Spirocyclic lactams as JAK2 v617f inhibitors

Abstract

The present application provides spirocyclic lactam compounds that modulate the activity of the V617F variant of JAK2, which are useful in the treatment of various diseases, including cancer.

Description

[Technical Field]

[0001] This invention provides a spirocyclic lactamine compound that modulates the activity of the V617F variant of JAK2 and can be used to treat diseases associated with the V617F variant of JAK2, including cancer. [Previous Technology]

[0002] Janus kinase (JAK) 2 plays a crucial role in signal transduction induced by several cytokine receptors. The mutant JAK2 V617F is the most common molecular event associated with myeloproliferative neoplasms. Selective targeting of the JAK2 V617F mutant can be used to treat various lesions while preserving essential JAK2 function. This application addresses this and other needs. [Summary of the Invention]

[0004] This invention relates particularly to compounds of formula I: I or a pharmaceutically acceptable salt thereof, wherein each of the constituent members is as defined herein.

[0005] 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.

[0006] The present invention further provides a method for inhibiting the activity of the V617F variant of JAK2 kinase, comprising contacting the kinase with a compound of formula I or a pharmaceutically acceptable salt thereof.

[0007] The present invention further provides a method for treating a patient’s disease or condition related to 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.

[0008] The present invention further provides a Formula I compound or a pharmaceutically acceptable salt thereof for use in any of the methods described herein.

[0009] 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 for use in any of the methods described herein.

Implementation Method

[0011] This application provides a compound of formula I: I or a pharmaceutically acceptable salt thereof, wherein: W is a CRW, C(RW)2, N, NRW, O or S; Y is a CRY, C(RY)2, N, NRY, O or S; wherein at least one W is a CRW or C(RW)2, or a Y is a CRY or C(RY)2; each RW is independently selected from H, a side-oxygen group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl; each RY is independently selected from H, a side-oxygen group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl; cyclic A is a C3-10 cycloalkyl or a 4-11 heterocyclic alkyl, wherein the C3-10 cycloalkyl and the 4-10 heterocyclic alkyl of cyclic A are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6 substituents as appropriate; The R2 series is selected from H, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa2, SRa2, NHORa 2. C(O)Rb2, C(O)NRc2Rd2, C(O)NRc2(ORa2), C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2NRc2 Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, C(=NRe2)Rb2, C(=NRe2)NRc2Rd2, NRc2C(=NRe2) NRc2Rd2, NRc2C(=NRe2)Rb2, NRc2S(O)Rb2, NRc2S(O)NRc2Rd2, NRc2S(O)2Rb2, NRc2S(O)(=NRe2)Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2, OS(O)(=NRe2)Rb2 and OS(O)2Rb2, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2A substituents, as appropriate;Each of Ra2, Rc2, and Rd2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra2, Rc2, and Rd2 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl-, C2-6 ynyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-. The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2A substituents, as appropriate; or, any Rc2 and Rd2 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R2A substituents, as appropriate; Each Rb2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl of Rb2 is... The following groups are substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2A substituents, depending on the situation: alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-6 alkyl, (5-10-membered heteroaryl)-C1-6 alkyl- and (4-10-membered heterocycloalkyl)-C1-6 alkyl-. Each Re2 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R2A group is selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa21, SRa21, NHORa21, C(O)Rb 21. C(O)NRc21Rd21, C(O)NRc21(ORa21), C(O)ORa21, OC(O)Rb21, OC(O)NRc21Rd21, NRc21Rd21, NRc21NRc21Rd2 1. NRc21C(O)Rb21, NRc21C(O)ORa21, NRc21C(O)NRc21Rd21, C(=NRe21)Rb21, C(=NRe21)NRc21Rd21, NRc21C(=NR e21)NRc21Rd21, NRc21C(=NRe21)Rb21, NRc21S(O)Rb21, NRc21S(O)NRc21Rd21, NRc21S(O)2Rb21, NRc21S(O)(= NRe21)Rb21, NRc21S(O)2NRc21Rd21, S(O)Rb21, S(O)NRc21Rd21, S(O)2Rb21, S(O)2NRc21Rd21, OS(O)(=NRe21)R b21 and OS(O)2Rb21, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2B substituents as appropriate;Each of Ra21, Rc21, and Rd21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra21 and Rc21 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2B substituents, as appropriate; or, any Rc21 and Rd21 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R2B substituents, as appropriate; Each Rb21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb21 is... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2B substituents as appropriate; Each Re21 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R2B is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa22, SRa22, NHORa22, C(O)R b22, C(O)NRc22Rd22, C(O)NRc22(ORa22), C(O)ORa22, OC(O)Rb22, OC(O)NRc22Rd22, NRc22Rd22, NRc22NRc22Rd 22. NRc22C(O)Rb22, NRc22C(O)ORa22, NRc22C(O)NRc22Rd22, C(=NRe22)Rb22, C(=NRe22)NRc22Rd22, NRc22C(=N Re22)NRc22Rd22, NRc22C(=NRe22)Rb22, NRc22S(O)Rb22, NRc22S(O)NRc22Rd22, NRc22S(O)2Rb22, NRc22S(O)( =NRe22)Rb22, NRc22S(O)2NRc22Rd22, S(O)Rb22, S(O)NRc22Rd22, S(O)2Rb22, S(O)2NRc22Rd22, OS(O)(=NRe22) Rb22 and OS(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2C substituents as appropriate;Each of Ra22, Rc22, and Rd22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra22 and Rc22 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2C substituents as appropriate; or, any Rc22 and Rd22 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3 or 4 independently selected R2C substituents as appropriate; Each Rb22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb22 is... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2C substituents, as appropriate; Each Re22 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R2C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa23, SRa23, NHORa23, C(O)Rb23, C( O)NRc23Rd23, C(O)NRc23(ORa23), C(O)ORa23, OC(O)Rb23, OC(O)NRc23Rd23, NRc23Rd23, NRc23NRc23Rd2 3. NRc23C(O)Rb23, NRc23C(O)ORa23, NRc23C(O)NRc23Rd23, C(=NRe23)Rb23, C(=NRe23)NRc23Rd23, NRc23 C(=NRe23)NRc23Rd23, NRc23C(=NRe23)Rb23, NRc23S(O)Rb23, NRc23S(O)NRc23Rd23, NRc23S(O)2Rb23, N Rc23S(O)(=NRe23)Rb23, NRc23S(O)2NRc23Rd23, S(O)Rb23, S(O)NRc23Rd23, S(O)2Rb23, S(O)2NRc23Rd23 OS(O)(=NRe23)Rb23 and OS(O)2Rb23, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected RM substituents as appropriate; Each of Ra23, Rc23, and Rd23 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra23 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents, as appropriate;Alternatively, any Rc23 and Rd23 attached to the same N atom, together with the N atom to which they are attached, form a 5-6-membered heteroaryl or a 4-7-membered heterocycloalkyl group, wherein the 5-6-membered heteroaryl or 4-7-membered heterocycloalkyl group is substituted by one, two, three, or four independently selected RM substituents, as appropriate; each Rb23 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb23 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents as appropriate; Each Re23 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-;The R3 group is selected from H, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa3, SRa3, NHORa 3. C(O)Rb3, C(O)NRc3Rd3, C(O)NRc3(ORa3), C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3NRc3 Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3) NRc3Rd3, NRc3C(=NRe3)Rb3, NRc3S(O)Rb3, NRc3S(O)NRc3Rd3, NRc3S(O)2Rb3, NRc3S(O)(=NRe3)Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3, OS(O)(=NRe3)Rb3 and OS(O)2Rb3, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3A substituents, as appropriate;Each Ra3, Rc3, and Rd3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra3, Rc3, and Rd3 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl-, C2-6 ynyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-. The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3A substituents, as appropriate; or, any Rc3 and Rd3 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R3A substituents, as appropriate; Each Rb3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl of Rb3 is... The following groups are substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3A substituents, depending on the circumstances: alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-6 alkyl, (5-10-membered heteroaryl)-C1-6 alkyl- and (4-10-membered heterocycloalkyl)-C1-6 alkyl-. Each Re3 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 member heteroaryl)-C1-6 alkyl- and (4-10 member heterocycloalkyl)-C1-6 alkyl-;Each R3A group is selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa31, SRa31, NHORa31, C(O)Rb 31. C(O)NRc31Rd31, C(O)NRc31(ORa31), C(O)ORa31, OC(O)Rb31, OC(O)NRc31Rd31, NRc31Rd31, NRc31NRc31Rd3 1. NRc31C(O)Rb31, NRc31C(O)ORa31, NRc31C(O)NRc31Rd31, C(=NRe31)Rb31, C(=NRe31)NRc31Rd31, NRc31C(=NR e31)NRc31Rd31, NRc31C(=NRe31)Rb31, NRc31S(O)Rb31, NRc31S(O)NRc31Rd31, NRc31S(O)2Rb31, NRc31S(O)(= NRe31)Rb31, NRc31S(O)2NRc31Rd31, S(O)Rb31, S(O)NRc31Rd31, S(O)2Rb31, S(O)2NRc31Rd31, OS(O)(=NRe31)R b31 and OS(O)2Rb31, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3B substituents as appropriate;Each of Ra31, Rc31, and Rd31 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra31 and Rc31 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3B substituents as appropriate; or, any Rc31 and Rd31 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3 or 4 independently selected R3B substituents as appropriate; Each Rb31 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb31... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3B substituents as appropriate; Each Re31 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R3B is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa32, SRa32, NHORa32, C(O)R b32, C(O)NRc32Rd32, C(O)NRc32(ORa32), C(O)ORa32, OC(O)Rb32, OC(O)NRc32Rd32, NRc32Rd32, NRc32NRc32Rd 32. NRc32C(O)Rb32, NRc32C(O)ORa32, NRc32C(O)NRc32Rd32, C(=NRe32)Rb32, C(=NRe32)NRc32Rd32, NRc32C(=N Re32)NRc32Rd32, NRc32C(=NRe32)Rb32, NRc32S(O)Rb32, NRc32S(O)NRc32Rd32, NRc32S(O)2Rb32, NRc32S(O)( =NRe32)Rb32, NRc32S(O)2NRc32Rd32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, S(O)2NRc32Rd32, OS(O)(=NRe32) Rb32 and OS(O)2Rb32, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3C substituents as appropriate;Each of Ra32, Rc32, and Rd32 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra32 and Rc32 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3C substituents as appropriate; or, any Rc32 and Rd32 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3 or 4 independently selected R3C substituents as appropriate; Each Rb32 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb32 is... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3C substituents, as appropriate; Each Re32 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R3C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa33, SRa33, NHORa33, C(O)Rb33, C( O)NRc33Rd33, C(O)NRc33(ORa33), C(O)ORa33, OC(O)Rb33, OC(O)NRc33Rd33, NRc33Rd33, NRc33NRc33Rd3 3. NRc33C(O)Rb33, NRc33C(O)ORa33, NRc33C(O)NRc33Rd33, C(=NRe33)Rb33, C(=NRe33)NRc33Rd33, NRc33 C(=NRe33)NRc33Rd33, NRc33C(=NRe33)Rb33, NRc33S(O)Rb33, NRc33S(O)NRc33Rd33, NRc33S(O)2Rb33, N Rc33S(O)(=NRe33)Rb33, NRc33S(O)2NRc33Rd33, S(O)Rb33, S(O)NRc33Rd33, S(O)2Rb33, S(O)2NRc33Rd33 OS(O)(=NRe33)Rb33 and OS(O)2Rb33, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected RM substituents as appropriate; Each of Ra33, Rc33, and Rd33 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra33 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents, as appropriate;Alternatively, any Rc33 and Rd33 attached to the same N atom, together with the N atom to which they are attached, form a 5-6-membered heteroaryl or a 4-7-membered heterocycloalkyl group, wherein the 5-6-membered heteroaryl or 4-7-membered heterocycloalkyl group is substituted by one, two, three, or four independently selected RM substituents, as appropriate; each Rb33 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb33 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents as appropriate; Each Re33 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-; R4 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, OH, NH2 and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN and NH2 as appropriate; R5 is selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, OH, CN, C(O)OH, C(O)NHRa5, NH2, and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN, and NH2 as appropriate; Ra5 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, OH, NH2, and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN, and NH2 as appropriate;Each R6 is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa6, SRa6, N HORa6, C(O)Rb6, C(O)NRc6Rd6, C(O)NRc6(ORa6), C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6N Rc6Rd6, NRc6C(O)Rb6, NRc6C(O)ORa6, NRc6C(O)NRc6Rd6, C(=NRe6)Rb6, C(=NRe6)NRc6Rd6, NRc6C(=NR e6)NRc6Rd6, NRc6C(=NRe6)Rb6, NRc6S(O)Rb6, NRc6S(O)NRc6Rd6, NRc6S(O)2Rb6, NRc6S(O)(=NRe6)Rb 6. NRc6S(O)2NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, S(O)2NRc6Rd6, OS(O)(=NRe6)Rb6 and OS(O)2Rb 6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6A substituents as appropriate;Each of Ra6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra6, Rc6, and Rd6 are selected from H, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, and 5-10 heteroaryl. , 4-10 member heterocyclic alkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 member heteroaryl)-C1-6 alkyl- and (4-10 member heterocyclic alkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6A substituents as appropriate, or any Rc6 and Rd6 connected to the same N atom together with the N atom to which they are connected to form a 5-10 member heteroaryl or a 4-10 member heterocyclic alkyl, wherein the 5-10 member heteroaryl or the 4-10 member heterocyclic alkyl is substituted with 1, 2, 3 or 4 independently selected R6A substituents as appropriate; Each Rb6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl of Rb6 is... The following groups are substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6A substituents, depending on the situation: alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-6 alkyl, (5-10-membered heteroaryl)-C1-6 alkyl- and (4-10-membered heterocycloalkyl)-C1-6 alkyl-. Each Re6 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R6A is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa61, SRa61, NHORa61, C(O)R b61, C(O)NRc61Rd61, C(O)NRc61(ORa61), C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61NRc61Rd 61. NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, C(=NRe61)Rb61, C(=NRe61)NRc61Rd61, NRc61C(=N Re61)NRc61Rd61, NRc61C(=NRe61)Rb61, NRc61S(O)Rb61, NRc61S(O)NRc61Rd61, NRc61S(O)2Rb61, NRc61S(O)( =NRe61)Rb61, NRc61S(O)2NRc61Rd61, S(O)Rb61, S(O)NRc61Rd61, S(O)2Rb61, S(O)2NRc61Rd61, OS(O)(=NRe61) Rb61 and OS(O)2Rb61, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6B substituents as appropriate;Each of Ra61, Rc61, and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra61 and Rc61 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R6B substituents, as appropriate; or, any Rc61 and Rd61 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R6B substituents, as appropriate; Each Rb61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb61 is... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6B substituents, as appropriate; Each Re61 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R6B is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 member heteroaryl, 4-7 member heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl-, (4-7 member heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa62, SRa62, NHORa62, C(O)Rb62, C( O)NRc62Rd62, C(O)NRc62(ORa62), C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62, NRc62NRc62Rd6 2. NRc62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, C(=NRe62)Rb62, C(=NRe62)NRc62Rd62, NRc62 C(=NRe62)NRc62Rd62, NRc62C(=NRe62)Rb62, NRc62S(O)Rb62, NRc62S(O)NRc62Rd62, NRc62S(O)2Rb62, N Rc62S(O)(=NRe62)Rb62, NRc62S(O)2NRc62Rd62, S(O)Rb62, S(O)NRc62Rd62, S(O)2Rb62, S(O)2NRc62Rd62 OS(O)(=NRe62)Rb62 and OS(O)2Rb62, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6C substituents as appropriate;Each of Ra62, Rc62, and Rd62 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra62, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with one, two, three, or four independently selected R6C substituents, as appropriate; or, any Rc62 and Rd62 attached to the same N atom together with the N atom to which they are attached form a 5-6 heteroaryl or a 4-7 heterocycloalkyl, wherein the 5-6 heteroaryl or 4-7 heterocycloalkyl is substituted with one, two, three, or four independently selected R6C substituents, as appropriate; Each Rb62 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb62 C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R6C substituents as appropriate; Each Re62 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-;Each R6C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa63, SRa63, NHORa63, C(O)Rb63, C( O)NRc63Rd63, C(O)NRc63(ORa63), C(O)ORa63, OC(O)Rb63, OC(O)NRc63Rd63, NRc63Rd63, NRc63NRc63Rd6 3. NRc63C(O)Rb63, NRc63C(O)ORa63, NRc63C(O)NRc63Rd63, C(=NRe63)Rb63, C(=NRe63)NRc63Rd63, NRc63 C(=NRe63)NRc63Rd63, NRc63C(=NRe63)Rb63, NRc63S(O)Rb63, NRc63S(O)NRc63Rd63, NRc63S(O)2Rb63, N Rc63S(O)(=NRe63)Rb63, NRc63S(O)2NRc63Rd63, S(O)Rb63, S(O)NRc63Rd63, S(O)2Rb63, S(O)2NRc63Rd63 OS(O)(=NRe63)Rb63 and OS(O)2Rb63, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected RM substituents as appropriate; Each of Ra63, Rc63, and Rd63 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra63 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents, as appropriate;Alternatively, any Rc63 and Rd63 attached to the same N atom, together with the N atom to which they are attached, form a 5-6-membered heteroaryl or a 4-7-membered heterocycloalkyl group, wherein the 5-6-membered heteroaryl or 4-7-membered heterocycloalkyl group is substituted by one, two, three, or four independently selected RM substituents, as appropriate; each Rb63 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb63 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents as appropriate; Each Re63 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-; Each RM is independently selected from H, OH, halogen, lateral oxy group, CN, C(O)OH, C(O)NH2, C(O)NH (C1-4 alkyl), C(O)N (C1-6 alkyl)2, NH2, NO2, SF5, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-.

[0012] In some embodiments: W-series CRW, C(RW)2, N, NRW, O, or S; Y-series CRY, C(RY)2, N, NRY, O, or S; wherein at least one W-series CRW or C(RW)2, or Y-series CRY or C(RY)2; each RW is independently selected from H, oxy-group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each RY is independently selected from H, oxy-group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; cycloA-series C3-10 cycloalkyl or 4-10 heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 heterocycloalkyl of cycloA are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R6 substituents as appropriate; The R2 series is selected from H, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa2, SRa2, NHORa 2. C(O)Rb2, C(O)NRc2Rd2, C(O)NRc2(ORa2), C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2NRc2 Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, C(=NRe2)Rb2, C(=NRe2)NRc2Rd2, NRc2C(=NRe2) NRc2Rd2, NRc2C(=NRe2)Rb2, NRc2S(O)Rb2, NRc2S(O)NRc2Rd2, NRc2S(O)2Rb2, NRc2S(O)(=NRe2)Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2, OS(O)(=NRe2)Rb2 and OS(O)2Rb2, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2A substituents, as appropriate;Each of Ra2, Rc2, and Rd2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra2, Rc2, and Rd2 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl-, C2-6 ynyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-. The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2A substituents, as appropriate; or, any Rc2 and Rd2 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R2A substituents, as appropriate; Each Rb2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl of Rb2 is... The following groups are substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2A substituents, depending on the situation: alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-6 alkyl, (5-10-membered heteroaryl)-C1-6 alkyl- and (4-10-membered heterocycloalkyl)-C1-6 alkyl-. Each Re2 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R2A group is selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa21, SRa21, NHORa21, C(O)Rb 21. C(O)NRc21Rd21, C(O)NRc21(ORa21), C(O)ORa21, OC(O)Rb21, OC(O)NRc21Rd21, NRc21Rd21, NRc21NRc21Rd2 1. NRc21C(O)Rb21, NRc21C(O)ORa21, NRc21C(O)NRc21Rd21, C(=NRe21)Rb21, C(=NRe21)NRc21Rd21, NRc21C(=NR e21)NRc21Rd21, NRc21C(=NRe21)Rb21, NRc21S(O)Rb21, NRc21S(O)NRc21Rd21, NRc21S(O)2Rb21, NRc21S(O)(= NRe21)Rb21, NRc21S(O)2NRc21Rd21, S(O)Rb21, S(O)NRc21Rd21, S(O)2Rb21, S(O)2NRc21Rd21, OS(O)(=NRe21)R b21 and OS(O)2Rb21, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2B substituents as appropriate;Each of Ra21, Rc21, and Rd21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra21 and Rc21 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2B substituents, as appropriate; or, any Rc21 and Rd21 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R2B substituents, as appropriate; Each Rb21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb21 is... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2B substituents as appropriate; Each Re21 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R2B is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa22, SRa22, NHORa22, C(O)R b22, C(O)NRc22Rd22, C(O)NRc22(ORa22), C(O)ORa22, OC(O)Rb22, OC(O)NRc22Rd22, NRc22Rd22, NRc22NRc22Rd 22. NRc22C(O)Rb22, NRc22C(O)ORa22, NRc22C(O)NRc22Rd22, C(=NRe22)Rb22, C(=NRe22)NRc22Rd22, NRc22C(=N Re22)NRc22Rd22, NRc22C(=NRe22)Rb22, NRc22S(O)Rb22, NRc22S(O)NRc22Rd22, NRc22S(O)2Rb22, NRc22S(O)( =NRe22)Rb22, NRc22S(O)2NRc22Rd22, S(O)Rb22, S(O)NRc22Rd22, S(O)2Rb22, S(O)2NRc22Rd22, OS(O)(=NRe22) Rb22 and OS(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2C substituents as appropriate;Each of Ra22, Rc22, and Rd22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra22 and Rc22 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2C substituents as appropriate; or, any Rc22 and Rd22 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3 or 4 independently selected R2C substituents as appropriate; Each Rb22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb22 is... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2C substituents, as appropriate; Each Re22 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R2C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa23, SRa23, NHORa23, C(O)Rb23, C( O)NRc23Rd23, C(O)NRc23(ORa23), C(O)ORa23, OC(O)Rb23, OC(O)NRc23Rd23, NRc23Rd23, NRc23NRc23Rd2 3. NRc23C(O)Rb23, NRc23C(O)ORa23, NRc23C(O)NRc23Rd23, C(=NRe23)Rb23, C(=NRe23)NRc23Rd23, NRc23 C(=NRe23)NRc23Rd23, NRc23C(=NRe23)Rb23, NRc23S(O)Rb23, NRc23S(O)NRc23Rd23, NRc23S(O)2Rb23, N Rc23S(O)(=NRe23)Rb23, NRc23S(O)2NRc23Rd23, S(O)Rb23, S(O)NRc23Rd23, S(O)2Rb23, S(O)2NRc23Rd23 OS(O)(=NRe23)Rb23 and OS(O)2Rb23, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected RM substituents as appropriate; Each of Ra23, Rc23, and Rd23 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra23 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents, as appropriate;Alternatively, any Rc23 and Rd23 attached to the same N atom, together with the N atom to which they are attached, form a 5-6-membered heteroaryl or a 4-7-membered heterocycloalkyl group, wherein the 5-6-membered heteroaryl or 4-7-membered heterocycloalkyl group is substituted by one, two, three, or four independently selected RM substituents, as appropriate; each Rb23 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb23 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents as appropriate; Each Re23 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-;The R3 group is selected from H, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa3, SRa3, NHORa 3. C(O)Rb3, C(O)NRc3Rd3, C(O)NRc3(ORa3), C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3NRc3 Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3) NRc3Rd3, NRc3C(=NRe3)Rb3, NRc3S(O)Rb3, NRc3S(O)NRc3Rd3, NRc3S(O)2Rb3, NRc3S(O)(=NRe3)Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3, OS(O)(=NRe3)Rb3 and OS(O)2Rb3, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3A substituents, as appropriate;Each Ra3, Rc3, and Rd3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra3, Rc3, and Rd3 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl-, C2-6 ynyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-. The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3A substituents, as appropriate; or, any Rc3 and Rd3 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R3A substituents, as appropriate; Each Rb3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl of Rb3 is... The following groups are substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3A substituents, depending on the circumstances: alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-6 alkyl, (5-10-membered heteroaryl)-C1-6 alkyl- and (4-10-membered heterocycloalkyl)-C1-6 alkyl-. Each Re3 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 member heteroaryl)-C1-6 alkyl- and (4-10 member heterocycloalkyl)-C1-6 alkyl-;Each R3A group is selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa31, SRa31, NHORa31, C(O)Rb 31. C(O)NRc31Rd31, C(O)NRc31(ORa31), C(O)ORa31, OC(O)Rb31, OC(O)NRc31Rd31, NRc31Rd31, NRc31NRc31Rd3 1. NRc31C(O)Rb31, NRc31C(O)ORa31, NRc31C(O)NRc31Rd31, C(=NRe31)Rb31, C(=NRe31)NRc31Rd31, NRc31C(=NR e31)NRc31Rd31, NRc31C(=NRe31)Rb31, NRc31S(O)Rb31, NRc31S(O)NRc31Rd31, NRc31S(O)2Rb31, NRc31S(O)(= NRe31)Rb31, NRc31S(O)2NRc31Rd31, S(O)Rb31, S(O)NRc31Rd31, S(O)2Rb31, S(O)2NRc31Rd31, OS(O)(=NRe31)R b31 and OS(O)2Rb31, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3B substituents as appropriate;Each of Ra31, Rc31, and Rd31 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra31 and Rc31 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3B substituents as appropriate; or, any Rc31 and Rd31 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3 or 4 independently selected R3B substituents as appropriate; Each Rb31 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb31... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3B substituents as appropriate; Each Re31 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R3B is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa32, SRa32, NHORa32, C(O)R b32, C(O)NRc32Rd32, C(O)NRc32(ORa32), C(O)ORa32, OC(O)Rb32, OC(O)NRc32Rd32, NRc32Rd32, NRc32NRc32Rd 32. NRc32C(O)Rb32, NRc32C(O)ORa32, NRc32C(O)NRc32Rd32, C(=NRe32)Rb32, C(=NRe32)NRc32Rd32, NRc32C(=N Re32)NRc32Rd32, NRc32C(=NRe32)Rb32, NRc32S(O)Rb32, NRc32S(O)NRc32Rd32, NRc32S(O)2Rb32, NRc32S(O)( =NRe32)Rb32, NRc32S(O)2NRc32Rd32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, S(O)2NRc32Rd32, OS(O)(=NRe32) Rb32 and OS(O)2Rb32, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3C substituents as appropriate;Each of Ra32, Rc32, and Rd32 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra32 and Rc32 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3C substituents as appropriate; or, any Rc32 and Rd32 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3 or 4 independently selected R3C substituents as appropriate; Each Rb32 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb32 is... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3C substituents, as appropriate; Each Re32 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R3C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa33, SRa33, NHORa33, C(O)Rb33, C( O)NRc33Rd33, C(O)NRc33(ORa33), C(O)ORa33, OC(O)Rb33, OC(O)NRc33Rd33, NRc33Rd33, NRc33NRc33Rd3 3. NRc33C(O)Rb33, NRc33C(O)ORa33, NRc33C(O)NRc33Rd33, C(=NRe33)Rb33, C(=NRe33)NRc33Rd33, NRc33 C(=NRe33)NRc33Rd33, NRc33C(=NRe33)Rb33, NRc33S(O)Rb33, NRc33S(O)NRc33Rd33, NRc33S(O)2Rb33, N Rc33S(O)(=NRe33)Rb33, NRc33S(O)2NRc33Rd33, S(O)Rb33, S(O)NRc33Rd33, S(O)2Rb33, S(O)2NRc33Rd33 OS(O)(=NRe33)Rb33 and OS(O)2Rb33, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected RM substituents as appropriate; Each of Ra33, Rc33, and Rd33 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra33 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents, as appropriate;Alternatively, any Rc33 and Rd33 attached to the same N atom, together with the N atom to which they are attached, form a 5-6-membered heteroaryl or a 4-7-membered heterocycloalkyl group, wherein the 5-6-membered heteroaryl or 4-7-membered heterocycloalkyl group is substituted by one, two, three, or four independently selected RM substituents, as appropriate; each Rb33 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb33 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents as appropriate; Each Re33 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-; R4 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, OH, NH2 and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN and NH2 as appropriate; R5 is selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, OH, CN, C(O)OH, C(O)NHRa5, NH2, and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN, and NH2 as appropriate; Ra5 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, OH, NH2, and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN, and NH2 as appropriate;Each R6 is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa6, SRa6, N HORa6, C(O)Rb6, C(O)NRc6Rd6, C(O)NRc6(ORa6), C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6N Rc6Rd6, NRc6C(O)Rb6, NRc6C(O)ORa6, NRc6C(O)NRc6Rd6, C(=NRe6)Rb6, C(=NRe6)NRc6Rd6, NRc6C(=NR e6)NRc6Rd6, NRc6C(=NRe6)Rb6, NRc6S(O)Rb6, NRc6S(O)NRc6Rd6, NRc6S(O)2Rb6, NRc6S(O)(=NRe6)Rb 6. NRc6S(O)2NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, S(O)2NRc6Rd6, OS(O)(=NRe6)Rb6 and OS(O)2Rb 6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6A substituents as appropriate;Each Ra6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra6, Rc6, and Rd6 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl-, C2-6 ynyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-. The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R6A substituents, as appropriate; or, any Rc6 and Rd6 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R6A substituents, as appropriate; Each Rb6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl of Rb6 is... The following groups are substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6A substituents, depending on the situation: alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-6 alkyl, (5-10-membered heteroaryl)-C1-6 alkyl- and (4-10-membered heterocycloalkyl)-C1-6 alkyl-. Each Re6 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R6A is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa61, SRa61, NHORa61, C(O)R b61, C(O)NRc61Rd61, C(O)NRc61(ORa61), C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61NRc61Rd 61. NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, C(=NRe61)Rb61, C(=NRe61)NRc61Rd61, NRc61C(=N Re61)NRc61Rd61, NRc61C(=NRe61)Rb61, NRc61S(O)Rb61, NRc61S(O)NRc61Rd61, NRc61S(O)2Rb61, NRc61S(O)( =NRe61)Rb61, NRc61S(O)2NRc61Rd61, S(O)Rb61, S(O)NRc61Rd61, S(O)2Rb61, S(O)2NRc61Rd61, OS(O)(=NRe61) Rb61 and OS(O)2Rb61, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6B substituents as appropriate;Each of Ra61, Rc61, and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra61 and Rc61 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R6B substituents, as appropriate; or, any Rc61 and Rd61 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R6B substituents, as appropriate; Each Rb61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb61 is... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6B substituents, as appropriate; Each Re61 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R6B is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 member heteroaryl, 4-7 member heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl-, (4-7 member heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa62, SRa62, NHORa62, C(O)Rb62, C( O)NRc62Rd62, C(O)NRc62(ORa62), C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62, NRc62NRc62Rd6 2. NRc62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, C(=NRe62)Rb62, C(=NRe62)NRc62Rd62, NRc62 C(=NRe62)NRc62Rd62, NRc62C(=NRe62)Rb62, NRc62S(O)Rb62, NRc62S(O)NRc62Rd62, NRc62S(O)2Rb62, N Rc62S(O)(=NRe62)Rb62, NRc62S(O)2NRc62Rd62, S(O)Rb62, S(O)NRc62Rd62, S(O)2Rb62, S(O)2NRc62Rd62 OS(O)(=NRe62)Rb62 and OS(O)2Rb62, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6C substituents as appropriate;Each of Ra62, Rc62, and Rd62 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra62, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with one, two, three, or four independently selected R6C substituents, as appropriate; or, any Rc62 and Rd62 attached to the same N atom together with the N atom to which they are attached form a 5-6 heteroaryl or a 4-7 heterocycloalkyl, wherein the 5-6 heteroaryl or 4-7 heterocycloalkyl is substituted with one, two, three, or four independently selected R6C substituents, as appropriate; Each Rb62 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb62 C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R6C substituents as appropriate; Each Re62 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-;Each R6C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa63, SRa63, NHORa63, C(O)Rb63, C( O)NRc63Rd63, C(O)NRc63(ORa63), C(O)ORa63, OC(O)Rb63, OC(O)NRc63Rd63, NRc63Rd63, NRc63NRc63Rd6 3. NRc63C(O)Rb63, NRc63C(O)ORa63, NRc63C(O)NRc63Rd63, C(=NRe63)Rb63, C(=NRe63)NRc63Rd63, NRc63 C(=NRe63)NRc63Rd63, NRc63C(=NRe63)Rb63, NRc63S(O)Rb63, NRc63S(O)NRc63Rd63, NRc63S(O)2Rb63, N Rc63S(O)(=NRe63)Rb63, NRc63S(O)2NRc63Rd63, S(O)Rb63, S(O)NRc63Rd63, S(O)2Rb63, S(O)2NRc63Rd63 OS(O)(=NRe63)Rb63 and OS(O)2Rb63, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected RM substituents as appropriate; Each of Ra63, Rc63, and Rd63 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra63 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents, as appropriate;Alternatively, any Rc63 and Rd63 attached to the same N atom, together with the N atom to which they are attached, form a 5-6-membered heteroaryl or a 4-7-membered heterocycloalkyl group, wherein the 5-6-membered heteroaryl or 4-7-membered heterocycloalkyl group is substituted by one, two, three, or four independently selected RM substituents, as appropriate; each Rb63 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb63 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents as appropriate; Each Re63 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-; Each RM is independently selected from H, OH, halogen, lateral oxy group, CN, C(O)OH, C(O)NH2, C(O)NH (C1-4 alkyl), C(O)N (C1-6 alkyl)2, NH2, NO2, SF5, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-.

[0013] In some embodiments: W-series CRW, C(RW)2, N, NRW, O, or S; Y-series CRY, C(RY)2, N, NRY, O, or S; wherein at least one W-series CRW or C(RW)2, or Y-series CRY or C(RY)2; each RW is independently selected from H, oxy-group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each RY is independently selected from H, oxy-group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; cycloA-series C3-10 cycloalkyl or 4-10 heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 heterocycloalkyl of cycloA are each substituted with 1, 2, 3, or 4 independently selected R6 substituents as appropriate; The R2 group is selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)NRc2(ORa2), C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2R d2, NRc2S(O)Rb2, NRc2S(O)NRc2Rd2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2 and OS(O)2Rb2, wherein R2 is a C1-6 alkyl, C2-6 alkenyl, or C2-6 alkyne. The alkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R2A substituents as appropriate;Each Ra2, Rc2, and Rd2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra2, Rc2, and Rd2 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl-, C2-6 alkenyl-, C6-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-. C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, or 4 independently selected R2A substituents as appropriate; or, any Rc2 and Rd2 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R2A substituents as appropriate; Each Rb2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C of Rb2 is... 1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R2A substituents as appropriate;Each R2A group is selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl. Base-, CN, NO2, ORa21, SRa21, C(O)Rb21, C(O)NRc21Rd21, C(O)NRc21(ORa21), C(O)ORa21, OC (O)Rb21, OC(O)NRc21Rd21, NRc21Rd21, NRc21C(O)Rb21, NRc21C(O)ORa21, NRc21C(O)NRc 21Rd21, NRc21S(O)Rb21, NRc21S(O)NRc21Rd21, NRc21S(O)2Rb21, NRc21S(O)2NRc21Rd21, S(O)Rb21, S(O)NRc21Rd21, S(O)2Rb21, S(O)2NRc21Rd21 and OS(O)2Rb21, wherein R2A is a C1-6 alkyl group, C 2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R2B substituents as appropriate; Each of Ra21, Rc21, and Rd21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 member heteroaryl)-C1-6 alkyl-, and (4-10 member heterocycloalkyl)-C1-6 alkyl-, wherein Ra21, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R2B substituents, as appropriate.Alternatively, any Rc21 and Rd21 attached to the same N atom, together with the N atom to which they are attached, form a 5-10-membered heteroaryl or a 4-10-membered heterocycloalkyl group, wherein the 5-10-membered heteroaryl or 4-10-membered heterocycloalkyl group is substituted by one, two, three, or four independently selected R2B substituents, as appropriate; each Rb21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10-membered heteroaryl)-C1-6 alkyl-, and (4-10-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb21 C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R2B substituents as appropriate;Each R2B is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1- 6Alkyl-, CN, NO2, ORa22, SRa22, C(O)Rb22, C(O)NRc22Rd22, C(O)NRc22(ORa22), C(O)ORa22, OC(O)Rb22, OC(O)NRc22Rd22, NRc22Rd22, NRc22C(O)Rb22, NRc22C(O)ORa22, NRc22C(O)NR c22Rd22, NRc22S(O)Rb22, NRc22S(O)NRc22Rd22, NRc22S(O)2Rb22, NRc22S(O)2NRc22Rd22, S(O)Rb22, S(O)NRc22Rd22, S(O)2Rb22, S(O)2NRc22Rd22 and OS(O)2Rb22, wherein the C1-6 alkyl group of R2B, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R2C substituents as appropriate; Each of Ra22, Rc22, and Rd22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 member heteroaryl)-C1-6 alkyl-, and (4-10 member heterocycloalkyl)-C1-6 alkyl-, wherein Ra22, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R2C substituents, depending on the situation.Alternatively, any Rc22 and Rd22 attached to the same N atom, together with the N atom to which they are attached, form a 5-10-membered heteroaryl or a 4-10-membered heterocycloalkyl group, wherein the 5-10-membered heteroaryl or 4-10-membered heterocycloalkyl group is substituted by one, two, three, or four independently selected R2C substituents, as appropriate; each Rb22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10-membered heteroaryl)-C1-6 alkyl-, and (4-10-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb22 C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R2C substituents, as appropriate; Each R2C is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 member heteroaryl, 4-7 member heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl-, (4-7 member heterocycloalkyl)-C1-6 alkyl-, CN, NO2. ORa23, SRa23, C(O)Rb23, C(O)NRc23Rd23, C(O)NRc23(ORa23), C(O)ORa23, OC(O)Rb23, OC(O)NRc23Rd23, NRc23Rd23, NRc23C(O)Rb23, NRc23C(O)ORa23, NRc23C(O)NRc23Rd23, NRc23S(O)Rb23, NRc23S(O)NRc23Rd23, NRc23S(O)2Rb23, NRc23S(O)2NRc23 Rd23, S(O)Rb23, S(O)NRc23Rd23, S(O)2Rb23, S(O)2NRc23Rd23 and OS(O)2Rb23; Each Ra23, Rc23, and Rd23 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-;Alternatively, any Rc23 and Rd23 attached to the same N atom, together with the N atom to which they are attached, form a 5-6-membered heteroaryl or a 4-7-membered heterocyclic alkyl group; each Rb23 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocyclic alkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocyclic alkyl)-C1-6 alkyl-; The R3 group is selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)NRc3(ORa3), C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3R d3, NRc3S(O)Rb3, NRc3S(O)NRc3Rd3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3 , S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3 and OS(O)2Rb3, where R3 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkyne The alkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3A substituents as appropriate;Each Ra3, Rc3, and Rd3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra3, Rc3, and Rd3 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-. C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, or 4 independently selected R3A substituents, as appropriate; or, any Rc3 and Rd3 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R3A substituents, as appropriate; Each Rb3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C of Rb3 is... 1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3A substituents as appropriate;Each R3A group is selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl. Base-, CN, NO2, ORa31, SRa31, C(O)Rb31, C(O)NRc31Rd31, C(O)NRc31(ORa31), C(O)ORa31, OC (O)Rb31, OC(O)NRc31Rd31, NRc31Rd31, NRc31C(O)Rb31, NRc31C(O)ORa31, NRc31C(O)NRc 31Rd31, NRc31S(O)Rb31, NRc31S(O)NRc31Rd31, NRc31S(O)2Rb31, NRc31S(O)2NRc31Rd31, S(O)Rb31, S(O)NRc31Rd31, S(O)2Rb31, S(O)2NRc31Rd31 and OS(O)2Rb31, wherein R3A is a C1-6 alkyl group, C 2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3B substituents as appropriate; Each of Ra31, Rc31, and Rd31 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 member heteroaryl)-C1-6 alkyl-, and (4-10 member heterocycloalkyl)-C1-6 alkyl-, wherein Ra31, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3B substituents, depending on the situation.Alternatively, any Rc31 and Rd31 attached to the same N atom, together with the N atom to which they are attached, form a 5-10-membered heteroaryl or a 4-10-membered heterocycloalkyl group, wherein the 5-10-membered heteroaryl or 4-10-membered heterocycloalkyl group is substituted by one, two, three, or four independently selected R3B substituents, as appropriate; each Rb31 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10-membered heteroaryl)-C1-6 alkyl-, and (4-10-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb31 C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3B substituents as appropriate;Each R3B is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1- 6Alkyl-, CN, NO2, ORa32, SRa32, C(O)Rb32, C(O)NRc32Rd32, C(O)NRc32(ORa32), C(O)ORa32, OC(O)Rb32, OC(O)NRc32Rd32, NRc32Rd32, NRc32C(O)Rb32, NRc32C(O)ORa32, NRc32C(O)NR c32Rd32, NRc32S(O)Rb32, NRc32S(O)NRc32Rd32, NRc32S(O)2Rb32, NRc32S(O)2NRc32Rd32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, S(O)2NRc32Rd32 and OS(O)2Rb32, wherein the C1-6 alkyl group of R3B, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3C substituents, as appropriate; Each of Ra32, Rc32, and Rd32 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 member heteroaryl)-C1-6 alkyl-, and (4-10 member heterocycloalkyl)-C1-6 alkyl-, wherein Ra32, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3C substituents, depending on the situation.Alternatively, any Rc32 and Rd32 attached to the same N atom, together with the N atom to which they are attached, form a 5-10-membered heteroaryl or a 4-10-membered heterocycloalkyl group, wherein the 5-10-membered heteroaryl or 4-10-membered heterocycloalkyl group is substituted by one, two, three, or four independently selected R3C substituents, as appropriate; each Rb32 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10-membered heteroaryl, 4-10-membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10-membered heteroaryl)-C1-6 alkyl-, and (4-10-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb32 C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3C substituents, depending on the case. Each R3C is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 member heteroaryl, 4-7 member heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl-, (4-7 member heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa33, SRa33, C(O)Rb33, C(O )NRc33Rd33, C(O)NRc33(ORa33), C(O)ORa33, OC(O)Rb33, OC(O)NRc33Rd33, NRc33Rd33, NRc33C(O)Rb 33. NRc33C(O)ORa33, NRc33C(O)NRc33Rd33, NRc33S(O)Rb33, NRc33S(O)NRc33Rd33, NRc33S(O)2Rb33, NRc33S(O)2NRc33Rd33, S(O)Rb33, S(O)NRc33Rd33, S(O)2Rb33, S(O)2NRc33Rd33 and OS(O)2Rb33; each Ra33, Rc33 and Rd33 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 member heteroaryl, 4-7 member heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl- and (4-7 member heterocycloalkyl)-C1-6 alkyl-;Alternatively, any Rc33 and Rd33 attached to the same N atom, together with the N atom to which they are attached, form a 5-6-membered heteroaryl or a 4-7-membered heterocyclic alkyl group; each Rb33 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocyclic alkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocyclic alkyl)-C1-6 alkyl-; R4 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, OH, NH2 and NHC1-6 alkyl, wherein the C1-6 alkyl group is substituted with OH, CN and NH2 as appropriate; R5 is selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, OH, CN, C(O)OH, C(O)NHRa5, NH2, and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN, and NH2 as appropriate; Ra5 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, OH, NH2, and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN, and NH2 as appropriate;Each R6 is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4 ... Heterocyclic alkyl)-C1-6 alkyl-, CN, NO2, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)NRc6(ORa6), C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)ORa6, NRc6C(O)N Rc6Rd6, NRc6S(O)Rb6, NRc6S(O)NRc6Rd6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, S(O)2NRc6Rd6 and OS(O)2Rb6, wherein R6 is a C1-6 alkyl, C2-6 alkenyl, C2- 6-alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R6A substituents as appropriate; Each Ra6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra6, Rc6, and Rd6 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-. C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, or 4 independently selected R6A substituents, as appropriate; or, any Rc6 and Rd6 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R6A substituents, as appropriate;Each Rb6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C of Rb6 is... 1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R6A substituents as appropriate; Each R6A is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1- 6-alkyl-, CN, NO2, ORa61, SRa61, C(O)Rb61, C(O)NRc61Rd61, C(O)NRc61(ORa61), C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NR c61Rd61, NRc61S(O)Rb61, NRc61S(O)NRc61Rd61, NRc61S(O)2Rb61, NRc61S(O)2NRc61Rd61, S(O)Rb61, S(O)NRc61Rd61, S(O)2Rb61, S(O)2NRc61Rd61 and OS(O)2Rb61, wherein the C1-6 alkyl group of R6A, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R6B substituents as appropriate;Each of Ra61, Rc61, and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 member heteroaryl)-C1-6 alkyl-, and (4-10 member heterocycloalkyl)-C1-6 alkyl-, wherein Ra61, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, or 4 independently selected R6B substituents, as appropriate; or, any Rc61 and Rd61 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R6B substituents, as appropriate; Each Rb61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Rb61 C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R6B substituents as appropriate;Each R6B is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa62, SRa62, C(O)Rb62, C(O)NRc62Rd62, C(O)NRc62(ORa62), C(O)ORa62, OC(O )Rb62, OC(O)NRc62Rd62, NRc62Rd62, NRc62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NR c62Rd62, NRc62S(O)Rb62, NRc62S(O)NRc62Rd62, NRc62S(O)2Rb62, NRc62S(O)2NRc6 2Rd62, S(O)Rb62, S(O)NRc62Rd62, S(O)2Rb62, S(O)2NRc62Rd62 and OS(O)2Rb62, among which R6B The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R6C substituents, as appropriate; Each of Ra62, Rc62, and Rd62 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra62, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with one, two, three, or four independently selected R6C substituents, as appropriate; or, any Rc62 and Rd62 attached to the same N atom together with the N atom to which they are attached form a 5-6 heteroaryl or a 4-7 heterocycloalkyl, wherein the 5-6 heteroaryl or 4-7 heterocycloalkyl is substituted with one, two, three, or four independently selected R6C substituents, as appropriate;Each Rb62 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb62 C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R6C substituents as appropriate; Each R6C is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 member heteroaryl, 4-7 member heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl-, (4-7 member heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa63, SRa63, C(O)Rb63, C(O)NRc63Rd63, C(O)NRc63(ORa63), C(O)ORa63, OC (O)Rb63, OC(O)NRc63Rd63, NRc63Rd63, NRc63C(O)Rb63, NRc63C(O)ORa63, NRc63C(O)NRc63Rd63, NRc63S(O)Rb63, NRc63S(O) NRc63Rd63, NRc63S(O)2Rb63, NRc63S(O)2NRc63Rd63, S(O)Rb63, S(O)NRc63Rd63, S(O)2Rb63, S(O)2NRc63Rd63 and OS(O)2Rb63; Each Ra63, Rc63, and Rd63 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-; or, any Rc63 and Rd63 attached to the same N atom together with the N atom to which they are attached form a 5-6-membered heteroaryl or a 4-7-membered heterocycloalkyl;Each Rb63 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-;

[0014] In some embodiments, W refers to C(RW)2, NRW, O, or S.

[0015] In some embodiments, W is C(RW)2 or NRW.

[0016] In some embodiments, W is C(RW)2.

[0017] In some embodiments, each RW is independently H or C1-6 alkyl.

[0018] In some embodiments, each RW is independently H or C1-6 alkyl, wherein one or more hydrogen atoms of the RW are replaced by deuterium atoms as appropriate.

[0019] In some embodiments, each RW is independently H or C1-3 alkyl.

[0020] In some embodiments, W is CH2.

[0021] In some embodiments, Y is C(RY)2, NRY, O or S.

[0022] In some embodiments, Y is C(RY)2 or NRY.

[0023] In some embodiments, Y is C(RY)2.

[0024] In some embodiments, each RY is independently H or C1-6 alkyl.

[0025] In some embodiments, each RY is independently H or C1-6 alkyl, wherein one or more hydrogen atoms of the RY are replaced by deuterium atoms as appropriate.

[0026] In some embodiments, each RY is independently H or C1-3 alkyl.

[0027] In some embodiments, Y is CH2.

[0028] In some embodiments: W is C(RW)2, NRW, O or S; and Y is C(RY)2, NRY, O or S.

[0029] In some embodiments: W is C(RW)2 or NRW; and Y is C(RY)2 or NRY.

[0030] In some embodiments: W is C(RW)2; and Y is C(RY)2.

[0031] In some embodiments: W-based C(RW)2; Y-based C(RY)2. Each RW is independently H or C1-6 alkyl; and each RY is independently H or C1-6 alkyl.

[0032] In some embodiments: W-based C(RW)2; Y-based C(RY)2. Each RW is independently H or C1-3 alkyl; and each RY is independently H or C1-3 alkyl.

[0033] In some embodiments, W and Y are each CH2.

[0034] In some embodiments, the cycloA-based C3-10 cycloalkyl group is substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6 substituents, as appropriate.

[0035] In some embodiments, the cycloalkenyl group is a C3-10 cycloalkyl group, which is substituted by one, two, three or four independently selected R6 substituents, as appropriate.

[0036] In some embodiments, the cycloalkenyl group is a C8-10 cycloalkyl group, which is substituted by one, two, three or four independently selected R6 substituents, as appropriate.

[0037] In some embodiments, the cycloA-type C3-7 cycloalkyl group is substituted with one, two, three or four independently selected R6 substituents, as appropriate.

[0038] In some embodiments, the cycloA-type C3-7 cycloalkyl group is substituted with one, two, three or four independently selected R6 substituents, depending on the situation.

[0039] In some embodiments, the cyclic A monocyclic C3-7 cycloalkyl group is substituted with one or two independently selected R6 substituents, depending on the case.

[0040] In some embodiments, the cycloA-based bicyclic C8-10 cycloalkyl group is substituted with one, two, three or four independently selected R6 substituents, depending on the situation.

[0041] In some embodiments, the cycloA-based bicyclic C8-10 cycloalkyl group is substituted with one or two independently selected R6 substituents, depending on the situation.

[0042] In some embodiments, the cycloA-system spirocyclic C7-10 cycloalkyl group is substituted with one, two, three or four independently selected R6 substituents, depending on the situation.

[0043] In some embodiments, the cycloA-system spirocyclic C7-10 cycloalkyl group is substituted with one or two independently selected R6 substituents, depending on the situation.

[0044] In some embodiments, cycloA is selected from cyclobutyl, cyclopentyl, cyclohexyl and dihydroindene, wherein the cyclobutyl, cyclopentyl, cyclohexyl and dihydroindene of cycloA are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0045] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl and 2,3-dihydro-1H-indenyl, wherein the cyclobutyl, cyclopentyl, cyclohexyl and 2,3-dihydro-1H-indenyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0046] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl and cyclohexyl, wherein the cyclobutyl, cyclopentyl and cyclohexyl of the ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0047] In some embodiments, cycloA is selected from cyclobutyl, cyclopentyl, cyclohexyl and dihydroindene, wherein the cyclobutyl, cyclopentyl, cyclohexyl and dihydroindene of cycloA are each substituted by one or two independently selected R6 substituents as appropriate.

[0048] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl and 2,3-dihydro-1H-indenyl, wherein the cyclobutyl, cyclopentyl, cyclohexyl and 2,3-dihydro-1H-indenyl of the ring A are each substituted by one or two independently selected R6 substituents as appropriate.

[0049] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl and cyclohexyl, wherein the cyclobutyl, cyclopentyl and cyclohexyl of the ring A are each substituted by one or two independently selected R6 substituents as appropriate.

[0050] In some embodiments, cycloA is an unsubstituted C3-10 cycloalkyl group.

[0051] In some embodiments, cycloA is an unsubstituted C8-10 cycloalkyl group.

[0052] In some embodiments, cycloA is an unsubstituted bicyclic C8-10 cycloalkyl group.

[0053] In some embodiments, the cycloA group is an unsubstituted C3-7 cycloalkyl group.

[0054] In some embodiments, cycloA is an unsubstituted monocyclic C3-7 cycloalkyl group.

[0055] In some embodiments, the cycloA system is selected from cyclobutyl, cyclopentyl, cyclohexyl and dihydroindenyl.

[0056] In some embodiments, the cycloA system is selected from cyclobutyl, cyclopentyl, cyclohexyl and 2,3-dihydro-1H-indenyl.

[0057] In some embodiments, the cycloA system is selected from cyclobutyl, cyclopentyl and cyclohexyl.

[0058] In some embodiments, the cycloA system consists of 4-11 heterocyclic alkyl groups, which may be substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6 substituents, as appropriate.

[0059] In some embodiments, the cycloA system consists of 4-10 heterocyclic alkyl groups, which are substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6 substituents, as appropriate.

[0060] In some embodiments, the cycloA system consists of 4-11 heterocyclic alkyl groups, which are substituted with 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0061] In some embodiments, the cycloA system consists of 4-10 heterocyclic alkyl groups, which are substituted with 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0062] In some embodiments, the ring A is a monocyclic 4-6-membered heterocyclic alkyl or a bicyclic 8-10-membered heterocyclic alkyl, wherein the monocyclic 4-6-membered heterocyclic alkyl and the bicyclic 8-10-membered heterocyclic alkyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0063] In some embodiments, the cyclic A group consists of a monocyclic 4-6-membered heterocyclic alkyl group, a bicyclic 8-10-membered heterocyclic alkyl group, or a spirocyclic 7-11-membered heterocyclic alkyl group, wherein the monocyclic 4-6-membered heterocyclic alkyl group, the bicyclic 8-10-membered heterocyclic alkyl group, and the spirocyclic 7-11-membered heterocyclic alkyl group are each substituted by one, two, three, or four independently selected R6 substituents as appropriate.

[0064] In some embodiments, the cyclic A group consists of a monocyclic 4-6-membered heterocyclic alkyl group, a bicyclic 8-10-membered heterocyclic alkyl group, or a spirocyclic 7-10-membered heterocyclic alkyl group, wherein the monocyclic 4-6-membered heterocyclic alkyl group, the bicyclic 8-10-membered heterocyclic alkyl group, and the spirocyclic 7-10-membered heterocyclic alkyl group are each substituted with 1, 2, 3, or 4 independently selected R6 substituents as appropriate.

[0065] In some embodiments, the ring A is selected from C3-10 cycloalkyl, monocyclic 4-6-membered heterocyclic alkyl and bicyclic 8-10-membered heterocyclic alkyl, wherein the C3-7 cycloalkyl, monocyclic 4-6-membered heterocyclic alkyl and bicyclic 8-10-membered heterocyclic alkyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0066] In some embodiments, the ring A is selected from C3-7 cycloalkyl, monocyclic 4-6-membered heterocyclic alkyl and bicyclic 8-10-membered heterocyclic alkyl, wherein the C3-7 cycloalkyl, monocyclic 4-6-membered heterocyclic alkyl and bicyclic 8-10-membered heterocyclic alkyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0067] In some embodiments, the ring A is selected from monocyclic C3-7 cycloalkyl, bicyclic C8-10 cycloalkyl, monocyclic 4-6-membered heterocyclic alkyl, bicyclic 8-10-membered heterocyclic alkyl and spirocyclic 7-11-membered heterocyclic alkyl, wherein the monocyclic C3-7 cycloalkyl, bicyclic C8-10 cycloalkyl, monocyclic 4-6-membered heterocyclic alkyl, bicyclic 8-10-membered heterocyclic alkyl and spirocyclic 7-11-membered heterocyclic alkyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0068] In some embodiments, the ring A is selected from monocyclic C3-7 cycloalkyl, bicyclic C8-10 cycloalkyl, monocyclic 4-6-membered heterocyclic alkyl, bicyclic 8-10-membered heterocyclic alkyl and spirocyclic 7-10-membered heterocyclic alkyl, wherein the monocyclic C3-7 cycloalkyl, bicyclic C8-10 cycloalkyl, monocyclic 4-6-membered heterocyclic alkyl, bicyclic 8-10-membered heterocyclic alkyl and spirocyclic 7-10-membered heterocyclic alkyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0069] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, dihydroindyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl, wherein the cyclobutyl, cyclopentyl, cyclohexyl, dihydroindyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl of the ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0070] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, dihydroindyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl, wherein the cyclobutyl, cyclopentyl, cyclohexyl, dihydroindyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl of the ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0071] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azacyclobutyl, piperidinyl, pyrrolidinyl, azacycloheptyl, dihydropyridinyl, azabicyclo[3.2.1]octyl, 2-azaspiro[3.3]heptyl and 7-azaspiro[3.5]nonyl, wherein the ring A is selected from cyclobutyl, cyclopentyl, cycloheptanyl, dihydropyridyl, azabicyclo[3.2.1]octyl, 2-azaspiro[3.3]heptyl and 7-azaspiro[3.5]nonyl. Butyl, cyclopentyl, cyclohexyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine heptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl are each substituted with 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0072] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azacyclobutyl, piperidinyl, pyrrolidinyl, azacycloheptyl, dihydropyridinyl, azabicyclo[3.2.1]octyl, 2-azaspiro[3.3]heptyl and 7-azaspiro[3.5]nonyl, wherein the ring A is selected from cyclobutyl, cyclopentyl, cycloheptanyl, dihydropyridyl, azabicyclo[3.2.1]octyl, 2-azaspiro[3.3]heptyl and 7-azaspiro[3.5]nonyl. Butyl, cyclopentyl, cyclohexyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine heptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl are each substituted with 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0073] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl, wherein the cyclobutyl, cyclopentyl, cyclohexyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0074] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, dihydroindyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl, wherein the cyclobutyl, cyclopentyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0075] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, dihydroindyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl, wherein the cyclobutyl, cyclopentyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0076] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azirspiro[3.3]heptyl and 7-azirspiro[3.5]nonyl, wherein the cyclobutyl, cyclopentyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azirspiro[3.3]heptyl and 7-azirspiro[3.5]nonyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0077] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine-heptyl, dihydropyridinyl, azirbis[3.2.1]octyl, 2-aziridine[3.3]heptyl and 7-aziridine[3.5]nonyl, wherein the cyclobutyl, cyclopentyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine-heptyl, dihydropyridinyl, azirbis[3.2.1]octyl, 2-aziridine[3.3]heptyl and 7-aziridine[3.5]nonyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0078] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl, wherein the tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0079] In some embodiments, the ring A is selected from tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine heptyl, dihydropyridinyl, azibicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl, wherein the tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine heptyl, dihydropyridinyl, azibicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0080] In some embodiments, the ring A is selected from tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine heptyl, dihydropyridinyl, azibicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl, wherein the tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine heptyl, dihydropyridinyl, azibicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0081] In some embodiments, the ring A is selected from tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl, wherein the tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl of ring A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate.

[0082] In some embodiments, the cycloA group is selected from cyclobutyl, cyclopentyl, cyclohexyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azacyclobutyl, piperidinyl, pyrrolidinyl, azacycloheptyl, dihydropyridinyl, azabicyclo[3.2.1]octyl, 2-azaspiro[3.3]heptyl and 7-azaspiro[3.5]nonyl, wherein the cycloA group is selected from cyclobutyl, cyclopentyl, cycloheptanyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azacyclobutyl, piperidinyl, pyrrolidinyl, azacycloheptyl, dihydropyridinyl, azabicyclo[3.2.1]octyl, 2-azaspiro[3.3]heptyl and 7-azaspiro[3.5]nonyl. Cyclobutyl, cyclopentyl, cyclohexyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl are each substituted with one or two independently selected R6 substituents as appropriate.

[0083] In some embodiments, the cycloA group is selected from cyclobutyl, cyclopentyl, cyclohexyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azacyclobutyl, piperidinyl, pyrrolidinyl, azacycloheptyl, dihydropyridinyl, azabicyclo[3.2.1]octyl, 2-azaspiro[3.3]heptyl and 7-azaspiro[3.5]nonyl, wherein the cycloA group is selected from cyclobutyl, cyclopentyl, cycloheptanyl, dihydropyridyl, azabicyclo[3.2.1]octyl, 2-azaspiro[3.3]heptyl and 7-azaspiro[3.5]nonyl. Cyclobutyl, cyclopentyl, cyclohexyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl are each substituted with one or two independently selected R6 substituents as appropriate.

[0084] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl, wherein the cyclobutyl, cyclopentyl, cyclohexyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl of ring A are each substituted by one or two independently selected R6 substituents as appropriate.

[0085] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl, wherein the tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl of ring A are each substituted by one or two independently selected R6 substituents as appropriate.

[0086] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, dihydroindyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine-heptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-aziridine[3.3]heptyl and 7-aziridine[3.5]nonyl, wherein the cyclobutyl, cyclopentyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine-heptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-aziridine[3.3]heptyl and 7-aziridine[3.5]nonyl of ring A are each substituted by one or two independently selected R6 substituents as appropriate.

[0087] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, dihydroindyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine-heptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-aziridine[3.3]heptyl and 7-aziridine[3.5]nonyl, wherein the cyclobutyl, cyclopentyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine-heptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-aziridine[3.3]heptyl and 7-aziridine[3.5]nonyl of ring A are each substituted by one or two independently selected R6 substituents as appropriate.

[0088] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine-heptyl, dihydropyridinyl, azirbis[3.2.1]octyl, 2-aziridine[3.3]heptyl and 7-aziridine[3.5]nonyl, wherein the cyclobutyl, cyclopentyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine-heptyl, dihydropyridinyl, azirbis[3.2.1]octyl, 2-aziridine[3.3]heptyl and 7-aziridine[3.5]nonyl of ring A are each substituted by one or two independently selected R6 substituents as appropriate.

[0089] In some embodiments, the ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl, 2,3-dihydro-1H-indenyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine-heptyl, dihydropyridinyl, azirbis[3.2.1]octyl, 2-aziridine[3.3]heptyl and 7-aziridine[3.5]nonyl, wherein the cyclobutyl, cyclopentyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine-heptyl, dihydropyridinyl, azirbis[3.2.1]octyl, 2-aziridine[3.3]heptyl and 7-aziridine[3.5]nonyl of ring A are each substituted by one or two independently selected R6 substituents as appropriate.

[0090] In some embodiments, the ring A is selected from tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl, wherein the tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl of ring A are each substituted by one or two independently selected R6 substituents as appropriate.

[0091] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc 6C(O)Rb6, NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

[0092] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc 6Rd6 and C(O)ORa6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

[0093] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, (4-7 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O) Rb6, NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

[0094] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, (4-6 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc 6Rd6 and C(O)ORa6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-6 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

[0095] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, (4-7 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C (O)Rb6, NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with one or two independently selected R6A substituents as appropriate.

[0096] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, (4-6 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)N Rc6Rd6 and C(O)ORa6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-6 heterocycloalkyl)-C1-6 alkyl- are each substituted by one or two independently selected R6A substituents as appropriate.

[0097] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C3-10 cycloalkyl-C1-6 alkyl-, C6-10 aryl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O) Rb6, NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C3-10 cycloalkyl-C1-6 alkyl-, C6-10 aryl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

[0098] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, (5-10 member heteroaryl)-C1-6 alkyl-, (4-10 member heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6 and C(O)ORa6, wherein the C1-6 alkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, (5-10 member heteroaryl)-C1-6 alkyl- and (4-10 member heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

[0099] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O)Rb6, NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl- Each can be substituted by one, two, three or four independently selected R6A substituents, depending on the situation.

[0100] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-6-membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6 and C(O)ORa6, wherein the C1-6 alkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

[0101] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C (O)Rb6, NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 5-6 member heteroaryl, 4-7 member heterocycloalkyl, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl- and (4-7 member heterocycloalkyl)-C1-6 alkyl- are each substituted by one or two independently selected R6A substituents as appropriate.

[0102] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-6-membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6 and C(O)ORa6, wherein the C1-6 alkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocycloalkyl)-C1-6 alkyl- are each substituted with one or two independently selected R6A substituents as appropriate.

[0103] In some embodiments, each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl and (4-10 member heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl and (4-10 member heterocycloalkyl)-C1-6 alkyl- of Ra6, Rb6, Rc6 and Rd6 are each substituted with 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

[0104] In some embodiments, each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 cycloalkyl, phenyl, (4-7 member heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 cycloalkyl, phenyl and (4-10 member heterocycloalkyl)-C1-6 alkyl- of Ra6, Rb6, Rc6 and Rd6 are each substituted with 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

[0105] In some embodiments, each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl groups of Ra6, Rb6, Rc6 and Rd6 are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

[0106] In some embodiments, each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl and (4-10 member heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl and (4-10 member heterocycloalkyl)-C1-6 alkyl- of Ra6, Rb6, Rc6 and Rd6 are each substituted with one or two independently selected R6A substituents as appropriate.

[0107] In some embodiments, each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 cycloalkyl, phenyl, (4-7 member heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 cycloalkyl, phenyl and (4-7 member heterocycloalkyl)-C1-6 alkyl- of Ra6, Rb6, Rc6 and Rd6 are each substituted with one or two independently selected R6A substituents as appropriate.

[0108] In some embodiments, each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl groups of Ra6, Rb6, Rc6 and Rd6 are each substituted by one or two independently selected R6A substituents as appropriate.

[0109] In some embodiments, each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C3-10 cycloalkyl, C6-10 aryl and 4-10 heterocyclic alkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C3-10 cycloalkyl, C6-10 aryl and 4-10 heterocyclic alkyl)-C1-6 alkyl- of Ra6, Rb6, Rc6 and Rd6 is substituted by one or two independently selected R6A substituents as appropriate.

[0110] In some embodiments, each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C3-7 cycloalkyl, phenyl and (4-7 member heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C3-7 cycloalkyl, phenyl and (4-10 member heterocycloalkyl)-C1-6 alkyl- of Ra6, Rb6, Rc6 and Rd6 are each substituted with one or two independently selected R6A substituents as appropriate.

[0111] In some embodiments, each Ra6, Rb6, Rc6 and Rd6 is independently selected from H or C1-6 alkyl groups, wherein the C1-6 alkyl groups of Ra6, Rb6, Rc6 and Rd6 are each substituted with one or two independently selected R6A substituents as appropriate.

[0112] In some embodiments, each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, cyclopropyl, cyclobutyl, phenyl and tetrahydropyranylmethyl, wherein the C1-6 alkyl, cyclopropyl, cyclobutyl, phenyl and tetrahydropyranylmethyl of Ra6, Rb6, Rc6 and Rd6 are each substituted by one or two independently selected R6A substituents as appropriate.

[0113] In some embodiments, each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, methyl, ethyl, propyl, cyclopropyl, cyclobutyl, phenyl and tetrahydropyranylmethyl, wherein the methyl, ethyl, propyl, cyclopropyl, cyclobutyl, phenyl and tetrahydropyranylmethyl groups of Ra6, Rb6, Rc6 and Rd6 are each substituted with one or two independently selected R6A substituents as appropriate.

[0114] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, C3-7 cycloalkyl-C1-6 alkyl-, phenyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O)Rb6, NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, C3- The 7-cycloalkyl-C1-6alkyl-, phenyl-C1-6alkyl-, (5-6-membered heteroaryl)-C1-6alkyl- and (4-7-membered heterocycloalkyl)-C1-6alkyl- are each substituted with one or two independently selected R6A substituents as appropriate; and each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6alkyl, C3-10cycloalkyl, C6-10 aryl and (4-10-membered heterocycloalkyl)-C1-6alkyl-, wherein the C1-6alkyl, C3-10cycloalkyl, C6-10 aryl and (4-10-membered heterocycloalkyl)-C1-6alkyl- of Ra6, Rb6, Rc6 and Rd6 are each substituted with one or two independently selected R6A substituents as appropriate.

[0115] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, C3-7 cycloalkyl-C1-6 alkyl-, phenyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O)Rb6, NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 5- The 6-membered heteroaryl, 4-7-membered heterocycloalkyl, C3-7 cycloalkyl-C1-6 alkyl-, phenyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl- are each substituted with one or two independently selected R6A substituents as appropriate; and each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, cyclopropyl, cyclobutyl, phenyl and tetrahydropyranylmethyl, wherein the C1-6 alkyl, cyclopropyl, cyclobutyl, phenyl and tetrahydropyranylmethyl of Ra6, Rb6, Rc6 and Rd6 are each substituted with one or two independently selected R6A substituents as appropriate.

[0116] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, C3-7 cycloalkyl-C1-6 alkyl-, phenyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O)Rb6, NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 5-6-membered... The heteroaryl, 4-7 member heterocycloalkyl, C3-7 cycloalkyl-C1-6 alkyl-, phenyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl- and (4-7 member heterocycloalkyl)-C1-6 alkyl- are each substituted with one or two independently selected R6A substituents as appropriate; and each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, methyl, ethyl, propyl, cyclopropyl, cyclobutyl, phenyl and tetrahydropyranylmethyl, wherein the methyl, ethyl, propyl, cyclopropyl, cyclobutyl, phenyl and tetrahydropyranylmethyl of Ra6, Rb6, Rc6 and Rd6 are each substituted with one or two independently selected R6A substituents as appropriate.

[0117] In some embodiments, each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, C3-7 cycloalkyl-C1-6 alkyl-, phenyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O)Rb6, NRc6S(O)2Rb6 and S (O)2Rb6, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, C3-7 cycloalkyl-C1-6 alkyl-, phenyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl- are each substituted with one or two independently selected R6A substituents as appropriate; and each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, methyl, ethyl, propyl, cyclopropyl, cyclobutyl, phenyl and tetrahydropyranylmethyl.

[0118] In some embodiments, each R6 is independently selected from C1-6 alkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl and C(O)Rb6, wherein the C1-6 alkyl, 5-10 member heteroaryl and 4-10 member heterocycloalkyl of R6 are each substituted with 1, 2, 3 or 4 independently selected R6A substituents as appropriate; and each Rb6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 ynyl of Rb6 are each substituted with 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

[0119] In some embodiments, each R6 is independently selected from C1-6 alkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl and C(O)Rb6, wherein the C1-6 alkyl, 5-6-membered heteroaryl and 4-6-membered heterocycloalkyl of R6 are each substituted with 1, 2, 3 or 4 independently selected R6A substituents as appropriate; and each Rb6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 ynyl of Rb6 are each substituted with 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

[0120] In some embodiments, each R6 is independently selected from C1-6 alkyl, 5-6-membered heteroaryl, 4-6-membered heterocyclic alkyl and C(O)Rb6, wherein the C1-6 alkyl, 5-6-membered heteroaryl and 4-6-membered heterocyclic alkyl of R6 are each substituted with one or two independently selected R6A substituents as appropriate; and each Rb6 is independently selected from H and C1-6 alkyl, wherein the C1-6 alkyl of Rb6 are each substituted with one or two independently selected R6A substituents as appropriate.

[0121] In some embodiments, each R6 is independently selected from C1-6 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolyl isopropyl, aziridine isopropyl, 2-azibicyclo[2.1.1]hexyl, bicyclo[1.1.1]pentyl, C(O)Rb6, NRc6C(O)Rb6, NRc6 S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolyl isopropyl, aziridine isopropyl, 2-azirbicyclo[2.1.1]hexyl and bicyclo[1.1.1]pentyl are each substituted by one or two independently selected R6A substituents as appropriate.

[0122] In some embodiments, each R6 is independently selected from ethyl, tributyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolyl isopropyl, aziridine isopropyl, 2-azibicyclo[2.1.1]hexyl, bicyclo[1.1.1]pentyl, methyl carbonyl, tetrahydropyranylmethyl carbonyl, propyl carbonyl, dimethylamino carbonyl, methoxy carbonyl, aniline carbonyl, ethyl sulfonyl, cyclobutylcarbonylamino, cyclopropyl sulfonyl and cyclopropyl sulfonylamino, wherein R 6. Ethyl, tributyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolylisopropyl, aziridineisopropyl, 2-azibicyclo[2.1.1]hexyl, bicyclo[1.1.1]pentyl, methylcarbonyl, tetrahydropyranylmethylcarbonyl, propylcarbonyl, dimethylaminocarbonyl, methoxycarbonyl, phenylaminocarbonyl, ethylsulfonylurea, cyclobutylcarbonylamino, cyclopropylsulfonylurea and cyclopropylsulfonylurea are each substituted with one or two independently selected R6A substituents as appropriate.

[0123] In some embodiments, each R6 is independently selected from ethyl, tributyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolyl isopropyl, aziridine isopropyl, 2-azibicyclo[2.1.1]hexyl, bicyclo[1.1.1]pentyl, methyl carbonyl, tetrahydropyranylmethyl carbonyl, propyl carbonyl, dimethylamino carbonyl, methoxy carbonyl, aniline carbonyl, ethyl Sulfoyl, cyclobutylcarbonylamino, cyclopropylsulfonyl and cyclopropylsulfonylamino, wherein the ethyl, tributyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, spiro[3.3]heptylmethyl, benzyl, triazolyl isopropyl, aziridine isopropyl, cyclobutylcarbonylamino, cyclopropylsulfonyl, 2-azirbicyclo[2.1.1]hexyl and bicyclo[1.1.1]pentyl are each substituted with one or two independently selected R6A substituents as appropriate.

[0124] In some embodiments, each R6 is independently selected from C1-6 alkyl, pyrazolyl, piperidinyl and C(O)Rb6, wherein the C1-6 alkyl, pyrazolyl and piperidinyl of R6 are each substituted with one or two independently selected R6A substituents as appropriate; and each Rb6 is independently selected from H or C1-6 alkyl, wherein the C1-6 alkyl of Rb6 is substituted with 5-6 heterocyclic alkyl groups as appropriate.

[0125] In some embodiments, each R6 is independently selected from C1-6 alkyl, pyrazolyl, piperidinyl and C(O)Rb6, wherein the C1-6 alkyl, pyrazolyl and piperidinyl of R6 are each substituted with one or two independently selected R6A substituents as appropriate; each Rb6 is independently selected from H or C1-6 alkyl, wherein the C1-6 alkyl of Rb6 is substituted with tetrahydropyranyl as appropriate.

[0126] In some embodiments, each R6A is independently selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, CN, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61 and OC(O)Rb61, wherein the C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl and 4-10 heterocycloalkyl of R6A are each substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate.

[0127] In some embodiments, each R6A is independently selected from phenyl, C3-7 cycloalkyl, 5-6 member heteroaryl, 4-6 member heterocycloalkyl, CN, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61 and OC(O)Rb61, wherein the phenyl, C3-7 cycloalkyl, 5-6 member heteroaryl and 4-6 member heterocycloalkyl of R6A are each substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate.

[0128] In some embodiments, each R6A is independently selected from phenyl, C3-7 cycloalkyl, 5-6 member heteroaryl, 4-6 member heterocycloalkyl, CN, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61 and OC(O)Rb61, wherein the phenyl, C3-7 cycloalkyl, 5-6 member heteroaryl and 4-6 member heterocycloalkyl of R6A are each substituted by one or two independently selected R6B substituents as appropriate.

[0129] In some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and C6-10 aryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and C6-10 aryl of Ra61, Rb61, Rc61 and Rd61 are each substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate.

[0130] In some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and C6-10 aryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and C6-10 aryl of Ra61, Rb61, Rc61 and Rd61 are each substituted by one or two independently selected R6B substituents as appropriate.

[0131] In some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and phenyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and phenyl of Ra61, Rb61, Rc61 and Rd61 are each substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate.

[0132] In some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and phenyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and phenyl of Ra61, Rb61, Rc61 and Rd61 are each substituted by one or two independently selected R6B substituents as appropriate.

[0133] In some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl and C6-10 aryl, wherein the C1-6 alkyl and C6-10 aryl groups of Ra61, Rb61, Rc61 and Rd61 are each substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate.

[0134] In some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl and C6-10 aryl, wherein the C1-6 alkyl and C6-10 aryl groups of Ra61, Rb61, Rc61 and Rd61 are each substituted with one or two independently selected R6B substituents as appropriate.

[0135] In some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl and phenyl, wherein the C1-6 alkyl and phenyl of Ra61, Rb61, Rc61 and Rd61 are each substituted with 1, 2, 3 or 4 independently selected R6B substituents as appropriate.

[0136] In some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl and phenyl, wherein the C1-6 alkyl and phenyl of Ra61, Rb61, Rc61 and Rd61 are each substituted with one or two independently selected R6B substituents as appropriate.

[0137] In some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl of Ra61, Rb61, Rc61 and Rd61 are each substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate.

[0138] In some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H and C1-6 alkyl groups, wherein the C1-6 alkyl groups of Ra61, Rb61, Rc61 and Rd61 are each substituted with 1, 2, 3 or 4 independently selected R6B substituents as appropriate.

[0139] In some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H and C1-6 alkyl groups, wherein the C1-6 alkyl groups of Ra61, Rb61, Rc61 and Rd61 are each substituted with one or two independently selected R6B substituents as appropriate.

[0140] In some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, methyl, ethyl and phenyl.

[0141] In some embodiments, each R6A is independently selected from halogen, side oxygen, C1-6 alkyl, 4-10 member heterocyclic alkyl, CN, ORa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61 and S(O)2Rb61, wherein each C1-6 alkyl and 4-10 member heterocyclic alkyl of R6A is substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate.

[0142] In some embodiments, each R6A is independently selected from halogen groups, side oxygen groups, C1-6 alkyl groups, 4-10 heterocyclic alkyl groups, CN, ORa61, C(O)Rb61, C(O)NRc61Rd61, C( R6A consists of R6A(O)Rb61, Rc61C(O)Rb61, Rc61C(O)Ra61, Rc61C(O)NRc61Rd61, Rc61S(O)2Rb61, and Rc61(O)2Rb61, wherein each of the C1-6 alkyl groups and the 4-10 heterocyclic alkyl groups of R6A are substituted with 1, 2, 3, or 4 independently selected R6B substituents as appropriate; and in some embodiments, each of R61, Rb61, Rc61, and Rd61 is independently selected from H, C1-6 alkyl groups, and C6-10 aryl groups, wherein each of the C1-6 alkyl groups and the C6-10 aryl groups of R61, Rb61, Rc61, and Rd61 is substituted with 1 or 2 independently selected R6B substituents as appropriate.

[0143] In some embodiments, each R6A is independently selected from halogen, oxy group, C1-6 alkyl, 4-10 heterocyclic alkyl, CN, ORa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61 and S(O)2Rb61. In some embodiments, each of the C1-6 alkyl groups and the 4-10 heterocyclic alkyl groups of R6A are substituted with 1, 2, 3 or 4 independently selected R6B substituents; and in some embodiments, each of Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl and C6-10 aryl, wherein the C1-6 alkyl and C6-10 aryl groups of Ra61, Rb61, Rc61 and Rd61 are each substituted with 1 or 2 independently selected R6B substituents.

[0144] In some embodiments, each R6A is independently selected from halogen groups, side oxygen groups, C1-6 alkyl groups, 4-10 heterocyclic alkyl groups, CN, ORa61, C(O)Rb61, C(O)NRc61Rd61, C( R6A comprises R6A(O)Rb61, R61C(O)Rb61, R61C(O)Ra61, R61C(O)NRc61Rd61, R61S(O)2Rb61 and S(O)2Rb61, wherein each C1-6 alkyl group and 4-10 heterocyclic alkyl group of R6A are substituted with 1, 2, 3 or 4 independently selected R6B substituents as appropriate; and in some embodiments, each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl and phenyl, wherein each C1-6 alkyl group and phenyl group of Ra61, Rb61, Rc61 and Rd61 are substituted with 1 or 2 independently selected R6B substituents as appropriate.

[0145] In some embodiments, each R6A is independently selected from halogen, side oxygen, C1-6 alkyl, 4-10 member heterocyclic alkyl, CN, ORa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61 and S(O)2Rb61, wherein each C1-6 alkyl and 4-10 member heterocyclic alkyl of R6A is substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate; and each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, methyl, ethyl and phenyl.

[0146] In some embodiments, each R6A is independently selected from 4-10 member heterocyclic alkyl, CN and C(O)Rb61, wherein the 4-10 member heterocyclic alkyl of R6A is substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate; and each Rb61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl of Rb61 is substituted by 1 or 2 independently selected R6B substituents as appropriate.

[0147] In some embodiments, each R6A is independently selected from 4-6 member heterocyclic alkyl, CN and C(O)Rb61, wherein the 4-6 member heterocyclic alkyl of R6A is substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate; and each Rb61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl of Rb61 is substituted by 1 or 2 independently selected R6B substituents as appropriate.

[0148] In some embodiments, each R6A is independently selected from 4-6 member heterocyclic alkyl groups, CN and C(O)Rb61, wherein the 4-6 member heterocyclic alkyl groups of R6A are each substituted with one or two independently selected R6B substituents as appropriate; and each Rb61 is independently selected from H and C1-6 alkyl groups, wherein the C1-6 alkyl groups of Rb61 are each substituted with one or two independently selected R6B substituents as appropriate.

[0149] In some embodiments, each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, CN and C(O)NRc62Rd62, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 ynyl groups of R6B are each substituted by 1, 2, 3 or 4 independently selected R6C substituents as appropriate.

[0150] In some embodiments, each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 ynyl of R6B are each substituted by 1, 2, 3 or 4 independently selected R6C substituents as appropriate.

[0151] In some embodiments, each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and CN and C(O)NRc62Rd62, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl of R6B are each substituted by one or two independently selected R6C substituents as appropriate; and each Rc62 and Rd62 is independently H or C1-6 alkyl.

[0152] In some embodiments, each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl and CN and C(O)NRc62Rd62, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 ynyl of R6B are each substituted by one or two independently selected R6C substituents as appropriate; and each Rc62 and Rd62 is independently H or C1-3 alkyl.

[0153] In some embodiments, each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 ynyl of R6B are each substituted by one or two independently selected R6C substituents as appropriate.

[0154] In some embodiments, each R6C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN and NO2.

[0155] In some embodiments, each R6C is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, CN and NO2.

[0156] In some embodiments, each R6C series CN.

[0157] In some embodiments, each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, CN and C(O)NRc62Rd62, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 ynyl are each substituted with CN as appropriate.

[0158] In some embodiments, each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 ynyl are each substituted with CN as appropriate.

[0159] In some embodiments, each R6B is independently selected from C1-6 alkyl, CN and C(O)NRc62Rd62, wherein the C1-6 alkyl of R6B is substituted with CN as appropriate, and each Rc62 and Rd62 is independently selected from H and C1-3 alkyl.

[0160] In some embodiments, each R6B is independently selected from C1-6 alkyl, CN and C(O)NH2, wherein the C1-6 alkyl of R6B is substituted with CN as appropriate.

[0161] In some embodiments, each R6B is independently selected from C1-6 alkyl groups, wherein the C1-6 alkyl groups of R6B are each substituted with CN as appropriate.

[0162] In some embodiments, each R6B is independently selected from methyl, CN and C(O)NH2, wherein each methyl group of R6B is substituted with CN as appropriate.

[0163] In some embodiments, each R6C series CN.

[0164] In some embodiments, each R6A is independently selected from fluorine, oxy, methyl, CN, methoxy, tetrahydropyranyl, methyl carbonyl, amino carbonyl, methyl carbonylamine, ethyl amino carbonyl, methoxy carbonyl, methoxy carbonylamine, ethyl amino carbonylamine, ethyl sulfonyl and benzene sulfonylamine, wherein each methyl group of R6A is substituted with CN or amino carbonyl as appropriate; and wherein each tetrahydropyranyl group of R6A is substituted with cyanomethyl as appropriate.

[0165] In some embodiments, each R6A is independently selected from fluorine, side-oxygen, methyl, CN, cyanomethyl, methoxy, tetrahydropyranyl, cyanomethyltetrahydropyranyl, methyl carbonyl, amino carbonyl, methyl carbonylamine, ethylamino carbonyl, methoxy carbonyl, methoxy carbonylamine, ethylamino carbonylamine, ethylsulfonylurea, and benzenesulfonylurea.

[0166] In some embodiments, each R6A is independently selected from cyano, tetrahydropyrano, cyanomethyltetrahydropyrano, and methylcarbonyl.

[0167] In some embodiments, R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein R2 is selected from H, C1-6 alkyl, C2-6 alkenyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-. C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with one, two, three or four independently selected R2A substituents, as appropriate.

[0168] In some embodiments, R2 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate.

[0169] In some embodiments, R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, phenyl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein each of the C1-6 alkyl, C2-6 alkenyl, phenyl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- is substituted with one or two independently selected R2A substituents as appropriate.

[0170] In some embodiments, R2 is selected from phenyl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the phenyl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- of R2 are each substituted with one or two independently selected R2A substituents as appropriate.

[0171] In some embodiments, R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, 5-10 heteroaryl and 4-10 heterocyclic alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, 5-10 heteroaryl and 4-10 heterocyclic alkyl of R2 are each substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate.

[0172] In some embodiments, R2 is selected from C6-10 aryl and 5-10 heteroaryl, wherein the C6-10 aryl and 5-10 heteroaryl of R2 are each substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate.

[0173] In some embodiments, R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, phenyl, C3-10 cycloalkyl, 5-10 heteroaryl and 4-10 heterocycloalkyl, wherein the phenyl, C3-10 cycloalkyl, 5-10 heteroaryl and 4-10 heterocycloalkyl of R2 are each substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate.

[0174] In some embodiments, R2 is selected from phenyl, C3-10 cycloalkyl, 5-10 heteroaryl and 4-10 heterocycloalkyl, wherein the phenyl, C3-10 cycloalkyl, 5-10 heteroaryl and 4-10 heterocycloalkyl of R2 are each substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate.

[0175] In some embodiments, R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, phenyl, 5-10 heteroaryl and 4-10 heterocyclic alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, phenyl, 5-10 heteroaryl and 4-10 heterocyclic alkyl of R2 are each substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate.

[0176] In some embodiments, R2 is selected from phenyl and 5-10 heteroaryl groups, wherein the phenyl and 5-10 heteroaryl groups of R2 are each substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate.

[0177] In some embodiments, R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, phenyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl and monocyclic 4-6-membered heterocyclic alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, phenyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl and monocyclic 4-6-membered heterocyclic alkyl of R2 are each substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate.

[0178] In some embodiments, R2 is selected from phenyl and 8-10 heteroaryl groups, wherein the phenyl and 5-10 heteroaryl groups of R2 are each substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate.

[0179] In some embodiments, R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, phenyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl and monocyclic 4-6-membered heterocyclic alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, phenyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl and monocyclic 4-6-membered heterocyclic alkyl of R2 are each replaced by one or two independently selected R2A substituents as appropriate.

[0180] In some embodiments, R2 is selected from phenyl and 8-10 heteroaryl groups, wherein the phenyl and 5-10 heteroaryl groups of R2 are each substituted by one or two independently selected R2A substituents as appropriate.

[0181] In some embodiments, R2 is selected from H, ethyl, vinyl, phenyl, indazole thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl and indole, wherein the ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl and indole of R2 are each substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate.

[0182] In some embodiments, R2 is selected from phenyl and indazole groups, wherein the phenyl and indazole groups of R2 are each substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate.

[0183] In some embodiments, R2 is selected from H, ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl and indole, wherein the ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl and indole of R2 are each substituted by one or two independently selected R2A substituents as appropriate.

[0184] In some embodiments, R2 is selected from phenyl and indazole groups, wherein the phenyl and indazole groups of R2 are each substituted by one or two independently selected R2A substituents as appropriate.

[0185] In some embodiments, each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN and ORa21, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl and (4-10 heterocycloalkyl)-C1-6 alkyl- of R2A are each substituted by 1, 2, 3 or 4 independently selected R2B substituents as appropriate.

[0186] In some embodiments, each R2A is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl of R2A are each substituted by 1, 2, 3, or 4 independently selected R2B substituents as appropriate.

[0187] In some embodiments, each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl, (4-6 heterocycloalkyl)-C1-6 alkyl-, CN and ORa21, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-6 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl and (4-6 heterocycloalkyl)-C1-6 alkyl- of R2A are each substituted by 1, 2, 3 or 4 independently selected R2B substituents as appropriate.

[0188] In some embodiments, each R2A is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, and 4-6 heterocyclic alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-6 cycloalkyl, 5-6 heteroaryl, and 4-6 heterocyclic alkyl of R2A are each substituted by 1, 2, 3, or 4 independently selected R2B substituents as appropriate.

[0189] In some embodiments, each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl, (4-6 heterocycloalkyl)-C1-6 alkyl-, CN and ORa21, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-6 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl and (4-6 heterocycloalkyl)-C1-6 alkyl- of R2A are each substituted by one or two independently selected R2B substituents as appropriate.

[0190] In some embodiments, each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, (4-6-membered heterocycloalkyl)-C1-6 alkyl-, CN and ORa21, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-6 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl and (4-6-membered heterocycloalkyl)-C1-6 alkyl- are each substituted with one or two independently selected R2B substituents as appropriate; and each Ra21 is independently selected from H, C1-6 alkyl and C1-6 haloalkyl.

[0191] In some embodiments, each R2A is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, and 4-6 heterocyclic alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-6 cycloalkyl, 5-6 heteroaryl, and 4-6 heterocyclic alkyl of R2A are each substituted by one or two independently selected R2B substituents as appropriate.

[0192] In some embodiments, each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 5-10 heteroaryl and (4-10 heterocycloalkyl)-C1-6 alkyl-, CN and ORa21, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 5-10 heteroaryl and (4-10 heterocycloalkyl)-C1-6 alkyl- of R2A are each substituted by 1, 2, 3 or 4 independently selected R2B substituents as appropriate.

[0193] In some embodiments, each R2A is independently selected from C1-6 alkyl and 5-10 heteroaryl groups, wherein the C1-6 alkyl and 5-10 heteroaryl groups of R2A are each substituted by 1, 2, 3 or 4 independently selected R2B substituents as appropriate.

[0194] In some embodiments, each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 5-10 heteroaryl, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN and ORa21, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 5-10 heteroaryl and (4-10 heterocycloalkyl)-C1-6 alkyl- of R2A are each substituted by one or two independently selected R2B substituents as appropriate.

[0195] In some embodiments, each R2A is independently selected from C1-6 alkyl and 5-10 heteroaryl groups, wherein the C1-6 alkyl and 5-10 heteroaryl groups of R2A are each substituted by one or two independently selected R2B substituents as appropriate.

[0196] In some embodiments, each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 5-6 member heteroaryl, (4-6 member heterocycloalkyl)-C1-6 alkyl-, CN and ORa21, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 5-6 member heteroaryl and (4-6 member heterocycloalkyl)-C1-6 alkyl- of R2A are each substituted by one or two independently selected R2B substituents as appropriate.

[0197] In some embodiments, each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 5-6 member heteroaryl, (4-6 member heterocycloalkyl)-C1-6 alkyl-, CN and ORa21, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, 5-6 member heteroaryl and (4-6 member heterocycloalkyl)-C1-6 alkyl- of R2A are each substituted by one or two independently selected R2B substituents as appropriate; and each Ra21 is independently selected from H, C1-6 alkyl and C1-6 haloalkyl.

[0198] In some embodiments, each R2A is independently selected from C1-6 alkyl and 5-6 heteroaryl groups, wherein the C1-6 alkyl and 5-6 heteroaryl groups of R2A are each substituted by one or two independently selected R2B substituents as appropriate.

[0199] In some embodiments, each R2A is independently selected from fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperidinemethyl, cyano, methoxy and trifluoromethoxy, wherein the methyl, cyclopropyl, pyrazolyl and piperidinemethyl are each substituted by one or two independently selected R2B substituents as appropriate.

[0200] In some embodiments, each R2A is independently selected from methyl and pyrazolyl groups, wherein the methyl and pyrazolyl groups are each substituted by one or two independently selected R2B substituents as appropriate.

[0201] In some embodiments, each R2B is independently selected from halogen, side oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, S(O)Rb22, and S(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl of R2B are each substituted by 1, 2, 3 or 4 independently selected R2C substituents as appropriate.

[0202] In some embodiments, each R2B is independently selected from halogen, side oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and S(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl of R2B are each substituted by 1, 2, 3 or 4 independently selected R2C substituents as appropriate.

[0203] In some embodiments, each Ra22, Rb22, Rc22 and Rd22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl.

[0204] In some embodiments, each R2B is independently selected from halogen, side oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and S(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl of R2B are each substituted by 1, 2, 3 or 4 independently selected R2C substituents as appropriate; and each Rb22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl.

[0205] In some embodiments, each R2B is independently selected from halogen, side oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and S(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl of R2B are each substituted by 1, 2, 3 or 4 independently selected R2C substituents as appropriate; and each Rb22 is independently selected from H or C1-6 alkyl.

[0206] In some embodiments, each R2B is independently selected from halogen, side oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl, wherein the C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl of R2B are each substituted by 1, 2, 3 or 4 independently selected R2C substituents as appropriate.

[0207] In some embodiments, each R2B is independently selected from C1-6 alkyl groups and S(O)2Rb22, wherein the C1-6 alkyl group of R2B is substituted by 1, 2, 3 or 4 independently selected R2C substituents as appropriate.

[0208] In some embodiments, each R2B is independently selected from C1-6 alkyl and S(O)2Rb22, wherein the C1-6 alkyl of R2B is substituted by 1, 2, 3 or 4 independently selected R2C substituents as appropriate; and each Rb22 is independently selected from H or C1-6 alkyl.

[0209] In some embodiments, each R2B is independently selected from C1-6 alkyl groups, wherein the C1-6 alkyl group of R2B is substituted by 1, 2, 3 or 4 independently selected R2C substituents as appropriate.

[0210] In some embodiments, each R2B is independently selected from C1-6 alkyl groups and S(O)2Rb22, wherein the C1-6 alkyl group of R2B is substituted by one or two independently selected R2C substituents as appropriate.

[0211] In some embodiments, each R2B is independently selected from C1-6 alkyl and S(O)2Rb22, wherein the C1-6 alkyl of R2B is substituted by one or two independently selected R2C substituents as appropriate; and each Rb22 is independently selected from H or C1-6 alkyl.

[0212] In some embodiments, each R2B is independently selected from C1-6 alkyl groups, wherein the C1-6 alkyl group of R2B is substituted by one or two independently selected R2C substituents as appropriate.

[0213] In some embodiments, each R2C is independently selected from halogen, side oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN and NO2.

[0214] In some embodiments, each R2C is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, CN and NO2.

[0215] In some embodiments, each R2C system is CN.

[0216] In some embodiments, each R2B is independently selected from cyanoisopropyl and S(O)2Rb22, wherein each Rb22 is independently selected from H or C1-6 alkyl.

[0217] In some embodiments, each R2B is independently selected from cyanomethyl and methanesulfonyl.

[0218] In some embodiments, each R2A is independently selected from fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperylmethyl, cyano, methoxy and trifluoromethoxy, wherein the methyl and pyrazolyl groups of R2A are respectively substituted with cyano-C1-6 alkyl groups as appropriate; and the piperylmethyl group of R2A is substituted with S(O)2Rb22 as appropriate; and each Rb22 is independently selected from H or C1-6 alkyl groups.

[0219] In some embodiments, each R2A is independently selected from fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperidinemethyl, cyano, methoxy and trifluoromethoxy, wherein the methyl and pyrazolyl groups of R2A are respectively substituted with cyano-C1-6 alkyl groups as appropriate; and the piperidinemethyl group of R2A is substituted with methanesulfonyl groups as appropriate.

[0220] In some embodiments, each R2A is independently selected from fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperidinemethyl, cyano, methoxy and trifluoromethoxy, wherein the pyrazolyl group of R2A is substituted with cyanoisopropyl as appropriate; and the piperidinemethyl group of R2A is substituted with methanesulfonyl as appropriate.

[0221] In some embodiments, each R2A is independently selected from methyl and pyrazolyl groups, wherein the methyl and pyrazolyl groups are respectively substituted with cyano-C1-6 alkyl groups as appropriate.

[0222] In some embodiments, R2 is selected from H, ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl and indolyl, wherein the phenyl and indazole groups of R2 are each substituted by one or two independent R2A substituents selected from: fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperylmethyl, cyano, methoxy and trifluoromethoxy, wherein the methyl and pyrazolyl groups of R2A are each substituted by cyano-C1-6 alkyl as appropriate; and the piperylmethyl group of R2A is substituted by methanesulfonyl as appropriate.

[0223] In some embodiments, R2 is selected from H, ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl and indolyl, wherein the phenyl and indazole groups of R2 are each substituted by one or two independent R2A substituents selected from: fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperylmethyl, cyano, methoxy and trifluoromethoxy, wherein the methyl and pyrazolyl groups of R2A are each substituted by cyano-C1-6 alkyl as appropriate; and the piperylmethyl group of R2A is substituted by methanesulfonyl as appropriate.

[0224] In some embodiments, R2 is selected from H, ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl and indole, wherein the phenyl and indazole groups of R2 are each substituted by one or two independent R2A substituents selected from: fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperidinemethyl, cyano, methoxy and trifluoromethoxy, wherein the pyrazolyl group of R2A is substituted by cyanoisopropyl; and the piperidinemethyl group of R2A is substituted by methanesulfonyl.

[0225] In some embodiments, R2 is selected from phenyl and indazole, wherein the phenyl and indazole groups of R2 are each substituted by one or two independent R2A substituents selected from: fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperidinemethyl, cyano, methoxy and trifluoromethoxy; wherein the pyrazolyl group of R2A is substituted by cyanoisopropyl; and wherein the piperidinemethyl group of R2A is substituted by methanesulfonyl.

[0226] In some embodiments, R2 is selected from phenyl and indazole, wherein the phenyl and indazole groups of R2 are each substituted by one or two independent R2A substituents selected from the following: fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperidinemethyl, cyano, methoxy and trifluoromethoxy; wherein the pyrazolyl group of R2A is substituted by cyanoisopropyl; and wherein the piperidinemethyl group of R2A is substituted by methanesulfonyl.

[0227] In some embodiments, R2 is selected from phenyl and indazole, wherein the phenyl and indazole groups of R2 are each substituted by one or two independent R2A substituents selected from methyl and pyrazolyl, and wherein the methyl and pyrazolyl groups of R2A are each substituted by cyano-C1-6 alkyl, depending on the situation.

[0228] In some embodiments, R2 is selected from methylindazole and trideuterium methylindazole.

[0229] In some embodiments, R3 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3A substituents as appropriate.

[0230] In some embodiments, R3 is selected from phenyl, C3-7 cycloalkyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl, monocyclic 4-6-membered heterocycloalkyl, bicyclic 8-10-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocycloalkyl)-C1-6 alkyl-, wherein the phenyl group of R3 is selected from... C3-7 cycloalkyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl, monocyclic 4-6-membered heterocyclic alkyl, bicyclic 8-10-membered heterocyclic alkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocyclic alkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3A substituents as appropriate.

[0231] In some embodiments, R3 is selected from phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocycloalkyl)-C1-6 alkyl-, wherein the phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3A substituents as appropriate.

[0232] In some embodiments, R3 is selected from phenyl, C3-7 cycloalkyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl, monocyclic 4-6-membered heterocycloalkyl, bicyclic 8-10-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocycloalkyl)-C1-6 alkyl-, wherein R3 The phenyl, C3-7 cycloalkyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl, monocyclic 4-6-membered heterocyclic alkyl, bicyclic 8-10-membered heterocyclic alkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocyclic alkyl)-C1-6 alkyl- are each substituted with one or two independently selected R3A substituents as appropriate.

[0233] In some embodiments, R3 is selected from phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocycloalkyl)-C1-6 alkyl-, wherein the phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocycloalkyl)-C1-6 alkyl- are each substituted with one or two independently selected R3A substituents as appropriate.

[0234] In some embodiments, R3 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl and 4-10 heterocycloalkyl, wherein the C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl and 4-10 heterocycloalkyl of R3 are each substituted by 1, 2, 3 or 4 independently selected R3A substituents as appropriate.

[0235] In some embodiments, R3 is selected from C6-10 aryl, C3-10 cycloalkyl and 5-10 heteroaryl, wherein the C6-10 aryl, C3-10 cycloalkyl and 5-10 heteroaryl of R3 are each substituted by 1, 2, 3 or 4 independently selected R3A substituents as appropriate.

[0236] In some embodiments, R3 is selected from phenyl, C3-7 cycloalkyl, monocyclic 5-6 member heteroaryl, bicyclic 8-10 member heteroaryl and bicyclic 8-10 member heterocyclic alkyl, wherein the phenyl, C3-7 cycloalkyl, monocyclic 5-6 member heteroaryl, bicyclic 8-10 member heteroaryl and bicyclic 8-10 member heterocyclic alkyl of R3 are each substituted by 1, 2, 3 or 4 independently selected R3A substituents as appropriate.

[0237] In some embodiments, R3 is selected from phenyl, C3-7 cycloalkyl and 5-6 heteroaryl, wherein the phenyl, C3-7 cycloalkyl and 5-6 heteroaryl of R3 are each substituted by 1, 2, 3 or 4 independently selected R3A substituents as appropriate.

[0238] In some embodiments, R3 is selected from phenyl, C3-7 cycloalkyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl and bicyclic 8-10-membered heterocyclic alkyl, wherein the phenyl, C3-7 cycloalkyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl and bicyclic 8-10-membered heterocyclic alkyl of R3 are each substituted by one or two independently selected R3A substituents as appropriate.

[0239] In some embodiments, R3 is selected from phenyl, C3-7 cycloalkyl and 5-6 heteroaryl, wherein the phenyl, C3-7 cycloalkyl and 5-6 heteroaryl of R3 are each substituted by one or two independently selected R3A substituents as appropriate.

[0240] In some embodiments, R3 is selected from phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl, wherein the benzene of R3 The pyrazolyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl are each substituted with one, two, three or four independently selected R3A substituents, depending on the situation.

[0241] In some embodiments, R3 is selected from phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl, wherein R3 The phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyridine, 3,4-dihydro-2H-benzo[b][1,4]pyridine, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl groups are each substituted with one or two independently selected R3A substituents, depending on the situation.

[0242] In some embodiments, R3 is selected from phenyl, cyclopropyl and pyrazolyl, wherein the phenyl, cyclopropyl and pyrazolyl groups of R3 are each substituted by 1, 2, 3 or 4 independently selected R3A substituents as appropriate.

[0243] In some embodiments, R3 is selected from phenyl, cyclopropyl and pyrazolyl, wherein the phenyl and pyrazolyl groups of R3 are each substituted by 1, 2, 3 or 4 independently selected R3A substituents as appropriate.

[0244] In some embodiments, R3 is selected from phenyl, cyclopropyl and pyrazolyl, wherein the phenyl and pyrazolyl groups of R3 are each substituted by one or two independently selected R3A substituents as appropriate.

[0245] In some embodiments, each R3A is independently selected from oxy-group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd 31, NRc31Rd31 and S(O)2Rb31, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate.

[0246] In some embodiments, each Ra31, Rb31, Rc31 and Rd31 is independently selected from H, C1-6 alkyl and 4-10 heterocyclic alkyl.

[0247] In some embodiments, each R3A is independently selected from oxy-group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd31, NRc31Rd31 and S(O)2Rb31. In R3A, the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate; and each Ra31, Rb31, Rc31 and Rd31 is independently selected from H, C1-6 alkyl and 4-10 heterocycloalkyl.

[0248] In some embodiments, each Ra31, Rb31, Rc31 and Rd31 is independently selected from H, C1-6 alkyl and 4-6 heterocyclic alkyl.

[0249] In some embodiments, each Ra31, Rb31, Rc31 and Rd31 is independently selected from H, C1-6 alkyl and 4-6 heterocyclic alkyl.

[0250] In some embodiments, each Ra31, Rb31, Rc31 and Rd31 is independently selected from H, C1-3 alkyl and 4-6 heterocyclic alkyl.

[0251] In some embodiments, each Ra31, Rb31, Rc31 and Rd31 is independently selected from H, methyl, ethyl and α-linyl.

[0252] In some embodiments, each R3A is independently selected from oxy-group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- In R3A, the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by one, two, three or four independently selected R3B substituents, depending on the situation.

[0253] In some embodiments, each R3A is independently selected from oxy-, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, (4-6 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd 31, NRc31Rd31 and S(O)2Rb31, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-6 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate.

[0254] In some embodiments, each R3A is independently selected from oxy-, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-6-membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd31, NRc31Rd31 and S(O)2Rb31, wherein R3 A's C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3B substituents as appropriate; and in some embodiments, each Ra31, Rb31, Rc31 and Rd31 is independently selected from H, C1-6 alkyl and 4-10-membered heterocycloalkyl.

[0255] In some embodiments, each R3A is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-6-membered heterocycloalkyl)-C1-6 alkyl-. The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-6 heterocycloalkyl)-C1-6 alkyl- are each substituted by one, two, three or four independently selected R3B substituents, depending on the situation.

[0256] In some embodiments, each R3A is independently selected from oxy-, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, (4-6 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31 Rd31, NRc31Rd31 and S(O)2Rb31, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-6 heterocycloalkyl)-C1-6 alkyl- are each substituted by one or two independently selected R3B substituents as appropriate.

[0257] In some embodiments, each R3A is independently selected from oxy-group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-6-membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd31, NRc31Rd31 and S(O)2 Rb31, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocycloalkyl)-C1-6 alkyl- are each substituted by one or two independently selected R3B substituents as appropriate; and each Rb31, Rc31 and Rd31 is independently selected from H, C1-6 alkyl and 4-10-membered heterocycloalkyl.

[0258] In some embodiments, each R3A is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocycloalkyl)-C1-6 alkyl- In R3A, the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-6 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-6 heterocycloalkyl)-C1-6 alkyl- are each substituted by one or two independently selected R3B substituents, as appropriate.

[0259] In some embodiments, each R3A is independently selected from oxy-group, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd 31, NRc31Rd31 and S(O)2Rb31, wherein the C1-6 alkyl, C3-10 cycloalkyl, 4-10 heterocyclic alkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocyclic alkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate.

[0260] In some embodiments, each R3A is independently selected from C1-6 alkyl, (5-10-membered heteroaryl)-C1-6 alkyl- and (4-10-membered heterocyclic alkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, (5-10-membered heteroaryl)-C1-6 alkyl- and (4-10-membered heterocyclic alkyl)-C1-6 alkyl- of R3A are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate.

[0261] In some embodiments, each R3A is independently selected from oxy-group, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-6 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-6 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, (4-6 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd 31, NRc31Rd31 and S(O)2Rb31, wherein the C1-6 alkyl, C3-7 cycloalkyl, 4-6 heterocyclic alkyl, phenyl-C1-6 alkyl-, C3-6 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-6 heterocyclic alkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate.

[0262] In some embodiments, each R3A is independently selected from C1-6 alkyl, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocyclic alkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocyclic alkyl)-C1-6 alkyl- of R3A are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate.

[0263] In some embodiments, each R3A is independently selected from oxy-, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-6 member heterocycloalkyl, phenyl-C1-6 alkyl-, C3-6 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl-, (4-6 member heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd31, NRc31Rd31 and S(O)2Rb31, wherein the C1-6 alkyl, C3-7 cycloalkyl, 4-6 member heterocycloalkyl, phenyl-C1-6 alkyl-, C3-6 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl- and (4-6 member heterocycloalkyl)-C1-6 alkyl- are each substituted with one or two independently selected R3B substituents as appropriate.

[0264] In some embodiments, each R3A is independently selected from C1-6 alkyl, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocyclic alkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocyclic alkyl)-C1-6 alkyl- of R3A are each substituted by one or two independently selected R3B substituents as appropriate.

[0265] In some embodiments, each R3B is independently selected from halogen, side oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, ORa32, C(O)Rb32, C(O)NRc32Rd32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, S(O)2NRc32Rd32, wherein each Ra32, Rb32, Rc32 and Rd32 is independently selected from H and C1-6 alkyl.

[0266] In some embodiments, each R3B is independently selected from halogen, side oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)Rb32, C(O)NRc32Rd32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, S(O)2NRc32Rd32, wherein each Rb32, Rc32 and Rd32 is independently selected from H and C1-6 alkyl.

[0267] In some embodiments, each R3B is independently selected from CN, ORa32, C(O)Rb32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32 and S(O)2NRc32Rd32, wherein each Ra32, Rb32, Rc32 and Rd32 is independently selected from H and C1-6 alkyl groups.

[0268] In some embodiments, each R3B is independently selected from S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32 and S(O)2NRc32Rd32, wherein each Rb32, Rc32 and Rd32 is independently selected from H and C1-6 alkyl groups.

[0269] In some embodiments, each R3B is independently selected from CN, ORa32, C(O)Rb32 and S(O)2Rb32, wherein each Ra32 and Rb32 is independently selected from H and C1-6 alkyl groups.

[0270] In some embodiments, each R3B is independently selected from S(O)2Rb32, wherein each Rb32 is independently selected from H and C1-6 alkyl groups.

[0271] In some embodiments, each R3B is independently selected from hydroxyl, methoxy, methanesulfonyl, methyl carbonyl and cyano.

[0272] In some embodiments, each R3B is independently selected from methylsulfonyl.

[0273] In some embodiments, each R3A is independently selected from methyl, trideuterylmethyl (i.e., -CD3), ethyl, isopropyl, isobutyl, difluoroethyl, trifluoroethyl, methoxy, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidinylmethyl, succinylmethyl, succinylethyl, succinylcarbonyl, dimethylaminocarbonyl, and ethylsulfonylutriyl, wherein the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridinylmethyl, piperidinylmethyl, succinylmethyl, and succinylethyl of R3A are each substituted with 1, 2, 3, or 4 independently selected R3B substituents as appropriate.

[0274] In some embodiments, each R3A is independently selected from methyl, trideuterylmethyl (i.e., -CD3), ethyl, isopropyl, isobutyl, difluoroethyl, trifluoroethyl, methoxy, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidinylmethyl, succinylmethyl, succinylethyl, succinylcarbonyl, dimethylaminocarbonyl, and ethylsulfonylutriyl, wherein the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidinylmethyl, succinylmethyl, and succinylethyl of R3A are each substituted with one or two independently selected R3B substituents as appropriate.

[0275] In some embodiments, each R3A is independently selected from methyl, trideuterylmethyl (i.e., -CD3), ethyl, isopropyl, isobutyl, difluoroethyl, trifluoroethyl, methoxy, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, sulfolinylmethyl, sulfolinylethyl, sulfolinylcarbonyl, dimethylaminocarbonyl and ethylsulfonyl, wherein the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, α-linylmethyl and α-linylethyl are each, as appropriate, substituted by 1, 2, 3 or 4 independently selected from the following R3B substituents: hydroxyl, methoxy, methylsulfonyl, methylcarbonyl and cyano.

[0276] In some embodiments, each R3A is independently selected from methyl, trideuterylmethyl (i.e., -CD3), ethyl, isopropyl, isobutyl, difluoroethyl, trifluoroethyl, methoxy, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, sulfolinylmethyl, sulfolinylethyl, sulfolinylcarbonyl, dimethyl The aminocarbonyl and ethylsulfonyl groups, wherein the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, α-linylmethyl and α-linylethyl groups of R3A are each substituted, as appropriate, by one or two independent substituents selected from the following: hydroxyl, methoxy, methylsulfonyl, methylcarbonyl and cyano.

[0277] In some embodiments, each R3A is independently selected from methyl, trideuterylmethyl (i.e., -CD3), methylpyridyl, methylpiperidyl, pyridylmethyl and piperidylmethyl, wherein the methylpyridyl, methylpiperidyl, pyridylmethyl and piperidylmethyl of R3A are each substituted with methanesulfonyl as appropriate.

[0278] In some embodiments, each R3A is independently selected from methyl, trideuterylmethyl (i.e., -CD3), pyridylmethyl and piperidylmethyl, wherein the pyridylmethyl and piperidylmethyl of R3A are respectively substituted with methanesulfonyl as appropriate.

[0279] In some embodiments, each R3A is independently selected from methyl, trideuteryl (i.e., -CD3), methylpyridinyl and methylpiperidinyl, wherein the methylpyridinyl and methylpiperidinyl of R3A are respectively substituted with methanesulfonyl as appropriate.

[0280] In some embodiments, each R3A is independently selected from methyl, trideuteryl (i.e., -CD3), methylpyridinyl and methylpiperidinyl, wherein the methylpiperidinyl group of R3A is substituted with methanesulfonyl as appropriate.

[0281] In some embodiments, each R3A is independently selected from methyl, trideuterylmethyl (i.e., -CD3), ethyl, isopropyl, isobutyl, difluoroethyl, trifluoroethyl, methoxy, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, sulfolinylmethyl, sulfolinylethyl, sulfolinylcarbonyl, dimethyl The aminocarbonyl and ethylsulfonyl groups, wherein the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, α-linylmethyl and α-linylethyl groups of R3A are each substituted, as appropriate, by one or two independent substituents selected from the following: hydroxyl, methoxy, methylsulfonyl, methylcarbonyl and cyano.

[0282] In some embodiments, each R3A is independently selected from methyl, trideuterylmethyl (i.e., -CD3), isopropyl, difluoroethyl, trifluoroethyl, methoxyethyl, hydroxymethylpropyl, hydroxyisobutyl, methoxyisobutyl, methoxy, cyclopropyl, cyclopentyl, (cyanophenyl)methyl, pyridylmethyl, piperidylmethyl, succinylmethyl, succinylethyl, cyclopropylmethyl, cyclopropylethyl, tetrahydrofuranyl, tetrahydropyranyl, methylcarbonylpiperidinyl, succinylcarbonyl, dimethylaminocarbonyl, and ethylsulfonyl, wherein the pyridylmethyl and piperidylmethyl of R3A are each substituted with methylsulfonyl as appropriate.

[0283] In some embodiments, R3 is selected from phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl, and pyrazolo[1, [5-a]pyrimidinyl, wherein R3 is phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl Each of the radicals may be substituted by one, two, three, or four independently selected R3A substituents, depending on the situation; and each R3A is independently selected from methyl, trideuteryl (i.e., -CD3), ethyl, isopropyl, isobutyl, difluoroethyl, trifluoroethyl, methoxy, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, α-linylmethyl, α-linylethyl, α- The R3A is composed of linyl carbonyl, dimethylamino carbonyl, and ethyl sulfonyl, wherein the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, α-linylmethyl, and α-linylethyl groups are each, as appropriate, substituted by one or two independent substituents selected from the following: hydroxyl, methoxy, methylsulfonyl, methyl carbonyl, and cyano.

[0284] In some embodiments, R3 is selected from phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl and pyrazolo[1,2-b]pyrazolyl. [,5-a]pyrimidinyl, wherein R3 is phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrazolyl. Each pyrimidinyl group is substituted with one or two independently selected R3A substituents, and each R3A is independently selected from methyl, trideuteryl (i.e., -CD3), ethyl, isopropyl, isobutyl, difluoroethyl, trifluoroethyl, methoxy, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, succinylmethyl, succinylethyl, succinyl R3A is composed of methyl carbonyl, dimethylamino carbonyl, and ethyl sulfonyl, wherein the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, α-linylmethyl, and α-linylethyl groups are each substituted by one or two independent substituents selected from the following: hydroxyl, methoxy, methylsulfonyl, methyl carbonyl, and cyano.

[0285] In some embodiments, R3 is selected from phenyl, cyclopropyl and pyrazolyl, wherein the phenyl, cyclopropyl and pyrazolyl groups of R3 are each substituted with one or two R3A substituents selected from methyl, trideuteryl, methylpyridinyl and methylpiperidinyl, and wherein the methylpyridinyl and methylpiperidinyl groups of R3A are each substituted with methanesulfonyl, as appropriate.

[0286] In some embodiments, R4 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, OH, NH2 and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN and NH2 as appropriate; and wherein each hydrogen atom of R4 (e.g., each hydrogen atom of the H of R4 or the C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, OH, NH2 and NHC1-6 alkyl) is substituted with a deuterium atom as appropriate.

[0287] In some embodiments, R4 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl and C1-6 haloalkoxy.

[0288] In some embodiments, R4 is selected from H and C1-6 alkyl groups.

[0289] In some embodiments, R4 is H.

[0290] In some embodiments, R4 is a C1-6 alkyl group.

[0291] In some embodiments, R4 is a C1-3 alkyl group.

[0292] In some embodiments, R4 is a methyl group or CD3.

[0293] In some embodiments, R4 is a methyl group.

[0294] In some embodiments, R4 is CD3.

[0295] In some embodiments, R5 is selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, OH, CN, C(O)OH, C(O)NHRa5, NH2 and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN and NH2 as appropriate; The Ra5 group consists of H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, OH, NH2, and NHC1-6 alkyl, wherein the C1-6 alkyl group is substituted with OH, CN, or NH2 as appropriate; and each hydrogen atom of R5 and Ra5 (e.g., each hydrogen atom of the H in R5 or the C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, OH, C(O)OH, C(O)NHRa5NH2, and NHC1-6 alkyl group) is substituted with a deuterium atom as appropriate.

[0296] In some embodiments, R5 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl and C2-6 alkynyl.

[0297] In some embodiments, R5 is selected from H and C1-6 alkyl groups.

[0298] In some embodiments, R5 is selected from H and C1-3 alkyl groups.

[0299] In some embodiments, R5 is H.

[0300] In some embodiments: R4 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl and C1-6 haloalkoxy; and R5 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl and C2-6 alkynyl.

[0301] In some embodiments: R4 is selected from H and C1-6 alkyl; and R5 is selected from H and C1-6 alkyl.

[0302] In some embodiments: R4 is selected from H and C1-3 alkyl; and R5 is selected from H and C1-3 alkyl.

[0303] In some embodiments, R4 is a C1-6 alkyl group and R5 is an H group.

[0304] In some embodiments, R4 is a C1-3 alkyl group and R5 is an H group.

[0305] In some embodiments, R4 is a methyl group or CD3; and R5 is an H group.

[0306] In some embodiments, R4 is a methyl group and R5 is an H group.

[0307] In some embodiments, R4 is CD3 alkyl and R5 is H.

[0308] In some embodiments, each RM is independently selected from H, OH, halogen, oxy group, CN, C(O)OH, C(O)NH2, C(O)NH (C1-4 alkyl), C(O)N (C1-6 alkyl)2, NH2, NO2, SF5, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl-; and each hydrogen atom of RM (e.g., H of RM or OH of RM, C(O)OH, C(O)NH2, C(O)NH (C1-4 alkyl), C( O)N(C1-6alkyl)2, NH2, C1-6alkyl, C1-6alkoxy, C1-6 haloalkoxy, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6alkyl-, C3-7 cycloalkyl-C1-6alkyl-, (5-6-membered heteroaryl)-C1-6alkyl- and (4-7-membered heterocycloalkyl)-C1-6alkyl- each hydrogen is substituted with a deuterium atom as appropriate.

[0309] In some embodiments: W-series C(RW)2; Y-series C(RY)2; Each RY is independently H or C1-6 alkyl; Each RY is independently H or C1-6 alkyl; Cyclic A-series C3-10 cycloalkyl or 4-11 heterocyclic alkyl, wherein the C3-10 cycloalkyl and 4-10 heterocyclic alkyl of cycloA are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate; R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocyclic alkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocyclic alkyl)-C1-6 alkyl-, wherein the C1-6 alkyl of R2, C2-6 alkenyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R2A substituents, depending on the case. Each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, (4-10 member heterocycloalkyl)-C1-6 alkyl-, CN, and ORa21, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, and (4-10 member heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, or 4 independently selected R2B substituents as appropriate; each Ra21 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; Each R2B is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, S(O)Rb22, and S(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl of R2B are each substituted by 1, 2, 3, or 4 independently selected R2C substituents as appropriate; each Rb22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R2C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, and NO2;R3 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein each of the C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- is substituted by 1, 2, 3 or 4 independently selected R3A substituents as appropriate; Each R3A is independently selected from oxy-, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd31, NRc3 1Rd31 and S(O)2Rb31, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate; Each Ra31, Rb31, Rc31, and Rd31 is independently selected from H, C1-6 alkyl, and 4-10 member heterocyclic alkyl; each R3B is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, ORa32, C(O)Rb32, C(O)NRc32Rd32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, S(O)2NRc32Rd32; each Ra32, Rb32, Rc32, and Rd32 is independently selected from H and C1-6 alkyl; the R4 series is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy. The R5 group is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl and C2-6 alkynyl;Each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O)Rb 6. NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate; Each Ra6, Rb6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl, and (4-10 member heterocyclic alkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl, and (4-10 member heterocyclic alkyl)-C1-6 alkyl- of Ra6, Rb6, Rc6, and Rd6 are each substituted by 1, 2, 3, or 4 independently selected R6A substituents as appropriate; Each R6A is independently selected from halogen, side oxygen, C1-6 alkyl, 4-10 member heterocyclic alkyl, CN, ORa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61 and S(O)2Rb61, wherein each C1-6 alkyl and 4-10 member heterocyclic alkyl of R6A is substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate; Each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and C6-10 aryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and C6-10 aryl of Ra61, Rb61, Rc61 and Rd61 are each substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate;Each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, CN, and C(O)NRc62Rd62, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl groups of R6B are each substituted by one, two, three, or four independently selected R6C substituents as appropriate; each Rc62 and Rd62 is independently H or C1-6 alkyl; each R6C is independently selected from halogen, side oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, CN, and NO2.

[0310] In some embodiments: W-series C(RW)2; Y-series C(RY)2; Each RW is independently H or C1-6 alkyl; Each RY is independently H or C1-6 alkyl; Cyclic A-series C3-10 cycloalkyl or 4-10 heterocyclic alkyl, wherein the C3-10 cycloalkyl and 4-10 heterocyclic alkyl of cycloA are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate; R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocyclic alkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocyclic alkyl)-C1-6 alkyl-, wherein the C1-6 alkyl of R2, C2-6 alkenyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R2A substituents, depending on the case. Each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, (4-10 member heterocycloalkyl)-C1-6 alkyl-, CN, and ORa21, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, and (4-10 member heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, or 4 independently selected R2B substituents as appropriate; each Ra21 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; Each R2B is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, S(O)Rb22, and S(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl of R2B are each substituted by 1, 2, 3, or 4 independently selected R2C substituents as appropriate; each Rb22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R2C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, and NO2;R3 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein each of the C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- is substituted by 1, 2, 3 or 4 independently selected R3A substituents as appropriate; Each R3A is independently selected from oxy-, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd31, NRc3 1Rd31 and S(O)2Rb31, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate; Each Ra31, Rb31, Rc31, and Rd31 is independently selected from H, C1-6 alkyl, and 4-10 member heterocyclic alkyl; each R3B is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, ORa32, C(O)Rb32, C(O)NRc32Rd32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, S(O)2NRc32Rd32; each Ra32, Rb32, Rc32, and Rd32 is independently selected from H and C1-6 alkyl; the R4 series is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy. The R5 group is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl and C2-6 alkynyl;Each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O)Rb 6. NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate; Each Ra6, Rb6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl, and (4-10 member heterocyclic alkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl, and (4-10 member heterocyclic alkyl)-C1-6 alkyl- of Ra6, Rb6, Rc6, and Rd6 are each substituted by 1, 2, 3, or 4 independently selected R6A substituents as appropriate; Each R6A is independently selected from halogen, side oxygen, C1-6 alkyl, 4-10 member heterocyclic alkyl, CN, ORa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61 and S(O)2Rb61, wherein each C1-6 alkyl and 4-10 member heterocyclic alkyl of R6A is substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate; Each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and C6-10 aryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and C6-10 aryl of Ra61, Rb61, Rc61 and Rd61 are each substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate;Each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, CN, and C(O)NRc62Rd62, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl groups of R6B are each substituted by one, two, three, or four independently selected R6C substituents as appropriate; each Rc62 and Rd62 is independently H or C1-6 alkyl; and each R6C is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, CN, and NO2.

[0311] In some embodiments: W-series C(RW)2; Y-series C(RY)2; Each RW is independently H or C1-6 alkyl; Each RY is independently H or C1-6 alkyl; Cycloaca is C3-10 cycloalkyl or 4-10 heterocyclic alkyl, wherein the C3-10 cycloalkyl and 4-10 heterocyclic alkyl of cycloaca are each substituted with 1, 2, 3 or 4 independently selected R6 substituents as appropriate; R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, 5-10 heteroaryl and 4-10 heterocyclic alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, 5-10 heteroaryl and 4-10 heterocyclic alkyl of R2 are each substituted with 1, 2, 3 or 4 independently selected R2A substituents as appropriate; Each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, (4-6-membered heterocycloalkyl)-C1-6 alkyl-, CN, and ORa21, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-6 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, and (4-6-membered heterocycloalkyl)-C1-6 alkyl- of R2A are each substituted by 1, 2, 3, or 4 independently selected R2B substituents as appropriate; each Ra21 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; Each R2B is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and S(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl of R2B are each substituted by 1, 2, 3, or 4 independently selected R2C substituents as appropriate; each Rb22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R2C is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, CN, and NO2; R3 is selected from phenyl, C3-7 cycloalkyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl and bicyclic 8-10-membered heterocyclic alkyl, wherein the phenyl, C3-7 cycloalkyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl and bicyclic 8-10-membered heterocyclic alkyl of R3 are each substituted by 1, 2, 3 or 4 independently selected R3A substituents as appropriate;Each R3A is independently selected from syloxy group, C1-6 alkyl group, C1-6 haloalkyl group, C3-7 cycloalkyl group, 4-6 member heterocycloalkyl group, phenyl-C1-6 alkyl-, C3-6 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl-, (4-6 member heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd31, NRc31Rd31 and S(O)2Rb31, wherein the C1-6 alkyl group, C3-7 cycloalkyl group, 4-6 member heterocycloalkyl group, phenyl-C1-6 alkyl-, C3-6 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl- and (4-6 member heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate; Each Rb31, Rc31, and Rd31 is independently selected from H, C1-6 alkyl groups, and 4-10 member heterocyclic alkyl groups; each R3B is independently selected from CN, ORa32, C(O)Rb32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, and S(O)2NRc32Rd32; each Ra32, Rb32, Rc32, and Rd32 is independently selected from H and C1-6 alkyl groups; the R4 series is selected from H and C1-6 alkyl groups; the R5 series is selected from H and C1-6 alkyl groups. Each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O)Rb6, NR c6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate; Each Ra6, Rb6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 cycloalkyl, phenyl, and (4-7 member heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 cycloalkyl, phenyl, and (4-10 member heterocycloalkyl)-C1-6 alkyl- of Ra6, Rb6, Rc6, and Rd6 are each substituted by 1, 2, 3, or 4 independently selected R6A substituents as appropriate;Each R6A is independently selected from halogen, side oxygen, C1-6 alkyl, 4-10 member heterocyclic alkyl, CN, ORa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61 and S(O)2Rb61, wherein each C1-6 alkyl and 4-10 member heterocyclic alkyl of R6A is substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate; Each Ra61, Rb61, Rc61, and Rd61 is independently selected from H, C1-6 alkyl, and phenyl, wherein the C1-6 alkyl and phenyl groups of Ra61, Rb61, Rc61, and Rd61 are each substituted with one or two independently selected R6B substituents as appropriate; each R6B is independently selected from C1-6 alkyl, CN, and C(O)NRc62Rd62, wherein the C1-6 alkyl group of each R6B is substituted with CN as appropriate; and each Rc62 and Rd62 is independently selected from H and C1-3 alkyl.

[0312] In some embodiments: W-series CH2; Y-series CH2; Cyclo-A series is selected from cyclobutyl, cyclopentyl, cyclohexyl, dihydroindyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl, wherein the cyclobutyl, cyclopentyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl of cyclo-A are each substituted by one or two independently selected R6 substituents as appropriate; R2 is selected from H, ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl, and indole, wherein the ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl, and indole groups of R2 are each substituted by 1, 2, 3, or 4 independently selected R2A substituents as appropriate; each R2A is independently selected from fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperylmethyl, cyano, methoxy, and trifluoromethoxy, wherein the methyl, cyclopropyl, pyrazolyl, and piperylmethyl groups are each substituted by 1 or 2 independently selected R2B substituents as appropriate; Each R2B is independently selected from C1-6 alkyl groups and S(O)2Rb22, wherein the C1-6 alkyl groups of R2B are each substituted with CN as appropriate; each Rb22 is independently selected from H or C1-6 alkyl groups; R3 is selected from phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolizo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl, wherein the phenyl, cyclopropyl, cyclohexenyl ... Hexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyridine, 3,4-dihydro-2H-benzo[b][1,4]pyridine, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl are each substituted with 1, 2, 3 or 4 independently selected R3A substituents as appropriate;Each R3A is independently selected from methyl, trideuterylmethyl, ethyl, isopropyl, isobutyl, difluoroethyl, trifluoroethyl, methoxy, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, succinylmethyl, succinylethyl, succinylcarbonyl, dimethylaminocarbonyl, and ethylsulfonylutriyl, wherein the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, succinylmethyl, and succinylethyl of R3A are each substituted by 1, 2, 3, or 4 independently selected R3B substituents as appropriate; In some embodiments, each R3B is independently selected from hydroxyl, methoxy, methylsulfonyl, methyl carbonyl, and cyano; R4 is selected from H and C1-6 alkyl; R5 is selected from H and C1-6 alkyl; each R6 is independently selected from ethyl, tributyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolyl isopropyl, aziridine isopropyl, 2-azibicyclo[2.1.1]hexyl, bicyclo[1.1.1]pentyl, methyl carbonyl, tetrahydropyranylmethyl carbonyl ethyl, propylcarbonyl, dimethylaminocarbonyl, methoxycarbonyl, anilinecarbonyl, ethylsulfonyl, cyclobutylcarbonylamino, cyclopropylsulfonyl and cyclopropylsulfonylamino, wherein R6 is ethyl, tributyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azacyclobutyl, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolylisopropyl The following groups are substituted with one or two independently selected R6A substituents, respectively: α-azabicyclo[2.1.1]hexyl, bicyclo[1.1.1]pentyl, methylcarbonyl, tetrahydropyranylmethylcarbonyl, propylcarbonyl, dimethylaminocarbonyl, methoxycarbonyl, phenylaminocarbonyl, ethylsulfonyl, cyclobutylcarbonylamino, cyclopropylsulfonyl, and cyclopropylsulfonylamino. R6A is independently selected from fluorine, oxy, methyl, CN, methoxy, tetrahydropyranyl, methyl carbonyl, amino carbonyl, methyl carbonylamino, ethylamino carbonyl, methoxy carbonyl, methoxy carbonylamino, ethylamino carbonylamino, ethylsulfonyl, and benzenesulfonylamino, wherein each methyl group of R6A is substituted with CN or amino carbonyl as appropriate; and each tetrahydropyranyl group of R6A is substituted with cyanomethyl as appropriate.

[0313] In some embodiments: W-series CH2; Y-series CH2; Cyclo-A series is selected from cyclobutyl, cyclopentyl, cyclohexyl, dihydroindyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl, wherein the cyclobutyl, cyclopentyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, azircyclobutyl, piperidinyl, pyrrolidinyl, azircycloheptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl of cyclo-A are each substituted by one or two independently selected R6 substituents as appropriate; R2 is selected from H, ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl, and indole, wherein the ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl, and indole groups of R2 are each substituted by 1, 2, 3, or 4 independently selected R2A substituents as appropriate; each R2A is independently selected from fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperylmethyl, cyano, methoxy, and trifluoromethoxy, wherein the methyl, cyclopropyl, pyrazolyl, and piperylmethyl groups are each substituted by 1 or 2 independently selected R2B substituents as appropriate; Each R2B is independently selected from C1-6 alkyl groups and S(O)2Rb22, wherein the C1-6 alkyl groups of R2B are each substituted with CN as appropriate; each Rb22 is independently selected from H or C1-6 alkyl groups; R3 is selected from phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolizo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl, wherein the phenyl, cyclopropyl, cyclohexenyl ... Hexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyridine, 3,4-dihydro-2H-benzo[b][1,4]pyridine, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl are each substituted with 1, 2, 3 or 4 independently selected R3A substituents as appropriate;Each R3A is independently selected from methyl, trideuterylmethyl, ethyl, isopropyl, isobutyl, difluoroethyl, trifluoroethyl, methoxy, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, succinylmethyl, succinylethyl, succinylcarbonyl, dimethylaminocarbonyl, and ethylsulfonylutriyl, wherein the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, succinylmethyl, and succinylethyl of R3A are each substituted by 1, 2, 3, or 4 independently selected R3B substituents as appropriate; Each R3B is independently selected from hydroxyl, methoxy, methylsulfonyl, methyl carbonyl, and cyano; R4 is selected from H and C1-6 alkyl; R5 is selected from H and C1-6 alkyl; each R6 is independently selected from ethyl, tributyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolyl isopropyl, aziridine isopropyl, 2-azibicyclo[2.1.1]hexyl, bicyclo[1.1.1]pentyl, methyl carbonyl, tetrahydropyranylmethyl carbonyl ethyl, propylcarbonyl, dimethylaminocarbonyl, methoxycarbonyl, anilinecarbonyl, ethylsulfonyl, cyclobutylcarbonylamino, cyclopropylsulfonyl and cyclopropylsulfonylamino, wherein R6 is ethyl, tributyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azacyclobutyl, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolylisopropyl The following groups are substituted with one or two independently selected R6A substituents, respectively: α-azabicyclo[2.1.1]hexyl, bicyclo[1.1.1]pentyl, methylcarbonyl, tetrahydropyranylmethylcarbonyl, propylcarbonyl, dimethylaminocarbonyl, methoxycarbonyl, phenylaminocarbonyl, ethylsulfonyl, cyclobutylcarbonylamino, cyclopropylsulfonyl, and cyclopropylsulfonylamino. R6A is independently selected from fluorine, oxy, methyl, CN, methoxy, tetrahydropyranyl, methyl carbonyl, amino carbonyl, methyl carbonylamino, ethylamino carbonyl, methoxy carbonyl, methoxy carbonylamino, ethylamino carbonylamino, ethylsulfonyl, and benzenesulfonylamino, wherein each methyl group of R6A is substituted with CN or amino carbonyl as appropriate; and each tetrahydropyranyl group of R6A is substituted with cyanomethyl as appropriate.

[0314] In some embodiments: W-series C(RW)2; Y-series C(RY)2; Each RW is independently H or C1-6 alkyl; Each RY is independently H or C1-6 alkyl; Cyclic A-series C3-10 cycloalkyl or 4-10 member heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 member heterocycloalkyl of cycloA are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate; R2 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein each of the C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- is substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate; Each R2A is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, and 4-10 heterocycloalkyl groups of R2A are each substituted by 1, 2, 3, or 4 independently selected R2B substituents as appropriate; each R2B is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl groups of R2B are each substituted by a cyano group as appropriate; R3 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein each of the C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- is substituted by 1, 2, 3 or 4 independently selected R3A substituents as appropriate;Each R3A is independently selected from oxy-, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein R3A C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R3B substituents as appropriate; Each R3B is independently selected from S(O)2Rb32; each Rb32 is independently selected from H or C1-6 alkyl; R4 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl and C1-6 haloalkoxy; R5 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl and C2-6 alkynyl; Each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6 and C( O)ORa6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate; Each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl groups of Ra6, Rb6, Rc6 and Rd6 are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate;Each R6A is independently selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, CN, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61 and OC(O)Rb61, wherein the C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl and 4-10 heterocycloalkyl of R6A are each substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate; Each Ra61, Rb61, Rc61, and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl groups of Ra61, Rb61, Rc61, and Rd61 are each substituted by one, two, three, or four independently selected R6B substituents as appropriate; and each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl groups is substituted by CN as appropriate.

[0315] In some embodiments: W-series C(RW)2; Y-series C(RY)2; Each RW is independently H or C1-6 alkyl; Each RY is independently H or C1-6 alkyl; Cycloaca is C3-10 cycloalkyl or 4-10 heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 heterocycloalkyl of cycloaca are each substituted with 1, 2, 3 or 4 independently selected R6 substituents as appropriate; R2 is selected from C6-10 aryl and 5-10 heteroaryl, wherein the C6-10 aryl and 5-10 heteroaryl of R2 are each substituted with 1, 2, 3 or 4 independently selected R2A substituents as appropriate; Each R2A is independently selected from C1-6 alkyl and 5-10 heteroaryl, wherein the C1-6 alkyl and 5-10 heteroaryl of R2A are each substituted with 1 or 2 independently selected R2B substituents as appropriate; Each R2B is independently selected from H and C1-6 alkyl, wherein the C1-6 alkyl of R2B is optionally substituted with a cyano group; R3 is selected from C6-10 aryl, C3-10 cycloalkyl and 5-10 heteroaryl, wherein the C6-10 aryl, C3-10 cycloalkyl and 5-10 heteroaryl of R3 are each optionally substituted with 1, 2, 3 or 4 independently selected R3A substituents; each R3A is independently selected from C1-6 alkyl, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each optionally substituted with 1, 2, 3 or 4 independently selected R3B substituents; Each R3B is independently selected from S(O)2Rb32; each Rb32 is independently selected from H or C1-6 alkyl; R4 is selected from H and C1-6 alkyl; R5 is selected from H and C1-6 alkyl; each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, (5-10 member heteroaryl)-C1-6 alkyl-, (4-10 member heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6 and C(O)ORa6, wherein the C1-6 alkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, (5-10 member heteroaryl)-C1-6 alkyl- and (4-10 member heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate; Each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl groups of Ra6, Rb6, Rc6 and Rd6 are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate;Each R6A is independently selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, CN, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61 and OC(O)Rb61, wherein the C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl and 4-10 heterocycloalkyl of R6A are each substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate; Each Ra61, Rb61, Rc61, and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl groups of Ra61, Rb61, Rc61, and Rd61 are each substituted by one, two, three, or four independently selected R6B substituents as appropriate; and each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl groups is substituted by CN as appropriate.

[0316] In some embodiments: W-series CH2; Y-series CH2; Cyclic A is selected from C3-7 cycloalkyl, monocyclic 4-6-membered heterocyclic alkyl, and bicyclic 8-10-membered heterocyclic alkyl, wherein the C3-7 cycloalkyl, monocyclic 4-6-membered heterocyclic alkyl, and bicyclic 8-10-membered heterocyclic alkyl of cycloalkyl A are each substituted with 1, 2, 3, or 4 independently selected R6 substituents as appropriate; R2 is selected from phenyl and indazole, wherein the phenyl and indazole of R2 are each substituted with 1, 2, 3, or 4 independently selected R2A substituents as appropriate; Each R2A is independently selected from C1-6 alkyl and 5-10-membered heteroaryl, wherein the C1-6 alkyl and 5-10-membered heteroaryl of R2A are each substituted with 1 or 2 independently selected R2B substituents as appropriate; Each R2B is independently selected from H and C1-6 alkyl, wherein the C1-6 alkyl of R2B is substituted with CN as appropriate; R3 is selected from phenyl, cyclopropyl, and pyrazolyl, wherein the phenyl, cyclopropyl, and pyrazolyl groups of R3 are each substituted by 1, 2, 3, or 4 independently selected R3A substituents as appropriate; each R3A is independently selected from C1-6 alkyl, (5-10-membered heteroaryl)-C1-6 alkyl-, and (4-10-membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, (5-10-membered heteroaryl)-C1-6 alkyl-, and (4-10-membered heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, or 4 independently selected R3B substituents as appropriate; each R3B is independently selected from S(O)2Rb32; each Rb32 is independently selected from H or C1-6 alkyl; R4 is selected from H and C1-6 alkyl; R5 is selected from H and C1-6 alkyl; Each R6 is independently selected from C1-6 alkyl, 5-10 member heteroaryl, 4-10 member heterocyclic alkyl, and C(O)Rb6, wherein the C1-6 alkyl, 5-10 member heteroaryl, and 4-10 member heterocyclic alkyl of R6 are each substituted with 1, 2, 3, or 4 independently selected R6A substituents as appropriate; Each Rb6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl of Rb6 are each substituted with 1, 2, 3, or 4 independently selected R6A substituents as appropriate; Each R6A is independently selected from 4-10 member heterocyclic alkyl, CN, and C(O)Rb61, wherein the 4-10 member heterocyclic alkyl of R6A are each substituted with 1, 2, 3, or 4 independently selected R6B substituents as appropriate; Each Rb61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl groups of Rb61 are each substituted by one or two independently selected R6B substituents as appropriate; each R2B is independently selected from C1-6 alkyl, wherein the C1-6 alkyl group of R6B is substituted by CN as appropriate.

[0317] In some embodiments: W-series CH2; Y-series CH2; Cyclo-A series is selected from cyclobutyl, cyclopentyl, cyclohexyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl, wherein cyclobutyl, cyclopentyl, cyclohexyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl and azirbicyclo[3.2.1]octyl.1] Octyl groups are each substituted with 1, 2, 3 or 4 independently selected R6 substituents as appropriate; R2 is selected from phenyl and indazole groups, wherein the phenyl and indazole groups of R2 are each substituted with 1, 2, 3 or 4 independently selected R2A substituents as appropriate; each R2A is independently selected from C1-6 alkyl and 5-10 heteroaryl groups, wherein the C1-6 alkyl and 5-10 heteroaryl groups of R2A are each substituted with 1 or 2 independently selected R2B substituents as appropriate; each R2B is independently selected from H and C1-6 alkyl, wherein the C1-6 alkyl group of R2B is substituted with CN as appropriate; R3 is selected from phenyl, cyclopropyl and pyrazolyl groups, wherein the phenyl, cyclopropyl and pyrazolyl groups of R3 are each substituted with 1, 2, 3 or 4 independently selected R3A substituents as appropriate; Each R3A is independently selected from C1-6 alkyl, (5-10 member heteroaryl)-C1-6 alkyl-, and (4-10 member heterocyclic alkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, (5-10 member heteroaryl)-C1-6 alkyl-, and (4-10 member heterocyclic alkyl)-C1-6 alkyl- of R3A are each substituted by 1, 2, 3, or 4 independently selected R3B substituents as appropriate; each R3B is independently selected from S(O)2Rb32; each Rb32 is independently selected from H or C1-6 alkyl; R4 series is selected from H and C1-6 alkyl; R5 series is selected from H and C1-6 alkyl; Each R6 is independently selected from C1-6 alkyl, 5-10 member heteroaryl, 4-10 member heterocyclic alkyl, and C(O)Rb6, wherein the C1-6 alkyl, 5-10 member heteroaryl, and 4-10 member heterocyclic alkyl of R6 are each substituted with 1, 2, 3, or 4 independently selected R6A substituents as appropriate; Each Rb6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl of Rb6 are each substituted with 1, 2, 3, or 4 independently selected R6A substituents as appropriate; Each R6A is independently selected from 4-10 member heterocyclic alkyl, CN, and C(O)Rb61, wherein the 4-10 member heterocyclic alkyl of R6A are each substituted with 1, 2, 3, or 4 independently selected R6B substituents as appropriate; Each Rb61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl groups of Rb61 are each substituted with one or two independently selected R6B substituents, as appropriate; each R6B is independently selected from C1-6 alkyl, wherein the C1-6 alkyl group of R6B is substituted with CN, as appropriate.

[0318] In some embodiments, the compound of formula I is a compound of formula II: II or a pharmaceutically acceptable salt thereof.

[0319] In some embodiments, the compound of formula I is a compound of formula IIa: IIa or a pharmaceutically acceptable salt thereof.

[0320] In some embodiments, the compound of formula I is a compound of formula IIb: IIb or a pharmaceutically acceptable salt thereof.

[0321] In some embodiments, the compound of formula I is a compound of formula III: III or a pharmaceutically acceptable salt thereof.

[0322] In some embodiments, the compound of formula I is a compound of formula IIIa: IIIa or a pharmaceutically acceptable salt thereof.

[0323] In some embodiments, the compound of formula I is a compound of formula IIIb: IIIb or a pharmaceutically acceptable salt thereof.

[0324] In some embodiments, the compound of formula I is a compound of formula IV: IV or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, 2, 3, 4 or 5.

[0325] In some embodiments, the compound of formula I is a compound of formula IVa: IVa or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, 2, 3, 4 or 5.

[0326] In some embodiments, the compound of formula I is a compound of formula IVb: IVb or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, 2, 3, 4 or 5.

[0327] In some embodiments, the compound of formula I is a compound of formula V: V or a pharmaceutically acceptable salt thereof.

[0328] In some embodiments, the compound of formula I is a compound of formula Va: Va or a pharmaceutically acceptable salt thereof.

[0329] In some embodiments, the compound of formula I is a compound of formula Vb: Vb or a pharmaceutically acceptable salt thereof.

[0330] In some embodiments, the compound of formula I is a compound of formula VI: VI or a pharmaceutically acceptable salt thereof.

[0331] In some embodiments, the compound of formula I is a compound of formula VIa: VIa or a pharmaceutically acceptable salt thereof.

[0332] In some embodiments, the compound of formula I is a compound of formula VIb: VIb or a pharmaceutically acceptable salt thereof.

[0333] In some embodiments, the compound of formula I is a compound of formula VII: VII or a pharmaceutically acceptable salt thereof.

[0334] In some embodiments, the compound of formula I is a compound of formula VIIa: VIIa or a pharmaceutically acceptable salt thereof.

[0335] In some embodiments, the compound of formula I is a compound of formula VIIb: VIIb or a pharmaceutically acceptable salt thereof.

[0336] In some embodiments, the compound of formula I is a compound of formula VIII: VIII or a pharmaceutically acceptable salt thereof.

[0337] In some embodiments, the compound of formula I is a compound of formula VIIIa: VIIIa or a pharmaceutically acceptable salt thereof.

[0338] In some embodiments, the compound of formula I is a compound of formula VIIIb: VIIIb or a pharmaceutically acceptable salt thereof.

[0339] In some embodiments, the compound of formula I is a compound of formula IX: IX or a pharmaceutically acceptable salt thereof, wherein n is 0, 1 or 2.

[0340] In some embodiments, the compound of formula I is a compound of formula IXa: IXa or a pharmaceutically acceptable salt thereof, wherein n is 0, 1 or 2.

[0341] In some embodiments, the compound of formula I is a compound of formula IXb: IXb or a pharmaceutically acceptable salt thereof, wherein n is 0, 1 or 2.

[0342] In some embodiments, the compound of formula I is a compound of formula X: X or a pharmaceutically acceptable salt thereof.

[0343] In some embodiments, the compound of formula I is a compound of formula Xa: Xa or a pharmaceutically acceptable salt thereof.

[0344] In some embodiments, the compound of formula I is a compound of formula Xb: Xb or a pharmaceutically acceptable salt thereof.

[0345] In some embodiments, the compounds provided herein (e.g., any of the compounds of formulas I-Xb) or their pharmaceutically acceptable salts contain at least one deuterium atom.

[0346] In some embodiments, the compounds provided herein (e.g., any of the compounds of formulas I-Xb) or their pharmaceutically acceptable salts contain two or more deuterium atoms.

[0347] In some embodiments, all hydrogen atoms of the compounds provided herein (e.g., any of the compounds of formulas I-Xb) or their pharmaceutically acceptable salts are replaced with deuterium atoms.

[0348] In some embodiments, the compounds provided herein are selected from: 6-methyl-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1-phenyl-2',3,3',5',6,6'-hexahydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-pyran]-7-one; 6-methyl-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1-phenyl-3,4',5',6-tetrahydro-2'H,7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-furan]-7-one; 1-(1-acetylopiperidin-4-yl)-6'-methyl-2'-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1'-phenyl-3',6'-dihydro-7'H-spiro[azacyclobutane-3,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; 3-(6-methyl-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,4'-piperidin]-1'-yl)propionitrile; 3-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)propionitrile; 2-(4-(4-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)-1H-pyrazol-1-yl)tetrahydro-2H-pyran-4-yl)acetonitrile; 3-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-(methyl-d3)-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)propionitrile; 6'-methyl-1'-(1-methyl-1H-indazol-5-yl)-2'-(1-(pyridin-4-ylmethyl)-1H-pyrazol-4-yl)-3',6'-dihydro-7'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridin]-7'-one; 2'-Cyclopropyl-6'-methyl-1'-(1-methyl-1H-indazol-5-yl)-3',6'-dihydro-7'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one;6'-Methyl-2'-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1'-phenyl-3',6'-dihydro-7'H-spiro[cyclobutane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; 6'-Methyl-2'-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1'-phenyl-3',6'-dihydro-7'H-spiro[cyclohexane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; 6-Methyl-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1-phenyl-1'-(2-(tetrahydro-2H-pyran-4-yl)acetyl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,3'-pyrrolidin]-7-one; 8-acetyl-6'-methyl-2'-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1'-phenyl-3',6'-dihydro-7'H-8-azaspiro[bicyclo[3.2.1]octane-3,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; 3-(4-(4-(6'-methyl-2'-(1-methyl-1H-pyrazol-4-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridin]-1'-yl)phenyl)-1H-pyrazol-1-yl)butyronitrile; 6-methyl-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1-phenyl-1'-(pyrimidin-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-7-one; (1R,3r,5S)-6'-methyl-2'-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1'-phenyl-8-(pyrimidin-4-yl)-3',6'-dihydro-7'H-8-azaspiro[bicyclo[3.2.1]octane-3,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; 6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1-(2-methylthiazolyl-5-yl)-1'-(pyrimidin-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,4'-piperidin]-7-one; 6-Methyl-2-(1-methyl-1H-pyrazol-4-yl)-1'-(pyrimidin-4-yl)-1-vinyl-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-7-one;1-Ethyl-6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1'-(pyrimidin-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-7-one; 1-(3,6-dihydro-2H-pyran-4-yl)-6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1'-(pyrimidin-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-7-one; N-(3-methoxyphenyl)-6-methyl-2-(4-((4-(methylsulfonyl)piperidin-1-yl)methyl)phenyl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,4'-piperidine]-1'-methylamine; 6'-methyl-2'-(1-methyl-1H-pyrazol-4-yl)-1'-(4-((4-(methylsulfonyl)piperidin-1-yl)methyl)phenyl)-3',6'-dihydro-7'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; 2-(1-(ethylsulfonyl)-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)azacyclobutane-3-yl)acetonitrile; 2-(1-acetyl-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)azacyclobutane-3-yl)acetonitrile; 3-(cyanomethyl)-N-ethyl-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)azacyclobutane-1-methylamine; 2-(4-fluorophenyl)-2-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)acetamide; (3-(cyanomethyl)-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)cyclobutyl)aminocarbamate;1-(3-(cyanomethyl)-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)-3-ethylurea; N-(3-(cyanomethyl)-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)benzenesulfonamide; 2-(1-(2-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(4-(1-(1-lin-4-carbonyl)cyclohex-1-en-1-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(4-(ethylsulfonylurea)phenyl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile;2-(1-(2-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(1-hydroxy-2-methylpropyl-2-yl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-(2-(N-pyrolinyl)ethyl)-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(3-cyclopropyl-1-methyl-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(1-acetylpiperidine-4-yl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrrolo-3-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-2-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile;2-(1-(2-(1-(2-methoxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-2-(1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-6-methyl-1-(1-(methyl-d3)-1H-indol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(1-(3,5-difluoro-4-methoxyphenyl)-2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-7-sideoxy-1-(thieno[3,2-c]pyridin-2-yl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(1-(4-cyclopropylphenyl)-2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-7-sideoxy-1-(4-(trifluoromethoxy)phenyl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 4-(1'-(1-(cyanomethyl)cyclobutyl)-2-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-6-methyl-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1-yl)benzonitrile;2-(1-(2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazole-4-yl)-6-methyl-7-sideoxy-1-(4-(trifluoromethyl)phenyl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)cyclobutyl)acetonitrile; (R)-1-(ethylsulfonylurea)-2'-(1-isopropyl-1H-pyrazole-4-yl)-6'-methyl-1'-(1-methyl-1H-indazol-5-yl)-3',6'-dihydro-7'H-spiro[azacycloheptane-4,8'-dipyrrolo[2,3-b:3',2'-d]pyridin]-7'-one; (S)-1-(ethylsulfonylurea)-2'-(1-isopropyl-1H-pyrazol-4-yl)-6'-methyl-1'-(1-methyl-1H-indazol-5-yl)-3',6'-dihydro-7'H-spiro[azacycloheptane-4,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; 1-(ethylsulfonylurea)-2''-(1-isopropyl-1H-pyrazol-4-yl)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; N-((1S,3R)-6'-methyl-1'-(1-methyl-1H-indazole-5-yl)-2'-(1-methyl-1H-pyrazol-4-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-3-yl)cyclopropanesulfonamide; N-((1R,3S)-6'-methyl-1'-(1-methyl-1H-indazole-5-yl)-2'-(1-methyl-1H-pyrazol-4-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-3-yl)cyclopropanesulfonamide; N-((1S,3S)-6'-methyl-1'-(1-(methyl-d3)-1H-indazol-5-yl)-2'-(1-methyl-1H-pyrazol-4-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-3-yl)cyclopropanesulfonamide; N-((1R,3R)-6'-methyl-1'-(1-(methyl-d3)-1H-indazol-5-yl)-2'-(1-methyl-1H-pyrazol-4-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-3-yl)cyclopropanesulfonamide;6-Methyl-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1',3,3',6-tetrahydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,2'-indene]-7-one; 6-Methyl-2-(1-methyl-1H-pyrazol-4-yl)-1-(1-(methyl-d3)-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidin]-1''-carboxylic acid methyl ester; 1''-Butyryl-6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3,6-dihydro-7H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidine]-7-one; N,N,6-trimethyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidine]-1''-methamide; 6-Methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidine]-1''-formate; 1''-((2-methoxyethyl)sulfonyl)-6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1-phenyl-3,6-dihydro-7H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidine]-7-one; 4-(1''-Butyryl-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,1'-cyclobutane-3',4''-piperidine]-2-yl)-N,N-dimethylcyclohexyl-3-en-1-methylamine; 1''-Butyryl-6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrrol-3-yl)-3,6-dihydro-7H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,1'-cyclobutane-3',4''-piperidine]-7-one;(R)-2-(1-((6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-1'-yl)methyl)cyclopropyl)acetonitrile; (S)-2-(1-((6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-1'-yl)methyl)cyclopropyl)acetonitrile; 2-(1-((6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-2-(3-sideoxy-3,4-dihydro-2H-benzo[b][1,4]carbazol-7-yl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidinyl]-1'-yl)methyl)cyclopropyl)acetonitrile; 2-(1-((6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-2-(pyrazolo[1,5-a]pyrimidin-3-yl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-1'-yl)methyl)cyclopropyl)acetonitrile; 4-((4-(1'-((1-(cyanomethyl)cyclopropyl)methyl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-2-yl)-1H-pyrazol-1-yl)methyl)benzonitrile; 2-(2-((6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-1'-yl)methyl)spiro[3.3]hept-2-yl)acetonitrile; 2-(1-((6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-1'-yl)sulfonyl)cyclopropyl)acetonitrile; 2-(1-((6-methoxy-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidinyl]-1'-yl)methyl)cyclopropyl)acetonitrile;2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)cyclopentyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-1'H,3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-pyridin]-1'-yl)cyclopropyl)acetonitrile; 2-(4-methoxy-1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)cyclohexyl)acetonitrile; 1'-(2-(1H-1,2,3-triazol-4-yl)propyl-2-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-7-one; 1'-(2-(4H-1,2,4-triazol-3-yl)propyl-2-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-7-one; 6-methyl-1'-(3-methyl-1,1-dioxo-tetrahydrothiophene-3-yl)-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-7-one; 2-(1-(2-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-6-methyl-1-(1-(methyl-d3)-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclopentyl)acetonitrile; (R)-4-methoxy-3-methyl-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1-(1-(methyl-d3)-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)butyronitrile;(S)-4-methoxy-3-methyl-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1-(1-(methyl-d3)-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)butyronitrile; 4-(cyanomethyl)-4-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)piperidine-1-carboxylic acid methyl ester; N-(3-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)bicyclo[1.1.1]pent-1-yl)acetamide; 4-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)-2-azabicyclo[2.1.1]hexane-2-carboxylic acid methyl ester; 1'-(2-(azacyclobutan-3-yl)propyl-2-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-7-one; 1-(ethylsulfonylurea)-6''-methyl-1''-(1-(methyl-d3)-1H-indazol-5-yl)-2''-(4-((N-pyrolinyl)methyl)phenyl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(ethylsulfonyl)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-2''-(1-methyl-1H-pyrazol-4-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one;2''-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-1-(ethylsulfonyl)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(ethylsulfonyl)-2''-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(ethylsulfonyl)-2''-(1-isopropyl-1H-pyrazol-4-yl)-6''-(methyl-d3)-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 2''-(1-cyclopentyl-1H-pyrazol-4-yl)-1-(ethylsulfonylurea)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(4-(1-(ethylsulfonyl)-6''-methyl-1''-(1-(methyl-d3)-1H-indazol-5-yl)-7''-sideoxy-6'',7''-dihydro-3''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-2''-yl)benzyl)piperidine-4-carboxynitrile; 1-(ethylsulfonylurea)-1''-(4-methoxyphenyl)-6''-(methyl-d3)-2''-(4-((N-pyrolinyl)methyl)phenyl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 2''-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-1-(ethylsulfonyl)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one;2''-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-1-(ethylsulfonylurea)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 2''-(1-ethyl-1H-pyrazol-4-yl)-1-(ethylsulfonylurea)-1''-(4-methoxyphenyl)-6''-(methyl-d3)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(ethylsulfonylurea)-2''-(1-(2-methoxy-2-methylpropyl)-1H-pyrazol-4-yl)-6''-methyl-1''-(1-(methyl-d3)-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(ethylsulfonylurea)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-2''-(1-((tetrahydro-2H-pyran-4-yl)) 2''-(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyridine-3-yl)-1-(ethylsulfonylurea)-6''-methyl-1''-(1-(methyl-d3)-1H-indazol-5-yl)-3'',6''-dihydro-7''-dispiro[azolo[3,1-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(ethylsulfonyl)-2''-(3-methoxy-1-methyl-1H-pyrazol-4-yl)-6''-methyl-1''-(1-(methyl-d3)-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one;1-(2-amino-2-sideoxyethyl)-N-((1S,3S)-6'-methyl-2'-(1-methyl-1H-pyrazol-4-yl)-1'-(1-(methyl-d3)-1H-indazol-5-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-3-yl)cyclobutane-1-methylamine; 1-(2-amino-2-sideoxyethyl)-N-((1R,3R)-6'-methyl-2'-(1-methyl-1H-pyrazol-4-yl)-1'-(1-(methyl-d3)-1H-indazol-5-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-3-yl)cyclobutane-1-methylamine; 1''-Butyryl-6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-(methyl-d3)-1H-pyrrolo-3-yl)-3,6-dihydro-7H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidine]-7-one; 1''-Butyryl-6-methyl-1-(1-(methyl-d3)-1H-indazol-5-yl)-2-(1-(methyl-d3)-1H-pyrrolo-3-yl)-3,6-dihydro-7H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidine]-7-one; 2'-(1-isopropyl-1H-pyrazol-4-yl)-6'-(methyl-d3)-1'-(1-methyl-1H-indazol-5-yl)-1-((1-methylcyclopropyl)sulfonyl)-3',6'-dihydro-7'H-spiro[azacycloheptane-4,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; and 2'-(1-(1-cyclopropylethyl)-1H-pyrazol-4-yl)-1-(ethylsulfonyl)-6'-(methyl-d3)-1'-(1-methyl-1H-indazol-5-yl)-3',6'-dihydro-7'H-spiro[azacycloheptane-4,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; Or a medically acceptable salt.

[0349] It should be further understood that, for clarity, certain features of the invention set forth in the context of individual embodiments may also be provided in combination in a single embodiment. Conversely, for brevity, various features of the invention set forth in the context of individual embodiments may also be provided individually or in any suitable sub-combination.

[0350] Divalent linking substituents are described at different locations in this specification. Each divalent linking substituent is explicitly intended to include both the forward and reverse forms of the linking substituent. For example, -NR(CR'R'')n- includes both -NR(CR'R'')n- and -(CR'R'')nNR-. Where the structure clearly requires a linking group, the Markush variable listed for that group should be understood as the linking group.

[0351] The term "n-membered" (where n is an integer) typically describes the number of cyclic atoms in a subset where the number of cyclic atoms is n. Examples include piperidinyl 6-membered heterocyclic alkyl rings, pyrazolyl 5-membered heteroaryl rings, pyridinyl 6-membered heteroaryl rings, and 1,2,3,4-tetrahydro-naphthalene 10-membered cycloalkyl rings.

[0352] As used herein, the phrase “substituted, as appropriate” means unsubstituted or substituted. Substituents are chosen independently, and substitution can occur at any chemically accessible position. As used herein, the term “substituted” means the removal of a hydrogen atom and substitution by a substituent. A single divalent substituent, such as a side oxygen group, can substitute for two hydrogen atoms. It should be understood that substitution at a given atom is limited by valence.

[0353] As used herein, the phrase “each ‘variable’ is selected independently” is intended to be substantially the same as “the ‘variable’ is selected each time it appears”.

[0354] Throughout the definition, the terms "Cn-m" and "Cm-n" refer to a range including the endpoints, where n and m are integers and represent the number of carbon atoms. Examples include C1-3, C1-4, C1-6, and similar cases.

[0355] As used herein, the term "Cn-m alkyl," used alone or in combination with other terms, refers to a saturated hydrocarbon group having n to m carbon atoms, which may be straight-chain or branched. Examples of alkyl groups include, but are not limited to, chemical groups such as: methyl (Me), ethyl (Et), n-propyl (n-Pr), isopropyl (iPr), n-butyl, tributyl, isobutyl, secondary butyl; higher homologues such as 2-methyl-1-butyl, n-pentyl, 3-pentyl, n-hexyl, 1,2,2-trimethylpropyl, and similar groups. In some embodiments, the alkyl group contains 1 to 6 carbon atoms, 1 to 4 carbon atoms, 1 to 3 carbon atoms, 2 to 6 carbon atoms, 2 to 4 carbon atoms, 2 to 3 carbon atoms, or 1 to 2 carbon atoms.

[0356] As used herein, "Cn-m alkenyl" refers to an alkyl group having one or more carbon-carbon double bonds and having n to m carbon atoms. Exemplary alkenyl groups include, but are not limited to, vinyl, n-propenyl, isopropenyl, n-butenyl, secondary butenyl, and similar groups. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

[0357] As used herein, "Cn-m ynyl" refers to an alkyl group having one or more carbon-carbon linkages and having n to m carbon atoms. Exemplary ynyl groups include, but are not limited to, ethynyl, propyn-1-yl, propyn-2-yl, and similar groups. In some embodiments, the ynyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

[0358] As used herein, the term "Cn-m alkoxy," used alone or in combination with other terms, refers to a group of the formula -O-alkyl, wherein the alkyl group has n to m carbon atoms. Exemplary alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), butoxy (e.g., n-butoxy and tert-butoxy), and similar groups. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0359] As used herein, the term "aryl" used alone or in combination with other terms refers to an aromatic hydrocarbon group, which may be monocyclic or polycyclic (e.g., having 2, 3, or 4 fused rings). The term "Cn-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, and similar groups. 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.

[0360] As used herein, "halogen group" means F, Cl, Br or I. In some embodiments, the halogen group is F, Cl or Br. In some embodiments, the halogen group is F or Cl. In some embodiments, the halogen group is F. In some embodiments, the halogen group is Cl.

[0361] As used herein, "Cn-m haloalkoxy" refers to a group of the formula -O-haloalkyl having n to m carbon atoms. Exemplary 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.

[0362] As used herein, the term "Cn-m haloalkyl" used alone or in combination with other terms refers to an alkyl group having one to 2s+1 halogen atoms, which may be the same or different, wherein "s" is the number of carbon atoms in the alkyl group, and wherein the alkyl group has n to m carbon atoms. In some embodiments, the haloalkyl group is only fluorinated. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. Exemplary haloalkyl groups include CF3, C2F5, CHF2, CH2F, CCl3, CHCl2, C2Cl5, and similar groups.

[0363] As used herein, "cycloalkyl" refers to a non-aromatic cyclic hydrocarbon, including cycloalkyl and alkenyl groups. A cycloalkyl group may include a monocyclic or polycyclic (e.g., having two fused rings) group, a spirocyclic group, and a bridging ring (e.g., a bridged bicyclic alkyl group). The cyclic carbon atom of a cycloalkyl group may be substituted with a side oxygen or sulfido group (e.g., C(O) or C(S)). The definition of cycloalkyl also includes portions having one or more aromatic rings fused to the cycloalkyl ring (i.e., having a common bond), such as benzo or thiophene derivatives of cyclopentane, cyclohexane, and similar groups. A cycloalkyl group containing a fused aromatic ring may be linked by any cyclic atom, including the cyclic atom of the fused aromatic ring. A cycloalkyl group may have 3, 4, 5, 6, 7, 8, 9, or 10 cyclic carbons (i.e., C3-10). In some embodiments, the cycloalkyl group is a C3-10 monocyclic or bicyclic cycloalkyl group. In some embodiments, the cycloalkyl group is a C3-7 monocyclic cycloalkyl group. In some embodiments, the cycloalkyl group is a C4-7 monocyclic cycloalkyl group. In some embodiments, the cycloalkyl group is a C4-10 spirocyclic or bridged cycloalkyl group (e.g., a bridged bicyclic cycloalkyl group). Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cyclohepttrienyl, norcamphenyl, 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, and similar groups. In some embodiments, the cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0364] As used herein, "heteroaryl" refers to a monocyclic or polycyclic aromatic heterocycle (e.g., having two fused rings) 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 heteroatom ring members independently selected 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 5-10 member monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, S, and B. In some embodiments, the heteroaryl is a 5-, 7-, 8-, 9-, or 10-member monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, S, and B. In some embodiments, the heteroaryl is a 5-10 member monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, and S. In some embodiments, the heteroaryl group is a 5-membered, 7-membered, 8-membered, 9-membered, or 10-membered monocyclic or bicyclic heteroaryl group, independently selected from heteroatom ring members of N, O, and S. In some embodiments, the heteroaryl group is a 5-6 membered monocyclic heteroaryl group, independently selected from heteroatom ring members of N, O, S, and B. In some embodiments, the heteroaryl group is a 5-membered monocyclic heteroaryl group, independently selected from heteroatom ring members of N, O, S, and B. In some embodiments, the heteroaryl group is a 5-membered monocyclic heteroaryl group, independently selected from heteroatom ring members of N, O, and S. In some embodiments, the heteroaryl group contains 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 a 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, acezolyl, pyrazolyl, isothiazolyl, isoacezolyl, 1,2,3-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-acezolyl, 1,2,4-triazolyl, 1,2 ,4-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-triazolyl, 1,3,4-thiadiazolyl, 1,3,4-thiadiazolyl and 1,2-dihydro-1,2-azaborane, pyridyl, pyrimidinyl, pyridine, pyridyl, pyridyl, azole, triazolyl, thiadiazolyl, quinolinyl, isoquinolinyl, indoleyl, benzothiophene, benzofuranyl, benzoisoazolyl, imidazo[1, [2-b]thiazolyl, purinyl, triazolyl, thieno[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, indazole and similar groups.

[0365] As used herein...

Claims

1. A compound of formula I: I or a pharmaceutically acceptable salt thereof, wherein: W-series CRW, C(RW)2, N, NRW, O, or S; Y-series CRY, C(RY)2, N, NRY, O, or S; wherein at least one W-series CRW or C(RW)2, or a Y-series CRY or C(RY)2; each RW is independently selected from H, oxy-group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each RY is independently selected from H, oxy-group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; cyclic A-series C3-10 cycloalkyl or 4-10 member heterocyclic alkyl, wherein the C3-10 cycloalkyl and 4-10 member heterocyclic alkyl of cyclic A are each substituted by 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R6 substituents as appropriate; The R2 series is selected from H, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa2, SRa2, NHORa 2. C(O)Rb2, C(O)NRc2Rd2, C(O)NRc2(ORa2), C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2NRc2 Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, C(=NRe2)Rb2, C(=NRe2)NRc2Rd2, NRc2C(=NRe2) NRc2Rd2, NRc2C(=NRe2)Rb2, NRc2S(O)Rb2, NRc2S(O)NRc2Rd2, NRc2S(O)2Rb2, NRc2S(O)(=NRe2)Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2, OS(O)(=NRe2)Rb2 and OS(O)2Rb2, The C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2A substituents, as appropriate;Each of Ra2, Rc2, and Rd2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra2, Rc2, and Rd2 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl-, C2-6 ynyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-. The C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2A substituents, as appropriate; or, any Rc2 and Rd2 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R2A substituents, as appropriate; Each Rb2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb2... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2A substituents as appropriate; Each Re2 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R2A group is selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa21, SRa21, NHORa21, C(O)Rb2 1. C(O)NRc21Rd21, C(O)NRc21(ORa21), C(O)ORa21, OC(O)Rb21, OC(O)NRc21Rd21, NRc21Rd21, NRc21NRc21Rd21 , NRc21C(O)Rb21, NRc21C(O)ORa21, NRc21C(O)NRc21Rd21, C(=NRe21)Rb21, C(=NRe21)NRc21Rd21, NRc21C(=NRe 21)NRc21Rd21, NRc21C(=NRe21)Rb21, NRc21S(O)Rb21, NRc21S(O)NRc21Rd21, NRc21S(O)2Rb21, NRc21S(O)(=N Re21)Rb21, NRc21S(O)2NRc21Rd21, S(O)Rb21, S(O)NRc21Rd21, S(O)2Rb21, S(O)2NRc21Rd21, OS(O)(=NRe21)Rb 21 and OS(O)2Rb21, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2B substituents as appropriate;Each of Ra21, Rc21, and Rd21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra21 and Rc21 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2B substituents, as appropriate; or, any Rc21 and Rd21 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R2B substituents, as appropriate; Each Rb21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1- of Rb21 6-alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2B substituents as appropriate; Each Re21 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R2B is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa22, SRa22, NHORa22, C(O)R b22, C(O)NRc22Rd22, C(O)NRc22(ORa22), C(O)ORa22, OC(O)Rb22, OC(O)NRc22Rd22, NRc22Rd22, NRc22NRc22Rd2 2. NRc22C(O)Rb22, NRc22C(O)ORa22, NRc22C(O)NRc22Rd22, C(=NRe22)Rb22, C(=NRe22)NRc22Rd22, NRc22C(=NR e22)NRc22Rd22, NRc22C(=NRe22)Rb22, NRc22S(O)Rb22, NRc22S(O)NRc22Rd22, NRc22S(O)2Rb22, NRc22S(O)(= NRe22)Rb22, NRc22S(O)2NRc22Rd22, S(O)Rb22, S(O)NRc22Rd22, S(O)2Rb22, S(O)2NRc22Rd22, OS(O)(=NRe22)R b22 and OS(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2C substituents as appropriate;Each of Ra22, Rc22, and Rd22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra22 and Rc22 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2C substituents, as appropriate; or, any Rc22 and Rd22 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R2C substituents, as appropriate; Each Rb22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1- of Rb22... 6-alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R2C substituents as appropriate; Each Re22 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R2C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa23, SRa23, NHORa23, C(O)Rb23, C( O)NRc23Rd23, C(O)NRc23(ORa23), C(O)ORa23, OC(O)Rb23, OC(O)NRc23Rd23, NRc23Rd23, NRc23NRc23Rd2 3. NRc23C(O)Rb23, NRc23C(O)ORa23, NRc23C(O)NRc23Rd23, C(=NRe23)Rb23, C(=NRe23)NRc23Rd23, NRc23 C(=NRe23)NRc23Rd23, NRc23C(=NRe23)Rb23, NRc23S(O)Rb23, NRc23S(O)NRc23Rd23, NRc23S(O)2Rb23, N Rc23S(O)(=NRe23)Rb23, NRc23S(O)2NRc23Rd23, S(O)Rb23, S(O)NRc23Rd23, S(O)2Rb23, S(O)2NRc23Rd23 OS(O)(=NRe23)Rb23 and OS(O)2Rb23, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected RM substituents as appropriate;Each of Ra23, Rc23, and Rd23 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra23, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, or 4 independently selected RM substituents as appropriate; or, any Rc23 and Rd23 attached to the same N atom together with the N atom to which they are attached form a 5-6 heteroaryl or a 4-7 heterocycloalkyl, wherein the 5-6 heteroaryl or 4-7 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected RM substituents as appropriate; Each Rb23 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb23 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents, as appropriate; Each Re23 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-;The R3 group is selected from H, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa3, SRa3, NHORa 3. C(O)Rb3, C(O)NRc3Rd3, C(O)NRc3(ORa3), C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3NRc3 Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3) NRc3Rd3, NRc3C(=NRe3)Rb3, NRc3S(O)Rb3, NRc3S(O)NRc3Rd3, NRc3S(O)2Rb3, NRc3S(O)(=NRe3)Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3, OS(O)(=NRe3)Rb3 and OS(O)2Rb3, The C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3A substituents, as appropriate;Each Ra3, Rc3, and Rd3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra3, Rc3, and Rd3 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl-, C2-6 ynyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-. The C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3A substituents, as appropriate; or, any Rc3 and Rd3 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R3A substituents, as appropriate; Each Rb3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb3... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3A substituents as appropriate; Each Re3 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 member heteroaryl)-C1-6 alkyl- and (4-10 member heterocycloalkyl)-C1-6 alkyl-;Each R3A group is selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa31, SRa31, NHORa31, C(O)Rb3 1. C(O)NRc31Rd31, C(O)NRc31(ORa31), C(O)ORa31, OC(O)Rb31, OC(O)NRc31Rd31, NRc31Rd31, NRc31NRc31Rd31 , NRc31C(O)Rb31, NRc31C(O)ORa31, NRc31C(O)NRc31Rd31, C(=NRe31)Rb31, C(=NRe31)NRc31Rd31, NRc31C(=NRe 31)NRc31Rd31, NRc31C(=NRe31)Rb31, NRc31S(O)Rb31, NRc31S(O)NRc31Rd31, NRc31S(O)2Rb31, NRc31S(O)(=N Re31)Rb31, NRc31S(O)2NRc31Rd31, S(O)Rb31, S(O)NRc31Rd31, S(O)2Rb31, S(O)2NRc31Rd31, OS(O)(=NRe31)Rb 31 and OS(O)2Rb31, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3B substituents as appropriate;Each of Ra31, Rc31, and Rd31 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra31 and Rc31 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3B substituents, as appropriate; or, any Rc31 and Rd31 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R3B substituents, as appropriate; Each Rb31 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1- of Rb31 6-alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3B substituents as appropriate; Each Re31 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R3B is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa32, SRa32, NHORa32, C(O)R b32, C(O)NRc32Rd32, C(O)NRc32(ORa32), C(O)ORa32, OC(O)Rb32, OC(O)NRc32Rd32, NRc32Rd32, NRc32NRc32Rd3 2. NRc32C(O)Rb32, NRc32C(O)ORa32, NRc32C(O)NRc32Rd32, C(=NRe32)Rb32, C(=NRe32)NRc32Rd32, NRc32C(=NR e32)NRc32Rd32, NRc32C(=NRe32)Rb32, NRc32S(O)Rb32, NRc32S(O)NRc32Rd32, NRc32S(O)2Rb32, NRc32S(O)(= NRe32)Rb32, NRc32S(O)2NRc32Rd32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, S(O)2NRc32Rd32, OS(O)(=NRe32)R b32 and OS(O)2Rb32, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3C substituents as appropriate;Each of Ra32, Rc32, and Rd32 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra32 and Rc32 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3C substituents, as appropriate; or, any Rc32 and Rd32 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R3C substituents, as appropriate; Each Rb32 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1- of Rb32 6-alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R3C substituents as appropriate; Each Re32 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R3C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa33, SRa33, NHORa33, C(O)Rb33, C( O)NRc33Rd33, C(O)NRc33(ORa33), C(O)ORa33, OC(O)Rb33, OC(O)NRc33Rd33, NRc33Rd33, NRc33NRc33Rd3 3. NRc33C(O)Rb33, NRc33C(O)ORa33, NRc33C(O)NRc33Rd33, C(=NRe33)Rb33, C(=NRe33)NRc33Rd33, NRc33 C(=NRe33)NRc33Rd33, NRc33C(=NRe33)Rb33, NRc33S(O)Rb33, NRc33S(O)NRc33Rd33, NRc33S(O)2Rb33, N Rc33S(O)(=NRe33)Rb33, NRc33S(O)2NRc33Rd33, S(O)Rb33, S(O)NRc33Rd33, S(O)2Rb33, S(O)2NRc33Rd33 OS(O)(=NRe33)Rb33 and OS(O)2Rb33, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected RM substituents as appropriate;Each of Ra33, Rc33, and Rd33 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra33, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, or 4 independently selected RM substituents, as appropriate; or, any Rc33 and Rd33 attached to the same N atom together with the N atom to which they are attached form a 5-6 heteroaryl or a 4-7 heterocycloalkyl, wherein the 5-6 heteroaryl or 4-7 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected RM substituents, as appropriate; Each Rb33 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb33 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents, as appropriate; Each Re33 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-; R4 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, OH, NH2 and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN and NH2 as appropriate;R5 is selected from H, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, OH, CN, C(O)OH, C(O)NHRa5, NH2, and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN, and NH2 as appropriate; Ra5 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, OH, NH2, and NHC1-6 alkyl, wherein the C1-6 alkyl is substituted with OH, CN, and NH2 as appropriate; Each R6 is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa6, SRa6, N HORa6, C(O)Rb6, C(O)NRc6Rd6, C(O)NRc6(ORa6), C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6N Rc6Rd6, NRc6C(O)Rb6, NRc6C(O)ORa6, NRc6C(O)NRc6Rd6, C(=NRe6)Rb6, C(=NRe6)NRc6Rd6, NRc6C(=NRe 6)NRc6Rd6, NRc6C(=NRe6)Rb6, NRc6S(O)Rb6, NRc6S(O)NRc6Rd6, NRc6S(O)2Rb6, NRc6S(O)(=NRe6)Rb6 , NRc6S(O)2NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, S(O)2NRc6Rd6, OS(O)(=NRe6)Rb6 and OS(O)2Rb6 In which the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6A substituents as appropriate;Each Ra6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra6, Rc6, and Rd6 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl-, C2-6 ynyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-. The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R6A substituents, as appropriate; or, any Rc6 and Rd6 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R6A substituents, as appropriate; Each Rb6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 of Rb6... Alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6A substituents, as appropriate; Each Re6 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R6A is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa61, SRa61, NHORa61, C(O)R b61, C(O)NRc61Rd61, C(O)NRc61(ORa61), C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61NRc61Rd6 1. NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, C(=NRe61)Rb61, C(=NRe61)NRc61Rd61, NRc61C(=NR e61)NRc61Rd61, NRc61C(=NRe61)Rb61, NRc61S(O)Rb61, NRc61S(O)NRc61Rd61, NRc61S(O)2Rb61, NRc61S(O)(= NRe61)Rb61, NRc61S(O)2NRc61Rd61, S(O)Rb61, S(O)NRc61Rd61, S(O)2Rb61, S(O)2NRc61Rd61, OS(O)(=NRe61)R b61 and OS(O)2Rb61, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6B substituents as appropriate;Each of Ra61, Rc61, and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein Ra61 and Rc61 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R6B substituents, as appropriate; or, any Rc61 and Rd61 attached to the same N atom together with the N atom to which they are attached form a 5-10 heteroaryl or a 4-10 heterocycloalkyl, wherein the 5-10 heteroaryl or 4-10 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected R6B substituents, as appropriate; Each Rb61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein the C1- of Rb61 6-alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, 4, 5, 6, 7 or 8 independently selected R6B substituents as appropriate; Each Re61 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-;Each R6B is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 member heteroaryl, 4-7 member heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl-, (4-7 member heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa62, SRa62, NHORa62, C(O)Rb62, C( O)NRc62Rd62, C(O)NRc62(ORa62), C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62, NRc62NRc62Rd62 , NRc62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, C(=NRe62)Rb62, C(=NRe62)NRc62Rd62, NRc62C (=NRe62)NRc62Rd62, NRc62C(=NRe62)Rb62, NRc62S(O)Rb62, NRc62S(O)NRc62Rd62, NRc62S(O)2Rb62, NR c62S(O)(=NRe62)Rb62, NRc62S(O)2NRc62Rd62, S(O)Rb62, S(O)NRc62Rd62, S(O)2Rb62, S(O)2NRc62Rd62, OS(O)(=NRe62)Rb62 and OS(O)2Rb62, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6C substituents as appropriate;Each of Ra62, Rc62, and Rd62 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra62, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with one, two, three, or four independently selected R6C substituents, as appropriate; or, any Rc62 and Rd62 attached to the same N atom together with the N atom to which they are attached form a 5-6 heteroaryl or a 4-7 heterocycloalkyl, wherein the 5-6 heteroaryl or 4-7 heterocycloalkyl is substituted with one, two, three, or four independently selected R6C substituents, as appropriate; Each Rb62 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb62 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R6C substituents, as appropriate; Each Re62 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-;Each R6C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa63, SRa63, NHORa63, C(O)Rb63, C( O)NRc63Rd63, C(O)NRc63(ORa63), C(O)ORa63, OC(O)Rb63, OC(O)NRc63Rd63, NRc63Rd63, NRc63NRc63Rd6 3. NRc63C(O)Rb63, NRc63C(O)ORa63, NRc63C(O)NRc63Rd63, C(=NRe63)Rb63, C(=NRe63)NRc63Rd63, NRc63 C(=NRe63)NRc63Rd63, NRc63C(=NRe63)Rb63, NRc63S(O)Rb63, NRc63S(O)NRc63Rd63, NRc63S(O)2Rb63, N Rc63S(O)(=NRe63)Rb63, NRc63S(O)2NRc63Rd63, S(O)Rb63, S(O)NRc63Rd63, S(O)2Rb63, S(O)2NRc63Rd63 OS(O)(=NRe63)Rb63 and OS(O)2Rb63, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected RM substituents as appropriate;Each of Ra63, Rc63, and Rd63 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Ra63, The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl-, and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, or 4 independently selected RM substituents, as appropriate; or, any Rc63 and Rd63 attached to the same N atom together with the N atom to which they are attached form a 5-6 heteroaryl or 4-7 heterocycloalkyl, wherein the 5-6 heteroaryl or 4-7 heterocycloalkyl is substituted with 1, 2, 3, or 4 independently selected RM substituents, as appropriate; Each Rb63 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-, wherein Rb63 The C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected RM substituents, as appropriate; Each Re63 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-7-membered heterocycloalkyl)-C1-6 alkyl-;Each RM is independently selected from H, OH, halogen, lateral oxy group, CN, C(O)OH, C(O)NH2, C(O)NH (C1-4 alkyl), C(O)N (C1-6 alkyl)2, NH2, NO2, SF5, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-7-membered heterocycloalkyl)-C1-6 alkyl-.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein W is C(RW)2.

3. The compound of claim 1 or 2 or its pharmaceutically acceptable salt, wherein each RW is independently H or C1-6 alkyl.

4. The compound of claim 1 or its pharmaceutically acceptable salt, wherein W is CH2.

5. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 4, wherein Y is C(RY)2.

6. A compound of any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof, wherein each RY is independently H or C1-6 alkyl.

7. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 4, wherein Y is CH2.

8. The compound of claim 1 or its pharmaceutically acceptable salt, wherein W and Y are each CH2.

9. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 8, wherein the ring A is a C3-10 cycloalkyl group, which is substituted by one, two, three or four independently selected R6 substituents, as appropriate.

10. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 8, wherein the ring A is a C3-7 cycloalkyl group, which is substituted by one, two, three or four independently selected R6 substituents, as appropriate.

11. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 8, wherein ring A is a bicyclic C8-10 cycloalkyl or a monocyclic C3-7 cycloalkyl, which is substituted by one, two, three or four independently selected R6 substituents, as appropriate.

12. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 8, wherein ring A is selected from cyclobutyl, cyclopentyl, cyclohexyl and dihydroindene, wherein the cyclobutyl, cyclopentyl, cyclohexyl and dihydroindene of ring A are each substituted by one, two, three or four independently selected R6 substituents, as appropriate.

13. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 8, wherein the ring A is a 4-10 member heterocyclic alkyl group, which is substituted by one, two, three or four independently selected R6 substituents, as appropriate.

14. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 8, wherein ring A is a monocyclic 4-6-membered heterocyclic alkyl, a bicyclic 8-10-membered heterocyclic alkyl, or a spirocyclic 7-10-membered heterocyclic alkyl, wherein the monocyclic 4-6-membered heterocyclic alkyl, bicyclic 8-10-membered heterocyclic alkyl, or spirocyclic 7-10-membered heterocyclic alkyl of ring A is substituted by one, two, three, or four independently selected R6 substituents, as appropriate.

15. A compound of any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, wherein ring A is selected from tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine-heptyl, dihydropyridinyl, azibicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl, wherein each of the tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine-heptyl, dihydropyridinyl, azibicyclo[3.2.1]octyl, 2-azispir[3.3]heptyl and 7-azispir[3.5]nonyl in ring A is substituted, as appropriate, by one, two, three or four independently selected R6 substituents.

16. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 10 and 13 to 15, wherein each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O)Rb6, NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

17. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 10 and 13 to 15, wherein each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, C3-10 cycloalkyl-C1-6 alkyl-, C6-10 aryl-C1-6 alkyl-, (5-10 member heteroaryl)-C1-6 alkyl-, (4-10 member heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O) ORa6, NRc6C(O)Rb6, NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C3-10 cycloalkyl-C1-6 alkyl-, C6-10 aryl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate.

18. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 10 and 13 to 17, wherein each Ra6, Rb6, Rc6 and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl and (4-10 member heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl and (4-10 member heterocycloalkyl)-C1-6 alkyl- of Ra6, Rb6, Rc6 and Rd6 is substituted by one, two, three or four independently selected R6A substituents as appropriate.

19. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 10 and 13 to 15, wherein each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C3-10 cycloalkyl-C1-6 alkyl-, C6-10 aryl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, ( 4-10 member heterocyclic alkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O)Rb6, NRc6S(O)2Rb6 and S(O)2Rb6, wherein R6 is a C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocyclic alkyl, C3-10 cycloalkyl-C1-6 Alkyl-, C6-10 aryl-C1-6 alkyl-, (5-10 member heteroaryl)-C1-6 alkyl-, and (4-10 member heterocyclic alkyl)-C1-6 alkyl- are each substituted with 1, 2, 3, or 4 independently selected R6A substituents, as appropriate; and each Ra6, Rb6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 Cycloalkyl, C6-10 aryl, and (4-10 member heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl, and (4-10 member heterocycloalkyl)-C1-6 alkyl- of Ra6, Rb6, Rc6, and Rd6 are each substituted with 1, 2, 3, or 4 independently selected R6A substituents as appropriate.

20. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 10 and 13 to 15, wherein each R6 is independently selected from ethyl, tributyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolylisopropyl, aziridineisopropyl, 2-azibicyclo[2.1.1]hexyl, bicyclo[1.1.1]pentyl, methylcarbonyl, tetrahydropyranylmethylcarbonyl, propylcarbonyl, dimethylaminocarbonyl, methoxycarbonyl, anilinecarbonyl, ethylsulfonylurea, cyclobutylcarbonylamino, cyclopropylsulfonylurea, and Cyclopropylsulfonylamino, wherein the ethyl, tributyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolylisopropyl, aziridineisopropyl, 2-azibicyclo[2.1.1]hexyl, bicyclo[1.1.1]pentyl, methylcarbonyl, tetrahydropyranylmethylcarbonyl, propylcarbonyl, dimethylaminocarbonyl, methoxycarbonyl, phenylaminocarbonyl, ethylsulfonyl, cyclobutylcarbonylamino, cyclopropylsulfonyl and cyclopropylsulfonylamino are each substituted by one or two independently selected R6A substituents as appropriate.

21. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 10 and 13 to 20, wherein each R6A is independently selected from a halogen group, a side oxygen group, a C1-6 alkyl group, a 4-10 member heterocyclic alkyl group, CN, ORa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61 and S(O)2Rb61, wherein each C1-6 alkyl group and the 4-10 member heterocyclic alkyl group of R6A are substituted with one, two, three or four independently selected R6B substituents, as appropriate.

22. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 10 and 13 to 21, wherein each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and C6-10 aryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and C6-10 aryl of Ra61, Rb61, Rc61 and Rd61 is substituted by one, two, three or four independently selected R6B substituents as appropriate.

23. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 10 and 13 to 20, wherein each R6A is independently selected from a halogen group, a side radical group, a C1-6 alkyl group, a 4-10 member heterocyclic alkyl group, a CN group, an ORa61 group, a C(O)Rb61 group, a C(O)NRc61Rd61 group, a C(O)ORa61 group, an NRc61 group, a C(O)NRc61Rd61 group, or an NRc61 group. S(O)2Rb61 and S(O)2Rb61, wherein each of the C1-6 alkyl groups and the 4-10 heterocyclic alkyl groups of R6A are substituted with 1, 2, 3 or 4 independently selected R6B substituents as appropriate; and each of Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl and phenyl, wherein each of the C1-6 alkyl and phenyl groups of Ra61, Rb61, Rc61 and Rd61 is substituted with 1, 2, 3 or 4 independently selected R6B substituents as appropriate.

24. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 10 and 13 to 23, wherein each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, CN and C(O)NRc62Rd62, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 ynyl are each substituted with CN as appropriate; and each Rc62 and Rd62 is independently H or C1-6 alkyl.

25. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 10 and 13 to 20, wherein each R6A is independently selected from fluorine, sero-oxygen, methyl, CN, methoxy, tetrahydropyranyl, methyl carbonyl, amino carbonyl, methyl carbonylamino, ethyl amino carbonyl, methoxy carbonyl, methoxy carbonylamino, ethyl amino carbonylamino, ethyl sulfonyl and benzene sulfonylamino, wherein each methyl group of R6A is substituted with CN or amino carbonyl as appropriate; and wherein each tetrahydropyranyl group of R6A is substituted with cyanomethyl as appropriate.

26. A compound of any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 Alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R2A substituents as appropriate.

27. A compound of any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, 5-10 heteroaryl and 4-10 heterocyclic alkyl, wherein each of the C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, 5-10 heteroaryl and 4-10 heterocyclic alkyl groups of R2 is substituted by one, two, three or four independently selected R2A substituents as appropriate.

28. A compound of any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl and indole, wherein the ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl and indole of R2 are each substituted by one, two, three or four independently selected R2A substituents as appropriate.

29. A compound of any one of claims 1 to 28 or a pharmaceutically acceptable salt thereof, wherein each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, and ORa21, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, and (4-10 heterocycloalkyl)-C1-6 alkyl- is substituted, as appropriate, by one, two, three, or four independently selected R2B substituents.

30. A compound of any one of claims 1 to 28 or a pharmaceutically acceptable salt thereof, wherein each R2A is independently selected from a halogen, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 5-10 heteroaryl, (4-10 heterocycloalkyl)-C1-6 alkyl-, CN, and ORa21, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 5-10 heteroaryl, and (4-10 heterocycloalkyl)-C1-6 alkyl- of R2A is substituted by one, two, three, or four independently selected R2B substituents as appropriate; and each Ra21 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

31. A compound of any one of claims 1 to 28 or a pharmaceutically acceptable salt thereof, wherein each R2A is independently selected from fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperidinemethyl, cyano, methoxy and trifluoromethoxy, wherein the methyl, cyclopropyl, pyrazolyl and piperidinemethyl are each substituted by one or two independently selected R2B substituents as appropriate.

32. A compound of any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl and indolyl, wherein the phenyl and indazole groups of R2 are each substituted, as appropriate, by one or two independent substituents selected from the following: fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperylmethyl, cyano, methoxy and trifluoromethoxy, wherein the methyl and pyrazolyl groups of R2A are each substituted, as appropriate, by cyano-C1-6 alkyl; and the piperylmethyl group of R2A is substituted, as appropriate, by methanesulfonyl.

33. A compound of any one of claims 1 to 32 or a pharmaceutically acceptable salt thereof, wherein R3 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, and (4-10 heterocycloalkyl)-C1-6 alkyl. R3 is substituted with one, two, three or four independently chosen R3A substituents, wherein the C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are respectively substituted with one, two, three or four independently chosen R3A substituents.

34. A compound of any one of claims 1 to 32 or a pharmaceutically acceptable salt thereof, wherein R3 is selected from phenyl, C3-7 cycloalkyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl, monocyclic 4-6-membered heterocycloalkyl, bicyclic 8-10-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, and (4-6-membered heterocycloalkyl)-C1-6 alkyl. R3 is substituted by one, two, three or four independently chosen R3A substituents, wherein the phenyl, C3-7 cycloalkyl, monocyclic 5-6-membered heteroaryl, bicyclic 8-10-membered heteroaryl, monocyclic 4-6-membered heterocyclic alkyl, bicyclic 8-10-membered heterocyclic alkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl- and (4-6-membered heterocyclic alkyl)-C1-6 alkyl- are respectively substituted by one, two, three or four independently chosen R3A substituents.

35. A compound of any one of claims 1 to 32 or a pharmaceutically acceptable salt thereof, wherein R3 is selected from phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl. The pyridyl group, wherein the phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl groups of R3 are each substituted by one, two, three or four independently chosen R3A substituents, as appropriate.

36. A compound of any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof, wherein each R3A is independently selected from oxy, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C( O)NRc31Rd31, NRc31Rd31 and S(O)2Rb31, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate.

37. A compound of any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof, wherein each R3A is independently selected from oxy-, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd31, NRc31Rd3 1 and S(O)2Rb31, wherein the C1-6 alkyl, C3-10 cycloalkyl, 4-10 heterocyclic alkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocyclic alkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate; and each Rb31, Rc31 and Rd31 is independently selected from H, C1-6 alkyl and 4-10 heterocyclic alkyl.

38. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 37, wherein each R3B is independently selected from CN, ORa32, C(O)Rb32 and S(O)2Rb32, wherein each Ra32 and Rb32 is independently selected from H and C1-6 alkyl groups.

39. A compound of any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof, wherein each R3A is independently selected from methyl, CD3, ethyl, isopropyl, isobutyl, difluoroethyl, trifluoroethyl, methoxy, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidinylmethyl, α-linylmethyl, α-linyl Ethyl, α-linyl carbonyl, dimethylamino carbonyl, and ethyl sulfonyl, wherein the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidylmethyl, α-linylmethyl, and α-linylethyl are each substituted with one, two, three, or four independently selected R3B substituents, depending on the situation.

40. A compound of any one of claims 1 to 32 or a pharmaceutically acceptable salt thereof, wherein R3 is selected from phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrroloyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrrolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrrolyl, 5,6-dihydro-4H-pyrrolo[ [1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl, wherein R3 is a phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl The methyl group and the pyrazolo[1,5-a]pyrimidinyl group are each substituted by one, two, three, or four independently selected R3A substituents, depending on the situation; and each R3A is independently selected from methyl, -CD3, ethyl, isopropyl, isobutyl, difluoroethyl, trifluoroethyl, methoxy, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridinylmethyl, piperidinylmethyl, α-linylmethyl, α-linylethyl R3A comprises 1, 2, 3 ...

41. A compound of any one of claims 1 to 40 or a pharmaceutically acceptable salt thereof, wherein R4 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl and C1-6 haloalkoxy.

42. A compound of any one of claims 1 to 40 or a pharmaceutically acceptable salt thereof, wherein R4 is selected from H and C1-6 alkyl groups.

43. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 40, wherein R4 is a methyl group or CD3.

44. A compound of any one of claims 1 to 43 or a pharmaceutically acceptable salt thereof, wherein R5 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl and C2-6 alkynyl.

45. A compound of any one of claims 1 to 43 or a pharmaceutically acceptable salt thereof, wherein R5 is selected from H and C1-6 alkyl groups.

46. ​​A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 43, wherein R5 is H.

47. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 40, wherein R4 is a C1-6 alkyl group and R5 is an H group.

48. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 40, wherein R4 is methyl or CD3; and R5 is H.

49. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein: W-series C(RW)2; Y-series C(RY)2; Each RW is independently H or C1-6 alkyl; Each RY is independently H or C1-6 alkyl; Cyclic A-series C3-10 cycloalkyl or 4-10 heterocyclic alkyl, wherein the C3-10 cycloalkyl and 4-10 heterocyclic alkyl of cycloA are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate; R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocyclic alkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocyclic alkyl)-C1-6 alkyl-, wherein the C1-6 alkyl of R2, C2-6 alkenyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted with 1, 2, 3 or 4 independently selected R2A substituents, depending on the case. Each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, (4-10 member heterocycloalkyl)-C1-6 alkyl-, CN, and ORa21, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 member heteroaryl, 4-10 member heterocycloalkyl, and (4-10 member heterocycloalkyl)-C1-6 alkyl- is substituted by 1, 2, 3, or 4 independently selected R2B substituents as appropriate; each Ra21 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; Each R2B is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, S(O)Rb22 and S(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl of R2B are each substituted by 1, 2, 3 or 4 independently selected R2C substituents as appropriate; each Rb22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl; each R2C is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN and NO2;R3 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl-, wherein each of the C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- is substituted by 1, 2, 3 or 4 independently selected R3A substituents as appropriate; Each R3A is independently selected from oxy-, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd31, NRc31 Rd31 and S(O)2Rb31, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate; Each Ra31, Rb31, Rc31, and Rd31 is independently selected from H, C1-6 alkyl, and 4-10 member heterocyclic alkyl; each R3B is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, ORa32, C(O)Rb32, C(O)NRc32Rd32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, S(O)2NRc32Rd32; each Ra32, Rb32, Rc32, and Rd32 is independently selected from H and C1-6 alkyl; the R4 series is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy. The R5 group is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl and C2-6 alkynyl;Each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl-, (4-10 heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O)Rb6 NRc6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 heteroaryl, 4-10 heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 heteroaryl)-C1-6 alkyl- and (4-10 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate; Each Ra6, Rb6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl, and (4-10 member heterocyclic alkyl)-C1-6 alkyl-, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, C6-10 aryl, and (4-10 member heterocyclic alkyl)-C1-6 alkyl- is substituted by 1, 2, 3, or 4 independently selected R6A substituents as appropriate; each R6A is independently selected from halogen, oxy group, C1-6 alkyl, 4-10 member heterocyclic alkyl, CN, ORa61, C(O)Rb61, C(O)NRc61Rd61, C( O)ORa61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61 and S(O)2Rb61, wherein each of the C1-6 alkyl groups and the 4-10 heterocyclic alkyl groups of R6A are substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate; Each Ra61, Rb61, Rc61 and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and C6-10 aryl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl and C6-10 aryl of Ra61, Rb61, Rc61 and Rd61 are each substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate;Each R6B is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, CN, and C(O)NRc62Rd62, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl groups of R6B are each substituted by one, two, three, or four independently selected R6C substituents as appropriate; each Rc62 and Rd62 is independently H or C1-6 alkyl; and each R6C is independently selected from halogen, oxy group, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, CN, and NO2.

50. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein: W-series C(RW)2; Y-series C(RY)2; Each RW is independently H or C1-6 alkyl; Each RY is independently H or C1-6 alkyl; Cyclic A-series C3-10 cycloalkyl or 4-10 member heterocyclic alkyl, wherein the C3-10 cycloalkyl and 4-10 member heterocyclic alkyl of cycloalkyl A are each substituted by 1, 2, 3 or 4 independently selected R6 substituents as appropriate; R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, 5-10 member heteroaryl and 4-10 member heterocyclic alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, 5-10 member heteroaryl and 4-10 member heterocyclic alkyl of R2 are each substituted by 1, 2, 3 or 4 independently selected R2A substituents as appropriate; Each R2A is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, (4-6-membered heterocycloalkyl)-C1-6 alkyl-, CN, and ORa21, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, phenyl, C3-6 cycloalkyl, 5-6-membered heteroaryl, 4-6-membered heterocycloalkyl, and (4-6-membered heterocycloalkyl)-C1-6 alkyl- is substituted by one, two, three, or four independently selected R2B substituents as appropriate; each Ra21 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; Each R2B is independently selected from halogen, lateral oxygen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and S(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl of R2B are each substituted by 1, 2, 3, or 4 independently selected R2C substituents as appropriate; each Rb22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R2C is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, CN, and NO2; R3 is selected from phenyl, C3-7 cycloalkyl, monocyclic 5-6 member heteroaryl, bicyclic 8-10 member heteroaryl and bicyclic 8-10 member heterocyclic alkyl, wherein the phenyl, C3-7 cycloalkyl, monocyclic 5-6 member heteroaryl, bicyclic 8-10 member heteroaryl and bicyclic 8-10 member heterocyclic alkyl of R3 are each substituted by 1, 2, 3 or 4 independently selected R3A substituents as appropriate;Each R3A is independently selected from oxy-, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-6 member heterocycloalkyl, phenyl-C1-6 alkyl-, C3-6 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl-, (4-6 member heterocycloalkyl)-C1-6 alkyl-, C(O)Rb31, C(O)NRc31Rd31, NRc31Rd31 and S(O)2Rb31, wherein each of the C1-6 alkyl, C3-7 cycloalkyl, 4-6 member heterocycloalkyl, phenyl-C1-6 alkyl-, C3-6 cycloalkyl-C1-6 alkyl-, (5-6 member heteroaryl)-C1-6 alkyl- and (4-6 member heterocycloalkyl)-C1-6 alkyl- is substituted by 1, 2, 3 or 4 independently selected R3B substituents as appropriate; Each Rb31, Rc31, and Rd31 is independently selected from H, C1-6 alkyl groups, and 4-10 member heterocyclic alkyl groups; each R3B is independently selected from CN, ORa32, C(O)Rb32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, and S(O)2NRc32Rd32; each Ra32, Rb32, Rc32, and Rd32 is independently selected from H and C1-6 alkyl groups; the R4 series is selected from H and C1-6 alkyl groups; the R5 series is selected from H and C1-6 alkyl groups. Each R6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6-membered heteroaryl, 4-7-membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6-membered heteroaryl)-C1-6 alkyl-, (4-7-membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6C(O)Rb6, NRc 6S(O)2Rb6 and S(O)2Rb6, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 heteroaryl, 4-7 heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 heteroaryl)-C1-6 alkyl- and (4-7 heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3 or 4 independently selected R6A substituents as appropriate; Each Ra6, Rb6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 cycloalkyl, phenyl, and (4-7 member heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 ynyl, C3-7 cycloalkyl, phenyl, and (4-10 member heterocycloalkyl)-C1-6 alkyl- are each substituted by 1, 2, 3, or 4 independently selected R6A substituents as appropriate;Each R6A is independently selected from halogen, side oxygen, C1-6 alkyl, 4-10 member heterocyclic alkyl, CN, ORa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61 and S(O)2Rb61, wherein each C1-6 alkyl and 4-10 member heterocyclic alkyl of R6A is substituted by 1, 2, 3 or 4 independently selected R6B substituents as appropriate; Each Ra61, Rb61, Rc61, and Rd61 is independently selected from H, C1-6 alkyl, and phenyl, wherein the C1-6 alkyl and phenyl groups of Ra61, Rb61, Rc61, and Rd61 are substituted with one or two independently selected R6B substituents as appropriate; each R6B is independently selected from C1-6 alkyl, CN, and C(O)NRc62Rd62, wherein each C1-6 alkyl group of R6B is substituted with CN as appropriate; and each Rc62 and Rd62 is independently selected from H and C1-3 alkyl.

51. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein: W-series CH2; Y-series CH2; Cyclic A is selected from C3-7 cycloalkyl, monocyclic 4-6-membered heterocyclic alkyl, and bicyclic 8-10-membered heterocyclic alkyl, wherein each of the C3-7 cycloalkyl, monocyclic 4-6-membered heterocyclic alkyl, and bicyclic 8-10-membered heterocyclic alkyl groups is substituted by 1, 2, 3, or 4 independently selected R6 substituents as appropriate; R2 is selected from phenyl and indazole, wherein each of the phenyl and indazole groups in R2 is substituted by 1, 2, 3, or 4 independently selected R2A substituents as appropriate; Each R2A is independently selected from C1-6 alkyl and 5-10-membered heteroaryl, wherein each of the C1-6 alkyl and 5-10-membered heteroaryl groups in R2A is substituted by 1 or 2 independently selected R2B substituents as appropriate; Each R2B is independently selected from H and C1-6 alkyl, wherein the C1-6 alkyl group in R2B is substituted by CN as appropriate; R3 is selected from phenyl, cyclopropyl, and pyrazolyl, wherein each of the phenyl, cyclopropyl, and pyrazolyl groups in R3 is substituted by one, two, three, or four independently selected R3A substituents as appropriate; each R3A is independently selected from C1-6 alkyl, (5-10-membered heteroaryl)-C1-6 alkyl-, and (4-10-membered heterocycloalkyl)-C1-6 alkyl-, wherein each of the C1-6 alkyl, (5-10-membered heteroaryl)-C1-6 alkyl-, and (4-10-membered heterocycloalkyl)-C1-6 alkyl- is substituted by one, two, three, or four independently selected R3B substituents as appropriate; each R3B is independently selected from S(O)2Rb32; each Rb32 is independently selected from H or C1-6 alkyl; R4 is selected from H and C1-6 alkyl; R5 is selected from H and C1-6 alkyl; Each R6 is independently selected from C1-6 alkyl, 5-10 member heteroaryl, 4-10 member heterocyclic alkyl, and C(O)Rb6, wherein the C1-6 alkyl, 5-10 member heteroaryl, and 4-10 member heterocyclic alkyl of R6 are each substituted by 1, 2, 3, or 4 independently selected R6A substituents as appropriate; Each Rb6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl of Rb6 are each substituted by 1, 2, 3, or 4 independently selected R6A substituents as appropriate; Each R6A is independently selected from 4-10 member heterocyclic alkyl, CN, and C(O)Rb61, wherein the 4-10 member heterocyclic alkyl of R6A are each substituted by 1, 2, 3, or 4 independently selected R6B substituents as appropriate; Each Rb61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 ynyl of Rb61 are each substituted by one or two independently selected R6B substituents as appropriate; each R6B is independently selected from C1-6 alkyl, wherein the C1-6 alkyl of R6B is substituted by CN as appropriate.

52. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein: W-series CH2; Y-series CH2; Cyclo-A series is selected from cyclobutyl, cyclopentyl, cyclohexyl, dihydroindyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine heptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-aziridine[3.3]heptyl and 7-aziridine[3.5]nonyl, wherein each of the cyclobutyl, cyclopentyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, aziridine, piperidinyl, pyrrolidinyl, aziridine heptyl, dihydropyridinyl, azirbicyclo[3.2.1]octyl, 2-aziridine[3.3]heptyl and 7-aziridine[3.5]nonyl in cyclo-A is substituted by one or two independently selected R6 substituents as appropriate; R2 is selected from H, ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl, and indole, wherein each of the ethyl, vinyl, phenyl, indazole, thiazolyl, thieno[3,2-c]pyridyl, 3,6-dihydro-2H-pyranyl, and indole groups of R2 is substituted by 1, 2, 3, or 4 independently selected R2A substituents as appropriate; each R2A is independently selected from fluorine, methyl, CD3, trifluoromethyl, cyclopropyl, pyrazolyl, piperylmethyl, cyano, methoxy, and trifluoromethoxy, wherein each of the methyl, cyclopropyl, pyrazolyl, and piperylmethyl groups is substituted by 1 or 2 independently selected R2B substituents as appropriate; Each R2B is independently selected from C1-6 alkyl and S(O)2Rb22, wherein the C1-6 alkyl group of R2B is substituted with CN as appropriate; each Rb22 is independently selected from H or C1-6 alkyl; R3 is selected from phenyl, cyclopropyl, cyclohexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]pyrazolyl, 5,6-dihydro-4H-pyrrolizo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl, wherein the phenyl, cyclopropyl, cyclohexenyl ... Hexenyl, pyrazolyl, pyrrolidinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyridine, 3,4-dihydro-2H-benzo[b][1,4]pyridine, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl and pyrazolo[1,5-a]pyrimidinyl are each substituted with 1, 2, 3 or 4 independently selected R3A substituents as appropriate;Each R3A is independently selected from methyl, trideuterylmethyl, ethyl, isopropyl, isobutyl, difluoroethyl, trifluoroethyl, methoxy, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidinylmethyl, succinylmethyl, succinylethyl, succinylcarbonyl, dimethylaminocarbonyl, and ethylsulfonylutriyl, wherein the methyl, ethyl, isopropyl, isobutyl, cyclopropyl, cyclopentyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclopropylethyl, benzyl, pyridylmethyl, piperidinylmethyl, succinylmethyl, and succinylethyl of R3A are each substituted by 1, 2, 3, or 4 independently selected R3B substituents as appropriate; Each R3B is independently selected from hydroxyl, methoxy, methylsulfonyl, methyl carbonyl, and cyano; R4 is selected from H and C1-6 alkyl; R5 is selected from H and C1-6 alkyl; each R6 is independently selected from ethyl, tributyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolyl isopropyl, aziridine isopropyl, 2-azibicyclo[2.1.1]hexyl, bicyclo[1.1.1]pentyl, methyl carbonyl, tetrahydropyranylmethyl carbonyl ethyl, propylcarbonyl, dimethylaminocarbonyl, methoxycarbonyl, anilinecarbonyl, ethylsulfonyl, cyclobutylcarbonylamino, cyclopropylsulfonyl and cyclopropylsulfonylamino, wherein R6 is ethyl, tributyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azacyclobutyl, tetrahydrothiophene, pyrazolyl, piperidinyl, pyrimidinyl, cyclopropylmethyl, spiro[3.3]heptylmethyl, benzyl, triazolyl iso propyl, azacyclobutylisopropyl, 2-azabicyclo[2.1.1]hexyl, bicyclo[1.1.1]pentyl, methylcarbonyl, tetrahydropyranylmethylcarbonyl, propylcarbonyl, dimethylaminocarbonyl, methoxycarbonyl, phenylaminocarbonyl, ethylsulfonylurea, cyclobutylcarbonylamino, cyclopropylsulfonylurea, and cyclopropylsulfonylurea are each substituted with one or two independently selected R6A substituents, as appropriate; and each R6A is independently selected from fluorine, oxy, methyl, CN, methoxy, tetrahydropyranyl, methyl carbonyl, amino carbonyl, methyl carbonylamino, ethylamino carbonyl, methoxy carbonyl, methoxy carbonylamino, ethylamino carbonylamino, ethylsulfonyl, and benzenesulfonylamino, wherein each methyl group of R6A is substituted with CN or amino carbonyl as appropriate; and each tetrahydropyranyl group of R6A is substituted with cyanomethyl as appropriate.

53. The compound of claim 1, wherein the compound of formula I is a compound of formula II: II or a pharmaceutically acceptable salt thereof.

54. The compound of claim 1, wherein the compound of formula I is a compound of formula III: III or a pharmaceutically acceptable salt thereof.

55. The compound of claim 1, wherein the compound of formula I is a compound of formula IV: IV or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, 2, 3, 4 or 5.

56. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 55, wherein the compound contains at least one deuterium atom.

57. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 56, wherein the compound contains two or more deuterium atoms.

58. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 57, wherein all hydrogen atoms in the compound are replaced by deuterium atoms.

59. The compound of claim 1 is selected from: 6-methyl-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1-phenyl-2',3,3',5',6,6'-hexahydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-pyran]-7-one; 6-methyl-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1-phenyl-3,4',5',6-tetrahydro-2'H,7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-furan]-7-one; 1-(1-acetylopiperidin-4-yl)-6'-methyl-2'-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1'-phenyl-3',6'-dihydro-7'H-spiro[azacyclobutane-3,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; 3-(6-methyl-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,4'-piperidin]-1'-yl)propionitrile; 3-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)propionitrile; 2-(4-(4-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)-1H-pyrazol-1-yl)tetrahydro-2H-pyran-4-yl)acetonitrile; 3-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-(methyl-d3)-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)propionitrile; 6'-methyl-1'-(1-methyl-1H-indazol-5-yl)-2'-(1-(pyridin-4-ylmethyl)-1H-pyrazol-4-yl)-3',6'-dihydro-7'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridin]-7'-one; 2'-Cyclopropyl-6'-methyl-1'-(1-methyl-1H-indazol-5-yl)-3',6'-dihydro-7'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one;6'-Methyl-2'-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1'-phenyl-3',6'-dihydro-7'H-spiro[cyclobutane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; 6'-Methyl-2'-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1'-phenyl-3',6'-dihydro-7'H-spiro[cyclohexane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; 6-Methyl-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1-phenyl-1'-(2-(tetrahydro-2H-pyran-4-yl)acetylurea)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,3'-pyrrolidin]-7-one; 8-Acetyl-6'-methyl-2'-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1'-phenyl-3',6'-dihydro-7'H-8-azaspiro[bicyclo[3.2.1]octane-3,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; and 3-(4-(4-(6'-methyl-2'-(1-methyl-1H-pyrazol-4-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-1'-yl)phenyl)-1H-pyrazol-1-yl)butyronitrile; or a pharmaceutically acceptable salt thereof.

60. The compound of claim 1 is selected from: 6-methyl-2-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1-phenyl-1'-(pyrimidin-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-7-one; (1R,3r,5S)-6'-methyl-2'-(4-((4-(methylsulfonylurea)piperidin-1-yl)methyl)phenyl)-1'-phenyl-8-(pyrimidin-4-yl)-3',6'-dihydro-7'H-8-azaspiro[bicyclo[3.2.1]octane-3,8'-dipyrrolo[2,3-b:3',2'-d]pyridin]-7'-one; 6-Methyl-2-(1-methyl-1H-pyrazol-4-yl)-1-(2-methylthiazo-5-yl)-1'-(pyrimidin-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-7-one; 6-Methyl-2-(1-methyl-1H-pyrazol-4-yl)-1'-(pyrimidin-4-yl)-1-vinyl-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-7-one; 1-Ethyl-6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1'-(pyrimidin-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-7-one; 1-(3,6-dihydro-2H-pyran-4-yl)-6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1'-(pyrimidin-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-7-one; N-(3-methoxyphenyl)-6-methyl-2-(4-((4-(methylsulfonyl)piperidin-1-yl)methyl)phenyl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,4'-piperidine]-1'-methylamine; 6'-methyl-2'-(1-methyl-1H-pyrazol-4-yl)-1'-(4-((4-(methylsulfonyl)piperidin-1-yl)methyl)phenyl)-3',6'-dihydro-7'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; 2-(1-(ethylsulfonyl)-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)azacyclobutane-3-yl)acetonitrile;2-(1-acetyl-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)azacyclobutane-3-yl)acetonitrile; 3-(cyanomethyl)-N-ethyl-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)azacyclobutane-1-methylamine; 2-(4-fluorophenyl)-2-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)acetamide; (3-(cyanomethyl)-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)aminocarbamate; 1-(3-(cyanomethyl)-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)-3-ethylurea; N-(3-(cyanomethyl)-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-1-phenyl-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)benzenesulfonamide; 2-(1-(2-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)cyclobutyl)acetonitrile;2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(4-(1-(1-lin-4-carbonyl)cyclohex-1-en-1-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(4-(ethylsulfonyl)phenyl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(1-hydroxy-2-methylpropyl-2-yl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-(2-(N-pyrolinyl)ethyl)-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(3-cyclopropyl-1-methyl-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile;2-(1-(2-(1-(1-acetylpiperidin-4-yl)-1H-pyrazole-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrrolo-3-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-2-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(2-methoxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-2-(1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-6-methyl-1-(1-(methyl-d3)-1H-indol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(1-(3,5-difluoro-4-methoxyphenyl)-2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-7-sideoxy-1-(thieno[3,2-c]pyridin-2-yl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile;2-(1-(1-(4-cyclopropylphenyl)-2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 2-(1-(2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-7-sideoxy-1-(4-(trifluoromethoxy)phenyl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; 4-(1'-(1-(cyanomethyl)cyclobutyl)-2-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-6-methyl-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1-yl)benzonitrile; 2-(1-(2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-6-methyl-7-sideoxy-1-(4-(trifluoromethyl)phenyl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclobutyl)acetonitrile; (R)-1-(ethylsulfonylurea)-2'-(1-isopropyl-1H-pyrazol-4-yl)-6'-methyl-1'-(1-methyl-1H-indazol-5-yl)-3',6'-dihydro-7'H-spiro[azacycloheptane-4,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; (S)-1-(ethylsulfonylurea)-2'-(1-isopropyl-1H-pyrazol-4-yl)-6'-methyl-1'-(1-methyl-1H-indazol-5-yl)-3',6'-dihydro-7'H-spiro[azacycloheptane-4,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; 1-(ethylsulfonyl)-2''-(1-isopropyl-1H-pyrazol-4-yl)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; N-((1S,3R)-6'-methyl-1'-(1-methyl-1H-indazol-5-yl)-2'-(1-methyl-1H-pyrazol-4-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-3-yl)cyclopropanesulfonamide;N-((1R,3S)-6'-methyl-1'-(1-methyl-1H-indazole-5-yl)-2'-(1-methyl-1H-pyrazol-4-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-3-yl)cyclopropanesulfonamide; N-((1S,3S)-6'-methyl-1'-(1-(methyl-d3)-1H-indazole-5-yl)-2'-(1-methyl-1H-pyrazol-4-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-3-yl)cyclopropanesulfonamide; N-((1R,3R)-6'-methyl-1'-(1-(methyl-d3)-1H-indazol-5-yl)-2'-(1-methyl-1H-pyrazol-4-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridin]-3-yl)cyclopropanesulfonamide; 6-methyl-2-(4-((4-(methylsulfonyluyl)piperidin-1-yl)methyl)phenyl)-1',3,3',6-tetrahydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,2'-indene]-7-one; 6-Methyl-2-(1-methyl-1H-pyrazol-4-yl)-1-(1-(methyl-d3)-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidine]-1''-formate methyl ester; 1''-Butyryl-6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3,6-dihydro-7H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidine]-7-one; N,N,6-Trimethyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidine]-1''-methylamine; methyl 6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidine]-1''-formate;1''-((2-methoxyethyl)sulfonyl)-6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1-phenyl-3,6-dihydro-7H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,1'-cyclobutane-3',4''-piperidine]-7-one; 4-(1''-butyryl-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,1'-cyclobutane-3',4''-piperidine]-2-yl)-N,N-dimethylcyclohexyl-3-ene-1-methylamine; 1''-Butyryl-6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrrolo-3-yl)-3,6-dihydro-7H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,1'-cyclobutane-3',4''-piperidin]-7-one; (R)-2-(1-((6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrrolo-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-1'-yl)methyl)cyclopropyl)acetonitrile; (S)-2-(1-((6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-1'-yl)methyl)cyclopropyl)acetonitrile; 2-(1-((6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-2-(3-sideoxy-3,4-dihydro-2H-benzo[b][1,4]carbazol-7-yl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidinyl]-1'-yl)methyl)cyclopropyl)acetonitrile; 2-(1-((6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-2-(pyrazolo[1,5-a]pyrimidin-3-yl)-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-1'-yl)methyl)cyclopropyl)acetonitrile; 4-((4-(1'-((1-(cyanomethyl)cyclopropyl)methyl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-2-yl)-1H-pyrazol-1-yl)methyl)benzonitrile;2-(2-((6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-1'-yl)methyl)spiro[3.3]hept-2-yl)acetonitrile; 2-(1-((6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-1'-yl)sulfonyl)cyclopropyl)acetonitrile; 2-(1-((6-methoxy-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,3'-pyrrolidin]-1'-yl)methyl)cyclopropyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)cyclopentyl)acetonitrile; 2-(1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-1'H,3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-pyridin]-1'-yl)cyclopropyl)acetonitrile; 2-(4-methoxy-1-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)cyclohexyl)acetonitrile; 1'-(2-(1H-1,2,3-triazol-4-yl)propyl-2-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-7-one; 1'-(2-(4H-1,2,4-triazol-3-yl)propyl-2-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-7-one;6-Methyl-1'-(3-methyl-1,1-dioxo-tetrahydrothiophene-3-yl)-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-7-one; 2-(1-(2-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-6-methyl-1-(1-(methyl-d3)-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)cyclopentyl)acetamide; (R)-4-methoxy-3-methyl-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1-(1-(methyl-d3)-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)butyronitrile; (S)-4-methoxy-3-methyl-3-(6-methyl-2-(1-methyl-1H-pyrazol-4-yl)-1-(1-(methyl-d3)-1H-indazol-5-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)butyronitrile; 4-(cyanomethyl)-4-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)piperidine-1-carboxylic acid methyl ester; N-(3-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidine]-1'-yl)bicyclo[1.1.1]pent-1-yl)acetamide; 4-(6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-7-sideoxy-6,7-dihydro-3H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-1'-yl)-2-azabicyclo[2.1.1]hexane-2-carboxylic acid methyl ester; 1'-(2-(azacyclobutan-3-yl)propyl-2-yl)-6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3,6-dihydro-7H-spiro[dipyrrolo[2,3-b:3',2'-d]pyridin-8,4'-piperidin]-7-one;1-(ethylsulfonyl)-6''-methyl-1''-(1-(methyl-d3)-1H-indazol-5-yl)-2''-(4-((N-hydroxylinyl)methyl)phenyl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(ethylsulfonyl)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-2''-(1-methyl-1H-pyrazol-4-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 2''-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-1-(ethylsulfonylurea)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(ethylsulfonyl)-2''-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(ethylsulfonylurea)-2''-(1-isopropyl-1H-pyrazol-4-yl)-6''-(methyl-d3)-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 2''-(1-cyclopentyl-1H-pyrazol-4-yl)-1-(ethylsulfonylurea)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(4-(1-(ethylsulfonyl)-6''-methyl-1''-(1-(methyl-d3)-1H-indazol-5-yl)-7''-sideoxy-6'',7''-dihydro-3''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-2''-yl)benzyl)piperidine-4-carboxynitrile;1-(ethylsulfonylurea)-1''-(4-methoxyphenyl)-6''-(methyl-d3)-2''-(4-((N-hydroxylinyl)methyl)phenyl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 2''-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-1-(ethylsulfonylutriyl)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 2''-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-1-(ethylsulfonylurea)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 2''-(1-ethyl-1H-pyrazol-4-yl)-1-(ethylsulfonylurea)-1''-(4-methoxyphenyl)-6''-(methyl-d3)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(ethylsulfonyl)-2''-(1-(2-methoxy-2-methylpropyl)-1H-pyrazol-4-yl)-6''-methyl-1''-(1-(methyl-d3)-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(ethylsulfonylurea)-6''-methyl-1''-(1-methyl-1H-indazol-5-yl)-2''-(1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridinium]-7''-one; 2''-(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]pyrrolidone-3-yl)-1-(ethylsulfonylurea)-6''-methyl-1''-(1-(methyl-d3)-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one;1-(ethylsulfonyl)-2''-(3-methoxy-1-methyl-1H-pyrazol-4-yl)-6''-methyl-1''-(1-(methyl-d3)-1H-indazol-5-yl)-3'',6''-dihydro-7''H-dispiro[azacyclobutane-3,1'-cyclobutane-3',8''-dipyrrolo[2,3-b:3',2'-d]pyridine]-7''-one; 1-(2-amino-2-sideoxyethyl)-N-((1S,3S)-6'-methyl-2'-(1-methyl-1H-pyrazol-4-yl)-1'-(1-(methyl-d3)-1H-indazol-5-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-3-yl)cyclobutane-1-methylamine; 1-(2-amino-2-sideoxyethyl)-N-((1R,3R)-6'-methyl-2'-(1-methyl-1H-pyrazol-4-yl)-1'-(1-(methyl-d3)-1H-indazol-5-yl)-7'-sideoxy-6',7'-dihydro-3'H-spiro[cyclopentane-1,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-3-yl)cyclobutane-1-methylamine; 1''-Butyryl-6-methyl-1-(1-methyl-1H-indazol-5-yl)-2-(1-(methyl-d3)-1H-pyrrolo-3-yl)-3,6-dihydro-7H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidine]-7-one; 1''-Butyryl-6-methyl-1-(1-(methyl-d3)-1H-indazol-5-yl)-2-(1-(methyl-d3)-1H-pyrrolo-3-yl)-3,6-dihydro-7H-dispiro[dipyrrolo[2,3-b:3',2'-d]pyridine-8,1'-cyclobutane-3',4''-piperidine]-7-one; 2'-(1-isopropyl-1H-pyrazol-4-yl)-6'-(methyl-d3)-1'-(1-methyl-1H-indazol-5-yl)-1-((1-methylcyclopropyl)sulfonyl)-3',6'-dihydro-7'H-spiro[azacycloheptane-4,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; and 2'-(1-(1-cyclopropylethyl)-1H-pyrazol-4-yl)-1-(ethylsulfonyl)-6'-(methyl-d3)-1'-(1-methyl-1H-indazol-5-yl)-3',6'-dihydro-7'H-spiro[azacycloheptane-4,8'-dipyrrolo[2,3-b:3',2'-d]pyridine]-7'-one; Or a medically acceptable salt.

61. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 60, wherein the compound is deuterated.

62. A pharmaceutical composition comprising a compound of any one of claims 1 to 61 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

63. A method for inhibiting the activity of a V617F variant of JAK2 kinase, the method comprising contacting the kinase with a compound of any one of claims 1 to 61 or a pharmaceutically acceptable salt thereof.

64. A method of treating cancer in a patient in need, the method comprising administering to the patient a therapeutically effective amount of any one of claims 1 to 61 or a medically acceptable salt thereof.

65. The method of claim 64, wherein the cancer is selected from bladder cancer, breast cancer, cervical cancer, colorectal cancer, small bowel cancer, colon cancer, rectal cancer, anal cancer, endometrial cancer, stomach 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.

66. The method of claim 64, wherein the cancer is a blood cancer.

67. The method of claim 64, 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 or non-Hodgkin's lymphoma (myeloproliferative neoplasm), myelodysplastic syndrome, chronic eosinophilic leukemia, Waldenstrom's macroglubulinemia, pilocellular lymphoma, chronic myeloid lymphoma, acute lymphoblastic lymphoma, AIDS-related lymphoma, and Burkitt's lymphoma.

68. A method for treating a patient with myeloproliferative disorders, the method comprising administering to the patient a therapeutically effective amount of any one of claims 1 to 61 or a medically acceptable salt thereof.

69. The method of claim 68, wherein the myeloproliferative disorder is selected from polycythemia vera, essential thrombocythemia, myelofibrosis with myelometaplasia, primary myelofibrosis, post-essential thrombocythemia myelofibrosis, post-polycythemia vera myelofibrosis, chronic myeloid leukemia, chronic myelomonocytic leukemia, eosinophilia syndrome, and systemic mast cell disease.

70. A method for treating myeloproliferative syndrome in a patient in need, the method comprising administering to the patient a therapeutically effective amount of any one of claims 1 to 61 or a medically acceptable salt thereof.