Bicyclic ureas as kinase inhibitors

Abstract

The present application provides bicyclic urea compounds that modulate JAK2 activity, which are useful in the treatment of various diseases, including cancer.

Description

[0001] sequence list This application contains a sequence list, which is submitted electronically as an XML file named "20443-0806WO1_SL_ST26.XML". The XML file was created on March 12, 2024, and is 2,281 bytes in size. The material of the XML file is incorporated herein by reference in its entirety. Technical Field

[0002] This invention provides bicyclic urea compounds that modulate JAK2 activity and can be used to treat JAK2-related diseases, including cancer. Background Technology

[0003] Jenners kinase (JAK) 2 plays a crucial role in signal transduction of several cytokine receptors. The mutant JAK2 V617F, located in the pseudokinase (JH2) domain, is the most common molecular event associated with myeloproliferative neoplasms (MPN). Currently, small molecule JAK2 inhibitors used to treat MPN are designed to target the JAK2 kinase (JH1) domain. Therefore, the JAK2V617F mutant, selectively targeting the JAK2 kinase (JH1) domain, could be used to treat various pathologies while preserving essential JAK2 function. This application addresses this and other needs. Summary of the Invention

[0004] This invention especially Compounds involving Formula I:

[0005]

[0006] I

[0007] Or a pharmaceutically acceptable salt thereof, wherein the constituent members are defined herein.

[0008] The present invention further provides a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

[0009] The present invention further provides a method for inhibiting the activity of the V617F variant of JAK2 kinase, the method comprising contacting the kinase with a compound of formula I or a pharmaceutically acceptable salt thereof.

[0010] The present invention further provides a method for treating a patient with a disease or condition associated with the expression or activity of the V617F variant of JAK2 kinase by administering to the patient a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof.

[0011] The present invention further provides a compound of formula I or a pharmaceutically acceptable salt thereof, which is used in any of the methods described herein.

[0012] The present invention further provides the use of a compound of formula I or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical agent used in any of the methods described herein. Detailed Implementation

[0013] This application provides a compound of formula I:

[0014]

[0015] I

[0016] Or its pharmaceutically acceptable salt, wherein:

[0017] R 1 Selected from C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, wherein R 1 The C mentioned 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl groups are each optionally represented by one, two, or three independently selected R groups. 1A Substituent substitution;

[0018] Each R 1A Independently selected from halogenated groups, oxo groups, CN, NO2, OR a11 SR a11 NHOR a11 C(O)R b11 C(O)NR c11 R d11 C(O)NR c11 (OR a11 ), C(O)OR a11 OC(O)R b11 OC(O)NR c11 R d11 NR c11 R d11 NR c11 NR c11 R d11 、 NR c11 C(O)R b11 NR c11 C(O)OR a11 NR c11 C(O)NR c11 R d11 C(=NR) e11 )R b11 C(=NR) e11 )NR c11 R d11 NR c11C(=NR e11 )NR c11 R d11 NR c11 C(=NR e11 )R b11 NR c11 S(O)R b11 NR c11 S(O)NR c11 R d11 NR c11 S(O)2R b11 NR c11 S(O)(=NR e11 )R b11 NR c11 S(O)2NR c11 R d11 S(O)R b11 S(O)NR c11 R d11 S(O)2R b11 S(O)2NR c11 R d11 OS(O)(=NR) e11 )R b11 and OS(O)2R b11 ;

[0019] Each R a11 R b11 R c11 and R d11 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group, wherein R a11 R b11 R c11 and R d11 The C mentioned 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Each alkynyl group is optionally represented by 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R groups. M Substituent substitution;

[0020] Each R e11 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl and C 2-6 alkynyl group;

[0021] Cy2 Selected from C 3-10 Cycloalkyl and 4-12 membered heterocyclic alkyl groups, wherein the C 3-10 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R groups. 2 Substituent substitution;

[0022] Each R 2 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl-, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a2 SR a2 NHOR a2 C(O)R b2 C(O)NR c2 R d2 C(O)NR c2 (OR a2 ), C(O)OR a2 OC(O)R b2 OC(O)NR c2 R d2 NR c2 R d2 NR c2 NR c2 R d2 、 NR c2 C(O)R b2 NR c2 C(O)OR a2 NR c2 C(O)NR c2 R d2 C(=NR) e2 )R b2 C(=NR) e2 )NR c2 R d2 NR c2 C(=NR e2 )NR c2 R d2 NRc2 C(=NR e2 )R b2 NR c2 S(O)R b2 NR c2 S(O)NR c2 R d2 NR c2 S(O)2R b2 NR c2 S(O)(=NR e2 )R b2 NR c2 S(O)2NR c2 R d2 S(O)R b2 S(O)NR c2 R d2 S(O)2R b2 S(O)2NR c2 R d2 OS(O)(=NR) e2 )R b2 OS(O)2R b2 SF5, P(O)R f2 R g2 OP(O)(OR) h2 (OR) i2 ), P(O)(OR h2 (OR) i2 ) and BR j2 R k2 , where R 2 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 2A Substituent substitution;

[0023] Each R a2 R c2 and R d2 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a2 R c2 and R d2 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 2A Substituent substitution;

[0024] or any R connected to the same N atom c2 and R d2 Together with the N atom to which it is attached, it forms a 5-10-membered heteroaryl or a 4-10-membered heterocyclic alkyl group, wherein the 5-10-membered heteroaryl or 4-10-membered heterocyclic alkyl group is optionally separated by 1, 2, 3 or 4 independently selected R atoms. 2A Substituent substitution;

[0025] Each R b2 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6alkyl-, where R b2 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 2A Substituent substitution;

[0026] Each R e2 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0027] Each R f2 and R g2 Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6alkyl-;

[0028] Each R h2 and R i2 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0029] Each R j2 and R k2 Independently selected from OH and C 1-6 Alkoxy and C 1-6 Halogenated alkoxy groups;

[0030] or any R connected to the same B atom j2 and R k2 Together with the B atom it is attached to, it forms a 5- or 6-membered heterocyclic alkyl group, wherein the heterocyclic alkyl group is optionally composed of 1, 2, 3, or 4 independently selected C atoms. 1-6 Alkyl and C 1-6 Substituents of haloalkyl groups;

[0031] Each R 2A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl-, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a21 SR a21 NHOR a21 C(O)R b21 C(O)NR c21 R d21、C(O)NR c21 (OR a21 )、C(O)OR a21 、OC(O)R b21 、OC(O)NR c21 R d21 、NR c21 R d21 、NR c21 NR c21 R d21 、 NR c21 C(O)R b21 、NR c21 C(O)OR a21 、NR c21 C(O)NR c21 R d21 、C(=NR e21 )R b21 、C(=NR e21 )NR c21 R d21 、NR c21 C(=NR e21 )NR c21 R d21 、NR c21 C(=NR e21 )R b21 、NR c21 S(O)R b21 、NR c21 S(O)NR c21 R d21 、NR c21 S(O)2R b21 、NR c21 S(O)(=NR e21 )R b21 、NR c21 S(O)2NR c21 R d21 、S(O)R b21 、S(O)NR c21 R d21 、S(O)2R b21 、S(O)2NR c21 R d21 、OS(O)(=NR e21 )R b21 、OS(O)2R b21 、SF5、P(O)R f21 R g21 、OP(O)(OR h21 )(OR i21 )、P(O)(OR h21(OR) i21 ) and BR j21 R k21 , where R 2A The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 2B Substituent substitution;

[0032] Each R a21 R c21 and R d21 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a21 R c21 and R d21 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R2B Substituent substitution;

[0033] or any R connected to the same N atom c21 and R d21 Together with the N atom to which it is attached, it forms a 5-10-membered heteroaryl or a 4-10-membered heterocyclic alkyl group, wherein the 5-10-membered heteroaryl or 4-10-membered heterocyclic alkyl group is optionally separated by 1, 2, 3 or 4 independently selected R atoms. 2B Substituent substitution;

[0034] Each R b21 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R b21 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 2B Substituent substitution;

[0035] Each R e21 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0036] Each R f21 and R g21 Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0037] Each R h21 and R i21 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0038] Each R j21 and R k21 Independently selected from OH and C 1-6 Alkoxy and C 1-6 Halogenated alkoxy groups;

[0039] or any R connected to the same B atom j21 and R k21Together with the B atom it is attached to, it forms a 5- or 6-membered heterocyclic alkyl group, wherein the heterocyclic alkyl group is optionally composed of 1, 2, 3, or 4 independently selected C atoms. 1-6 Alkyl and C 1-6 Substituents of haloalkyl groups;

[0040] Each R 2B Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl-, (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a22 SR a22 NHOR a22 C(O)R b22 C(O)NR c22 R d22 C(O)NR c22 (OR a22 ), C(O)OR a22 OC(O)R b22 OC(O)NR c22 R d22 NR c22 R d22 NR c22 NR c22 R d22 、 NR c22 C(O)R b22 NR c22 C(O)OR a22 NR c22 C(O)NR c22 R d22 C(=NR) e22 )R b22 C(=NR) e22 )NR c22 R d22 NR c22 C(=NR e22 )NR c22 R d22 NR c22 C(=NR e22 )R b22 NR c22S(O)R b22 NR c22 S(O)NR c22 R d22 NR c22 S(O)2R b22 NR c22 S(O)(=NR e22 )R b22 NR c22 S(O)2NR c22 R d22 S(O)R b22 S(O)NR c22 R d22 S(O)2R b22 S(O)2NR c22 R d22 OS(O)(=NR) e22 )R b22 and OS(O)2R b22 , where R 2C The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl-, (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution;

[0041] Each R a22 R c22 and R d22 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a22 R c22 and R d22 The C mentioned 1-6 Alkyl, C2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution;

[0042] or any R connected to the same N atom c22 and R d22 Together with the N atom to which it is attached, it forms a 5-6-membered heteroaryl or a 4-7-membered heterocyclic alkyl group, wherein the 5-6-membered heteroaryl or 4-7-membered heterocyclic alkyl group is optionally separated by 1, 2, 3 or 4 independently selected R atoms. M Substituent substitution;

[0043] Each R b22 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-, where R b22 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution;

[0044] Each R e22 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0045] R 3 Selected from H, halogenated group, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0046] Cy 4 Selected from C 6-10 aryl and 5-14 heteroaryl, wherein the C 6-10 The aryl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R groups. 4 Substituent substitution;

[0047] Each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl-, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a4 SR a4 NHOR a4 C(O)R b4 C(O)NR c4 R d4 C(O)NR c4 (OR a4 ), C(O)OR a4 OC(O)R b4 OC(O)NR c4 R d4 NRc4 R d4 NR c4 NR c4 R d4 、 NR c4 C(O)R b4 NR c4 C(O)OR a4 NR c4 C(O)NR c4 R d4 C(=NR) e4 )R b4 C(=NR) e4 )NR c4 R d4 NR c4 C(=NR e4 )NR c4 R d4 NR c4 C(=NR e4 )R b4 NR c4 S(O)R b4 NR c4 S(O)NR c4 R d4 NR c4 S(O)2R b4 NR c4 S(O)(=NR e4 )R b4 NR c4 S(O)2NR c4 R d4 S(O)R b4 S(O)NR c4 R d4 S(O)2R b4 S(O)2NR c4 R d4 OS(O)(=NR) e4 )R b4 OS(O)2R b4 SF5, P(O)R f4 R g4 OP(O)(OR) h4 (OR) i4 ), P(O)(OR h4 (OR) i4 ) and BR j4 R k4 , where R 4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 4A Substituent substitution;

[0048] Each R a4 R c4 and R d4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a4 R c4 and R d4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 4A Substituent substitution;

[0049] or any R connected to the same N atom c4 and R d4Together with the N atom to which it is attached, it forms a 5-10-membered heteroaryl or a 4-10-membered heterocyclic alkyl group, wherein the 5-10-membered heteroaryl or 4-10-membered heterocyclic alkyl group is optionally separated by 1, 2, 3 or 4 independently selected R atoms. 4A Substituent substitution;

[0050] Each R b4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R b4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 4A Substituent substitution;

[0051] Each R e4 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0052] Each R f4 and R g4 Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0053] Each R h4 and R i4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0054] Each R j4 and R k4 Independently selected from OH and C 1-6 Alkoxy and C 1-6 Halogenated alkoxy groups;

[0055] or any R connected to the same B atom j4 and R k4 Together with the B atom it is attached to, it forms a 5- or 6-membered heterocyclic alkyl group, wherein the heterocyclic alkyl group is optionally composed of 1, 2, 3, or 4 independently selected C atoms. 1-6 Alkyl and C 1-6 Substituents of haloalkyl groups;

[0056] Each R 4A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl-, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a41 SR a41 NHOR a41 C(O)R b41 C(O)NR c41 R d41 C(O)NR c41 (OR a41 ), C(O)OR a41 OC(O)R b41 OC(O)NR c41 R d41 NR c41 R d41 NR c41 NR c41 R d41 、 NR c41 C(O)R b41 NR c41 C(O)OR a41 NR c41 C(O)NR c41 R d41 C(=NR) e41 )R b41 C(=NR) e41 )NR c41 R d41 NR c41 C(=NR e41 )NR c41 R d41 NR c41 C(=NR e41 )R b41 NR c41 S(O)R b41 NR c41 S(O)NR c41 R d41 NR c41S(O)2R b41 NR c41 S(O)(=NR e41 )R b41 NR c41 S(O)2NR c41 R d41 S(O)R b41 S(O)NR c41 R d41 S(O)2R b41 S(O)2NR c41 R d41 OS(O)(=NR) e41 )R b41 OS(O)2R b41 SF5, P(O)R f41 R g41 OP(O)(OR) h41 (OR) i41 ), P(O)(OR h41 (OR) i41 ) and BR j41 R k41 , where R 41 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 4B Substituent substitution;

[0057] Each R a41 R c41 and R d41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a41 R c41 and R d41 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 4B Substituent substitution;

[0058] or any R connected to the same N atom c41 and R d41 Together with the N atom to which it is attached, it forms a 5-10-membered heteroaryl or a 4-10-membered heterocyclic alkyl group, wherein the 5-10-membered heteroaryl or 4-10-membered heterocyclic alkyl group is optionally separated by 1, 2, 3 or 4 independently selected R atoms. 4B Substituent substitution;

[0059] Each R b41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R b41 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 4B Substituent substitution;

[0060] Each R e41 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0061] Each R f41 and R g41 Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0062] Each R h41 and R i41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0063] Each R j41 and R k41 Independently selected from OH and C 1-6 Alkoxy and C 1-6 Halogenated alkoxy groups;

[0064] or any R connected to the same B atom j41 and R k41 Together with the B atom it is attached to, it forms a 5- or 6-membered heterocyclic alkyl group, wherein the heterocyclic alkyl group is optionally composed of 1, 2, 3, or 4 independently selected C atoms. 1-6 Alkyl and C 1-6 Substituents of haloalkyl groups;

[0065] Each R 4B Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl-, (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a42 SR a42 NHOR a42 C(O)R b42 C(O)NR c42 R d42 C(O)NR c42 (OR a42 ), C(O)OR a42 OC(O)R b42 OC(O)NR c42 R d42 NR c42 R d42 NR c42 NR c42 Rd42 、 NR c42 C(O)R b42 NR c42 C(O)OR a42 NR c42 C(O)NR c42 R d42 C(=NR) e42 )R b42 C(=NR) e42 )NR c42 R d42 NR c42 C(=NR e42 )NR c42 R d42 NR c42 C(=NR e42 )R b42 NR c42 S(O)R b42 NR c42 S(O)NR c42 R d42 NR c42 S(O)2R b42 NR c42 S(O)(=NR e42 )R b42 NR c42 S(O)2NR c42 R d42 S(O)R b42 S(O)NR c42 R d42 S(O)2R b42 S(O)2NR c42 R d42 OS(O)(=NR) e42 )R b42 and OS(O)2R b42 , where R 4C The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution;

[0066] Each R a42 R c42 and R d42 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a42 R c42 and R d42 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution;

[0067] or any R connected to the same N atom c42 and R d42 Together with the N atom to which it is attached, it forms a 5-6-membered heteroaryl or a 4-7-membered heterocyclic alkyl group, wherein the 5-6-membered heteroaryl or 4-7-membered heterocyclic alkyl group is optionally separated by 1, 2, 3 or 4 independently selected R atoms. M Substituent substitution;

[0068] Each R b42 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6alkyl-, where R b42 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution;

[0069] Each R e42 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0070] R 5 Selected from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, C 6-10 Aryl, 5-12 membered heteroaryl, 4-12 membered heterocycloalkyl, OR w2 SR w2 NR w2 R w3 C(O)R w2 C(O)NR w2 R w3 C(O)OR w2 OC(O)R w2 OC(NR) w3 )R w2 OC(O)NR w2 R w3 NR w3 C(O)R w2 NR w3C(O)OR w2 NR w3 C(O)NR w2 R w3 NR w3 S(O)R w2 NR w3 S(O)NR w2 R w3 NR w3 S(O)2R w2 S(O)R w2 S(O)NR w2 R w3 S(O)2R w2 and S(O)2NR w2 R w3 ;

[0071] Where R 5 The C mentioned 1-6 Alkyl and C 6-10 Each aryl group is controlled by one R. w1 Substituents and optionally substituted 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 5A Substituent substitution; or

[0072] R 5 The C mentioned 6-10 Aryl is 1 R w5 Substituents and optionally substituted 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 5A Substituent substitution; and

[0073] R 5 The C mentioned 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, 4, 5, 6, 7, or 8 independently selected Rs. 5A Substituent substitution;

[0074] R w1 Selected from C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, 5-12 membered heteroaryl, C 6-12 Aryl, 4-12 membered heterocyclic alkyl, OR w4 NHR w4 NR w3 R w4 SR w4 S(O)2R w4 C(O)R w4 C(O)NHR w4C(O)NR w3 R w4 OC(O)R w4 S(O)R w3 S(O)NR w3 R w3 S(O)2R w2 and S(O)2NR w3 R w3 , where R w1 The C mentioned 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, 5-12 membered heteroaryl, C 6-12 The aryl group and the 4-12 membered heterocyclic alkyl group are each optionally represented by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R groups. 5A Substituent substitution;

[0075] Each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, 4, 5, 6, 7, or 8 independently selected Rs. 5A Substituent substitution;

[0076] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R w3 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 5A Substituent substitution;

[0077] Each R w4 Selected independently from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a51 R c51 and R d51 The C mentioned 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 5B Substituent substitution;

[0078] R w5 C 1-6 Alkyl group, wherein the alkyl group is oxidized, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6alkyl-, (4-10 membered heterocycloalkyl)-C 1-6 alkyl-, CN, NO2, OR a51 , SR a51 , NHOR a51 , C(O)R b51 , C(O)NR c51 R d51 , C(O)NR c51 (OR a51 ), C(O)OR a51 , OC(O)R b51 , OC(O)NR c51 R d51 , NR c51 R d51 , NR c51 NR c51 R d51 、 NR c51 C(O)R b51 , NR c51 C(O)OR<000138​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​e51 )R b51 OS(O)2R b51 SF5, P(O)R f51 R g51 OP(O)(OR) h51 (OR) i51 ), P(O)(OR h51 (OR) i51 ) or BR j51 R k51 Replace, where R w5 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 5B Substituent substitution;

[0079] Each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl-, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a51 SR a51 NHOR a51 C(O)R b51 C(O)NR c51 R d51 C(O)NR c51 (OR a51 ), C(O)OR a51 OC(O)R b51 OC(O)NRc51 R d51 、 NR c51 R d51 、 NR c51 NR c51 R d51 、 NR c51 C(O)R b51 、 NR c51 C(O)OR a51 、 NR c51 C(O)NR c51 R d51 、 C(=NR e51 )R b51 、 C(=NR e51 )NR c51 R d51 、 NR c51 C(=NR e51 )NR c51 R d51 、 NR c51 C(=NR e51 )R b51 、 NR c51 S(O)R b51 、 NR c51 S(O)NR c51 R d51 、 NR c51 S(O)2R b51 、 NR c51 S(O)(=NR e51 )R b51 、 NR c51 S(O)2NR c51 R d51 、 S(O)R b51 、 S(O)NR c51 R d51 、 S(O)2R b51 、 S(O)2NR c51 R d51 、 OS(O)(=NR e51 )R b51 、 OS(O)2R b51 、 SF5、 P(O)R f51 R g51 、 OP(O)(OR h51 )(OR i51 )、 P(O)(OR h51 )(OR i51 ) and BR j51 R k51 wherein R 5A the C 1-6 alkyl, C2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 5B Substituent substitution;

[0080] Each R a51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a51 R c51 and R d51 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 5B Substituent substitution;

[0081] or any R connected to the same N atom c51 and R d51Together with the N atom to which it is attached, it forms a 5-10-membered heteroaryl or a 4-10-membered heterocyclic alkyl group, wherein the 5-10-membered heteroaryl or 4-10-membered heterocyclic alkyl group is optionally separated by 1, 2, 3 or 4 independently selected R atoms. 5B Substituent substitution;

[0082] Each R b51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R b51 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 5B Substituent substitution;

[0083] Each R e51 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0084] Each R f51 and R g51 Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0085] Each R h51 and R i51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-;

[0086] Each R j51 and R k51 Independently selected from OH and C 1-6 Alkoxy and C 1-6 Halogenated alkoxy groups;

[0087] or any R connected to the same B atom j51 and R k51 Together with the B atom it is attached to, it forms a 5- or 6-membered heterocyclic alkyl group, wherein the heterocyclic alkyl group is optionally composed of 1, 2, 3, or 4 independently selected C atoms. 1-6 Alkyl and C 1-6 Substituents of haloalkyl groups;

[0088] Each R 5B Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl-, (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a52 SR a52 NHOR a52 C(O)R b52 C(O)NR c52 R d52 C(O)NR c52 (OR a52 ), C(O)OR a52 OC(O)R b52 OC(O)NR c52 R d52 NR c52 R d52 NR c52 NR c52 R d52 、 NR c52 C(O)R b52 NR c52 C(O)OR a52 NR c52 C(O)NR c52 R d52 C(=NR) e52 )R b52 C(=NR) e52 )NR c52 R d52 NR c52 C(=NR e52 )NR c52 R d52 NR c52 C(=NR e52 )R b52 NR c52 S(O)R b52 NR c52 S(O)NR c52 R d52 NR c52 S(O)2R b52 NRc52 S(O)(=NR e52 )R b52 NR c52 S(O)2NR c52 R d52 S(O)R b52 S(O)NR c52 R d52 S(O)2R b52 S(O)2NR c52 R d52 OS(O)(=NR) e52 )R b52 and OS(O)2R b52 , where R 5B The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution;

[0089] Each R a52 R c52 and R d52 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a52 R c52 and R d52 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution;

[0090] or any R connected to the same N atom c52 and R d52 Together with the N atom to which it is attached, it forms a 5-6-membered heteroaryl or a 4-7-membered heterocyclic alkyl group, wherein the 5-6-membered heteroaryl or 4-7-membered heterocyclic alkyl group is optionally separated by 1, 2, 3 or 4 independently selected R atoms. M Substituent substitution;

[0091] Each R b52 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-, where R b52 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution;

[0092] Each R e52 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-; and

[0093] Each R M Independently selected from H, OH, halogenated groups, oxo groups, CN, C(O)OH, NH2, NO2, SF5, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl;

[0094] Its limitations are:

[0095] (i) Cy 4 Not triazolidine; and

[0096] (ii) R 5 Not morpholino or piperazine; and

[0097] (iii) When Cy 4 When it is phenyl, R 5 It is not pyridinyl or pyrimidinyl.

[0098] In some implementations, Cy 4 Selected from C 6-10 Aryl and 5-14 heteroaryl groups, of which Cy 4 The C mentioned 6-10 The aryl and 5-12 heteroaryl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 4 Substituent substitution;

[0099] Its limitations are:

[0100] (i) Cy 4 Not triazolidine; and

[0101] (ii) R 5 Not morpholino or piperazine; and

[0102] (iii) When Cy 4 When it is phenyl, R 5 It is not pyridinyl or pyrimidinyl.

[0103] In some implementations, Cy 4 Selected from phenyl and 5-14-membered heteroaryl groups, wherein Cy 4 The phenyl group and the 5-14 heteroaryl group are each optionally separated by 1, 2, 3 or 4 independently selected R groups. 4 Substituent substitution;

[0104] Its limitations are:

[0105] (i) Cy 4 Not triazolidine; and

[0106] (ii) R 5 Not morpholino or piperazine; and

[0107] (iii) When Cy 4 When it is phenyl, R 5 It is not pyridinyl or pyrimidinyl.

[0108] In some implementations, Cy 4 Selected from phenyl, monocyclic 5-6-membered heteroaryl, and bicyclic 8-14-membered heteroaryl, wherein Cy 4 The phenyl, monocyclic 5-6-membered heteroaryl, and bicyclic 8-14-membered heteroaryl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4 Substituent substitution;

[0109] Its limitations are:

[0110] (i) Cy 4 Not triazolidine; and

[0111] (ii) R 5 Not morpholino or piperazine; and

[0112] (iii) When Cy 4 When it is phenyl, R 5 It is not pyridinyl or pyrimidinyl.

[0113] In some implementations, Cy 4Selected from phenyl, thiazolyl, pyrazolyl, pyridinyl, pyrimidinyl, quinolinyl, imidazo[1,2-b]pyridazinyl, pyrazol[1,5-a]pyrimidinyl, pyrrolo[3,2-b]pyridinyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, and pyrazol[4,3-b]pyridinyl, wherein Cy 4 The phenyl, thiazolyl, pyrazolyl, pyridinyl, pyrimidinyl, quinolinyl, imidazo[1,2-b]pyridazinyl, pyrazol[1,5-a]pyrimidinyl, pyrrolo[3,2-b]pyridinyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one and pyrazololo[4,3-b]pyridinyl groups are each optionally selected by 1, 2, 3 or 4 independently chosen R groups. 4 Substituent substitution;

[0114] Its limitations are:

[0115] (i) R 5 Not morpholino or piperazine; and

[0116] (ii) When Cy 4 When it is phenyl, R 5 It is not pyridinyl or pyrimidinyl.

[0117] In some implementations, Cy 4 Selected from phenyl, thiazolyl, pyrazolyl, pyridyl, pyrimidinyl, quinolinyl, imidazo[1,2-b]pyridazinyl, and pyrazol[1,5-a]pyrimidinyl, wherein Cy 4 The phenyl, thiazolyl, pyrazolyl, pyridyl, pyrimidinyl, quinolinyl, imidazo[1,2-b]pyridazinyl and pyrazol[1,5-a]pyrimidinyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 4 Substituent substitution;

[0118] Its limitations are:

[0119] (i) R 5 Not morpholino or piperazine; and

[0120] (ii) When Cy 4 When it is phenyl, R 5 It is not pyridinyl or pyrimidinyl.

[0121] In some implementations, Cy 4 The phenyl group is optionally represented by 1, 2, 3, or 4 independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino, piperazine, pyridinyl, or pyrimidinyl.

[0122] In some implementations, Cy 4Selected from thiazolyl, pyrazolyl, pyridinyl, pyrimidinyl, quinolinyl, imidazo[1,2-b]pyridazinyl, and pyrazol[1,5-a]pyrimidinyl, wherein Cy 4 The thiazolyl, pyrazolyl, pyridinyl, pyrimidinyl, quinolinyl, imidazo[1,2-b]pyridazinyl, pyrazol[1,5-a]pyrimidinyl, pyrrolo[3,2-b]pyridinyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one and pyrazol[4,3-b]pyridinyl groups are each optionally selected by 1, 2, 3 or 4 independently chosen R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0123] In some implementations, Cy 4 Selected from thiazolyl, pyrazolyl, pyridinyl, pyrimidinyl, quinolinyl, imidazo[1,2-b]pyridazinyl, and pyrazol[1,5-a]pyrimidinyl, wherein Cy 4 The thiazolyl, pyrazolyl, pyridyl, pyrimidinyl, quinolinyl, imidazo[1,2-b]pyridazinyl and pyrazol[1,5-a]pyrimidinyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0124] In some implementations, Cy 4 Selected from thiazolyl, pyrazolyl, pyridinyl, and pyrimidinyl, wherein Cy 4 The thiazolyl, pyrazolyl, pyridyl, and pyrimidinyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0125] In some implementations, Cy 4 The thiazolyl group is optionally composed of one or two independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0126] In some implementations, Cy 4 The pyrazolyl group is optionally surrounded by one or two independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0127] In some implementations, Cy 4 The pyridinyl group is optionally composed of 1, 2, 3, or 4 independently selected R groups. 4Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0128] In some implementations, Cy 4 The pyrimidinyl group is optionally represented by 1, 2, 3, or 4 independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0129] In some implementations, Cy 4 Selected from quinolinyl, imidazo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyrimidinyl, pyrrolo[3,2-b]pyridinyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, and pyrazolo[4,3-b]pyridinyl, wherein Cy 4 The quinolinyl, imidazo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyrimidinyl, pyrrolo[3,2-b]pyridinyl, 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one, and pyrazolo[4,3-b]pyridinyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0130] In some implementations, Cy 4 Selected from quinolinyl, imidazo[1,2-b]pyridazinyl and pyrazolo[1,5-a]pyrimidinyl, wherein Cy 4 The quinolinyl, imidazo[1,2-b]pyridazinyl and pyrazolo[1,5-a]pyrimidinyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0131] In some implementations, Cy 4 The quinolinyl group is optionally composed of 1, 2, 3, or 4 independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0132] In some implementations, Cy 4 The imidazo[1,2-b]pyridazinyl group is optionally surrounded by 1, 2, 3, or 4 independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0133] In some implementations, Cy4 The pyrazolo[1,5-a]pyrimidinyl group is optionally composed of 1, 2, 3, or 4 independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0134] In some implementations, Cy 4 The pyrrolo[3,2-b]pyridyl group is optionally composed of 1, 2, 3, or 4 independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0135] In some implementations, Cy 4 The 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one group is optionally surrounded by 1, 2, 3 or 4 independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0136] In some implementations, Cy 4 The pyrazolo[4,3-b]pyridinyl group is optionally represented by 1, 2, 3, or 4 independently selected R groups. 4 Substituent substitution, the limiting condition being R 5 It is not morpholino or piperazine.

[0137] In some embodiments, the compound of formula I is a compound of formula II:

[0138]

[0139] II

[0140] Or its pharmaceutically acceptable salt.

[0141] In some embodiments, the compound of formula I is a compound of formula IIa:

[0142]

[0143] IIa

[0144] Or a pharmaceutically acceptable salt thereof, wherein m is 0, 1, 2, 3, 4, 5, 6 or 7.

[0145] In some embodiments, the compound of formula I is a compound of formula IIb:

[0146]

[0147] IIb

[0148] Or a pharmaceutically acceptable salt thereof, wherein m is 0, 1, 2, 3, 4, 5, 6 or 7.

[0149] In some implementations of formulas IIa and IIb, m is 0, 1, 2, 3, or 4.

[0150] In some implementations of formulas IIa and IIb, m is 0, 1, 2, or 3.

[0151] In some implementations of formulas IIa and IIb, m is 0, 1, or 2.

[0152] In some implementations of formulas IIa and IIb, m is 0 or 1.

[0153] In some embodiments, the compound of formula I is a compound of formulas IIIa, IIIb, IIIc, IIId, IIIe, IIIf, IIIg, IIIh, IIIi, IIIj, IIIk, IIIm, or IIIn.

[0154]

[0155]

[0156] Or its pharmaceutically acceptable salt.

[0157] In some embodiments, the compound of formula I is a compound of formula IIIa, IIIb, IIIc, IIId, IIIe, IIIf, IIIg, IIIh, IIIi, or IIIj:

[0158]

[0159] Or its pharmaceutically acceptable salt.

[0160] In some embodiments, the compound of formula I is a compound of formula IIIa or a pharmaceutically acceptable salt thereof.

[0161] In some embodiments, the compound of formula I is a compound of formula IIIb or a pharmaceutically acceptable salt thereof.

[0162] In some embodiments, the compound of formula I is a compound of formula IIIc or a pharmaceutically acceptable salt thereof.

[0163] In some embodiments, the compound of formula I is a compound of formula IIId or a pharmaceutically acceptable salt thereof.

[0164] In some embodiments, the compound of formula I is a compound of formula IIIe or a pharmaceutically acceptable salt thereof.

[0165] In some embodiments, the compound of formula I is a compound of formula IIIf or a pharmaceutically acceptable salt thereof.

[0166] In some embodiments, the compound of formula I is a compound of formula IIIg or a pharmaceutically acceptable salt thereof.

[0167] In some embodiments, the compound of formula I is a compound of formula IIIh or a pharmaceutically acceptable salt thereof.

[0168] In some embodiments, the compound of formula I is a compound of formula IIIi or a pharmaceutically acceptable salt thereof.

[0169] In some embodiments, the compound of formula I is a compound of formula IIIj or a pharmaceutically acceptable salt thereof.

[0170] In some embodiments, the compound of formula I is a compound of formula IIIk or a pharmaceutically acceptable salt thereof.

[0171] In some embodiments, the compound of formula I is a compound of formula IIIm or a pharmaceutically acceptable salt thereof.

[0172] In some embodiments, the compound of formula I is a compound of formula IIIn or a pharmaceutically acceptable salt thereof.

[0173] In some embodiments, the compound of formula I is a compound of formula IVa, IVb, IVc, IVd, IVe, IVf, IVg, IVh, IVVi, IVj, IVk, IVm, IVn, IVo, IVp, IVq, IVr, IVs, IVt, IVu, or IVv.

[0174]

[0175]

[0176] Or its pharmaceutically acceptable salt.

[0177] In some embodiments, the compound of formula I is a compound of formulas IVa, IVb, IVc, IVd, IVe, IVf, IVg, IVh, IVVi, IVj, IVk, IVm, IVn, IVo:

[0178]

[0179]

[0180] Or its pharmaceutically acceptable salt.

[0181] In some embodiments, the compound of formula I is a compound of formula IVa, IVb, IVc, IVd, IVe, IVf, IVg, IVh, or IVi:

[0182]

[0183] Or its pharmaceutically acceptable salt.

[0184] In some embodiments, the compound of formula I is a compound of formula IVa or a pharmaceutically acceptable salt thereof.

[0185] In some embodiments, the compound of formula I is a compound of formula IVb or a pharmaceutically acceptable salt thereof.

[0186] In some embodiments, the compound of formula I is a compound of formula IVc or a pharmaceutically acceptable salt thereof.

[0187] In some embodiments, the compound of formula I is a compound of formula IVd or a pharmaceutically acceptable salt thereof.

[0188] In some embodiments, the compound of formula I is a compound of formula IVe or a pharmaceutically acceptable salt thereof.

[0189] In some embodiments, the compound of formula I is a compound of formula IVf or a pharmaceutically acceptable salt thereof.

[0190] In some embodiments, the compound of formula I is a compound of formula IVg or a pharmaceutically acceptable salt thereof.

[0191] In some embodiments, the compound of formula I is a compound of formula IVh or a pharmaceutically acceptable salt thereof.

[0192] In some embodiments, the compound of formula I is a compound of formula IVi or a pharmaceutically acceptable salt thereof.

[0193] In some embodiments, the compound of formula I is a compound of formula IVj or a pharmaceutically acceptable salt thereof.

[0194] In some embodiments, the compound of formula I is a compound of formula IVk or a pharmaceutically acceptable salt thereof.

[0195] In some embodiments, the compound of formula I is a compound of formula IVm or a pharmaceutically acceptable salt thereof.

[0196] In some embodiments, the compound of formula I is a compound of formula IVn or a pharmaceutically acceptable salt thereof.

[0197] In some embodiments, the compound of formula I is a compound of formula IVo or a pharmaceutically acceptable salt thereof.

[0198] In some embodiments, the compound of formula I is a compound of formula IVp or a pharmaceutically acceptable salt thereof.

[0199] In some embodiments, the compound of formula I is a compound of formula IVq or a pharmaceutically acceptable salt thereof.

[0200] In some embodiments, the compound of formula I is a compound of formula IVr or a pharmaceutically acceptable salt thereof.

[0201] In some embodiments, the compound of formula I is a compound of formula IVs or a pharmaceutically acceptable salt thereof.

[0202] In some embodiments, the compound of formula I is a compound of formula IVt or a pharmaceutically acceptable salt thereof.

[0203] In some embodiments, the compound of formula I is a compound of formula IVu or a pharmaceutically acceptable salt thereof.

[0204] In some embodiments, the compound of formula I is a compound of formula IVv or a pharmaceutically acceptable salt thereof.

[0205] In some embodiments, the compound of formula I is a compound of formula Va, Vb, Vc, Vd, Ve, Vf, Vg, Vh, VIi, Vj, Vk, Vm, or Vn:

[0206]

[0207]

[0208] Or its pharmaceutically acceptable salt.

[0209] In some embodiments, the compound of formula I is a compound of formula Va or a pharmaceutically acceptable salt thereof.

[0210] In some embodiments, the compound of formula I is a compound of formula Vb or a pharmaceutically acceptable salt thereof.

[0211] In some embodiments, the compound of formula I is a compound of formula Vc or a pharmaceutically acceptable salt thereof.

[0212] In some embodiments, the compound of formula I is a compound of formula Vd or a pharmaceutically acceptable salt thereof.

[0213] In some embodiments, the compound of formula I is a compound of formula Ve or a pharmaceutically acceptable salt thereof.

[0214] In some embodiments, the compound of formula I is a compound of formula Vf or a pharmaceutically acceptable salt thereof.

[0215] In some embodiments, the compound of formula I is a compound of formula Vg or a pharmaceutically acceptable salt thereof.

[0216] In some embodiments, the compound of formula I is a compound of formula Vh or a pharmaceutically acceptable salt thereof.

[0217] In some embodiments, the compound of formula I is a compound of formula Vi or a pharmaceutically acceptable salt thereof.

[0218] In some embodiments, the compound of formula I is a compound of formula Vj or a pharmaceutically acceptable salt thereof.

[0219] In some embodiments, the compound of formula I is a compound of formula Vk or a pharmaceutically acceptable salt thereof.

[0220] In some embodiments, the compound of formula I is a compound of formula Vm or a pharmaceutically acceptable salt thereof.

[0221] In some embodiments, the compound of formula I is a compound of formula Vn or a pharmaceutically acceptable salt thereof.

[0222] In some implementations of the formula Va-Vn, m is 0, 1, 2, 3 or 4.

[0223] In some implementations of the formula Va-Vn, m is 0, 1, 2 or 3.

[0224] In some implementations of the formula Va-Vn, m is 0, 1, or 2.

[0225] In some implementations of the formula Va-Vn, m is 0 or 1.

[0226] In some embodiments, the compound of formula I is a compound of formula VIa, VIb, VIc, VId, VIe, VIf, VIg, VIh, VIi, VIj, VIk, VIm, or VIn:

[0227]

[0228]

[0229] Or its pharmaceutically acceptable salt.

[0230] In some embodiments, the compound of formula I is a compound of formula VIa or a pharmaceutically acceptable salt thereof.

[0231] In some embodiments, the compound of formula I is a compound of formula VIb or a pharmaceutically acceptable salt thereof.

[0232] In some embodiments, the compound of formula I is a compound of formula VIc or a pharmaceutically acceptable salt thereof.

[0233] In some embodiments, the compound of formula I is a compound of formula VId or a pharmaceutically acceptable salt thereof.

[0234] In some embodiments, the compound of formula I is a compound of formula VIe or a pharmaceutically acceptable salt thereof.

[0235] In some embodiments, the compound of formula I is a compound of formula VIf or a pharmaceutically acceptable salt thereof.

[0236] In some embodiments, the compound of formula I is a compound of formula VIg or a pharmaceutically acceptable salt thereof.

[0237] In some embodiments, the compound of formula I is a compound of formula VIh or a pharmaceutically acceptable salt thereof.

[0238] In some embodiments, the compound of formula I is a compound of formula VIi or a pharmaceutically acceptable salt thereof.

[0239] In some embodiments, the compound of formula I is a compound of formula VIj or a pharmaceutically acceptable salt thereof.

[0240] In some embodiments, the compound of formula I is a compound of formula VIk or a pharmaceutically acceptable salt thereof.

[0241] In some embodiments, the compound of formula I is a compound of formula VIm or a pharmaceutically acceptable salt thereof.

[0242] In some embodiments, the compound of formula I is a compound of formula VIn or a pharmaceutically acceptable salt thereof.

[0243] In some implementations of formula VIa-VIn, m is 0, 1, 2, 3 or 4.

[0244] In some implementations of formula VIa-VIn, m is 0, 1, 2 or 3.

[0245] In some implementations of formula VIa-VIn, m is 0, 1, or 2.

[0246] In some implementations of formula VIa-VIn, m is 0 or 1.

[0247] In some embodiments, the compound of formula I is a compound of formula VIIa, VIIb, VIIc, VIId, VIIe, VIIf, VIIg, VIIh, VIIi, VIIj, VIIk, VIIm, VIIn, or VIIo:

[0248]

[0249]

[0250] Or its pharmaceutically acceptable salt.

[0251] In some embodiments, the compound of formula I is a compound of formula VIIa or a pharmaceutically acceptable salt thereof.

[0252] In some embodiments, the compound of formula I is a compound of formula VIIb or a pharmaceutically acceptable salt thereof.

[0253] In some embodiments, the compound of formula I is a compound of formula VIIc or a pharmaceutically acceptable salt thereof.

[0254] In some embodiments, the compound of formula I is a compound of formula VIId or a pharmaceutically acceptable salt thereof.

[0255] In some embodiments, the compound of formula I is a compound of formula VIIe or a pharmaceutically acceptable salt thereof.

[0256] In some embodiments, the compound of formula I is a compound of formula VIIf or a pharmaceutically acceptable salt thereof.

[0257] In some embodiments, the compound of formula I is a compound of formula VIIg or a pharmaceutically acceptable salt thereof.

[0258] In some embodiments, the compound of formula I is a compound of formula VIIh or a pharmaceutically acceptable salt thereof.

[0259] In some embodiments, the compound of formula I is a compound of formula VIIi or a pharmaceutically acceptable salt thereof.

[0260] In some embodiments, the compound of formula I is a compound of formula VIIj or a pharmaceutically acceptable salt thereof.

[0261] In some embodiments, the compound of formula I is a compound of formula VIIk or a pharmaceutically acceptable salt thereof.

[0262] In some embodiments, the compound of formula I is a compound of formula VIIm or a pharmaceutically acceptable salt thereof.

[0263] In some embodiments, the compound of formula I is a compound of formula VIIn or a pharmaceutically acceptable salt thereof.

[0264] In some embodiments, the compound of formula I is a compound of formula VIIo or a pharmaceutically acceptable salt thereof.

[0265] In some implementations of formulas VIIa-VIIo, m is 0, 1, 2, 3 or 4.

[0266] In some implementations of formulas VIIa-VIIo, m is 0, 1, 2 or 3.

[0267] In some implementations of formulas VIIa-VIIo, m is 0, 1, or 2.

[0268] In some implementations of formulas VIIa-VIIo, m is 0 or 1.

[0269] In some embodiments, the compound of formula I is a compound of formula VIIIa, VIIIb, VIIIc, VIIId, VIIIe, VIIIf, VIIIg, VIIIh, VIIIi, VIIIj, VIIIk, VIIIm, VIIIn, or VIIIo:

[0270]

[0271]

[0272]

[0273] Or its pharmaceutically acceptable salt.

[0274] In some embodiments, the compound of formula I is a compound of formula VIIIa or a pharmaceutically acceptable salt thereof.

[0275] In some embodiments, the compound of formula I is a compound of formula VIIIb or a pharmaceutically acceptable salt thereof.

[0276] In some embodiments, the compound of formula I is a compound of formula VIIIc or a pharmaceutically acceptable salt thereof.

[0277] In some embodiments, the compound of formula I is a compound of formula VIIId or a pharmaceutically acceptable salt thereof.

[0278] In some embodiments, the compound of formula I is a compound of formula VIIIe or a pharmaceutically acceptable salt thereof.

[0279] In some embodiments, the compound of formula I is a compound of formula VIIIf or a pharmaceutically acceptable salt thereof.

[0280] In some embodiments, the compound of formula I is a compound of formula VIIIg or a pharmaceutically acceptable salt thereof.

[0281] In some embodiments, the compound of formula I is a compound of formula VIIIh or a pharmaceutically acceptable salt thereof.

[0282] In some embodiments, the compound of formula I is a compound of formula VIIIi or a pharmaceutically acceptable salt thereof.

[0283] In some embodiments, the compound of formula I is a compound of formula VIIIj or a pharmaceutically acceptable salt thereof.

[0284] In some embodiments, the compound of formula I is a compound of formula VIIIk or a pharmaceutically acceptable salt thereof.

[0285] In some embodiments, the compound of formula I is a compound of formula VIIIm or a pharmaceutically acceptable salt thereof.

[0286] In some embodiments, the compound of formula I is a compound of formula VIIIn or a pharmaceutically acceptable salt thereof.

[0287] In some embodiments, the compound of formula I is a compound of formula VIIIo or a pharmaceutically acceptable salt thereof.

[0288] In some implementations of formulas VIIIa-VIIIo, m is 0, 1, 2, 3 or 4.

[0289] In some implementations of formulas VIIIa-VIIIo, m is 0, 1, 2 or 3.

[0290] In some implementations of formulas VIIIa-VIIIo, m is 0, 1, or 2.

[0291] In some implementations of formulas VIIIa-VIIIo, m is 0 or 1.

[0292] In some implementations of any of formulas I-VIIIo, each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs.4A Substituent substitution.

[0293] In some implementations of any of formulas I-VIIIo, each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, (4-10 heterocycloalkyl)-C 1-6 Alkyl-, OR a4 and C(O)R b4 , where R 4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl and (4-10-membered heterocycloalkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution.

[0294] In some implementations of any of formulas I-VIIIo, each R 4 Independently selected from halogenated groups and oxygenated groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 4A Substituent substitution.

[0295] In some implementations of any of formulas I-VIIIo, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 6-10 aryl, 5-6 membered heteroaryl, 4-10 membered heterocyclic alkyl, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl-, ORa4 and C(O)R b4 , where R 4 The C mentioned 1-6 Alkyl, C 6-10 aryl, 5-6 membered heteroaryl, 4-10 membered heterocyclic alkyl and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently selected R 4A Substituent substitution.

[0296] In some implementations of any of formulas I-VIIIo, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 6-10 Aryl and 4-10 membered heterocyclic alkyl groups, wherein R 4 The C mentioned 1-6 Alkyl, C 6-10 The aryl group and the 4-10 membered heterocyclic alkyl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 4A Substituent substitution.

[0297] In some implementations of any of formulas I-VIIIo, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, phenyl, 5-6 membered heteroaryl, 8-10 membered heterocyclic alkyl, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl-, OR a4 and C(O)R b4 , where R 4 The C mentioned 1-6 Alkyl, phenyl, 5-6 membered heteroaryl, 8-10 membered heterocyclic alkyl, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution.

[0298] In some implementations of any of formulas I-VIIIo, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, phenyl and 8-10 membered heterocyclic alkyl groups, wherein R 4 The C mentioned 1-6 Alkyl, phenyl, and 8-10 membered heterocyclic alkyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4A Substituent substitution.

[0299] In some implementations of any of formulas I-VIIIo, each R 4Independently selected from fluorine, methyl, isopropyl, methoxy, morpholinylcarbonyl, phenyl, pyrazolyl, piperidinyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl, wherein R 4 The methyl, isopropyl, phenyl, pyrazolyl, piperidinyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 4A Substituent substitution.

[0300] In some implementations of any of formulas I-VIIIo, each R 4 Independently selected from fluorine, methyl, phenyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl, wherein R 4 The methyl, phenyl, and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4A Substituent substitution.

[0301] In some implementations of any of formulas I-VIIIo, R 4 Selected from C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The C mentioned 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 4A Substituent substitution.

[0302] In some implementations of any of formulas I-VIIIo, R 4 Selected from phenyl, C 3-7 Cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, and 4-7-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 4A Substituent substitution.

[0303] In some implementations of any of formulas I-VIIIo, R 4 Selected from phenyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, OR a4 and NR c4 C(O)ORa4 , where R 4 The phenyl, 5-6-membered heteroaryl and 4-7-membered heterocyclic alkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 4A Substituent substitution.

[0304] In some implementations of any of formulas I-VIIIo, R 4 Selected from phenyl, tetrahydropyranyl, pyrazolyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The phenyl, tetrahydropyranyl, and pyrazolyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4A Substituent substitution.

[0305] In some implementations of any of formulas I-VIIIo, each R 4 Selected from phenyl, tetrahydropyranyl, pyrazolyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The phenyl, tetrahydropyranyl, and pyrazolyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4A Substituent substitution.

[0306] In some implementations of any of formulas I-VIIIo, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne and 5-6 heteroaryl groups, wherein R 4 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl and 5-6 heteroaryl groups are optionally separated by 1, 2, 3 or 4 independently selected R groups. 4A Substituent substitution.

[0307] In some implementation schemes, R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and 5-6-membered heteroaryl groups, wherein R 4 Each C 1-6 Alkyl groups and 5-6 heteroaryl groups are optionally separated by 1, 2, 3 or 4 independently selected R groups. 4A Substituent substitution.

[0308] In some implementations of any of formulas I-VIIIo, each R 4Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0309] In some implementations of any of formulas I-VIIIo, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

[0310] In some implementations of any of formulas I-VIIIo, each R 4 Selected independently from C 1-6 Halogenated alkyl groups.

[0311] In some implementations of any of formulas I-VIIIo, each R 4 Independently selected from fluorine, methyl, trifluoromethyl, phenyl, pyrazolyl, tetrahydropyranyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl, wherein R 4 The methyl, phenyl, pyrazolyl, tetrahydropyranyl, and 2,3-dihydrobenzo[b][1,4]dioxaneyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4A Substituent substitution.

[0312] In some implementations of any of formulas I-VIIIo, each R 4 It is independently selected from fluorine, methyl, hydroxymethyl, hydroxyisopropyl, methoxy, (methylcarbonyl)piperidinyl, methylpyrazolyl, trifluoromethyl, cyanophenyl, pyrazolyl, tetrahydropyranyl, 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl, (difluoromethylazacyclobutyl)methyl and morpholinylcarbonyl.

[0313] In some implementations of any of formulas I-VIIIo, each R 4 It is independently selected from fluorine, methyl, trifluoromethyl, cyanophenyl, pyrazolyl, tetrahydropyranyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl.

[0314] In some implementations of any of formulas I-VIIIo, R 4 Independently selected from fluorine, methyl, hydroxymethyl, hydroxyisopropyl, methoxy, (methylcarbonyl)piperidinyl, methylpyrazolyl, cyanophenyl, 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl and (difluoromethylazacyclobutyl)methyl and morpholinylcarbonyl.

[0315] In some implementations of any of formulas I-VIIIo, R 4It is independently selected from fluorine, methyl, cyanophenyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl.

[0316] In some implementations of any of formulas I-VIIIo, R 4 It is trifluoromethyl.

[0317] In some implementations of any of formulas I-VIIIo, each R a4 R b4 R c4 and R d4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0318] In some implementations of any of formulas I-VIIIo, each R a4 and R c4 Independently selected from H and C 1-6 alkyl.

[0319] In some implementations of any of formulas I-VIIIo, each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a41 and C(O)R b41 .

[0320] In some implementations of any of formulas I-VIIIo, each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a41 .

[0321] In some implementations of any of formulas I-VIIIo, each R a41 and R b41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0322] In some implementations of any of formulas I-VIIIo, each R a41 Independently selected from H and C 1-6 Alkyl, C 1-6Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0323] In some implementations of any of formulas I-VIIIo, each R a41 Independently selected from H and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

[0324] In some implementations of any of formulas I-VIIIo, each R a41 Independently selected from H and C 1-6 alkyl.

[0325] In some implementations of any of formulas I-VIIIo, each R b41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0326] In some implementations of any of formulas I-VIIIo, each R b41 Independently selected from H and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

[0327] In some implementations of any of formulas I-VIIIo, each R b41 Independently selected from H and C 1-6 alkyl.

[0328] In some implementations of any of formulas I-VIIIo, each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a41 and C(O)R b41 ;and

[0329] Each R a41 and R b41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0330] In some implementations of any of formulas I-VIIIo, each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C2-6 alkenyl, C 2-6 Alkyne, CN, OR a41 and C(O)R b41 ;and

[0331] Each R a41 and R b41 Independently selected from H and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

[0332] In some implementations of any of formulas I-VIIIo, each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a41 and C(O)R b41 ;and

[0333] Each R a41 and R b41 Independently selected from H and C 1-6 alkyl.

[0334] In some implementations of any of formulas I-VIIIo, each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a41 ;and

[0335] Each R a41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0336] In some implementations of any of formulas I-VIIIo, each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a41 ;and

[0337] Each R a41 Independently selected from H and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

[0338] In some implementations of any of formulas I-VIIIo, each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a41 ;and

[0339] Each R a41 Independently selected from H and C 1-6 alkyl.

[0340] In some implementations of any of formulas I-VIIIo, each R 4A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne group and CN.

[0341] In some implementations, each R 4A Selected independently from C 1-6 Halogenated alkyl groups, CN and OR a41 .

[0342] In some implementations, each R 4A Selected independently from C 1-6 Halogenated alkyl groups, CN and OR a41 ;and

[0343] Each R a41 Independently selected from H and C 1-6 alkyl.

[0344] In some implementations of any of formulas I-VIIIo, each R 4A Selected independently from C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne group and CN.

[0345] In some implementations of any of formulas I-VIIIo, each R 4A Selected independently from C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and CN.

[0346] In some implementations of any of formulas I-VIIIo, each R 4A Selected independently from C 1-6 Alkyl groups and CN.

[0347] In some implementations of any of formulas I-VIIIo, each R4A It is independently selected from methyl, difluoromethyl, CN, OH and methyl carbonyl.

[0348] In some implementations of any of formulas I-VIIIo, each R 4A It is independently selected from methyl and CN.

[0349] In some implementations of any of formulas I-VIIIo, each R 4A For CN.

[0350] In some implementation schemes, R 4 Selected independently from C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and 5-6-membered heteroaryl groups, wherein R 4 Each C 1-6 Alkyl groups and 5-6 heteroaryl groups are optionally surrounded by 1, 2, 3 or 4 R groups. 4A Substituent substitution;

[0351] Each R 4A Selected independently from C 1-6 Halogenated alkyl groups, CN and OR a41 ;and

[0352] Each R a41 Independently selected from H and C 1-6 alkyl.

[0353] In some implementations of any of formulas I-VIIIo, R 4 Selected from methyl, ethyl, isopropyl, trifluoromethyl, and pyridyl, wherein R 4 Each of the methyl, ethyl, isopropyl, and pyridyl groups is optionally represented by one or two independently selected from C10. 1-3 Halogenated alkyl groups, CN, OH and C 1-3 alkoxy R 4A Substituent substitution.

[0354] In some implementations of any of formulas I-VIIIo, R 5 Selected from C 1-6 Alkyl, C 3-12 Cycloalkyl, phenyl, 5-12-membered heteroaryl, pyrrolyl, piperidinyl, tetrahydropyranyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NR w2 R w3 C(O)R w2 C(O)NR w2 R w3 C(O)R w2 NRw3 C(O)R w2 NR w3 C(O)OR w2 and NR w3 S(O)2R w2 , where R 5 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution; and

[0355] Where R 5 The C mentioned 1-6 Alkyl and phenyl groups are each surrounded by one R group w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0356] R 5 The phenyl group is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution.

[0357] In some implementations of any of formulas I-VIIIo, R 5 Selected from C 1-6 Alkyl, C 3-12 Cycloalkyl, phenyl, triazolyl, pyrazolyl, imidazolyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NR w2 R w3 C(O)R w2 C(O)NR w2 R w3 C(O)R w2 NR w3 C(O)R w2 NR w3 C(O)OR w2 and NR w3 S(O)2R w2 R 5 The C mentioned 3-12Cycloalkyl, triazolyl, imidazolyl, pyrazolyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution; and

[0358] Where R 5 The C mentioned 1-6 Alkyl and phenyl groups are each surrounded by one R group w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0359] R 5 The phenyl group is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution.

[0360] In some implementations of any of formulas I-VIIIo, R 5 Selected from C 1-6 Alkyl, C 3-7 Cycloalkyl, phenyl, triazolyl, pyrazolyl, imidazolyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NHR w2 C(O)R w2 C(O)NHR w2 C(O)R w2 ,NHC(O)R w2 ,NHC(O)OR w2 and NHS(O)2R w2 , where R 5 The C mentioned 3-12 Cycloalkyl, triazolyl, imidazolyl, pyrazolyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution; and

[0361] Where R 5 The C mentioned 1-6 Alkyl and phenyl groups are each surrounded by one R group w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0362] R 5 The phenyl group is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution.

[0363] In some implementations of any of formulas I-VIIIo, R 5 Selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, NR w2 R w3 and C(O)R w2 , where R 5 The C mentioned 3-12 The cycloalkyl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution.

[0364] In some implementations of any of formulas I-VIIIo, R 5 Selected from C 3-12 Cycloalkyl, 5-12 membered heteroaryl, NHR w2 and C(O)R w2 , where R 5 The C mentioned 3-12 The cycloalkyl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution.

[0365] In some implementations of any of formulas I-VIIIo, R 5 Selected from C 1-6 Alkyl, C 3-7 Cycloalkyl, phenyl, 5-10 membered heteroaryl, pyrrolyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NHR w2 C(O)R w2 and C(O)NHR w2 ;

[0366] Where R 5 The C mentioned 1-6 Alkyl and phenyl groups are each surrounded by one R group w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0367] R 5 The phenyl group is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; and

[0368] R 5 The C mentioned 3-7 Cycloalkyl, 5-10-membered heteroaryl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0369] In some implementations of any of formulas I-VIIIo, R 5 Selected from C 1-6 Alkyl, C 3-12 cycloalkyl, C 6-10 Aryl, 5-12-membered heteroaryl, pyrrolyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NR w2 R w3 C(O)R w2 and C(O)NR w2 R w3 ;

[0370] Where R 5 The C mentioned 1-6 Alkyl and C 6-10 Each aryl group is controlled by one R. w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0371] R 5 The C mentioned 6-10 Aryl is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; and

[0372] R 5 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0373] In some implementations of any of formulas I-VIIIo, R 5 Selected from C 1-6 Alkyl, C 3-12 cycloalkyl, C6-10 Aryl, 5-12-membered heteroaryl, pyrrolyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NHR w2 C(O)R w2 and C(O)NHR w2 ;

[0374] Where R 5 The C mentioned 1-6 Alkyl and C 6-10 Each aryl group is controlled by one R. w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0375] R 5 The C mentioned 6-10 Aryl is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; and

[0376] R 5 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0377] In some implementations of any of formulas I-VIIIo, R 5 Selected from -CH2R w1 C 3-7 cycloalkyl, -phenyl-R w1 ,-phenyl-R w5 , pyrazolyl, pyridinyl, indazole, quinolinyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NHR w2 C(O)R w2 and C(O)NHR w2 , where R 5 The C mentioned 3-7Cycloalkyl, phenyl, pyrazolyl, pyridinyl, indazolyl, quinolinyl, pyrrolyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0378] In some implementations of any of formulas I-VIIIo, R 5 Selected from triazolyl, pyrazolyl, piperidinyl, tetrahydropyranyl, NR w2 R w3 NR w3 C(O)R w2 NR w3 C(O)OR w2 and NR w3 S(O)2R w2 , where R 5 The triazolyl, pyrazolyl, piperidinyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution.

[0379] In some implementations of any of formulas I-VIIIo, R 5 Selected from triazolyl, pyrazolyl, piperidinyl, tetrahydropyranyl, NHR w2 ,NHC(O)R w2 ,NHC(O)OR w2 and NHS(O)2R w2 , where R 5 The triazolyl, pyrazolyl, piperidinyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution.

[0380] In some implementations of any of formulas I-VIIIo, R 5 Selected from C 3-7 cycloalkyl, 5-6 membered heteroaryl, NHR w2 and C(O)R w2 , where R 5 The C mentioned 3-7 The cycloalkyl group and the 5-6-membered heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution.

[0381] In some implementations of any of formulas I-VIIIo, R 5 Selected from cyclopropyl, pyrazolyl, imidazole, and NHR w2 and C(O)R w2 , where R 5The cyclopropyl, pyrazolyl, and imidazole groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution.

[0382] In some implementations of any of formulas I-VIIIo, R w1 Selected from C 3-12 Cycloalkyl, 4-12 membered heterocyclic alkyl, OR w4 and NHR w4 , where R w1 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution.

[0383] In some implementations of any of formulas I-VIIIo, R w1 Selected from C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, OR w4 and NHR w4 , where R w1 The C mentioned 3-7 The cycloalkyl group and the 4-7 membered heterocycloalkyl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution.

[0384] In some implementations of any of formulas I-VIIIo, R w1 It is selected from cyclopropyl, fluoropyrrolyl, morpholinyl, trifluoromethoxy and cyclopentylamino.

[0385] In some implementations of any of formulas I-VIIIo, R w2 Selected from C 3-7 Cycloalkyl, bicyclic 8-12-membered heteroaryl, monocyclic 4-7-membered heterocyclic alkyl, and bicyclic 8-12-membered heterocyclic alkyl, wherein R w2 The C mentioned 3-7 Cycloalkyl, bicyclic 8-12-membered heteroaryl, monocyclic 4-7-membered heterocycloalkyl, and bicyclic 8-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution.

[0386] In some implementations of any of formulas I-VIIIo, R w2 Selected from C 3-7 Cycloalkyl, 4-8 membered monocyclic heterocyclic alkyl and 6-10 membered bicyclic heterocyclic alkyl, wherein R w2 The C mentioned 3-7 Cycloalkyl, 4-8 membered monocyclic heterocyclic alkyl and 6-10 membered bicyclic heterocyclic alkyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0387] In some implementations of any of formulas I-VIIIo, R w2 Selected independently from C 3-12 Cycloalkyl 4-12 membered heterocyclic alkyl groups, wherein R w2 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0388] In some implementations of any of formulas I-VIIIo, each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution;

[0389] In some implementations of any of formulas I-VIIIo, each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution;

[0390] In some implementations of any of formulas I-VIIIo, each R w2 Selected independently from C 3-7 Cycloalkyl, 5-6-membered heteroaryl and 4-7-membered heterocycloalkyl, wherein R w2 The C mentioned 3-7 Cycloalkyl, 5-6-membered heteroaryl, and 4-7-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution.

[0391] In some implementations of any of formulas I-VIIIo, R w2 Selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolyl, piperidinyl, morpholinyl, tetrahydropyranyl, oxazolyl, octahydro-2H-pyrido[1,2-a]pyrazinyl, quinolinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, and 2-oxa-5-azabicyclo[4.1.0]heptyl, wherein R w2The cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl, oxazolyl, octahydro-2H-pyrido[1,2-a]pyrazinyl, quinolinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, and 2-oxa-5-azabicyclo[4.1.0]heptyl are each optionally selected by 1, 2, 3, or 4 independently chosen R 5A Substituent substitution.

[0392] In some implementations of any of formulas I-VIIIo, R w2 Selected from cyclobutyl, cyclopentyl, cyclohexyl, pyrrolyl, piperidinyl, morpholinyl, tetrahydropyranyl, octahydro-2H-pyrido[1,2-a]pyrazinyl, quinolinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, and 2-oxa-5-azabicyclo[4.1.0]heptyl, wherein R w2 The cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl, octahydro-2H-pyrido[1,2-a]pyrazinyl, quinolinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and 2-oxa-5-azabicyclo[4.1.0]heptyl are each optionally replaced by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0393] In some implementations of any of formulas I-VIIIo, R w2 Selected from cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl, octahydro-2H-pyrido[1,2-a]pyrazinyl, quinolinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, and 2-oxa-5-azabicyclo[4.1.0]heptyl, wherein R w2 The cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl, octahydro-2H-pyrido[1,2-a]pyrazinyl, quinolinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and 2-oxa-5-azabicyclo[4.1.0]heptyl are each optionally replaced by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0394] In some implementations of any of formulas I-VIIIo, R w2Selected from cyclobutyl, cyclopentyl, piperidinyl, morpholinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and 2-oxa-5-azabicyclo[4.1.0]heptyl, wherein R w2 The cyclobutyl, cyclopentyl, piperidinyl, morpholinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and 2-oxa-5-azabicyclo[4.1.0]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0395] In some implementations of any of formulas I-VIIIo, R w2 Selected from cyclopentyl, piperidinyl, morpholinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and 2-oxa-5-azabicyclo[4.1.0]heptyl, wherein R w2 The cyclopentyl, piperidinyl, morpholinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and 2-oxa-5-azabicyclo[4.1.0]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0396] In some implementations of any of formulas I-VIIIo, R w2 Selected from cyclobutyl, cyclopentyl, cyclohexyl, quinolinyl, tetrahydropyranyl, piperidinyl, morpholinyl, pyrrolidinyl and octahydro-2H-pyrido[1,2-a]pyrazinyl, wherein R w2 The cyclobutyl, cyclopentyl, cyclohexyl, quinolinyl, tetrahydropyranyl, piperidinyl, morpholinyl, pyrrolidinyl, and octahydro-2H-pyrido[1,2-a]pyrazinyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution.

[0397] In some implementations of any of formulas I-VIIIo, R w2 Selected from cyclopentyl, cyclohexyl, quinolinyl, tetrahydropyranyl, piperidinyl, morpholinyl, pyrrolidinyl and octahydro-2H-pyrido[1,2-a]pyrazinyl, wherein R w2 The cyclopentyl, cyclohexyl, quinolinyl, tetrahydropyranyl, piperidinyl, morpholinyl, pyrrolidinyl, and octahydro-2H-pyrido[1,2-a]pyrazinyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution.

[0398] In some implementations of any of formulas I-VIIIo, each R w2 Independently selected from cyclopropyl, cyclobutyl, oxazolyl, and tetrahydropyranyl, wherein R w2 The cyclopropyl, cyclobutyl, oxazolyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution.

[0399] In some implementations of any of formulas I-VIIIo, each R w3 Independently selected from H and C 1-6 alkyl.

[0400] In some implementations of any of formulas I-VIIIo, each R w3 For H.

[0401] In some implementations of any of formulas I-VIIIo, each R w4 Selected independently from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl.

[0402] In some implementations of any of formulas I-VIIIo, each R w4 Selected from C 1-6 Halogenated alkyl groups and C 3-7 Cycloalkyl.

[0403] In some implementations of any of formulas I-VIIIo, R w5 C 1-6 Alkyl group, wherein the alkyl group is coated with CN or OR a51 replace.

[0404] In some implementations of any of formulas I-VIIIo, R w5 Selected from cyanomethyl and hydroxymethyl.

[0405] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, NO2, OR a51 SR a51 NHOR a51 C(O)R b51 C(O)NR c51R d51 C(O)NR c51 (OR a51 ), C(O)OR a51 OC(O)R b51 OC(O)NR c51 R d51 NR c51 R d51 NR c51 NR c51 R d51 、 NR c51 C(O)R b51 NR c51 C(O)OR a51 NR c51 C(O)NR c51 R d51 NR c51 S(O)R b51 NR c51 S(O)NR c51 R d51 NR c51 S(O)2R b51 NR c51 S(O)2NR c51 R d51 S(O)R b51 S(O)NR c51 R d51 S(O)2R b51 and S(O)2NR c51 R d51 , where R 5A Each C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl group is optionally composed of 1, 2, 3 or 4 independently selected R groups. 5B Substituent substitution.

[0406] In some implementations, each R 5B Selected independently from OR a52 .

[0407] In some implementations, each R a52 Independently selected from H and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

[0408] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C2-6 alkenyl, C 2-6 Alkyne, CN, NO2, OR a51 SR a51 NHOR a51 C(O)R b51 C(O)NR c51 R d51 C(O)NR c51 (OR a51 ), C(O)OR a51 OC(O)R b51 OC(O)NR c51 R d51 NR c51 R d51 NR c51 NR c51 R d51 、 NR c51 C(O)R b51 NR c51 C(O)OR a51 NR c51 C(O)NR c51 R d51 NR c51 S(O)R b51 NR c51 S(O)NR c51 R d51 NR c51 S(O)2R b51 NR c51 S(O)2NR c51 R d51 S(O)R b51 S(O)NR c51 R d51 S(O)2R b51 and S(O)2NR c51 R d51 , where R 5A Each C 1-6 Alkyl groups may optionally be replaced by OH.

[0409] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, NO2, OR a51 SR a51 NHOR a51 C(O)R b51C(O)NR c51 R d51 C(O)NR c51 (OR a51 ), C(O)OR a51 OC(O)R b51 OC(O)NR c51 R d51 NR c51 R d51 NR c51 NR c51 R d51 、 NR c51 C(O)R b51 NR c51 C(O)OR a51 NR c51 C(O)NR c51 R d51 NR c51 S(O)R b51 NR c51 S(O)NR c51 R d51 NR c51 S(O)2R b51 NR c51 S(O)2NR c51 R d51 S(O)R b51 S(O)NR c51 R d51 S(O)2R b51 and S(O)2NR c51 R d51 .

[0410] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 C(O)R b51 and C(O)OR a51 , where R 5A The C mentioned 1-6 The alkyl group is optionally represented by one, two, three, or four independently selected R groups. 5B Substituent substitution.

[0411] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 C(O)Rb51 and C(O)OR a51 , where R 5A The C mentioned 1-6 Alkyl groups may optionally be replaced by OH.

[0412] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 C(O)R b51 and C(O)OR a51 .

[0413] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a51 NR base c51 R d51 , where R 5A Each C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl group is optionally composed of 1, 2, 3 or 4 independently selected R groups. 5B Substituent substitution.

[0414] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a51 and NR c51 R d51 , where R 5A Each C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl group may optionally be replaced by OH.

[0415] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a51 and NR c51 Rd51 .

[0416] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 , where R 5A Each C 1-6 The alkyl group is optionally represented by one, two, three, or four independently selected R groups. 5B Substituent substitution.

[0417] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 , where R 5A Each C 1-6 Alkyl groups may optionally be replaced by OH.

[0418] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 .

[0419] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a51 .

[0420] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, CN and OR a51 .

[0421] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl and C(O)OR a51 .

[0422] In some implementations of any of formulas I-VIIIo, each R 5A It is independently selected from fluorine, methyl, trideuteryl, fluoromethyl, difluoromethyl, trifluoromethyl, CN, hydroxyl, methoxy, amino and ethoxycarbonyl.

[0423] In some implementations of any of formulas I-VIIIo, each R 5A It is independently selected from fluorine, methyl, trideuterylmethyl, fluoromethyl, trifluoromethyl, CN, hydroxyl, methoxy, amino and ethoxycarbonyl.

[0424] In some implementations of any of formulas I-VIIIo, each R 5A It is independently selected from fluoromethyl and ethoxycarbonyl.

[0425] In some implementations of any of formulas I-VIIIo, each R 5A It is independently selected from chlorine, fluorine, methyl, hydroxyisopropyl, difluoromethyl, trifluoromethyl, CN, methoxy and amino.

[0426] In some implementations of any of formulas I-VIIIo, each R 5A It is independently selected from fluorine, methyl, trifluoromethyl, CN, methoxy and amino.

[0427] In some implementations of any of formulas I-VIIIo, each R 5A It is independently selected from fluorine, methyl, trideuteryl, difluoromethyl, trifluoromethyl, CN and hydroxyl.

[0428] In some implementations of any of formulas I-VIIIo, each R 5A It is independently selected from fluorine, methyl, trideuteryl, CN and hydroxyl.

[0429] In some implementations of any of formulas I-VIIIo, each R a51 R b51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0430] In some implementations of any of formulas I-VIIIo, each R a51 and R b51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6Alkyne group.

[0431] In some implementations of any of formulas I-VIIIo, each R a51 R b51 R c51 and R d51 Independently selected from H and C 1-6 alkyl.

[0432] In some implementations of any of formulas I-VIIIo, each R a51 and R b51 Independently selected from H and C 1-6 alkyl.

[0433] In some implementations of any of formulas I-VIIIo, each R a51 Independently selected from H and C 1-6 alkyl.

[0434] In some implementations of any of formulas I-VIIIo, each R b51 Independently selected from H and C 1-6 alkyl.

[0435] In some implementations of any of formulas I-VIIIo, each R c51 Independently selected from H and C 1-6 alkyl.

[0436] In some implementations of any of formulas I-VIIIo, each R d51 Independently selected from H and C 1-6 alkyl.

[0437] In some implementations of any of formulas I-VIIIo:

[0438] R 4 Selected from C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The C mentioned 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 4A Substituent substitution;

[0439] Each R a4 R c4 and R d4 Independently selected from H and C 1-6 Alkyl, C1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0440] Each R 4A Selected independently from C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group and CN;

[0441] R 5 Selected from triazolyl, pyrazolyl, piperidinyl, tetrahydropyranyl, NR w2 R w3 NR w3 C(O)R w2 NR w3 C(O)OR w2 and NR w3 S(O)2R w2 , where R 5 The triazolyl, pyrazolyl, piperidinyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution;

[0442] Each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution;

[0443] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0444] Each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, NO2, OR a51 SR a51 NHOR a51 C(O)R b51 C(O)NR c51 R d51 C(O)NR c51 (ORa51 ), C(O)OR a51 OC(O)R b51 OC(O)NR c51 R d51 NR c51 R d51 NR c51 NR c51 R d51 、 NR c51 C(O)R b51 NR c51 C(O)OR a51 NR c51 C(O)NR c51 R d51 NR c51 S(O)R b51 NR c51 S(O)NR c51 R d51 NR c51 S(O)2R b51 NR c51 S(O)2NR c51 R d51 S(O)R b51 S(O)NR c51 R d51 S(O)2R b51 and S(O)2NR c51 R d51 ;and

[0445] Each R a51 R b51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0446] In some implementations of any of formulas I-VIIIo:

[0447] Each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, C2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 4A Substituent substitution;

[0448] Each R 4A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group and CN;

[0449] R 5 Selected from C 1-6 Alkyl, C 3-12 cycloalkyl, C 6-10 Aryl, 5-12-membered heteroaryl, pyrrolyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NR w2 R w3 C(O)R w2 and C(O)NR w2 R w3 ;

[0450] Where R 5 The C mentioned 1-6 Alkyl and C 6-10 Each aryl group is controlled by one R. w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0451] R 5 The C mentioned 6-10 Aryl is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; and

[0452] R 5 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution;

[0453] R w1 Selected from C3-12 Cycloalkyl, 4-12 membered heterocyclic alkyl, OR w4 and NHR w4 , where R w1 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0454] Each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution;

[0455] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0456] Each R w4 Selected independently from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl;

[0457] R w5 C 1-6 Alkyl group, wherein the alkyl group is coated with CN or OR a51 replace;

[0458] Each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a51 and NR c51 R d51 ;and

[0459] Each R a51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6Alkyne group.

[0460] In some implementations of any of formulas I-VIIIo:

[0461] Each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0462] R 5 Selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, NR w2 R w3 and C(O)R w2 , where R 5 The C mentioned 3-12 The cycloalkyl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0463] Each R w2 Selected independently from C 3-12 Cycloalkyl and 4-12 membered heterocyclic alkyl groups, wherein R w2 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0464] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 alkynyl group;

[0465] Each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a51 ;and

[0466] Each R a51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0467] In some implementations of any of formulas I-VIIIo, each R 4 Selected from phenyl, tetrahydropyranyl, pyrazolyl, ORa4 and NR c4 C(O)OR a4 , where R 4 The phenyl, tetrahydropyranyl, and pyrazolyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4A Substituent substitution; and

[0468] Each R a4 and R c4 Independently selected from H and C 1-6 Alkyl; and

[0469] Each R 4A Selected independently from C 1-6 Alkyl groups and CN.

[0470] In some implementations of any of formulas I-VIIIo, R 5 Selected from triazolyl, pyrazolyl, piperidinyl, tetrahydropyranyl, NHR w2 ,NHC(O)R w2 ,NHC(O)OR w2 and NHS(O)2R w2 , where R 5 The triazolyl, pyrazolyl, piperidinyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution;

[0471] Each R w2 Independently selected from cyclopropyl, cyclobutyl, oxazolyl, and tetrahydropyranyl, wherein R w2 The cyclopropyl, cyclobutyl, oxazolyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution;

[0472] Each R 5A Independently selected from halogenated groups, C 1-6 Alkyl and C(O)OR a51 ;and

[0473] Each R a51 Independently selected from H and C 1-6 alkyl.

[0474] In some implementations of any of formulas I-VIIIo, R w1 Selected from cyclopropyl, fluoropyrroleyl, morpholinyl, OR w4 and NHR w4 ;and

[0475] R w4 Selected from C 1-6 Halogenated alkyl groups and C 3-7 Cycloalkyl.

[0476] In some implementations of any of formulas I-VIIIo, R w5 C 1-6 Alkyl group, wherein the alkyl group is coated with CN or OR a51 Replace; and

[0477] R a51 Selected from H and C 1-3 alkyl.

[0478] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, NO2, OR a51 SR a51 NHOR a51 C(O)R b51 C(O)NR c51 R d51 C(O)NR c51 (OR a51 ), C(O)OR a51 OC(O)R b51 OC(O)NR c51 R d51 NR c51 R d51 NR c51 NR c51 R d51 、 NR c51 C(O)R b51 NR c51 C(O)OR a51 NR c51 C(O)NR c51 R d51 NR c51 S(O)R b51 NR c51 S(O)NR c51 R d51 NR c51 S(O)2R b51 NR c51 S(O)2NR c51 R d51 S(O)R b51 S(O)NR c51 R d51 S(O)2R b51 and S(O)2NR c51R d51 ;and

[0479] Each R a51 R b51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0480] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 C(O)R b51 and C(O)OR a51 ;and

[0481] Each R a51 and R b51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0482] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl and C(O)OR a51 ;and

[0483] Each R a51 Independently selected from H and C 1-6 alkyl.

[0484] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 ;and

[0485] Each R a51 R c51 and R d51 Independently selected from H and C 1-6 alkyl.

[0486] In some implementations of any of formulas I-VIIIo, each R 5A Independently selected from halogenated groups, C1-6 Alkyl, C 1-6 Halogenated alkyl groups, CN and OR a51 ;and

[0487] Each R a51 Independently selected from H and C 1-6 alkyl.

[0488] In some embodiments, the compound of formula I is a compound of formula II:

[0489]

[0490] II

[0491] Or its pharmaceutically acceptable salt, wherein:

[0492] R 4 Selected from C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The C mentioned 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 4A Substituent substitution;

[0493] Each R a4 R c4 and R d4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0494] Each R 4A Selected independently from C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group and CN;

[0495] R 5 Selected from triazolyl, pyrazolyl, piperidinyl, tetrahydropyranyl, NR w2 R w3 NR w3 C(O)R w2 NR w3 C(O)OR w2 and NR w3 S(O)2R w2 , where R5 The triazolyl, pyrazolyl, piperidinyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution;

[0496] Each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution;

[0497] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0498] Each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, NO2, OR a51 SR a51 NHOR a51 C(O)R b51 C(O)NR c51 R d51 C(O)NR c51 (OR a51 ), C(O)OR a51 OC(O)R b51 OC(O)NR c51 R d51 NR c51 R d51 NR c51 NR c51 R d51 、 NR c51 C(O)R b51 NR c51 C(O)OR a51 NR c51 C(O)NR c51 R d51 NR c51 S(O)R b51 NR c51 S(O)NR c51 R d51NR c51 S(O)2R b51 NR c51 S(O)2NR c51 R d51 S(O)R b51 S(O)NR c51 R d51 S(O)2R b51 and S(O)2NR c51 R d51 ;and

[0499] Each R a51 R b51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0500] In some implementations of either Formula I or II, R 4 Selected from phenyl, C 3-7 Cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, and 4-7-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 4A Substituent substitution.

[0501] In some implementations of either Formula I or II, R 4 Selected from phenyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The phenyl, 5-6-membered heteroaryl and 4-7-membered heterocyclic alkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 4A Substituent substitution.

[0502] In some implementations of either Formula I or II, R 4 Selected from phenyl, tetrahydropyranyl, pyrazolyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The phenyl, tetrahydropyranyl, and pyrazolyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4ASubstituent substitution.

[0503] In some implementations of either Formula I or II, R 4 Selected from phenyl, tetrahydropyranyl, pyrazolyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The phenyl, tetrahydropyranyl, and pyrazolyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4A Substituent substitution.

[0504] In some implementations of either Equation I or II, each R a4 R b4 R c4 and R d4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0505] In some implementations of either Equation I or II, each R a4 and R c4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0506] In some implementations of either Equation I or II, each R a4 Base R c4 Independently selected from H and C 1-6 alkyl.

[0507] In some implementations of either Equation I or II, each R a4 and R c4 Independently selected from H and C 1-3 alkyl.

[0508] In some implementations of either Formula I or II, R 4 Selected from phenyl, tetrahydropyranyl, pyrazolyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The phenyl, tetrahydropyranyl, and pyrazolyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4A Substituent substitution; and

[0509] Each R a4 and R c4 Independently selected from H and C1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0510] In some implementations of either Equation I or II, each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne group and CN.

[0511] In some implementations of either Equation I or II, each R 4A Selected independently from C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and CN.

[0512] In some implementations of either Equation I or II, each R 4A Selected independently from C 1-6 Alkyl groups and CN.

[0513] In some implementations of either Equation I or II, each R 4A Selected independently from C 1-3 Alkyl groups and CN.

[0514] In some implementations of either Equation I or II, each R 4A It is independently selected from methyl and CN.

[0515] In some implementations of either Formula I or II, R 4 Selected from phenyl, tetrahydropyranyl, pyrazolyl, OR a4 and NR c4 C(O)OR a4 , where R 4 The phenyl, tetrahydropyranyl, and pyrazolyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4A Substituent substitution; and

[0516] Each R a4 and R c4 Independently selected from H and C 1-6 Alkyl; and

[0517] Each R 4A Selected independently from C 1-6 Alkyl groups and CN.

[0518] In some implementations of either Formula I or II, R 5 Selected from triazolyl, pyrazolyl, piperidinyl, tetrahydropyranyl, NHR w2,NHC(O)R w2 ,NHC(O)OR w2 and NHS(O)2R w2 , where R 5 The triazolyl, pyrazolyl, piperidinyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution.

[0519] In some implementations of either Equation I or II, each R w2 Selected independently from C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R w2 The C mentioned 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution.

[0520] In some implementations of either Equation I or II, each R w2 Selected independently from C 3-7 Cycloalkyl, 5-6-membered heteroaryl and 4-7-membered heterocycloalkyl, wherein R w2 The C mentioned 3-7 Cycloalkyl, 5-6-membered heteroaryl, and 4-7-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution.

[0521] In some implementations of either Equation I or II, each R w2 Independently selected from cyclopropyl, cyclobutyl, oxazolyl, and tetrahydropyranyl, wherein R w2 The cyclopropyl, cyclobutyl, oxazolyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution.

[0522] In some implementations of either Equation I or II, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 C(O)R b51 and C(O)OR a51 .

[0523] In some implementations of either Equation I or II, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl and C(O)OR a51 .

[0524] In some implementations of either Equation I or II, each R a51 R b51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0525] In some implementations of either Equation I or II, each R a51 R b51 R c51 and R d51 Independently selected from H and C 1-6 alkyl.

[0526] In some implementations of either Equation I or II, each R a51 R b51 R c51 and R d51 Independently selected from H and C 1-3 alkyl.

[0527] In some implementations of either Equation I or II, each R a51 and R b51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0528] In some implementations of either Equation I or II, each R a51 Base R b51 Independently selected from H and C 1-6 alkyl.

[0529] In some implementations of either Equation I or II, each R a51 Base R b51 Independently selected from H and C 1-3 alkyl.

[0530] In some implementations of either Equation I or II, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 C(O)R b51 and C(O)OR a51 ;and

[0531] Each R a51 and R b51 Independently selected from H and C1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0532] In some implementations of either Equation I or II, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl and C(O)OR a51 ;and

[0533] Each R a51 Independently selected from H and C 1-6 alkyl.

[0534] In some implementations of either Equation I or II, each R 5A It is independently selected from fluoromethyl and ethoxycarbonyl.

[0535] In some implementations of either Formula I or II, R 5 Selected from triazolyl, pyrazolyl, piperidinyl, tetrahydropyranyl, NHR w2 ,NHC(O)R w2 ,NHC(O)OR w2 and NHS(O)2R w2 , where R 5 The triazolyl, pyrazolyl, piperidinyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution;

[0536] Each R w2 Independently selected from cyclopropyl, cyclobutyl, oxazolyl, and tetrahydropyranyl, wherein R w2 The cyclopropyl, cyclobutyl, oxazolyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution;

[0537] Each R 5A Independently selected from halogenated groups, C 1-6 Alkyl and C(O)OR a51 ;and

[0538] Each R a51 Independently selected from H and C 1-6 alkyl.

[0539] In some embodiments, the compound of formula I is a compound of formula IIIa, IIIb, IIIc, IIId, IIIe, IIIf, IIIg, IIIh, IIIi, or IIIj:

[0540]

[0541]

[0542] Or its pharmaceutically acceptable salt, wherein:

[0543] Each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 4A Substituent substitution;

[0544] Each R 4A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group and CN;

[0545] R 5 Selected from C 1-6 Alkyl, C 3-12 cycloalkyl, C 6-10 Aryl, 5-12-membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NR w2 R w3 C(O)R w2 and C(O)NR w2 R w3 ;

[0546] Where R 5 The C mentioned 1-6 Alkyl and C 6-10 Each aryl group is controlled by one R. w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0547] R 5 The C mentioned 6-10Aryl is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; and

[0548] R 5 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution;

[0549] R w1 Selected from C 3-12 Cycloalkyl, 4-12 membered heterocyclic alkyl, OR w4 and NHR w4 , where R w1 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0550] Each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution;

[0551] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0552] Each R w4 Selected independently from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl;

[0553] R w5 C 1-6 Alkyl group, wherein the alkyl group is coated with CN or OR a51 replace;

[0554] Each R5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a51 and NR c51 R d51 , where R 5A The C mentioned 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl groups are each optionally ORed a52 And substituted with 1, 2, 3, 4, 5, 6 or 7 independently selected halogen groups; and

[0555] Each R a51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group; and

[0556] Each R a52 Independently selected from H and C 1-6 alkyl.

[0557] In some implementation schemes of the previous implementation scheme:

[0558] Each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 4A Substituent substitution;

[0559] Each R 4A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group and CN;

[0560] R 5 Selected from C 1-6 Alkyl, C 3-12 cycloalkyl, C 6-10 Aryl, 5-12-membered heteroaryl, pyrrolyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NR w2 R w3 C(O)R w2 and C(O)NR w2 R w3 ;

[0561] Where R 5 The C mentioned 1-6 Alkyl and C 6-10 Each aryl group is controlled by one R. w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0562] R 5 The C mentioned 6-10 Aryl is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; and

[0563] R 5 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution;

[0564] R w1 Selected from C 3-12 Cycloalkyl, 4-12 membered heterocyclic alkyl, OR w4 and NHR w4 , where R w1 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0565] Each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution;

[0566] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0567] Each R w4 Selected independently from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl;

[0568] R w5 C 1-6 Alkyl group, wherein the alkyl group is coated with CN or OR a51 replace;

[0569] Each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a51 and NR c51 R d51 ;and

[0570] Each R a51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0571] In some embodiments, the compound of formula I is a compound of formula IIIa, IIIb, IIIc, IIId, IIIe, IIIf, IIIg, IIIh, IIIi, or IIIj:

[0572]

[0573] Or its pharmaceutically acceptable salt, wherein:

[0574] Each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 4A Substituent substitution;

[0575] Each R 4A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group and CN;

[0576] R 5 Selected from C 1-6 Alkyl, C 3-12 cycloalkyl, C 6-10 Aryl, 5-12-membered heteroaryl, pyrrolyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NR w2 R w3 C(O)R w2 and C(O)NR w2 R w3 ;

[0577] Where R 5 The C mentioned 1-6 Alkyl and C 6-10 Each aryl group is controlled by one R. w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0578] R 5 The C mentioned 6-10 Aryl is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; and

[0579] R 5 The C mentioned 3-12Cycloalkyl, 5-12-membered heteroaryl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution;

[0580] R w1 Selected from C 3-12 Cycloalkyl, 4-12 membered heterocyclic alkyl, OR w4 and NHR w4 , where R w1 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0581] Each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution;

[0582] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0583] Each R w4 Selected independently from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl;

[0584] R w5 C 1-6 Alkyl group, wherein the alkyl group is coated with CN or OR a51 replace;

[0585] Each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a51 and NR c51 Rd51 ;and

[0586] Each R a51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0587] In some embodiments, the compound of formula I is a compound of formula Va, Vb, Vc, Vd, Ve, Vf, Vg, Vh, VIi, Vj, Vk, Vm, or Vn:

[0588]

[0589]

[0590] Or its pharmaceutically acceptable salt, wherein:

[0591] Each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, (4-10 heterocycloalkyl)-C 1-6 Alkyl-, OR a4 and C(O)R b4 , where R 4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl and (4-10-membered heterocycloalkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution;

[0592] Each R a4 and R b4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne groups and 4-6 membered heterocyclic alkyl groups;

[0593] Each R 4AIndependently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a41 and C(O)R b41 ;

[0594] Each R a41 and R b41 Independently selected from H and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups;

[0595] R 5 Selected from C 1-6 Alkyl, C 3-12 cycloalkyl, C 6-10 Aryl, 5-12-membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NR w2 R w3 C(O)R w2 and C(O)NR w2 R w3 ;

[0596] Where R 5 The C mentioned 1-6 Alkyl and C 6-10 Each aryl group is controlled by one R. w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0597] R 5 The C mentioned 6-10 Aryl is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; and

[0598] R 5 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution;

[0599] R w1 Selected from C 3-12Cycloalkyl, 4-12 membered heterocyclic alkyl, OR w4 and NHR w4 , where R w1 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0600] Each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution;

[0601] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0602] Each R w4 Selected independently from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl;

[0603] R w5 C 1-6 Alkyl group, wherein the alkyl group is coated with CN or OR a51 replace;

[0604] Each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a51 and NR c51 R d51 , where R 5A The C mentioned 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl groups are each optionally ORed a52 Substitution with 1, 2, 3, 4, 5, 6 or 7 independently selected halogen groups;

[0605] Each R a51 Rc51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group; and

[0606] Each R a52 Independently selected from H and C 1-6 alkyl.

[0607] In some implementation schemes of the previous implementation scheme:

[0608] Each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 4A Substituent substitution;

[0609] Each R 4A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group and CN;

[0610] R 5 Selected from C 1-6 Alkyl, C 3-12 cycloalkyl, C 6-10 Aryl, 5-12-membered heteroaryl, pyrrolyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NR w2 R w3 C(O)R w2 and C(O)NR w2 R w3 ;

[0611] Where R 5 The C mentioned1-6 Alkyl and C 6-10 Each aryl group is controlled by one R. w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0612] R 5 The C mentioned 6-10 Aryl is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; and

[0613] R 5 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution;

[0614] R w1 Selected from C 3-12 Cycloalkyl, 4-12 membered heterocyclic alkyl, OR w4 and NHR w4 , where R w1 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0615] Each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution;

[0616] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0617] Each R w4 Selected independently from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10Cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl;

[0618] R w5 C 1-6 Alkyl group, wherein the alkyl group is coated with CN or OR a51 replace;

[0619] Each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a51 and NR c51 R d51 ;and

[0620] Each R a51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0621] In some embodiments, the compound of formula I is a compound of formula VIa, VIb, VIc, VId, VIe, VIf, VIg, VIh, VIi, VIj, VIk, VIm, or VIn:

[0622]

[0623]

[0624] Or its pharmaceutically acceptable salt, wherein:

[0625] Each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, (4-10 heterocycloalkyl)-C 1-6 Alkyl-, OR a4 and C(O)R b4 , where R 4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl and (4-10-membered heterocycloalkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution;

[0626] Each R a4 and R b4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne groups and 4-6 membered heterocyclic alkyl groups;

[0627] Each R 4A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a41 and C(O)R b41 ;

[0628] Each R a41 and R b41 Independently selected from H and C 1-6 Alkyl and C 1-6 Halogenated alkyl groups;

[0629] R 5 Selected from C 1-6 Alkyl, C 3-12 cycloalkyl, C 6-10 Aryl, 5-12-membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NR w2 R w3 C(O)R w2 and C(O)NR w2 R w3 ;

[0630] Where R 5 The C mentioned 1-6 Alkyl and C 6-10 Each aryl group is controlled by one R. w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0631] R 5 The C mentioned 6-10 Aryl is 1 R w5Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; and

[0632] R 5 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution;

[0633] R w1 Selected from C 3-12 Cycloalkyl, 4-12 membered heterocyclic alkyl, OR w4 and NHR w4 , where R w1 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0634] Each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution;

[0635] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0636] Each R w4 Selected independently from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl;

[0637] R w5 C 1-6 Alkyl group, wherein the alkyl group is coated with CN or OR a51 replace;

[0638] Each R 5A Independently selected from halogenated, oxo, and C groups.1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a51 and NR c51 R d51 , where R 5A The C mentioned 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl groups are each optionally ORed a52 Substitution with 1, 2, 3, 4, 5, 6 or 7 independently selected halogen groups;

[0639] Each R a51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group; and

[0640] Each R a52 Independently selected from H and C 1-6 alkyl.

[0641] In some implementation schemes of the previous implementation scheme:

[0642] Each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 4A Substituent substitution;

[0643] Each R 4A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group and CN;

[0644] R 5Selected from C 1-6 Alkyl, C 3-12 cycloalkyl, C 6-10 Aryl, 5-12-membered heteroaryl, pyrrolyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NR w2 R w3 C(O)R w2 and C(O)NR w2 R w3 ;

[0645] Where R 5 The C mentioned 1-6 Alkyl and C 6-10 Each aryl group is controlled by one R. w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0646] R 5 The C mentioned 6-10 Aryl is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; and

[0647] R 5 The C mentioned 3-12 Cycloalkyl, 5-12-membered heteroaryl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution;

[0648] R w1 Selected from C 3-12 Cycloalkyl, 4-12 membered heterocyclic alkyl, OR w4 and NHR w4 , where R w1 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0649] Each R w2 Selected independently from C 3-12 Cycloalkyl, 5-12-membered heteroaryl and 4-12-membered heterocycloalkyl, wherein R w2 The C mentioned 3-12Cycloalkyl, 5-12-membered heteroaryl, and 4-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution;

[0650] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0651] Each R w4 Selected independently from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl;

[0652] R w5 C 1-6 Alkyl group, wherein the alkyl group is coated with CN or OR a51 replace;

[0653] Each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a51 and NR c51 R d51 ;and

[0654] Each R a51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0655] In some implementations, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 6-10 aryl, 5-6 membered heteroaryl, 4-10 membered heterocyclic alkyl, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl-, OR a4 and C(O)R b4 , where R 4 The C mentioned 1-6 Alkyl, C 6-10aryl, 5-6 membered heteroaryl, 4-10 membered heterocyclic alkyl and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently selected R 4A Substituent substitution; and

[0656] Each R a4 and R b4 Independently selected from H and C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and 4-6 membered heterocyclic alkyl groups.

[0657] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, phenyl, 5-6 membered heteroaryl, 4-10 membered heterocyclic alkyl, (4-6 membered heterocyclic alkyl)-C 1-6 Alkyl-, OR a4 and C(O)R b4 , where R 4 The C mentioned 1-6 Alkyl, phenyl, 5-6 membered heteroaryl, 4-10 membered heterocyclic alkyl and (4-6 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution

[0658] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-Vin, each R a4 and R b4 Selected independently from C 1-6 Alkyl groups and 4-6 membered heterocyclic alkyl groups.

[0659] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, phenyl, 5-6 membered heteroaryl, 4-10 membered heterocyclic alkyl, (4-6 membered heterocyclic alkyl)-C 1-6 Alkyl-, OR a4 and C(O)R b4 , where R 4 The C mentioned 1-6 Alkyl, phenyl, 5-6 membered heteroaryl, 4-10 membered heterocyclic alkyl and (4-6 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution; and

[0660] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-Vin, each R a4 and R b4 Selected independently from C 1-6 Alkyl groups and 4-6 membered heterocyclic alkyl groups.

[0661] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 6-10 Aryl and 4-10 membered heterocyclic alkyl groups, wherein R 4 The C mentioned 1-6 Alkyl, C 6-10 The aryl group and the 4-10 membered heterocyclic alkyl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 4A Substituent substitution.

[0662] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, phenyl and 8-10 membered heterocyclic alkyl groups, wherein R 4 The C mentioned 1-6 Alkyl, phenyl, and 8-10 membered heterocyclic alkyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4A Substituent substitution.

[0663] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, phenyl and bicyclic 8-10 membered heterocyclic alkyl groups, wherein R 4 The C mentioned 1-6 Alkyl, phenyl, and bicyclic 8-10-membered heterocyclic alkyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4A Substituent substitution.

[0664] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4 Independently selected from fluorine, methyl, trideuteryl, isopropyl, methoxy, morpholinylcarbonyl, phenyl, pyrazolyl, pyridyl, tetrahydropyranyl, piperidinyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl, wherein R 4 The methyl, isopropyl, phenyl, pyrazolyl, piperidinyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups.4A Substituent substitution.

[0665] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4 Independently selected from fluorine, methyl, phenyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl, wherein R 4 The methyl, phenyl, and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 4A Substituent substitution.

[0666] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4A Selected independently from C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a41 and C(O)R b41 .

[0667] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R a41 and R b41 Independently selected from H and C 1-6 alkyl.

[0668] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4A Selected independently from C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a41 and C(O)R b41 ;and

[0669] Each R a41 and R b41 Independently selected from H and C 1-6 alkyl.

[0670] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4A It is selected from methyl, difluoromethyl, trifluoromethyl, CN, OH and methyl carbonyl.

[0671] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4A Selected independently from C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and CN.

[0672] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4A For CN.

[0673] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4 Independently selected from fluorine, methyl, trideuteryl, isopropyl, methoxy, morpholinylcarbonyl, phenyl, pyrazolyl, pyridyl, tetrahydropyranyl, piperidinyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl, wherein R 4 The methyl, isopropyl, phenyl, pyrazolyl, piperidinyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 4A Substituent substitution;

[0674] Each R 4A Selected independently from C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a41 and C(O)R b41 ;and

[0675] Each R a41 and R b41 Independently selected from H and C 1-6 alkyl.

[0676] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4 Independently selected from fluorine, methyl, trideuteryl, isopropyl, methoxy, morpholinylcarbonyl, phenyl, pyrazolyl, pyridyl, tetrahydropyranyl, piperidinyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl, wherein R 4 The methyl, isopropyl, phenyl, pyrazolyl, piperidinyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 4A Substituent substitution; and

[0677] Each R 4A It is selected from methyl, difluoromethyl, trifluoromethyl, CN, OH and methyl carbonyl.

[0678] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 4 It is independently selected from fluorine, methyl, cyanophenyl and 2,3-dihydrobenzo[b][1,4]dioxane-hexenyl.

[0679] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R 5 Selected from C 1-6 Alkyl, C 3-7 Cycloalkyl, phenyl, 5-10 membered heteroaryl, pyrrolyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NHR w2 C(O)R w2 and C(O)NHR w2 , where R 5 The C mentioned 3-7 Cycloalkyl, 5-10-membered heteroaryl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution; and

[0680] Where R 5 The C mentioned 1-6 Alkyl and phenyl groups are each surrounded by one R group w1 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution; or

[0681] R 5 The phenyl group is 1 R w5 Substituents and optionally substituted one or two independently selected R groups 5A Substituent substitution.

[0682] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R 5 Selected from -CH2R w1 C 3-7 cycloalkyl, -phenyl-R w1 ,-phenyl-R w5 5-10-membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NHR w2 C(O)R w2 and C(O)NHR w2 , where R 5 The C mentioned 3-7Cycloalkyl, phenyl, 5-10-membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0683] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R 5 Selected from -CH2R w1 C 3-7 cycloalkyl, -phenyl-R w1 ,-phenyl-R w5 5-10-membered heteroaryl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NHR w2 C(O)R w2 and C(O)NHR w2 , where R 5 The C mentioned 3-7 Cycloalkyl, phenyl, 5-10 heteroaryl, pyrrolyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0684] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R 5 Selected from -CH2R w1 C 3-7 cycloalkyl, -phenyl-R w1 ,-phenyl-R w5 Thiazolyl, thiophenyl, pyrazolyl, pyridinyl, indazole, quinolinyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NHR w2 C(O)R w2 and C(O)NHR w2 , where R 5 The C mentioned 3-7Cycloalkyl, phenyl, pyrazolyl, pyridinyl, indazolyl, quinolinyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0685] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R 5 Selected from -CH2R w1 C 3-7 cycloalkyl, -phenyl-R w1 ,-phenyl-R w5 Thiazolyl, thiophenyl, pyrazolyl, pyridinyl, indazole, quinolinyl, pyrrolylyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, azaspiro[2,4]heptyl, OR w2 NHR w2 C(O)R w2 and C(O)NHR w2 , where R 5 The C mentioned 3-7 Cycloalkyl, phenyl, pyrazolyl, pyridinyl, indazolyl, quinolinyl, pyrrolyl, piperidinyl, 2,3-dihydrobenzo[b][1,4]dioxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl and azaspiro[2,4]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0686] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w1 Selected from C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, OR w4 and NHR w4 , where R w1 The C mentioned 3-7 The cycloalkyl group and the 4-7 membered heterocycloalkyl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution.

[0687] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w1 Selected from C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, OR w4 and NHR w4 , where R w1The C mentioned 3-7 Cycloalkyl and 4-7 membered heterocycloalkyl groups are each optionally represented by one or two independently selected R groups. 5A Substituent substitution.

[0688] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w1 Selected from cyclopropyl, fluoropyrroleyl, morpholinyl, OR w4 and NHR w4 .

[0689] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w4 Selected from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl.

[0690] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w4 Selected from C 1-6 Haloalkyl, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl.

[0691] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w4 Selected from C 1-6 Halogenated alkyl groups and C 3-10 Cycloalkyl.

[0692] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w4 Selected from C 1-6 Halogenated alkyl groups and C 3-7 Cycloalkyl.

[0693] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w1 Selected from cyclopropyl, fluoropyrroleyl, morpholinyl, OR w4 and NHR w4 ;and

[0694] R w4 Selected from C 1-6 Halogenated alkyl groups and C 3-10 Cycloalkyl.

[0695] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w1 Selected from cyclopropyl, fluoropyrroleyl, morpholinyl, OR w4 and NHR w4 ;and

[0696] R w4 Selected from C 1-6 Halogenated alkyl groups and C 3-7 Cycloalkyl.

[0697] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w1 It is selected from cyclopropyl, fluoropyrrolyl, morpholinyl, trifluoromethoxy and cyclopentylamino.

[0698] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w2 Selected from C 3-7 Cycloalkyl, bicyclic 8-12-membered heteroaryl, monocyclic 4-7-membered heterocyclic alkyl, and bicyclic 8-12-membered heterocyclic alkyl, wherein R w2 The C mentioned 3-7 Cycloalkyl, bicyclic 8-12-membered heteroaryl, monocyclic 4-7-membered heterocycloalkyl, and bicyclic 8-12-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 5A Substituent substitution.

[0699] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w2 Selected from cyclobutyl, cyclopentyl, cyclohexyl, quinolinyl, tetrahydropyranyl, piperidinyl, morpholinyl, pyrrolidinyl and octahydro-2H-pyrido[1,2-a]pyrazinyl, wherein R w2 The cyclobutyl, cyclopentyl, cyclohexyl, quinolinyl, tetrahydropyranyl, piperidinyl, morpholinyl, pyrrolidinyl, and octahydro-2H-pyrido[1,2-a]pyrazinyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution.

[0700] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w5 C 1-6 Alkyl group, wherein the alkyl group is coated with CN or OR a51 replace.

[0701] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R a51R b51 R c51 and R d51 Independently selected from H and C 1-6 alkyl.

[0702] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R a51 Independently selected from H and C 1-6 alkyl.

[0703] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R a51 Independently selected from H and C 1-3 alkyl.

[0704] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R a51 Independently for C 1-3 alkyl.

[0705] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w5 C 1-6 Alkyl group, wherein the alkyl group is coated with CN or OR a51 Replace; and

[0706] R a51 Selected from H and C 1-3 alkyl.

[0707] In some implementations of any of formulas I, IIIa-IIIn, Va-Vn, and VIa-VIn, R w5 Selected from cyanomethyl and hydroxymethyl.

[0708] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5A Selected independently from each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 Wherein C 1-6 The alkyl group is optionally represented by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R groups. 5B Substituent substitution.

[0709] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 , where R 5A The C mentioned 1-6 The alkyl group is optionally represented by one, two, three, or four independently selected R groups. 5B Substituent substitution.

[0710] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 , where R 5A The C mentioned 1-6 Alkyl groups are optionally represented by one or two independently selected R groups. 5B Substituent substitution.

[0711] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5B Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and OH.

[0712] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5B It is independently selected from OH and halogenated groups.

[0713] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5B It is OH.

[0714] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5A Selected independently from each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 Wherein C 1-6 The alkyl group is optionally substituted with OH and 1, 2, 3, 4, 5, 6 or 7 independently selected halogroups.

[0715] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 , where R 5A The C mentioned 1-6 Alkyl groups may optionally be replaced by OH.

[0716] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 .

[0717] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 , where R 5A The C mentioned 1-6 Alkyl groups are optionally represented by one or two independently selected R groups. 5B Substituent substitution; and

[0718] Each R a51 R c51 and R d51 Independently selected from H and C 1-6 alkyl.

[0719] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 , where R 5A The C mentioned 1-6 The alkyl group is optionally substituted with OH; and

[0720] Each R a51 R c51and R d51 Independently selected from H and C 1-6 alkyl.

[0721] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl, CN, OR a51 and NR c51 R d51 ;and

[0722] Each R a51 R c51 and R d51 Independently selected from H and C 1-6 alkyl.

[0723] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5A It is independently selected from chlorine, fluorine, methyl, hydroxyisopropyl, hydroxyhexafluoroisopropyl, difluoromethyl, trifluoromethyl, CN, methoxy, ethoxy and amino.

[0724] In some implementations of any of Equations I, IIIa-IIIn, Va-Vn, and VIa-VIn, each R 5A It is independently selected from chlorine, fluorine, methyl, hydroxyisopropyl, difluoromethyl, trifluoromethyl, CN, methoxy and amino.

[0725] In some embodiments, the compound of formula I is a compound of formula IVa, IVb, IVc, IVd, IVe, IVf, IVg, IVh, IVVi, IVj, IVk, IVm, IVn, IVo, IVp, IVq, IVr, IVs, IVt, IVu, or IVv.

[0726]

[0727]

[0728] Or its pharmaceutically acceptable salt, wherein:

[0729] Each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6alkyl-, where R 4 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 Alkyl group - optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution;

[0730] Each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a41 ;

[0731] Each R a41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0732] R 5 Selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, NR w2 R w3 and C(O)R w2 , where R 5 The C mentioned 3-12 The cycloalkyl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0733] Each R w2 Selected independently from C 3-12 Cycloalkyl and 4-12 membered heterocyclic alkyl groups, wherein R w2 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0734] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 alkynyl group;

[0735] Each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a51 ;and

[0736] Each R a51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0737] In some embodiments, the compound of formula I is a compound of formula IVa, IVb, IVc, IVd, IVe, IVf, IVg, IVh, IVVi, IVj, IVk, IVm, IVn, or IVo:

[0738]

[0739]

[0740] Or its pharmaceutically acceptable salt, wherein:

[0741] Each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 alkyl-, where R 4 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 Alkyl group - optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution;

[0742] Each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a41 ;

[0743] Each R a41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C2-6 alkenyl and C 2-6 alkynyl group;

[0744] R 5 Selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, NR w2 R w3 and C(O)R w2 , where R 5 The C mentioned 3-12 The cycloalkyl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0745] Each R w2 Selected independently from C 3-12 Cycloalkyl and 4-12 membered heterocyclic alkyl groups, wherein R w2 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0746] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 alkynyl group;

[0747] Each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a51 ;and

[0748] Each R a51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0749] In some implementation schemes of the previous implementation scheme:

[0750] Each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne and 5-6 heteroaryl groups, wherein R 4 Each C 1-6 Alkyl, C 2-6 alkenyl, C2-6 The alkynyl and 5-6 heteroaryl groups are optionally separated by 1, 2, 3 or 4 independently selected R groups. 4A Substituent substitution;

[0751] Each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a41 ;

[0752] Each R a41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0753] R 5 Selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, NR w2 R w3 and C(O)R w2 , where R 5 The C mentioned 3-12 The cycloalkyl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0754] Each R w2 Selected independently from C 3-12 Cycloalkyl and 4-12 membered heterocyclic alkyl groups, wherein R w2 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0755] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 alkynyl group;

[0756] Each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a51 ;and

[0757] Each R a51 Independently selected from H and C 1-6Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0758] In some embodiments, the compound of formula I is a compound of formula IVa, IVb, IVc, IVd, IVe, IVf, IVg, IVh, or IVi:

[0759]

[0760] Or its pharmaceutically acceptable salt, wherein:

[0761] Each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 alkyl-, where R 4 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 Alkyl group - optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution;

[0762] Each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a41 ;

[0763] Each R a41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0764] R 5 Selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, NR w2 R w3 and C(O)R w2 , where R 5 The C mentioned 3-12The cycloalkyl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0765] Each R w2 Selected independently from C 3-12 Cycloalkyl and 4-12 membered heterocyclic alkyl groups, wherein R w2 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0766] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 alkynyl group;

[0767] Each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a51 ;and

[0768] Each R a51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0769] In some implementation schemes of the previous implementation scheme:

[0770] Each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0771] R 5 Selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, NR w2 R w3 and C(O)R w2 , where R 5 The C mentioned 3-12 The cycloalkyl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0772] Each R w2Selected independently from C 3-12 Cycloalkyl and 4-12 membered heterocyclic alkyl groups, wherein R w2 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0773] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 alkynyl group;

[0774] Each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a51 ;and

[0775] Each R a51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0776] In some embodiments, the compound of formula I is a compound of formula VIIa, VIIb, VIIc, VIId, VIIe, VIIf, VIIg, VIIh, VIIi, VIIj, VIIk, VIIm, VIIn, or VIIo:

[0777]

[0778]

[0779] Or its pharmaceutically acceptable salt, wherein:

[0780] Each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 alkyl-, where R 4 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 Alkyl group - optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution;

[0781] Each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a41 ;

[0782] Each R a41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0783] R 5 Selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, NR w2 R w3 and C(O)R w2 , where R 5 The C mentioned 3-12 The cycloalkyl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0784] Each R w2 Selected independently from C 3-12 Cycloalkyl and 4-12 membered heterocyclic alkyl groups, wherein R w2 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0785] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 alkynyl group;

[0786] Each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a51 ;and

[0787] Each R a51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0788] In some implementation schemes of the previous implementation scheme:

[0789] Each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne and 5-6 heteroaryl groups, wherein R 4 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl and 5-6 heteroaryl groups are optionally separated by 1, 2, 3 or 4 independently selected R groups. 4A Substituent substitution;

[0790] Each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a41 ;

[0791] Each R a41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0792] R 5 Selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, NR w2 R w3 and C(O)R w2 , where R 5 The C mentioned 3-12 The cycloalkyl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0793] Each R w2 Selected independently from C 3-12 Cycloalkyl and 4-12 membered heterocyclic alkyl groups, wherein R w2 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups.5A Substituent substitution;

[0794] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 alkynyl group;

[0795] Each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a51 ;and

[0796] Each R a51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0797] In some embodiments, the compound of formula I is a compound of formula VIIIa, VIIIb, VIIIc, VIIId, VIIIe, VIIIf, VIIIg, VIIIh, VIIIi, VIIIj, VIIIk, VIIIm, VIIIn, or VIIIo:

[0798]

[0799]

[0800] Or its pharmaceutically acceptable salt, wherein:

[0801] Each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 alkyl-, where R 4 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 Alkyl group - optionally selected by 1, 2, 3 or 4 independently chosen R4A Substituent substitution;

[0802] Each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a41 ;

[0803] Each R a41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0804] R 5 Selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, NR w2 R w3 and C(O)R w2 , where R 5 The C mentioned 3-12 The cycloalkyl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0805] Each R w2 Selected independently from C 3-12 Cycloalkyl and 4-12 membered heterocyclic alkyl groups, wherein R w2 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0806] Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 alkynyl group;

[0807] Each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a51 ;and

[0808] Each R a51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6alkenyl and C 2-6 Alkyne group.

[0809] In some implementation schemes of the previous implementation scheme:

[0810] Each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne and 5-6 heteroaryl groups, wherein R 4 Each C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl and 5-6 heteroaryl groups are optionally separated by 1, 2, 3 or 4 independently selected R groups. 4A Substituent substitution;

[0811] Each R 4A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a41 ;

[0812] Each R a41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group;

[0813] R 5 Selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, NR w2 R w3 and C(O)R w2 , where R 5 The C mentioned 3-12 The cycloalkyl group and the 5-12 heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0814] Each R w2 Selected independently from C 3-12 Cycloalkyl and 4-12 membered heterocyclic alkyl groups, wherein R w2 The C mentioned 3-12 Cycloalkyl and 4-12 membered heterocycloalkyl groups are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution;

[0815] Each R w3 Independently selected from H and C 1-6 Alkyl, C1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 alkynyl group;

[0816] Each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a51 ;and

[0817] Each R a51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0818] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 alkyl-, where R 4 Each C 1-6 Alkyl, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 Alkyl group - optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution.

[0819] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R 4A Selected independently from C 1-6 Halogenated alkyl groups, CN and OR a41 .

[0820] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R a41 Independently selected from H and C 1-6 alkyl.

[0821] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R 4 Independently selected from halogenated groups, C1-6 Alkyl, C 1-6 Haloalkyl, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 alkyl-, where R 4 Each C 1-6 Alkyl, C 3-7 Cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl and C 3-7 cycloalkyl-C 1-6 Alkyl group - optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution;

[0822] Each R 4A Selected independently from C 1-6 Halogenated alkyl groups, CN and OR a41 ;and

[0823] Each R a41 Independently selected from H and C 1-6 alkyl.

[0824] In some embodiments of any of formulas I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, R 4 Selected from methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclohexyl, tetrahydropyranyl, deuterated tetrahydropyranyl, pyridyl, and cyclopropylmethyl, wherein R 4 Each of the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclohexyl, tetrahydropyranyl, deuterated tetrahydropyranyl, pyridyl, and cyclopropylmethyl groups is optionally selected independently by one or two groups from C10. 1-3 Halogenated alkyl groups, CN, OH and C 1-3 alkoxy R 4A Substituent substitution.

[0825] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R 4 Independently selected from halogenated groups, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

[0826] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R 4 Selected independently from C 1-6 Halogenated alkyl groups.

[0827] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R4 Selected independently from C 1-3 Halogenated alkyl groups.

[0828] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R 4 It is trifluoromethyl.

[0829] In some embodiments of any of formulas I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, R 5 Selected from C 3-7 cycloalkyl, 5-6 membered heteroaryl, NHR w2 and C(O)R w2 , where R 5 The C mentioned 3-7 The cycloalkyl group and the 5-6-membered heteroaryl group are each optionally represented by 1, 2, 3 or 4 independently selected R groups. 5A Substituent substitution.

[0830] In some embodiments of any of formulas I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, R 5 Selected from cyclopropyl, cyclobutyl, cyclohexyl, pyrazolyl, imidazolyl, pyridyl, NHR w2 and C(O)R w2 , where R 5 The cyclopropyl, cyclobutyl, cyclohexyl, pyrazolyl, imidazoleyl, and pyridyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution.

[0831] In some embodiments of any of formulas I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, R 5 Selected from cyclopropyl, pyrazolyl, imidazole, and NHR w2 and C(O)R w2 , where R 5 The cyclopropyl, pyrazolyl, and imidazole groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 5A Substituent substitution.

[0832] In some embodiments of any of formulas I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, R w2 Selected from C 3-7 Cycloalkyl, 4-8 membered monocyclic heterocyclic alkyl and 6-10 membered bicyclic heterocyclic alkyl, wherein R w2 The C mentioned 3-7Cycloalkyl, 4-8 membered monocyclic heterocyclic alkyl and 6-10 membered bicyclic heterocyclic alkyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0833] In some embodiments of any of formulas I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, R w2 Selected from cyclopentyl, piperidinyl, morpholinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and 2-oxa-5-azabicyclo[4.1.0]heptyl, wherein R w2 The cyclopentyl, piperidinyl, morpholinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and 2-oxa-5-azabicyclo[4.1.0]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 5A Substituent substitution.

[0834] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R 5A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, CN and OR a51 .

[0835] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R a51 R b51 R c51 and R d51 Independently selected from H and C 1-6 alkyl.

[0836] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R a51 Independently selected from H and C 1-6 alkyl.

[0837] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R a51 Independently selected from H and C 1-3 alkyl.

[0838] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R 5AIndependently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, CN and OR a51 ;and

[0839] Each R a51 Independently selected from H and C 1-6 alkyl.

[0840] In some implementations of any of Equations I, IVa-IVv, VIIa-VIIo, and VIIIa-VIIIo, each R 5A It is independently selected from fluorine, methyl, trideuteryl, CN and hydroxyl.

[0841] In some implementations of any of formulas I-VIIIo, R 1 C 1-6 Alkyl groups, wherein the alkyl group is optionally composed of one, two, or three independently selected R groups. 1A Substituent substitution.

[0842] In some implementations of any of formulas I-VIIIo, R 1 C 1-6 alkyl.

[0843] In some implementations of any of formulas I-VIIIo, R 1 C 1-3 alkyl.

[0844] In some implementations of any of formulas I-VIIIo, R 1 It is methyl or trideuteryl.

[0845] In some implementations of any of formulas I-VIIIo, R 1 It is a methyl group.

[0846] In some implementations of any of formulas I-VIIIo, R 1 It is trideuteryl.

[0847] In some embodiments of any of formulas I-VIIIo, Cy 2 Selected from monocyclic C 3-10 cycloalkyl, spirocyclic C 6-10 Cycloalkyl, monocyclic 4-7 membered heterocyclic alkyl, bicyclic C 6-10 Cycloalkyl, spirocyclic 6-10-membered heterocyclic alkyl, and bicyclic 5-10-membered heterocyclic alkyl, wherein the monocyclic C 3-10 cycloalkyl, spirocyclic C 6-10 Cycloalkyl, monocyclic 4-7 membered heterocyclic alkyl, bicyclic C 6-10 Cycloalkyl, spirocyclic 6-10-membered heterocyclic alkyl, and bicyclic 5-10-membered heterocyclic alkyl are each selected by 1, 2, 3, or 4 independently chosen Rs2 Substituent substitution.

[0848] In some embodiments of any of formulas I-VIIIo, Cy 2 Selected from monocyclic C 3-10 cycloalkyl, spirocyclic C 6-10 Cycloalkyl, monocyclic 4-7 membered heterocyclic alkyl, spirocyclic 6-10 membered heterocyclic alkyl, and bicyclic 5-10 membered heterocyclic alkyl, wherein the monocyclic C 3-10 cycloalkyl, spirocyclic C 6-10 Cycloalkyl, monocyclic 4-7-membered heterocyclic alkyl, spirocyclic 6-10-membered heterocyclic alkyl, and bicyclic 5-10-membered heterocyclic alkyl are each selected by 1, 2, 3, or 4 independently chosen Rs 2 Substituent substitution.

[0849] In some embodiments of any of formulas I-VIIIo, Cy 2 Selected from cyclobutyl, cyclopentyl, deuterated cyclopentyl, cyclohexyl, tetrahydrofuranyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl and 2-azabicyclo[2.2.1]heptyl, wherein Cy 2 The cyclobutyl, cyclopentyl, deuterated cyclopentyl, cyclohexyl, tetrahydrofuranyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl and 2-azabicyclo[2.2.1]heptyl are each optionally 1, 2, 3 or 4 independently selected R 2 Substituent substitution.

[0850] In some embodiments of any of formulas I-VIIIo, Cy 2 Selected from cyclobutyl, cyclopentyl, deuterated cyclopentyl, cyclohexyl, tetrahydrofuranyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl and 2-azabicyclo[2.2.1]heptyl, wherein Cy 2 The cyclobutyl, cyclopentyl, deuterated cyclopentyl, cyclohexyl, tetrahydrofuranyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl and 2-azabicyclo[2.2.1]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 2 Substituent substitution.

[0851] In some embodiments of any of formulas I-VIIIo, Cy 2Selected from cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl and 2-azabicyclo[2.2.1]heptyl, wherein Cy 2 The cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl and 2-azabicyclo[2.2.1]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 2 Substituent substitution.

[0852] In some embodiments of any of formulas I-VIIIo, Cy 2 Selected from:

[0853]

[0854] Where n is 0, 1, or 2.

[0855] In some embodiments of any of formulas I-VIIIo, Cy 2 Selected from:

[0856]

[0857] Where n is 0, 1, or 2.

[0858] In some embodiments of any of formulas I-VIIIo, Cy 2 Selected from:

[0859]

[0860] Where n is 0, 1, or 2.

[0861] In some embodiments of any of formulas I-VIIIo, Cy 2 Selected from

[0862]

[0863] In some embodiments of any of formulas I-VIIIo, Cy 2 Selected from:

[0864]

[0865] In some embodiments of any of formulas I-VIIIo, Cy 2 Selected from:

[0866]

[0867] In some embodiments of any of formulas I-VIIIo, Cy2 Selected from:

[0868]

[0869] In some embodiments of any of formulas I-VIIIo, Cy 2 Selected from:

[0870]

[0871] In some embodiments of any of formulas I-VIIIo, Cy 2 Selected from:

[0872]

[0873] In some implementations of any of formulas I-VIIIo, each R 2 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a2 C(O)R b2 C(O)NR c2 R d2 C(O)OR a2 NR c2 R d2 NR c2 C(O)R b2 NR c2 C(O)OR a2 NR c2 C(O)NR c2 R d2 NR c2 S(O)R b2 NR c2 S(O)2R b2 S(O)R b2 S(O)NR c2 R d2 S(O)2R b2 and S(O)2NR c2 R d2 , where R 2 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 2A Substituent substitution.

[0874] In some implementations of any of formulas I-VIIIo, each R 2Independently selected from halogenated groups, C 1-6 Alkyl, CN, OR a2 C(O)R b2 C(O)NR c2 R d2 C(O)OR a2 NR c2 C(O)R b2 NR c2 C(O)OR a2 and NR c2 S(O)2R b2 , where R 2 The C mentioned 1-6 Each alkyl group is optionally represented by one, two, three, or four independently selected R groups. 2A Substituent substitution.

[0875] In some implementations of any of formulas I-VIIIo, each R 2 Independently selected from halogenated groups, C 1-6 Alkyl, CN, C(O)R b2 C(O)OR a2 NR c2 C(O)R b2 NR c2 C(O)OR a2 and NR c2 S(O)2R b2 , where R 2 The C mentioned 1-6 Each alkyl group is optionally represented by one, two, three, or four independently selected R groups. 2A Substituent substitution.

[0876] In some implementations of any of formulas I-VIIIo, each R a2 R b2 R c2 and R d2 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R a2 R b1 R c2 and R d2 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 2A Substituent substitution.

[0877] In some implementations of any of formulas I-VIIIo, each R a2 R b2 R c2 and R d2 Independently selected from H and C 1-6 Alkyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R a2 R b1 R c2 and R d2 The C mentioned 1-6 Alkyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 2A Substituent substitution.

[0878] In some implementations of any of formulas I-VIIIo, each R a2 R b2 R c2 and R d2 Independently selected from H and C 1-6 Alkyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl and 4-7-membered heterocycloalkyl, wherein R a2 R b1 R c2 and R d2 The C mentioned 1-6 Alkyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, and 4-7-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 2A Substituent substitution.

[0879] In some implementations of any of formulas I-VIIIo, each R a2 R b2 R c2 and R d2 Independently selected from H, methyl, trideuteryl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl, wherein R a2 R b1 R c2 and Rd2 The methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 2A Substituent substitution.

[0880] In some implementations of any of formulas I-VIIIo, each R a2 R b2 R c2 and R d2 Independently selected from H, methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl, wherein R a2 R b1 R c2 and R d2 The methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 2A Substituent substitution.

[0881] In some implementations of any of formulas I-VIIIo, each R 2 Independently selected from halogenated groups, C 1-6 Alkyl, CN, C(O)R b2 C(O)OR a2 NR c2 C(O)R b2 NR c2 C(O)OR a2 and NR c2 S(O)2R b2 , where R 2 The C mentioned 1-6 Each alkyl group is optionally represented by one, two, three, or four independently selected R groups. 2A Substituent substitution; and

[0882] Each R a2 R b2 R c2 and R d2 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R a2 R b1 R c2 and R d2 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 2A Substituent substitution.

[0883] In some implementations of any of formulas I-VIIIo, each R 2 Independently selected from halogenated groups, C 1-6 Alkyl, CN, C(O)R b2 C(O)OR a2 NR c2 C(O)R b2 NR c2 C(O)OR a2 and NR c2 S(O)2R b2 , where R 2 The C mentioned 1-6 Each alkyl group is optionally represented by one, two, three, or four independently selected R groups. 2A Substituent substitution; and

[0884] Each R a2 R b2 R c2 and R d2 Independently selected from H and C 1-6 Alkyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R a2 R b1 R c2 and R d2 The C mentioned 1-6 Alkyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 2A Substituent substitution.

[0885] In some implementations of any of formulas I-VIIIo, each R 2 Independently selected from halogenated groups, C 1-6 Alkyl, CN, C(O)R b2 C(O)OR a2 NR c2 C(O)R b2 NR c2 C(O)OR a2 and NR c2 S(O)2Rb2 , where R 2 The C mentioned 1-6 Each alkyl group is optionally represented by one, two, three, or four independently selected R groups. 2A Substituent substitution; and

[0886] Each R a2 R b2 R c2 and R d2 Independently selected from H and C 1-6 Alkyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl and 4-7-membered heterocycloalkyl, wherein R a2 R b1 R c2 and R d2 The C mentioned 1-6 Alkyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, and 4-7-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 2A Substituent substitution.

[0887] In some implementations of any of formulas I-VIIIo, each R 2 Independently selected from halogenated groups, C 1-6 Alkyl, CN, C(O)R b2 C(O)OR a2 NR c2 C(O)R b2 NR c2 C(O)OR a2 and NR c2 S(O)2R b2 , where R 2 The C mentioned 1-6 Each alkyl group is optionally represented by one, two, three, or four independently selected R groups. 2A Substituent substitution; and

[0888] Each R a2 R b2 R c2 and R d2 Independently selected from H, methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl, wherein R a2 R b1 R c2 and R d2 The methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl groups are each optionally selected by one or two independently chosen R groups. 2A Substituent substitution.

[0889] In some implementations of any of formulas I-VIIIo, each R 2A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a21 , where R 2A The C mentioned 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 2B Substituent substitution.

[0890] In some implementations of any of formulas I-VIIIo, each R 2A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a21 .

[0891] In some implementations of any of formulas I-VIIIo, each R 2A Independently selected from halogenated groups and OR a21 .

[0892] In some implementations of any of formulas I-VIIIo, each R a21 R b21 R c21 and R d21 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0893] In some implementations of any of formulas I-VIIIo, each R a21 R b21 R c21 and R d21 Independently selected from H and C 1-6 alkyl.

[0894] In some implementations of any of formulas I-VIIIo, each R a21 R b21 R c21 and R d21 Independently selected from H and C 1-3 alkyl.

[0895] In some implementations of any of formulas I-VIIIo, each Ra21 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

[0896] In some implementations of any of formulas I-VIIIo, each R a21 Independently selected from H and C 1-6 alkyl.

[0897] In some implementations of any of formulas I-VIIIo, each R a21 Independently selected from H and C 1-3 alkyl.

[0898] In some implementations of any of formulas I-VIIIo, each R a21 It is independently selected from H and methyl.

[0899] In some implementations of any of formulas I-VIIIo, each R 2A Independently selected from halogenated groups and OR a21 ;and

[0900] Each R a21 Independently selected from H and C 1-6 alkyl.

[0901] In some implementations of any of formulas I-VIIIo, each R 2A It is independently selected from fluorine, hydroxyl and methoxy.

[0902] In some implementations of any of formulas I-VIIIo, each R 2A It is independently selected from fluorine and methoxy groups.

[0903] In some implementations of any of formulas I-VIIIo, R 3 Selected from H and C 1-6 alkyl.

[0904] In some implementations of any of formulas I-VIIIo, R 3 Selected from H and C 1-3 alkyl.

[0905] In some implementations of any of formulas I-VIIIo, R 3 For H.

[0906] In some implementations of any of formulas I-VIIIo:

[0907] R 1 Selected from C 1-6 Alkyl, C 2-6alkenyl and C 2-6 alkynyl group;

[0908] Cy 2 Selected from monocyclic C 3-10 cycloalkyl, spirocyclic C 6-10 Cycloalkyl, monocyclic 4-7 membered heterocyclic alkyl, bicyclic C 6-10 Cycloalkyl, spirocyclic 6-10-membered heterocyclic alkyl, and bicyclic 5-10-membered heterocyclic alkyl, wherein the monocyclic C 3-10 Cycloalkyl, bicyclic C 6-10 cycloalkyl, spirocyclic C 6-10 Cycloalkyl, monocyclic 4-7-membered heterocyclic alkyl, spirocyclic 6-10-membered heterocyclic alkyl, and bicyclic 5-10-membered heterocyclic alkyl are each selected by 1, 2, 3, or 4 independently chosen Rs 2 Substituent substitution;

[0909] Each R 2 Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a2 C(O)R b2 C(O)NR c2 R d2 C(O)OR a2 NR c2 R d2 NR c2 C(O)R b2 NR c2 C(O)OR a2 NR c2 C(O)NR c2 R d2 NR c2 S(O)R b2 NR c2 S(O)2R b2 S(O)R b2 S(O)NR c2 R d2 S(O)2R b2 and S(O)2NR c2 R d2 , where R 2 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 2A Substituent substitution;

[0910] Each R a2 R b2 Rc2 and R d2 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R a2 R b1 R c2 and R d2 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 2A Substituent substitution;

[0911] Each R 2A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a21 ;

[0912] Each R a21 Independently selected from H and C 1-6 Alkyl; and

[0913] R 3 Selected from H and C 1-6 alkyl.

[0914] In some implementation schemes of the previous implementation scheme, Cy 2 Selected from monocyclic C 3-10 cycloalkyl, spirocyclic C 6-10 Cycloalkyl, monocyclic 4-7 membered heterocyclic alkyl, spirocyclic 6-10 membered heterocyclic alkyl, and bicyclic 5-10 membered heterocyclic alkyl, wherein the monocyclic C 3-10 cycloalkyl, spirocyclic C 6-10 Cycloalkyl, monocyclic 4-7-membered heterocyclic alkyl, spirocyclic 6-10-membered heterocyclic alkyl, and bicyclic 5-10-membered heterocyclic alkyl are each selected by 1, 2, 3, or 4 independently chosen Rs 2 Substituent substitution;

[0915] In some implementations of any of formulas I-VIIIo:

[0916] R 1 Selected from C 1-6 alkyl;

[0917] Cy 2 Selected from monocyclic C 3-10 cycloalkyl, spirocyclic C 6-10 Cycloalkyl, monocyclic 4-7 membered heterocyclic alkyl, bicyclic C 6-10 Cycloalkyl, spirocyclic 6-10-membered heterocyclic alkyl, and bicyclic 5-10-membered heterocyclic alkyl, wherein the monocyclic C 3-10 Cycloalkyl, bicyclic C 6-10 cycloalkyl, spirocyclic C 6-10 Cycloalkyl, monocyclic 4-7-membered heterocyclic alkyl, spirocyclic 6-10-membered heterocyclic alkyl, and bicyclic 5-10-membered heterocyclic alkyl are each selected by 1, 2, 3, or 4 independently chosen Rs 2 Substituent substitution;

[0918] Each R 2 Independently selected from halogenated groups, C 1-6 Alkyl, CN, OR a2 C(O)R b2 C(O)NR c2 R d2 C(O)OR a2 NR c2 C(O)R b2 NR c2 C(O)OR a2 and NR c2 S(O)2R b2 , where R 2 The C mentioned 1-6 Each alkyl group is optionally represented by one, two, three, or four independently selected R groups. 2A Substituent substitution;

[0919] Each R a2 R b2 R c2 and R d2 Independently selected from H and C 1-6 Alkyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl and 4-7-membered heterocycloalkyl, wherein R a2 R b1 R c2 and R d2 The C mentioned 1-6 Alkyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, and 4-7-membered heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 2A Substituent substitution;

[0920] Each R 2A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a21 ;

[0921] Each R a21 Independently selected from H and C 1-6 Alkyl; and

[0922] R 3 For H.

[0923] In some implementation schemes of the previous implementation scheme:

[0924] Cy 2 Selected from monocyclic C 3-10 cycloalkyl, spirocyclic C 6-10 Cycloalkyl, monocyclic 4-7 membered heterocyclic alkyl, spirocyclic 6-10 membered heterocyclic alkyl, and bicyclic 5-10 membered heterocyclic alkyl, wherein the monocyclic C 3-10 cycloalkyl, spirocyclic C 6-10 Cycloalkyl, monocyclic 4-7-membered heterocyclic alkyl, spirocyclic 6-10-membered heterocyclic alkyl, and bicyclic 5-10-membered heterocyclic alkyl are each selected by 1, 2, 3, or 4 independently chosen Rs 2 Substituent substitution; and

[0925] Each R 2 Independently selected from halogenated groups, C 1-6 Alkyl, CN, C(O)R b2 C(O)OR a2 NR c2 C(O)R b2 NR c2 C(O)OR a2 and NR c2 S(O)2R b2 , where R 2 The C mentioned 1-6 Each alkyl group is optionally represented by one, two, three, or four independently selected R groups. 2A Substituent substitution.

[0926] In some implementations of any of formulas I-VIIIo:

[0927] R 1 C 1-3 alkyl;

[0928] Cy 2 Selected from cyclobutyl, cyclopentyl, deuterated cyclopentyl, cyclohexyl, tetrahydrofuranyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl and 2-azabicyclo[2.2.1]heptyl, wherein Cy 2The cyclobutyl, cyclopentyl, deuterated cyclopentyl, cyclohexyl, tetrahydrofuranyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl and 2-azabicyclo[2.2.1]heptyl are each optionally 1, 2, 3 or 4 independently selected R 2 Substituent substitution;

[0929] Each R 2 Independently selected from halogenated groups, C 1-6 Alkyl, CN, OR a2 C(O)R b2 C(O)NR c2 R d2 C(O)OR a2 NR c2 C(O)R b2 NR c2 C(O)OR a2 and NR c2 S(O)2R b2 , where R 2 The C mentioned 1-6 Each alkyl group is optionally represented by one, two, three, or four independently selected R groups. 2A Substituent substitution;

[0930] Each R a2 R b2 R c2 and R d2 Independently selected from H, methyl, trideuteryl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl, wherein R a2 R b1 R c2 and R d2 The methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 2A Substituent substitution;

[0931] Each R 2A Independently selected from halogenated groups and OR a21 ;

[0932] Each R a21 Independently selected from H and C 1-6 Alkyl; and

[0933] R 3 For H.

[0934] In some implementation schemes of the previous implementation scheme:

[0935] Cy 2Selected from cyclobutyl, cyclopentyl, deuterated cyclopentyl, cyclohexyl, tetrahydrofuranyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl and 2-azabicyclo[2.2.1]heptyl, wherein Cy 2 The cyclobutyl, cyclopentyl, deuterated cyclopentyl, cyclohexyl, tetrahydrofuranyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl and 2-azabicyclo[2.2.1]heptyl are each optionally represented by 1, 2, 3 or 4 independently selected R 2 Substituent substitution;

[0936] Each R 2 Independently selected from halogenated groups, C 1-6 Alkyl, CN, C(O)R b2 C(O)OR a2 NR c2 C(O)R b2 NR c2 C(O)OR a2 and NR c2 S(O)2R b2 , where R 2 The C mentioned 1-6 Each alkyl group is optionally represented by one, two, three, or four independently selected R groups. 2A Substituent substitution; and

[0937] Each R a2 R b2 R c2 and R d2 Independently selected from H, methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl, wherein R a2 R b1 R c2 and R d2 The methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl groups are each optionally represented by 1, 2, 3, or 4 independently selected R groups. 2A Substituent substitution.

[0938] In some embodiments, the compounds provided herein are selected from:

[0939] 2-((3'-cyano-5-((1-((1) R ,3 R )-3-((methoxycarbonyl)amino)cyclopentyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1,1'-Biphenyl]-3-yl)amino)oxazol-5-carboxylic acid ethyl ester;

[0940] ((1 R ,3 R )-3-(6-((3'-cyano-5-(4-fluorotetrahydro-2 H -pyran-4-carboxylamino)-[1,1'-biphenyl]-3-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0941] ((1 R ,3 R )-3-(3-(methyl- d 3)-6-((4-(1-methyl-1,6-diazaspiro[3.3]heptane-6-carbonyl)-8-(trifluoromethyl)quinolin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0942] ((1 R ,3 R )-3-(6-((6-(4-(hydroxymethyl)-3-methylphenyl)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0943] ((1 R ,3 R )-3-(6-((6'-methoxy-[2,3'-bipyridine]-6-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0944] ((1 R ,3 R )-3-(6-((4-(4-cyanopiperidin-1-carbonyl)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0945] ((1 R ,3 R )-3-(3-methyl-6-((6-(3-methyl-1 H-Indazol-5-yl)pyridin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0946] ((1 R ,3 R )-3-(6-((6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0947] ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((6-(quinolin-6-yl)pyridin-2-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0948] ((1 R ,3 R )-3-(6-((4-(1-hydroxy-3-azabicyclo[3.1.0]hexane-3-carbonyl)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0949] ((1 R ,3 R )-3-(3-methyl-6-((6-(4-methyl-3,4-dihydro-2) H -benzo[ b [1,4]Oxazin-7-yl)pyridin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0950] ((1 R ,3 R )-3-(6-((4-(2-oxa-5-azabicyclo[2.2.1]heptane-5-carbonyl)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0951] ((1 R ,3 R )-3-(6-((4-(2-oxa-5-azabicyclo[4.1.0]heptane-5-carbonyl)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0952] (3-((1-((1 R ,3 R )-3-((methoxycarbonyl)amino)cyclopentyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H methyl 1,2,3-triazol-4-yl)phenyl)carbamate;

[0953] (3-((1-((1 R ,3 R )-3-((methoxycarbonyl)amino)cyclopentyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c Methyl pyridin-6-yl)amino)-5-(1-methylpiperidin-4-yl)phenyl)carbamate;

[0954] ((1 R ,3 R )-3-(6-((4-(3,3-difluoropiperidin-1-carbonyl)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0955] ((1 R ,3 R )-3-(6-((3-(( R )-2,2-difluorocyclopropane-1-formamide)-5-(tetrahydro-2 H -pyran-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5-c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0956] ((1 R ,3 R )-3-(6-((6-((3,3-difluorocyclopentyl)amino)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0957] ((1 R ,3 R )-3-(6-((3-(cyclobutaneformamido)-5-(tetrahydro-2 H -pyran-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -Imidazo[4,5-c]pyridin-1-yl)cyclopentyl)carbamate methyl ester;

[0958] ((1 R ,3 R )-3-(3-(methyl- d 3)-6-((6-(1-methyl-1 H -pyrazol-4-yl)-8-(trifluoromethyl)quinoline-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0959] (3-((1-((1 R ,3 R )-3-((methoxycarbonyl)amino)cyclopentyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(tetrahydro-2 H methyl pyran-3-yl)phenyl)carbamate;

[0960] ((1 R ,3 R )-3-(6-((6-(((4-cyanocyclohexyl)oxy)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0961] ((1 R ,3R )-3-(3-methyl-2-oxo-6-((6-(quinolin-6-yloxy)pyridin-2-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0962] (3-((1-((1 r ,3 r )-3-(cyclopropaneformylamino)cyclobutyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H 4-pyrazole-4-yl)phenyl)carbamate methyl ester;

[0963] (3-((1-(6-((ethoxycarbonyl)amino)spiro[3.3]hept-2-yl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H 4-pyrazole-4-yl)phenyl)carbamate methyl ester;

[0964] (3-((1-(6-(cyclopropanesulfonylamino)spiro[3.3]hept-2-yl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H 4-pyrazole-4-yl)phenyl)carbamate methyl ester;

[0965] 6-(6-((3-((methoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c Methyl pyridin-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate;

[0966] (3-((1-((1r,3r)-3-cyanocyclobutyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H 4-pyrazole-4-yl)phenyl)carbamate methyl ester;

[0967] (3-((1-((1r,3r)-3-((methoxycarbonyl)amino)-3-methylcyclobutyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H 4-pyrazole-4-yl)phenyl)carbamate methyl ester;

[0968] ( R )-(3-((1-(3,3-difluorocyclopentyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H 4-pyrazole-4-yl)phenyl)carbamate methyl ester;

[0969] (3-((1-((1 R ,3 S )-3-Fluorocyclopentyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H 4-pyrazole-4-yl)phenyl)carbamate methyl ester;

[0970] ((1 R ,3 R )-3-(3-methyl-6-((6-(1-methyl-1 H -pyrazol-4-yl)quinoline-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0971] ((1 R ,3 R )-3-(3-methyl-6-((8-(1-methyl-1 H -pyrazol-4-yl)quinoline-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0972] ((1 R ,3 R )-3-(3-methyl-6-((3-(1-methyl-1) H -pyrazol-4-yl)imidazo[1,2-b]pyridazine-6-yl)amino)-2-oxo-2,3-dihydro-1 H-imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0973] ((1 R ,3 R )-3-(3-methyl-6-((2-(1-methyl-1) H -pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0974] ((1 R ,3 R )-3-(3-methyl-6-((3-(1-methyl-1) H -pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0975] ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((6-((tetrahydro-2) H -pyran-4-yl)oxy)pyridin-2-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0976] ((1 R ,3 R )-3-(3-methyl-6-((3-(1-methyl-1) H -imidazol-5-yl)imidazo[1,2-b]pyridazine-6-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0977] (1 R 5 S )-6-(6-((3-((methoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c Methyl pyridin-1-yl)-3-azabicyclo[3.1.0]hexane-3-carboxylate;

[0978] (3-((1-(2-acetyl-2-azabicyclo[2.2.1]hept-5-yl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c methyl pyridin-6-yl)amino)-5-(1-methyl-1H-pyrazol-4-yl)phenyl)carbamate;

[0979] ((1 R ,3 R )-3-(6-((3-((3,3-difluorocyclobutane)-1-sulfonamide)-5-(tetrahydro-2 H -pyran-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0980] (3-((1-(4-((methoxycarbonyl)amino)-4-methylcyclohexyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5-c]pyridin-6-yl)amino)-5-(1-methyl-1 H 4-pyrazole-4-yl)phenyl)carbamate methyl ester;

[0981] ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 2-Methoxyethyl pyridin-1-yl)cyclopentyl)carbamate;

[0982] ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(tetrahydro-2 H -pyran-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0983] ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate cyclobutyl ester;

[0984] ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate;

[0985] ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate prop-2-yn-1-yl ester;

[0986] ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl)tetrahydro-2-carbamate H -Pyran-4-yl ester;

[0987] ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 4-fluorophenyl pyridin-1-yl)cyclopentyl)carbamate;

[0988] ((1 R ,3 R )-3-(6-((6-cyclopropylpyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0989] ((1 R ,3 R )-3-(6-((6-(3-cyanophenyl)-4-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0990] ((1 R ,3 R )-3-(3-(methyl- d 3)-6-((4-(morpholin-4-carbonyl)-8-(trifluoromethyl)quinolin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -Imidazo[4,5-c]pyridin-1-yl)cyclopentyl)carbamate methyl ester;

[0991] ((1 R ,3 R )-3-(6-((3-((methoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0992] ((1 R ,3 R )-3-(6-((3-Cyclopropylimidazo[1,2-b]pyridazine-6-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -Imidazo[4,5-c]pyridin-1-yl)cyclopentyl)carbamate methyl ester;

[0993] ((1 R ,3 R )-3-(6-((3-((cyclopropoxycarbonyl)amino)-5-methoxyphenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0994] ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H-pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0995] ((1 R ,3 R )-3-(6-((3-(cyclopropaneformamido)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0996] ((1 R ,3 R )-3-(3-(methyl- d 3)-6-((8-(1-methylcyclopropyl)quinolin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -Imidazo[4,5-c]pyridin-1-yl)cyclopentyl)carbamate methyl ester;

[0997] ((1 R ,3 R )-3-(6-((3-(3-fluoro-1-(methyl- d 3)-1 H -pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0998] ((1 R ,3 R )-3-(6-((4-(cyclobutoxymethyl)-6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[0999] ((1 R ,3 R )-3-(6-((6-(3-aminopyrrolidone-1-yl)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5-c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1000] ((1 R ,3 R )-3-(6-((4-((cyclopentylamino)methyl)-6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1001] ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((2-(piperidin-1-yl)pyrimidin-4-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1002] ((1 R ,3 R )-3-(6-((2'-methoxy-4-methyl-[2,4'-bipyridine]-6-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1003] ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((4-(pyridin-4-yl)thiazo-2-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1004] ((1 R ,3 R )-3-(6-((3-fluoro-6'-(trifluoromethyl)-[2,3'-bipyridine]-6-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1005] ((1 R ,3 R)-3-(6-((6-(2,3-dihydrobenzo[b][1,4]dioxane-6-yl)-4-((( S )-3-fluoropyrrolidone-1-yl)methyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1006] ((1 R ,3 R )-3-(6-((6-(4-(cyanomethyl)phenyl)-5-fluoropyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1007] ((1 R ,3 R )-3-(6-((6-(4-cyclopropylphenyl)-5-fluoropyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1008] ((1 R ,3 R )-3-(6-((5-fluoro-6-(4-(trifluoromethoxy)phenyl)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1009] ((1 R ,3 R )-3-(6-((6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)-4-(morpholinylmethyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1010] ((1 R ,3 R )-3-(6-((2-(2-methoxypyridin-4-yl)pyrimidin-4-yl)amino)-3-(methyl- d3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1011] ((1 R ,3 R )-3-(6-((6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)-4-(octahydro-2 H -pyrido[1,2- a ]pyrazine-2-carbonyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1012] ((1 R ,3 R )-3-(6-((2-(5-azaspiro[2.4]hept-5-yl)pyrimidin-4-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1013] ((1 R ,3 R )-3-(6-((2-(3,3-difluoropyrrolidone-1-yl)pyrimidin-4-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1014] ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((2-(4-(trifluoromethyl)piperidin-1-yl)pyrimidin-4-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1015] ((1 R ,3 R )-3-(6-((6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)-4-(( R )-3-fluoropyrrolidine-1-carbonyl)pyridin-2-yl)amino)-3-(methyl- d3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1016] ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((1-(pyridin-4-yl)-1 H -pyrazole-3-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1017] ((1 R ,3 R )-3-(6-((6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)-4-(morpholin-4-carbonyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1018] ((1 R ,3 R )-3-(6-((2-((3,3-difluorocyclopentyl)amino)pyrimidin-4-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1019] ((1 R ,3 R )-3-(6-((2-(3,3-difluoropyrrolidone-1-yl)-6-methylpyrimidin-4-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1020] ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((2-((tetrahydro-2) H -pyran-4-yl)amino)pyrimidin-4-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1021] ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((6-(piperidin-1-carbonyl)pyridin-2-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; and

[1022] ((1 R ,3 R )-3-(6-((6-(cyclohexylaminocarbamoyl)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1023] Or its pharmaceutically acceptable salt.

[1024] In some embodiments, this application provides compounds selected from the following:

[1025] (3-((1-Cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1-) H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H 4-pyrazole-4-yl)phenyl)carbamate cyclobutyl ester;

[1026] (3-((1-Cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1-) H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-cyclopropyl-1 H 4-pyrazole-4-yl)phenyl)carbamate cyclobutyl ester;

[1027] (3-(1-Cyclopropyl-1) H -pyrazol-4-yl)-5-((3-methyl-2-oxo-1-(tetrahydrofuran-3-yl)-2,3-dihydro-1 H -imidazo[4,5- c Cyclobutyl pyridinium (6-yl)amino)phenyl)carbamate;

[1028] ((1 R ,3 R )-3-(6-((1-(2-methoxyethyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-3-(methyl-d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1029] ((1 R ,3 R )-3-(6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-1-methyl-2-oxo-7-(4-(trifluoromethyl)pyridin-3-yl)-2,3-dihydro-1 H -imidazo[4,5- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1030] N -(6-(3-(methyl- d 3)-6-((4-(morpholin-4-carbonyl)-8-(trifluoromethyl)quinolin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)spiro[3.3]hept-2-yl)cyclopropaneformamide;

[1031] N -((1 s, 4 s )-1-Methyl-4-(3-(methyl- d 3)-6-((2-methyl-3-(1-(trifluoromethyl)-1 H -pyrazole-4)-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclohexyl)cyclopropaneformamide;

[1032] N -((1 S ,3 R )-3-(6-((6-(5-chlorothiazol-2-yl)-4-(2-hydroxypropyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c]pyridin-1-yl)-1-methylcyclopentyl)cyclopropaneformamide;

[1033] ((1 R ,3 R )-3-(6-((6-(5-chlorothiazol-2-yl)-4-(2-hydroxypropyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1034] ((1 R ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(1-methyl-1 H -pyrazol-4-yl)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1035] ((1 R ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(2-(trifluoromethyl)thiazolyl-5-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1036] ((1 R ,3 R )-3-(6-((8-(2-cyanopropyl-2-yl)-4-(morpholin-4-carbonyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1037] ((1 R ,3 R )-3-(6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-2-methyl-8-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-] b ]pyridazine-6-yl)amino)-3-(methyl- d3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-3- d )Methyl carbamate;

[1038] ((1 R ,3 R )-3-(6-((5-methoxy-6-(5-(trifluoromethyl)thiazo-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1039] ((1 R ,3 R )-3-(6-((6-(5-((2-hydroxypropyl-2-yl)thiazolyl)-4-methylpyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -Imidazo[4,5-c]pyridin-1-yl)cyclopentyl)carbamate methyl ester;

[1040] ((1 R ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1041] ((1 R ,3 R )-3-(6-((4-((3-(difluoromethyl)azacyclobut-1-yl)methyl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1042] ((1 R ,3 R )-3-(6-((6-cyclobutoxy-5-(1-methyl-1 H -pyrazol-4-yl)-4-(morpholin-4-carbonyl)pyridin-2-yl)amino)-3-(methyl-d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1043] ((1 R ,3 R )-3-(6-((2-(5-(difluoromethyl)thiophen-2-yl)-6-(hydroxymethyl)pyrimidin-4-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1044] ((1 R ,3 R )-3-(6-((6-(5-(difluoromethyl)thiophen-2-yl)-4-(morpholin-4-carbonyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1045] ((1 R ,3 R )-3-(6-((4-(1-acetylpiperidin-4-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1046] 6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-2-methyl-8-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-] b ]pyridazine-6-yl)amino)-1-((1 r ,3 r )-3-(2-hydroxypropyl-2-yl)cyclobutyl)-3-(methyl- d 3)-1,3-dihydro-2 H -imidazo[4,5- c ]Pyridin-2-one;

[1047] ((1 R ,3 R)-3-(6-((6-(5-(2-hydroxypropyl-2-yl)thiazolyl-2-yl)-4-(1-methyl-1 H -pyrazol-4-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1048] ((1 R ,3 R )-3-(3-(methyl- d 3)-2-oxo-6-((6-(4-(trifluoromethyl)-1 H -pyrazol-1-yl)pyridin-2-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1049] ((1 R ,3 R )-3-(3-(methyl- d 3)-2-oxo-6-((1-(tetrahydro-2) H -pyran-4-yl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1050] ((1 R ,3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1051] ((3 R )-3-(3-(methyl- d 3)-2-oxo-6-((1-(tetrahydro-2) H-pyran-4-yl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1052] ((3 R )-3-(3-(methyl- d 3)-2-oxo-6-((1-(tetrahydro-2) H -pyran-4-yl-4- d )-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1053] ((3 R )-3-(6-((1-(1-cyanocyclopropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1054] ((1 R ,3 R )-3-(6-((1-((1-cyanocyclopropyl)methyl)-3-(1-(difluoromethyl)-1 H -pyrazole-4-yl)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1055] ((1R ,3 R )-3-(6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-7-(2-hydroxypropyl-2-yl)-2-methyl-3-yl) H -imidazo[4,5- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1056] N -((1 R ,3 R )-1-Methyl-3-(3-(methyl- d 3)-6-((4-(morpholin-4-carbonyl)-8-(trifluoromethyl)quinolin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)cyclopropaneformamide;

[1057] N -((1 S ,3 R )-3-(6-((7-(hydroxymethyl)-2-methyl-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)cyclopropaneformamide;

[1058] ((1 R ,3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3 )-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1059] N -((1 S ,3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)cyclopropaneformamide;

[1060] N -((1 s 4 s )-4-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3 )-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclohexyl)cyclopropaneformamide;

[1061] N -((1 S ,3 R )-3-(6-((2-((1 s ,3 s )-3-hydroxycyclobutyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)cyclopropaneformamide;

[1062] ((1 R ,3 R )-3-(6-((2-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-2 H -pyrazolo[4,3- b]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1063] N -((1 S ,3 R )-3-(6-((2-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)cyclopropaneformamide;

[1064] ((3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3 )-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1065] ((3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1066] N -((1 s 4 s )-4-(6-((1-((1 r 4r )-4-hydroxycyclohexyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclohexyl)cyclopropaneformamide;

[1067] N -((1 s 4 s )-1-Methyl-4-(3-(methyl- d 3)-6-((2-methyl-7-(morpholin-4-carbonyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclohexyl)cyclopropaneformamide;

[1068] ((1 S ,3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridin-1-yl)-1-methylcyclopentyl)carbamate;

[1069] N -((1 S ,3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3 )-2-oxo-2,3-dihydro-1 H -imidazo[4,5- cpyridin-1-yl)-1-methylcyclopentyl)acetamide;

[1070] ((3 R )-3-(6-((7-(2-hydroxypropyl-2-yl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1071] ((3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-1-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[2,3- b ]pyridin-6-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1072] ((3 R )-3-(3-(methyl- d 3)-2-oxo-6-((1-(tetrahydro-2) H -pyran-4-yl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1073] ((3 R )-3-(6-((1-((1-cyanocyclopropyl)methyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H-imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1074] ((3 R )-3-(6-((2-((1-cyanocyclopropyl)methyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1075] ((1 R ,3 R )-3-(3-(methyl- d 3)-6-((6-methyl-4-(morpholin-4-carbonyl)-8-(trifluoromethyl)quinolin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1076] N -((1 S ,3 R )-3-(6-((6-(5-chlorothiazol-2-yl)-4-(2-hydroxypropyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c pyridin-1-yl)-1-methylcyclopentyl)acetamide;

[1077] 4-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)- N -(methyl- d 3) Bicyclo[2.2.2]octane-1-carboxamide;

[1078] N-Cyclopropyl-4-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazo-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c [Pyridin-1-yl]bicyclo[2.2.2]octane-1-carboxamide;

[1079] 4-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c [Pyridin-1-yl]bicyclo[2.2.2]octane-1-carboxamide;

[1080] N -(4-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazo-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c [2.2.2]Octo-1-yl)acetamide;

[1081] 4-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c [2.2.1]Pyridin-1-yl)bicyclo[2.2.1]heptane-1-carboxamide;

[1082] N -(4-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazo-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3 )-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c [2.2.1]Pyridin-1-yl)bicyclo[2.2.1]hept-1-yl)acetamide;

[1083] N -((1 S ,3 R)-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)propionamide;

[1084] ((1 R ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(2-hydroxypropyl-2-yl)thiazolyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1085] ((1 R ,3 R )-3-(6-((6-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropyl-2-yl)thiazolyl-2-yl)-4-(2-hydroxypropyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1086] N -((1 S ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(2-(trifluoromethyl)thiazolyl-5-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c pyridin-1-yl)-1-methylcyclopentyl)acetamide;

[1087] ((1 R ,3 R )-3-(6-((6-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropyl-2-yl)thiazolyl-2-yl)-4-(2-hydroxypropyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1-d )Methyl carbamate;

[1088] ((1 R ,3 R )-3-(6-((6-(5-((2-hydroxypropyl-2-yl)thiazolyl)-4-methylpyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1089] ((1 R ,3 R )-3-(6-((5-fluoro-6-(5-(2-hydroxypropyl-2-yl)thiazolyl)-4-methylpyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopentyl-1-d)carbamate;

[1090] ((1 R ,3 R )-3-(6-((6-(5-(2-hydroxypropyl-2-yl)thiazolyl-2-yl)-4-(methyl- d 3)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1091] N -((1 S ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(2-isopropoxythiazo-5-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c pyridin-1-yl)-1-methylcyclopentyl)acetamide;

[1092] N -((1 S ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(2-methoxythiazo-5-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1H -imidazo[4,5- c pyridin-1-yl)-1-methylcyclopentyl)acetamide;

[1093] N -((1 S ,3 R )-3-(6-((6-(2-ethoxythiazolyl-5-yl)-4-(2-hydroxypropyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c pyridin-1-yl)-1-methylcyclopentyl)acetamide;

[1094] ((1 R ,3 R )-3-(6-((6'-(5-(difluoromethyl)thiophen-2-yl)-4-(trifluoromethyl)-[3,4'-bipyridine]-2'-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1095] ((1 S ,2 S 4 S )-2-hydroxy-4-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1096] ((1 R ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-3- d )Methyl carbamate;

[1097] ((1 R ,3 R )-3-(3-(methyl- d3)-6-((4-(1-methylpiperidin-4-yl)-6-(5-(trifluoromethyl)thiazo-2-yl)pyridin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1098] ((1 R ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1099] ((1 S ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1100] ((1 S ,3 R )-3-(6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-2-methyl-8-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-] b ]pyridazine-6-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1101] ((1 R ,3 R )-3-(6-((6-(5-(2-hydroxypropyl-2-yl)thiazolyl)-4-(tetrahydro-2-yl) H -pyran-4-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5-c 1-pyridinyl)cyclopentyl)carbamate methyl ester;

[1102] ((1 R ,3 R )-3-(6-((6-(5-(2-hydroxypropyl-2-yl)thiazolyl)-4-(tetrahydro-2-yl) H -pyran-4-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1103] ((1 S ,3 R )-3-(6-((6-(5-(2-hydroxypropyl-2-yl)thiazolyl)-4-(tetrahydro-2-yl) H -pyran-4-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1104] ((1 R ,3 R )-3-(6-((6'-(5-(2-hydroxypropyl-2-yl)thiazolyl)-4-(trifluoromethyl)-[3,4'-bipyridine]-2'-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1105] ((1 S ,3 R )-3-(6-((6'-(5-(2-hydroxypropyl-2-yl)thiazolyl)-4-(trifluoromethyl)-[3,4'-bipyridine]-2'-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1106] ((1 R ,3R )-3-(6-((6-(5-(2-hydroxypropyl-2-yl)thiazolyl-2-yl)-4-(1-methylpiperidin-4-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1107] ((1 R ,3 R )-3-(6-((6'-(5-(2-hydroxypropyl-2-yl)thiazolyl)-2-(trifluoromethyl)-[3,4'-bipyridine]-2'-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate;

[1108] N -((1 S ,3 R )-3-(6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-2-methyl-8-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-] b ]pyridazine-6-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)acetamide; and

[1109] ((1 R ,3 R )-3-(6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-7-(2-hydroxypropyl-2-yl)-2-methyl-3-yl) H -imidazo[4,5- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d methyl carbamate

[1110] Or its pharmaceutically acceptable salt.

[1111] It should be further understood that certain features of the invention described in the context of individual embodiments for clarity may also be provided in combination in a single embodiment. Conversely, various features of the invention described in the context of a single embodiment for simplicity may also be provided individually or in any suitable combination.

[1112] Divalent linking substituents are described in various locations throughout this specification. It is explicitly anticipated that each divalent linking substituent includes both its forward and backward forms. For example, -NR(CR'R''). n -Including-NR(CR'R'') n - and -(CR'R'') n NR - Both. When the structure clearly requires a linking group, the Markush variables listed for that group should be understood as linking groups.

[1113] The term "n-membered" (where n is an integer) typically describes the number of cyclic atoms in a portion, where the number of cyclic atoms is n. For example, piperidinyl is an example of a 6-membered heterocyclic alkyl ring, pyrazolyl is an example of a 5-membered heteroaryl ring, pyridinyl is an example of a 6-membered heteroaryl ring, and 1,2,3,4-tetrahydro-naphthalene is an example of a 10-membered cycloalkyl ring.

[1114] As used herein, the phrase “optionally substituted” means unsubstituted or substituted. Substituents are independently chosen, and substitution can occur at any chemically accessible position. As used herein, the term “substituted” means that a hydrogen atom has been removed and replaced by a substituent. A single divalent substituent (e.g., oxo) can substitute for two hydrogen atoms. It should be understood that substitution at a given atom is limited by valence.

[1115] As used in this article, the phrase “each ‘variable’ is selected independently” means essentially the same as “each time it appears, the ‘variable’ is selected”.

[1116] Throughout the definition, the term "C" n-m The indication includes the range of endpoints, where n and m are integers and indicate the number of carbons. Examples include C. 1-3 C 1-4 C 1-6 wait.

[1117] As used herein, the term "C" is used alone or in combination with other terms. n-m "Alkyl" refers to a saturated hydrocarbon group that can be straight-chain or branched and has n to m carbon atoms. Examples of alkyl moiety include, but are not limited to, chemical groups such as methyl (Me), ethyl (Et), etc. just propyl ( n -Pr), isopropyl (iPr) just Butyl, Uncle Ding alkyl, isobutyl, Zhong Ding Group; high-carbon homologs, such as 2-methyl-1-butyl, just pentyl, 3-pentyl, just Hexyl, 1,2,2-trimethylpropyl, etc. In some embodiments, the alkyl group contains 1 to 6 carbon atoms, 1 to 4 carbon atoms, 1 to 3 carbon atoms, or 1 to 2 carbon atoms. The term "C" n-m "alkyl" should be understood to include deuterated analogs of alkyl groups as defined herein, including but not limited to groups such as trideutermethyl (CD3), pentadeuterethyl (CD2CD3), etc.

[1118] As used in this article, "C" n-m "Alkenyl" refers to an alkyl group having one or more carbon-carbon double bonds and having n to m carbons. Examples of alkenyl groups include, but are not limited to, vinyl groups. just Acrylic, isopropyl, just Butenyl, Zhong Ding Alkenyl groups, etc. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. The term "C" is used in this context. n-m "Alkenyl" should be understood to include deuterated analogs of alkenyl as defined herein, including but not limited to groups such as trideuteryl vinyl (-CD=CD2), tetradeuteryl propenyl (-CD=CD-CD2), etc.

[1119] As used in this article, "C" n-m "Alynyl" refers to an alkyl group having one or more carbon-carbon triple bonds and having n to m carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl (e.g., propyn-1-yl, propyn-2-yl, propyn-2-yl-1-yl), etc. In some embodiments, the alkynyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. The term "C" n-m "Alkyne" should be understood to include deuterated analogs of alkynyl as defined herein, including but not limited to groups such as deuterynyl (-C≡CD), trideuteryn-1-yl (-C≡CCD3), etc.

[1120] As used herein, the term "C" is used alone or in combination with other terms. n-m "Alkoxy" refers to a group of the formula -O-alkyl, wherein the alkyl group has n to m carbons. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, and propoxy (e.g., just propoxy and isopropoxy), butoxy (e.g., just butoxy and Uncle Ding (e.g., alkyl groups). In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. The term "C" is used in this context. n-m"Alkoxy" should be understood as a deuterated analogue including the alkyl portion of an alkoxy group as defined herein, including but not limited to groups such as trideuterium methoxy (-OCD3), pentadeuterium ethoxy (-OCD2CD3), etc.

[1121] As used herein, the term "amino" refers to a group of the formula -NH2.

[1122] As used herein, the term "aryl" alone or in combination with other terms refers to an aromatic hydrocarbon group, which can be monocyclic or polycyclic (e.g., having 2, 3, or 4 fused rings). The term "C n-m "Aryl" refers to an aryl group having n to m ring carbon atoms. Aryl groups include, for example, phenyl, naphthyl, anthracene, phenanthryl, dihydroindenyl, indenyl, etc. In some embodiments, the aryl group has 5 to 10 carbon atoms. In some embodiments, the aryl group is phenyl or naphthyl. In some embodiments, the aryl group is phenyl. The term "aryl" should be understood to include deuterated analogs of aryl groups as defined herein, including but not limited to pentadeuterylphenyl (…). Right now All-deuterium phenyl, phenyl- d 5 ), and groups such as deuterated naphthyl.

[1123] As used herein, "halogenated group" refers to F, Cl, Br, or I. In some embodiments, the halogenated group is F, Cl, or Br. In some embodiments, the halogenated group is F or Cl. In some embodiments, the halogenated group is F. In some embodiments, the halogenated group is Cl.

[1124] As used in this article, "C" n-m "Haloalkoxy" refers to a group of the formula -O-haloalkyl having n to m carbon atoms. Examples of haloalkoxy groups include OCF3 and OCHF2. In some embodiments, the haloalkoxy group is only fluorinated. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. The term "C" is used in this context. n-m "Haloalkoxy" should be understood as a deuterated analogue of the alkyl halo group as defined herein, including but not limited to groups such as deuterated difluoromethoxy (-OCDF2), dideuterated fluoromethoxy (-OCD2F), etc.

[1125] As used herein, the term "C" is used alone or in combination with other terms. n-m"Halogenated alkyl" refers to an alkyl group having 1 to 2s+1 potentially identical or different halogen atoms, where "s" is the number of carbon atoms in the alkyl group, and the alkyl group has n to m carbon atoms. In some embodiments, the halogenated alkyl group is only fluorinated. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. Examples of halogenated alkyl groups include CF3, C2F5, CHF2, CH2F, CCl3, CHCl2, C2Cl5, etc. The term "C" is used in this context. n-m "Halogenated alkyl" should be understood to include deuterated analogs of halogenated alkyl as defined herein, including but not limited to groups such as deuterated difluoromethyl (-CDF2), dideuterated fluoromethyl (-CD2F), etc.

[1126] As used herein, the term "carbonyl" alone or in combination with other terms refers to the -C(O)- group.

[1127] As used in this article, the term "C" n-m "alkyl carbonyl" refers to a group of the formula -C(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1128] As used in this article, the term "C" n-m "alkylsulfonyl" refers to a group of the formula -S(O)2-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1129] As used herein, the term "carboxyl" refers to a group of the formula -C(O)OH.

[1130] As used in this article, the term "two (C)" n-m "alkyl)amino" refers to a group of the formula -N(alkyl)2, wherein each of the two alkyl groups independently has n to m carbon atoms. In some embodiments, each alkyl group independently has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[1131] As used herein, “cycloalkyl” refers to a non-aromatic cyclic hydrocarbon, including cycloalkyl and alkenyl groups. Cycloalkyl groups may include monocyclic or polycyclic (e.g., having two fused rings) groups, spirocyclic, and bridging rings (e.g., bridged bicyclic alkyl). The cyclic carbon atom of a cycloalkyl group may optionally be substituted with an oxo or sulfide ion group (e.g., C(O) or C(S)). The definition of cycloalkyl also includes groups having a ring fused with the cycloalkyl ring (…). Right now A cycloalkyl group is a portion of one or more aromatic rings (with a shared bond), such as benzo or thiophene derivatives of cyclopentane, cyclohexane, etc. The cycloalkyl group containing the fused aromatic ring can be linked via any cyclic atom (including the cyclic atom of the fused aromatic ring). The cycloalkyl group can have 3, 4, 5, 6, 7, 8, 9, or 10 cyclic carbons (i.e., C1, C2, C3, C4, C5, C6, C7, C9, C10 ...3-10 In some embodiments, the cycloalkyl group is C10. 3-10 Monocyclic or bicyclic cycloalkyl group. In some embodiments, the cycloalkyl group is C10. 3-7 Monocyclic cycloalkyl group. In some embodiments, the cycloalkyl group is C10. 4-7 Monocyclic cycloalkyl group. In some embodiments, the cycloalkyl group is C10. 4-10 Spirocyclic or bridged cycloalkyl groups (e.g., bridged bicycloalkyl groups). Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cyclohepttrienyl, norbornyl, norpinyl, norcarnyl, cubane, adamantane, bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, spiro[3.3]heptyl, azaspiro[2.4]heptyl, etc. In some embodiments, the cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. The term “cycloalkyl” should be understood to include deuterated analogs of cycloalkyl as defined herein, including but not limited to groups such as perdeuterium cyclopropyl, perdeuterium cyclobutyl, perdeuterium cyclopentyl, perdeuterium cyclohexyl, etc.

[1132] As used herein, "heteroaryl" refers to a monocyclic or polycyclic (e.g., having two fused rings) aromatic heterocycle having at least one heteroatom ring member selected from N, O, S, and B. In some embodiments, the heteroaryl ring has 1, 2, 3, or 4 independently selected heteroatom ring members from N, O, S, and B. In some embodiments, any cyclic N in the heteroaryl moiety may be an N-oxide. In some embodiments, the heteroaryl is a 5- to 10-membered monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 independently selected heteroatom ring members from N, O, S, and B. In some embodiments, the heteroaryl is a 5- to 10-membered monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 independently selected heteroatom ring members from N, O, and S. In some embodiments, the heteroaryl is a 5- to 6-membered monocyclic heteroaryl having 1 or 2 independently selected heteroatom ring members from N, O, S, and B. In some embodiments, the heteroaryl group is a 5-6 membered monocyclic heteroaryl group having one or two independent heteroatom ring members selected from N, O, and S. In some embodiments, the heteroaryl group contains 3 to 10, 4 to 10, 5 to 10, 5 to 7, 3 to 7, or 5 to 6 cyclic atoms. In some embodiments, the heteroaryl group has 1 to 4 cyclic heteroatoms, 1 to 3 cyclic heteroatoms, 1 to 2 cyclic heteroatoms, or 1 cyclic heteroatomum. When the heteroaryl group contains more than one heteroatom ring member, the heteroatoms may be the same or different. Examples of heteroaryl groups include, but are not limited to, thienyl / thiophenyl, furyl / furanyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, isoxazolyl, 1,2,3-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-triazolyl, 1,2,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-triazolyl, 1,3,4-thiadiazolyl, 1,3,4-oxadiazolyl and 1,2-dihydro-1,2-azaborane, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, azole, and triazolyl. Thiadiazolyl, quinolinyl, isoquinolinyl, indolyl, benzothiophenyl, benzofuranyl, benzoisoxazolyl, imidazo[1,2-b]thiazolyl, purine, triazine, thienzo[3,2-b]pyridyl, imidazo[1,2-a]pyridyl, 1,5-naphthidyl, 1H-pyrazolo[4,3-b]pyridyl, triazolo[4,3-a]pyridyl, 1H-pyrrolo[3,2-b]pyridyl, 1H-pyrrolo[2,3-b]pyridyl, pyrazolo[1,5-a]pyridyl, pyrazolo[1,5-a]pyrimidinyl, inzolyl, imidazo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyrimidinyl, etc. The term “heteroaryl” should be understood to include deuterated analogs of heteroaryl as defined herein, including but not limited to groups such as perdeuterpyridyl, perdeuterpyrazinyl, perdeuterpyrimidinyl, etc.

[1133] As used herein, “heterocyclic alkyl” means a monocyclic or polycyclic heterocycle having at least one non-aromatic ring (saturated or partially unsaturated ring), wherein one or more cyclic carbon atoms of the heterocyclic alkyl group are replaced by heteroatoms selected from N, O, S, and B, and wherein the cyclic carbon atoms and heteroatoms of the heterocyclic alkyl group may optionally be substituted with one or more oxo or sulfide ionic groups (e.g., C(O), S(O), C(S), or S(O)2, etc.). When the cyclic carbon atoms or heteroatoms of the heterocyclic alkyl group are optionally substituted with one or more oxo or sulfide groups, the O or S of the group is other than the number of cyclic atoms specified herein (e.g., 1-methyl-6-oxo-1,6-dihydropyridazin-3-yl is a 6-membered heterocyclic alkyl group in which the cyclic carbon atoms are substituted with oxo atoms, and wherein the 6-membered heterocyclic alkyl group is further substituted with methyl groups). Heterocyclic alkyl groups include monocyclic and polycyclic (e.g., having two fused rings) systems. Heterocyclic alkyl groups include monocyclic and polycyclic 3- to 10-membered, 4- to 10-membered, 5- to 10-membered, 4- to 7-membered, 5- to 7-membered, or 5- to 6-membered heterocyclic alkyl groups. Heterocyclic alkyl groups may also include spirocyclic and bridging rings (e.g., 5- to 10-membered bridged bicyclic alkyl rings, wherein one or more cyclic carbon atoms are replaced by heteroatoms independently selected from N, O, S, and B). Heterocyclic alkyl groups may be linked via cyclic carbon atoms or cyclic heteroatoms. In some embodiments, the heterocyclic alkyl group contains 0 to 3 double bonds. In some embodiments, the heterocyclic alkyl group contains 0 to 2 double bonds. The term "heterocyclic alkyl" should be understood to include deuterated analogs of heterocyclic alkyl groups as defined herein, including but not limited to groups such as perdeuterium-azo-heterocyclic butyl, perdeuterium-pyrrolidinyl, perdeuterium-piperidinyl, etc.

[1134] The definition of heterocyclic alkyl also includes having one or more fused with non-aromatic heterocycles ( Right nowThe heterocyclic alkyl group is a portion of an aromatic ring (with a shared bond), such as benzo[a] or thiophene derivatives of piperidine, morpholine, aziridine, heptatriene, etc. The heterocyclic alkyl group containing the fused aromatic ring can be linked via any cyclic atom (including the cyclic atom of the fused aromatic ring). In some embodiments, the heterocyclic alkyl group contains 3 to 10 cyclic atoms, 4 to 10 cyclic atoms, 3 to 7 cyclic atoms, or 5 to 6 cyclic atoms. In some embodiments, the heterocyclic alkyl group has 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms, or 1 heteroatomation. In some embodiments, the heterocyclic alkyl group is a monocyclic 4-6 membered heterocyclic alkyl group having 1 or 2 heteroatoms independently selected from N, O, S, and B and having one or more oxide ring members. In some embodiments, the heterocyclic alkyl group is a monocyclic or bicyclic 5-10 membered heterocyclic alkyl group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, S, and B and having one or more oxide ring members. In some embodiments, the heterocyclic alkyl group is a monocyclic or bicyclic 5- to 10-membered heterocyclic alkyl group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S and having one or more oxide ring members. In some embodiments, the heterocyclic alkyl group is a monocyclic 5- to 6-membered heterocyclic alkyl group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S and having one or more oxide ring members.

[1135] Examples of heterocyclic alkyl groups include pyrrolidine-2-one (or 2-oxopyrrolidine), 1,3-isoxazolidinyl-2-one, pyranyl, tetrahydropyranyl, oxacyclobutyl, azirrobutyl, morpholinyl, thiomorpholinyl, piperazinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, pyrrolidine, isoxazolidinyl, isothiazolidinyl, pyrazolidine, oxazolidinyl, thiazolidinyl, imidazolidinyl, azirroheptanyl, 1,2,3,4-tetrahydroisoquinoline, benzozazapene, azirrobicyclo[3.1.0]hexyl, diazirrobicyclo[3.1.0]. 0] Hexyl, oxobicyclo[2.1.1] Hexyl, azabicyclo[2.2.1] Heptyl, diazabicyclo[2.2.1] Heptyl, azabicyclo[3.1.1] Heptyl, diazabicyclo[3.1.1] Heptyl, azabicyclo[3.2.1] Octyl, diazabicyclo[3.2.1] Octyl, oxobicyclo[2.2.2] Octyl, azabicyclo[2.2.2] Octyl, azaadamantyl, diazaadamantyl, oxo-adamantyl, azaspiro[3.3] Heptyl, diazaspiro[3.3] Heptyl, oxo-azaspiro[3.3] Heptyl 3,4]octyl, diazaspiro[3,4]octyl, oxo-diazaspiro[3,4]octyl, diazaspiro[2,5]octyl, diazaspiro[2,5]octyl, diazaspiro[4,4]nonyl, diazaspiro[4,4]nonyl, oxo-diazaspiro[4,4]nonyl, diazaspiro[4,5]decyl, diazaspiro[4,5]decyl, diazaspiro[4,4]nonyl, oxo-diazaspiro[4,4]nonyl, oxo-dihydropyridazinyl, oxo-2,6-diazaspiro[3,4]octyl, oxohexahydropyrrolo[1,2-a]pyr Zinyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl, 3-oxopiperazinyl, oxo-pyrrolidinyl, oxo-pyridinyl, 2,3-dihydrobenzo[b][1,4]dioxacyclohexenyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, octahydro-2H-pyrido[1,2-a]pyrazinyl, 1,6-diazaspiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and 2-oxa-5-azabicyclo[4.1.0]heptyl, etc.

[1136] As used in this article, "C" o-p cycloalkyl-C n-m "alkyl-" refers to a group of the formula cycloalkyl-alkylene-, wherein the cycloalkyl group has 0 to p carbon atoms and the alkylene linking group has n to m carbon atoms.

[1137] As used in this article, "C" o-p Aryl-C n-m "alkyl-" refers to a group of the formula aryl-alkylene-, wherein the aryl group has 0 to p carbon atoms and the alkylene linking group has n to m carbon atoms.

[1138] As used in this article, "heteroaryl-C" n-m "alkyl-" refers to a group of the formula heteroaryl-alkylene-, wherein the alkylene linking group has n to m carbon atoms.

[1139] As used in this article, "heterocyclic alkyl-C" n-m "alkyl-" refers to a group of the formula heterocyclic alkyl-alkylene-, wherein the alkylene linking group has n to m carbon atoms.

[1140] As used herein, "alkyl linking group" is a divalent straight-chain or branched alkyl linking group ("alkylene"). For example, "C o-p cycloalkyl-C n-m Alkyl-", "C o-p Aryl-C n-m Alkyl-", "Phenyl-C" n-m Alkyl-", "Heteroaryl-C" n-m alkyl- and heterocyclic alkyl-C n-m The 'alkyl-' designation contains an alkyl linking group. Examples of 'alkyl linking group' or 'alkylene' include methylene, ethyl-1,1-diyl, ethyl-1,2-diyl, propyl-1,3-diyl, propyl-1,2-diyl, propyl-1,1-diyl, etc. The terms 'alkyl linking group' and 'alkylene linking group' should be understood to include deuterated analogs of alkylene as defined herein.

[1141] In some places, the definition or embodiment refers to a specific ring (e.g., an azacyclic butane ring, a pyridine ring, etc.). Unless otherwise indicated, these rings may be attached to any ring member, subject to the limitation that the valence of the atoms does not exceed the limit. For example, an azacyclic butane ring may be attached at any position on the ring, while a pyridine-3-yl ring may be attached at the 3-position.

[1142] As used herein, the term “oxo” refers to an oxygen atom (i.e., =O) as a divalent substituent, which, when attached to a carbon, forms a carbonyl group (e.g., C=O or C(O)), or is attached to a nitrogen or sulfur heteroatom to form a nitrosyl, sulfinyl, or sulfonyl group.

[1143] As used herein, the term "independently selected" means each occurrence of a variable or substituent (e.g., each Ri) M Each time it appears, it is selected independently from the applicable list.

[1144] The compounds described herein may be asymmetric (e.g., having one or more stereocenters). Unless otherwise indicated, all stereoisomers, such as enantiomers and diastereomers, are contemplated. The compounds of this disclosure containing asymmetrically substituted carbon atoms can be isolated in optically active or racemic form. Methods for preparing the optically active form from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of alkenes, C=N double bonds, etc., may also be present in the compounds described herein, and all such stable isomers are covered in this invention. Cis and trans geometric isomers of the compounds of this disclosure are described and can be isolated as mixtures or individual isomers. In some embodiments, the compounds have… (R)- Configuration. In some embodiments, the compound has (S)- Configuration. The formulas provided herein (e.g., Formula I, Formula Ia, etc.) include stereoisomers of the compounds.

[1145] Resolution of racemic mixtures of compounds can be performed by any of a variety of methods known in the art. Exemplary methods include fractional recrystallization using a chiral resolving acid, which is an optically active, salt-forming organic acid. Suitable resolving agents for fractional recrystallization methods are, for example, optically active acids such as tartaric acid in D and L forms, diacetyl tartaric acid, dibenzoyl tartaric acid, mandelic acid, malic acid, lactic acid, or various optically active camphorsulfonic acids, such as β-camphorsulfonic acid. Other resolving agents suitable for fractional crystallization methods include the stereoisomer pure form of α-methylbenzylamine (e.g., S and R (in diastereomers or pure diastereomers), 2-phenylglycine, norephedrine, ephedrine, N-methylephedrine, cyclohexylethylamine, 1,2-diaminocyclohexane, etc.

[1146] Resolution of racemic mixtures can also be performed by elution on a column packed with an optically active resolving agent (e.g., dinitrobenzoylphenylglycine). Suitable elution solvent compositions can be determined by those skilled in the art.

[1147] The compounds described herein also include tautomer forms. Tautomer forms arise from the exchange of single bonds with adjacent double bonds and the accompanying proton migration. Tautomer forms include proton-transfer tautomers, which are protonated states of isomers having the same empirical formula and total charge. Examples of proton-transfer tautomers include keto-enol pairs, amide-imine pairs, lactam-lactamimide pairs, enamine-imine pairs, and cyclic forms in which protons can occupy two or more positions in the heterocyclic system, such as 1H- and 3H-imidazolium, 1H-, 2H- and 4H-1,2,4-triazoles, 1H- and 2H-isoindole, 2-hydroxypyridine and 2-pyridone, and 1H- and 2H-pyrazoles. Tautomer forms can exist in equilibrium or be sterically locked into one form through appropriate substitution.

[1148] All compounds and their pharmaceutically acceptable salts can be found together with other substances such as water and solvents (e.g., hydrates and solvates) or can be isolated.

[1149] In some embodiments, the preparation of the compound may involve adding an acid or base to influence, for example, the catalysis of the desired reaction or the formation of a salt form (such as an acid addition salt).

[1150] In some embodiments, the compounds or salts thereof provided herein are substantially isolated. "Substantially isolated" means that the compound is at least partially or substantially isolated from the environment in which it is formed or detected. Partial isolation may include, for example, compositions rich in the compounds provided herein. Substantially isolated may include compositions containing at least about 50% by weight, at least about 60% by weight, at least about 70% by weight, at least about 80% by weight, at least about 90% by weight, at least about 95% by weight, at least about 97% by weight, or at least about 99% by weight of the compounds or salts thereof provided herein.

[1151] As used herein, the term "compound" is intended to include all stereoisomers, geometric isomers, tautomers, and isotopes of the described structure. Unless otherwise specified, compounds identified herein as a particular tautomer form by name or structure are intended to include other tautomer forms.

[1152] The phrase “pharmaceutically acceptable” is used herein to refer to those compounds, materials, compositions, and / or dosage forms that, to a reasonable medical judgment, are suitable for contact with tissues in humans and animals without excessive toxicity, irritation, allergic reactions, or other problems or complications, and that are commensurate with a reasonable benefit / risk ratio.

[1153] This application also includes pharmaceutically acceptable salts of the compounds described herein. As used herein, a “pharmaceutically acceptable salt” refers to a derivative of the disclosed compound wherein the parent compound is modified by converting the present acid or base moiety into its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, inorganic or organic acid salts of basic residues (such as amines); alkali metal or organic salts of acidic residues (such as carboxylic acids); etc. Pharmaceutically acceptable salts of this disclosure include conventional non-toxic salts of parent compounds formed from, for example, non-toxic inorganic or organic acids. Pharmaceutically acceptable salts of this disclosure can be synthesized by conventional chemical methods from parent compounds containing a basic or acidic moiety. Typically, such salts are prepared by reacting the free acid or base form of these compounds with a stoichiometric amount of a suitable base or acid in water, in an organic solvent, or in a mixture of both; typically, a non-aqueous medium such as diethyl ether, ethyl acetate, alcohols (e.g., methanol, ethanol, isopropanol, or butanol), or acetonitrile (ACN) is preferred. A list of suitable salts is available at [link to relevant documentation]. Remington's Pharmaceutical Sciences , 17th edition, Mack Publishing Company, Easton, Pa., 1985, page 1418 and Journal of Pharmaceutical Science In , 66, 2 (1977), each of which is incorporated herein by reference in its entirety.

[1154] synthesis

[1155] As those skilled in the art will understand, the compounds (including their salts and stereoisomers) provided herein can be prepared using known organic synthesis techniques and can be synthesized according to any of a number of possible synthetic routes.

[1156] Compounds of formula (I) can be prepared, for example, using the method shown in Scheme 1. In the method depicted in Scheme 1, compounds of formula 1-1 (where L1 is a halogen (e.g., F, Cl, or Br)) can be prepared via a nucleophilic aromatic substitution reaction (e.g., in a reaction such as...) N , N -Diisopropylethylamine reacts with compounds 1-2 in the presence of a base, subsequently reducing the nitro group in compounds 1-3 (e.g., under reducing conditions, such as treatment with Zn powder, H2O, and NH4Cl), resulting in the formation of compounds 1-4. Compounds 1-4 can be reacted under standard conditions (e.g., in carbonic acid) NCompounds of formula 1-5 can be converted to cycloureas 1-5 via CN bond formation (e.g., in the presence of an alkyl halide (e.g., iodomethane) and a base (e.g., cesium carbonate)). Compounds of formula 1-6 (where L2 is a halogen (e.g., Cl or Br)) are further conjugated with compounds of formula 1-7 via a Buchwald-Hartwig cross-coupling reaction (e.g., in the presence of tris(dibenzylacetone)dipalladium(O), Xantphos, and cesium carbonate) to generate compounds of formula I.

[1157] Alternatively, compounds of formulas 1-6 can be used to prepare compounds of formulas 1-8 via a Buchwald-Hartwig cross-coupling reaction (e.g., in the presence of tris(dibenzylacetone)dipalladium(0), BrettPhos, and cesium carbonate), followed by NH deprotection of the protecting group (e.g., treatment with HCl or TFA). Compounds of formulas 1-8 can then be coupled with compounds of formulas 1-9 (where X is a halogen (e.g., Cl or Br)) in a Buchwald-Hartwig cross-coupling reaction (e.g., in the presence of tris(dibenzylacetone)dipalladium(0), Xantphos, and cesium carbonate) to give compounds of formula I.

[1158] Option 1.

[1159]

[1160] When Cy 4 When the ring is a 6-membered aryl or heteroaryl ring, compounds of formulas 1-7 and 1-9 can be prepared using the method shown in Scheme 2. Compound 2-1 (where X is a halogen (e.g., Cl, Br, or I)) can be reacted with compound 2-2 (M is B(OR)2, Sn(alkyl)3, Zn-hal, etc.) under standard Suzuki cross-coupling conditions (e.g., in the presence of a palladium catalyst and a suitable ligand / base), or under standard Stille cross-coupling conditions (e.g., in the presence of a palladium catalyst and a suitable ligand), or under standard Root-Kishi cross-coupling conditions (e.g., in the presence of a palladium catalyst and a suitable ligand) to generate compound 2-3. Compound 1-7 can be prepared by functionalizing compound 2-3 (e.g., amide coupling, cross-coupling, Grignard addition, etc.).

[1161] Alternatively, compounds of formulas 2-4 (where X is a halogen (e.g., Cl, Br, or I)) can be converted to compounds 2-5 (M is B(OR)2, Sn(alkyl)3, etc.) under standard conditions (e.g., in the presence of a palladium catalyst and a suitable ligand). Compounds of formulas 2-5 can be further converted to compounds of formulas 2-7 (1-9) via a cross-coupling reaction with compounds of formula 2-6 under standard conditions (e.g., in the presence of a palladium catalyst and a suitable ligand / base). Compounds of formulas 1-7 can be prepared by functionalizing compounds 2-7 (e.g., amide coupling, cross-coupling, Grignard addition, etc.).

[1162] Compounds of formulas 1-9 can also be derived from compounds of formulas 2-4 (where X is a halogen (e.g., Cl, Br, or I)) via a nucleophilic aromatic substitution reaction with compounds 2-8 (e.g., in a reaction such as...). N , N The compounds 2-9 are prepared by functionalizing them (e.g., amide coupling, cross-coupling, Grignard addition, etc.) in the presence of a base of diisopropylethylamine. In Scheme 2, at least one R Q The group corresponds to the variable R as defined in this paper. 5 And each additional R Q The group corresponds to H or, as defined herein, the variable R. 4 .

[1163] Option 2.

[1164]

[1165] When Cy 4 1 H -pyrrolo[3,2- b ]Pyridine or 1 H -pyrazolo[4,3- b When the pyridine ring is present, compounds of formulas 1-7 and 1-9 can be prepared using the method shown in Scheme 3. Compounds of formula 3-1 can undergo halogenation (e.g., in...). N In the presence of iodosuccinimide, it is subsequently alkylated with compound 2-2 (L is a halogen, OM, etc.) to provide compound 3-3. Compound 3-3 can be reacted with compound 3-4 (e.g., M is B(OR)2) under standard cross-coupling conditions (e.g., in the presence of a palladium catalyst and a suitable ligand / base) to generate derivatives of formula 3-5. After functionalizing compound 3-5 (e.g., amide coupling, cross-coupling, Grignard addition, etc.), compounds of formulas 1-7 (if Y = NHPG) and 1-9 (if Y = halogen) can be prepared. In scheme 3, at least one R Q The group corresponds to the variable R as defined in this paper. 5 And each additional R QThe group corresponds to H or, as defined herein, the variable R. 4 .

[1166] Option 3.

[1167]

[1168] When Cy 4 3 H -imidazo[4,5- b ]Pyridine or 1,3-dihydro-2 H -imidazole[4,5- b When the pyridin-2-one ring is present, compounds of formulas 1-9 can be prepared using the method shown in Scheme 4. Compounds of formula 4-1 (where L1 is a halogen (e.g., F, Cl, or Br)) can be prepared via nucleophilic aromatic substitution reactions (e.g., in reactions such as...) N , N -Diisopropylethylamine (in the presence of a base) reacts with compound 4-2 to give compound 4-3. The nitro group in compound 4-3 is reduced (e.g., under reducing conditions, such as treatment with Zn powder, H2O, and NH4Cl), followed by a cyclization reaction (e.g., in the presence of CDI or methyl orthoformate) to give compound 4-4. Following functionalization of compound 4-4 (e.g., amide coupling, cross-coupling, Grignard addition, etc.), compounds 1-9 can be prepared. In scheme 4, at least one R... Q The group corresponds to the variable R as defined in this paper. 5 And each additional R Q The group corresponds to H or, as defined herein, the variable R. 4 .

[1169] Option 4.

[1170]

[1171] When Cy 4 imidazo[1,2- b When the pyridazine ring is present, compounds of formulas 1-7 can be prepared using the method shown in Scheme 5. Compound 5-1 can be coupled with compound 5-2 (e.g., M is B(OR)2Zn-hal, etc.) under standard Suzuki cross-coupling conditions (e.g., in the presence of a palladium catalyst and a suitable ligand / base), or under standard root-bank cross-coupling conditions (e.g., in the presence of a palladium catalyst and a suitable ligand), to generate compound 5-3. Iodination of compound 5-3 (e.g., in...) NCompound 5-4 is obtained in the presence of iodosuccinimide. Compound 5-4 can be reacted with compound 5-5 (e.g., M is B(OR)2) under standard cross-coupling conditions (e.g., in the presence of a palladium catalyst and a suitable ligand / base) to generate compounds 5-6 (1-9). Compound 5-6 can be processed into compounds 1-7 via a Buchwald-Hartwig cross-coupling reaction (e.g., in the presence of a palladium catalyst and a suitable ligand), followed by NH deprotection of the protecting group (e.g., treatment with HCl or TFA). In scheme 5, at least one R... Q The group corresponds to the variable R as defined in this paper. 5 And each additional R Q The group corresponds to H or, as defined herein, the variable R. 4 .

[1172] Option 5.

[1173]

[1174] The reactions used to prepare the compounds described herein can be carried out in suitable solvents that can be readily selected by those skilled in the art of organic synthesis. At the temperature at which the reaction takes place (e.g., a temperature within the range of the solvent's freezing point to its boiling point), a suitable solvent may not substantially react with the starting materials (reactants), intermediates, or products. The given reaction can be carried out in one solvent or a mixture of more than one solvent. Depending on the specific reaction step, a solvent suitable for the particular reaction step can be selected by those skilled in the art.

[1175] As used herein, the terms “ambient temperature” or “room temperature” or “rt” are as understood in the art and generally refer to a temperature approximately equal to the room temperature at which the reaction takes place (e.g., the reaction temperature), such as a temperature of approximately 20°C to approximately 30°C.

[1176] The preparation of the compounds described herein may involve the protection and deprotection of various chemical groups. Those skilled in the art can readily determine the need for protection and deprotection and the selection of appropriate protecting groups. The chemistry of protecting groups can be found, for example, in TW Greene and PGM Wuts, Protective Groups in Organic Synthesis, 3rd Edition, Wiley & Sons, Inc., New York (1999).

[1177] The reaction can be monitored using any suitable method known in the art. For example, it can be monitored using spectroscopic means (such as nuclear magnetic resonance spectroscopy, e.g.) 1 H or 13C) Product formation can be monitored by infrared spectroscopy, spectrophotometry (e.g., UV-Vis light), or mass spectrometry, or by chromatographic methods (such as high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LCMS), or thin-layer chromatography (TLC)). The compound can be purified by those skilled in the art using various methods, including high-performance liquid chromatography (HPLC) and normal-phase silica chromatography.

[1178] How to use

[1179] The compounds described herein can inhibit the V617F variant of the protein-tyrosine kinase JAK2 ( Right now The activity of "V617F" (or "JAK2V617F") is inhibited. Compounds that inhibit V617F can be used to provide a mechanism for preventing tumor growth or inducing apoptosis in tumors (particularly by inhibiting angiogenesis). Therefore, the compounds disclosed herein are expected to be used for the treatment or prevention of proliferative conditions such as cancer. Specifically, tumors with activated mutants of receptor tyrosine kinases or with upregulated receptor tyrosine kinases may be particularly sensitive to inhibitors.

[1180] In some embodiments, this disclosure provides a method for treating V617F-related conditions in a patient in need, the method comprising the step of administering a compound of this disclosure or a pharmaceutically acceptable composition thereof to the patient.

[1181] Myeloproliferative disorders (MPDs) are pluripotent hematopoietic stem cell diseases characterized by the overproduction of various blood cells. MPNs include polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF). It has been reported that approximately 95% of PV patients, 35% to 70% of ET patients, and 50% of IMF patients have the JAK2 V617F mutation. Furthermore, JAK2 exon 12 mutations have been detected in some V617F-negative PV patients (Ma et al., J. Mol. Diagn., 11: 49-53, 2009). In some embodiments, the compounds disclosed herein can be used to treat myeloproliferative disorders (e.g., myeloproliferative neoplasms) in patients in need, such as polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia (MMM), primary myelofibrosis (PMF), chronic myeloid leukemia (CML), chronic myeloid monocytic leukemia (CMML), eosinophilic syndrome (HES), systemic mast cell disease (SMCD), etc.

[1182] In some implementations, the myeloproliferative disorders are selected from polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis.

[1183] In some implementations, the myeloproliferative disorder is a myeloproliferative tumor.

[1184] In some implementations, the myeloproliferative disorder is myelofibrosis (e.g., primary myelofibrosis (PMF) or post-PV / ET myelofibrosis (PV / ET post-MF)).

[1185] In some implementations, the myeloproliferative disorder is primary myelofibrosis (PMF).

[1186] In some implementations, the myeloproliferative disorder is post-essential thrombocytosis myelofibrosis (post-ET MF).

[1187] In some implementations, the myeloproliferative disorder is post-polycythemia vera myelofibrosis (post-PV MF).

[1188] In some implementations, the myeloproliferative disorder is selected from primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocythemia (ET).

[1189] In some implementations, the myeloproliferative tumor is primary myelofibrosis (PMF).

[1190] In some implementations, the myeloproliferative neoplasm is polycythemia vera (PV).

[1191] In some implementations, the myeloproliferative neoplasm is primary thrombocythemia (ET).

[1192] Myeloproliferative disorders include conditions involving bone marrow or lymph node-derived cell types, such as white blood cells. Myeloproliferative disorders can manifest as abnormal cell division, leading to abnormal levels of specific populations of blood cells. The underlying abnormal cell division in proliferative blood disorders is often cellular and not a normal physi...

Claims

1. A compound of Formula I: Formula I or a pharmaceutically acceptable salt thereof, wherein: I with the proviso that: R 1 selected from C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein R 1 each said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl is optionally substituted with 1, 2, or 3 independently selected R 1A substituents; each R 1A is independently selected from halo, oxo, CN, NO2, OR a11 , SR a11 , NHOR a11 , C(O)R b11 , C(O)NR c11 R d11 , C(O)NR c11 (OR a11 ), C(O)OR a11 , OC(O)R b11 , OC(O)NR c11 R d11 , NR c11 R d11 , NR c11 NR c11 R d11 、 NR c11 C(O)R b11 , NR c11 C(O)OR a11 , NR c11 C(O)NR c11 R d11 , C(=NR e11 )R b11 , C(=NR e11 )NR c11 R d11 , NR c11 C(=NR e11 )NR c11 R d11 , NR c11 C(=NR e11 )R b11 , NR c11 S(O)R b11 , NR c11 S(O)NR c11 R d11 , NR c11 S(O)2R b11 , NR c11 S(O)(=NR e11 )R b11 , NR c11 S(O)2NR c11 R d11 , S(O)R b11 , S(O)NR c11 R d11 , S(O)2R b11 , S(O)2NR c11 R d11 , OS(O)(=NR e11 R b11 and OS(O)2R b11 ; each R a11 , b11 , c11 , d11 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein said C a11 alkyl, C b11 alkenyl, and C c11 alkynyl of R d11 , 1-6 , 2-6 , 2-6 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 R M substituents; Each R e11 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl and C 2-6 alkynyl group; Cy 2 selected from C 3-10 cycloalkyl and 4- to 12-membered heterocycloalkyl, wherein said C 3-10 cycloalkyl and 4- to 12-membered heterocycloalkyl are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 2 substituents; Each R 2 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl-, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a2 SR a2 NHOR a2 C(O)R b2 C(O)NR c2 R d2 C(O)NR c2 (OR a2 ), C(O)OR a2 OC(O)R b2 OC(O)NR c2 R d2 NR c2 R d2 NR c2 NR c2 R d2 、 NR c2 C(O)R b2 NR c2 C(O)OR a2 NR c2 C(O)NR c2 R d2 C(=NR) e2 )R b2 C(=NR) e2 )NR c2 R d2 NR c2 C(=NR e2 )NR c2 R d2 NR c2 C(=NR e2 )R b2 NR c2 S(O)R b2 NR c2 S(O)NR c2 R d2 NR c2 S(O)2R b2 NR c2 S(O)(=NR e2 )R b2 NR c2 S(O)2NR c2 R d2 S(O)R b2 S(O)NR c2 R d2 S(O)2R b2 S(O)2NR c2 R d2 OS(O)(=NR) e2 )R b2 OS(O)2R b2 SF5, P(O)R f2 R g2 OP(O)(OR) h2 (OR) i2 ), P(O)(OR h2 (OR) i2 ) and BR j2 R k2 , where R 2 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 2A Substituent substitution; Each R a2 R c2 and R d2 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a2 R c2 and R d2 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 2A Substituent substitution; or any R attached to the same N atom c2 and R d2 together with the N atom to which they are attached form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl, wherein said 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 2A substituents; each R is independently selected from H, C1-C6alkyl, b2 H, C1-C6alkyl, 1-6 C1-C6alkyl, 1-6 C1-C6haloalkyl, 2-6 C1-C6alkenyl, 2-6 C1-C6alkynyl, 6-10 C1-C6alkyl, 3-10 C1-C6alkyl, 6-10 C1-C6alkyl, 1-6 C1-C6alkyl, 3-10 C1-C6alkyl, 1-6 C1-C6alkyl, 1-6 C1-C6alkyl, and 1-6 C1-C6alkyl, wherein each R b2 C1-C6alkyl, 1-6 C1-C6alkyl, 2-6 C1-C6alkyl, 2-6 C1-C6alkyl, 6-10 C1-C6alkyl, 3-10 C1-C6alkyl, 6-10 C1-C6alkyl, 1-6 C1-C6alkyl, 3-10 C1-C6alkyl, 1-6 C1-C6alkyl, 1-6 C1-C6alkyl, and 1-6 each R is independently selected from 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 2A substituents; Each R e2 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; Each R f2 and R g2 Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; Each R h2 and R i2 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; each R is independently selected from the group consisting of OH, C j2 and R k2 is independently selected from the group consisting of OH, C 1-6 alkoxy and C 1-6 haloalkoxy; or any R attached to the same B atom j2 and R k2 together with the B atom to which they are attached form a 5- or 6-membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl; Each R 2A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl-, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a21 SR a21 NHOR a21 C(O)R b21 C(O)NR c21 R d21 C(O)NR c21 (OR a21 ), C(O)OR a21 OC(O)R b21 OC(O)NR c21 R d21 NR c21 R d21 NR c21 NR c21 R d21 、 NR c21 C(O)R b21 NR c21 C(O)OR a21 NR c21 C(O)NR c21 R d21 C(=NR) e21 )R b21 C(=NR) e21 )NR c21 R d21 NR c21 C(=NR e21 )NR c21 R d21 NR c21 C(=NR e21 )R b21 NR c21 S(O)R b21 NR c21 S(O)NR c21 R d21 NR c21 S(O)2R b21 , NR c21 S(O)(=NR e21 )R b21 , NR c21 S(O)2NR c21 R d21 , S(O)R b21 , S(O)NR c21 R d21 , S(O)2R b21 , S(O)2NR c21 R d21 , OS(O)(=NR e21 )R b21 , OS(O)2R b21 , SF5, P(O)R f21 R g21 , OP(O)(OR h21 )(OR i21 ), P(O)(OR h21 )(OR i21 ), and BR j21 R k21 wherein said C 2A alkyl, C 1-6 alkenyl, C 2-6 alkynyl, C 2-6 aryl, C 6-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 3-10 aryl-C 6-10 alkyl-, C 1-6 cycloalkyl-C 3-10 alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-6 alkyl- of R 1-6 is optionally substituted by 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 2B substituents; Each R a21 R c21 and R d21 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a21 R c21 and R d21 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 2B Substituent substitution; or any R attached to the same N atom c21 and R d21 together with the N atom to which they are attached form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl, wherein said 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 2B substituents; Each R b21 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R b21 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 2B Substituent substitution; Each R e21 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; Each R f21 and R g21 Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; Each R h21 and R i21 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; Each R j21 and R k21 Independently selected from OH and C 1-6 Alkoxy and C 1-6 Halogenated alkoxy groups; or any R attached to the same B atom j21 and R k21 together with the B atom to which they are attached form a 5- or 6-membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl; Each R 2B Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl-, (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a22 SR a22 NHOR a22 C(O)R b22 C(O)NR c22 R d22 C(O)NR c22 (OR a22 ), C(O)OR a22 OC(O)R b22 OC(O)NR c22 R d22 NR c22 R d22 NR c22 NR c22 R d22 、 NR c22 C(O)R b22 NR c22 C(O)OR a22 NR c22 C(O)NR c22 R d22 C(=NR) e22 )R b22 C(=NR) e22 )NR c22 R d22 NR c22 C(=NR e22 )NR c22 R d22 NR c22 C(=NR e22 )R b22 NR c22 S(O)R b22 NR c22 S(O)NR c22 R d22 NR c22 S(O)2R b22 NR c22 S(O)(=NR e22 )R b22 NR c22 S(O)2NR c22 R d22 S(O)R b22 S(O)NR c22 R d22 S(O)2R b22 S(O)2NR c22 R d22 OS(O)(=NR) e22 )R b22 and OS(O)2R b22 , where R 2C The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl-, (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution; Each R a22 R c22 and R d22 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a22 R c22 and R d22 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution; or any R attached to the same N atom c22 and R d22 together with the N atom to which they are attached form a 5-6 membered heteroaryl or 4-7 membered heterocycloalkyl, wherein said 5-6 membered heteroaryl or 4-7 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R M substituents; each R is independently selected from H, C b22 haloalkyl, C 1-6 alkenyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-6 alkyl-, C 3-7 cycloalkyl-C 1-6 alkyl-, (5-6 membered heteroaryl)-C 1-6 alkyl- and (4-7 membered heterocycloalkyl)-C 1-6 alkyl-, each optionally substituted with 1, 2, 3, or 4 independently selected R b22 substituents; and 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-6 alkyl-, C 3-7 cycloalkyl-C 1-6 alkyl-, (5-6 membered heteroaryl)-C 1-6 alkyl- and (4-7 membered heterocycloalkyl)-C 1-6 alkyl-, each optionally substituted with 1, 2, 3, or 4 independently selected R M substituents; and Each R e22 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-; R 3 selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl; Cy 4 selected from C 6-10 aryl and 5-14 membered heteroaryl, wherein the C 6-10 aryl and 5-12 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 4 substituents; Each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl-, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a4 SR a4 NHOR a4 C(O)R b4 C(O)NR c4 R d4 C(O)NR c4 (OR a4 ), C(O)OR a4 OC(O)R b4 OC(O)NR c4 R d4 NR c4 R d4 NR c4 NR c4 R d4 、 NR c4 C(O)R b4 NR c4 C(O)OR a4 NR c4 C(O)NR c4 R d4 C(=NR) e4 )R b4 C(=NR) e4 )NR c4 R d4 NR c4 C(=NR e4 )NR c4 R d4 NR c4 C(=NR e4 )R b4 NR c4 S(O)R b4 NR c4 S(O)NR c4 R d4 NR c4 S(O)2R b4 , NR c4 S(O)(=NR e4 )R b4 , NR c4 S(O)2NR c4 R d4 , S(O)R b4 , S(O)NR c4 R d4 , S(O)2R b4 , S(O)2NR c4 R d4 , OS(O)(=NR e4 )R b4 , OS(O)2R b4 , SF5, P(O)R f4 R g4 , OP(O)(OR h4 )(OR i4 ), P(O)(OR h4 )(OR i4 ), and BR j4 R k4 , wherein the C 4 alkyl, C 1-6 alkenyl, C 2-6 alkynyl, C 2-6 aryl, C 6-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 3-10 aryl-C 6-10 alkyl-, C 1-6 cycloalkyl-C 3-10 alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-6 alkyl- of R 1-6 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 4A substituents; Each R a4 R c4 and R d4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a4 R c4 and R d4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 4A Substituent substitution; or any R attached to the same N atom c4 and R d4 together with the N atom to which they are attached form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl, wherein said 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 4A substituents; Each R b4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R b4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 4A Substituent substitution; Each R e4 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; Each R f4 and R g4 Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; Each R h4 and R i4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; Each R j4 and R k4 Independently selected from OH and C 1-6 Alkoxy and C 1-6 Halogenated alkoxy groups; or any R attached to the same B atom j4 and R k4 together with the B atom to which they are attached form a 5- or 6-membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl; Each R 4A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl-, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a41 SR a41 NHOR a41 C(O)R b41 C(O)NR c41 R d41 C(O)NR c41 (OR a41 ), C(O)OR a41 OC(O)R b41 OC(O)NR c41 R d41 NR c41 R d41 NR c41 NR c41 R d41 、 NR c41 C(O)R b41 NR c41 C(O)OR a41 NR c41 C(O)NR c41 R d41 C(=NR) e41 )R b41 C(=NR) e41 )NR c41 R d41 NR c41 C(=NR e41 )NR c41 R d41 NR c41 C(=NR e41 )R b41 NR c41 S(O)R b41 NR c41 S(O)NR c41 R d41 NR c41 S(O)2R b41 , NR c41 S(O)(=NR e41 )R b41 , NR c41 S(O)2NR c41 R d41 , S(O)R b41 , S(O)NR c41 R d41 , S(O)2R b41 , S(O)2NR c41 R d41 , OS(O)(=NR e41 )R b41 , OS(O)2R b41 , SF5, P(O)R f41 R g41 , OP(O)(OR h41 )(OR i41 ), P(O)(OR h41 )(OR i41 ) and BR j41 R k41 wherein said C 41 alkyl, C 1-6 alkenyl, C 2-6 alkynyl, C 2-6 aryl, C 6-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 3-10 aryl-C 6-10 alkyl-, C 1-6 cycloalkyl-C 3-10 alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-C 1-6 alkyl- of R 1-6 is optionally substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R 4B substituents; Each R a41 R c41 and R d41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a41 R c41 and R d41 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 4B Substituent substitution; or any R attached to the same N atom c41 and R d41 together with the N atom to which they are attached form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl, wherein said 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 4B substituents; each R is independently selected from H, C1-C6alkyl, b41 H, C1-C6alkyl, 1-6 C1-C6alkyl, 1-6 C1-C6alkyl, 2-6 C1-C6alkyl, 2-6 C1-C6alkyl, 6-10 C1-C6alkyl, 3-10 C1-C6alkyl, 6-10 C1-C6alkyl, 1-6 C1-C6alkyl, 3-10 C1-C6alkyl, 1-6 C1-C6alkyl, 1-6 C1-C6alkyl, 1-6 C1-C6alkyl, wherein each R is independently optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R b41 C1-C6alkyl, 1-6 C1-C6alkyl, 2-6 C1-C6alkyl, 2-6 C1-C6alkyl, 6-10 C1-C6alkyl, 3-10 C1-C6alkyl, 6-10 C1-C6alkyl, 1-6 C1-C6alkyl, 3-10 C1-C6alkyl, 1-6 C1-C6alkyl, 1-6 C1-C6alkyl, 1-6 each R is independently optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 4B substituent; each R is independently selected from H, OH, CN, C e41 haloalkyl, C 1-6 haloalkoxy, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-6 alkyl-, C 3-10 cycloalkyl-C 1-6 alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-C 1-6 alkyl-; Each R f41 and R g41 Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; Each R h41 and R i41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; each R is independently selected from the group consisting of OH, C j41 and R k41 is independently selected from the group consisting of OH, C 1-6 alkoxy and C 1-6 haloalkoxy; or any R attached to the same B atom j41 and R k41 together with the B atom to which they are attached form a 5- or 6-membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl; Each R 4B Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl-, (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a42 SR a42 NHOR a42 C(O)R b42 C(O)NR c42 R d42 C(O)NR c42 (OR a42 ), C(O)OR a42 OC(O)R b42 OC(O)NR c42 R d42 NR c42 R d42 NR c42 NR c42 R d42 、 NR c42 C(O)R b42 NR c42 C(O)OR a42 NR c42 C(O)NR c42 R d42 C(=NR) e42 )R b42 C(=NR) e42 )NR c42 R d42 NR c42 C(=NR e42 )NR c42 R d42 NR c42 C(=NR e42 )R b42 NR c42 S(O)R b42 NR c42 S(O)NR c42 R d42 NR c42 S(O)2R b42 NR c42 S(O)(=NR e42 )R b42 , NR c42 S(O)2NR c42 R d42 , S(O)R b42 , S(O)NR c42 R d42 , S(O)2R b42 , S(O)2NR c42 R d42 , OS(O)(=NR e42 )R b42 , and OS(O)2R b42 , wherein the C 4C alkyl, C 1-6 alkenyl, C 2-6 alkynyl, phenyl, C 2-6 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 3-7 alkyl-, C 1-6 cycloalkyl-C 3-7 alkyl-, (5-6 membered heteroaryl)-C 1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C 1-6 alkyl- of R 1-6 are each optionally substituted with 1, 2, 3, or 4 R M substituents; Each R a42 R c42 and R d42 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a42 R c42 and R d42 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution; or any R attached to the same N atom c42 and R d42 together with the N atom to which they are attached form a 5-6 membered heteroaryl or 4-7 membered heterocycloalkyl, wherein said 5-6 membered heteroaryl or 4-7 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R M substituents; each R is independently selected from H, C1-C6alkyl, b42 H, C1-C6alkyl, 1-6 C1-C6alkyl, C1-C6haloalkyl, 1-6 C1-C6alkenyl, C1-C6alkynyl, 2-6 phenyl, C3-C6cycloalkyl, 2-6 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, 3-7 phenyl-C1-C6alkyl-, C3-C6cycloalkyl-C1-C6alkyl-, 1-6 C1-C6alkyl-, (5-6 membered heteroaryl)-C1-C6alkyl-, 3-7 C3-C6cycloalkyl-C1-C6alkyl-, 1-6 C1-C6alkyl-, (5-6 membered heteroaryl)-C1-C6alkyl-, 1-6 C1-C6alkyl- and (4-7 membered heterocycloalkyl)-C1-C6alkyl-, 1-6 C1-C6alkyl-, wherein R b42 of the C3-C6cycloalkyl- is optionally substituted with 1, 2, 3, or 4 independently selected R 1-6 C1-C6alkyl, 2-6 C1-C6alkenyl, C1-C6alkynyl, 2-6 phenyl, C3-C6cycloalkyl, 3-7 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, 1-6 C1-C6alkyl-, C1-C6haloalkyl-, 3-7 C3-C6cycloalkyl-C1-C6alkyl-, 1-6 C1-C6alkyl-, (5-6 membered heteroaryl)-C1-C6alkyl-, 1-6 C1-C6alkyl- and (4-7 membered heterocycloalkyl)-C1-C6alkyl-, 1-6 each R is independently selected from H, C1-C6alkyl, M 1, 2, 3, or 4 independently selected R each R is independently selected from H, OH, CN, C e42 haloalkyl, C 1-6 haloalkoxy, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-6 alkyl-, C 3-7 cycloalkyl-C 1-6 alkyl-, (5-6 membered heteroaryl)-C 1-6 alkyl- and (4-7 membered heterocycloalkyl)-C 1-6 alkyl-; R 5 selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, C 6-10 aryl, 5-12 membered heteroaryl, 4-12 membered heterocycloalkyl, OR w2 , SR w2 , NR w2 R w3 , C(O)R w2 , C(O)NR w2 R w3 , C(O)OR w2 , OC(O)R w2 , OC(NR w3 )R w2 , OC(O)NR w2 R w3 , NR w3 C(O)R w2 , NR w3 C(O)OR w2 , NR w3 C(O)NR w2 R w3 , NR w3 S(O)R w2 , NR w3 S(O)NR w2 R w3 , NR w3 S(O)2R w2 , S(O)R w2 , S(O)NR w2 R w3 , S(O)2R w2 , and S(O)2NR w2 R w3 ; wherein R 5 the C 1-6 alkyl and C 6-10 aryl groups are each substituted with 1 R w1 substituent and optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 5A substituents; or R 5 the C 6-10 aryl group is substituted with 1 R w5 substituent and optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 5A substituents; and R 5 the C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 5-12 membered heteroaryl, and 4-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 5A substituents; R w1 Selected from C 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, 5-12 membered heteroaryl, C 6-12 Aryl, 4-12 membered heterocyclic alkyl, OR w4 NHR w4 NR w3 R w4 SR w4 S(O)2R w4 C(O)R w4 C(O)NHR w4 C(O)NR w3 R w4 OC(O)R w4 S(O)R w3 S(O)NR w3 R w3 S(O)2R w2 and S(O)2NR w3 R w3 , where R w1 The C mentioned 2-6 alkenyl, C 2-6 alkynyl group, C 3-12 cycloalkyl, 5-12 membered heteroaryl, C 6-12 The aryl group and the 4-12 membered heterocyclic alkyl group are each optionally represented by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R groups. 5A Substituent substitution; each R w2 is independently selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, and 4-12 membered heterocycloalkyl, wherein R w2 each said C 3-12 cycloalkyl, 5-12 membered heteroaryl, and 4-12 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 5A substituents; Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R w3 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 5A Substituent substitution; each R w4 is independently selected from C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-6 alkyl-, C 3-10 cycloalkyl-C 1-6 alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-C 1-6 alkyl-, wherein R a51 , R c51 and R d51 are each independently selected from the group consisting of halo, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-6 alkyl-, C 3-10 cycloalkyl-C 1-6 alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl- and (4-10 membered heterocycloalkyl)-C 1-6 alkyl- are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 5B substituents; R w5 is C 1-6 alkyl, which alkyl is substituted by oxo, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-6 alkyl-, C 3-10 cycloalkyl-C 1-6 alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl-, (4-10 membered heterocycloalkyl)-C 1-6 alkyl-, CN, NO2, OR a51 , SR a51 , NHOR a51 , C(O)R b51 , C(O)NR c51 R d51 , C(O)NR c51 (OR a51 ), C(O)OR a51 , OC(O)R b51 , OC(O)NR c51 R d51 , NR c51 R d51 , NR c51 NR c51 R d51 、 NR c51 C(O)R b51 , NR c51 C(O)OR a51 , NR c51 C(O)NR c51 R d51 , C(=NR e51 )R b51 , C(=NR e51 )NR c51 R d51 , NR c51 C(=NR e51 )NR c51 R d51 , NR c51 C(=NR e51 )R b51 , NR c51 S(O)R b51 , NR c51 S(O)NR c51 R d51 , NR c51 S(O)2R b51 , NR c51 S(O)(=NR e51 )R b51 , NR c51 S(O)2NR c51 R d51 , S(O)R b51 , S(O)NR c51 R d51 , S(O)2R b51 , S(O)2NR c51 R d51 , OS(O)(=NR e51 )R b51 , OS(O)2R b51 , SF5, P(O)R f51 R g51 , OP(O)(OR h51 )(OR i51 ), P(O)(OR h51 )(OR i51 ), or BR j51 R k51 substituted, wherein the C w5 alkyl, C 1-6 alkenyl, C 2-6 alkynyl, C 2-6 aryl, C 6-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 3-10 aryl-C 6-10 alkyl-, C 1-6 cycloalkyl-C 3-10 alkyl-, (5-10 membered heteroaryl)-C 1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-6 alkyl- of R 1-6 is each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 R 5B substituents; Each R 5A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl-, (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a51 SR a51 NHOR a51 C(O)R b51 C(O)NR c51 R d51 C(O)NR c51 (OR a51 ), C(O)OR a51 OC(O)R b51 OC(O)NR c51 R d51 NR c51 R d51 NR c51 NR c51 R d51 、 NR c51 C(O)R b51 NR c51 C(O)OR a51 NR c51 C(O)NR c51 R d51 C(=NR) e51 )R b51 C(=NR) e51 )NR c51 R d51 NR c51 C(=NR e51 )NR c51 R d51 NR c51 C(=NR e51 )R b51 NR c51 S(O)R b51 NR c51 S(O)NR c51 R d51 NR c51 S(O)2R b51 , NR c51 S(O)(=NR e51 )R b51 , NR c51 S(O)2NR c51 R d51 , S(O)R b51 , S(O)NR c51 R d51 , S(O)2R b51 , S(O)2NR c51 R d51 , OS(O)(=NR e51 )R b51 , OS(O)2R b51 , SF5, P(O)R f51 R g51 , OP(O)(OR h51 )(OR i51 ), P(O)(OR h51 )(OR i51 ) and BR j51 R k51 , wherein said C 5A 1-6 alkyl, C 1-6 2-6 alkenyl, C 2-6 2-6 alkynyl, C 2-6 6 aryl, C 6-10 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 3-10 6 aryl-C 6-10 1-6 alkyl-, C 1-6 3-10 cycloalkyl-C 3-10 1-6 alkyl-, (5-10 membered heteroaryl)-C 1-6 1-6 alkyl- and (4-10 membered heterocycloalkyl)-C 1-6 1-6 alkyl- of R 1-6 is optionally substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R 5B substituents; Each R a51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a51 R c51 and R d51 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3, 4, 5, 6, 7 or 8 independently chosen R 5B Substituent substitution; or any R attached to the same N atom c51 and R d51 together with the N atom to which they are attached form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl, wherein said 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 5B substituents; each R is independently selected from H, C1-C6alkyl, b51 H, C1-C6alkyl, 1-6 C1-C6alkyl, 1-6 C1-C6haloalkyl, 2-6 C1-C6alkenyl, 2-6 C1-C6alkynyl, 6-10 C1-C6alkyl, 3-10 C1-C6alkyl, 6-10 C1-C6alkyl, 1-6 C1-C6alkyl, 3-10 C1-C6alkyl, 1-6 C1-C6alkyl, 1-6 C1-C6alkyl, and 1-6 C1-C6alkyl, wherein each R b51 C1-C6alkyl, 1-6 C1-C6alkyl, 2-6 C1-C6alkyl, 2-6 C1-C6alkyl, 6-10 C1-C6alkyl, 3-10 C1-C6alkyl, 6-10 C1-C6alkyl, 1-6 C1-C6alkyl, 3-10 C1-C6alkyl, 1-6 C1-C6alkyl, 1-6 C1-C6alkyl, and 1-6 each R is independently selected from 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 5B substituents; Each R e51 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; Each R f51 and R g51 Independently selected from H and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; Each R h51 and R i51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl-; each R is independently selected from the group consisting of OH, C j51 and R k51 is independently selected from the group consisting of OH, C 1-6 alkoxy and C 1-6 haloalkoxy; or any R attached to the same B atom j51 and R k51 together with the B atom to which they are attached form a 5- or 6-membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl and C 1-6 haloalkyl; Each R 5B Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl-, (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl group, CN, NO2, OR a52 SR a52 NHOR a52 C(O)R b52 C(O)NR c52 R d52 C(O)NR c52 (OR a52 ), C(O)OR a52 OC(O)R b52 OC(O)NR c52 R d52 NR c52 R d52 NR c52 NR c52 R d52 、 NR c52 C(O)R b52 NR c52 C(O)OR a52 NR c52 C(O)NR c52 R d52 C(=NR) e52 )R b52 C(=NR) e52 )NR c52 R d52 NR c52 C(=NR e52 )NR c52 R d52 NR c52 C(=NR e52 )R b52 NR c52 S(O)R b52 NR c52 S(O)NR c52 R d52 NR c52 S(O)2R b52 NR c52 S(O)(=NR e52 )R b52 NR c52 S(O)2NR c52 R d52 S(O)R b52 S(O)NR c52 R d52 S(O)2R b52 S(O)2NR c52 R d52 OS(O)(=NR) e52 )R b52 and OS(O)2R b52 , where R 5B The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution; Each R a52 R c52 and R d52 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-, where R a52 R c52 and R d52 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R M Substituent substitution; or any R attached to the same N atom c52 and R d52 together with the N atom to which they are attached form a 5-6 membered heteroaryl or 4-7 membered heterocycloalkyl, wherein said 5-6 membered heteroaryl or 4-7 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R M substituents; each R is independently selected from H, C1-C6alkyl, b52 H, C1-C6alkyl, 1-6 C1-C6alkyl, C1-C6haloalkyl, 1-6 C1-C6alkyl, C1-C6haloalkyl, 2-6 C1-C6alkyl, C1-C6haloalkyl, 2-6 C1-C6alkyl, C1-C6haloalkyl, 3-7 C1-C6alkyl, C1-C6haloalkyl, 1-6 C1-C6alkyl, C1-C6haloalkyl, 3-7 C1-C6alkyl, C1-C6haloalkyl, 1-6 C1-C6alkyl, C1-C6haloalkyl, 1-6 C1-C6alkyl, C1-C6haloalkyl, 1-6 C1-C6alkyl, C1-C6haloalkyl, b52 C1-C6alkyl, C1-C6haloalkyl, 1-6 C1-C6alkyl, C1-C6haloalkyl, 2-6 C1-C6alkyl, C1-C6haloalkyl, 2-6 C1-C6alkyl, C1-C6haloalkyl, 3-7 C1-C6alkyl, C1-C6haloalkyl, 1-6 C1-C6alkyl, C1-C6haloalkyl, 3-7 C1-C6alkyl, C1-C6haloalkyl, 1-6 C1-C6alkyl, C1-C6haloalkyl, 1-6 C1-C6alkyl, C1-C6haloalkyl, 1-6 each R is independently selected from H, C1-C6alkyl, M C1-C6alkyl, C1-C6haloalkyl, Each R e52 Independently selected from H, OH, CN, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 Cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C 1-6 Alkyl-, C 3-7 cycloalkyl-C 1-6 Alkyl-, (5-6-membered heteroaryl)-C 1-6 Alkyl- and (4-7 membered heterocyclic alkyl)-C 1-6 alkyl-; and Each R M Independently selected from H, OH, halogenated group, oxo, CN, C(O)OH, NH2, NO2, SF5, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C 6-10 Aryl-C 1-6 Alkyl-, C 3-10 cycloalkyl-C 1-6 Alkyl-, (5-10-membered heteroaryl)-C 1-6 Alkyl- and (4-10 membered heterocyclic alkyl)-C 1-6 alkyl; 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula II: (i) Cy 4 is not triazolopyridinyl; and (ii) R 5 is not morpholinyl or piperazinyl; and (iii) When Cy 4 When it is phenyl, R 5 It is not pyridinyl or pyrimidinyl. Formula II or a pharmaceutically acceptable salt thereof, wherein:

18. The compound of claim 1 or 17, wherein the compound of Formula I is a compound of Formula IIIa, IIIb, IIIc, IIId, IIIe, IIIf, IIIg, IIIh, IIIi, IIIj, IIIk, IIIm, or IIIn: or a pharmaceutically acceptable salt thereof. R 4 selected from C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, OR a4 and NR c4 C(O)OR a4 wherein R 4 the C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 R 4A substituents, each R Each R a4 R c4 and R d4 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group; Each R 4A Selected independently from C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group and CN; R 5 selected from triazolyl, pyrazolyl, piperidinyl, tetrahydropyranyl, NR w2 R w3 , NR w3 C(O)R w2 , NR w3 C(O)OR w2 , and NR w3 S(O)2R w2 , wherein said triazolyl, pyrazolyl, piperidinyl, and tetrahydropyranyl of R 5 are each optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents; each R w2 is independently selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, and 4-12 membered heterocycloalkyl, wherein R w2 each said C 3-12 cycloalkyl, 5-12 membered heteroaryl, and 4-12 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents; Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group; each R 5A is independently selected from halo, oxo, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, NO2, OR a51 , SR a51 , NHOR a51 , C(O)R b51 , C(O)NR c51 R d51 , C(O)NR c51 (OR a51 ), C(O)OR a51 , OC(O)R b51 , OC(O)NR c51 R d51 , NR c51 R d51 , NR c51 NR c51 R d51 、 NR c51 C(O)R b51 , NR c51 C(O)OR a51 , NR c51 C(O)NR c51 R d51 , NR c51 S(O)R b51 , NR c51 S(O)NR c51 R d51 , NR c51 S(O)2R b51 , NR c51 S(O)2NR c51 R d51 , S(O)R b51 , S(O)NR c51 R d51 , S(O)2R b51 , and S(O)2NR c51 R d51 ; and each R a51 , R b51 , R c51 and R d51 are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl.

3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from phenyl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, OR a4 and NR c4 C(O)OR a4 wherein each R 4 is independently selected from halo, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, each optionally substituted with 1, 2, 3, or 4 R 4A substituents.

4. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, OR a4 and NR c4 C(O)OR a4 wherein R 4 each of said phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 4A substituents.

5. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from phenyl, tetrahydropyranyl, pyrazolyl, OR a4 and NR c4 C(O)OR a4 wherein R 4 each of said phenyl, tetrahydropyranyl, and pyrazolyl is optionally substituted with 1, 2, 3, or 4 independently selected R 4A substituents; and each R is independently selected from the group consisting of H, C a4 and R c4 is independently selected from the group consisting of H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl.

6. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein each R 4A is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, and CN.

7. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein each R 4A is independently selected from C 1-6 alkyl and CN.

8. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein each R 4A is independently selected from methyl and CN.

9. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from phenyl, tetrahydropyranyl, pyrazolyl, OR a4 and NR c4 C(O)OR a4 wherein R 4 each of said phenyl, tetrahydropyranyl, and pyrazolyl is optionally substituted with 1 or 2 independently selected R 4A substituents; and Each R a4 and R c4 Independently selected from H and C 1-6 Alkyl; and Each R 4A Selected independently from C 1-6 Alkyl groups and CN.

10. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein R 5 is selected from triazolyl, pyrazolyl, piperidinyl, tetrahydropyranyl, NHR w2 , NHC(O)R w2 , NHC(O)OR w2 , and NHS(O)2R w2 , wherein each of said triazolyl, pyrazolyl, piperidinyl, and tetrahydropyranyl of R 5 is optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents.

11. The compound of any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein each R w2 is independently selected from C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, wherein R w2 the C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 R 5A substituents independently selected.

12. The compound of any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein each R w2 is independently selected from cyclopropyl, cyclobutyl, oxazolyl, and tetrahydropyranyl, wherein the cyclopropyl, cyclobutyl, oxazolyl, and tetrahydropyranyl of R w2 are each optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents.

13. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein each R 5A is independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, CN, OR a51 , C(O)R b51 , and C(O)OR a51 ; and each R is independently selected from the group consisting of H, C a51 and R b51 is independently selected from the group consisting of H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl.

14. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein each R 5A is independently selected from halo, C 1-6 alkyl, and C(O)OR a51 ; and Each R a51 Independently selected from H and C 1-6 alkyl.

15. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein each R 5A is independently selected from fluoro, methyl, and ethoxycarbonyl.

16. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein R 5 is selected from triazolyl, pyrazolyl, piperidinyl, tetrahydropyranyl, NHR w2 , NHC(O)R w2 , NHC(O)OR w2 , and NHS(O)2R w2 , wherein each of said triazolyl, pyrazolyl, piperidinyl, and tetrahydropyranyl of R 5 is optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents. each R w2 is independently selected from the group consisting of cyclopropyl, cyclobutyl, oxazolyl, and tetrahydropyranyl, wherein the cyclopropyl, cyclobutyl, oxazolyl, and tetrahydropyranyl of R w2 are each optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents; each R is independently selected from halo, C 5A alkyl and C(O)OR 1-6 alkyl and C(O)OR a51 ; and Each R a51 Independently selected from H and C 1-6 alkyl.

17. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Cy 4 is selected from thiazolyl, pyrazolyl, pyridinyl, and pyrimidinyl, wherein the thiazolyl, pyrazolyl, pyridinyl, and pyrimidinyl of Cy 4 are each optionally substituted with 1, 2, 3, or 4 independently selected R 4 substituents.

19. The compound of any one of claims 1, 17, and 18, or a pharmaceutically acceptable salt thereof, wherein:

38. The compound of claim 1 or 37, wherein the compound of Formula I is a compound of Formula IVa, IVb, IVc, IVd, IVe, IVf, IVg, IVh, IVi, IVj, IVk, IVm, IVn, IVo, IVp, IVq, IVr, IVs, IVt, IVu, or IVv: or a pharmaceutically acceptable salt thereof. Each R 4 Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, (4-10-membered heterocycloalkyl)-C 1-6 Alkyl-, OR a4 and C(O)R b4 , where R 4 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl and (4-10-membered heterocycloalkyl)-C 1-6 Alkyl groups - each optionally selected by 1, 2, 3 or 4 independently chosen R 4A Substituent substitution; each R is independently selected from the group consisting of H, C a4 and R b4 is independently selected from the group consisting of H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl and 4-6 membered heterocycloalkyl; Each R 4A Independently selected from halogenated, oxo, and C groups. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN, OR a41 and C(O)R b41 ; each R is independently selected from the group consisting of H, C a41 and R b41 is independently selected from the group consisting of H, C 1-6 alkyl and C 1-6 haloalkyl; R 5 selected from C 1-6 alkyl, C 3-12 cycloalkyl, C 6-10 aryl, 5-12 membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3- dihydrobenzo[b][l,4]dioxepinyl, 3,4-dihydro-2H-benzo[b][l,4]oxazinyl, azaspiro[2.4]heptyl, OR w2 , NR w2 R w3 , C(O)R w2 , and C(O)NR w2 R w3 ; wherein R 5 each of the C 1-6 alkyl and C 6-10 aryl groups is substituted with 1 R w1 substituent and optionally substituted with 1 or 2 independently selected R 5A substituents; or R 5 the C 6-10 aryl is substituted with 1 R w5 substituent and optionally substituted with 1 or 2 independently selected R 5A substituents; and R 5 the C 3-12 cycloalkyl, 5-12 membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][l,4]dioxepinyl, 3,4-dihydro-2H- benzo[b][l,4]oxazinyl, and azaspiro[2.4]heptyl are each optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents; R w1 selected from C 3-12 cycloalkyl, 4-12 membered heterocycloalkyl, OR w4 and NHR w4 , wherein R w1 each R 3-12 cycloalkyl and 4-12 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents; each R w2 is independently selected from C 3-12 w2 cycloalkyl, 5-12 membered heteroaryl, and 4-12 membered heterocycloalkyl, wherein R 3-12 each said C 5A cycloalkyl, 5-12 membered heteroaryl, and 4-12 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R​ Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group; Each R w4 Selected independently from C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl; R w5 is C 1-6 alkyl, which alkyl is substituted by CN or OR a51 ; each R 5A is independently selected from halo, oxo, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, OR a51 and NR c51 R d51 wherein the C 5A alkyl, C 1-6 alkenyl, and C 2-6 alkynyl of R 2-6 are each optionally substituted with OR a52 and 1, 2, 3, 4, 5, 6, or 7 independently selected halo; Each R a51 R c51 and R d51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group; and Each R a52 Independently selected from H and C 1-6 alkyl.

20. The compound of any one of claims 1 and 17 to 19, or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently selected from halo, C 1-6 alkyl, C 6-10 aryl, 5-6 membered heteroaryl, 4-10 membered heterocycloalkyl, (4-10 membered heterocycloalkyl)-C 1-6 alkyl-, OR a4 and C(O)R b4 wherein R 4 is the C 1-6 alkyl, C 6-10 aryl, 5-6 membered heteroaryl, 4-10 membered heterocycloalkyl, and (4-10 membered heterocycloalkyl)-C 1-6 alkyl- are each optionally substituted with 1, 2, 3, or 4 independently selected R 4A substituents; and each R is independently selected from H, C a4 and R b4 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl and 4-6 membered heterocycloalkyl.

21. The compound of any one of claims 1 and 17-19, or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently selected from halo, C 1-6 alkyl, phenyl, 5-6 membered heteroaryl, 4-10 membered heterocycloalkyl, (4-6 membered heterocycloalkyl)-C 1-6 alkyl-, OR a4 and C(O)R b4 wherein R 4 is independently selected from halo, C 1-6 alkyl, phenyl, 5-6 membered heteroaryl, 4-10 membered heterocycloalkyl, and (4-6 membered heterocycloalkyl)-C 1-6 alkyl- are each optionally substituted with 1, 2, 3, or 4 independently selected R 4A substituents; and Each R a4 and R b4 Selected independently from C 1-6 Alkyl groups and 4-6 membered heterocyclic alkyl groups.

22. The compound of any one of claims 1 and 17 to 19, or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently selected from fluoro, methyl, trideuteromethyl, isopropyl, methoxy, morpholinylcarbonyl, phenyl, pyrazolyl, pyridinyl, tetrahydropyranyl, piperidinyl, and 2,3-dihydrobenzo[ ] [1,4]dioxinyl, wherein the methyl, isopropyl, phenyl, pyrazolyl, piperidinyl, and 2,3-dihydrobenzo[ ] [1,4]dioxinyl of R 4 are each optionally substituted with 1, 2, 3, or 4 independently selected R 4A substituents.

23. The compound of any one of claims 1 and 17 to 22, or a pharmaceutically acceptable salt thereof, wherein each R 4A is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, CN, OR a41 and C(O)R b41 ; and Each R a41 and R b41 Independently selected from H and C 1-6 alkyl.

24. The compound of any one of claims 1 and 17 to 22, or a pharmaceutically acceptable salt thereof, wherein each R 4A is selected from methyl, difluoromethyl, trifluoromethyl, CN, OH, and methylcarbonyl.

25. The compound of any one of claims 1 and 17 to 19, or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently selected from fluoro, methyl, hydroxymethyl, hydroxyisopropyl, methoxy, (methylcarbonyl)piperidinyl, methylpyrazolyl, cyanophenyl, 2,3-dihydrobenzo[ ] [1,4]dioxinyl, (difluoromethylazetidinyl)methyl, and morpholinylcarbonyl.

26. The compound of any one of claims 1 and 17 to 25, or a pharmaceutically acceptable salt thereof, wherein R 5 is selected from C 1-6 alkyl, C 3-7 cycloalkyl, phenyl, 5-10 membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[ ] [1,4]dioxepinyl, 3,4-dihydro-2H- benzo[ ] [1,4]oxazinyl, azaspiro[2.4]heptyl, OR w2 , NHR w2 , C(O)R w2 , and C(O)NHR w2 ; wherein R 5 1-6 alkyl and phenyl are each substituted with 1 R w1 substituent and optionally substituted with 1 or 2 independently selected R 5A substituents; or​ R 5 The phenyl of said phenyl is substituted with 1 R w5 substituent and optionally substituted with 1 or 2 independently selected R 5A substituents; and R 5 the C 3-7 cycloalkyl, 5-10 membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][l,4]dioxepinyl, 3,4-dihydro-2H- benzo[b][l,4]oxazinyl, and azaspiro[2.4]heptyl are each optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents.

27. The compound of any one of claims 1 and 17 to 25, or a pharmaceutically acceptable salt thereof, wherein R 5 is selected from -CH2R w1 , -CH2R 3-7 cycloalkyl, -phenyl-R w1 , -phenyl-R w5 , 5-10 membered heteroaryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][l,4]dioxepinyl, 3,4-dihydro-2H- benzo[b][l,4]oxazinyl, azaspiro[2.4]heptyl, OR w2 , NHR w2 , C(O)R w2 , and C(O)NHR w2 , wherein the C 5 cycloalkyl, phenyl, 5-10 membered heteroaryl, pyrrolidinyl, piperidinyl, 2,3-dihydrobenzo[b][l,4]dioxepinyl, 3,4-dihydro-2H- benzo[b][l,4]oxazinyl, and azaspiro[2.4]heptyl of R 3-7 are each optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents.

28. The compound of any one of claims 1 and 17 to 27, or a pharmaceutically acceptable salt thereof, wherein R w1 is selected from C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, OR w4 and NHR w4 wherein R w1 the C 3-7 cycloalkyl and 4-7 membered heterocycloalkyl are each optionally substituted with 1 or 2 independently selected R 5A substituents.

29. The compound of any one of claims 1 and 17 to 27, or a pharmaceutically acceptable salt thereof, wherein R w1 is selected from cyclopropyl, fluoropyrrolidinyl, morpholinyl, OR w4 and NHR w4 ; and R w4 selected from C 1-6 haloalkyl and C 3-7 cycloalkyl.

30. The compound of any one of claims 1 and 17 to 27, or a pharmaceutically acceptable salt thereof, wherein R w1 is selected from cyclopropyl, fluoropyrrolidinyl, morpholinyl, trifluoromethoxy, and cyclopentylamino.

31. The compound of any one of claims 1 and 17-30, or a pharmaceutically acceptable salt thereof, wherein R w2 is selected from C 3-7 cycloalkyl, bicyclic 8-12 membered heteroaryl, monocyclic 4-7 membered heterocycloalkyl, and bicyclic 8-12 membered heterocycloalkyl, wherein R w2 each R 3-7 cycloalkyl, bicyclic 8-12 membered heteroaryl, monocyclic 4-7 membered heterocycloalkyl, and bicyclic 8-12 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents.

32. The compound of any one of claims 1 and 17-30, or a pharmaceutically acceptable salt thereof, wherein R w2 is selected from cyclobutyl, cyclopentyl, cyclohexyl, quinolinyl, tetrahydropyranyl, piperidinyl, morpholinyl, pyrrolidinyl, and octahydro-2H-pyrido[l,2- a]pyrazinyl, wherein the cyclobutyl, cyclopentyl, cyclohexyl, quinolinyl, tetrahydropyranyl, piperidinyl, morpholinyl, pyrrolidinyl, and octahydro-2H-pyrido[l,2- a]pyrazinyl of R w2 are each optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents.

33. The compound of any one of claims 1 and 17 to 32, or a pharmaceutically acceptable salt thereof, wherein R w5 is C 1-6 alkyl, said alkyl being substituted with CN or OR a51 ; and R a51 selected from H and C 1-3 alkyl.

34. The compound of any one of claims 1 and 17 to 32, or a pharmaceutically acceptable salt thereof, wherein R w5 is selected from cyanomethyl and hydroxymethyl.

35. The compound of any one of claims 1 and 17 to 34, or a pharmaceutically acceptable salt thereof, wherein each R 5A is independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, CN, OR a51 and NR c51 R d51 wherein the C 1-6 alkyl is optionally substituted with OH and 1, 2, 3, 4, 5, 6, or 7 independently selected halo; and Each R a51 R c51 and R d51 Independently selected from H and C 1-6 alkyl.

36. The compound of any one of claims 1 and 17 to 34, or a pharmaceutically acceptable salt thereof, wherein each R 5A is independently selected from chloro, fluoro, methyl, hydroxyisopropyl, hydroxyhexafluoroisopropyl, difluoromethyl, trifluoromethyl, CN, methoxy, ethoxy, and amino.

37. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Cy 4 is selected from quinolinyl, imidazo[l,2-b]pyridazinyl, and pyrazolo[l,5-a]pyrimidinyl, wherein each of said quinolinyl, imidazo[l,2-b]pyridazinyl, and pyrazolo[l,5-a]pyrimidinyl is optionally substituted with 1, 2, 3, or 4 independently selected R 4 substituents.

39. The compound of any one of claims 1, 37, and 38, or a pharmaceutically acceptable salt thereof, wherein: wherein n is 0, 1, or 2.

68. The compound of any one of claims 1 to 48, or a pharmaceutically acceptable salt thereof, wherein: each R 4 is independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C 3-7 cycloalkyl-C 1-6 alkyl-, wherein R 4 each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C 3-7 cycloalkyl-C 1-6 alkyl- optionally substituted with 1, 2, 3, or 4 independently selected R 4A substituents; each R is independently selected from halo, C 4A haloalkyl, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN and OR a41 ; Each R a41 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 alkynyl group; R 5 selected from C 3-12 cycloalkyl, 5-12 membered heteroaryl, NR w2 R w3 and C(O)R w2 wherein R 5 the C 3-12 cycloalkyl and 5-12 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 R 5A substituents independently selected; each R w2 is independently selected from C 3-12 cycloalkyl and 4-12 membered heterocycloalkyl, wherein R w2 the C 3-12 cycloalkyl and 4-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents; Each R w3 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl or C 2-6 alkynyl group; each R is independently selected from halo, C 5A haloalkyl, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN and OR a51 ; and Each R a51 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl and C 2-6 Alkyne group.

40. The compound of any one of claims 1 and 37 to 39, or a pharmaceutically acceptable salt thereof, wherein R 4 is independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C 3-7 cycloalkyl-C 1-6 alkyl-, wherein R 4 each C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C 3-7 cycloalkyl-C 1-6 alkyl- optionally substituted with 1, 2, 3, or 4 independently selected R 4A substituents.

41. The compound of any one of claims 1 and 37-39, or a pharmaceutically acceptable salt thereof, wherein R 4 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C 3-7 cycloalkyl-C 1-6 alkyl-, wherein R 4 each C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C 3-7 cycloalkyl-C 1-6 alkyl- optionally substituted with 1, 2, 3, or 4 R 4A substituents; Each R 4A Selected independently from C 1-6 Halogenated alkyl groups, CN and OR a41 ;and Each R a41 Independently selected from H and C 1-6 alkyl.

42. The compound of any one of claims 1 and 37 to 39, or a pharmaceutically acceptable salt thereof, wherein R 4 Selected from methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclohexyl, tetrahydropyranyl, deuterated tetrahydropyranyl, pyridyl, and cyclopropylmethyl, wherein R 4 Each of the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclohexyl, tetrahydropyranyl, deuterated tetrahydropyranyl, pyridyl, and cyclopropylmethyl groups is optionally selected independently by one or two groups from C10. 1-3 Halogenated alkyl groups, CN, OH and C 1-3 alkoxy R 4A Substituent substitution.

43. The compound of any one of claims 1 and 37 to 42, or a pharmaceutically acceptable salt thereof, wherein R 5 is selected from C 3-7 cycloalkyl, 5-6 membered heteroaryl, NHR w2 and C(O)R w2 wherein R 5 the C 3-7 cycloalkyl and 5-6 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 R 5A substituents independently selected.

44. The compound of any one of claims 1 and 37 to 42, or a pharmaceutically acceptable salt thereof, wherein R 5 is selected from cyclopropyl, cyclobutyl, cyclohexyl, pyrazolyl, imidazolyl, pyridinyl, NHR w2 and C(O)R w2 wherein R 5 each of said cyclopropyl, cyclobutyl, cyclohexyl, pyrazolyl, imidazolyl, and pyridinyl is optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituents.

45. The compound of any one of claims 1 and 37 to 44, or a pharmaceutically acceptable salt thereof, wherein R w2 is selected from C 3-7 cycloalkyl, 4-8 membered monocyclic heterocycloalkyl, and 6-10 membered bicyclic heterocycloalkyl, wherein R w2 each R 3-7 cycloalkyl, 4-8 membered monocyclic heterocycloalkyl, and 6-10 membered bicyclic heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R 5A substituents, which are independently selected.

46. The compound of any one of claims 1 and 37 to 44, or a pharmaceutically acceptable salt thereof, wherein R w2 selected from cyclopentyl, piperidinyl, morpholinyl, 1,6-diazaspiro[3.3]heptyl, 3- azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[2.2.1]pentyl, 2.2.1] heptyl and 2-oxa-5-azabicyclo[4.1.0]heptyl, wherein R w2 the cyclopentyl, piperidinyl, morpholinyl, 1,6-diazaspiro[3.3]heptyl, 3- azabicyclo[3.1.0]hexyl, 2-oxa-5-azabicyclo[4.1.0]heptyl, 2.2.1] each optionally substituted with 1, 2, 3, or 4 independently selected R 5A substituted with 1, 2, 3, or 4 independently selected R 47. The compound of any one of claims 1 and 37 to 46, or a pharmaceutically acceptable salt thereof, wherein each R 5A is independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, CN, and OR a51 ; and Each R a51 Independently selected from H and C 1-6 alkyl.

48. The compound of any one of claims 1 and 37 to 46, or a pharmaceutically acceptable salt thereof, wherein each R 5A is independently selected from fluoro, methyl, trideuteromethyl, difluoromethyl, trifluoromethyl, CN, and hydroxyl.

49. The compound of any one of claims 1 to 48, or a pharmaceutically acceptable salt thereof, wherein R 1 is C 1-6 alkyl, said alkyl being optionally substituted with 1, 2, or 3 independently selected R 1A substituents.

50. The compound of any one of claims 1 to 49, or a pharmaceutically acceptable salt thereof, wherein R 1 is C 1-6 alkyl.

51. The compound of any one of claims 1 to 49, or a pharmaceutically acceptable salt thereof, wherein R 1 is methyl or trideuteromethyl.

52. The compound of any one of claims 1-51, or a pharmaceutically acceptable salt thereof, wherein Cy 2 cycloalkyl, bicyclic C 3-10 cycloalkyl, bicyclic C 6-10 cycloalkyl, spiro C 6-10 cycloalkyl, monocyclic 4-7 membered heterocycloalkyl, spiro 6-10 membered heterocycloalkyl, and bicyclic 5-10 membered heterocycloalkyl, wherein the monocyclic C 3-10 cycloalkyl, bicyclic C 6-10 cycloalkyl, spiro C 6-10 cycloalkyl, monocyclic 4-7 membered heterocycloalkyl, spiro 6-10 membered heterocycloalkyl, and bicyclic 5-10 membered heterocycloalkyl, are each substituted with 1, 2, 3, or 4 independently selected R 2 substituents.

53. The compound of any one of claims 1 to 51, or a pharmaceutically acceptable salt thereof, wherein Cy 2 Selected from cyclobutyl, cyclopentyl, deuterated cyclopentyl, cyclohexyl, tetrahydrofuranyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl and 2-azabicyclo[2.2.1]heptyl, wherein Cy 2 The cyclobutyl, cyclopentyl, deuterated cyclopentyl, cyclohexyl, tetrahydrofuranyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl and 2-azabicyclo[2.2.1]heptyl are each optionally 1, 2, 3 or 4 independently selected R 2 Substituent substitution.

54. The compound of any one of claims 1 to 51, or a pharmaceutically acceptable salt thereof, wherein Cy 2 is selected from:

69. The compound of any one of claims 1 to 48, or a pharmaceutically acceptable salt thereof, wherein:

55. The compound of any one of claims 1 to 51, or a pharmaceutically acceptable salt thereof, wherein Cy 2 is selected from:

56. The compound of any one of claims 1-51, or a pharmaceutically acceptable salt thereof, wherein Cy 2 is selected from:

57. The compound of any one of claims 1 to 56, or a pharmaceutically acceptable salt thereof, wherein each R 2 is independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O)2R b2 , S(O)R b2 , S(O)NR c2 R d2 , S(O)2R b2 , and S(O)2NR c2 R d2 , wherein the C 2 alkyl, C 1-6 alkenyl, C 2-6 alkynyl of R 2-6 are each optionally substituted with 1, 2, 3, or 4 independently selected R 2A substituents.

58. The compound of any one of claims 1 to 56, or a pharmaceutically acceptable salt thereof, wherein each R 2 is independently selected from halo, C 1-6 alkyl, CN, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , and NR c2 S(O)2R b2 , wherein the C 2 alkyl of R 1-6 is each optionally substituted with 1, 2, 3, or 4 independently selected R 2A substituents.

59. The compound of any one of claims 1-58, or a pharmaceutically acceptable salt thereof, wherein each R a2 , R b2 , R c2 , and R d2 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, wherein the C a2 alkyl, C b1 alkenyl, C c2 alkynyl, C d2 aryl, C 1-6 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl of R 2-6 , R 2-6 , R 6-10 , and R 3-10 is optionally substituted with 1, 2, 3, or 4 independently selected R 2A substituents.

60. The compound of any one of claims 1-58, or a pharmaceutically acceptable salt thereof, wherein each R a2 , R b2 , R c2 , and R d2 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 3-7 alkynyl, phenyl, C a2 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, wherein the C b1 alkyl, phenyl, C c2 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl of R d2 , R 1-6 , R 3-7 , and R 2A is each optionally substituted with 1, 2, 3, or 4 independently selected R 61. The compound of any one of claims 1 to 58, or a pharmaceutically acceptable salt thereof, wherein each R a2 , R b2 , R c2 , and R d2 is independently selected from H, methyl, trideuteromethyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl, wherein the methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl of R a2 , R b1 , R c2 , and R d2 are each optionally substituted with 1, 2, 3, or 4 independently selected R 2A substituents.

62. The compound of any one of claims 1 to 56, or a pharmaceutically acceptable salt thereof, wherein each R 2 is independently selected from halo, C 1-6 alkyl, CN, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , and NR c2 S(O)2R b2 , wherein the C 2 alkyl of R 1-6 is each optionally substituted with 1, 2, 3, or 4 independently selected R 2A substituents; and each R a2 , R b2 , R c2 , and R d2 is independently selected from H, methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl, wherein the methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl of R a2 , R b1 , R c2 , and R d2 are each optionally substituted with 1 or 2 independently selected R 2A substituents.

63. The compound of any one of claims 1 to 62, or a pharmaceutically acceptable salt thereof, wherein each R 2A is independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, and OR a21 .

64. The compound of any one of claims 1 to 62, or a pharmaceutically acceptable salt thereof, wherein each R 2A is independently selected from halo and OR a21 ; and each R a21 is independently selected from H and C 1-6 alkyl.

65. The compound of any one of claims 1 to 62, or a pharmaceutically acceptable salt thereof, wherein each R 2A is independently selected from fluoro, hydroxyl, and methoxy.

66. The compound of any one of claims 1 to 65, or a pharmaceutically acceptable salt thereof, wherein R 3 is selected from H and C 1-6 alkyl.

67. The compound of any one of claims 1 to 65, or a pharmaceutically acceptable salt thereof, wherein R 3 is H.

70. The compound of any one of claims 1 to 48, or a pharmaceutically acceptable salt thereof, wherein: R 1 selected from C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl; Cy 2 monocyclic C 3-10 cycloalkyl, bicyclic C 6-10 cycloalkyl, spiro C 6-10 cycloalkyl, monocyclic 4-7 membered heterocycloalkyl, spiro 6-10 membered heterocycloalkyl, and bicyclic 5-10 membered heterocycloalkyl, wherein the monocyclic C 3-10 cycloalkyl, bicyclic C 6-10 cycloalkyl, spiro C 6-10 cycloalkyl, monocyclic 4-7 membered heterocycloalkyl, spiro 6-10 membered heterocycloalkyl, and bicyclic 5-10 membered heterocycloalkyl, each substituted with 1, 2, 3, or 4 independently selected R 2 substituents; each R 2 is independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O)2R b2 , S(O)R b2 , S(O)NR c2 R d2 , S(O)2R b2 , and S(O)2NR c2 R d2 , wherein the C 2 alkyl, C 1-6 alkenyl, C 2-6 alkynyl of R 2-6 are each optionally substituted with 1, 2, 3, or 4 independently selected R 2A substituents; Each R a2 R b2 R c2 and R d2 Independently selected from H and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10-membered heteroaryl and 4-10-membered heterocycloalkyl, wherein R a2 R b1 R c2 and R d2 The C mentioned 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl, C 3-10 Cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl are each optionally represented by 1, 2, 3, or 4 independently selected Rs. 2A Substituent substitution; each R is independently selected from halo, C 2A haloalkyl, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN and OR a21 ; Each R a21 Independently selected from H and C 1-6 Alkyl; and R 3 selected from H and C 1-6 alkyl.

71. The compound of claim 1, selected from: R 1 selected from C 1-6 alkyl; Cy 2 monocyclic C 3-10 cycloalkyl, bicyclic C 6-10 cycloalkyl, spiro C 6-10 cycloalkyl, monocyclic 4-7 membered heterocycloalkyl, spiro 6-10 membered heterocycloalkyl, and bicyclic 5-10 membered heterocycloalkyl, wherein the monocyclic C 3-10 cycloalkyl, bicyclic C 6-10 cycloalkyl, spiro C 6-10 cycloalkyl, monocyclic 4-7 membered heterocycloalkyl, spiro 6-10 membered heterocycloalkyl, and bicyclic 5-10 membered heterocycloalkyl, each substituted with 1, 2, 3, or 4 independently selected R 2 substituents; each R 2 is independently selected from halo, C 1-6 alkyl, CN, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , and NR c2 S(O)2R b2 , wherein the C 2 atoms of said R 1-6 are each optionally substituted with 1, 2, 3, or 4 independently selected R 2A substituents; each R a2 , R b2 , R c2 , and R d2 is independently selected from H, C 1-6 1-6 alkyl, C 2-6 2-6 alkenyl, C 3-7 2-6 alkynyl, phenyl, C a2 3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, wherein the C b1 1-6 alkyl, C c2 2-6 alkenyl, C d2 2-6 alkynyl, phenyl, C 1-6 3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl of R 3-7 , R 2A is each optionally substituted with 1, 2, 3, or 4 independently selected R Each R 2A Independently selected from halogenated groups, C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Alkyne, CN and OR a21 ; Each R a21 Independently selected from H and C 1-6 Alkyl; and R 3 is H. or a pharmaceutically acceptable salt thereof. R 1 is C 1-3 alkyl; Cy 2 is selected from cyclobutyl, cyclopentyl, deuterated cyclopentyl, cyclohexyl, tetrahydrofuranyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl, and 2-azabicyclo[2.2.1]heptyl, wherein the cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, spiro[3.3]heptyl, 3-azabicyclo[3.1.0]hexyl, 2-azaspiro[3.3]heptyl, and 2-azabicyclo[2.2.1]heptyl of Cy 2 is each optionally substituted with 1, 2, 3, or 4 independently selected R 2 substituents; each R 2 is independently selected from halo, C 1-6 alkyl, CN, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , and NR c2 S(O)2R b2 , wherein the C 2 alkyl groups of R 1-6 are each optionally substituted with 1, 2, 3, or 4 independently selected R 2A substituents; each R a2 , R b2 , R c2 , and R d2 is independently selected from H, methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl, wherein the methyl, ethyl, propynyl, cyclopropyl, cyclobutyl, phenyl, and tetrahydropyranyl of R a2 , R b1 , R c2 , and R d2 are each optionally substituted with 1, 2, 3, or 4 independently selected R 2A substituents; each R is independently selected from halo and OR 2A is independently selected from halo and OR a21 ; Each R a21 Independently selected from H and C 1-6 Alkyl; and R 3 is H.

72. A compound selected from: 2-((3'-cyano-5-((1-((1) R ,3 R )-3-((methoxycarbonyl)amino)cyclopentyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1,1'-Biphenyl]-3-yl)amino)oxazol-5-carboxylic acid ethyl ester; ((1 R ,3 R )-3-(6-((3'-cyano-5-(4-fluorotetrahydro-2 H -pyran-4-carboxylamino)-[1,1'-biphenyl]-3-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-(methyl- d 3)-6-((4-(1-methyl-1,6-diazaspiro[3.3]heptane-6-carbonyl)-8-(trifluoromethyl)quinolin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(4-(hydroxymethyl)-3-methylphenyl)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6'-methoxy-[2,3'-bipyridine]-6-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((4-(4-cyanopiperidin-1-carbonyl)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-6-((6-(3-methyl-1 H -indazole-5-yl)pyridin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((6-(quinolin-6-yl)pyridin-2-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((4-(1-hydroxy-3-azabicyclo[3.1.0]hexane-3-carbonyl)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-6-((6-(4-methyl-3,4-dihydro-2) H -benzo[ b [1,4]Oxazin-7-yl)pyridin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((4-(2-oxa-5-azabicyclo[2.2.1]heptane-5-carbonyl)-8-(trifluoromethyl)quinolin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H - imidazo [4, 5- c ] pyridin- 1 -yl) cyclopentyl) carbamic acid methyl ester ; ((1 R ,3 R )-3-(6-((4-(2-oxa-5-azabicyclo[4.1.0]heptane-5-carbonyl)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; (3-((1-((1 R ,3 R )-3-((methoxycarbonyl)amino)cyclopentyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H methyl 1,2,3-triazol-4-yl)phenyl)carbamate; (3-((1-((1 R ,3 R )-3-((methoxycarbonyl)amino)cyclopentyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c Methyl pyridin-6-yl)amino)-5-(1-methylpiperidin-4-yl)phenyl)carbamate; ((1 R ,3 R )-3-(6-((4-(3,3-difluoropiperidin-1-carbonyl)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-(( R )-2,2-difluorocyclopropane-1-formamide)-5-(tetrahydro-2 H -pyran-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-((3,3-difluorocyclopentyl)amino)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-(cyclobutaneformamido)-5-(tetrahydro-2 H -pyran-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -Imidazo[4,5-c]pyridin-1-yl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-(methyl- d 3)-6-((6-(1-methyl-1 H -pyrazol-4-yl)-8-(trifluoromethyl)quinoline-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; (3-((1-((1 R ,3 R )-3-((methoxycarbonyl)amino)cyclopentyl)-3-methyl-2-oxo-2,3-dihydro-1 H - imidazo [4, 5- c ] pyridin-6-yl) amino) -5- (tetrahydro-2 H -pyran-3-yl) phenyl) carbamic acid methyl ester; ((1 R ,3 R )-3-(6-((6-(((4-cyanocyclohexyl)oxy)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((6-(quinolin-6-yloxy)pyridin-2-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; (3-((1 r ,3 r )-3-(cyclopropanecarboxamido)cyclobutyl)-3-methyl-2-oxo-2,3-dihydro-1 H -3-(cyclopropanecarboxamido)cyclobutyl)-3-methyl-2-oxo-2,3-dihydro-1 c -3-(cyclopropanecarboxamido)cyclobutyl)-3-methyl-2-oxo-2,3-dihydro-1 H -3-(cyclopropanecarboxamido)cyclobutyl)-3-methyl-2-oxo-2,3-dihydro-1 (3-((1-(6-((ethyloxy carbonyl)amino)spiro[3.3]heptan-2-yl)-3-methyl-2-oxo-2,3-dihydro-1 H - imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H - pyrazol-4-yl)phenyl)carbamic acid methyl ester; (3-((1-(6-(cyclopropanesulfonylamido)spiro[3.3]heptan-2-yl)-3-methyl-2-oxo-2,3- dihydro-1 H-isoindol-5-yl)methyl)azetidin-3-yl)methanol; H - imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H - pyrazol-4-yl)phenyl)carbamic acid methyl ester; 6-(6-((3-((methoxycarbonyl)amino)-5-(1-methyl-1 H -2-oxo-2,3-dihydro-1 H -2-oxo-2,3-dihydro-1 c ]pyridin-1-yl)-2-azaspiro[3.3]heptane-2-carboxylic acid methyl ester; (3-((1-((1r,3r)-3-cyanocyclobutyl)-3-methyl-2-oxo-2,3-dihydro-1 H - imidazo [4, 5- c ] pyridin-6-yl) amino) -5- (1-methyl-1 H - pyrazol-4-yl) phenyl) carbamic acid methyl ester; (3-((1-((1r,3r)-3-((methoxycarbonyl)amino)-3-methylcyclobutyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H 4-pyrazole-4-yl)phenyl)carbamate methyl ester; ( R )-(3-((1-(3,3-difluorocyclopentyl)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H 4-pyrazole-4-yl)phenyl)carbamate methyl ester; (3-((1 R ,3 S )-3-Fluorocyclopentyl)-3-methyl-2-oxo-2,3-dihydro-1 H -Imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)carbamate; ((1 R ,3 R )-3-(3-methyl-6-((6-(1-methyl-1 H -pyrazol-4-yl)quinoline-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-6-((8-(1-methyl-1 H -pyrazol-4-yl)quinoline-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-6-((3-(1-methyl-1) H -pyrazol-4-yl)imidazo[1,2-b]pyridazine-6-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-6-((2-(1-methyl-1) H -pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-6-((3-(1-methyl-1) H -pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((6-((tetrahydro-2) H -pyran-4-yl)oxy)pyridin-2-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-6-((3-(1-methyl-1) H -imidazol-5-yl)imidazo[1,2-b]pyridazine-6-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; (1 R 5 S )-6-(6-((3-((methoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c Methyl pyridin-1-yl)-3-azabicyclo[3.1.0]hexane-3-carboxylate; (3-((1-(2-acetyl-2-azabicyclo[2.2.1]heptan-5-yl)-3-methyl-2-oxo-2,3-dihydro-1 H - imidazo[4,5- c ]pyridin-6-yl)amino)-5-(1-methyl-1H-pyrazol-4-yl)phenyl)carbamate; ((1 R ,3 R )-3-(6-((3-((3,3-difluorocyclobutane)-1-sulfonamide)-5-(tetrahydro-2 H -pyran-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; (3-((1-(4-((methoxycarbonyl)amino)-4-methylcyclohexyl)-3-methyl-2-oxo-2,3- dihydro-1 H-isoindol-5-yl)methyl)azetidin-3-yl)methanol; H - imidazo[4,5-c]pyridin-6-yl)aminol methyl; and H - pyrazol-4-yl)phenyl)carbamic acid methyl ester; ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 2-Methoxyethyl pyridin-1-yl)cyclopentyl)carbamate; ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(tetrahydro-2 H -pyran-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate cyclobutyl ester; ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate; ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate prop-2-yn-1-yl ester; ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl)tetrahydro-2-carbamate H -Pyran-4-yl ester; ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 4-fluorophenyl pyridin-1-yl)cyclopentyl)carbamate; ((1 R ,3 R )-3-(6-((6-cyclopropylpyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(3-cyanophenyl)-4-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-(methyl- d 3)-6-((4-(morpholin-4-carbonyl)-8-(trifluoromethyl)quinolin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -Imidazo[4,5-c]pyridin-1-yl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-((methoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-Cyclopropylimidazo[1,2-b]pyridazine-6-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -Imidazo[4,5-c]pyridin-1-yl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-((cyclopropoxycarbonyl)amino)-5-methoxyphenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-((cyclobutoxycarbonyl)amino)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-(cyclopropaneformamido)-5-(1-methyl-1 H -pyrazol-4-yl)phenyl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-(methyl- d 3)-6-((8-(1-methylcyclopropyl)quinolin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -Imidazo[4,5-c]pyridin-1-yl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-(3-fluoro-1-(methyl- d 3)-1 H -pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((4-(cyclobutoxymethyl)-6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(3-aminopyrrolidone-1-yl)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((4-((cyclopentylamino)methyl)-6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((2-(piperidin-1-yl)pyrimidin-4-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((2'-methoxy-4-methyl-[2,4'-bipyridine]-6-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((4-(pyridin-4-yl)thiazo-2-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-fluoro-6'-(trifluoromethyl)-[2,3'-bipyridine]-6-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(2,3-dihydrobenzo[b][1,4]dioxane-6-yl)-4-((( S )-3-fluoropyrrolidone-1-yl)methyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(4-(cyanomethyl)phenyl)-5-fluoropyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(4-cyclopropylphenyl)-5-fluoropyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((5-fluoro-6-(4-(trifluoromethoxy)phenyl)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)-4-(morpholinylmethyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((2-(2-methoxypyridin-4-yl)pyrimidin-4-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)-4-(octahydro-2 H -pyrido[1,2- a ]pyrazine-2-carbonyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((2-(5-azaspiro[2.4]hept-5-yl)pyrimidin-4-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((2-(3,3-difluoropyrrolidone-1-yl)pyrimidin-4-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((2-(4-(trifluoromethyl)piperidin-1-yl)pyrimidin-4-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)-4-(( R )-3-fluoropyrrolidine-1-carbonyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((1-(pyridin-4-yl)-1 H -pyrazole-3-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(2,3-dihydrobenzo[ b [1,4]dioxane-6-yl)-4-(morpholin-4-carbonyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((2-((3,3-difluorocyclopentyl)amino)pyrimidin-4-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((2-(3,3-difluoropyrrolidone-1-yl)-6-methylpyrimidin-4-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((2-((tetrahydro-2) H -pyran-4-yl)amino)pyrimidin-4-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(3-methyl-2-oxo-6-((6-(piperidin-1-carbonyl)pyridin-2-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; and ((1 R ,3 R )-3-(6-((6-(cyclohexylaminocarbamoyl)pyridin-2-yl)amino)-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; or a pharmaceutically acceptable salt thereof.

73. The compound of claim 1, selected from: (3-((1 -cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1 H - imidazo [4,5- c ] pyridin-6-yl) amino) -5- (1 -methyl-1 H - pyrazol-4-yl) phenyl) carbamic acid cyclobutyl ester; (3-((1 -cyclopentyl-3-methyl-2-oxo-2,3-dihydro-1 H - imidazo [4,5- c ] pyridin-6-yl) amino) -5- (1 - cyclopropyl-1 H - pyrazol-4-yl) phenyl) carbamic acid cyclobutyl ester; and (3-(1-cyclopropyl-1 H - pyrazol-4-yl)-5-((3-methyl-2-oxo-1-(tetrahydrofuran-3-yl)-2,3-dihydro-1 H - imidazo[4,5- c ]pyridin-6-yl)amino)phenyl)carbamic acid cyclobutyl ester; or a pharmaceutically acceptable salt thereof.

74. The compound of claim 1, selected from: ((1 R ,3 R )-3-(6-((1-(2-methoxyethyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-1-methyl-2-oxo-7-(4-(trifluoromethyl)pyridin-3-yl)-2,3-dihydro-1 H -imidazo[4,5- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; N - (6-(3-(methyl- d 3)-6-((4-(morpholine-4-carbonyl)-8-(trifluoromethyl)quinolin-2-yl)amino)-2-oxo-2,3-dihydro-1 H - imidazo[4,5- c ]pyridin-1-yl)spiro[3.3]heptan-2-yl)cyclopropanecarboxamide; N -((1 s, 4 s )-1-Methyl-4-(3-(methyl- d 3)-6-((2-methyl-3-(1-(trifluoromethyl)-1 H -pyrazole-4)-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclohexyl)cyclopropaneformamide; N -((1 S ,3 R )-3-(6-((6-(5-chlorothiazol-2-yl)-4-(2-hydroxypropyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)cyclopropaneformamide; ((1 R ,3 R )-3-(6-((6-(5-chlorothiazol-2-yl)-4-(2-hydroxypropyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(1-methyl-1 H -pyrazol-4-yl)-8-(trifluoromethyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(2-(trifluoromethyl)thiazolyl-5-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((8-(2-cyanopropyl-2-yl)-4-(morpholin-4-carbonyl)quinoline-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-2-methyl-8-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-] b ]pyridazine-6-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-3- d )Methyl carbamate; ((1 R ,3 R )-3-(6-((5-methoxy-6-(5-(trifluoromethyl)thiazo-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(5-((2-hydroxypropyl-2-yl)thiazolyl)-4-methylpyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -Imidazo[4,5-c]pyridin-1-yl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((4-((3-(difluoromethyl)azacyclobut-1-yl)methyl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-cyclobutoxy-5-(1-methyl-1 H -pyrazol-4-yl)-4-(morpholin-4-carbonyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((2-(5-(difluoromethyl)thiophen-2-yl)-6-(hydroxymethyl)pyrimidin-4-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(5-(difluoromethyl)thiophen-2-yl)-4-(morpholin-4-carbonyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((4-(1-acetylpiperidin-4-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; 6-((3-(1-(di fluoromethyl)-1 H - pyrazol-4-yl)-2-methyl-8-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2- b ]pyridin-2-one; and r ,3 r -3-(2-hydroxypropan-2-yl)cyclobutyl)-3-(methyl- d 3)-1,3-dihydro-2 H - imidazo[4,5- c ]pyridin-2-one; and ((1 R ,3 R )-3-(6-((6-(5-(2-hydroxypropyl-2-yl)thiazolyl-2-yl)-4-(1-methyl-1 H -pyrazol-4-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; and ((1 R ,3 R )-3-(3-(methyl- d 3)-2-oxo-6-((6-(4-(trifluoromethyl)-1 H -pyrazol-1-yl)pyridin-2-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; or a pharmaceutically acceptable salt thereof.

75. The compound of any one of claims 1 to 74, or a pharmaceutically acceptable salt thereof, wherein the compound is deuterated. ((1 R ,3 R )-3-(3-(methyl- d 3)-2-oxo-6-((1-(tetrahydro-2) H -pyran-4-yl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((3 R )-3-(3-(methyl- d 3)-2-oxo-6-((1-(tetrahydro-2 H -oxo-6-((1-(tetrahydro-2 H -oxo-6-((1-(tetrahydro-2 H -oxo-6-((1-(tetrahydro-2 b ]pyridin-5-yl)amino)-2,3-dihydro-1 H ]pyridin-5-yl)amino)-2,3-dihydro-1 c ]pyridin-5-yl)amino)-2,3-dihydro-1 d ]pyridin-5-yl)amino)-2,3-dihydro-1 ((3 R )-3-(3-(methyl- d 3)-2-oxo-6-((1-(tetrahydro-2) H -pyran-4-yl-4- d )-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((3 R )-3-(6-((1-(1-cyanocyclopropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((1 R ,3 R )-3-(6-((1-((1-cyanocyclopropyl)methyl)-3-(1-(difluoromethyl)-1 H -pyrazole-4-yl)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-7-(2-hydroxypropyl-2-yl)-2-methyl-3-yl) H -imidazo[4,5- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; N -((1 R ,3 R )-1-Methyl-3-(3-(methyl- d 3)-6-((4-(morpholin-4-carbonyl)-8-(trifluoromethyl)quinolin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)cyclopropaneformamide; N -((1 S ,3 R )-3-(6-((7-(hydroxymethyl)-2-methyl-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)cyclopropaneformamide; ((1 R ,3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3 )-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; N -((1 S ,3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)cyclopropaneformamide; N -((1 s 4 s )-4-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3 )-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclohexyl)cyclopropaneformamide; N -((1 S ,3 R )-3-(6-((2-((1 s ,3 s )-3-hydroxycyclobutyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)cyclopropaneformamide; ((1 R ,3 R )-3-(6-((2-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; N -((1 S ,3 R )-3-(6-((2-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)cyclopropaneformamide; ((3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3 )-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; N -((1 s 4 s )-4-(6-((1-((1 r 4 r )-4-hydroxycyclohexyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclohexyl)cyclopropaneformamide; N -((1 s 4 s )-1-Methyl-4-(3-(methyl- d 3)-6-((2-methyl-7-(morpholin-4-carbonyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclohexyl)cyclopropaneformamide; ((1 S ,3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridin-1-yl)-1-methylcyclopentyl)carbamate; N -((1 S ,3 R )-3-(6-((1-(2-hydroxy-2-methylpropyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3 )-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c pyridin-1-yl)-1-methylcyclopentyl)acetamide; ((3 R )-3-(6-((7-(2-hydroxypropyl-2-yl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-1-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrrolo[2,3- b ]pyridin-6-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((3 R )-3-(3-(methyl- d 3)-2-oxo-6-((1-(tetrahydro-2 H -oxo-6-((1-(tetrahydro-2 H -oxo-6-((1-(tetrahydro-2 H -oxo-6-((1-(tetrahydro-2 b ]pyridin-5-yl)amino)-2,3-dihydro-1 H ]pyridin-5-yl)amino)-2,3-dihydro-1 c ]pyridin-5-yl)amino)-2,3-dihydro-1 d ]pyridin-5-yl)amino)-2,3-dihydro-1 ((3 R )-3-(6-((1-((1-cyanocyclopropyl)methyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-1 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((3 R )-3-(6-((2-((1-cyanocyclopropyl)methyl)-3-(1-(trifluoromethyl)-1 H -pyrazole-4-yl)-2 H -pyrazolo[4,3- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((1 R ,3 R )-3-(3-(methyl- d 3)-6-((6-methyl-4-(morpholin-4-carbonyl)-8-(trifluoromethyl)quinolin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; N -((1 S ,3 R )-3-(6-((6-(5-chlorothiazol-2-yl)-4-(2-hydroxypropyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c pyridin-1-yl)-1-methylcyclopentyl)acetamide; 4-(6-((4-(2-hydroxypropan-2-yl)-6-(5-(trifluoromethyl)thiazol-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)- N -(methyl- d 3)bicyclo[2.2.2]octane-1-carboxamide; N - cyclopropyl-4-(6-((4-(2-hydroxypropan-2-yl)-6-(5-(trifluoromethyl)thiazol-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H - imidazo[4,5- c ]pyridin-1-yl)bicyclo[2.2.2]octane-1-carboxamide; 4-(6-((4-(2-hydroxypropan-2-yl)-6-(5-(trifluoromethyl)thiazol-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)bicyclo[2.2.2]octane-1-carboxamide; N - (4-(6-((4-(2-hydroxypropan-2-yl)-6-(5-(trifluoromethyl)thiazol-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H - imidazo[4,5- c ]pyridin-1-yl)bicyclo[2.2.2]oct-1-yl)acetamide; 4-(6-((4-(2-hydroxypropan-2-yl)-6-(5-(trifluoromethyl)thiazol-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)bicyclo[2.2.1]heptane-1-carboxamide; N - (4-(6-((4-(2-hydroxypropan-2-yl)-6-(5-(trifluoromethyl)thiazol-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3 )-2-oxo-2,3-dihydro-1 H - imidazo [4,5- c ] pyridin-1-yl) bicyclo [2.2.1] heptan-1-yl) acetamide; N -((1 S ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)propionamide; ((1 R ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(2-hydroxypropyl-2-yl)thiazolyl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropyl-2-yl)thiazolyl-2-yl)-4-(2-hydroxypropyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; N -((1 S ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(2-(trifluoromethyl)thiazolyl-5-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c pyridin-1-yl)-1-methylcyclopentyl)acetamide; ((1 R ,3 R )-3-(6-((6-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropyl-2-yl)thiazolyl-2-yl)-4-(2-hydroxypropyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((1 R ,3 R )-3-(6-((6-(5-((2-hydroxypropyl-2-yl)thiazolyl)-4-methylpyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((1 R ,3 R )-3-(6-((5-fluoro-6-(5-(2-hydroxypropyl-2-yl)thiazolyl)-4-methylpyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)cyclopentyl-1-d)carbamate; ((1 R ,3 R )-3-(6-((6-(5-(2-hydroxypropyl-2-yl)thiazolyl-2-yl)-4-(methyl- d 3)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; N -((1 S ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(2-isopropoxythiazo-5-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c pyridin-1-yl)-1-methylcyclopentyl)acetamide; N -((1 S ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(2-methoxythiazo-5-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c pyridin-1-yl)-1-methylcyclopentyl)acetamide; N -((1 S ,3 R )-3-(6-((6-(2-ethoxythiazolyl-5-yl)-4-(2-hydroxypropyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c pyridin-1-yl)-1-methylcyclopentyl)acetamide; ((1 R ,3 R )-3-(6-((6'-(5-(difluoromethyl)thiophen-2-yl)-4-(trifluoromethyl)-[3,4'-bipyridine]-2'-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 S ,2 S 4 S )-2-hydroxy-4-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-3- d )Methyl carbamate; ((1 R ,3 R )-3-(3-(methyl- d 3)-6-((4-(1-methylpiperidin-4-yl)-6-(5-(trifluoromethyl)thiazo-2-yl)pyridin-2-yl)amino)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((1 S ,3 R )-3-(6-((4-(2-hydroxypropyl-2-yl)-6-(5-(trifluoromethyl)thiazolyl-2-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((1 S ,3 R )-3-(6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-2-methyl-8-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-] b ]pyridazine-6-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((1 R ,3 R )-3-(6-((6-(5-(2-hydroxypropyl-2-yl)thiazolyl)-4-(tetrahydro-2-yl) H -pyran-4-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c 1-pyridinyl)cyclopentyl)carbamate methyl ester; ((1 R ,3 R )-3-(6-((6-(5-(2-hydroxypropyl-2-yl)thiazolyl)-4-(tetrahydro-2-yl) H -pyran-4-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((1 S ,3 R )-3-(6-((6-(5-(2-hydroxypropyl-2-yl)thiazolyl)-4-(tetrahydro-2-yl) H -pyran-4-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((1 R ,3 R )-3-(6-((6'-(5-(2-hydroxypropyl-2-yl)thiazolyl)-4-(trifluoromethyl)-[3,4'-bipyridine]-2'-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((1 S ,3 R )-3-(6-((6'-(5-(2-hydroxypropyl-2-yl)thiazolyl)-4-(trifluoromethyl)-[3,4'-bipyridine]-2'-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((1 R ,3 R )-3-(6-((6-(5-(2-hydroxypropyl-2-yl)thiazolyl-2-yl)-4-(1-methylpiperidin-4-yl)pyridin-2-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; ((1 R ,3 R )-3-(6-((6'-(5-(2-hydroxypropyl-2-yl)thiazolyl)-2-(trifluoromethyl)-[3,4'-bipyridine]-2'-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; N -((1 S ,3 R )-3-(6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-2-methyl-8-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-] b ]pyridazine-6-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)-1-methylcyclopentyl)acetamide; and ((1 R ,3 R )-3-(6-((3-(1-(difluoromethyl)-1 H -pyrazol-4-yl)-7-(2-hydroxypropyl-2-yl)-2-methyl-3-yl) H -imidazo[4,5- b ]pyridin-5-yl)amino)-3-(methyl- d 3)-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]pyridin-1-yl)cyclopentyl-1- d )Methyl carbamate; 76. A pharmaceutical composition comprising a compound of any one of claims 1 to 75, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

77. A method of inhibiting the activity of a V617F variant of JAK2 kinase, comprising contacting the kinase with a compound of any one of claims 1 to 75, or a pharmaceutically acceptable salt thereof.

78. A method of treating cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of any one of claims 1 to 75, or a pharmaceutically acceptable salt thereof. ​ ​ 79. The method of claim 78, wherein the cancer is selected from bladder cancer, breast cancer, cervical cancer, colorectal cancer, small intestine cancer, colon cancer, rectal cancer, anal cancer, endometrial cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, testicular cancer, uterine cancer, vulvar cancer, esophageal cancer, gallbladder cancer, pancreatic cancer, stomach cancer, thyroid cancer, parathyroid cancer, neuroendocrine cancer, skin cancer, and brain cancer.

80. The method of claim 78, wherein the cancer is a hematological cancer.

81. The method of claim 78, wherein the cancer is selected from leukemia, lymphoma, multiple myeloma, chronic lymphocytic lymphoma, adult T-cell leukemia, acute myeloid leukemia, B-cell lymphoma, cutaneous T-cell lymphoma, acute myeloid leukemia, Hodgkin’s lymphoma or non-Hodgkin’s lymphoma, myeloproliferative neoplasm, myelodysplastic syndrome, chronic eosinophilic leukemia, Waldenstrom macroglobulinemia, hairy cell lymphoma, chronic myeloid lymphoma, acute lymphoblastic lymphoma, AIDS-related lymphoma, and Burkitt’s lymphoma.

82. A method of treating a myeloproliferative disorder in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound of any one of claims 1-75, or a pharmaceutically acceptable salt thereof.

83. The method of claim 82, wherein the myeloproliferative disorder is selected from polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, primary myelofibrosis, post-essential thrombocythemia myelofibrosis, post-polycythemia vera myelofibrosis, chronic myeloid leukemia, chronic myelomonocytic leukemia, hypereosinophilic syndrome, and systemic mast cell disease.

84. A method of treating myelodysplastic syndrome in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound of any one of claims 1-75, or a pharmaceutically acceptable salt thereof.

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