrogen, R 1b -N(H)C(O)R 15 And R 15 However, one, two, or three R 20f C replaced as needed 1~9Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, R 1b and R 1c is hydrogen, R 1a -N(H)C(O)R 15 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 1b and R 1c is hydrogen, R 1a -N(H)C(O)R 15 And R 15 However, one, two, or three R 20f C replaced as needed 1~9 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are heteroaryl compounds, or pharmaceutically acceptable salts or solvates thereof.

[0195] In some embodiments, Q 1 is C(R 1d ), the formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij) Compounds of (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 1d However, hydrogen and one, two, or three R 20a C replaced as needed 1~6 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, selected from alkyl groups, are provided. In some embodiments, Q 1 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where N is N.

[0196] In some embodiments, [ka] However, R is 1 or greater than 1. 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered heterocycloalkyl rings optionally substituted with . In some embodiments, [ka] R is selected from piperazinyl and piperidinyl, and piperazinyl and piperidinyl are present in 1 or more R values. 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, R is 1 or greater than 1. 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are piperazinyl compounds substituted as needed. In some embodiments, [ka] However, R is 1 or greater than 1. 11 The piperidinyl compounds are as needed, as shown in formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih Compounds of (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, [ka] However, the R is a 3- to 12-membered heterocycloalkyl ring selected from spirocyclic heterocycloalkyl rings and fused heterocycloalkyl rings, and the spirocyclic heterocycloalkyl ring and fused heterocycloalkyl ring have 1 or more R 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, R is 1 or greater than 1. 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered spirocyclic heterocycloalkyl rings substituted as needed. In some embodiments, [ka] However, R is 1 or greater than 1. 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered condensed heterocycloalkyl rings optionally substituted with . [ka] However, R is 1 or greater than 1. 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered cycloalkyl rings optionally substituted with . In some embodiments, [ka] However, R is 1 or greater than 1. 11 Formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg) are cyclohexyl rings substituted as needed. Compounds of (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, [ka] However, the R is a 3- to 12-membered cycloalkyl ring selected from a spirocyclic cycloalkyl ring and a fused cycloalkyl ring, and the spirocyclic cycloalkyl ring and the fused cycloalkyl ring are 1 or more R 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, R is 1 or greater than 1. 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered spirocyclic cycloalkyl rings substituted as needed. In some embodiments, [ka] However, R is 1 or greater than 1. 11 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered condensed cycloalkyl rings optionally substituted with . [ka] Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, in which the element is absent.

[0197] In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered heterocycloalkyl rings optionally substituted with . In some embodiments, [ka] R is selected from piperazinyl and piperidinyl, and piperazinyl and piperidinyl are present in 1 or more R values. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are piperidinyl as needed. In some embodiments, [ka] However, R is 1 or greater than 1. 10Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are piperazinyl compounds substituted as needed. In some embodiments, [ka] However, the R is a 3- to 12-membered heterocycloalkyl ring selected from spirocyclic heterocycloalkyl rings and fused heterocycloalkyl rings, and the spirocyclic heterocycloalkyl ring and fused heterocycloalkyl ring have 1 or more R 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered spirocyclic heterocycloalkyl rings substituted as needed. In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered condensed heterocycloalkyl rings optionally substituted with . [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered cycloalkyl rings optionally substituted with . In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where the cyclohexyl ring is optionally substituted with . In some embodiments, [ka] However, the R is a 3- to 12-membered cycloalkyl ring selected from a spirocyclic cycloalkyl ring and a fused cycloalkyl ring, and the spirocyclic cycloalkyl ring and the fused cycloalkyl ring are 1 or more R 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered spirocyclic cycloalkyl rings substituted as needed. In some embodiments, [ka] However, R is 1 or greater than 1. 10 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are 3- to 12-membered condensed cycloalkyl rings optionally substituted with . [ka] Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, in which the element is absent.

[0198] In some embodiments, L 1 However, the bond, C1~C6 alkyl, -N(R 26 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, selected from - and -C(O)-. In some embodiments, L 1 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, in which L is a bond. In some embodiments, L 1 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein the base is C1-C6 alkyl.

[0199] In some embodiments, L 2However, compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, selected from bond, C1-C6 alkyl, and -C(O)-. In some embodiments, L 2 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, in which L is a bond. In some embodiments, L 2 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein the base is C1-C6 alkyl.

[0200] In some embodiments, R 2 However, hydrogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , and -N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9One, two, or three heteroaryl R 20b Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, R 2 However, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , and -N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 One, two, or three heteroaryl R 20b Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, R 2 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), where is hydrogen, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 2 However, one, two, or three R 20b C replaced as needed 1~6Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are alkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 2 is non-substituted C 1~6 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are alkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 2 However, one, two, or three R 20b C replaced as needed 3~6 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are cycloalkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 2 However, one, two, or three R 20b C replaced as needed 2~9 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are heterocycloalkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 2 However, one, two, or three R 20b C replaced as needed 6~10Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are aryl compounds, or pharmaceutically acceptable salts or solvates thereof. In some embodiments, R 2 However, one, two, or three R 20b C replaced as needed 1~9 These are heteroaryl compounds, given by formulas (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf) Compounds of (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided.

[0201] In some embodiments, R 2 ga-OR 12 , -SR 12 , and -N(R 12 )(R 13 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, selected from ). In some embodiments, R 2 ga-OR 12 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 2 ga-SR 12Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 2 ga-N(R 12 )(R 13 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 12 However, C 1~6 Alkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Selected from heteroaryls, C 1~6 Alkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 One, two, or three heteroaryl R 20d Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, R 12 However, one, two, or three R 20d C replaced as needed 1~6Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are alkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 12 However, one, two, or three R 20d C replaced as needed 2~9 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are heterocycloalkyl, or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 12 However, one, two, or three R 20d -CH2-C substituted as needed 2~9 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), selected from heterocycloalkyls, or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, R 12 However, one, two, or three R 20d C replaced as needed 6~10 Aryl, formula (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), Alternatively, compounds of (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 12 However, one, two, or three R 20d -CH2-C substituted as needed 6~10Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), which are aryl compounds, or pharmaceutically acceptable salts or solvates thereof. In some embodiments, R 12 However, one, two, or three R 20d C replaced as needed 1~9 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj) that are heteroaryl compounds, or pharmaceutically acceptable salts or solvates thereof are provided.

[0202] In some embodiments, R 2 but [ka] [ka] Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (If), (Ig), (Ih), (Ij), (Ik), (Im), (II), (IIa), (IIb), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, selected from the above.

[0203] In some embodiments, L 1 However, the bond, C1~C6 alkyl, -N(R 26Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, selected from - and -C(O)-. In some embodiments, L 1 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, in which L is a bond. In some embodiments, L 1 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where is a C1-C6 alkyl group. In some embodiments, L 1 ga-N(R 26 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, L 1Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein L 1 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein the base is -C(O)-.

[0204] In some embodiments, R 1 However, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , and -N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 One, two, or three heteroaryl R 20a Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, with substitution as necessary. In some embodiments, R 1However, one, two, or three R 20a C replaced as needed 1~6 Alkyl compounds, formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), Compounds of (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided. In some embodiments, R 1 is one R 20a C replaced as needed 1~6 It is alkyl, R 20a However, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected from heteroaryls, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls are 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 )(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)2R25 , -C(O)R 25 -S(O)2R 25 -S(O)2N(R 22 )(R 23 ), and -OC(O)R 25 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are optionally substituted with one, two, or three groups independently selected from R. 1 is one R 20a C replaced as needed 1~6 It is alkyl, R 20a However, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected from heteroaryls, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, in which the heteroaryl is unsubstituted. In some embodiments, R 1 is one R 20a C replaced by 1~6 It is alkyl, R 20a is non-substituted C 2~9Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided.

[0205] In some embodiments, R 8 However, hydrogen, halogen, -CN, C 1~6 Alkyl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), and -C(O)OR 12 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, selected from R. 8 However, compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, selected from hydrogen, halogen, -CN, CF3, -OH, or -SH. 8 is chloroform, formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (I Compounds of i), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof are provided. In some embodiments, R 8 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein R is fluoro. In some embodiments, R 8 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein (I) is hydrogen.

[0206] In some embodiments, R 16 However, hydrogen, halogen, -CN, C 1~6 Alkyl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), and -C(O)OR 12 Compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, selected from R. 16However, compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, selected from hydrogen, halogen, -CN, CF3, -OH, or -SH. 16 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein R is chloro. In some embodiments, R 16 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein R is fluoro. In some embodiments, R 16 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein (I) is hydrogen.

[0207] In some embodiments, R 18 However, hydrogen, halogen, -CN, C 1~6 Alkyl, -OR 12 , -SR 12 , -N(R 12)(R 13 ), and -C(O)OR 12 A compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), selected from the above, or its pharmaceutically acceptable properties. A salt or solvate that can be tolerated is provided. In some embodiments, R 18 However, compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, selected from hydrogen, halogen, -CN, CF3, -OH, or -SH. 18 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein R is chloro. In some embodiments, R 18 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein R is fluoro. In some embodiments, R 18Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, wherein (I) is hydrogen.

[0208] In some embodiments, R 4 Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where is hydrogen. In some embodiments, R 4 However, compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, which are groups other than the electrophilic moiety that can form a covalent bond with the cysteine ​​residue at position 12 of the KRAS protein. 4 However, -H, -NH2, -OH, -NH(C 1~6 Alkyl), [ka] [ka] Compounds of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Im), (In), (Io), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIj), or pharmaceutically acceptable salts or solvates thereof, are provided, where m is 0, 1, 2, or 3, if present.

[0209] In some embodiments, [ka] A compound selected from the above; or a pharmaceutically acceptable salt or solvate thereof is provided.

[0210] In some embodiments, [ka] [ka] A compound selected from the above; or a pharmaceutically acceptable salt or solvate thereof is provided.

[0211] In this embodiment, the compound is of formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c ,A,V,Z,W,X,Y,U,R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ia', Z, X, and U are not all N at the same time. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, J, Z, W, X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ih', Z is not N. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , R 3 , L 2 , and R 4The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , L 2 , and R 4 The embodiment includes (as described herein, including any embodiment). The compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18, Z 1 , Z 2 , Z 3 X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , Z 2 , Z 3 X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , Z 2 , Z 3 X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c ,A,V,Z,W,X,Y,U,R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ia'', Z, X, and U are not all N at the same time. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, J, Z, W, X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ih'', Z is not N. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 Q 2 , R 1, R 1a , R 1b , R 1c A, V, Z, W, R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , R 3 , L 2 , and R 4 (This includes any embodiments as described herein.) In this embodiment, the compound is of formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , Z 1 , Z 2 , Z 3 X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R1a , R 1b , R 1c , A, R 16 , R 18 , Z 2 , Z 3 X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , Z 2 , Z 3 X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c ,A,V,Z,W,X,Y,U,R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, J, Z, W, X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1, R 1a , R 1b , R 1c A, V, Z, W, R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ih''', Z is not N. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , L 2 , and R 4 This includes any embodiments as described herein. In this state, the compound is, formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2, L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , Z 1 , Z 2 , Z 3 X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , Z 2 , Z 3 X, Y, U, R 2 , R 3 ,n,L 2 , and R4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , Z 2 , Z 3 X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 (This includes any embodiments as described herein.)

[0212] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] That is the case.

[0213] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] That is the case.

[0214] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In this embodiment, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] In some embodiments, R 5 but [ka] That is the case.

[0215] In this embodiment, R 1 However, hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -C(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -CH2C(O)N(R 12 )(R 13 ), and -CH2N(R 14 )C(O)R 15 Selected from, C 1~6 Alkyl, C 2~6 Alkenyl and C 2~6 Alkinyl has one, two, or three R 20a It is replaced as needed.

[0216] In this embodiment, R 1 is hydrogen and -N(R 12 )(R 13 ) will be selected from.

[0217] In this embodiment, R 1d However, hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected independently of C 1~6 Alkyl, C 2~6Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 A heteroaryl group has one, two, or three R 20a It is replaced as needed. In the embodiment, R 1d However, hydrogen, -CN, C 1~6 Alkyl, and C 1~6 Independently selected from haloalkyls, C 1~6 Alkyl is one, two, or three R 20a It is replaced as needed.

[0218] In some embodiments, A is a bond. In some embodiments, A is O. In some embodiments, A is C(R 1f )(R 1g ) In some embodiments, A is CH2.

[0219] In the embodiment, the compound is [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] Selected from.

[0220] In one embodiment, the present disclosure relates to a compound of formula (A): [ka] (In the formula, [ka] R is absent, a 3-12 membered heterocycloalkyl ring, a 6-10 membered aryl ring, a 5-10 membered heteroaryl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring, 6-10 membered aryl ring, 5-10 membered heteroaryl ring, and 3-12 membered cycloalkyl ring have 1 or more R 10 It is replaced as needed; [ka] is absent, a 3-12 membered heterocycloalkyl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring and the 3-12 membered cycloalkyl ring have 1 or more R 11 It is replaced as needed; A is a bond, O, S, N(R) 1e ), or C(R 1f )(R 1g ) and; Q 1 is N or C(R 1d ) and; Q 2 is either S or O; X is either C or N; Y is C, S(O), S(O)2, C(O), or N; U is C, S(O), S(O)2, C(O), or N; Z is N or C(R 8 ) and; V and J are N, C(R 5 ), and C(R 16 ) is selected independently from, and one of V and J is C(R 5 ) and; W is N or C(R 18 ) and; L 1 and L 2 This is a bond, C1-C6 alkyl, -O-, -N(R 26 )-, -C(O)-, -N(R 26 )C(O)-, -C(O)N(R 26 )-, -S-, -S(O)2-, -S(O)-, -S(O)2N(R 26 ), -S(O)N(R 26 ), -N(R 26 )S(O)-, -N(R 26 )S(O)2-,-OCON(R 26 )-,-N(R 26 )C(O)O-, and -N(R 26 )C(O)N(R 26 )- Selected independently of; R 1 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14)C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , and R 1g Hydrogen, halogen, -CN, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15, -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) are independently selected from each, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; or R 1a and R 1b These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1b and R 1c These combine to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and consist of a 4-7 member heterocycloalkyl ring, a phenyl ring, and a 5-6 member heteroaryl ring. A ring, or a 4- to 7-membered cycloalkyl ring, has one, two, or three R 20a It is replaced as needed; or R 1f and R 1g These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; R 2 Halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20b It is replaced as needed; Each R 3 These are hydrogen, halogen, oxo, C1-C6 alkyl, C1-C6 haloalkyl, -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 Selected independently from; R 4 This refers to a group other than the electrophilic moiety that can form a covalent bond with hydrogen or the cysteine ​​residue at position 12 of the KRAS protein; R 5 teeth [ka] and; R 8 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20c It is replaced as needed; Each R 10 and each R 11 These include halogens, oxo, C1-C6 alkyl, and C1-C6 ammonium compounds. Kill-CN, C1-C6 haloalkyl, -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; Each R 12 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, C 1~9 Heteroaryls, and -CH2-C 1~9 Selected independently from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, -CH2-C 1~9 Heteroaryls, and C 1~9 Heteroaryls have one, two, or three R 20d It is replaced as needed; Each R 13 is hydrogen, C 1~6 Alkyl, and C 1~6 Selected independently of haloalkyl; or R 12 and R 13 These, together with the nitrogen they are bonded to, form one, two, or three R atoms. 20eC replaced as needed 2~9 Forming a heterocycloalkyl ring; Each R 14 is hydrogen, C 1~6 Alkyl, and C 1~6 Independently selected from haloalkyl groups; Each R 15 C is selected independently 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 It is a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20f It is replaced as needed; R 16 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15-OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20g It is replaced as needed; R 18 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ant , and C 1~9 Heteroaryls have one, two, or three R 20h It is replaced as needed; Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R 20h , and R 20i Halogen, oxo, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, C 1~9 Heteroaryl, -CH2-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 Each is independently selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, -CH2-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, C1~6 Haloalkoxy, -OR 21 , -SR 21 , -N(R 22 )(R 23 ), -C(O)OR 22 ,-C(O)N(R 22 )(R 23 ), -C(O)C(O)N(R 22 )(R 23 ), -OC(O)N(R 22 )(R 23 ), -N(R 24 )C(O)N(R 22 )(R 23 ), -N(R 24 )C(O)OR 25 , -N(R 24 )C(O)R 25 , -N(R 24 )S(O)2R 25 , -C(O)R 25 -S(O)2R 25 -S(O)2N(R 22 )(R 23 ), and -OC(O)R 25 It is replaced as needed with one, two, or three elements selected independently from it; Each R 21 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 22 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 23H and C 1~6 Selected independently of alkyl; Each R 24 H and C 1~6 Selected independently of alkyl; Each R 25 C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected from heteroaryls; Each R 26 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20i It is replaced as needed; n is 0, 1, or 2; [ka] (This indicates a single or double bond in which all valencies are satisfied.) The present invention provides a pharmaceutically acceptable salt or solvate thereof.

[0221] In another aspect, the present disclosure relates to a compound of formula (B): [ka] (In the formula, [ka] R is absent, a 3-12 membered heterocycloalkyl ring, a 6-10 membered aryl ring, a 5-10 membered heteroaryl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring, 6-10 membered aryl ring, 5-10 membered heteroaryl ring, and 3-12 membered cycloalkyl ring have 1 or more R 10 It is replaced as needed; [ka] is absent, a 3-12 membered heterocycloalkyl ring, or a 3-12 membered cycloalkyl ring, and the 3-12 membered heterocycloalkyl ring and the 3-12 membered cycloalkyl ring have 1 or more R 11 It is replaced as needed; A is a bond, O, S, N(R) 1e ), or C(R 1f )(R 1g ) and; Q 1 is N or C(R 1d ) and; Q 2 is either S or O; X is either C or N; Y is C, C(O), or N; Z 1 is N or C(R 6 ) and; Z 2 is N(R 7 ) or C(R 8 )(R 9 ) and; Z 3 is non-existent, N(R) 17 ), or C(R 27 )(R 28 ) and; U is C, S(O), S(O)2, C(O), or N; L 1 and L 2 This is a bond, C1-C6 alkyl, -O-, -N(R 26 )-, -C(O)-, -N(R 26)C(O)-, -C(O)N(R 26 )-, -S-, -S(O)2-, -S(O)-, -S(O)2N(R 26 ), -S(O)N(R 26 ), -N(R 26 )S(O)-, -N(R 26 )S(O)2-,-OCON(R 26 )-,-N(R 26 )C(O)O-, and -N(R 26 )C(O)N(R 26 )- Selected independently of; R 1 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(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(R12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , and R 1g Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(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 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) are independently selected from each, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20a It is replaced as needed; or R 1a and R 1b These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1b and R 1c These rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; or R 1f and R 1gThese rings bond to form a 4-7 member heterocycloalkyl ring, a phenyl ring, a 5-6 member heteroaryl ring, or a 4-7 member cycloalkyl ring, and the 4-7 member heterocycloalkyl ring, phenyl ring, 5-6 member heteroaryl ring, or 4-7 member cycloalkyl ring has one, two, or three R atoms. 20a It is replaced as needed; R 2 Halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15, and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20b It is replaced as needed; Each R 3 These are hydrogen, halogen, oxo, C1-C6 alkyl, C1-C6 haloalkyl, -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 , -OC(O)N (R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; R 4 This refers to a group other than the electrophilic moiety that can form a covalent bond with hydrogen or the cysteine ​​residue at position 12 of the KRAS protein; R 5 teeth [ka] and; R 6 is hydrogen and C 1~6 Selected from alkyl groups; R 7 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -C(O)OR 12 , -C(O)R 15,-S(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected from, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20c It is replaced as needed; R 8 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15-S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20c It is replaced as needed; R 9 is hydrogen and C 1~6 Selected from alkyl groups; Each R 10 and each R 11 These include halogens, oxo, C1-C6 alkyl, C1-C6 alkyl-CN, C1-C6 haloalkyl, and -OR 12 , -N(R 12 )(R 13 ), -CN, -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -C(O)R 15 -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected independently of; Each R 12 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, C 1~9 Heteroaryls, and -CH2-C 1~9 Selected independently from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, -CH2-C 1~9 Heteroaryl and C 1~9 Heteroaryls have one, two, or three R 20d It is replaced as needed; Each R 13 is hydrogen, C 1~6 Alkyl, and C 1~6 Selected independently of haloalkyl; or R 12 and R 13 These, together with the nitrogen they are bonded to, form one, two, or three R atoms. 20e C replaced as needed 2~9 Forming a heterocycloalkyl ring; Each R 14 is hydrogen, C 1~6 Alkyl, and C 1~6 Independently selected from haloalkyl groups; Each R 15 C is selected independently 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 It is a heteroaryl, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20f It is replaced as needed; R 16 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20g It is replaced as needed; R 17 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -C(O)OR 12 , -C(O)R 15 ,-S(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -S(O)2R 15 , and -S(O)2N(R 12 )(R 13 )- Selected from, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20k It is replaced as needed; R 18 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, 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 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20h It is replaced as needed; Each R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , R 20g , R20h , R 20i , R 20j and R 20k Halogen, oxo, -CN, C 1~6 Alki Ru, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, C 1~9 Heteroaryl, -CH2-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 Each is independently selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Ariel, -CH2-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 )(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 It is replaced as needed with one, two, or three elements selected independently from it; Each R 21 H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 22H, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls; Each R 23 H and C 1~6 Selected independently of alkyl; Each R 24 H and C 1~6 Selected independently of alkyl; Each R 25 C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Selected from heteroaryls; Each R 26 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Aryl, and C 1~9 Heteroaryls have one, two, or three R 20i It is replaced as needed; R 27 Hydrogen, halogen, -CN, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C2~9 Heterocycloalkyl, C 6~10 Ariel, C 1~9 Heteroaryl, -OR 12 , -SR 12 , -N(R 12 )(R 13 ), -C(O)OR 12 ,-OC(O)N(R 12 )(R 13 ), -N(R 14 )C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)OR 15 , -N(R 14 )S(O)2R 15 , -C(O)R 15 ,-S(O)R 15 -OC(O)R 15 ,-C(O)N(R 12 )(R 13 ), -C(O)C(O)N(R 12 )(R 13 ), -N(R 14 )C(O)R 15 -S(O)2R 15 -S(O)2N(R 12 )(R 13 )-, S(=O)(=NH)N(R 12 )(R 13 ), -CH2C(O)N(R 12 )(R 13 ), -CH2N(R 14 )C(O)R 15 -CH2S(O)2R 15 , and -CH2S(O)2N(R 12 )(R 13 ) is selected from C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, C 6~10 Ant , and C 1~9 Heteroaryls have one, two, or three R 20j It is replaced as needed; R 28is hydrogen and C 1~6 Selected from alkyl groups; n is 0, 1, or 2; [ka] (This indicates a single or double bond in which all valencies are satisfied.) The present invention provides a pharmaceutically acceptable salt or solvate thereof.

[0222] In this embodiment, the compound is of formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Iha, Z is not N. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ihb, Z is not N. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c V, Z, W, R 2 , L 2, and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ihc, Z is not N. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ihd, Z is not N. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ihe, Z is not N. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ihf, Z is not N. In embodiments, the compound is of formula: [ka] (In the formula, Q 1, R 1 , R 1a , R 1b , R 1c , R 8 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , R 8 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , R 8 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 8 , R 16 , R 2 , L 2 , and R 4The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , R 8 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , R 8 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 12 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R1 , R 1a , R 1b , R 1c , R 12 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , R 12 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 12 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , R 12 , R 16 , R 2 , L 2 , and R 4The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , R 12 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1a , R 1b , R 1c , R 12 , and R 2 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1a , R 1b , R 1c , R 12 , and R 2 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1a , R 1b , R 1c , R 12 , and R 2 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1a , R 1b , R 1c , R 12 , and R 2 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1a , R 1b , R 1c , R 12 , and R 2 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1a , R 1b , R 1c , R 12 , and R 2 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 8 , R 10 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R1 , R 1a , R 1b , R 1c , R 8 , R 10 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , R 8 , R 10 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 8 , R 10 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , R 8 , R 10 , R 16 , R2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 Q 2 , R 1 , R 1a , R 1b , R 1c , R 8 , R 10 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 1d , R 8 , R 10 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 1d , R 8 , R 10 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c ,A,V,Z,W,X,Y,U,R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ia', Z, X, and U are not all N at the same time. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, J, Z, W, X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , R3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ih', Z is not N. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R1c A, J, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c A, J, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R1b , R 1c A, J, Z, W, R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , Z 1 , Z 2 , Z 3 X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , Z 2 , Z 3 X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , Z2 , Z 3 X, Y, U, R 2 , R 3 ,n,L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q1 , R 1 , R 1a , R 1b , R 1c , A, R 16 , R 18 , R 8 , R 2 , R 3 , L 2 , and R 4 (This includes any embodiments as described herein.) In this embodiment, the compound is of formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c V, Z, W, R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In embodiments of formula Ihf, Z is not N. In embodiments, the compound is of formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 8 , R 16 , R 2 , L 2 , and R 4The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 8 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 12 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 12 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1a , R 1b , R 1c , R12 , and R 2 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1a , R 1b , R 1c , R 12 , and R 2 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 8 , R 10 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 8 , R 10 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R1c , R 1d , R 8 , R 10 , R 16 , R 2 , L 2 , and R 4 The compound has (as described herein, including any embodiments). In the embodiments, the compound has the formula: [ka] (In the formula, Q 1 , R 1 , R 1a , R 1b , R 1c , R 1d , R 8 , R 10 , R 16 , R 2 , L 2 , and R 4 (This includes any embodiments as described herein.)

[0223] In this embodiment, R 2 However, one, two, or three R 20d -O-CH2-C substituted as needed 2~9 It is heterocycloalkyl, R 20d However, independently, it is a halogen (for example, F). In the embodiment, R 2 However, one, two, or three R 20d -O-CH2-C substituted as needed 2~9 It is heterocycloalkyl, R 20d but , independently, C 1~6 It is an alkyl group (for example, methyl). In this embodiment, R 2 but [ka] In this embodiment, R 2 but [ka] In this embodiment, R 2 but [ka] In this embodiment, R 2 but [ka] In this embodiment, R 2 but [ka] That is the case.

[0224] In this embodiment, R 8 ga-OR 12 And R 12 However, hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 A heteroaryl group has one, two, or three R 20d It is replaced as needed. In the embodiment, R 12 However, independently, it is hydrogen. In the embodiment, R 12 However, independently, one, two, or three R 20d C replaced as needed 1~6It is alkyl. In this embodiment, R 12 However, independently, one, two, or three R 20d C replaced as needed 2~6 It is an alkenyl. In this embodiment, R 12 However, independently, one, two, or three R 20d C replaced as needed 2~6 It is alkynyl. In the embodiment, R 12 However, independently, one, two, or three R 20d C replaced as needed 3~6 It is a cycloalkyl group. In this embodiment, R 12 However, independently, one, two, or three R 20d -CH2-C substituted as needed 3~6 It is a cycloalkyl group. In this embodiment, R 12 However, independently, one, two, or three R 20d C replaced as needed 2~9 It is heterocycloalkyl. In the embodiment, R 12 However, independently, one, two, or three R 20d -CH2-C substituted as needed 2~9 It is heterocycloalkyl. In the embodiment, R 12 However, independently, C 1~6 It is alkyl. In this embodiment, R 12 However, independently, C 2~6 Al It is Kenil. In this embodiment, R 12 However, independently, C 2~6 It is alkynyl. In the embodiment, R 12 However, independently, C 3~6 It is a cycloalkyl group. In this embodiment, R 12 However, independently, -CH2-C 3~6 It is a cycloalkyl group. In this embodiment, R 12 However, independently, C 2~9 It is heterocycloalkyl. In the embodiment, R 12 However, independently, -CH2-C 2~9 It is heterocycloalkyl.

[0225] In this embodiment, R 20d However, halogen, -CN, and C 1~6 Selected independently of alkyl. In this embodiment, R 20d However, independently, it is a halogen (for example, F). In the embodiment, R 20d However, independently, it is -CN. In the embodiment, R 20d However, independently, C 1~6 It is alkyl. In this embodiment, R 13 However, independently, C 1~6 It is alkyl. In this embodiment, R 13 However, independently, C 1~6 It is a haloalkyl group.

[0226] In this embodiment, R 8 ga-N(R 12 )(R 13 ) and R 12 However, hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 Selected independently from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 3~6 Cycloalkyl, -CH2-C 3~6 Cycloalkyl, C 2~9 Heterocycloalkyl, -CH2-C 2~9 Heterocycloalkyl, C 6~10 Ariel, -CH2-C 6~10 Aryl, and C 1~9 A heteroaryl group has one, two, or three R 20d It is replaced as needed; R 13 However, hydrogen, C 1~6 Alkyl, and C 1~6is selected independently of haloalkyl. In an embodiment, R 8 is -NH(R 12 ).

[0227] In an embodiment, R 12 is, independently, hydrogen. In an embodiment, R 12 is, independently, C 20d alkyl optionally substituted with one, two, or three R 1~6 . In an embodiment, R 12 is, independently, C 20d alkenyl optionally substituted with one, two, or three R 2~6 . In an embodiment, R 12 is, independently, C 20d alkynyl optionally substituted with one, two, or three R 2~6 . In an embodiment, R 12 is, independently, C 20d cycloalkyl optionally substituted with one, two, or three R 3~6 . In an embodiment, R 12 is, independently, -CH2-C 20d cycloalkyl optionally substituted with one, two, or three R 3~6 . In an embodiment, R 12 is, independently, C 20d heterocycloalkyl optionally substituted with one, two, or three R 2~9 . In an embodiment, R 12 is, independently, -CH2-C 20d heterocycloalkyl optionally substituted with one, two, or three R 2~9 . In an embodiment, R 12 is, independently, C 1~6 alkyl. In an embodiment, R 12 is, independently, C 2~6 alkenyl. In an embodiment, R 12 is, independently, C 2~6 alkynyl. In an embodiment, R 12 is, independently, C 3~6 cycloalkyl. In an embodiment, R12 However, independently, -CH2-C 3~6 It is a cycloalkyl group. In this embodiment, R 12 However, independently, C 2~9 It is heterocycloalkyl. In the embodiment, R 12 However, independently, -CH2-C 2~9 It is heterocycloalkyl.

[0228] In this embodiment, R 20d However, halogen, -CN, and C 1~6 Selected independently of alkyl. In this embodiment, R 20d However, independently, it is a halogen (for example, F). In the embodiment, R 20d However, independently, it is -CN. In the embodiment, R 20d However, independently, C 1~6 It is alkyl. In this embodiment, R 20d However, independently, halogen, oxo, -CN, C 1~6 Alkyl, and C 1~6 C is optionally substituted with one, two, or three groups independently selected from the haloalkyl group. 1~6 It is alkyl.

[0229] In this embodiment, R 13 However, independently, it is hydrogen. In the embodiment, R 13 However, independently, C 1~6 It is alkyl. In this embodiment, R 13 However, independently, C 1~6 It is a haloalkyl group.

[0230] In this embodiment, R 8 is hydrogen. In this embodiment, R 8 is a halogen. In this embodiment, R 8 is -CN. In the embodiment, R 8 However, independently, it is hydrogen. In the embodiment, R 8 However, independently, one, two, or three R 20c C replaced as needed 1~6 It is alkyl. In this embodiment, R 8However, independently, one, two, or three R 20c C replaced as needed 2~6 It is an alkenyl. In this embodiment, R 8 However, independently, one, two, or three R 20c C replaced as needed 2~6 It is alkynyl. In the embodiment, R 8 However, independently, one, two, or three R 20c C replaced as needed 3~6 It is a cycloalkyl group. In this embodiment, R 8 However, independently, one, two, or three R 20c -CH2-C substituted as needed 3~6 It is a cycloalkyl group. In this embodiment, R 8 However, independently, one, two, or three R 20c C replaced as needed 2~9 It is heterocycloalkyl. In the embodiment, R 8 However, independently, one, two, or three R 20c -CH2-C substituted as needed 2~9 It is heterocycloalkyl. In the embodiment, R 8 However, independently, C 1~6 It is alkyl. In this embodiment, R 8 However, independently, C 2~6 It is an alkenyl. In this embodiment, R 8 However, independently, C 2~6 It is alkynyl. In the embodiment, R 8 However, independently, C 3~6 It is a cycloalkyl group. In this embodiment, R 8 However, independently, -CH2-C 3~6 It is a cycloalkyl group. In this embodiment, R 8 However, independently, C 2~9 It is heterocycloalkyl. In the embodiment, R 8 However, independently, -CH2-C 2~9 It is heterocycloalkyl.

[0231] In this embodiment, R 20c However, halogen, -CN, and C1~6 Selected independently of alkyl. In this embodiment, R 20c However, independently, it is a halogen (for example, F). In the embodiment, R 20c However, independently, it is -CN. In the embodiment, R 20c However, independently, C 1~6 It is alkyl.

[0232] In this embodiment, R 20c C 2~6 Selected independently from alkenyls. In embodiments, R 20c However, independently, C 2~6 It is alkynyl. In the embodiment, R 20c However, independently, C 3~6 It is a cycloalkyl group. In this embodiment, R 20c However, independently, -CH2-C 3~6 It is a cycloalkyl group. In this embodiment, R 20c However, independently, C 2~9 It is heterocycloalkyl. In the embodiment, R 20c However, independently, -CH2-C 2~9 It is heterocycloalkyl. In the embodiment, R 20c However, independently, C 6~10 It is an arrow. In this embodiment, R 20c Howeve...

Claims

[Claim 1] The invention described in the specification.

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