6-(2-((piperidin-4-yl)amino)pyrimidin-4-yl)-1h-indole-3-carboxamide and 6-(2-(((tetrahydro-2h-pyran-4-yl)amino)pyrimidin-4-yl)-1h-indole-3-carboxamide derivatives as CDK4 inhibitors for the treatment of cancer

Abstract

The present invention relates to compounds of formula (I) as inhibitors of cyclin-dependent kinase 4 (CDK4) for use in methods of treatment of cancer.

Description

[0001] inhibitors and there remains a need to discover CDK inhibitors having novel activityprofiles, in particular those targeting CDK4 that spare off-target CDKs with associated toxicities, including CDK6 and CDK1 associated hematopoietic and / or gastrointestinal toxicities. This application is directed to this need and others.

[0002] SUMMARY

[0003] The present invention relates to, inter alia, compounds of Formula (I):

[0004]

[0005] or pharmaceutically acceptable salts thereof, wherein the constituent members are defined herein.

[0006] The present invention further provides pharmaceutical compositions comprising a compound described herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0007] The present invention further provides methods of inhibiting, comprising contacting the CDK4 with a compound described herein, or a pharmaceutically acceptable salt thereof.

[0008] The present invention further provides methods of inhibiting CDK4 in a patient, comprising administering to the patient a compound described herein, or a pharmaceutically acceptable salt thereof.

[0009] The present invention further provides methods of treating a disease or disorder associated with CDK4 in a patient, comprising administering to the patient a compound described herein, or a pharmaceutically acceptable salt thereof.

[0010] The present invention further provides compounds described herein, or a pharmaceutically acceptable salt thereof, for use in any of the methods described herein.

[0011] The present invention further provides uses of a compound described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for use in any of the methods described herein. DETAILED DESCRIPTION

[0012] The present application provides, inter alia, a compound of Formula (I):

[0013]

[0014] or a pharmaceutically acceptable salt thereof, wherein:

[0015] n is 0, 1, 2, 3. 4, 5, or 6;

[0016] X is O, S, S(O)2, S(O)NRC, or N(-L-R4);

[0017] L is S(O)2, S(O)(=NRb), or S(O)2NRa;

[0018] Ra, Rb, and Rcare each independently selected fromH, Ci-6 alky l and Ci-6 haloalky 1; or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0019] R1is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-14 membered aryl, 4-15 membered heterocycloalkyl, 5-14 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-14 membered aryl-Ci-4 alkyl, 4-15 membered heterocycloalkyl-Ci-4 alkyl, and 5-14 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0020] each R1Ais independently selected fromH, D, halo, CN, NO2, Ci-6 alkyl, C2-6alkenyl, C2-6alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1.4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, NH0Ra11, C(O)Rb11, C(O)NRollRd11, C(O)NRoll(ORa11), C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NR011Rd11, NRcllNRcllRd11, NRcllC(O)Rb11. NRollC(O)ORa11, NRollC(O)NRollRd11.

[0021] NRcllRd11, NRcllC(=NRell)NRcllRd11, NRcllC(=NRell)Rb11,lS(O)Rb11, NRcllS(O)2Rb11, NRcllS(O)(=NRell)Rb11, )Rb11, S(O)NRollRd11, S(O)2Rb11, S(O)2NRcllRd11, )2Rb11, S(O)(=NRell)Rb11, SF5, P(O)RfllRg11,

[0022]

[0023] )(ORhll)(ORni), and BRjllRk11, wherein said Ci-6alkyl. C2.6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0024] each Ra11, Rc11, and Rd11is independently selected fromH, Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaiyl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0025] or, any Rcl1and Rdl1attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2. 3, or 4 independently selected R1Bsubstituents;

[0026] each Rbnis independently selected from C1-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;

[0027] each Rel1is independently selected from H, OH, CN, Ci-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0028] each Rfl1and Rgl1are independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0029] each Rhnand R111is independently selected from H, Ci-6 alkyd, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl; each R'11and Rkl1is independently selected from OH. Ci-6 alkoxy, and Ci-6 haloalkoxy;

[0030] or any R'" and Rkl1attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyd group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-6 alkyl and Ci-6 haloalkyl; each R1Bis independently selected from H, D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl. ORa12, SRa12, NHORa12, C(O)Rb12, C(O)NRcl2Rd12, C(O)NRc12(ORa12), C(O)ORa12, OC(O)Rb12, OC(O)NRol2Rd12, NRcl2Rd12, NRcl2NRcl2Rd12, NRcl2C(O)Rb12. NRol2C(O)ORa12, NRcl2C(O)NRol2Rd12.

[0031] C(=NRel2)Rb12, C(=NRel2)NRcl2Rd12, NRcl2C(=NRel2)NRcl2Rd12, NRcl2C(=NRel2)Rb12, NRol2S(O)NRcl2Rd12, NRcl2S(O)Rb12, NRcl2S(O)2Rb12, NRcl2S(O)(=NRel2)Rb12, NRol2S(O)2NRcl2Rd12, S(O)Rb12, S(O)NRol2Rd12, S(O)2Rb12, S(O)2NRol2Rd12, OS(O)(=NRel2)Rb12, OS(O)2Rb12, S(O)(=NRel2)Rb12, SF5, P(O)Rfl2Rg12, OP(O)(OR1112)(ORi12), P(O)(ORhl2)(ORi12), and BR'l2Rkl2. wherein said Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyL Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cloalkyl-C 1-4 alky 1, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaiyl-Ci-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected RGsubstituents;

[0032] each Ra12, Rc12, and Rd12is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cloalkyl-C 1-4 alky 1, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl. C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalky I-C1-4 alkyl, and 5-6 membered heteroary 1-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0033] or, any Rcl2and Rdl2attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0034] each Rb12is independently selected from C1-6alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cy cloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0035] each Rel2is independently selected from H, OH, CN, Ci-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0036] each Rtl2and Rgl2are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0037] each Rhl2and R112is independently selected from H, Ci-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky I-C1-4 alkyl, phenyl-Ci-4 alky l, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0038] each R'12and Rkl2is independently selected from OH, Ci-6 alkoxy, and Ci-6 haloalkoxy;

[0039] or any R'12and Rkl2attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyd group optionally substituted with 1. 2. 3, or 4 substituents independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0040] R2A, R2B, and R2Care each independently selected from H, D, halo, CN, Ci-6 alkyl, Cu 6 haloalkyl, C3-7 cycloalkyd, phenyl, 4-8 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl. ORa2, SRa2, NHORa2, C(O)Rb2, C(O)NRo2Rd2, C(O)NRc2(ORa2), C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2NRc2Rd2, NRo2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, C(=NRe2)Rb2, C(=NRe2)NRc2Rd2, NRc2C(=NRe2)NRc2Rd2, NRo2C(=NRe2)Rb2, NRc2S(0)NRo2Rd2, NRo2S(0)Rb2, NRc2S(O)2Rb2, NRc2S(O)(=NRe2)Rb2, NRc2S(O)2NRo2Rd2, S(O)Rb2. S(O)NRo2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryd, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-8 membered heterocycloalkyd-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyd are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0041] each Ra2, Rc2. and Rd2is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalky 4, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryd, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0042] or, any Rc2and Rd2attached to the same N atom, together with the N atom to which they are attached, form a 4-8 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0043] each Rb2is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0044] each Re2is independently selected from H. OH, CN. C1-6 alkyl, C1-6 alkoxy. C1-6 haloalkyl, and C 1-6 haloalkoxy;

[0045] each R3is independently selected from D, halo, CN, C1-6 alkyl, C 1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl. OR13. SRa3. NHORa3, C(O)Rb3, C(O)NRc3Rd3.

[0046] C(O)NRc3(ORa3), C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3NRc3Rd3, NRo3C(O)Rb3, NRo3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3C(=NRe3)Rb3, NRc3S(O)NRc3Rd3, NRc3S(O)Rb3, NRo3S(O)2Rb3. NRc3S(O)(=NRe3)Rb3, NRc3S(O)2NRo3Rd3. S(O)Rb3. S(O)NRo3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3, wherein said Cue alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0047] each Ra3, Rc3, and Rd3is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl- Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0048] each Rb3is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0049] each Re3is independently selected from H, OH, CN, C1-6 alkyd, C1-6 alkoxy, C1-6 haloalkyl, and C 1-6 haloalkoxy;

[0050] R4is selected from C1-6 alkyl, C1-6 haloalky l, C3-10 cycloalky l, 6-10 membered ary l, 4-10 membered heterocycloalkyl, 5-10 membered heteroary l. C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl; wherein said C1-6 alkyd, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered ary l, 4-10 membered heterocycloalkyl, 5-10 membered heteroai 1, C3-10 cycloalkyl-C 1-4 alky l, 6-10 membered aryd-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0051] each R4Ais independently selected from D, halo, CN, NO2, C1-6 alky 1, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl. 5-6 membered heteroar l-C 1.4 alkyl, ORa41, SRa41, NHORa41, C(O)Rb41, C(O)NRc41Rd41, C(O)NRc41(ORa41), C(O)ORa41, OC(O)Rb41, OC(O)NRo41Rd41, NRc41Rd41, NRc41NRc41Rd41, NRc4lC(O)Rb41, NRo41C(O)ORa41, NRc41C(O)NRc41Rd41, C(=NRe41)Rb41, C(=NRe41)NRo41Rd41, NRo41C(=NRe41)NRc41Rd41, NRc41C(=NRe41)Rb41. NRo41S(O)NRo41Rd41, NRc41S(O)Rb41, NRc41S(O)2Rb41, NRc41S(O)(=NRe41)Rb41, NRc41S(O)2NRc41Rd41, S(O)Rb41, S(O)NRc41Rd41, S(O)2Rb41, S(O)2NRc41Rd41, OS(O)(=NRe41)Rb41, and OS(O)2Rb41, S(O)(=NRe41)Rb41, wherein said Ci-6 alkyl, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0052] each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl. phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0053] or, any Rc41and Rd41attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered helerocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0054] each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0055] each Re41is independently selected from H, OH, CN, Ci-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, Ci-6 haloalkoxy, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0056] each R4Bis independently selected from D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered lietcroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl. OR142, SRa42. NHORa42, C(O)Rb42. C(O)NRc42Rd42, C(O)NRc42(ORa42), C(O)ORa42, OC(O)Rb42, OC(O)NRo42Rd42, NRc42Rd42, NRc42NRc42Rd42, NRo42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRo42Rd42, C(=NRe42)Rb42, C(=NRe42)NRo42Rd42, NRc42C(=NRe42)NRc42Rd42, NRc42C(=NRe42)Rb42, NRc42S(O)NRc42Rd42, NRc42S(O)Rb42, NRo42S(O)2Rb42. NRo42S(O)(=NRe42)Rb42. NRo42S(O)2NRo42Rd42, S(O)Rb42. S(O)NRc42Rd42, S(O)2Rb42, S(O)2NRc42Rd42, OS(O)(=NRe42)Rb42, and OS(O)2Rb42, S(O)(=NRe42)Rb42, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0057] each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl. phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected RGsubstituents;

[0058] each Rb42is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C 3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0059] each Re42is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, Ci-6 haloalkoxy, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0060] R3is selected from halo, CN, C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 alkoxy, C 1-3 haloalkoxy, amino, C 1-3 alkylamino, di(Ci-3 alkyl)amino, cyano-C 1-4 alkyl, HO-C1-4 alkyl, C1-3 alkoxy-Ci-4 alkyl. and C3-4 cycloalkyl;

[0061] R6is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl; which are each optionally substituted by 1, 2, 3. 4, 5, or 6 independently selected R6Asubstituents;

[0062] R7is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl. C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1.4 alky l, 4-8 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0063] or R6and R7, together with the nitrogen atom to which they are attached, form a 4-15 membered heterocycloalkyl moiety or a 5-10 membered heteroaryl moiety, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents;

[0064] each R6Ais independently selected from D, halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl- Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl-Ci-4 alkyl,

[0065]

[0066] OP(O)(ORh61)(OR161), P(O)(ORh61)(OR161), and BRj61Rk61, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0067] each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alky l, wherein said Ci-6 alkyl, C2-6alkenyl, C2-6alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl. 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0068] or, any Rc61and Rd61attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0069] each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0070] each Re61is independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, C 1-6 haloalkoxy, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;

[0071] each R161and Rg61are independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;

[0072] each Rh61and R161is independently selected from H, Ci-6 alkyd, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalky l, 5-10 membered heteroary l, C3-10 cycloalkyl-Ci-4 alky l, 6-10 membered aryl-C1-4alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;

[0073] each R'61and Rk61is independently selected from OH, Ci-6 alkoxy, and Ci-6 haloalkoxy;

[0074] or any R'61and Rk61attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyd group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0075] each R6Bis independently selected from D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalky l, C3-10 cycloalky 1, 6-10 membered ary l, 4-10 membered heterocycloalk l, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl-Ci-4 alkyl.

[0076]

[0077] OP(O)(ORh62)(ORi62), P(O)(ORh62)(ORi62), and BRj62Rk62, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C1-4alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0078] each Ra62, Rc62, and Rd62is independently selected from H, C1-6alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C1-4alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0079] or, any Rc62and Rd62attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyd group, which is optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0080] each Rb62is independently selected from Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10cycloalkyl-C1-4alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-C1-4alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1. 2, 3, or 4 independently selected R6Csubstituents;

[0081] each Re62is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalky l, 5-10 membered heteroary l, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C1-4alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl;

[0082] each Rf62and Rg62are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkeny l, C2-6 alkyny l, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroary l, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C1-4alkyl;

[0083] each Rh62and Ri62is independently selected from H, C1-6alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered ary l, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl;

[0084] each Rj62and Rk62is independently selected from OH, Ci-6 alkoxy, and Ci-6 haloalkoxy;

[0085] or any R'62and Rk62attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6alkyl and C1-6haloalkyl; each R6Cis independently selected from D, halo, CN, NO2, C1-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa63, SRa63, NHORa63,

[0086]

[0087] OP(O)(ORh63)(ORi63), P(O)(ORh63)(ORi63), and BRj63Rk63, wherein said Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroary l-C 1-4 alky l are each optionally substituted with 1, 2. 3, or 4 independently selected RGsubstituents;

[0088] each Ra63, Rc63, and Rd63is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cy cloalkyl-C 1-4 alky 1, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0089] or, any Rc63and Rd63attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0090] each Rb63is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0091] each Re63is independently selected from H, OH. CN, Ci-6 alkyl. Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0092] each R163and Rg63are independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl;

[0093] each R1’63and R163is independently selected from H, C1-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alky 1, 4-7 membered heterocycloalky 1-C 1-4 alky 1, and 5-6 membered heteroaryl-C 1-4 alkyl;

[0094] each R'63and Rk63is independently selected from OH. C1-6 alkoxy, and C1-6 haloalkoxy;

[0095] or any Rj63and Rk63attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalky 1 group optionally substituted with 1, 2. 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl;

[0096] R8is selected from H, D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-C1-4 alkyl, 4-8 membered heterocy cloalkyl-Ci-4 alky l, 5-6 membered heteroary 1-C 1-4 alky 1, ORa8, SRa8, NHORa8, C(O)Rb8, C(O)NRc8Rd8, C(O)NRc8(ORa8), C(O)ORa8, OC(O)Rb8, OC(O)NRc8Rd8, NRc8Rd8, NRc8NRc8Rd8. NRc8C(O)Rb8, NRc8C(O)ORa8, NRc8C(O)NRc8Rd8, C(=NRe8)Rb8, C(=NRe8)NRc8Rd8, NRc8C(=NRe8)NRc8Rd8, NRc8C(=NRe8)Rb8, NRc8S(O)NRc8Rd8, NRc8S(O)Rb8, NRc8S(O)2Rb8, NRc8S(O)(=NRe8)Rb8, NRc8S(O)2NRc8Rd8, S(O)Rb8, S(O)NRc8Rd8, S(O)2Rb8, and S(O)2NRc8Rd8, wherein said C1-6alkyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0097] each Ra8, Rc8, and Rd8is independently selected from H, C1-6alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6alkyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl. 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-8 membered heterocy cloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl- Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0098] or, any Rc8and Rd8attached to the same N atom, together with the N atom to which they are attached, form a 4-8 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0099] each Rb8is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0100] each Re8is independently selected from H, OH, CN, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, and C1-6 haloalkoxy; and

[0101] each RGis independently selected from OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino. thio, Ci-3 alkylthio, C1-3 alkylsulfmyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3alkylcarbonylamino, C1-3 alkoxy carbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alky lsulfonylamino, aminosulfonyl, C1-3 alky laminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl )aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.

[0102] In some embodiments, n is 0, 1, or 2.

[0103] In some embodiments, n is 1 or 2.

[0104] In some embodiments, n is 0.

[0105] In some embodiments, n is 1.

[0106] In some embodiments, n is 2.

[0107] In some embodiments, X is O, S(O)2, or N(-L-R4).

[0108] In some embodiments, X is O.

[0109] In some embodiments, X is S.

[0110] In some embodiments, X is S(O)2.

[0111] In some embodiments, X is S(O)NRC.

[0112] In some embodiments, X is N(-L-R4).

[0113] In some embodiments, Lis S(O)2. In some embodiments, L is S(O)2NRa, wherein Rais H, Ci-6 alkyl, or Ci-6 haloalky 1, or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

[0114] In some embodiments, R1is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl. C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0115] In some embodiments, R1is selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0116] In some embodiments, R1is selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0117] In some embodiments, R1is selected from C1-6 alkyl, C1-6 haloalkyl, and C3-10 cycloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0118] In some embodiments, R1is selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, and 4-7 membered heterocycloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0119] In some embodiments, R1is selected from C1-6 alkyl, C1-6 haloalkyl, and C3-7 cycloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0120] In some embodiments, R1is selected from C1-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1. 2, 3, or 4 independently selected R1Asubstituents.

[0121] In some embodiments, R1is C3-7 cycloalkyl, which is optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0122] In some embodiments, R1is selected from C1-6 alky l, C1-6 haloalkyl, and C3-7 cycloalkyl.

[0123] In some embodiments, R1is C1-6 alkyl.

[0124] In some embodiments, R1is C3-7 cycloalky 1. In some embodiments:

[0125] each R1Ais independently selected from H, D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)ORa11, NRc11C(O)NRc11Rd11, NRc11S(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRc11Rd11, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1.4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;

[0126] each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, C1-6 haloalky l, C2-6 alkeny l, C2-6 alky nyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky 1, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alky l. phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, pheny l, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;

[0127] each Rb11is independently selected from C1-6alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalky l-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl. and 5- 6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0128] each R1Bis independently selected from H, D, halo, CN, Ci-6 alky l, C1-6 haloalkyl, C3- 7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa12, SRa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRc12Rd12, NRc12C(O)Rb12, NRc12C(O)ORa12, NRc12C(O)NRc12Rd12, NRc12S(O)2Rb12, NRc12S(O)2NRc12Rd12, S(O)2Rb12, and S(O)2NRc12Rd12, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0129] each Ra12, Rc12, and Rd12is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents; and

[0130] each Rb12is independently selected from C1-6alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

[0131] In some embodiments:

[0132] each R1Ais independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1.4 alkyl. ORa11, SRa11. C(O)Rb11, C(O)NRcllRd11. C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRc11C(O)NRc11Rd11, NRc11S(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRc11Rd11, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0133] each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalky I-C1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents; each Rb11is independently selected from C1-6alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0134] each R1Bis independently selected from H, D, halo, CN, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaiyl-Ci-4 alkyl, ORa12, SRa12, C(O)Rb12, C(O)NRcl2Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRcl2Rd12, NRc12Rd12, NRc12C(O)Rbl2, NRcl2C(O)ORa12, NRcl2C(O)NRcl2Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rdl2_ S(O)2Rb12, and S(O)2NRcl2Rd12;

[0135] each Ra12, Rc12, and Rd12is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl; and

[0136] each Rb12is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0137] In some embodiments:

[0138] each R1Ais independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaiyl-Ci-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRollRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rbll_ NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRollS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C1-6alkyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0139] each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalky l are each optionally substituted with 1 or 2 independently selected R1Bsubstituents;

[0140] each Rb11is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1 or 2 independently7selected R1Bsubstituents;

[0141] each R1Bis independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa12, SRa12. C(O)Rb12, C(O)NRol2Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRol2Rd12, NRc12Rd12, NRc12C(O)Rb12NRol2C(O)ORa12, NRcl2C(O)NRcl2Rd12, NRol2S(O)2Rbl2_ NRcl2S(O)2NRcl2Rd12, S(O)2Rb12, and S(O)2NRcl2Rd12; each Ra12, Rc12, and Rd12is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and

[0142] each Rb12is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0143] In some embodiments:

[0144] each R1Ais independently selected fromH, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, 4-5 membered heterocycloalkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRollRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11. NRcllC(O)NRcllRd11, NRollS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11;

[0145] each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl; and

[0146] each Rb11is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0147] In some embodiments:

[0148] each R1Ais independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa11, SRa11, C(O)Rb11, C(O)NRollRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NR011Rd11, NRcllC(O)Rb11, NRollC(O)ORa11, NRcllC(O)NRollRd11. NRollS(O)2Rb11.

[0149] NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRc11Rd11; and

[0150] each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0151] each Rb11is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0152] In some embodiments:

[0153] each R1Ais independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa11, andNRc11Rd11; and

[0154] each Ra11, Rcl1, and Rdnis independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl.

[0155] In some embodiments, R2A, R2B, and R2Care each independently selected from H, D, halo, CN, Ci-6 alky l, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alky l, phenyl-C 1-4 alkyl, 4-8 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said C1-6alkyl, C1-6haloalkyl, C3-7 cycloalkyl, pheny l, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-8 membered heterocycloalky I-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents. In some embodiments, R2A, R2B, and R2Care each independently selected from H, D, halo, CN, Ci-6 alkyl, Cue haloalky 1, C(O)Rb2, C(O)NRo2Rd2, C(O)ORa2. OC(O)Rb2.

[0156] OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said Ci-6alkyl and Ci-6haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents.

[0157] In some embodiments, R2A, R2B, and R2Care each independently selected from H, D, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl.

[0158] In some embodiments, R2A, R2B, and R2Care each independently selected from H, halo, CN, Ci-3 alky l, and C1-3 haloalkyl.

[0159] In some embodiments, R2A, R2B, and R2Care each independently selected from H, halo, and CN.

[0160] In some embodiments, R2A, R2B, and R2Care each independently selected from H, halo, and ORa2.

[0161] In some embodiments, R2A, R2B, and R2Care each independently selected from H and halo.

[0162] In some embodiments, R2A, R2B, and R2Care each independently selected from H and F.

[0163] In some embodiments, R2Ais H or halo; R2Bis H; and R2Cis halo.

[0164] In some embodiments, R2Ais H or F; R2Bis H; and R2Cis F.

[0165] In some embodiments:

[0166] each Ra2, Rc2, and Rd2is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and

[0167] each Rb2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0168] In some embodiments, each R3is independently selected from D, halo, CN, Ci-6 alkyl, C1.6 haloalkyl, C3-4 cycloalkyl, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRo3C(0)NRo3Rd3, NRc3S(O)2Rb3, NRc3S(O)2NRo3Rd?, S(O)2Rb3, and S(O)2NRc3Rd3, wherein said Cu6alkyl, Ci-6haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents.

[0169] In some embodiments, each R3is independently selected from D, halo, CN, Ci-6 alkyd, Ci-6 haloalkyl, ORa3, andNRc?Rd3, wherein said Ci-6 alkyd and Ci-6 haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents. In some embodiments, each R- is independently selected from halo, CN, C1-3 alkyl, Ci-shaloalkyl, OR“3, and NRo3Rd3. wherein said C1-3 alkyl and C1-3 haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents.

[0170] In some embodiments, each Ra3, Rc3, and Rd3is independently selected from H, C1-6 alky l, and Ci-6 haloalky l, wherein said C1-6 alkyl and C1-6 haloalkyl are each optionally substituted with 1, 2. 3, or 4 independently selected RGsubstituents; and each Rb3is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

[0171] In some embodiments, each Ra3, R°3, and Rd3is independently selected from H, Ci-6 alky l, and Ci-6 haloalky l; and each Rb3is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0172] In some embodiments, each R3is independently selected from -C1-4 alkylene-OR‘13, -Ci-4alkylene-NRo3Rd3, ORa3, and NRc3Rd3.

[0173] In some embodiments, each R- is OH.

[0174] In some embodiments, R4is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl; yvherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

[0175] In some embodiments, R4is selected from Ci-6 alkyd and Ci-6 haloalkyl; wherein said Ci-6 alkyl and Ci-6 haloalk l are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

[0176] In some embodiments, R4is selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0177] In some embodiments:

[0178] each R4Ais independently selected from D, halo, CN, Ci-6 alky l, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroar l, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alky 1, 5-6 membered heteroatyl-Ci-4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRo41Rd41, NRc41Rd41, NRo41C(O)Rb41, NRc41C(O)ORa41, NRo41C(O)NRc41Rd41, NRo41S(O)2Rb41, NRo41S(O)2NRc41Rd41. S(O)2Rb41, and S(O)2NRo41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0179] each Ra41, R°41, and Rd41is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0180] each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaiyl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0181] each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1.4 alkyl, ORa42, SRa42, C(O)Rb42, C(O)NRo42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42C(O)Rb42. NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRo42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42, wherein said C1-6alkyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0182] each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, Ci-6 haloalky 1, C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary 1, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroary 1-C1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected RGsubstituents; and each Rb42is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

[0183] In some embodiments:

[0184] each R4Ais independently selected from D, halo, CN, NO2. C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaiyl-C 1.4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41_ NRo41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0185] each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0186] each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0187] each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa42, SRa42, C(O)Rb42, C(O)NRo42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRo42Rd42, NRo42C(O)Rb42, NRo42C(O)ORa42, NRc42C(O)NRo42Rd42, NRo42S(O)2Rb42.

[0188] NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42; each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and

[0189] each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0190] In some embodiments:

[0191] each R4Ais independently selected from D, halo, CN, NO2, C1-6 alky l, Ci-6 haloalkyl, ORa41, SRa41. C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rh41, OC(O)NRo41Rd41, NRc41Rd41, NRc41C(O)Rb41NRo41C(O)ORa41, NRc41C(O)NRc41Rd41, NRo41S(O)2Rb41.

[0192] NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said Ci-6alkyl and Ci-6haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0193] each Ra41, Rc41. and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0194] each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0195] each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa42, SRa42, C(O)Rb42, C(O)NRo42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRo42Rd42, NRo42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRo42Rd42, NRc42S(O)2Rb42, NRo42S(O)2NRo42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;

[0196] each Ra42, Rc42. and Rd42is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and

[0197] each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalk l.

[0198] In some embodiments:

[0199] each R4Ais independently selected from D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl. ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRo41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41;

[0200] each Ra41, R°41. and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and

[0201] each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0202] In some embodiments, R5is selected from halo, CN, C1-4 alkyl, C1-4 haloalky l, cyano-C1-4 alkyl, HO-C1-4 alkyl. C1-3 alkoxy-Ci-4 alkyl, and C3-4 cycloalkyl.

[0203] In some embodiments, R5is selected from halo. CN, C1-4 alkyl, and C1-4 haloalkyl. In some embodiments, R3is selected from halo and CN. In some embodiments, R5is selected from F, Cl, and CN.

[0204] In some embodiments, R5is halo.

[0205] In some embodiments, R5is F.

[0206] In some embodiments, R3is Cl.

[0207] In some embodiments, R5is CN.

[0208] In some embodiments:

[0209] R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alky l, 6-10 membered aryl-Ci-4 alky l, 4-10 membered heterocycloalkyl-Ci-4 alky l, and 5-10 membered heteroaryl-C 1-4 alkyl; which are each optionally substituted by 1, 2, 3. or 4 independently selected R6Asubstituents;

[0210] R7is selected from H, C1-6 alkyl, and Ci-6 haloalkyl, each of which are optionally substituted by 1, 2, 3, or 4 independently selected RGsubstituents;

[0211] or R6and R7, together with the nitrogen atom to which they are attached, form a 4-15 membered heterocycloalkyl moiety or a 5-10 membered heteroaryl moiety, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents.

[0212] In some embodiments:

[0213] R6is selected from C1-6 alkyl, C1-6 haloalky l, C3-10 cycloalkyl, 6-10 membered ary l, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl; which are each optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents;

[0214] R7is selected fromH, Ci-6 alkyl, and Ci-6 haloalky l;

[0215] or R6and R7. together with the nitrogen atom to which they are attached, form a 4-10 membered heterocycloalkyl moiety or a 5-6 membered heteroaryl moiety7, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents.

[0216] In some embodiments:

[0217] R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyd, 6-10 membered aryl-Ci-4 alkyd, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyd; which are each optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents; and

[0218] R7is selected from H, Ci-6 alkyl, and Ci-6 haloalkyl, each of which are optionally substituted by 1, 2, 3, or 4 independently selected RGsubstituents. In some embodiments:

[0219] R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl. 6-10 membered aryl. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyd, 6-10 membered aryl-Ci-4 alkyd, 4-10 membered heterocycloalkyl-Ci-4 alkyd, and 5-10 membered heteroaryd-C 1-4 alkyd; which are each optionally substituted by 1, 2, 3, or 4 independently-selected R6Asubstituents; and

[0220] R7is selected from H, C1-6 alkyl, and Ci-6 haloalkyl.

[0221] In some embodiments, each R6Ais independently selected from halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-10 cy cloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyd, 5-10 membered heteroaryl, ORa61, NRc61Rd61. and S(O)2Rb61, wherein said Ci-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl. 6-10 membered aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents.

[0222] In some embodiments, each R6Ais independently selected from halo, CN, C1-3 alkyd, C1-3 haloalkyl, C3-7 cycloalkyl, 4-6 membered heterocycloalkyd, 5-6 membered heteroaryl, ORa61, NRc61Rd61, and S(O)2Rb61, wherein said C1-3 alkyl, C3-7 cycloalky 1, and 5-6 membered heteroaryl are each optionally substituted with 1, 2, or 3 independently selected R6Bsubstituents.

[0223] In some embodiments:

[0224] each R6Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C -iocycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryd-C 1-4 alkyl,

[0225]

[0226] lkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyd, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R6Bsubstituents;

[0227] each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyd, Ci-6 haloalky l, C2-6 alkenyl, C2-6 alky nyl, C3-10 cycloalkyd, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C1-4alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0228] or, any Rc61and Rd61attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyd group, which is optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0229] each Rb61is independently selected from Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10cycloalkyl-C1-4alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-C1-4alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1. 2, 3, or 4 independently selected R6Bsubstituents;

[0230] each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalky 4, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary 4, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa62, SRa62, C(O)Rb62, C(O)NRo62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62, NRc62C(O)Rb62. NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, NRo62S(O)2Rb62, NRc62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62, wherein said C1-6 alkyd, Ci-6 haloalkyl, C3-7 cycloalkyl, pheny l, 4-7 membered heterocycloalky l, 5-6 membered heteroaiyl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0231] each Ra62, Rc62, and Rd62is independently selected from H, C1-6alkyl, Ci-6 haloalky 1, C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary 4, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary!, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroar 4-C1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected R6Csubstituents; each Rb62is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0232] each R6Cis independently selected from D, halo, CN, C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaiyl-Ci-4alkyl, ORa63, SRa63, C(O)Rb63, C(O)NRc63Rd63, C(O)ORa63, OC(O)Rb63, OC(O)NRc63Rd63, NRc63Rd63, NRc63C(O)Rb63, NRc63C(O)ORa63, NRc63C(O)NRc63Rd63, NRc63S(O)2Rb63, NRc63S(O)2NRc63Rd63. S(O)2Rb63, and S(O)2NRc63Rd63, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0233] each Ra63, Rc63, and Rd63is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents; and

[0234] each Rb63is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

[0235] In some embodiments:

[0236] each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6alkenyl, C2-6alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, ORa61, SRa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61. NRo61S(O)2Rb61, NRc61S(O)2NRc61Rd61, S(O)2Rb61, and S(O)2NRc61Rd61, wherein said Ci-6alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selectedR6Bsubstituents;

[0237] eachRa61,Rc61, andRd61is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyd, 6-10 membered aryl, 4-10 membered heterocycloalky l, 5-10 membered heteroaryl, C3-10 cycloalky I-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C 1.4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alky l are each optionally substituted with 1, 2, 3, or 4 independently selectedR6Bsubstituents;

[0238] eachRb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cy cloalky l, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selectedR6Bsubstituents;

[0239] eachR6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl. 5-6 membered heteroaiyl-C 1.4 alkyl, ORa62, SRa62, C(O)Rb62, C(O)NRc62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRo62Rd62, NRc62Rd62, NRc62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, NR°62S(O)2Rb62, NRc62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRo62Rd62, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selectedR6Csubstituents;

[0240] eachRa62,R°62, andRd62is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0241] each Rb62is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0242] each R6Cis independently selected from D, halo, CN, C1-6 alkyl, Ci-6 haloalkyl. ORa63, SRa63, C(O)Rb63, C(O)NRc63Rd63, C(O)ORa63, OC(O)Rb63, OC(O)NRc63Rd63, NRc63Rd63, NRo63C(O)Rb63, NRc63C(O)ORa63, NRc63C(O)NRc63Rd63, NRc63S(O)2Rb63, NRo63S(O)2NRc63Rd63, S(O)2Rb63, and S(O)2NRc63Rd63;

[0243] each Ra63, R°63. and Rd63is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; and

[0244] each Rb63is independently selected from C1-6 alkyl and C1-6 haloalkyl.

[0245] In some embodiments:

[0246] each R6Ais independently selected from D, halo, CN, C1-6 alkyl, C1-6 haloalkyl. C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaiyl-Ci-4alkyl, ORa61, SRa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRo61S(O)2Rb61, NRo61S(O)2NRo61Rd61. S(O)2Rb61, and S(O)2NRo61Rd61, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0247] each Ra61, Rc61, and Rd61is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl- Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0248] each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0249] each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1.4 alkyl, ORa62, SRa62. C(O)Rb62, C(O)NRo62Rd62. C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62, NRc62C(O)Rb62, NRc62C(O)ORa62, NRo62C(O)NRc62Rd62, NRc62S(O)2Rb62, NRc62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRo62Rd62, wherein said C1-6 alkyl, Ci-6 haloalky l, C3-7 cycloalky 1, pheny l, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0250] each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, C1-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected R6Csubstituents;

[0251] each Rb62is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0252] each R6Cis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalky l, ORa63, SRa63, C(O)Rb63, C(O)NRo63Rd63, C(O)ORa63, OC(O)Rb63. OC(O)NRc63Rd63, NRo63Rd63, NRc63C(O)Rb63, NRc63C(O)ORa63. NRc63C(O)NRc63Rd63, NRc63S(O)2Rb63.

[0253] NRc63S(O)2NRc63Rd63, S(O)2Rb63, and S(O)2NRc63Rd63; each Ra63, Rc63, and Rd63is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and

[0254] each Rb63is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0255] In some embodiments:

[0256] each R6Ais independently selected from D, halo, CN, Ci-6 alky l, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaiyl-C 1.4 alkyl, ORa61, SRa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRo61Rd61, NRc61Rd61, NRo61C(O)Rb61, NRc61C(O)ORa61, NRc6lC(O)NRc61Rd61, NRc61S(O)2Rb61, NRo61S(O)2NRo61Rd61, S(O)2Rb61, and S(O)2NRc61Rd61, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0257] each Ra61, R°61. and Rd61is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alky 1, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0258] each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cy cloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0259] each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. ORa62, SRa62, C(O)Rb62, C(O)NRc62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62, NRc62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, NRc62S(O)2Rb62, NRo62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62;

[0260] each Ra62, R°62, and Rd62is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and

[0261] each Rb62is independently selected from Ci-6 alkyl and Ci-6 haloalkyl. In some embodiments:

[0262] each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. C3-5 cycloalkyl, 4-5 membered heterocycloalkyd, ORa61, SRa61, C(O)Rb61, C(O)NRo61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRo61C(O)NRc61Rd61, NRo61S(O)2Rb61, NRc61S(O)2NRc61Rd61, S(O)2Rb61, and S(O)2NRo61Rd61, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents; each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-5 cycloalkyd, and 4-5 membered heterocycloalkyl, wherein said Ci-6 alky l, C1-6 haloalkyl, C1-6 alkyl, Ci-6 haloalky l, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl are each optionally substituted with 1 or 2 independently selected R6Bsubstituents;

[0263] each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyd, and 4-5 membered heterocycloalkyl, which are each optionally substituted with 1 or 2 independently selected R6Bsubstituents;

[0264] each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalky l. ORa62, SRa62, C(O)Rb62, C(O)NRc62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62, NRc62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, NRc62S(O)2Rb62, NRo62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62;

[0265] each Ra62, R°62, and Rd62is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and

[0266] each Rb62is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0267] In some embodiments:

[0268] each R6Ais independently selected from halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl. 4-5 membered heterocycloalkyd. ORa61, SRa61, C(O)Rb61, C(O)NRo61Rd61.

[0269] C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61C(O)Rh61, NRo61C(O)ORa61, NRo61C(O)NRo61Rd61, NRc61S(O)2Rb61, NRc61S(O)2NRc61Rd61, S(O)2Rb61, and S(O)2NRo61Rd61, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalky l are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents; each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl, wherein said C1-6alkyl, C1-6haloalkyl, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl are each optionally substituted with 1 or 2 independently selected R6Bsubstituents; each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl, which are each optionally substituted with 1 or 2 independently selected R6Bsubstituents; and

[0270] each R6Bis independently selected from OH, CN, halo, C1-3 alkyl, C1-3 haloalkyl, cyano-Ci-3 alky l, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, and C1-3 alkylcarbonylamino.

[0271] In some embodiments:

[0272] each R6Ais independently selected from halo, CN, Ci-6 alkyl, and C1-6 haloalkyl, wherein said C1-6 alkyl and Ci-6 haloalkyl. are each optionally substituted with 1 or 2 independently selected R6Bsubstituents; and

[0273] each R6Bis independently selected from OH, CN, halo, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, C 1-3 haloalkoxy, amino, C 1-3 alkylamino, and di(Ci-3 alkyl)amino.

[0274] In some embodiments:

[0275] each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, ORa61, NRo61Rd61, and S(O)2Rb61, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl. 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3. or 4 independently selected R6Bsubstituents;

[0276] each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0277] each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, and C3-10 cycloalkyl;

[0278] each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered ary l, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, ORa62, NRo62Rd62, and S(O)2Rb62;

[0279] each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyd, 6-10 membered aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroary l; and

[0280] each Rb62is independently selected from Ci-s alkyl and Ci-6 haloalkyl.

[0281] In some embodiments: each R6Ais independently selected from halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl. ORa61, NRc61Rd61, and S(O)2Rb61, wherein said Ci-6 alkyl, C3.10 cycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 independently selected R6Bsubstituents;

[0282] each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;

[0283] each Rb61is independently selected from Ci-6 alkyl and C3-10 cycloalkyl;

[0284] each R6Bis independently selected from D, halo, CN, C1-6 alkyl, ORa62, andNRc62Rd62.and

[0285] each Ra62, R°62, and Rd62is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl.

[0286] In some embodiments, R8is selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, 4-6 membered heterocycloalkyl, ORa8, SRa8, C(O)Rb8, C(O)NRc8Rd8, C(O)ORa8, OC(O)Rb8, OC(O)NRc8Rd8, NRc8Rd8, NRc8C(O)Rb8, NRo8C(O)ORa8, NRc8C(O)NRc8Rd8. NRo8S(O)2Rb8. NRo8S(O)2NRc8Rd8, S(O)2Rb8, and S(O)2NRo8Rd8. wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-6 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

[0287] In some embodiments, R8is selected from H, D, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents.

[0288] In some embodiments, R8is selected from H, D, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl.

[0289] In some embodiments, R8is selected from H, D, halo, CN, C1-3 alkyl, and C1-3 haloalkyl.

[0290] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-10 membered heterocycloalkyl moiety or a 5-6 membered heteroaryl moiety, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents.

[0291] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyd moiety' or a 5-6 membered heteroaryl moiety7, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents. In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-membered heterocycloalkyl, which is optionally substituted by 1, 2. 3, or 4 independently selected R6Asubstituents.

[0292] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 5-membered heterocy cloalkyl moiety, which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents.

[0293] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 6-membered heterocycloalkyd moiety, which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents.

[0294] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety’, which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents.

[0295] In some embodiments, each R6Ais independently selected from halogen, Ci-6 alkyl, and Ci-6 haloalky 1, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1, 2. 3, or 4 substituents selected from D. halo. CN, NO2, and OH.

[0296] In some embodiments, each R6Ais independently selected from from F, methyl, -CF3, -CH2OH, and -CD2OH.

[0297] In some embodiments, each R6Ais independently selected from halogen and -CH2OH. In some embodiments, each R6Ais independently selected from F and -CH2OH. In some embodiments, each R6Ais independently selected from Cl and -CH2OH. In some embodiments, each R6Ais independently selected from halogen and -CH2OH, wherein the-CH2OH is attached in the (S)-con figuration.

[0298] In some embodiments, each R6Ais independently selected from F and -CH2OH, wherein the-CH2OH is attached in the (^-configuration.

[0299] In some embodiments, each R6Ais independently selected from Cl and -CH2OH, wherein the-CH2OH is attached in the (^-configuration.

[0300] In some embodiments, each R6Ais independently selected from F, methyl, -CF3, -CH2OH. and -CD2OH, wherein the -CH2OH and -CD2OH are attached in the (Ciconfiguration.

[0301] In some embodiments, at least one R6Ais -CH2OH.

[0302] In some embodiments, at least one R6Ais -CD2OH.

[0303] In some embodiments, at least one R6Ais -CH2OH attached in the (^-configuration. In some embodiments, at least one R6Ais -CD2OH attached in the (^-configuration. In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety’, which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents; and each R6Ais independently selected from halogen and -CH2OH.

[0304] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety, which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents; and each R6Ais independently selected from halogen, C1-6 alkyl, and C1-6 haloalkyl, wherein said C1-6 alkyl and C1-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents selected from D, halo, CN, NO2, and OH.

[0305] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety, which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents; and each R6Ais independently selected from F and -CH2OH.

[0306] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety, which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents selected from from F, methyl, -CF3, -CH2OH, and -CD2OH.

[0307] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety’, which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents; and each R6Ais independently selected from Cl and -CH2OH.

[0308] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety’, which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents; and each R6Ais independently selected from halogen and -CH2OH, wherein the-CH2OH is attached in the (^-configuration.

[0309] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety’, which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents; and each R6Ais independently selected from halogen, C1-6 alkyl, and C1-6 haloalkyl, wherein said C1-6 alkyl and C1-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents selected from D, halo, CN, NO2, and OH, wherein the -CH2OH and -CD2OH are attached in the (< S)-configuration.

[0310] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety, which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents; and each R6Ais independently selected from F and -CH2OH. wherein the-CFROH is attached in the (^-configuration.

[0311] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyd moiety', which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents; and each R6Ais independently selected from F, methyl, -CF3, -CH2OH, and -CD2OH, wherein the -CH2OH and -CD2OH are attached in the (^-configuration.

[0312] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety', which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents; and each R6Ais independently selected from Cl and -CH2OH, wherein the-CFFOH is attached in the (^-configuration.

[0313] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety', which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents; and at least one R6Ais selected from -CH2OH, wherein the-CFFOH is attached in the (^-configuration.

[0314] In some embodiments, R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety', which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents; and at least one R6Ais -CD2OH, wherein the -CD2OH is attached in the (^-configuration.

[0315] In some embodiments:

[0316] each Ra8, Rc8, and Rd8is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents; and

[0317] each Rb8is independently selected from C1-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

[0318] In some embodiments:

[0319] each Ra8, Rc8, and Rd8is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; and

[0320] each Rb8is independently selected from C1-6 alkyl and C1-6 haloalkyl.

[0321] In some embodiments:

[0322] n is 0, 1, or 2;

[0323] X is O, S(O)2, orN(-L-R4); L is S(0)2or S(O)2NRa;

[0324] Rais selected fromH, Ci-6 alkyl and Ci-6 haloalky 1;

[0325] or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0326] R1is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryL C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0327] each R1Ais independently selected from H, D. halo. CN, Ci-6 alkyl. C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaiyl-Ci-4alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRollRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRollRd11, NRcllRd11, NRollC(O)Rb11. NRollC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;

[0328] each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1.4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0329] each Rb11is independently selected from C1-6alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents; each R1Bis independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa12, SRa12, C(O)Rb12, C(O)NRcl2Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRol2Rd12, NRcl2Rd12, NRol2C(O)Rb12, NRol2C(O)ORa12, NRol2C(O)NRcl2Rd12, NRol2S(O)2Rb12, NRol2S(O)2NRol2Rd12. S(O)2Rb12, and S(O)2NRol2Rd12;

[0330] each Ra12, Rc12, and Rd12is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;

[0331] each Rb12is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0332] R2A, R2B, and R2Care each independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. ORa2, C(O)Rb2, C(O)NRo2Rd2. C(O)ORa2. OC(O)Rb2. OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said Ci-6 alk l and Ci-6 haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents;

[0333] each R“2, Rc2. and Rd2is independently selected from H. Ci-6 alkyl, and Ci-6 haloalkyl; each Rb2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0334] each R3is independently selected from D, halo, CN, Ci-6 alkyl, C 1-6 haloalkyl, ORa3, andNRc3Rd3, wherein said C 1-6 alkyl and Ci-6 haloalky l are each optionally substituted with 1 or 2 independently selected RGsubstituents;

[0335] each Ra3, Rc3. and Rd3is independently selected from H. Ci-6 alkyl, and Ci-6 haloalkyl; each Rb3is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0336] R4is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl; wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted by 1, 2. 3, or 4 independently selected R4Asubstituents;

[0337] each R4Ais independently selected from D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd, 5-6 membered heteroary 1-C 1.4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRo41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41. NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRo41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0338] each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected R4Bsubstituents;

[0339] each Rb41is independently selected from C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0340] each R4Bis independently selected from D, halo, CN, C1-6 alkyl, Ci-6 haloalky l, ORa42, SRa42, C(O)Rb42, C(O)NRo42Rd42, C(O)ORa42, OC(O)Rb42. OC(O)NRc42Rd42, NRo42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42.

[0341] NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;

[0342] each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0343] each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0344] R5is selected from halo, CN, C1-4 alkyl, and C1-4 haloalkyl;

[0345] R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents;

[0346] R7is selected fromH, Ci-6 alkyl, and Ci-6 haloalky l;

[0347] or, R6and R7, together with the nitrogen atom to which they are attached, form a 4-10 membered heterocycloalkyl moiety or a 5-6 membered heteroaryl moiety, each of which is optionally substituted by' 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents; each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-iocycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, ORa61, SRa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRo61Rd61, NRc61Rd61NRc61C(O)Rb61, NRo61C(O)ORa61, NRc61C(O)NRo61Rd61, NRc61S(O)2Rb61, NRc61S(O)2NRc61Rd61. S(O)2Rb61, and S(O)2NRc61Rd61, wherein said Ci-6alkyL C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyd, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalky 1-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R6Bsubstituents;

[0348] each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, C1-6 haloalky 1, C2-6 alkenyl, C2-6 alky nyl, C3-10 cycloalky l, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyd, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyd, 6-10 membered ary l, 4-10 membered heterocycloalkyd, 5-10 membered heteroary l, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alky 1 are each optionally substituted with 1, 2. 3, or 4 independently selected R6Bsubstituents;

[0349] or, any Rc61and Rd61attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyd group, which is optionally substituted with 1, 2. 3, or 4 independently selected R6Bsubstituents;

[0350] each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10cycloalkyl-C1-4alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0351] each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C i-4alkyl. ORa62, SRa62. C(O)Rb62, C(O)NRo62Rd62. C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62, NRc62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, NRc62S(O)2Rb62, NRc62S(O)2NRo62Rd62, S(O)2Rb62, and S(O)2NRo62Rd62, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0352] each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl. Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0353] each Rb62is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cy cloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0354] each R6Cis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alkyl, 5-6 membered heteroaiyl-Ci-4alkyl, ORa63, SRa63, C(O)Rb63, C(O)NRc63Rd63, C(O)ORa63, OC(O)Rb63, OC(O)NRc63Rd63, NRc63Rd63, NRc63C(O)Rb63, NRc63C(O)ORa63, NRc63C(O)NRc63Rd63, NRo63S(O)2Rb63, NRo63S(O)2NRo63Rd63. S(O)2Rb63, and S(O)2NRo63Rd63, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0355] each Ra63, Rc63, and Rd63is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl- Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents; and

[0356] each Rb63is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0357] R8is selected from H, D, halo, CN, C1-6 alkyl, and C1-6 haloalkyl, wherein said C1-6 alkyd and C1-6 haloalky l are each optionally substituted with 1 or 2 independently selected RGsubstituents; and

[0358] each RGis independently selected from OH. NO2. CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Cu 3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkyl carbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl. C1-3 alkylcarbonyloxy. C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(C 1-3 alky l)aminosulfonyl, aminosulfonylamino, C1-3 alky laminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylammo. and di(Ci-3 alkyl)aminocarbonylamino.

[0359] In some embodiments:

[0360] n is 0, 1, or 2;

[0361] X is O, S(O)2, orN(-L-R4);

[0362] L is S(O)2or S(O)2NRa;

[0363] Rais selected fromH, C1-6 alkyd and C1-6 haloalkyl;

[0364] or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0365] R1is selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalky l, 6-10 membered ary l. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyd, 6-10 membered aryl-Ci-4 alkyd, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered hcteroaiy l-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0366] each R1Ais independently selected from H, D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11. C(O)Rb11, C(O)NRollRd11. C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rbn, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C1-6 alkyd, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalky I-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0367] each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, C1-6 haloalky l, C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1.4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroar l-C1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected R1Bsubstituents;

[0368] each Rbnis independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1. 2, 3, or 4 independently selected R1Bsubstituents;

[0369] each R1Bis independently selected from H, D, halo, CN, Ci-6 alky l, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl. 5-6 membered heteroaiyl-C 1.4 alkyl, ORa12, SRa12, C(O)Rb12, C(O)NRcl2Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRol2Rd12, NRcl2Rd12, NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRol2C(O)NRcl2Rd12, NRol2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12, S(O)2Rb12, and S(O)2NRol2Rd12;

[0370] each Ral2, R°12. and Rdl2is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0371] each Rb12is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0372] R2A, R2B, and R2Care each independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. C(O)Rb2. C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRo2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2. NRc2C(O)NRc2Rd2, NRc2S(O)2Rb2, NRo2S(O)2NRc2Rd2. S(O)2Rb2, and S(O)2NRc2Rd2, wherein said Ci-6 alkyl and Ci-6 haloalky 1 are each optionally substituted with 1 or 2 independently selected RGsubstituents;

[0373] each R3is independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa3, andNRc3Rd3, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents;

[0374] each Ra3, Rc3. and Rd3is independently selected from H. Ci-s alkyl, and Ci-6 haloalkyl; each Rb3is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0375] R4is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky I-C1-4 alkyl, and 5-6 membered heteroary 1-C 1-4 alkyl; wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0376] each R4Ais independently selected from D, halo, CN, NO2, C1-6 alkyl, C1-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroary 1-C 1.4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRo41Rd41, NRc41Rd41, NRo41C(O)Rb41. NRo41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRo41S(O)2NRo41Rd41. S(O)2Rb41, and S(O)2NRc41Rd41, wherein said Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary!, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky I-C1-4 alkyl, and 5-6 membered heteroary 1-C 1-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R4Bsubstituents;

[0377] each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroary 1-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0378] each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl. phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0379] each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa42, SR“42, C(O)Rb42, C(O)NRo42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NR°42Rd42, NRo42Rd42, NRo42C(O)Rb42, NRo42C(O)ORa42, NRc42C(O)NRo42Rd42, NRo42S(O)2Rb42.

[0380] NRc42S(O)2NRc42Rd42. S(O)2Rb42, and S(O)2NRc42Rd42;

[0381] each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0382] each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0383] R5is selected from halo, CN. CM alkyl, and Ci-4 haloalkyl;

[0384] R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alky l, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl; which are each optionally substituted by 1, 2, 3. or 4 independently selected R6Asubstituents;

[0385] R7is selected from H, Ci-6 alkyl, and C1-6 haloalkyl;

[0386] or R6and R7, together with the nitrogen atom to which they are attached, form a 4-10 membered heterocycloalkyl moiety or a 5-6 membered heteroaryl moiety, each of which is optionally substituted by 1, 2, 3. 4, 5, or 6 independently selected R6Asubstituents;

[0387] each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl. ORa61, SRa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61, NRo61S(O)2NRc61Rd61, S(O)2Rb61, and S(O)2NRc61Rd61, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-iocycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyd are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0388] each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C1-4alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0389] or, any Rc61and Rd61attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyd group, which is optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0390] each Rb61is independently selected from Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10cycloalkyl-C1-4alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-C1-4alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1. 2, 3, or 4 independently selected R6Bsubstituents;

[0391] each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalky 4, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary 4, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa62, SRa62, C(O)Rb62, C(O)NRo62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62, NRc62C(O)Rb62. NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, NRo62S(O)2Rb62, NRc62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62, wherein said C1-6 alkyd, Ci-6 haloalkyl, C3-7 cycloalkyl, pheny l, 4-7 membered heterocycloalky l, 5-6 membered heteroaiyl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0392] each Ra62, Rc62, and Rd62is independently selected from H, C1-6alkyl, Ci-6 haloalky 1, C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary 4, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary!, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroar 4-C1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected R6Csubstituents; each Rb62is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0393] each R6Cis independently selected from D, halo, CN, C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaiyl-Ci-4alkyl, ORa63, SRa63, C(O)Rb63, C(O)NRc63Rd63, C(O)ORa63, OC(O)Rb63, OC(O)NRc63Rd63, NRc63Rd63, NRc63C(O)Rb63, NRc63C(O)ORa63, NRc63C(O)NRc63Rd63, NRc63S(O)2Rb63, NRc63S(O)2NRc63Rd63. S(O)2Rb63, and S(O)2NRc63Rd63, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0394] each Ra63, Rc63, and Rd63is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents; and

[0395] each Rb63is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0396] R8is selected from H, D, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalky l are each optionally substituted with 1 or 2 independently selected RGsubstituents; and

[0397] each RGis independently selected from OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Ci- 3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl. C1-3 alkylcarbonyloxy. C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(C 1-3 alky l)aminosulfonyl, aminosulfonylamino, C1-3 alky laminosulfonylamino, di(C 1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylammo. and di(Ci-3 alkyl)aminocarbonylamino.

[0398] In some embodiments:

[0399] n is 0, 1, or 2;

[0400] X is O, S(O)2, orN(-L-R4);

[0401] L is S(O)2or S(O)2NRa;

[0402] Rais selected from H, C1-6 alkyl and Ci-6 haloalkyl;

[0403] R1is selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alky l, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl. which are each optionally substituted with 1, 2, 3. or 4 independently selected R1Asubstituents;

[0404] each R1Ais independently selected from H, D, halo, CN, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1.4 alkyl. OR111, SRa11. C(O)Rb11, C(O)NRcllRd11. C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRollC(O)NRcllRd11, NRollS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRc11Rd11, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1.4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0405] each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1 or 2 independently selected R1Bsubstituents;

[0406] each Rbnis independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1 or 2 independently selected R1Bsubstituents;

[0407] each R1Bis independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa12, SRa12. C(O)Rb12, C(O)NRol2Rd12. C(O)ORa12, OC(O)Rb12, OC(O)NRcl2Rd12,NROi2Rdi2 NR012C(O)Rb12, NRcl2C(O)ORa12, NRol2C(0)NRcl2Rdl2. NRol2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12, S(O)2Rb12, and S(O)2NRcl2Rd12;

[0408] each Ra12, Rc12, and Rd12is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0409] each Rb12is independently selected from Ci-6 alkyl and Ci-6 haloalky l;

[0410] R2ARBANC|R2Care each indepenciently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. and ORa2;

[0411] each Ra2is independently selected from H and Ci-6 alkyl;

[0412] each R3is independently selected from halo, CN, C1-3 alkyl, C1-3 haloalky l, ORa3, and NRc3Rd3, wherein said C1-3 alkyl and C1-3 haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents.

[0413] each Ra3, Rc3, and Rd3is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; R4is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl; wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alky l, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted by 1, 2. 3, or 4 independently selected R4Asubstituents;

[0414] each R4Ais independently selected from D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl. ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41NRc41C(O)Rb41, NRc41C(O)ORa41, NRo41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc4lS(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41;

[0415] each Ra41, R°41. and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0416] each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0417] R5is selected from halo and CN;

[0418] R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyd, 6-10 membered aryl-Ci-4 alkyd, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroar 1-C 1-4 alky 1, which are each optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents;

[0419] R7is selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; or, R6and R7, together with the nitrogen atom to which they are attached, form a 4-10 membered heterocycloalkyl moiety or a 5-6 membered heteroaryl moiety, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents;

[0420] each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl. ORa61, SRa61. C(O)Rb61, C(O)NRc61Rd61. C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRo61C(O)NRo61Rd61, NRo61S(O)2Rb61, NRc61S(O)2NRc61Rd61, S(O)2Rb61, and S(O)2NRo61Rd61, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0421] each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected R6Bsubstituents;

[0422] each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0423] each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa62, SRa62, C(O)Rb62, C(O)NRc62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRo62Rd62, NRc62Rd62, NRo62C(O)Rb62, NRc62C(O)ORa62, NRo62C(O)NRc62Rd62, NRo62S(O)2Rb62, NRo62S(O)2NRc62Rd62. S(O)2Rh62, and S(O)2NRo62Rd62, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroar l. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0424] each Ra62, R°62, and Rd62is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0425] each Rb62is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaiyl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0426] each R6Cis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa63, SRa63, C(O)Rb63, C(O)NRo63Rd63, C(O)ORa63, OC(O)Rb63, OC(O)NRc63Rd63, NRo63Rd63, NRo63C(O)Rb63, NRc63C(O)ORa63, NRc63C(O)NRo63Rd63, NRc63S(O)2Rb63, NRo63S(O)2NRo63Rd63, S(O)2Rb63, and S(O)2NRc63Rd63;

[0427] each Ra63, Rc63. and Rd63is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0428] each Rb63is independently selected from Ci-6 alkyl and Ci-6 haloalk l:

[0429] R8is selected fromH, D, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl; and

[0430] each RGis independently selected from OH. NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Ci-3 alkylthio, C1-3 alkydsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alk l carbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl. C1-3 alkylcarbonyloxy. C1-3 alkylcarbonylamino, C1-3 alkoxy carbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(C 1-3 alky l)aminosulfonyl, aminosulfonylamino, C1-3 alky laminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.

[0431] In some embodiments:

[0432] n is 0, 1, or 2; X is O, S(O)2, orN(-L-R4);

[0433] L is S(O)2or S(O)2NRa;

[0434] Rais selected from H, Ci-6 alkyl and Ci-6 haloalkyl;

[0435] R1is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0436] each R1Ais independently selected fromH, D, halo, CN, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl. 5-6 membered heteroaiyl-C 1.4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRollRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRollC(O)NRcllRd11, NRollS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRc11Rd11, wherein said Cue alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0437] each Ral1, R011, and Rdl1is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1 or 2 independently selected R1Bsubstituents;

[0438] each Rb11is independently selected from Ci-6 alkyl and Ci-6 haloalk l. which are each optionally substituted with 1 or 2 independently selected R1Bsubstituents;

[0439] each R1Bis independently selected from H, D. halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa12, SRa12, C(O)Rb12, C(O)NRcl2Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRcl2Rd12,NROi2Rdi2NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRcl2C(O)NRcl2Rd12, NRcl2S(O)2Rb12, NRol2S(O)2NRcl2Rd12, S(O)2Rb12, and S(O)2NRcl2Rd12;

[0440] each Ral2, R°12. and Rdl2is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0441] each Rb12is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0442] R2A, R2B, and R2Care each independently selected from H, D, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl; each R3is independently selected from halo. CN, C1-3 alkyl, C 1-3 haloalky 1, ORa3, and NRc3Rd3, wherein said C1-3 alkyl and C1-3 haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents.

[0443] each Ra3, R°3, and Rd3is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; R4is selected from C1-6 alkyl, C1-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl; wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaiyl-Ci-4 alkyl are each optionally substituted by 1, 2. 3, or 4 independently selected R4Asubstituents;

[0444] each R4Ais independently selected from D, halo, CN, NO2, C1-6 alkyl, Ci-6 haloalkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41NRo41C(O)Rb41, NRc41C(O)ORa41, NRo41C(O)NRc41Rd41, NRo41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41;

[0445] each Ra41, R°41, and Rd41is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

[0446] each Rb41is independently selected from C1-6 alkyl and C1-6 haloalky l

[0447] R5is selected from halo and CN;

[0448] R6is selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl. 6-10 membered aryl. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alky l, 6-10 membered aryl-Ci-4 alky l, 4-10 membered heterocycloalkyl-Ci-4 alky l, and 5-10 membered heteroaryl-Ci-4 alkyl; which are each optionally substituted by 1, 2, 3. or 4 independently selected R6Asubstituents;

[0449] R7is selected from H, C1-6 alkyl, and C1-6 haloalkyl;

[0450] or R6and R7, together with the nitrogen atom to which they are attached, form a 4- 10 membered heterocycloalkyl moiety' or a 5-6 membered heteroaryl moiety, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents;

[0451] each R6Ais independently selected from D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaiyl-Ci-4 alkyl, ORa61, SRa61, C(O)Rb61, C(O)NRo61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61C(O)Rb61. NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRo61S(O)2Rb61, NRc61S(O)2NRc61Rd61, S(O)2Rb61, and S(O)2NRc61Rd61, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0452] each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected R6Bsubstituents;

[0453] each Rb61is independently selected from C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0454] each R6Bis independently selected from D, halo, CN, C1-6 alkyl, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl. 5-6 membered heteroaryl-C 1.4 alkyl, ORa62, SRa62, C(O)Rb62, C(O)NRc62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRo62Rd62, NRc62Rd62, NRo62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, NRc62S(O)2Rb62, NRo62S(O)2NRo62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaiyl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0455] each Ra62, R°62. and Rd62is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6alkyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl- Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0456] each Rb62is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;

[0457] each R6Cis independently selected from D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, ORa63, SRa63, C(O)Rb63, C(O)NRc63Rd63, C(O)ORa63, OC(O)Rb63, OC(O)NRc63Rd63, NRc63Rd63, NRc63C(O)Rb63, NRo63C(O)ORa63, NRc63C(O)NRc63Rd63, NRc63S(O)2Rb63.

[0458] NRc63S(O)2NRc63Rd63, S(O)2Rb63, and S(O)2NRc63Rd63;

[0459] each Ra63, Rc63, and Rd63is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;

[0460] each Rb63is independently selected from C1-6 alkyl and C1-6 haloalkyl;

[0461] R8is selected from H, D. halo. CN, C1-6 alkyl, and C1-6 haloalkyl; and

[0462] each RGis independently selected from OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Ci-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1.3 alkylcarbonyl, C1-3 alkoxycarbonyl. C1-3 alkylcarbonyloxy. C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alkydsulfonylamino, aminosulfonyl, C1-3 alkydaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C 1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkydaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.

[0463] In some embodiments:

[0464] n is 0 or 1;

[0465] X is O, S(O)2, orN(-L-R4);

[0466] L is S(O)2;

[0467] R1is selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalky I-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0468] each R1Ais independently selected from H, D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-5 cycloalkyl, 4-5 membered heterocycloalkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRollRd11, NRollRd11, NRollC(O)Rb11, NRollC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRollS(O)2NRc11Rd11. S(O)2Rb11, and S(O)2NRc11Rd11;

[0469] each Ral1, R011, and Rdl1is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0470] each Rb11is independently selected from Ci-6 alkyl and Ci-6 haloalky l;

[0471] R2AR2BANC|R2Care each independently selected from H, halo, CN, and ORa2; each Ra2is independently selected from H and Ci-6 alkyl;

[0472] each R3is independently selected from halo, CN, C1-3 alkyl, C1-3 haloalkyl, ORa3, and NRo3Rd3, wherein said C1-3 alkyl and C1-3 haloalkyl are each optionally substituted a substituent selected from OH, C1-3 alkoxy, amino, C1-3 alkylamino, and di(Ci-3 alkyl)amino;

[0473] each Ra3, Rc3. and Rd3is independently selected from H. C1-3 alkyl, and C1-3 haloalkyl; R4is selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl; wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0474] each R4Ais independently selected from D, halo, CN, NO2, C1-6 alkyl, Ci-6 haloalkyl. ORa41, SRa41. C(O)Rb41, C(O)NRo41Rd41. C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41,NR04iRd4i NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRo41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRo41Rd41;

[0475] each Ra41, R°41, and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0476] each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0477] R3is selected from F, Cl, and CN;

[0478] R6is selected from Ci-6 alkyl, Ci-6 haloalky l, C3-10 cycloalkyl, 6-10 membered ary l, 4- 10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl; which are each optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents;

[0479] R7is selected fromH, Ci-6 alkyl, and Ci-6 haloalkyl; or, R6and R7, together with the nitrogen atom to which they are attached, form a 4-10 membered heterocycloalkyl moiety or a 5-6 membered heteroaryl moiety, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents;

[0480] each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1.4 alkyl. ORa61, SRa61. C(O)Rb61, C(O)NRc61Rd61. C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRo61C(O)NRo61Rd61, NRo61S(O)2Rb61, NRc61S(O)2NRc61Rd61, S(O)2Rb61, and S(O)2NRo61Rd61, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0481] each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected R6Bsubstituents;

[0482] each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0483] each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalky l, ORa62, SRa62, C(O)Rb62, C(O)NRo62Rd62, C(O)ORa62, OC(O)Rb62. OC(O)NRc62Rd62, NRo62Rd62, NRc62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, NRc62S(O)2Rb62, NRc62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62;

[0484] each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0485] each Rb62is independently selected from Ci-6 alkyl and Ci-6 haloalkyl; and

[0486] R8is selected from H, D, halo, CN, C1.3 alkyl, and C1-3 haloalky l. In some embodiments:

[0487] n is 0 or 1;

[0488] X is O, S(O)2, orN(-L-R4);

[0489] L is S(O)2;

[0490] R1is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0491] each R1Ais independently selected fromH, D, halo, CN, Ci-6 alkyl, C1-6 haloalkyl, C3-5 cycloalkyl, 4-5 membered heterocycloalkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcl lRdn, C(O)ORa11, OC(O)Rb11, OC(O)NRollRd11. NRollRd11. NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRdnNRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11;

[0492] each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;

[0493] each Rb11is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0494]

[0495] selected from H, halo, and CN;

[0496] each R3is independently selected from halo, CN, C1-3 alkyl, C1-3 haloalkyl, ORa3, and NRc3Rd3, wherein said C1-3 alkyl and C1-3 haloalkyl are each optionally substituted a substituent selected from OH, C1-3 alkoxy, amino, C1-3 alkylamino, and di(Ci-3 alkyl)amino;

[0497] each Ra3, Rc3. and Rd3is independently selected from H. C1-3 alkyl, and C1-3 haloalkyl; R4is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky I-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl; wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyd are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0498] each R4Ais independently selected from D, halo, CN, NO2, CI-6 alkyl, Ci-6 haloalkyl. ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRo41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41;

[0499] each Ra41, R°41, and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0500] each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl; R5is selected from F, Cl, and CN;

[0501] R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl. 6-10 membered aryl. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyd, 6-10 membered aryl-Ci-4 alkyd, 4-10 membered heterocycloalkyl-Ci-4 alkyd, and 5-10 membered heteroaryl-C 1-4 alkyl; which are each optionally substituted by 1, 2, 3, or 4 independently-selected R6Asubstituents;

[0502] R7is selected from H, C1-6 alkyl, and Ci-6 haloalkyl;

[0503] or R6and R7, together with the nitrogen atom to which they are attached, form a 4- 10 membered heterocycloalkyd moiety7or a 5-6 membered heteroary 4 moiety-, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents;

[0504] each R6Ais independently selected from D, halo, CN, C1-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalky 4, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky d-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalky d-C 1-4 alkyd, 5-6 membered heteroary I-C1.4 alkyl, ORa61, SRa61, C(O)Rb61, C(O)NRo61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRo61Rd61, NRc61Rd61, NRo61C(O)Rb61. NRo61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61, NRc61S(O)2NRc61Rd61, S(O)2Rb61, and S(O)2NRc61Rd61, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary!, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R6Bsubstituents;

[0505] each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyd, Ci-6 haloalky7!, C3-7 cycloalky7!, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary7!, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;

[0506] each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroar 4-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents; each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa62, SRa62, C(O)Rb62, C(O)NRo62Rd62, C(O)ORa62, OC(O)Rb62. OC(O)NRc62Rd62, NRo62Rd62, NRc62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, NRo62S(O)2Rb62, NRc62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62;

[0507] each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0508] each Rb62is independently selected from Ci-6 alkyl and Ci-6 haloalkyl; and

[0509] R8is selected from H, D, halo, CN, C1-3 alkyl, and C1-3 haloalky l.

[0510] In some embodiments:

[0511] n is 0 or 1;

[0512] X is O, S(O)2, orN(-L-R4);

[0513] L is S(O)2;

[0514] R1is selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently-selected R1Asubstituents;

[0515] each R1Ais independently selected from H, D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NR011Rd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRollC(O)NRcllRdl1, NRcllS(O)2Rb11, NRollS(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRcllRd11;

[0516] each Ral1, Rcl1. and Rdl1is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;

[0517] each Rb11is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0518] R2A, R2B, and R2Care each independently selected from H, halo, and ORa2;

[0519] each Ra2is Ci-6 alkyl;

[0520] each R3is independently selected from -Ci-4alkylene-ORa3, -C 1.4 alky lene-NRo3Rd3, ORa3, and NRc3Rd3;

[0521] each Ra3is H;

[0522] each R°3and Rd3is independently selected fromH and C1-3 alkyl;

[0523] R4is selected from Ci-6 alkyl and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0524] each R4Ais independently selected from D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl, ORa41, SRa41, C(O)Rh41, C(O)NRo41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41NR°41C(O)Rb41, NRc41C(O)ORa41, NRo41C(O)NRc41Rd41. NRo41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41;

[0525] each Ra41, R°41, and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0526] each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalky l;

[0527] R5is selected from F, Cl, and CN;

[0528] R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alky l, 6-10 membered aryl-Ci-4 alky l, 4-10 membered heterocycloalkyl-Ci-4 alky l, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents;

[0529] R7is selected from H, C1-6 alkyl, and Ci-6 haloalkyl;

[0530] or, R6and R7, together with the nitrogen atom to which they are attached, form a 4-10 membered heterocycloalkyl moiety' or a 5-6 membered heteroaryl moiety, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents;

[0531] each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, 4-5 membered heterocycloalkyd, ORa61, SRa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRo61C(O)Rb61, NRc61C(O)ORa61, NRo61C(O)NRc61Rd61, NRo61S(O)2Rb61, NRo61S(O)2NRo61Rd61. S(O)2Rb61, and S(O)2NRo61Rd61, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl are each optionally7substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents; each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, Ci-6 haloalky l, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl are each optionally substituted with 1 or 2 independently selected R6Bsubstituents;

[0532] each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl, which are each optionally substituted with 1 or 2 independently selected R6Bsubstituents;

[0533] each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa62, SRa62, C(O)Rb62, C(O)NRo62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRo62Rd62, NRo62C(O)Rb62, NRo62C(O)ORa62, NRc62C(O)NRc62Rd62, NRc62S(O)2Rb62, NRo62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62;

[0534] each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alky l, and Ci-6 haloalkyl; each Rb62is independently selected from Ci-6 alkyl and Ci-6 haloalkyl; and

[0535] R8is selected from H, C1-3 alkyl, and C1-3 haloalkyl.

[0536] In some embodiments:

[0537] n is 0 or 1;

[0538] X is O, S(O)2, orN(-L-R4);

[0539] L is S(O)2;

[0540] R1is selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyL and 4-10 membered heterocycloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0541] each R1Ais independently selected fromH, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa11, SRa11. C(O)Rb11, C(O)NRollRd11. C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)RbnNRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRollS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11;

[0542] each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;

[0543] each Rb11is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0544] R2A, R2B, and R2Care each independently selected from H and halo;

[0545] each R3is independently selected from -Ci-4alkylene-ORa3, -C 1-4 alky lene-NRc3Rd3, ORa3, and NRo3Rd3;

[0546] each Ra3is H;

[0547] each Rc3and Rd3is independently selected from H and C1-3 alkyl;

[0548] R4is selected from Ci-6 alkyl and Ci-6 haloalkyl; wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0549] each R4Ais independently selected from D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41NRo41C(O)Rb41, NRc41C(O)ORa41, NRo41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRo41S(O)2NRo41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41;

[0550] each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0551] each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalk l;

[0552] R5is selected from F, Cl, and CN;

[0553] R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyL 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alky l, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl; which are each optionally substituted by 1, 2, 3. or 4 independently selected R6Asubstituents;

[0554] R7is selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0555] or R6and R7, together with the nitrogen atom to which they are attached, form a 4-10 membered heterocycloalkyl moiety or a 5-6 membered heteroaryl moiety, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents;

[0556] each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, 4-5 membered heterocycloalkyd, ORa61, SRa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRo61Rd61, NRc61Rd61, NRc61C(O)Rb61, NRo61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61, NRc61S(O)2NRc61Rd61. S(O)2Rb61, and S(O)2NRc61Rd61, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents; each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, Ci-6 haloalky l, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl are each optionally substituted with 1 or 2 independently7selected R6Bsubstituents;

[0557] each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl, which are each optionally substituted with 1 or 2 independently selected R6Bsubstituents;

[0558] each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa62, SRa62, C(O)Rb62, C(O)NRc62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62, NRc62C(O)Rb62, NRo62C(O)ORa62, NRc62C(O)NRc62Rd62, NRc62S(O)2Rb62.

[0559] NRc62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62;

[0560] each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0561] each Rb62is independently selected from Ci-6 alkyl and Ci-6 haloalky l; and

[0562] R8is selected fromH, C1-3 alkyl, and C1-3 haloalkyl.

[0563] In some embodiments:

[0564] n is 0 or 1;

[0565] X is O orN(-L-R4);

[0566] L is S(O)2;

[0567] R1is selected from Ci-6 alkyl, Ci-6 haloalkyl, and C3-10 cycloalkyl;

[0568] R2A, R2B, and R2Care each independently selected from H, halo, and ORa2; each Ra2is Ci-6 alkyl;

[0569] each R3is 0Ra3;

[0570] each Ra3is H;

[0571] R4is Ci-6 alkyl;

[0572] R5is selected from halo and CN;

[0573] R6is selected from Ci-6 alkyl and C3-10 cycloalkyl-Ci-4 alkyl; which are each optionally substituted by 1 or 2 independently selected R6Asubstituents;

[0574] R7is selected from H and Ci-6 alkyl;

[0575] or, R6and R7, together with the nitrogen atom to which they are attached, form a 4-15 membered heterocycloalkyl moiety, which is optionally substituted by 1, 2, 3, 4, or 5 independently selected R6Asubstituents;

[0576] each R6Ais independently selected from halo, CN, Ci-6 alkyd, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, ORa61, NRc61Rd61, and S(O)2Rb61, wherein said C1-6 alkyl, C3-10 cycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1. 2, 3, or 4 independently selected R6Bsubstituents;

[0577] each Ra61, R°61, and Rd61is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

[0578] each Rb61is independently selected from Ci-6 alkyl and C3-10 cycloalkyl;

[0579] each R6Bis independently selected from D, halo, CN, C1-6 alkyl, ORa62, andNRc62Rd62.

[0580] each Ra62, Rc62, and Rd62is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; and

[0581] R8is selected fromH and Ci-6 alkyl.

[0582] In some embodiments, the compound is a compound of Formula (la):

[0583]

[0584] or a pharmaceutically acceptable salt thereof.

[0585] In some embodiments, the compound is a compound of Formula (lb):

[0586]

[0587] or a pharmaceutically acceptable salt thereof.

[0588] In some embodiments, the compound is perdeuterated.

[0589] In some embodiments, at least one alky l group is perdeuterated.

[0590] In some embodiments, the compound comprises at least one deuterium atom.

[0591] In some embodiments, the compound comprises two or more deuterium atoms.

[0592] In some embodiments, the compound comprises from 1 to 6 deuterium atoms.

[0593] In some embodiments, the compound comprises from 1 to 3 deuterium atoms.

[0594] In some embodiments, the compound comprises 1 deuterium atom.

[0595] In some embodiments, the compound comprises 2 deuterium atoms.

[0596] In some embodiments, the compound comprises 3 deuterium atoms.

[0597] In some embodiments, 1 to 8 hydrogen atoms attached to carbon atoms of alkyl, alkenyl, alkynyl, haloalky 1, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, cycloalkyl-alkyl, aryl-alkyl, heterocycloalkyl-alkyl, and heteroaryl-alkyl are replaced by deuterium atoms.

[0598] In some embodiments, 1 to 3 hydrogen atoms attached to carbon atoms of alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyd, ary l. heterocycloalkyd, heteroaryl, cycloalkyl-alkyl, aryl-alkyl, heterocycloalkyl-alkyl, and heteroar l-alkyl are replaced by deuterium atoms.

[0599] In some embodiments, the compound is selected from:

[0600] 4-fluoro-6-(5-fluoro-2-(((37?, R)-3-hydroxy-l-(methylsulfonyl)piperidin-4-yl)amino)pyrimidin-4-yl)-I-isopropyl-A'-methyl-177-indole-3-carboxamide;

[0601] 4-fluoro-6-(5-fluoro-2-(((3S',47?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl- V-methyl-127-indole-3-carboxamide;

[0602] 4-fluoro-6-(5-fluoro-2-(((37?,47?)-3-hydroxy-l-(methylsulfonyl)piperidin-4-yl)amino)pyrimidin-4-yl)-I-isopropyl-jV-(2-(pyrimidin-2-yl)ethyl)-17f-indole-3-carboxamide;

[0603] 6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-4-fluoro-l-isopropyl- V-((l-methyl-177-indazol-6-yl)methyl)-l / f-indole-3-carboxamide; 6-(5-cyano-2-(((3S,4. R)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrirnidin-4-yl)-4-fluoro-l-isopropyl-iV-((l-methyl-l / 7-indazol-6-yl)methyl)-17f-indole-3-carboxamide;

[0604] 6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-4-fluoro-l-isopropyl-, 2-dimethyl-177-indole-3-carboxamide;

[0605] l-cyclopentyl-4,7-difluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pynmidin-4-yl)-; V-melhyl- l / 7-indole-3-carboxamide:

[0606] (4-fluoro-6-(5-fluoro-2-(((35,4A)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-I-isopropyl-177-indol-3-yl)(3-(trifluoromethyl)azetidin-l-yl)methanone;

[0607] (4-fluoro-6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- 177-indol-3-yl)((<S’)-2-(hydroxymethyl)azetidin-l-yl)methanone;

[0608] (4-fluoro-6-(5-fluoro-2-(((3S,4J?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-l / / -indol-3-yl)((2S,3S)-2-(hydroxymethyl)-3-methylazetidin- 1 -y l)methanone;

[0609] ((25,4A)-4-fluoro-2-(hydroxymethyl)pyrrolidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((35,4J?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-177-indol-3-yl)methanone; and

[0610] ((S)-4,4-difluoro-2-(hydroxymethyl)pyrrolidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((35',4 )-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- l / f-indol-3-yl)methanone;

[0611] or a pharmaceutically acceptable salt thereof.

[0612] In some embodiments, the compound is selected from:

[0613] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;

[0614] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((R)-4-(hy droxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone; and

[0615] (4-fluoro-6-(5-fluoro-2-(((3< S',47?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-17 / -indol-3-yl)((7?)-2-(hydroxymethyl)azetidin-l-yl)methanone;

[0616] or a pharmaceutically acceptable salt thereof.

[0617] In some embodiments, the compound is selected from: (4-fluoro-6-(5-fluoro-2-(((3S,4J?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- l -indol-3-yl)((25,3S)-2-(hydroxymethyl-J2)-3-methyl azetidin- 1 -y l)methanone;

[0618] ((2R, 3S)-3-(difluoromethoxy)-2-(hydroxymethyl)azeti din-1 -yl)(4-fluoro-6-(5-fluoro-2-(((35,4J?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0619] or a pharmaceutically acceptable salt thereof.

[0620] In some embodiments, the compound is selected from:

[0621] (6-(5-fluoro-2-(((3£,4J?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-127-indol-3-yl)((2S,3S)-2-(hydroxymethyl-6 / 2)-3-methylazetidin-l-yl)methanone;

[0622] (l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2J7-pyran-4-yl)amino)pyrimidin-4-yl)-l#-indol-3-yl)((2S,3 )-2-(hydroxymethyl-ti2)-3-methylazetidin-l-yl)methanone;

[0623] (4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyri mi din-4-yl)- 1 -methyl- 17 / -indol-3-yl)(3-(trifluoromethy l)azeti din- 1 -yl)methanone;

[0624] (4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimi din-4-yl)-l-methyl-17f-indol-3-yl)(3-(2-fluoropropan-2-yl)azeti din-1 -yl)methanone;

[0625] (5,5-difluoro-2-azaspiro[3.3]heptan-2-yl)(4-fluoro-6-(5-fluoro-2-(((3<S’,47?)-3-hydroxytetrahydro-2 / V-pyran-4-yl)amino)pyrimidin-4-yl)- 1 -methyl-l H-indol-3-yl)methanone;

[0626] (4-fluoro-6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)- 1 -methyl- 17 / -indol-3-yl)((?)-2-methylazetidin- 1 -yl)methanone;

[0627] (l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)- l-methyl-IH-indol-3-yl)methanone;

[0628] (6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-4-lluoro-l -isopropyl- 1 / ¥-indol-3-yl) S'.3 )-2-(tiydroxyiTielhyl)-3-methylazetidin- 1-yl)methanone;

[0629] (6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-4-11 uoro- 1 -isopropyl- 1 H-indol-3-yl)((2.3. S')-2-(hydroxymelhyl-d2)-3-melhyla / etidin- 1-yl)methanone; (l-ethyl-4-fluoro-6-(5-fluoro-2-(((3< S’,47?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-17 / -indol-3-yl)((2S,3< S)-2-(hydroxymethyl-t / 2)-3-methylazeti din-1 -yl)methanone;

[0630] ((27?, 31S’)-3-(difluoromethoxy)-2-(hydroxymethyl)azeti din-1 -yl)(l -ethyl-4-fluoro-6-(5-fluoro-2-(((35',47?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-17 / -indol-3-yl)methanone;

[0631] 7V-((S)-l-cyclopropyl-2-hydroxyethyl)-l-ethyl-4-fluoro-6-(5-lluoro-2-(((35,47?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-177-indole-3-carboxamide;

[0632] (l-ethyl-4-fluoro-6-(5-fluoro-2-(((3iS\47?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-17 / -indol-3-yl)((S)-2-(trifluoromethyl)azetidin-l-yl)methanone;

[0633] (l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxylelrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-177-indol-3-yl)melhanone;

[0634] (l,l-dilluoro-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-lluoro-2-(((3S,47?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-177-indol-3-yl)methanone;

[0635] (l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-2 7-pyran-4-yl)amino)pyrimidin-4-yl)-17f-indol-3-yl)((2S',3< S)-2-(hydroxymelhyl)-3-(trifluoromethy l)azetidin- 1 -y l)methanone;

[0636] (l-ethyl-4-fluoro-6-(5-fluoro-2-(((35,4?)-3-hydroxytetrahydro-2 / -pyran-4-yl)amino)pyrimidin-4-yl)-17f-indol-3-yl)((2S',3< S,)-2-(hydroxymethyl-t / 2)-3-(trifluoromethyl)azeti din-1 -yl)methanone;

[0637] (4-fluoro-6-(5-fluoro-2-(((3S,4?)-3-hydroxytetrahydro-2 / -pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-177-indol-3-yl)((25,3. S)-2-(hydroxymethyl)-3-(trifluoromethyl)azetidin-l-yl)methanone;

[0638] (4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-17 / -indol-3-yl)((25,3S)-2-(hydroxymethyl-<72)-3-(trifluoromethyl)azetidin-l-yl)methanone;

[0639] (4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-2 / f-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-17 / -indol-3-yl)((2S.3< S’)-2-(hydroxymethyl)-3-(tri fluoromethyl)azeti din-1 -yl)methanone; (l-ethyl-6-(5-fluoro-2-(((3<S',47?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-17 / -indol-3-yl)((2S,3< S)-2-(hydroxymethyl)-3-(trifluoromethyl)azetidin- 1 -y l)methanone;

[0640] (6-(5-fluoro-2-(((3<. S',47?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)- I -methyl- 1 H-indol-3-y l)((2.3 )-2-(hydroxymethyl )-3-(tri fluoromethyl Jazetidin- 1 -yl)methanone;

[0641] (4-fluoro-6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-2 / f-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- l7 / -mdol-3-\l)((2 / <3 / ?)-2-(hydrox meth l)-3-meth oxy -3 -methyl azeti din- 1 -y 1 )methan on e;

[0642] (l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-17f-indol-3-yl)((27?,3J?)-2-(hydroxymethyl)-3-methoxy-3-methylazetidin-l-yl)methanone;

[0643] (4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyri mi din-4-yl)-l -methyl- l / / -indol-3-yl)((2 / ?.3 / ?)-2-(hydroxymethyl)-3-methoxy-3-methy lazetidin- 1 -yl)methanone;

[0644] (6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-177-indol-3-yl)((27?,3> S’)-2-(hydroxymethyl)-3-(trifluoromethoxy)azetidin-l-yl)methanone;

[0645] (4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyri mi din-4-yl)-l -methyl- 17 / -indol-3-yl)((2.3S)-2-(hydroxymethyl)-3-(trifluoromethoxy)azetidin- 1 -y l)methanone;

[0646] (4-fluoro-6-(5-fluoro-2-(((3>. S',47?)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-177-indol-3-yl)((27?,3S)-2-(hydroxymethyl)-3-(trifluoromethoxy )azetidin- 1 -y l)methanone;

[0647] (6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-4-fluoro-l -isopropyl-1 7-indol-3-yl)((27?, 3< S)-2-(hy droxymethyl)-3-(trifluoromethoxy )azetidin- 1 -y l)methanone;

[0648] (l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-17f-indol-3-yl)((2.3< S’)-2-(hydroxymethyl)-3-(trifluoromethoxy)azetidin-l-yl)methanone;

[0649] (6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-4-fluoro-17f-indol-3-yl)((2J?,3S)-2-(hydroxymethyl)-3-(trifluoromethoxy)azeti din-1 -yl)methanone; (l-(2,2-difluoroethyl)-4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-117-indol-3-yl)(5-azaspiro[2.3]hexan-5-yl)methanone;

[0650] (l-(2.2-difluoroethyl)-6-(5-fluoro-2-(((3S.4R)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)p\rimidin-4-yl)-l / / -indol-3-yl)((2. S'.31S')-2-(hydroxymethyl-c / 2)-3-methyla / etidin-l -yl)methanone;

[0651] (6-(5-chloro-2-(((3S,4?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-4-fluoro-17 / -indol-3-yl)((S)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;

[0652] (6-(5-chloro-2-(((3iS',47?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-4-fluoro-17f-indol-3-yl)((J?)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;

[0653] (3-(rert-butyl)-3-hydroxyazetidin-l-yl)(6-(5-chloro-2-(((35'.47?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-4-fluoro-17 / -indol-3-yl)methanone;

[0654] (6-(5-chloro-2-(((35',4J?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-4-fluoro-17 / -indol-3-yl)(3-((difluoromethoxy)methyl)azetidin-l-yl)methanone;

[0655] (6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-1 -ethyl -4-fluoro-17 / -indol-3-yl)((25,3< S’)-2-(hydroxymethyl-J2)-3-methylazeti din- 1-yl)methanone;

[0656] (6-(5-chloro-2-(((3S,4J?)-3-hydroxytetrahydro-21 / -pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-4-fluoro-177-indol-3-yl)(3-(difluoromethyl)azetidin-l-yl)methanone;

[0657] (6-(5-chloro-2-(((3S 47?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-1 -ethyl -4-fluoro- 17 / -indol-3-y I )((2 / ?.35')-3-(di fluoromethoxy )-2-(hydroxymethyl)azetidin-l -yl)methanone;

[0658] (l-ethyl-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-17 / -indol-3-yl)((S)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;

[0659] (l-ethyl-6-(5-fluoro-2-(((35',4i?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-17 / -indol-3-yl)((J?)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;

[0660] (6-(5-fluoro-2-(((3< S',4^)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-l / / -indol-3-yl)(( )-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone; (6-(5-fluoro-2-(((3<S',4J?)-3-hydroxytetrahydro-27 -pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-l / 7-indol-3-yl)((f?)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;

[0661] ((4<S’)-l.l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(6-(5-fluoro-2-(((3lS’,47?)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl-1 H-indol-3-yl)methanone;

[0662] ((4i?)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(6-(5-fluoro-2-(((3S.4J?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0663] (6-(5-fluoro-2-(((3< S',47?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-l / / -indol-3-yl)((1S)-l-(hydroxymethyl)-2-azaspiro[3.3]heptan-2-yl)methanone;

[0664] (6-(5-fluoro-2-(((31S',4i?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-1 -methyl- 1 / / -indol-3-y I )(( / )- 1 -(hy droxymethyl)-2-azaspiro[3,3]heptan-2-yl)methanone;

[0665] (6-(5-fluoro-2-(((35,47?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-1 -methyl- l / 7-indol-3-yl)((2S,35)-2-(hydroxymethyl)-3-methylazeti din-1 -yl)methanone;

[0666] 2-(GS’)-l-(6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- 17f-indole-3-carbonyl)azetidin-2-yl)acetonitrile;

[0667] ((2R, 3S)-3-(difluoromethoxy)-2-(hydroxymethyl)azeti din-1 -yl)(l -ethyl-6-(5-fluoro-2-(((3S,4J?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-177-indol-3-yl)methanone;

[0668] (6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-217-pyran-4-yl)amino)pyrimidin-4-yl)- l-elhyl-l / / -indol-3-yl)((25'.3 )-2-(hydroxymethyl-t / 2)-3-methylazetidin-l-yl)methanone; and (6-(5-chloro-2-(((3iS',47?)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-17 / -indol-3-yl)((2J?,35)-3-(difluoromethoxy)-2-(hydroxymethyl)azetidin-l-yl)methanone;

[0669] or a pharmaceutically acceptable salt thereof.

[0670] In some embodiments, the compound is selected from:

[0671] (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)(5-azaspiro[2.3]hexan-5-yl)methanone;

[0672] (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-1 -methyl- lH-indol-3-yl)(3-(trifluoromethyl)azetidin- 1 -yl)methanone; (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((R)-2-methylazetidin-l-yl)methanone;

[0673] (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((S)-2-(hydroxymethyl)azetidin-l-yl)methanone;

[0674] (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((S)-2-((methylsulfonyl)methyl)azetidin-l-yl)methanone;

[0675] (5,5-difluoro-2-azaspiro[3.3]heptan-2-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0676] N-((S)-l-cyclopropyl-2-hydroxyethyl)-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indole-3-carboxami de:

[0677] (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)(3-hydroxy-3-(trifluoromethyl)azetidin-l-yl)methanone;

[0678] (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2R,3R)-3-hydroxy-2-methylazetidin-l-yl)methanone;

[0679] (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2R,3S)-3-hydroxy-2-methylazetidin-l-yl)methanone;

[0680] ((2S,3S)-2-((cyclopropylsulfonyl)methyl)-3-methylazetidin-l-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0681] ((2R,3S)-3-(difluoromethoxy)-2-(hydroxymethyl)azetidin-l-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0682] ((2S,4R)-4-(difluoromethoxy)-2-(hydroxymethyl)pyrrolidin-l-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0683] (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-1 -methyl- 1 H-indol-3-yl)((2S, 4R)-2-(hydroxy methyl)-4-(trifluoromethoxy)pyrrolidin-l-yl)methanone;

[0684] (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2S,4R)-2-(hydroxymethyl)-4-(trifluoromethyl)pyrrolidin-l-yl)methanone; ((S)-4,4-difluoro-2-(hydroxymethyl)pyrrolidin-l-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0685] (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)- 1-methyl-lH-indol-3-yl)((S)-2-(hydroxymethyl)-4,4-dimethylpyrrolidin-l-yl)methanone;

[0686] (l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)(3-(trifluoromethyl)azetidin-l-yl)methanone;

[0687] ((2S,4R)-4-(difluoromethoxy)-2-(hydroxymethyl)pyrrolidin-l-yl)(l-ethyl-6-(5-fluoro- 2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0688] (l-ethyl-6-(5-fluoro-2-(((3S.4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((2S,4R)-2-(hydroxymethyl)-4-(trifluoromethoxy)py rrolidin- 1 -yl)methanone;

[0689] (l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((2S,4R)-2-(hydroxymethyl)-4-(trifluoromethy l)pyrrolidin- 1 -yl)methanone;

[0690] (l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((2S,4R)-4-fluoro-2-(hydroxymethyl)pyrrolidin-l-yl)methanone;

[0691] (l-ethyl-6-(5-fluoro-2-(((3S.4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((S)-2-(hydroxymethyl)-4,4-dimethylpyrrolidin-l-yl)methanone;

[0692] (l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((S)-6-(hydroxymethyl)-5-azaspiro[2.4]heptan-5-yl)methanone;

[0693] ((S)-4,4-difluoro-2-(hydroxymethyl)pyrrolidin-l-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)- 3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)rnethanone;

[0694] ((3S,6S)-l,l-difluoro-6-(hydroxymethyl)-5-azaspiro[2.4]heptan-5-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0695] 2-((S)-l-(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indole-3-carbonyl)azetidin-2-yl)acetonitrile; (l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((S)-2-((methylsulfonyl)methyl)azetidin-l-yl)methanone;

[0696] (l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0697] (5,5-difluoro-2-azaspiro[3.3]heptan-2-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0698] (l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)(3-(2-fluoropropan-2-yl)azetidin-l-yl)methanone;

[0699] (l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimi din-4-yl)-lH-indol-3-yl)((R)-3-(tri fluoromethoxy )pyrrolidin-l-yl)methanone;

[0700] (l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)(5-azaspiro[2.3]hexan-5-yl)methanone;

[0701] N-((S)-l-cyclopropyl-2-hydroxyethyl)-l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indole-3-carboxamide;

[0702] (l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)(5-azaspiro[2.4]heptan-5-yl)methanone;

[0703] (3-(difluoromethyl)-3-hydroxyazetidin-l-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0704] (l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)(3-hydroxy-3-(trifluoromethyl)azeti din-1-yl)methanone;

[0705] ((4S)-lJ-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0706] ((4R)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0707] ((2S,3S)-2-((cyclopropylsulfonyl)methyl)-3-methylazetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0708] 2-((S)-l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indole-3-carbonyl)azetidin-2-yl)acetonitrile; ((2S,4R)-4-(difluoromethoxy)-2-(hydroxymethyl)pyrrolidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0709] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-mdol-3-yl)((2S,4R)-2-(hydroxymethyl)-4-(trifluoromethoxy)pyrrolidin- 1 -yl)methanone;

[0710] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)((2S,4R)-2-(hydroxymethyl)-4-(trifluoromethyl)pyrrolidin- 1 -yl)methanone;

[0711] ((3S,6S)-l,l-difluoro-6-(hydroxymethyl)-5-azaspiro[2.4]heptan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S.4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0712] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2S,4S)-2-(hydroxymethyl)-4-methoxy-4-(trifluoromethyl)pyrrolidin- 1 -yl)methanone;

[0713] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)((2S,4S)-4-hydroxy-2-(hydroxymethyl)-4-(trifluoromethyl)pyrrolidin- 1 -yl)methanone;

[0714] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)((R)-3-(trifluoromethoxy)pyrrolidin-l -yl)methanone;

[0715] ((R)-3-(difluoromethoxy)pyrrolidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0716] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)(5-azaspiro[2.3]hexan-5-yl)methanone;

[0717] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2S.3S)-2-(hydroxymethyl-d2)-3-methyl azetidin- 1 -y l)methanone;

[0718] ((2R,3S)-3-(difluoromethoxy)-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro- 2-(((3 S,4R)-3-hydroxy tetrahy dro-2H-pyran-4-yl)amino)pyrimidin-4-yl)- 1 -methyl- IH-indol- 3-yl)methanone; ((S)-2-(difluoromethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0719] (S)-l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indole-3-carbonyl)azetidine-2-carbonitrile;

[0720] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)(3-hy droxyazeti din-1 -yl)methanone;

[0721] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)(3-methylazetidin-l-yl)methanone;

[0722] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)(3-methoxyazetidin-l-yl)methanone;

[0723] (3-(l,l-difluoroethyl)-3-methylazetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0724] (1,1 -difluoro-2,2-dimethyl-5 -azaspiro [2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0725] (6-(5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-1 -ethyl-lH-indol-3-yl)(3-(trifluoromethyl)azetidin- 1 -yl)methanone;

[0726] (6-(5-chloro-2-(((3S.4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-lH-indol-3-yl)((R)-2-methylazetidin-l-yl)methanone;

[0727] (6-(5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-lH-indol-3-yl)((2S,4R)-4-(difluoromethoxy)-2-(hydroxymethyl)pyrrolidin-l-yl)methanone;

[0728] (6-(5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)- 1-ethyl-lH-indol-3-yl)((2S,4R)-4-fluoro-2-(hydroxymethyl)pyrrolidin-l-yl)methanone;

[0729] (5,5-difluoro-2-azaspiro[3.3]heptan-2-yl)(l-(2,2-difluoroethyl)-4-fluoro-6-(5-fluoro- 2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0730] (l-(2,2-difluoroethyl)-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((2S,3S)-2-(hydroxymethyl-d2)-3-methylazetidin- 1 -yl)methanone; (l-(2,2-difluoroethyl)-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)(3-(2-fluoropropan-2-yl)azetidin-l-yl)methanone;

[0731] (l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(l-(2,2-difluoroethyl)-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0732] (6-(5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-4-fluoro-l-methyl-lH-indol-3-yl)(3-(2-fluoropropan-2-yl)azetidin-l-yl)methanone;

[0733] (6-(5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-4-fluoro-l-methyl-lH-indol-3-yl)(l,l-difluoro-2,2-dimethyl-5-azaspiro[2.3]hexan-5-yl)methanone;

[0734] (l-(2,2-difluoroethyl)-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((S)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;

[0735] (l-(2.2-difluoroethyl)-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((R)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;

[0736] ((4S)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(l-(2,2-difluoroethyl)-6-(5-fluoro-2-(((3S.4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0737] ((4R)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(l-(2,2-difluoroethyl)-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0738] (l-(2.2-difluoroethyl)-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((S)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;

[0739] (l-(2,2-difluoroethyl)-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((R)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;

[0740] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((S)-l-(hydroxymethyl)-2-azaspiro [3.3]heptan-2-y l)methanone; (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((R)-l-(hydroxymethyl)-2-azaspiro [ 3.3 ]heptan-2-y 1 )methanone;

[0741] ((4S)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-1 H-indol-3 -y l)methanone;

[0742] ((4R)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl-lH-indol-3-yl)methanone;

[0743] ((2S,3S)-3-(difluoromethyl)-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0744] ((2R,3R)-3-(difluoromethyl)-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0745] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((lR,4S,5R)-5-(hydroxymethyl)-2-azabi cy clo [2.1.0] pentan-2-y l)methanone;

[0746] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((lS,4R,5S)-5-(hydroxymethyl)-2-azabi cyclo[2.1,0]pentan-2-yl)methanone;

[0747] (2S,3S)-l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indole-3-carbonyl)-2-(hydroxymethyl)azetidine-3-carbonitrile;

[0748] (2R,3R)-l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indole-3-carbonyl)-2-(hydroxymethyl)azetidine-3-carbonitrile;

[0749] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((2R,3R)-2-(hydroxymethyl)-3-(methylsulfonyl)azetidin- 1 -yl)methanone;

[0750] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((2S,3S)-2-(hydroxymethyl)-3-(methylsulfonyl)azetidin- 1 -y l)methanone; (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((2R,3S)-2-(hydroxymethyl)-3-(methylsulfonyl)azetidin- 1 -y l)methanone;

[0751] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((2S,3R)-2-(hydroxymethyl)-3-(methylsulfonyl)azetidin-l-yl)methanone;

[0752] ((4R)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0753] ((4S)-1,1-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(l-ethyl-6-(5-fluoro- 2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0754] ((4R)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol- 3-yl)methanone;

[0755] ((4S)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0756] (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)mehthanone;

[0757] (6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((R)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;

[0758] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((2S,3S)-2-(hydroxymethyl)-3-((trifluoromethoxy)methyl)azetidin- 1 -yl)methanone;

[0759] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((2R,3R)-2-(hydroxymethyl)-3-((trifluoromethoxy )methyl)azeti din- 1 -yl)methanone;

[0760] ((2S,3S)-3-((difluoromethoxy)methyl)-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0761] ((2R, 3R)-3-((difluoromethoxy)rnethyl)-2-(hydroxymethyl)azeti din-1 -yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone; ((4S)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0762] ((4R)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;

[0763] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((R)-l-(hydroxymethyl)-2-azaspiro[3.3]heptan-2-yl)methanone;

[0764] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((S)-l-(hydroxymethyl)-2-azaspiro[3.3]heptan-2-yl)methanone;

[0765] ((R)-3,3-difluoro-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0766] ((S)-3,3-difluoro-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0767] 4-fluoro-6-(5-fluoro-2-(((3A.4J?)-3-hydroxy-l-(methylsulfonyl)piperidin-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-A^, JV-dimethyl-17 / -indole-3-carboxamide;

[0768] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-2-(methoxymethyl)azeti din-1 -yl)methanone;

[0769] 2-((S)-l-(4-fluoro-6-(5-fluoro-2-(((3S.4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indole-3-carbonyl)azetidin-2-yl)acetonitrile;

[0770] ((S)-2-((dimethylamino)methyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0771] ((S)-2-(2,2-difluoroethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0772] (l,l-difluoro-5-azaspiro[2.4]heptan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone; (5,5-difluoro-2-azaspiro[3.3]heptan-2-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0773] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-2-(hydroxymethyl)-2-methylazetidin-l-yl)methanone;

[0774] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((2S,3R)-2-(hydroxymethyl)-3-methylazetidin- 1 -yl)methanone;

[0775] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)- 1 -isopropyl- lH-indol-3-yl)((S)-2-(2-hy droxy ethyl)azetidin- 1 -yl)methanone;

[0776] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-2-(2-hydroxypropan-2-yl)azetidin-l-yl)methanone;

[0777] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((2S,3S)-3-methyl-2-((methy Isulfony l)methyl)azetidin- 1 -y l)methanone;

[0778] ((S)-2-((cyclopropylsulfonyl)methyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)- 1 -isopropyl- lH-indol-3-yl)methanone;

[0779] (l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0780] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-(pyrrolidin-l-yl)azetidin-l-yl)methanone;

[0781] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)(6-methyl -2, 6-diazaspiro[3.3]heptan-2-yl)methanone;

[0782] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(6-oxa-2-azaspiro[3.4]octan-2-yl)methanone; (3-(dimethylamino)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0783] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-2-(fluoromethyl)azetidin-l-yl)methanone;

[0784] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-hydroxyazetidin-l-yl)methanone;

[0785] (3-(difluoromethoxy)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0786] (4-fluoro-6-(5-fluoro-2-(((3R,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-(pyrrolidin-l-yl)azetidin-l-yl)methanone;

[0787] azetidin-l-yl(4-fluoro-6-(5-fluoro-2-(((3S.4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)methanone;

[0788] (3-aminoazetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0789] (3-(difluoromethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0790] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-fluoroazetidin-l-yl)methanone;

[0791] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-methylazetidin-l-yl)methanone;

[0792] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)- 1 -isopropyl- lH-indol-3-yl)((R)-2-methylazeti din- 1 -yl)methanone;

[0793] ((2R,4R)-2.4-dimethylazetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S.4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0794] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(5-azaspiro[2.3]hexan-5-yl)methanone:

[0795] l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indole-3-carbonyl)azetidine-3-carbonitrile; (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)(pyrrolidin-l-yl)methanone;

[0796] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((R)-3-fluoropyrrolidin-l-yl)methanone;

[0797] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((R)-3-hydroxypyrrolidin-l-yl)methanone;

[0798] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-3-hydroxypyrrolidin-l-yl)methanone;

[0799] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-hydroxy-3-(trifluoromethyl)azetidin-l-yl)methanone;

[0800] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((S)-2-(hydroxymethyl)pyrrolidin-l-yl)methanone;

[0801] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((R)-2-(hydroxymethyl)pyrrolidin-l-yl)methanone;

[0802] (3,3-difluoropyrrolidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0803] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((lR,2S,5S)-2-(hydroxymethyl)-3-azabicy clo [3.1.0]hexan-3 -yl)methanone;

[0804] (S)-l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indole-3-carbonyl)pyrrolidine-3-carbonitrile;

[0805] (R)- 1 -(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indole-3-carbonyl)pyrrolidine-3-carbonitrile;

[0806] (3-fluoro-3-(trifluoromethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)methanone;

[0807] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)(5-azaspiro[2.4]heptan-5-yl)methanone; (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)(3-methyl-3-(trifluoromethyl)azetidin-l-yl)methanone;

[0808] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-isopropoxyazetidin-l-yl)methanone;

[0809] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)(3-(hydroxymethyl)azetidin-l-yl)methanone;

[0810] (3-((difluoromethoxy)methyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;

[0811] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-(2-(trifluoromethoxy)ethyl)azetidin-l-yl)methanone;

[0812] (l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((S)-2-(hydroxymethyl)azetidin-l-yl)methanone;

[0813] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-(trifluoromethoxy)azetidin-l-yl)methanone;

[0814] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-((tri fluoromethoxy )methyl)azeti din-l-yl)methanone;

[0815] (3-(difluoromethoxy)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0816] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-2-(l-hydroxycyclopropyl)azetidin-l-yl)methanone;

[0817] (4,7-difluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)(l, l-difluoro-5-az aspiro[2.3]hexan-5-yl)methanone;

[0818] (l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(7-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-1-methyl-1H-indol-3-yl)methanone; (7-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2S.3S)-2-(hydroxymethyl-d2)-3-methyl azetidin- 1 -yl)methanone;

[0819] (4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l,7-dimethyl-lH-indol-3-yl)((2S,3S)-2-(hydroxymethyl-d2)-3-methylazetidin-l-yl)methanone;

[0820] (l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(6-(5-fluoro-2-(((3S.4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l,7-dimethyl-lH-indol-3-yl)methanone;

[0821] (4,5-difluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)- 1 -methyl- lH-indol-3-yl)( 1.1 -difluoro-5-azaspiro[2.3]hexan-5-yl)methanone;

[0822] (l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(5-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;

[0823] (5-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)((2S, 3S)-2-(hydroxymethyl-d2)-3-methylazetidin- 1 -yl)methanone; and

[0824] (l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-5-methoxy-l-methyl-lH-indol-3-yl)methanone;

[0825] or a pharmaceutically acceptable salt thereof.

[0826] In some embodiments, 1. 2, 3, 4, 5, 6, 7, or 8 hydrogen atoms, attached to carbon atoms of “alkyl”, “alkenyl”, “alkynyl”, “aryl”, “pheny l”, “cycloalkyl”, “heterocycloalkyl”, or “heteroaryl” substituents or “-C1-4 alkyl-” and “alkylene” linking groups, as described herein, are optionally replaced by deuterium atoms.

[0827] It is further appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment as if the embodiments were claims written in multiple dependent form. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination.

[0828] At various places in the present specification, divalent linking substituents are described. Unless otherwise specified, it is specifically intended that each divalent linking substituent include both the forward and backward 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 variables listed for that group are understood to be linking groups.

[0829] The term “n-membered” where n is an integer typically describes the number of ringforming atoms in a moiety where the number of ring-forming atoms is n. For example, piperidinyl is an example of a 6-membered heterocycloalkyl ring, pyrazolyl is an example of a 5-membered heteroaryl ring, pyridyl is an example of a 6-membered heteroaryl ring, and 1,2,3,4-tetrahydro-naphthalene is an example of a 10-membered cycloalkyl group.

[0830] As used herein, the phrase “optionally substituted'’ means unsubstituted or substituted. The substituents are independently selected, and substitution may be at any chemically accessible position. As used herein, the term “substituted” means that a hydrogen atom is removed and replaced by a substituent. A single divalent substituent, e.g., oxo, can replace two hydrogen atoms. It is to be understood that substitution at a given atom is limited by valency, that the designated atom’s normal valency is not exceeded, and that the substitution results in a stable compound.

[0831] As used herein, the term “independently selected from” means that each occurrence of a variable or substituent are independently selected at each occurrence from the applicable list.

[0832] As used herein, the phrase “each ‘variable’ is independently selected from” means substantially the same as wherein “at each occurrence ‘variable’ is selected from.” When any variable (e.g., RG) occurs more than one time in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 1, 2, 3, or 4 independently selected RGsubstituents, then said group may optionally be substituted with up to four RGgroups and RGat each occurrence is selected independently from the definition of RG.

[0833] In some embodiments, substituents are indicated as floating substituents — e.g., (R?)nin Formula (I):

[0834]

[0835] It is understood that substituent R3can occur n number of times on the ring, and R3can be a different moiety at each occurrence. It is to be understood that each R group may replace any hydrogen atom attached to a ring atom, except that R3may not replace -L-R4in the variable X. (R5)Pis another example of a floating substituent.

[0836] Throughout the definitions, the term “Cn-m” indicates a range which includes the endpoints, wherein n and m are integers and indicate the number of carbons. Examples include C 1-3, C1-4, Ci-6, and the like.

[0837] As used herein, the term “Cn-m alkyd’; employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chain or branched, having n to m carbons. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl (Me), ethyl (Et), n-propyl («-Pr), isopropyl ( / -Pr), n-butyl, tert-butyl, isobutyl, sec-butyl; higher homologs such as 2-methyl-l -butyl, / ?-pentyl. 3-pentyl, / ?-hexyl, 1,2,2-trimethylpropyl, and the like. In some embodiments, the alkyl group contains from 1 to 6 carbon atoms, from 1 to 4 carbon atoms, from 1 to 3 carbon atoms, or 1 to 2 carbon atoms.

[0838] As used herein, “Cn-malkenyl” refers to an alkyl group having one or more double carbon-carbon bonds and having n to m carbons. Example alkenyl groups include, but are not limited to, ethenyl, w-propenyl, isopropenyl. «-butenyl, sec-butenyl, and the like. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

[0839] As used herein, “Cn-malkynyl” refers to an alkyl group having one or more triple carbon-carbon bonds and having n to m carbons. Example alky ny l groups include, but are not limited to, ethynyl. propyn-l-yl, propyn-2-yl, and the like. In some embodiments, the alkynyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. As used herein, the term "‘Cn-m alkoxy”, employed alone or in combination with other terms, refers to a group of formula-O-alkyl, wherein the alkyl group has n to m carbons. Example alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy (e.g., w-propoxy and isopropoxy), butoxy (e.g. n- butoxy and / e / 7-butoxy). and the like. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0840] As used herein, the term "amino" refers to a group of formula -NH2.

[0841] As used herein, the term “aryl,” employed alone or in combination with other terms, refers to an aromatic hydrocarbon group, which may be monocyclic or polycyclic (e.g., having 2 fused rings). The term “Cn-maryl” refers to an aryl group having from n to m ring carbon atoms. In some embodiments, the aryl group has 6 to 10 carbon atoms. In some embodiments, the aryl group is phenyl or naphthyl. In some embodiments, the aryl is phenyl.

[0842] As used herein, “halo” refers to F, Cl, Br, or I. In some embodiments, halo is F, Cl, or Br. In some embodiments, halo is F or Cl. In some embodiments, halo is F. In some embodiments, halo is Cl.

[0843] As used herein, “Cn-m haloalkoxy” refers to a group of formula -O-haloalkyl having n to m carbon atoms. Example haloalkoxy groups include OCF3 and OCHF2. In some embodiments, the haloalkoxy group is fluorinated only. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0844] As used herein, the term “Cn-m haloalkyl,” employed alone or in combination with other terms, refers to an alkyl group having from one halogen atom to 2s+l halogen atoms which may be the same or different, where “s” is the number of carbon atoms in the alky l group, wherein the alkyl group has n to m carbon atoms. In some embodiments, the haloalkyl group is fluorinated only. In some embodiments, the alkyl group of the haloalkyl has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. Example haloalkyl groups include CFs, C2F5, CHF2, CH2F, CCh, CHCI2, C2CI5 and the like.

[0845] As used herein, the term “thio” refers to a group of formula -SH.

[0846] As used herein, the term “Cn-malkvlammo" refers to a group of formula -NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alk l group of the alkylamino has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0847] As used herein, the term “Cn-malkoxy carbonyl” refers to a group of formula -C(O)O-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkoxy carbonyl has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0848] As used herein, the term “Cn malkylcarbonyl” refers to a group of formula -C(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylcarbonyl has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0849] As used herein, the term “Cn-m alk Icarbonylamino” refers to a group of formula -NHC(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylcarbonylamino has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0850] As used herein, the term "‘Cn-m alkoxy carbonylamino” refers to a group of formula -NHC(O)O(Cn-m alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkoxycarbonylamino has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0851] As used herein, the term ”Cn-m alky I sulfon l ami no" refers to a group of formula -NHS(O)2-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alky l group of the alkylsulfonylamino has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0852] As used herein, the term “aminosulfonyl” refers to a group of formula -S(O)2NH2. As used herein, the term "‘Cn-m alkylaminosulfonyl" refers to a group of formula -S(O)2NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylaminosulfonyl has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0853] As used herein, the term '‘di(Cn-m alkyl)aminosulfonyl” refers to a group of formula -S(O)2N(alkyl)2, wherein each alkyl group independently has n to m carbon atoms. In some embodiments, each alkyl group of the dialkylaminosulfonyl has, independently, 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0854] As used herein, the term "aminosulfonyl ammo" refers to a group of formula -NHS(O)2NH2.

[0855] As used herein, the term “Cn-m alkylaminosulfonylamino” refers to a group of formula -NHS(O)2NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylaminosulfonylamino has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0856] As used herein, the term “di(Cn-malkyl)aminosulfonylamino” refers to a group of formula -NHS(O)2N(alkyl)2, wherein each alkyl group independently has n to m carbon atoms. In some embodiments, each alkyl group of the dialkylaminosulfonylamino has, independently, 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0857] As used herein, the term '‘aminocarbonylamino,” employed alone or in combination with other terms, refers to a group of formula -NHC(0)NH2.

[0858] As used herein, the term “Cn-malkylaminocarbonylamino” refers to a group of formula -NHC(O)NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylaminocarbonylamino has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0859] As used herein, the term “di(Cn-m alkyl)aminocarbonylamino” refers to a group of formula -NHC(O)N(alkyl)2, wherein each alkyl group independently has n to m carbon atoms. In some embodiments, each alkyl group of the dialkylaminocarbonylamino has, independently, 1 to 6, 1 to 4. or 1 to 3 carbon atoms.

[0860] As used herein, the term “Cn-m alkylcarbamyl” refers to a group of formula -C(O)-NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alk l group of the alky lcarbamyl has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0861] As used herein, the term “Cn-malkylthio" refers to a group of formula -S-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alky l group of the alkylthio has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0862] As used herein, the term “Cn-m alkylsulfinyl” refers to a group of formula -S(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alky l group of the alk lsulfin l has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0863] As used herein, the term “Cn-m alkylsulfonyf’ refers to a group of formula -S(O)2-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylsulfonyl has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0864] As used herein, the term “cyano-Cn-malkyl” refers to a group of formula -(Cn-m alkylene)-CN, wherein the alkylene group has n to m carbon atoms. As used herein, the term “cyano-Ci-6 alkyl” refers to a group of formula -(Ci-6 alkylene)-CN. As used herein, the term “cyano-Ci-3 alkyl” refers to a group of formula -(C1-3 alkylene)-CN.

[0865] As used herein, the term “HO-Cn-malkyl” refers to a group of formula -(Cn-m alkylene)-OH, wherein the alkylene group has n to m carbon atoms. As used herein, the term “HO-C1-3 alkyl” refers to a group of formula -(C1-3 alkylene)-OH.

[0866] As used herein, the term “Cn-m alkoxy-Co-Palkyl” refers to a group of formula -(Cn-malkylene)-O(Co-p alky l), wherein the alkylene group has n to m carbon atoms and the alky l group has 0 to p carbon atoms. As used herein, the term “C1-6 alkoxy-Ci-6 alkyl” refers to a group of formula -(C1-6 alky lene)-O(C 1-6 alkyl). As used herein, the term “C1-3 alkoxy-Ci-3 alkyl” refers to a group of formula -(C1-3 alkylene)-O(Ci-3 alkyl).

[0867] As used herein, the term “carboxy” refers to a group of formula -C(O)OH.

[0868] As used herein, the term “di(Cn-m-alkyl)amino” refers to a group of formula -N(alkyl)2, wherein the two alkyl groups each has, independently, n to m carbon atoms. In some embodiments, each alkyl group of the dialkylamino independently has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0869] As used herein, the term “di(Cn-m-alkyl)carbamyl” refers to a group of formula -C(O)N(alkyl)2, wherein the two alkyl groups each has, independently, n to m carbon atoms. In some embodiments, each alkyl group of the dialkylcarbamyl independently has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0870] As used herein, the term “Cn-m alkylcarbonyloxy” is a group of formula -OC(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alk l group of the alkylcarbonyloxy has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0871] As used herein, “aminocarbonyloxy” is a group of formula -0C(0)-NH2.

[0872] As used herein. “Cn-malkylaminocarbonyloxy” is a group of formula -OC(O)-NH-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylaminocarbonyloxy has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0873] As used herein, “di(Cn-malkyl)aminocarbonyloxy” is a group of formula -OC(O)-N(alkyl)2, wherein each alkyl group has, independently, n to m carbon atoms. In some embodiments, each alkyl group of the dialkylaminocarbonyloxy independently has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0874] As used herein “Cn-malkoxycarbonylamino” refers to a group of formula -NHC(O)-O-alkyl, wherein the alkyl group has n to m carbon atoms.

[0875] As used herein, the term “carbamyl” to a group of formula -C(0)NH2.

[0876] As used herein, the term “carbonyl,” employed alone or in combination with other terms, refers to a -C(O)- group.

[0877] As used herein, “cycloalkyl” refers to non-aromatic cyclic hydrocarbons including cyclized alkyl and alkenyl groups. Cycloalkyl groups can include mono- or polycyclic (e.g., having 2, 3 or 4 fused rings) groups, spirocycles, and bridged rings (e.g., a bridged bicycloalkyl group). Ring-forming carbon atoms of a cycloalkyd group can be optionally substituted by oxo or sulfido (e.g., C(O) or C(S)). Also included in the definition of cycloalkyd are moi eties that have one or more aromatic rings fused (z.e., having a bond in common with) to the cycloalkyl ring, for example, benzo or thienyl derivatives of cyclopentane, cyclohexane, and the like. A cycloalkyl group containing a fused aromatic ring can be attached through any ring-forming atom including a ring-forming atom of the fused aromatic ring. Cycloalkyl groups can have 3, 4, 5. 6, 7, 8, 9, or 10 ring-forming carbons (z.e., C3-10). In some embodiments, the cycloalkyl is a C3-10 monocyclic or bicyclic cycloalkyl. In some embodiments, the cycloalkyl is a C3-7 monocyclic cycloalkyd. In some embodiments, the cycloalkyl is a C4-7 monocyclic cycloalkyl. In some embodiments, the cycloalkyl is a C4-10 spirocycle or bridged cycloalkyl (e.g., a bridged bicycloalkyl group). Example cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptatrienyl, norbomyl, norpinyl, norcamyl, cubane, adamantane, bicyclo[l.l.l]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptanyl, bicyclo[3.1.1]heptanyl, bicyclo[2.2.2]octanyl, spiro[3.3]heptanyl. and the like. In some embodiments, cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0878] As used herein, “heteroaryl” refers to a monocyclic or polycyclic (e.g., having 2, 3, or 4 fused rings) aromatic heterocycle having at least one heteroatom ring member selected from N, O, or S. In some embodiments, any ring-forming N in a heteroaryl moiety can be an N-oxide. In some embodiments, the heteroaryl is a 5-10 membered monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected fromN, O, and S. In some embodiments, the heteroaryl is a 5-6 monocyclic heteroaryl having 1 or 2 heteroatom ring members independently selected fromN, O, and S. In some embodiments, the heteroaryl group contains 5 to 10 or 5 to 6 ring-forming atoms. In some embodiments, the heteroaryl group has 1 to 4 ring-forming heteroatoms, 1 to 3 ring-forming heteroatoms, 1 to 2 ring-forming heteroatoms or 1 ring-forming heteroatom. When the heteroaryl group contains more than one heteroatom ring member, the heteroatoms may be the same or different.

[0879] Example heteroaryl groups include, but are not limited to, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrazolyl, azolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, furyl, thienyl, triazolyl (e.g., 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-triazolyl), tetrazolyl, thiadiazolyl (e.g., 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl), quinolinyl, isoquinolinyl, indolyl, benzothienyl, benzofuranyl, benzisoxazolyl, imidazo[l,2-b]thiazolyl, purinyl, triazinyl, thieno[3,2-d]pyridinyl, imidazo[I,2-«]pyridinyl, 1.5-naphthyridinyl, 17 / -pyrazolo[4,3-?]pyridinyl, oxadiazolyl (e.g., 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl), l,2-dihydro-l,2-azoborinyl, and the like.

[0880] As used herein, “heterocycloalkyl” refers to monocyclic or polycyclic heterocycles having at least one non-aromatic ring (saturated or partially unsaturated ring), wherein one or more of the ring-forming carbon atoms of the heterocycloalkyd is replaced by a heteroatom selected from N, O, or S, and wherein the ring-forming carbon atoms and heteroatoms of the heterocycloalkyl group can be optionally substituted by one or more oxo or sulfido (e.g., C(O), S(O), C(S), or S(O)2, etc.). Heterocycloalkyl groups include monocyclic and polycyclic e.g, having 2 fused rings) systems. Included in heterocycloalkyl are monocyclic and polycyclic 4-10-, 4-7-, and 5-6-membered heterocycloalkyl groups. Heterocycloalkyl groups can also include spirocycles and bridged rings. The heterocycloalkyl group can be attached through a ring-forming carbon atom or a ring-forming heteroatom. In some embodiments, the heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, the heterocycloalkyl group contains 0 to 2 double bonds.

[0881] Also included in the definition of heterocycloalkyl are moi eties that have one or more aromatic rings fused (z.e., having a bond in common with) to the non-aromatic heterocyclic ring, for example, benzo or thienyl derivatives of piperidine, morpholine, azepine, etc. A heterocycloalkyl group containing a fused aromatic ring can be attached through any ringforming atom including a ring-forming atom of the fused aromatic ring. In some embodiments, the heterocy cloalkyl group contains 4 to 10 ring-forming atoms, 4 to 7 ringforming atoms. 4 to 6 ring-forming atoms or 5 to 6 ring-forming atoms. In some embodiments, the heterocycloalkyl group has 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms or 1 heteroatom.

[0882] In some embodiments, the heterocycloalkyl is a 4-10 membered monocyclic, bicyclic, or tricyclic heterocycloalkyl having 1. 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, wherein 1, 2, 3, or 4 ring-forming carbon or heteroatoms can be optionally substituted by7one or more oxo or sulfido. In some embodiments, the heterocycloalkyl is a 4-10 membered bicyclic heterocycloalkyl having 1, 2, 3, or 4 ringforming heteroatoms independently selected fromN, O, and S, wherein 1, 2, 3. or 4 ringforming carbon or heteroatoms can be optionally substituted by one or more oxo or sulfido. In some embodiments, the heterocycloalkyl is a 4-7 membered monocyclic heterocycloalkyl having 1 or 2 ring-forming heteroatoms independently selected from N, O, and S, and wherein 1, 2 or 3 ring-forming carbon or heteroatoms can be optionally substituted by one or more oxo or sulfido. In some embodiments, the heterocycloalky7! is a monocyclic 4-6 membered heterocycloalkyl having 1 or 2 heteroatoms independently selected from N, O, S, and B and having one or more oxidized ring members.

[0883] Examples of heterocycloalkyl groups include pyrrolidin-2-one, l,3-isoxazolidin-2-one, pyranyl. tetrahydropyran, oxetanyl. azetidinyl, morpholino, thiomorpholino, piperazinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, pyrrolidinyl, isoxazolidinyl, isothiazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, azepanyl, benzazapene, 1,2,3,4-tetrahydroisoquinoline, azabicyclo[3.1.0]hexanyl, diazabicyclo[3.1.0]hexanyl, oxabicyclo[2.1.1]hexanyl, azabicyclo[2.2. l]heptanyl, azabicyclo[2.2.1]heptan-7-yl, azabicyclo[2.2.1]heptan-2-yl, diazabicyclo[2.2. IJheptanyL azabicyclo[3.1,l]heptanyl, diazabicyclo[3.1 l]heptanyl, azabicyclo[3.2. l]octanyl, diazabicyclo[3.2.1]octanyl, oxabicyclo[2.2.2]octanyl, azabicyclo[2.2.2]octanyl, azaadamantanyl, diazaadamantanyl, oxa-adamantanyl, azaspiro[3.3]heptanyl, diazaspiro[3.3]heptanyl, oxa-azaspiro[3.3]heptanyl, azaspiro [3.4] octanyl, diazaspiro[3.4]octanyl, oxa-azaspiro[3.4]octanyl, azaspiro[2.5]octanyl, diazaspiro[2.5]octanyl, azaspiro[4.4]nonanyl, diazaspiro[4.4]nonanyl, oxa-azaspiro[4.4]nonanyl, azaspiro[4.5]decanyl, diazaspiro[4.5]decanyl, diazaspiro[4.4]nonanyl, oxa-diazaspiro[4.4]nonanyL and the like.

[0884] As used herein, “Co pcycloalkyl-Cn-m alkyl-” refers to a group of formula cycloalkylalkydene-, wherein the cycloalkyl has o to p carbon atoms and the alkylene linking group has n to m carbon atoms.

[0885] As used herein “Co-Paryl-Cn-m alkyl-” refers to a group of formula aryl-alkylene-. wherein the aryl has o to p carbon ring members and the alkylene linking group has n to m carbon atoms.

[0886] As used herein, “heteroary l -Cn-malk 1-” refers to a group of formula heteroarylalkylene-, wherein alky lene linking group has n to m carbon atoms.

[0887] As used herein “heterocycloalkyl-Cn-m alkyl-” refers to a group of formula heterocycloalkyl-alkylene-, wherein alkylene linking group has n to m carbon atoms.

[0888] As used herein, the term “alky lene” refers a divalent straight chain or branched alky 1 linking group. Examples of “alky lene groups” include methylene, ethan- 1,1 -diyl. ethan- 1,2-diyl, propan-1.3-dilyl, propan- 1.2-diyl, propan- 1,1 -diyl and the like.

[0889] As used herein, the term “alkenylene” refers a divalent straight chain or branched alkenyl linking group. Examples of “alkenylene groups” include ethen- 1,1 -diyl, ethen-1,2-diyl, propen-1, 3-diyl, 2-buten-l,4-diyl, 3-penten-l,5-diyl, 3-hexen-l,6-diyl, 3-hexen-l,5-diyl, and the like.

[0890] As used herein, the term “alkynylene” refers a divalent straight chain or branched alkynyl linking group. Examples of “alkynylene groups” include propyn-1, 3-diyl, 2-butyn-1,4-diyl, 3-pentyn-l,5-diyl, 3-hexyn-l,6-diyl, 3-hexyn-l,5-diyl, and the like.

[0891] As used herein, an “alkyl linking group” is a bivalent straight chain or branched alkyl linking group (“alkylene group”). For example, “Co-Pcycloalkyl-Cn-m alkyl-”, “Co-Paryl-Cn-m alkyl-”, “phenyl-Cn-m alkyl-”, “heteroary 1-Cn-m alkyl-”, and “heterocycloalkyl-Cn-m alkyl-” contain alkyl linking groups. Examples of “alkyl linking groups” or “alkylene groups” include methylene, ethan- 1,1 -diyl, ethan- 1,2-diyl, propan- 1, 3-dilyl, propan- 1,2-diyl, propan-1,1 -diyl and the like. As used herein, the term “oxo” refers to an oxygen atom (i.e., =0) as a divalent substituent, forming a carbonyl group when attached to a carbon (e.g, C=0 or C(0)), or attached to a nitrogen or sulfur heteroatom forming a nitroso, sulfinyl or sulfonyl group.

[0892] As used herein, the term “independently selected from” means that each occurrence of a variable or substituent are independently selected at each occurrence from the applicable list.

[0893] At certain places, the definitions or embodiments refer to specific rings (e.g, an azetidine ring, a pyridine ring, etc.). Unless otherwise indicated, these rings can be attached to any ring member provided that the valency of the atom is not exceeded. For example, an azetidine ring may be attached at any position of the ring, whereas a pyridin-3-yl ring is attached at the 3-position.

[0894] The compounds described herein can be asymmetric (e.g, having one or more stereocenters). All stereoisomers, such as enantiomers and diastereomers, are intended unless otherwise indicated. Compounds of the present disclosure that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present disclosure are described and may be isolated as a mixture of isomers or as separated isomeric forms. In some embodiments, the compound has the (R) -configuration. In some embodiments, the compound has the ^-configuration. The Formulas (e.g, Formula (I), (II), etc.) provided herein include stereoisomers of the compounds.

[0895] Resolution of racemic mixtures of compounds can be carried out by any of numerous methods known in the art. An example method includes fractional recrystallization using a chiral resolving acid which is an optically active, salt-forming organic acid. Suitable resolving agents for fractional recrystallization methods are, for example, optically active acids, such as the D and L forms of tartaric acid, di acetyl tartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid or the various optically active camphorsulfonic acids such as P-camphorsulfonic acid. Other resolving agents suitable for fractional crystallization methods include stereoisomerically pure forms of a-methylbenzylamine (e., S and R forms, or diastereomerically pure forms), 2-phenylglycinol, norephedrine, ephedrine, N-methylephedrine, cyclohexylethylamine, 1,2-di aminocyclohexane, and the like. Resolution of racemic mixtures can also be carried out by elution on a column packed with an optically active resolving agent (e.g., dinitrobenzoylphenylglycine). Suitable elution solvent composition can be determined by one skilled in the art.

[0896] Compounds provided herein also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone-enol pairs, amide- imidic acid pairs, lactam-lactim pairs, enamine-imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H- isoindole, 2-hydroxypyridine and 2-pyridone, and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. It is intended that the claims to one tautomer cover both tautomers even if not specified.

[0897] All compounds, and pharmaceutically acceptable salts thereof, can be found together with other substances such as water and solvents (e.g., hydrates and solvates) or can be isolated.

[0898] In some embodiments, preparation of compounds can involve the addition of acids or bases to affect, for example, catalysis of a desired reaction or formation of salt forms such as acid addition salts.

[0899] In some embodiments, the compounds provided herein, or salts thereof, are substantially isolated. By “substantially isolated” is meant that the compound is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched in the compounds provided herein. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compounds provided herein, or salt thereof. Methods for isolating compounds and their salts are routine in the art.

[0900] The term “compound” as used herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted. Compounds herein identified by name or structure as one particular tautomeric form are intended to include other tautomeric forms unless otherwise specified.

[0901] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0902] The present application also includes pharmaceutically acceptable salts of the compounds described herein. As used herein, “pharmaceutically acceptable salts” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts of the present disclosure include the conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present disclosure can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, non-aqueous media like ether, ethyl acetate, alcohols (e.g., methanol, ethanol, iso-propanol, or butanol) or acetonitrile (ACN) are preferred. Lists of suitable salts are found in Remington 's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science. 66. 2 (1977). each of which is incorporated herein by reference in its entirety7.

[0903] Synthesis

[0904] As will be appreciated by those skilled in the art, the compounds provided herein, including salts and stereoisomers thereof, can be prepared using known organic synthesis techniques and can be synthesized according to any of numerous possible synthetic routes, such as those provided in the Schemes below.

[0905] The reactions for preparing compounds described herein can be carried out in suitable solvents which can be readily selected by one of skill in the art of organic synthesis. Suitable solvents can be substantially non-reactive with the starting materials (reactants), the intermediates or products at the temperatures at which the reactions are carried out, e.g, temperatures which can range from the solvent’s freezing temperature to the solvent’s boiling temperature. A given reaction can be carried out in one solvent or a mixture of more than one solvent. Depending on the particular reaction step, suitable solvents for a particular reaction step can be selected by the skilled artisan.

[0906] The expressions, '‘ambient temperature” or “room temperature” or “r.t.” as used herein, are understood in the art, and refer generally to a temperature, e.g., a reaction temperature, that is about the temperature of the room in which the reaction is carried out, for example, a temperature from about 20 °C to about 30 °C.

[0907] Preparation of compounds of the invention can involve the protection and deprotection of various chemical groups. The need for protection and deprotection, and the selection of appropriate protecting groups, can be readily determined by one skilled in the art. The chemistry of protecting groups is described, e.g., in Kocienski, Protecting Groups, (Thieme. 2007); Robertson, Protecting Group Chemistry. (Oxford University Press, 2000); Smith et al., March ’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6thEd. (Wiley, 2007); Peturssion et al., “Protecting Groups in Carbohydrate Chemistry,” J. Chem. Educ., 1997, 7 (11), 1297; and Wuts et al., Protective Groups in Organic Synthesis, 4th Ed., (Wiley, 2006).

[0908] Reactions can be monitored according to any suitable method known in the art. For example, product formation can be monitored by spectroscopic means, such as nuclear magnetic resonance spectroscopy (e.g.,1H or13C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), mass spectrometry or by chromatographic methods such as high performance liquid chromatography (HPLC), liquid chromatography-mass spectroscopy (LCMS), or thin layer chromatography (TLC). Compounds can be purified by those skilled in the art by a variety of methods, including high performance liquid chromatography (HPLC) and normal phase silica chromatography.

[0909] The Schemes below provide general guidance in connection with preparing the compounds of the invention. One skilled in the art would understand that the preparations shown in the Schemes can be modified or optimized using general knowdedge of organic chemistry to prepare various compounds of the invention.

[0910] As will be appreciated by those skilled in the art, the compounds provided herein, including salts and stereoisomers thereof, can be prepared using known organic synthesis techniques and can be synthesized according to any of numerous possible synthetic routes.

[0911] Compounds of Formula 1-5 can be synthesized, for example, according to the process shown in Scheme 1. As depicted in Scheme 1. nucleophilic substitution reactions of compounds of Formula 1-1 (i.e.. w here Hal is a suitable halogen, such as CL Br, or I) and electrophiles of the general Formula 1-2 (i.e., where LG is a suitable leaving group, such as a halogen or mesylate group) under appropriate conditions (e.g., in the presence of abase, such as CS2CO3. in a suitable solvent, such as dimethylformamide) generates compounds of Formula 1-3. Compounds of Formula 1-1 are commercially available or can be readily synthesized according to methods known by persons skilled in the art. Formylation of compounds of Formula 1-3 (e.g., via Vilsmeier-Haack reaction, for example, using POCI3 and DMF) generates compounds of Formula 1-4. Oxidation of compounds of Formula 1-4 under appropriate conditions (e.g.. via Pinnick oxidation) furnishes compounds of Formula 1-5.

[0912] Scheme 1.

[0913]

[0914] 1-1 1-3 1-4 1-5 Compounds of Formula (I) can be synthesized, for example, using the process illustrated in Scheme 2. In the process depicted in Scheme 2, esterification of compounds of Formula 1-5 under appropriate conditions (e.g., in the presence of trimethylsilyldiazomethane) generates compounds of Formula 2-1. Borylation of compounds of Formula 2-1 under appropriate conditions (e.g., using aborylating reagent, such as bis(pinacolato)diboron, in the presence of a suitable catalyst, such as Pd(dppf)Ch, and a base, such as KOAc. in an appropriate solvent, such as 1,4-dioxane) affords compounds of Formula 2-2. Suzuki reactions of compounds of Formula 2-2 and pyrimidines of Formula 2-3 (z.e.. where each Hal is a suitable halogen, such as Cl, Br, or I) under appropriate conditions (e.g., using a suitable palladium catalyst, such as Pd(dppf)C12, and a base, such as K2CO3, in an appropriate solvent, such as l,4-dioxane / H2O) affords compounds of Formula 2-4. A number of methods (e.g.. a suitable cross-coupling reaction or nucleophilic aromatic substitution) can be used to access compounds of Formula 2-6. For example, transition metal (e.g., Pd, Cu, Ni) catalyzed reactions (including, but not limited to, Buchwald couplings) of compounds 2-4 and appropriate amine nucleophiles of the general Formula 2-5 under appropriate conditions (e.g, in the presence of a suitable catalyst, such as GPhos Pd G6 TES, a base, such as NaOTMS, in a suitable solvent, such as THF) affords compounds of Formula 2-6.

[0915] Alternatively, compounds of Formula 2-4 (z.e., where Hal is a suitable halogen, such as Cl) can be reacted with an appropriate amine nucleophile of Formula 2-5 under appropriate conditions (e.g., in the presence of abase, such as A, A-diisopropylethylamine, in an appropriate solvent, such as dimethylformamide) to generate compounds of Formula 2-6.

[0916] Saponification of compounds of Formula 2-6 under appropriate conditions (e.g.. using a suitable reagent, such as Li OH) furnishes compounds of Formula 2-7. Amidation of compounds of Formula 2-7 and amines of Formula 2-8 under appropriate conditions (e.g., in the presence of an amide coupling reagent, such as HATU, and a base, such as N, N-diisopropylethylamine) affords compounds of Formula (1).

[0917] Scheme 2.

[0918]

[0919] Compounds of Formula (I) can be synthesized, for example, according to the process show n in Scheme 3. As depicted in Scheme 3, amidation of compounds of Formula 1-5 and amines of Formula 2-8 under appropriate conditions (e.g., in the presence of an amide coupling reagent, such as HATU, and a base, such as A, A-diisopropylethylamine) affords compounds of Formula 3-1. Borylation of compounds of Formula 3-1 under appropriate conditions (e.g., using a borylating reagent, such as bis(pinacolato)diboron, in the presence of a suitable catalyst, such as Pd(dppf)C12, and a base, such as KO Ac, in an appropriate solvent, such as 1,4-di oxane) affords compounds of Formula 3-2. Suzuki reactions of compounds of Formula 3-2 and pyrimidines of Formula 2-3 (i.e., where each Hal is a suitable halogen, such as Cl, Br, or I) under appropriate conditions (e.g., using a suitable palladium catalyst, such as Pd(dppf)Ch, and abase, such as K2CO3, in an appropriate solvent, such as 1,4-di oxane / H2O) affords compounds of Formula 3-3. A number of methods (e.g.. a suitable cross-coupling reaction or nucleophilic aromatic substitution) can be used to access compounds of Formula 3-3. For example, transition metal (e.g., Pd, Cu, Ni) catalyzed reactions (including, but not limited to, Buchwald couplings) of compounds 3-3 and appropriate amine nucleophiles of the general Formula 2-5 under appropriate conditions (e.g., in the presence of a suitable catalyst, such as GPhos Pd G6 TES, a base, such as NaOTMS, in a suitable solvent, such as THF) affords compounds of Formula (I). Alternatively, compounds of Formula 3-3 (i.e., where Hal is a suitable halogen, such as Cl) can be reacted with an appropriate amine nucleophile of Formula 2-5 under appropriate conditions (e.g, in the presence of a base, such as A, A-diisopropylethylamine, in an appropriate solvent, such as dimethylformamide) to generate compounds of Formula (I).

[0920]

[0921] Compounds of Formula 4-5 can be synthesized, for example, using the process illustrated in Scheme 4. In the process depicted in Scheme 4, nucleophilic aromatic substitution reactions of compounds of Formula 4-1 (i.e., where Hal is a suitable halogen, such as Cl, Br, or I) and primary amines of the general Formula 4-2 under appropriate conditions (e.g. in the presence of a base, such as CS2CO3, in a suitable solvent, such as dimethylformamide, followed by treatment with an acid, such as HC1) generates compounds of Formula 4-3. Compounds of Formula 4-1 are commercially available or can be readily synthesized according to methods known by persons skilled in the art. Formation of the indole ring occurs via reaction of compounds of Formula 4-3 with alpha-diazo esters of Formula 4-4 (e.g, ethyl diazoacetate) under appropriate conditions (e.g., in the presence of a Lewis acid, such as BF3 Et2O, in a suitable solvent, such as CH2CI2) generates compounds of Formula 4-5. In certain cases, Formula 4-5 is a version of Formula 2-1 where R8is H.

[0922] Scheme 4.

[0923]

[0924] 4-1 4-3 4-5 Methods of Use

[0925] Compounds of the present disclosure (and pharmaceutically acceptable salts thereof) can inhibit CDK4 and therefore are useful for treating diseases wherein the underlying pathology is, wholly or partially, mediated by CDK4. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, inhibit CDK4. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, are selective for CDK.4 over CDK1, CDK6, and / or CDK7. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, are selective for CDK4 over CDK1. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, are selective for CDK4 over CDK.7. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, are selective for CDK4 over CDK6. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, inhibit CDK2 and CDK4. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, are selective for CDK4 over CDK.6. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, are selective for CDK4 over CDK.6. In some embodimetns, the selectivity referenced in each of the embodiments of this paragraph is at least 2-fold, at least 3-fold, at least 5-fold, or at least 10-fold. Such diseases include cancer and other diseases with proliferation disorder. In some embodiments, the present disclosure provides treatment of an individual or a patient in vivo using a compound of Formula (I) or a salt thereof such that growth of cancerous tumors is inhibited. A compound of Formula (I) or of any of the formulas as described herein, or a compound as recited in any of the claims and described herein, or a salt thereof, can be used to inhibit the growth of cancerous tumors with aberrations that activate the CDK4 kinase activity. These include, but are not limited to, disease (e.g, cancers) that are characterized by amplification or overexpression of CCNE1 such as ovarian cancer, uterine carcinosarcoma and breast cancer and p27 inactivation such as breast cancer and melanomas. Accordingly, in some embodiments of the methods, the patient has been previously determined to have an amplification of the cyclin El (CCNE1) gene and / or an expression level of CCNE1 in a biological sample obtained from the human subject that is higher than a control expression level of CCNE1. Alternatively, a compound of Formula (I) or of any of the formulas as described herein, or a compound as recited in any of the claims and described herein, or a salt thereof, can be used in conjunction with other agents or standard cancer treatments, as described below. In one embodiment, the present disclosure provides a method for inhibiting grow th of tumor cells in vitro. The method includes contacting the tumor cells in vitro with a compound of Formula (I) or of any of the formulas as described herein, or of a compound as recited in any of the claims and described herein, or of a salt thereof. In another embodiment, the present disclosure provides a method for inhibiting growth of tumor cells w ith CCNE1 amplification and overexpression in an individual or a patient. The method includes administering to the individual or patient in need thereof a therapeutically effective amount of a compound of Formula (I) or of any of the formulas as described herein, or of a compound as recited in any of the claims and described herein, or a salt or a stereoisomer thereof.

[0926] In some embodiments, provided herein is a method of inhibiting CDK4, comprising contacting the CDK4 with a compound of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or a salt thereof. In some embodiments, provided herein is a method of inhibiting CDK4 in a patient, comprising administering to the patient a compound of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or a salt thereof.

[0927] In some embodiments, provided herein is a method for treating cancer. The method includes administering to a patient (in need thereof), a therapeutically effective amount of a compound of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or a salt thereof. In another embodiment, the cancer is characterized by amplification or overexpression of CCNE1. In some embodiments, the cancer is ovarian cancer or breast cancer, characterized by amplification or overexpression of CCNE1.

[0928] In some embodiments, provided herein is a method of treating a disease or disorder associated with CDK4 in a patient, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or a salt thereof. In some embodiments, the disease or disorder associated with CDK4 is associated with an amplification of the cyclin El (CCNE1) gene and / or overexpression of CCNE1.

[0929] In another embodiment, the cancer is characterized by amplification or overexpression of CCNE1. In some embodiments, the cancer is characterized by amplification or overexpression of CCND1. In some embodiments, the cancer is characterized by amplification or overexpression of CCND1 and CCNE1.

[0930] In some embodiments, the cancer is ovarian cancer or breast cancer, characterized by amplification or overexpression of CCNE1. In some embodiments, the cancer is ovarian cancer or breast cancer, characterized by amplification or overexpression of CCND1. In some embodiments, the cancer is ovarian cancer or breast cancer, characterized by amplification or overexpression of CCNE1 and CCND1.

[0931] In some embodiments, the cancer is hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-). In some embodiments, the cancer is breast cancer which is hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-). In some embodiments, the cancer is metastatic breast cancer which is hormone receptor positive (HR+) and human epidermal grow th factor receptor 2 negative (HER2-). In some embodiments, the cancer is metastatic breast cancer.

[0932] In some embodiments, the cancer is a cancer which is platinum sensitive. In some embodiments, the cancer is gynecological cancer which is platinum sensitive. In some embodiments, the cancer is gynecological cancer which is platinum resistant. Such gynecological cancers include ovarian, breast, prostate, pancreatic or uterine cancer. In some embodiments, the cancer is ovarian cancer which is platinum sensitive. As used herein, platinum refers to platinum-based chemotherapy treatment.

[0933] In some embodiments, the cancer is a cancer which is platinum resistant. In some embodiments, the cancer is ovarian cancer which is platinum resistant. In some embodiments, the cancer is endometrioid cancer or a cancer with amplification or overexpression of CCNE1 or CCD1. In some embodiments, the cancer is a cancer driven by CDK4 or CCND1 signaling (e.g, CDK+ solid tumors). In some embodiments, the CDK+ cancer is breast cancer, a gynecological cancer, a gastrointestinal cancer, prostate cancer, a sarcoma or melanoma. In some embodiments, the cancer is a cancer driven by CDK4 or CCND1 signaling (e.g, CDK+ solid tumors). In some embodiments, the CDK+ cancer is HR+ / HER2- breast cancer, HR+ / HER2+ breast cancer, metastatic castration-resistant prostate cancer, ovarian cancer, endometrial cancer, esophageal cancer, gastric cancer, colorectal cancer, liposarcoma, Ewing sarcoma, or melanoma.

[0934] In some embodiments, the cancer is breast cancer. In some embodiments, the cancer is ovarian cancer. In some embodiments, the cancer is a gynecological cancer. In some embodiments, the cancer is a gastrointestinal cancer. In some embodiments, the cancer is prostate cancer. In some embodiments, the cancer is a sarcoma. In some embodiments, the cancer is melanoma. In some embodiments, the cancer is HR+ / HER2- breast cancer. In some embodiments, the cancer is HR+ / HER2+ breast cancer. In some embodiments, the cancer is metastatic castration-resistant prostate cancer. In some embodiments, the cancer is endometrial cancer. In some embodiments, the cancer is esophageal cancer. In some embodiments, the cancer is gastric cancer. In some embodiments, the cancer is colorectal cancer. In some embodiments, the cancer is liposarcoma. In some embodiments, the cancer is Ewing sarcoma. In some embodiments, the cancer is melanoma.

[0935] In some embodiments, the disease or disorder associated with CDK.4 is N-myc amplified neuroblastoma cells (see Molenaar, et al., Proc Natl Acad Sci USA 106(31): 12968-12973) K-Ras mutant lung cancers (see Hu, S., et al., Mol Cancer Ther, 2015. 14(11): 2576-85, and cancers with FBW7 mutation and CCNE1 overexpression (see Takadac / al., Cancer Res, 2017. 77(18): 4881-4893).

[0936] In some embodiments, the disease or disorder associated with CDK.4 is lung squamous cell carcinoma, lung adenocarcinoma, pancreatic adenocarcinoma, breast invasive carcinoma, uterine carcinosarcoma, ovarian serous cystadenocarcinoma, stomach adenocarcinoma, esophageal carcinoma, bladder urothelial carcinoma, mesothelioma, or sarcoma.

[0937] In some embodiments, the disease or disorder associated with CDK4 is lung adenocarcinoma, breast invasive carcinoma, uterine carcinosarcoma, ovarian serous cystadenocarcinoma, or stomach adenocarcinoma.

[0938] In some embodiments, the disease or disorder associated with CDK.4 is an adenocarcinoma, carcinoma, or cystadenocarcinoma. In some embodiments, the disease or disorder associated with CDK4 is uterine cancer, ovarian cancer, stomach cancer, esophageal cancer, lung cancer, bladder cancer, pancreatic cancer, or breast cancer.

[0939] In some embodiments, the disease or disorder associated with CDK4 is a cancer.

[0940] In some embodiments, the cancer is characterized by amplification or overexpression of CCNE1. In some embodiments, the cancer is ovarian cancer or breast cancer, characterized by amplification or overexpression of CCNE1.

[0941] In some embodiments, the breast cancer is chemotherapy or radiotherapy resistant breast cancer, endocrine resistant breast cancer, trastuzumab resistant breast cancer, or breast cancer demonstrating primary or acquired resistance to CDK4 / 6 inhibition. In some embodiments, the breast cancer is advanced or metastatic breast cancer.

[0942] Examples of cancers that are treatable using the compounds of the present disclosure include, but are not limited to, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, endometrial cancer, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin’s Disease, non-Hodgkin’s lymphoma, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, chronic or acute leukemias including acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, solid tumors of childhood, lymphocytic lymphoma, cancer of the bladder, cancer of the kidney or urethra, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary’ CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi’s sarcoma, epidermoid cancer, squamous cell cancer, T-cell lymphoma, environmentally induced cancers including those induced by asbestos, and combinations of said cancers. The compounds of the present disclosure are also useful for the treatment of metastatic cancers.

[0943] In some embodiments, cancers treatable with compounds of the present disclosure include melanoma (e.g., metastatic malignant melanoma, BRAF and HSP90 inhibition-resistant melanoma), renal cancer (e.g., clear cell carcinoma), prostate cancer (e.g., hormone refractory’ prostate adenocarcinoma), breast cancer, colon cancer, lung cancer (e.g, non-small cell lung cancer and small cell lung cancer), squamous cell head and neck cancer, urothelial cancer (e.g., bladder) and cancers with high microsatellite instability' (MSIhlgh). Additionally, the disclosure includes refractory or recurrent malignancies whose growth may be inhibited using the compounds of the disclosure.

[0944] In some embodiments, cancers that are treatable using the compounds of the present disclosure include, but are not limited to, solid tumors (e.g., prostate cancer, colon cancer, esophageal cancer, endometrial cancer, ovarian cancer, uterine cancer, renal cancer, hepatic cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, cancers of the head and neck, thyroid cancer, glioblastoma, sarcoma, bladder cancer, etc.), hematological cancers (e.g, lymphoma, leukemia such as acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), DLBCL, mantle cell lymphoma. Non-Hodgkin lymphoma (including follicular lymphoma, including relapsed or refractory NHL and recurrent follicular), Hodgkin lymphoma or multiple myeloma) and combinations of said cancers.

[0945] In some embodiments, cancers that are treatable using the compounds of the present disclosure include, but are not limited to, cholangiocarcinoma, bile duct cancer, triple negative breast cancer, rhabdomyosarcoma, small cell lung cancer, leiomyosarcoma, hepatocellular carcinoma, Ewing’s sarcoma, brain cancer, brain tumor, astrocytoma, neuroblastoma, neurofibroma, basal cell carcinoma, chondrosarcoma, epithelioid sarcoma, eye cancer, Fallopian tube cancer, gastrointestinal cancer, gastrointestinal stromal tumors, hairy cell leukemia, intestinal cancer, islet cell cancer, oral cancer, mouth cancer, throat cancer, laryngeal cancer, lip cancer, mesothelioma, neck cancer, nasal cavity cancer, ocular cancer, ocular melanoma, pelvic cancer, rectal cancer, renal cell carcinoma, salivary gland cancer, sinus cancer, spinal cancer, tongue cancer, tubular carcinoma, urethral cancer, and ureteral cancer.

[0946] In some embodiments, the compounds of the present disclosure can be used to treat sickle cell disease and sickle cell anemia.

[0947] In some embodiments, diseases and indications that are treatable using the compounds of the present disclosure include, but are not limited to hematological cancers, sarcomas, lung cancers, gastrointestinal cancers, genitourinary tract cancers, liver cancers, bone cancers, nervous system cancers, gynecological cancers, and skin cancers.

[0948] Exemplary hematological cancers include lymphomas and leukemias such as acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), acute promyelocytic leukemia (APL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), diffuse large B-cell lymphoma (DLBCL). mantle cell lymphoma, Non-Hodgkin lymphoma (including relapsed or refractory NHL and recurrent follicular), Hodgkin lymphoma, myeloproliferative diseases (e.g, primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocytosis (ET), myelodysplasia syndrome (MDS), T-cell acute lymphoblastic lymphoma (T-ALL) and multiple myeloma (MM).

[0949] Exemplary sarcomas include chondrosarcoma, Ewing’s sarcoma, osteosarcoma, rhabdomyosarcoma, angiosarcoma, fibrosarcoma, liposarcoma, myxoma, rhabdomyoma, rhabdosarcoma, fibroma, lipoma, harmatoma, and teratoma.

[0950] Exemplary lung cancers include non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), bronchogenic carcinoma, squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma, alveolar (bronchiolar) carcinoma, bronchial adenoma, chondromatous hamartoma, and mesothelioma.

[0951] Exemplary gastrointestinal cancers include cancers of the esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors, vipoma), small bowel (adenocarcinoma, lymphoma, carcinoid tumors, Kaposi’s sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large bowel (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma), and colorectal cancer.

[0952] Exemplary genitourinary tract cancers include cancers of the kidney (adenocarcinoma, Wilm’s tumor [nephroblastoma]), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), and testis (seminoma, teratoma, embryonal carcinoma, teratocarcinoma. choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumors, lipoma).

[0953] Exemplary liver cancers include hepatoma (hepatocellular carcinoma), cholangiocarcinoma. hepatoblastoma, angiosarcoma, hepatocellular adenoma, and hemangioma.

[0954] Exemplary bone cancers include, for example, osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing’s sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochrondroma (osteocartilaginous exostoses), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma, and giant cell tumors.

[0955] Exemplary7nervous system cancers include cancers of the skull (osteoma, hemangioma, granuloma, xanthoma, osteitis deformans), meninges (meningioma, meningiosarcoma, gliomatosis), brain (astrocytoma, medulloblastoma, glioma, ependymoma, germinoma (pinealoma), glioblastoma, glioblastoma multiform, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors), and spinal cord (neurofibroma, meningioma, glioma, sarcoma), as well as neuroblastoma and Lhermitte-Duclos disease.

[0956] Exemplary gynecological cancers include cancers of the uterus (endometrial carcinoma), cervix (cervical carcinoma, pre -tumor cervical dysplasia), ovaries (ovarian carcinoma (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa-thecal cell tumors, Sertoli-Leydig cell tumors, dysgerminoma, malignant teratoma), vulva (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, botry oid sarcoma (embry onal rhabdomyosarcoma), and fallopian tubes (carcinoma).

[0957] Exemplary skin cancers include melanoma, basal cell carcinoma, Merkel cell carcinoma, squamous cell carcinoma, Kaposi’s sarcoma, moles dysplastic nevi, lipoma, angioma, dermatofibroma, and keloids. In some embodiments, diseases and indications that are treatable using the compounds of the present disclosure include, but are not limited to, sickle cell disease (e.g, sickle cell anemia), triple-negative breast cancer (TNBC), myelodysplastic syndromes, testicular cancer, bile duct cancer, esophageal cancer, and urothelial carcinoma.

[0958] It is believed that compounds of Formula (I), or any of the embodiments thereof, may possess satisfactory’ pharmacological profile and promising biopharmaceutical properties, such as toxicological profile, metabolism and pharmacokinetic properties, solubility, and permeability. It will be understood that determination of appropriate biopharmaceutical properties is within the knowledge of a person skilled in the art, e.g., determination of cytotoxicity' in cells or inhibition of certain targets or channels to determine potential toxicity.

[0959] The terms "individual”, "patient.” and “subject” used interchangeably, refer to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and most preferably humans.

[0960] The phrase “therapeutically effective amount” refers to the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue, system, animal, individual or human that is being sought by a researcher, veterinarian, medical doctor or other clinician.

[0961] As used herein, the term “treating” or “treatment” refers to one or more of (1) inhibiting the disease; e.g.. inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (z.e., arresting further development of the pathology and / or symptomatology ); and (2) ameliorating the disease; e.g., ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and / or symptomatology) such as decreasing the severity of disease.

[0962] In some embodiments, the compounds of the invention are useful in preventing or reducing the risk of developing any of the diseases referred to herein; e.g., preventing or reducing the nsk of developing a disease, condition or disorder in an individual who may be predisposed to the disease, condition or disorder but does not yet experience or display the pathology' or symptomatology of the disease.

[0963] Combination Therapies

[0964] I. Cancer therapies

[0965] Cancer cell growth and survival can be impacted by dysfunction in multiple signaling pathways. Thus, it is useful to combine different enzyme / protein / receptor inhibitors, exhibiting different preferences in the targets which they modulate the activities of, to treat such conditions. Targeting more than one signaling pathway (or more than one biological molecule involved in a given signaling pathway) may reduce the likelihood of drug-resistance arising in a cell population, and / or reduce the toxicity of treatment.

[0966] In some embodiments, the one or more additional pharmaceutical agents is an aromatase inhibitor, luteinizing hormone-releasing hormone (LHRH) agonist, an antiandrogen, therapy targeting the PI3K / AKT / mT0R (PAM) pathway, a selective estrogen receptor degrader (SERD). a CDK2 inhibitor, a CDK4 / 6 inhibitor, a CDK4 inhibitor, or VEGF-A inhibitor, or a combination thereof.

[0967] In some embodiments, the VEGF-A inhibitor is bevacizumab.

[0968] In some embodiments, the PAM therapy is alpelisib, capivasertib, or everolimus, or a pharmaceutically acceptable salt thereof.

[0969] In some embodiments, the SERD is fluvestrant, camizestrant, amcenestrant, elacestrant, giredestrant, imlunestrant, rintodestrant, AZD9496, borestrant, taragarestrant, and ZN-c5, or a pharmaceutically acceptable salt thereof.

[0970] In some embodiments, the CDK4 / 6 inhibitor is albociclib, ribociclib, albociclib, abemaciclib, or dalpiciclib, or a pharmaceutically acceptable salt thereof. In some embodiments, the CDK4 inhibitor is atirmociclib or a pharmaceutically acceptable salt thereof. In some embodiments, the CDK2 inhibitor is ebvaciclib, or a pharmaceutically acceptable salt thereof. In some embodiments, the CDK2 inhibitor is an Example compound (or a pharmaceutically acceptable salt thereof) disclosed in the specifications of US Patent Nos. 11,066,404, 11,384,083, 11,472,791, 11,919,904, 11,440,914, 11,447,494, 11,427,567, 11,851,426, and 11,981,671 and US Patent Publ. Nos. US 20220340579, US 20230192706, and US 20230183250, each of which is incorporated herein by reference in its entirety. In some embodiments, the CDK2 inhibitor is 8-ethoxy-N-((3R,4S)-3-methyl-l-(methylsulfonyl)piperidin-4-yl)-7-(lH-pyrazol-4-yl)-[l,2,4]triazolo[l,5-a]pyridin-2-amine; N-((3R,4S)-l-(cyclopropylsulfonyl)-3-methylpiperidin-4-yl)-8-ethoxy-7-(lH-pyrazol-4-yl)-[l,2,4]triazolo[l,5-a]pyridin-2-amine; 8-isopropoxy-N-((3R,4S)-3-methyl-l-(methylsulfonyl)piperidin-4-yl)-7-(lH-pyrazol-4-yl)-[1.2.4]tri azolof l,5-c]pyrimidin-2-amine; 8-(ethoxy-d5)-N-((3R,4S)-3-methyl-l-(methylsulfonyl)piperidin-4-yl)-7-(lH-pyrazol-4-yl)-[l,2,4]triazolo[l,5-a]pyridin-2-amine; or 8-isopropoxy-N-((3R,4S)-3-methyl-l-(methylsulfonyl)piperidin-4-yl)-7-(lH-pyrazol-4-yl)-[l,2,4]triazolo[l,5-a]pyridin-2-amine; or a

[0971] In some embodiments, the aromatase inhibitor is anastrozole, exemestane, letrozole, vorozole, formestane, or fadrozole (or a pharmaceutically acceptable salt thereof).

[0972] In some embodiments, the LHRH agonist is leuprolide, goserelin, triptorelin, histrelin, or buserelin (or a pharmaceutically acceptable salt thereof).

[0973] In some embodiments, the anti-androgen is spironolactone, finasteride, dutasteride. bicalutamide, flutamide, enzalutamide, apalutamide, cyproterone, abiraterone, chlormadinone, clascoterone, megestrol, nilutamide, or darolutamide (or a pharmaceutically acceptable salt thereof).

[0974] One or more additional pharmaceutical agents such as, for example, chemotherapeutics, anti-inflammatory agents, steroids, immunosuppressants, immune-oncology agents, metabolic enzy me inhibitors, chemokine receptor inhibitors, and phosphatase inhibitors, as well as targeted therapies such as Bcr-Abl, Flt-3, EGFR, HER2, JAK, c-MET, VEGFR, PDGFR. c-Kit, IGF-1R. RAF. FAK, and CDK4 / 6 kinase inhibitors such as, for example, those described in WO 2006 / 056399 can be used in combination with the compounds of the present disclosure for treatment of CDK4 -associated diseases, disorders or conditions. Other agents such as therapeutic antibodies can be used in combination with the compounds of the present disclosure for treatment of CDK.4 -associated diseases, disorders or conditions. The one or more additional pharmaceutical agents can be administered to a patient simultaneously or sequentially. In some embodiments, the compound or salt is administered or used in combination with a BCL2 inhibitor.

[0975] The compounds as disclosed herein can be used in combination with one or more other enzyme / protein / receptor inhibitors therapies for the treatment of diseases, such as cancer and other diseases or disorders described herein. Examples of diseases and indications treatable with combination therapies include those as described herein. Examples of cancers include solid tumors and non-solid tumors, such as liquid tumors, and blood cancers.

[0976] Examples of infections include viral infections, bacterial infections, fungus infections or parasite infections. For example, the compounds of the present disclosure can be combined with one or more inhibitors of the following kinases for the treatment of cancer: Aktl, Akt2, Akt3, BCL2, CDK4 / 6, TGF-0R, PKA, PKG, PKC, CaM-kinase, phosphorylase kinase, MEKK, ERK, MAPK, mTOR, EGFR, HER2, HER3, HER4, INS-R, IDH2, IGF-1R, IR-R, PDGFaR, PDGF R, PI3K (alpha, beta, gamma, delta, and multiple or selective), CSF1R, KIT, FLK-II. KDR / FLK-1, FLK-4, flt-1, FGFR1. FGFR2, FGFR3. FGFR4, c-Met, PARP. Ron, Sea, TRKA, TRKB, TRKC, TAM kinases (Axl, Mer, Tyro3), FLT3, VEGFR / F1I2, Flt4, EphAl, EphA2, EphA3, EphB2, EphB4, Tie2, Src, Fyn, Lek, Fgr, Btk, Fak, SYK, FRK, JAK, ABL, ALK and B-Raf. In some embodiments, the compounds of the present disclosure can be combined with one or more of the following inhibitors for the treatment of cancer or infections. Non-limiting examples of inhibitors that can be combined with the compounds of the present disclosure for treatment of cancer and infections include an FGFR inhibitor (FGFR1, FGFR2, FGFR3 or FGFR4, e.g., pemigatinib (INCB54828), INCB62079), an EGFR inhibitor (also known as ErB-1 or HER-1; e.g.. erlotinib, gefitinib, vandetanib, orsimertinib. cetuximab, necitumumab, or panitumumab), a VEGFR inhibitor or pathway blocker (e.g., bevacizumab, pazopanib, sunitinib, sorafenib, axitinib, regorafenib, ponatinib, cabozantinib, vandetanib, ramucirumab, lenvatinib, ziv-aflibercept), a PARP inhibitor (e.g., olaparib, rucaparib, veliparib or niraparib), a JAK inhibitor (JAK1 and / or JAK2, e.g., ruxolitinib or baricitinib; JAK1, e.g., itacitinib (INCB39110). INCB052793, or INCB054707), an IDO inhibitor (e.g., epacadostat, NLG919, or BMS-986205, MK7162), an LSD1 inhibitor (e.g., GSK2979552, INCB59872 and INCB60003), a TDO inhibitor, a PI3K-delta inhibitor (e.g., parsaclisib (INCB50465) or INCB50797), a PI3K-gamma inhibitor such as PI3K-gamma selective inhibitor, a Pirn inhibitor (e.g., INCB53914), a CSF1R inhibitor, a TAM receptor tyrosine kinases (Tyro-3, Axl, and Mer; e.g., INCB081776), an adenosine receptor antagonist (e g., A2a / A2b receptor antagonist), an HPK1 inhibitor, a chemokine receptor inhibitor (e.g., CCR2 or CCR5 inhibitor), a SHP1 / 2 phosphatase inhibitor, a histone deacetylase inhibitor (HD AC) such as an HD AC 8 inhibitor, an angiogenesis inhibitor, an interleukin receptor inhibitor, bromo and extra terminal family members inhibitors (for example, bromodomain inhibitors or BET inhibitors such as INCB54329 and INCB57643), c-MET inhibitors (e.g, capmatinib), an anti-CD19 antibody (e.g, tafasitamab), an ALK2 inhibitor (e.g., INCB00928); or combinations thereof.

[0977] In some embodiments, the compound or salt described herein is administered with a PI3K5 inhibitor. In some embodiments, the compound or salt described herein is administered with a JAK inhibitor. In some embodiments, the compound or salt described herein is administered with a JAK1 or JAK2 inhibitor (e.g, baricitinib or ruxolitinib). In some embodiments, the compound or salt described herein is administered with a JAK1 inhibitor. In some embodiments, the compound or salt described herein is administered with a JAK1 inhibitor, which is selective over JAK2.

[0978] Example antibodies for use in combination therapy include, but are not limited to, trastuzumab (e.g., anti-HER2), ranibizumab (e.g., anti-VEGF-A). bevacizumab (AVASTIN™, e.g., anti-VEGF), panitumumab (e.g, anti-EGFR), cetuximab (e.g, anti-EGFR), rituxan (e.g., anti-CD20), and antibodies directed to c-MET.

[0979] One or more of the following agents may be used in combination with the compounds of the present disclosure and are presented as a non-limiting list: a cytostatic agent, cisplatin, doxorubicin, taxotere, taxol. etoposide, irinotecan, camptosar, topotecan. paclitaxel, docetaxel, epothilones, tamoxifen, 5-fluorouracil, methotrexate, temozolomide, cyclophosphamide, SCH 66336, R115777, L778,123, BMS 214662, IRESSA™(gefitinib), TARCEVA™ (erlotinib), antibodies to EGFR, intron. ara-C, adriamycin. cytoxan, gemcitabine, uracil mustard, chlormethine, ifosfamide, melphalan, chlorambucil, pipobroman, triethylenemelamine, triethylenethiophosphoramine, busulfan, carmustine, lomustine, streptozocin, dacarbazine, floxuridine, cytarabine, 6-mercaptopurine, 6-thioguanine, fludarabine phosphate, oxaliplatin, leucovirin, ELOXATIN™ (oxaliplatin), pentostatine, vinblastine, vincristine, vindesine, bleomycin, dactinomycin, daunorubicin. doxorubicin, epirubicin, idarubicin, mithramycin, deoxy coformycin, mitomycin-C, L-asparaginase, teniposide, 17-alpha-ethinylestradiol, diethylstilbestrol, testosterone, prednisone, fluoxymesterone, dromostanolone propionate, testolactone, megestrolacetate, methylprednisolone, methyltestosterone, prednisolone, triamcinolone, chlorotrianisene, hydroxyprogesterone, aminoglutethimide, estramustine. medroxyprogesterone acetate, leuprolide, flutamide, toremifene, goserelin, carboplatin, hydroxyurea, amsacrine, procarbazine, mitotane, mitoxantrone, levamisole, navelbene, anastrazole, letrazole, capecitabine. reloxafine, droloxafme, hexamethylmelamine, avastin, HERCEPTIN™ (trastuzumab), BEXXAR™ (tositumomab), VELCADE™ (bortezomib), ZEVALIN™ (ibritumomab tiuxetan), TRISENOX™ (arsenic trioxide), XELODA™ (capecitabine), vinorelbine, porfimer, ERBITUX™ (cetuximab), thiotepa, altretamine, melphalan, trastuzumab, lerozole, fulvestrant, exemestane, ifosfomide, rituximab, C225 (cetuximab), Campath (alemtuzumab), clofarabine, cladribine, aphidicolon, rituxan, sunitinib, dasatinib, tezacitabine, Smll, fludarabine, pentostatin, triapine, didox, trimidox, amidox, 3-AP, and MDL-101,731.

[0980] The compounds of the present disclosure can further be used in combination with other methods of treating cancers, for example by chemotherapy, irradiation therapy, tumor-targeted therapy, adjuvant therapy, immunotherapy or surgery. Examples of immunotherapy include cytokine treatment (e.g., interferons, GM-CSF, G-CSF, IL-2), CRS-207 immunotherapy, cancer vaccine, monoclonal antibody, bispecific or multi-specific antibody, antibody drug conjugate, adoptive T cell transfer, Toll receptor agonists, RIG-I agonists, oncolytic virotherapy and immunomodulating small molecules, including thalidomide or JAK1 / 2 inhibitor, PI3K5 inhibitor and the like. The compounds can be administered in combination with one or more anti-cancer drugs, such as a chemotherapeutic agent. Examples of chemotherapeutics include any of: abarelix, aldesleukin, alemtuzumab, alitretinoin, allopurinol, altretamine, anastrozole, arsenic trioxide, asparaginase, azacitidine, bevacizumab, bexarotene, baricitinib, bleomycin, bortezomib, busulfan intravenous, busulfan oral, calusterone, capecitabine, carboplatin, carmustine, cetuximab, chlorambucil, cisplatin, cladribine, clofarabine, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, dalteparin sodium, dasatinib, daunorubicin. decitabine. denileukin, denileukin diftitox, dexrazoxane, docetaxel, doxombicin, dromostanolone propionate, eculizumab, epirubicin, erlotinib, estramustine, etoposide phosphate, etoposide, exemestane, fentanyl citrate, filgrastim, floxuridine, fludarabine, fluorouracil, fulvestrant, gefitinib, gemcitabine, gemtuzumab ozogamicin, goserelin acetate, histrelin acetate, ibritumomab tiuxetan, idarubicin, ifosfamide, imatinib mesylate, interferon alfa 2a, irinotecan, lapatinib ditosylate, lenalidomide, letrozole, leucovorin, leuprolide acetate, levamisole, lomustine, meclorethamine, megestrol acetate, melphalan, mercaptopurine, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, nandrolone phenpropionate, nelarabine, nofetumomab. oxaliplatin, paclitaxel, pamidronate, panitumumab. pegaspargase, pegfilgrastim, pemetrexed disodium, pentostatin, pipobroman, plicamycin, procarbazine, quinacrine, rasburicase, rituximab, ruxolitinib, sorafenib, streptozocin, sunitinib, sunitinib maleate, tamoxifen, temozolomide, teniposide, testolactone, thalidomide, thioguanine, thiotepa. topotecan, toremifene. tositumomab, trastuzumab, tretinoin, uracil mustard, valrubicin, vinblastine, vincristine, vinorelbine, vorinostat, and zoledronate.

[0981] Additional examples of chemotherapeutics include proteasome inhibitors (e.g., bortezomib), thalidomide, revlimid, and DNA-damaging agents such as melphalan, doxorubicin, cyclophosphamide, vincristine, etoposide, carmustine. and the like.

[0982] Example steroids include corticosteroids such as dexamethasone or prednisone.

[0983] Example Bcr-Abl inhibitors include imatinib mesylate (GLEEVAC™), nilotinib, dasatinib, bosutinib, and ponatinib, and pharmaceutically acceptable salts. Other example suitable Bcr-Abl inhibitors include the compounds, and pharmaceutically acceptable salts thereof, of the genera and species disclosed in U. S. Pat. No. 5,521,184, WO 04 / 005281, and U. S. Ser. No. 60 / 578,491.

[0984] Example suitable Flt-3 inhibitors include midostaurin, lestaurtinib, linifanib, sunitinib, sunitinib. maleate, sorafenib, quizartinib, crenolanib, pacritinib. tandutinib. PLX3397 and ASP2215, and their pharmaceutically acceptable salts. Other example suitable Flt-3 inhibitors include compounds, and their pharmaceutically acceptable salts, as disclosed in WO 03 / 037347, WO 03 / 099771, and WO 04 / 046120.

[0985] Example suitable RAF inhibitors include dabrafenib, sorafenib, and vemurafenib, and their pharmaceutically acceptable salts. Other example suitable RAF inhibitors include compounds, and their pharmaceutically acceptable salts, as disclosed in WO 00 / 09495 and WO 05 / 028444.

[0986] Example suitable FAK inhibitors include VS -4718, VS-5095, VS-6062, VS-6063, BI853520, and GSK2256098, and their pharmaceutically acceptable salts. Other example suitable FAK inhibitors include compounds, and their pharmaceutically acceptable salts, as disclosed in WO 04 / 080980, WO 04 / 056786, WO 03 / 024967, WO 01 / 064655, WO 00 / 053595, and WO 01 / 014402.

[0987] Example suitable CDK4 / 6 inhibitors include palbociclib, ribociclib. trilaciclib, lerociclib, and abemaciclib, and their pharmaceutically acceptable salts. Other example suitable CDK4 / 6 inhibitors include compounds, and their pharmaceutically acceptable salts, as disclosed in WO 09 / 085185, WO 12 / 129344, WO 11 / 101409, WO 03 / 062236, WO 10 / 075074. and WO 12 / 061156. In some embodiments, the compounds of the disclosure can be used in combination with one or more other kinase inhibitors including imatinib, particularly for treating patients resistant to imatinib or other kinase inhibitors.

[0988] In some embodiments, the compounds of the disclosure can be used in combination with a chemotherapeutic in the treatment of cancer, and may improve the treatment response as compared to the response to the chemotherapeutic agent alone, without exacerbation of its toxic effects. In some embodiments, the compounds of the disclosure can be used in combination with a chemotherapeutic provided herein. For example, additional pharmaceutical agents used in the treatment of multiple myeloma, can include, without limitation, melphalan, melphalan plus prednisone [MP], doxorubicin, dexamethasone, and V el cade (bortezomib). Further additional agents used in the treatment of multiple myeloma include Bcr-Abl, Flt-3, RAF and FAK kinase inhibitors. In some embodiments, the agent is an alky lating agent, a proteasome inhibitor, a corticosteroid, or an immunomodulatory agent. Examples of an alkylating agent include cyclophosphamide (CY), melphalan (MEL), and bendamustine. In some embodiments, the proteasome inhibitor is carfilzomib. In some embodiments, the corticosteroid is dexamethasone (DEX). In some embodiments, the immunomodulatory agent is lenalidomide (LEN) or pomalidomide (POM). Additive or synergistic effects are desirable outcomes of combining a compound or salt of the present disclosure with an additional agent.

[0989] The agents can be combined with the present compound in a single or continuous dosage form, or the agents can be administered simultaneously or sequentially as separate dosage forms.

[0990] The compounds of the present disclosure can be used in combination with one or more other inhibitors or one or more therapies for the treatment of infections. Examples of infections include viral infections, bacterial infections, fungus infections or parasite infections.

[0991] In some embodiments, a corticosteroid such as dexamethasone is administered to a patient in combination with the compounds of the disclosure where the dexamethasone is administered intermittently as opposed to continuously.

[0992] The compounds of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or salts thereof can be combined with another immunogenic agent, such as cancerous cells, purified tumor antigens (including recombinant proteins, peptides, and carbohydrate molecules), cells, and cells transfected with genes encoding immune stimulating cytokines. Non-limiting examples of tumor vaccines that can be used include peptides of melanoma antigens, such as peptides of gplOO, MAGE antigens, Trp-2, MARTI and / or tyrosinase, or tumor cells transfected to express the cytokine GM-CSF.

[0993] The compounds of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or salts thereof can be used in combination with a vaccination protocol for the treatment of cancer. In some embodiments, the tumor cells are transduced to express GM-CSF. In some embodiments, tumor vaccines include the proteins from viruses implicated in human cancers such as Human Papilloma Viruses (HPV), Hepatitis Viruses (HBV and HCV) and Kaposi’s Herpes Sarcoma Virus (KHSV). In some embodiments, the compounds of the present disclosure can be used in combination with tumor specific antigen such as heat shock proteins isolated from tumor tissue itself. In some embodiments, the compounds of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or salts thereof can be combined with dendritic cells immunization to activate potent anti-tumor responses.

[0994] The compounds of the present disclosure can be used in combination with bispecific macrocyclic peptides that target Fe alpha or Fe gamma receptor-expressing effectors cells to tumor cells. The compounds of the present disclosure can also be combined with macrocyclic peptides that activate host immune responsiveness.

[0995] In some further embodiments, combinations of the compounds of the disclosure with other therapeutic agents can be administered to a patient prior to, during, and / or after a bone marrow transplant or stem cell transplant. The compounds of the present disclosure can be used in combination with bone marrow transplant for the treatment of a variety of tumors of hematopoietic origin.

[0996] The compounds of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or salts thereof can be used in combination with vaccines, to stimulate the immune response to pathogens, toxins, and self -antigens. Examples of pathogens for which this therapeutic approach may be particularly useful include pathogens for which there is currently no effective vaccine, or pathogens for which conventional vaccines are less than completely effective. These include, but are not limited to, HIV, Hepatitis (A, B, & C), Influenza, Herpes, Giardia, Malaria, Leishmania, Staphylococcus aureus, Pseudomonas Aeruginosa.

[0997] Viruses causing infections treatable by methods of the present disclosure include, but are not limited to human papillomavirus, influenza, hepatitis A, B, C or D viruses, adenovirus, poxvirus, herpes simplex viruses, human cytomegalovirus, severe acute respiratory syndrome virus, Ebola virus, measles vims, herpes virus (e.g., N N, HSV-1, HAV-6, HSV-II, and CMV, Epstein Barr virus), flaviviruses, echovirus, rhinovirus, coxsackie vims, comovirus, respiratory syncytial vims, mumps vims, rotavirus, measles virus, rubella vims, parvovirus, vaccinia vims, HTLV vims, dengue virus, papillomavirus, molluscum virus, poliovims. rabies virus, JC virus and arboviral encephalitis virus.

[0998] Pathogenic bacteria causing infections treatable by methods of the disclosure include, but are not limited to, chlamydia, rickettsial bacteria, mycobacteria, staphylococci, streptococci, pneumococci, meningococci and conococci, klebsiella, proteus, serratia, pseudomonas, legionella, diphtheria, salmonella, bacilli, cholera, tetanus, botulism, anthrax, plague, leptospirosis, and Lyme’s disease bacteria.

[0999] Pathogenic fungi causing infections treatable by methods of the disclosure include, but are not limited to, Candida (albicans, krusei, glabrata, tropicalis, etc.), Cryptococcus neoformans, Aspergillus (fumigatus, niger, etc.), Genus Mucorales (mucor, absidia, rhizophus). Sporothrix schenkii, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Coccidioides immitis and Histoplasma capsulatum.

[1000] Pathogenic parasites causing infections treatable by methods of the disclosure include, but are not limited to, Entamoeba histolytica, Balantidium coli, Naegleriafowleri, Acanthamoeba sp.. Giardia lambia, Cryptosporidium sp., Pneumocystis carinii, Plasmodium vivax, Babesia microti, Trypanosoma bmcei, Trypanosoma cmzi, Leishmania donovani. Toxoplasma gondi, and Nippostrongylus brasiliensis.

[1001] When more than one pharmaceutical agent is administered to a patient, they can be administered simultaneously, separately, sequentially, or in combination (e, for more than two agents).

[1002] Methods for the safe and effective administration of most of these chemotherapeutic agents are known to those skilled in the art. In addition, their administration is described in the standard literature. For example, the administration of many of the chemotherapeutic agents is described in the ‘“Physicians’ Desk Reference” (PDR, e.g, 1996 edition, Medical Economics Company, Montvale, NJ), the disclosure of which is incorporated herein by reference as if set forth in its entirety'.

[1003] II. Immune-checkpoint therapies

[1004] Compounds of the present disclosure can be used in combination with one or more immune checkpoint inhibitors for the treatment of diseases, such as cancer or infections. Exemplary immune checkpoint inhibitors include inhibitors against immune checkpoint molecules such as CBL-B, CD20, CD28, CD40, CD70, CD122, CD96, CD73, CD47, CDK2, CDK4. GITR, CSF1R. JAK. PI3K delta, PI3K gamma, TAM, arginase, HPK1. CD137 (also known as 4-1BB), ICOS, A2AR, B7-H3, B7-H4, BTLA, CTLA-4, LAG3, TIM3, TLR (TLR7 / 8), TIGIT, CD112R, VISTA, PD-1, PD-L1 and PD-L2. In some embodiments, the immune checkpoint molecule is a stimulatory checkpoint molecule selected from CD27, CD28, CD40, ICOS, 0X40, GITR and CD137. In some embodiments, the immune checkpoint molecule is an inhibitory checkpoint molecule selected from A2AR, B7-H3, B7-H4, BTLA, CTLA-4, IDO, KIR, LAG3, PD-1, TIM3, TIGIT, and VISTA. In some embodiments, the compounds provided herein can be used in combination with one or more agents selected from KIR inhibitors, TIGIT inhibitors, LAIR1 inhibitors, CD 160 inhibitors, 2B4 inhibitors and TGFR beta inhibitors.

[1005] In some embodiments, the compounds provided herein can be used in combination with one or more agonists of immune checkpoint molecules, e.g., 0X40, CD27, GITR, and CD137 (also known as 4-1BB).

[1006] In some embodiments, the inhibitor of an immune checkpoint molecule is anti-PDl antibody, anti-PD-Ll antibody, or anti-CTLA-4 antibody.

[1007] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of PD-1 or PD-L1, e.g., an anti-PD-1 or anti-PD-Ll monoclonal antibody. In some embodiments, the anti-PD-1 or anti-PD-Ll antibody is nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab. cemiplimab, atezolizumab, avelumab. tislelizumab. spartalizumab (PDR001), cetrelimab (JNJ-63723283), toripalimab (JS001), camrelizumab (SHR-1210), sintilimab (IBI308), AB122 (GLS-010), AMP-224, AMP-514 / MEDI-0680, BMS936559, JTX-4014, BGB-108, SHR-1210, MEDI4736, FAZ053, BCD-100. KN035, CS1001, BAT1306, LZM009, AK105, HLX10. SHR-1316. CBT-502 (TQB2450). A167 (KL-A167), STI-A101 (ZKAB001), CK-301, BGB-A333, MSB-2311, HLX20, TSR-042, or LY3300054. In some embodiments, the inhibitor of PD-1 or PD-L1 is one disclosed in U. S. Pat. Nos. 7,488,802, 7,943,743, 8,008,449, 8,168,757, 8,217, 149, WO 03042402, WO 2008156712. WO 2010089411, WO 2010036959, WO 2011066342, WO 2011159877, WO 2011082400, or WO 2011161699, which are each incorporated herein by reference in its entirety.

[1008] In some embodiments, the an...

Claims

What is claimed is:

1. A compound of Formula (I):or a pharmaceutically acceptable salt thereof, wherein:n is 0, 1, 2, 3, 4, 5, or 6;X is O, S, S(O)2, S(O)NRC, orN(-L-R4);L is S(O)2, S(O)(=NRb), or S(O)2NRa;Ra, Rb, and Rcare each independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;R1is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-14 membered aryl. 4-15 membered heterocycloalkyl, 5-14 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyd, 6-14 membered aryl-Ci-4 alkyd, 4-15 membered heterocycloalkyl-Ci-4 alkyl, and 5-14 membered hcteroaiy l-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each R1Ais independently selected from H, D. halo. CN, NO2, Ci-6 alkyl. C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky d-C 1-4 alkyd, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalky I-C1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa", SRa”, NH0Ra",OP(O)(ORhll)(ORin), P(O)(ORhll)(ORin), and BRjllRk11, wherein said Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1.4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alky l, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;or, any Rcl1and Rdl1attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rb11is independently selected from C1-6alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl. 4-7 membered heterocy cloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyd, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Re11is independently selected from H, OH. CN, Ci-6 alkyl. Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy. C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl;each Rfl1and Rgl1is independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy. C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl;each Rhl1and R111is independently selected from H, Ci-6 alky l, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocy cloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;each R'11and Rkl1is independently selected from OH. Ci-6 alkoxy, and Ci-6 haloalkoxy;or, any R'" and Rkl1attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-6 alkyl and Ci-6 haloalkyl; each R1Bis independently selected from H, D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky l-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl. ORa12, SRa12, NH0Ra12, C(O)Rb12, C(O)NRcl2Rd12, C(O)NRc12(ORa12), C(O)ORa12, OC(O)Rb12, OC(O)NRol2Rd12, NRcl2Rd12, NRcl2NRcl2Rd12, NRcl2C(O)Rb12. NRol2C(O)ORa12, NRcl2C(O)NRol2Rd12.C(=NRel2)Rb12, C(=NRel2)NRcl2Rd12, NRcl2C(=NRel2)NRcl2Rd12, NRcl2C(=NRel2)Rb12, NRol2S(O)NRcl2Rd12, NRcl2S(O)Rb12, NRcl2S(O)2Rb12, NRcl2S(O)(=NRel2)Rb12, NRol2S(O)2NRcl2Rd12, S(O)Rb12, S(O)NRol2Rd12, S(O)2Rb12, S(O)2NRol2Rd12, OS(O)(=NRel2)Rb12, OS(O)2Rb12, S(O)(=NRel2)Rb12, SF5, P(O)Rfl2Rg12, OP(O)(OR1112)(ORi12), P(O)(ORhl2)(ORi12), and BRjl2Rk12, wherein said Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyL Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaiyl-Ci-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected RGsubstituents;each Ra12, Rc12, and Rd12is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cloalkyl-C 1-4 alky 1, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl. C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalky I-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;or, any Rcl2and Rdl2attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Rb12is independently selected from C1-6alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl,C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Rel2is independently selected from H, OH, CN, Ci-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;each Rtl2and Rgl2is independently selected from H, Ci-6 alkyd, CM alkoxy, C1-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;each Rhl2and R112is independently selected from H, Ci-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalky I-C1-4 alkyl, phenyl-Ci-4 alky l, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;each R'12and Rkl2is independently selected from OH, Ci-6 alkoxy, and Ci-6 haloalkoxy;or, any R'12and Rkl2attached to the same B atom, together w ith the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1.

2. 3, or 4 substituents independently selected from Ci-6 alkyl and Ci-6 haloalkyl;R2A, R2B, and R2Care each independently selected from H, D, halo, CN, Ci-6 alkyl, Cu 6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalky 1-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl. ORa2, SRa2, NH0Ra2, C(O)Rb2, C(O)NRo2Rd2, C(O)NRc2(ORa2), C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2NRc2Rd2, NRo2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, C(=NRe2)Rb2, C(=NRe2)NRc2Rd2, NRc2C(=NRe2)NRc2Rd2, NRo2C(=NRe2)Rb2, NRc2S(0)NRo2Rd2, NRo2S(0)Rb2, NRc2S(O)2Rb2, NRc2S(O)(=NRe2)Rb2, NRc2S(O)2NRo2Rd2, S(O)Rb2. S(O)NRo2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-8 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ra2, Rc2. and Rd2is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;or, any Rc2and Rd2attached to the same N atom, together with the N atom to which they are attached, form a 4-8 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Rb2is independently selected from C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Re2is independently selected from H. OH, CN. C1-6 alkyl, C1-6 alkoxy. C1-6 haloalkyl, and C 1-6 haloalkoxy;each R3is independently selected from D, halo, CN, C1-6 alkyl, C 1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl. OR13. SRa3. NH0Ra3, C(O)Rb3, C(O)NRc3Rd3.C(O)NRc3(ORa3), C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3NRc3Rd3, NRo3C(O)Rb3, NRo3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3C(=NRe3)Rb3, NRc3S(O)NRc3Rd3, NRc3S(O)Rb3, NRo3S(O)2Rb3. NRc3S(O)(=NRe3)Rb3, NRc3S(O)2NRo3Rd3. S(O)Rb3. S(O)NRo3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3, wherein said Cue alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ra3, Rc3, and Rd3is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Rb3is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Re3is independently selected from H, OH, CN, C1-6 alkyd, C1-6 alkoxy, C1-6 haloalkyl, and C 1-6 haloalkoxy;R4is selected from C1-6 alkyl, C1-6 haloalky l, C3-10 cycloalky l, 6-10 membered ary l, 4-10 membered heterocycloalkyl, 5-10 membered heteroary l. C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyd, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alky l, 6-10 membered aryd-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;each R4Ais independently selected from D, halo, CN, NO2, C1-6 alky 1, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl. 5-6 membered heteroar l-C 1.4 alkyl, ORa41, SRa41, NHORa41, C(O)Rb41, C(O)NRc41Rd41, C(O)NRc41(ORa41), C(O)ORa41, OC(O)Rb41, OC(O)NRo41Rd41, NRc41Rd41, NRc41NRc41Rd41, NRc4lC(O)Rb41, NRo41C(O)ORa41, NRc41C(O)NRc41Rd41, C(=NRe41)Rb41, C(=NRe41)NRo41Rd41, NRo41C(=NRe41)NRc41Rd41, NRc41C(=NRe41)Rb41. NRo41S(O)NRo41Rd41, NRc41S(O)Rb41, NRc41S(O)2Rb41, NRc41S(O)(=NRe41)Rb41, NRc41S(O)2NRc41Rd41, S(O)Rb41, S(O)NRc41Rd41, S(O)2Rb41, S(O)2NRc41Rd41, OS(O)(=NRe41)Rb41, OS(O)2Rb41, and S(O)(=NRe41)Rb41, wherein said Ci-6 alkyl, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl.phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;or, any Rc41and Rd41attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered helerocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Re41is independently selected from H, OH, CN, Ci-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, Ci-6 haloalkoxy, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;each R4Bis independently selected from D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered hetcroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl. OR142, SRa42. NHORa42, C(O)Rb42. C(O)NRc42Rd42, C(O)NRc42(ORa42), C(O)ORa42, OC(O)Rb42, OC(O)NRo42Rd42, NRc42Rd42, NRc42NRc42Rd42, NRo42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRo42Rd42, C(=NRe42)Rb42, C(=NRe42)NRo42Rd42, NRc42C(=NRe42)NRc42Rd42, NRc42C(=NRe42)Rb42, NRc42S(O)NRc42Rd42, NRc42S(O)Rb42, NRo42S(O)2Rb42. NRo42S(O)(=NRe42)Rb42. NRo42S(O)2NRo42Rd42, S(O)Rb42. S(O)NRc42Rd42, S(O)2Rb42, S(O)2NRc42Rd42, OS(O)(=NRe42)Rb42, OS(O)2Rb42, and S(O)(=NRe42)Rb42, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl.phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected RGsubstituents;each Rb42is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C 3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Re42is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, Ci-6 haloalkoxy, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;R3is selected from halo, CN, C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 alkoxy, C 1-3 haloalkoxy, amino, C 1-3 alkylamino, di(Ci-3 alkyl)amino, cyano-C 1-4 alkyl, HO-C1-4 alkyl, C1-3 alkoxy-Ci-4 alkyl. and C3-4 cycloalkyl;R6is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted by 1, 2, 3. 4, 5, or 6 independently selected R6Asubstituents;R7is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl. C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1.4 alky l, 4-8 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;or, R6and R7, together with the nitrogen atom to which they are attached, form a 4-15 membered heterocycloalkyl moiety or a 5-10 membered heteroaryl moiety, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents;each R6Ais independently selected from D, halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl-Ci-4 alkyl,OP(O)(ORh61)(OR161), P(O)(ORh61)(OR161), and BRj61Rk61, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alky l, wherein said Ci-6 alkyl, C2-6alkenyl, C2-6alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl. 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;or, any Rc61and Rd61attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each Re61is independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, C 1-6 haloalkoxy, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyd;each R161and Rg61is independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalky l, 5-10 membered heteroary l, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;each Rh61and R161is independently selected from H, Ci-6 alkyd, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalky l, 5-10 membered heteroary l, C3-10 cycloalkyl-Ci-4 alky l, 6-10 membered aryl-C1-4alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;each R'61and Rk61is independently selected from OH, Ci-6 alkoxy, and Ci-6 haloalkoxy;or, any R'61and Rk61attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-6 alkyl and Ci-6 haloalkyl;each R6Bis independently selected from D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalky l, C3-10 cycloalk 1, 6-10 membered ary l, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl-Ci-4 alkyl.OP(O)(ORh62)(ORi62), P(O)(ORh62)(ORi62), and BRj62Rk62, wherein said Ci-6alky l, C2-6alkenyl, C2-6 alkynyl, Ci-6 haloalkyl. C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 memberedheterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C1-4alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;or, any Rc62and Rd62attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyd group, which is optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;each Rb62is independently selected from Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10cycloalkyl-C1-4alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-C1-4alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1. 2, 3, or 4 independently selected R6Csubstituents;each Re62is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalky l, 5-10 membered heteroary l, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C1-4alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl;each R162and Rg62is independently selected from H, Ci-6 alkyd, C1-6 alkoxy, C1-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryd-Ci.4 alkyl;each Rh62and R162is independently selected from H, Ci-6 alkyd, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkyny l, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-C1-4alkyl, and 5-10 membered heteroaryl-C 1-4 alkyd;each Rj62and Rk62is independently selected from OH, Ci-6 alkoxy, and Ci-6 haloalkoxy;or, any R'62and Rk62attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-6 alkyd and C 1-6 haloalkyl;each R6Cis independently selected from D, halo, CN, NO2, Ci-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa63, SRa63, NHORa63,OP(O)(ORh63)(ORi63), P(O)(ORh63)(ORi63), and BRj63Rk63, wherein said Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroary l-C 1-4 alky l are each optionally substituted with 1, 2. 3, or 4 independently selected RGsubstituents;each Ra63, Rc63, and Rd63is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cy cloalkyl-C 1-4 alky 1, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;or, any Rc63and Rd63attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Rb63is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Re63is independently selected from H, OH. CN, Ci-6 alkyl. Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 memberedheterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;each R163and Rg63is independently selected from H, Ci-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl;each R1’63and R163is independently selected from H, C1-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alky 1, 4-7 membered heterocycloalky 1-C 1-4 alky 1, and 5-6 membered heteroaryl-C 1-4 alkyl;each R'63and Rk63is independently selected from OH. C1-6 alkoxy, and C1-6 haloalkoxy;or, any R'63and Rk63attached to the same B atom, together wi th the B atom to which they are attached, form a 5- or 6-membered heterocycloalky l group optionally substituted with 1, 2. 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl;R8is selected from H, D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-C1-4 alkyl, 4-8 membered heterocy cloalkyl-Ci-4 alky l, 5-6 membered heteroary 1-C 1-4 alky 1, ORa8, SRa8, NHORa8, C(O)Rb8, C(O)NRc8Rd8, C(O)NRc8(ORa8), C(O)ORa8, OC(O)Rb8, OC(O)NRc8Rd8, NRc8Rd8, NRc8NRc8Rd8. NRc8C(O)Rb8, NRc8C(O)ORa8, NRc8C(O)NRc8Rd8, C(=NRe8)Rb8, C(=NRe8)NRc8Rd8, NRc8C(=NRe8)NRc8Rd8, NRc8C(=NRe8)Rb8, NRc8S(O)NRc8Rd8, NRc8S(O)Rb8, NRc8S(O)2Rb8, NRc8S(O)(=NRe8)Rb8, NRc8S(O)2NRc8Rd8, S(O)Rb8, S(O)NRc8Rd8, S(O)2Rb8, and S(O)2NRc8Rd8, wherein said C1-6alkyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ra8, Rc8, and Rd8is independently selected from H, C1-6alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6alkyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl. 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-8 membered heterocy cloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;or, any Rc8and Rd8attached to the same N atom, together with the N atom to which they are attached, form a 4-8 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Rb8is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-8 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-8 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Re8is independently selected from H, OH, CN, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, and C1-6 haloalkoxy; andeach RGis independently selected from OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino. thio, Ci-3 alkylthio, C1-3 alkylsulfmyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3alkylcarbonylamino, C1-3 alkoxy carbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alky lsulfonylamino, aminosulfonyl, C1-3 alky laminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl )aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2.

3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein n is 1.

4. The compound of any one of claims 1-3, or a pharmaceutically acceptable salt thereof, wherein X is O, S(O)2, or N(-L-R4).

5. The compound of any one of claims 1-3, or a pharmaceutically acceptable salt thereof, wherein X is O.

6. The compound of any one of claims 1-3, or a pharmaceutically acceptable salt thereof, wherein X is N(-L-R4).

7. The compound of any one of claims 1-6. or a pharmaceutically acceptable salt thereof, wherein L is S(O)2.

8. The compound of any one of claims 1-7. or a pharmaceutically acceptable salt thereof, wherein R1is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyd, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

9. The compound of any one of claims 1-7. or a pharmaceutically acceptable salt thereof, wherein R1is selected from C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, and 4-7 membered heterocycloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

10. The compound of any one of claims 1-7, or a pharmaceutically acceptable salt thereof, wherein R1is selected from C1-6 alkyl, Ci-6 haloalky 1, and C3-7 cycloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

11. The compound of any one of claims 1-7. or a pharmaceutically acceptable salt thereof, wherein R1is selected from Ci-6 alkyl, Ci-6 haloalkyl, and C3-7 cycloalkyl.

12. The compound of any one of claims 1-10, or a pharmaceutically acceptable salt thereof, wherein:each R1Ais independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa11, SRa11. C(O)Rb11, C(O)NRollRd11. C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRollC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRc11Rd11, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rb11is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1Bis independently selected from H, D. halo, CN, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaiyl-Ci-4 alkyl, ORa12, SRa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRc12Rd12, NRc12C(O)Rb12, NRc12C(O)ORa12, NRc12C(O)NRc12Rd12, NRc12S(O)2Rb12, NRc12S(O)2NRc12Rd12, S(O)2Rb12, and S(O)2NRc12Rd12;each Ra12, Rc12, and Rd12is independently selected from H, C1-6 alkyl, and Ci-6 haloalkyl; andeach Rb12is independently selected from C1-6 alkyl and C1-6 haloalkyl.

13. The compound of any one of claims 1-10, or a pharmaceutically acceptable salt thereof, wherein:each R1Ais independently selected from H, D, halo, CN, Ci-6 alkyl, C1-6 haloalkyl, ORa11, and NRc11Rd11; andeach Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl.

14. The compound of any one of claims 1-13, or a pharmaceutically acceptable salt thereof, wherein R2A, R2B, and R2Care each independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRo2Rd2, NRo2C(O)Rb2, NRo2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)2Rb2, NRo2S(O)2NRo2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said Ci-6alkyl and Ci-6haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents.

15. The compound of any one of claims 1-13, or a pharmaceutically acceptable salt thereof, wherein R2A, R2B, and R2Care each independently selected from H, halo, and ORa2.

16. The compound of any one of claims 1-15, or a pharmaceutically acceptable salt thereof, wherein:each Ra2, Rc2, and Rd2is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; andeach Rb2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

17. The compound of any one of claims 1-16, or a pharmaceutically acceptable salt thereof, wherein each R3is independently selected from -Ci-4alkylene-ORa3, -C 1-4 alky lene-NRc3Rd3, ORa3, and NRo3Rd3.

18. The compound of any one of claims 1-16, or a pharmaceutically acceptable salt thereof, wherein each R3is OH.

19. The compound of any one of claims 1-18, or a pharmaceutically acceptable salt thereof, wherein R4is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alky l, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

20. The compound of any one of claims 1-18, or a pharmaceutically acceptable salt thereof, wherein R4is selected from Ci-6 alkyl and Ci-6 haloalky l.

21. The compound of any one of claims 1-19, or a pharmaceutically acceptable salt thereof, wherein:each R4Ais independently selected from D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd, 5-6 membered heteroaiyl-Ci-4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRo41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRo41Rd41, NRc41Rd41, NRc41C(O)Rb41. NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1.4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Rb41is independently selected from Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalky l, ORa42, SRa42, C(O)Rb42, C(O)NRo42Rd42, C(O)ORa42, OC(O)Rb42. OC(O)NRc42Rd42, NRo42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; andeach Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

22. The compound of any one of claims 1-19, or a pharmaceutically’ acceptable salt thereof, wherein:each R4Ais independently selected from D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41,NRC4iRd4iNRc4iC(O)Rb4i NRo41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; andeach Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

23. The compound of any one of claims 1-22, or a pharmaceutically acceptable salt thereof, wherein R5is selected from halo, CN. C1-4 alkyl, C1-4 haloalkyl, cyano-Ci-4 alkyl, HO-C1.4 alkyl, C1-3 alkoxy-Ci-4 alkyl, and C3-4 cycloalkyl.

24. The compound of any one of claims 1-22, or a pharmaceutically acceptable salt thereof, wherein R5is selected from halo and CN.

25. The compound of any one of claims 1-24, or a pharmaceutically acceptable salt thereof, wherein:R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alky l, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted by 1, 2, 3. or 4 independently selected R6Asubstituents;R7is selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;or, R6and R7, together with the nitrogen atom to which they are attached, form a 4-10 membered heterocycloalkyl moiety or a 5-6 membered heteroaryl moiety, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents.

26. The compound of any one of claims 1-24, or a pharmaceutically’ acceptable salt thereof, wherein R6and R7, together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl moiety or a 5-6 membered heteroaryl moiety7, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents.

27. The compound of any one of claims 1-26, or a pharmaceutically acceptable salt thereof, wherein each R6Ais independently selected from halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, ORa61, NRc61Rd61, and S(O)2Rb61, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents.

28. The compound of any one of claims 1-26, or a pharmaceutically acceptable salt thereof, wherein each R6Ais independently selected from halogen, Ci-6 alkyl, and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents selected from D, halo, CN, NO2, and OH.

29. The compound of any one of claims 1-26, or a pharmaceutically acceptable salt thereof, wherein:each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 memberedheterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl-Ci-4 alkyl, ORa61, SRa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRo61Rd61,NRO6iRd6i, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61, NRo61S(O)2NRc61Rd61, S(O)2Rb61, and S(O)2NRc61Rd61, wherein said Ci-6alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyd are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each Ra61, Rc61. and Rd61is independently selected from H, Ci-6 alkyl. C1-6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalky 1-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl. C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alky l, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyd, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1.4 alkyd, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1. 2, 3, or 4 independently selected R6Bsubstituents;each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa62, SRa62, C(O)Rb62, C(O)NRc62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62, NRc62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, NRc62S(O)2Rb62, NRc62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62, wherein said C1-6alkyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky d-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, Ci-6 haloalky 1, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1.4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;each Rb62is independently selected from Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;each R6Cis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalky l, ORa63, SRa63, C(O)Rb63, C(O)NRo63Rd63, C(O)ORa63, OC(O)Rb63. OC(O)NRc63Rd63, NRo63Rd63, NRc63C(O)Rb63, NRc63C(O)ORa63, NRc63C(O)NRc63Rd63, NRc63S(O)2Rb63, NRc63S(O)2NRc63Rd63, S(O)2Rb63, and S(O)2NRc63Rd63;each Ra63, Rc63, and Rd63is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; andeach Rb63is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

30. The compound of any one of claims 1-26, or a pharmaceutically’ acceptable salt thereof, wherein:each R6Ais independently selected from halo, CN, Ci-6 alky l, Ci-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, ORa61, NRc61Rd61, and S(O)2Rb61, wherein said Ci-6 alkyl, C3-10 cycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 independently selected R6Bsubstituents;each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb61is independently selected from Ci-6 alkyl and C3-10 cycloalkyl;each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, ORa62. andNRc62Rd62.an(jeach Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl.

31. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt thereof, wherein R8is selected fromH, D, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents.

32. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt thereof, wherein R8is selected from H, D, halo, CN, C1-3 alkyl, and C1-3 haloalkyl.

33. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt thereof, wherein:each Ra8, Rc8, and Rd8is independently selected from H, C1-6 alkyl, and Ci-6 haloalkyl; andeach Rb8is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

34. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: n is 0, 1, or 2;X is O, S(O)2, orN(-L-R4);L is S(O)2or S(O)2NRa;Rais selected fromH, C1-6 alkyd and C1-6 haloalkyl;or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;R1is selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalky l, 6-10 membered aryl. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroar 1-C 1-4 alky 1, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each R1Ais independently selected from H, D. halo. CN, Ci-6 alkyl. C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alky l, 5-6 membered heteroaiyl-C 1.4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRollRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRollRd11, NRcllRd11, NRcllC(O)Rb11. NRollC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 memberedheterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroary 1-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered lietcroar l. C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R, Bsubstituents;each Rb11is independently selected from C1-6alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1Bis independently selected from H, D, halo, CN, Ci-6 alky l, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl. OR112, SRa12. C(O)Rb12, C(O)NRcl2Rd12. C(O)ORa12, OC(O)Rb12, OC(O)NRcl2Rd12, NRcl2Rd12, NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRol2C(0)NRol2Rdl2, NRol2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12, S(O)2Rb12, and S(O)2NRol2Rd12;each Ra12, R°12, and Rdl2is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb12is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;R2A, R2B, and R2Care each independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6haloalkyl, ORa2, C(O)Rb2, C(O)NRo2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRo2Rd2, NRo2Rd2, NRo2C(O)Rb2, NRo2C(O)ORa2. NRc2C(O)NRo2Rd2, NRo2S(O)2Rb2, NRo2S(O)2NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents;each Ra2, Rc2, and Rd2is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; each Rb2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;each R3is independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa3, andNRo3Rd3. wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents;each Ra3, R°3, and Rd3is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; each Rb3is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;R4is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl; wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;each R4Ais independently selected from D, halo, CN, NO?, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alkyl, 5-6 membered heteroaiyl-C 1-4 alkyl, ORa41, SRa41, C(O)Rh41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rh41, OC(O)NRo41Rd41, NRc41Rd41, NRc41C(O)Rb41, NRc41C(O)ORa41, NRo41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRo41Rd41, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, R°41, and Rd41is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alky l, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2. 3, or 4 independently selected R4Bsubstituents;each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa42, SRa42, C(O)Rb42, C(O)NRo42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRo42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRo42Rd42, NRc42S(O)2Rb42, NRo42S(O)2NRo42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalk l;R5is selected from halo, CN. CH alkyl, and Ci-4 haloalkyl;R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl. 6-10 membered aryl. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyd, 4-10 membered heterocycloalkyl-Ci-4 alkyd, and 5-10 membered heteroaryl-C 1-4 alk 1, which are each optionally substituted by 1, 2, 3, or 4 independently-selected R6Asubstituents;R7is selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;or, R6and R7, together with the nitrogen atom to which they are attached, form a 4-10 membered heterocycloalky 1 moiety- or a 5-6 membered heteroaryl moiety, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents;each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyd, 5-10 membered heteroaryl, C3-10 cycloalkyd-C 1-4 alkyl, 6-10 membered aryd-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, ORa61, SRa61. C(O)Rb61, C(O)NRo61Rd61. C(O)ORa61, OC(O)Rb61, OC(O)NRo61Rd61, NRc61Rd61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61, NRo61S(O)2NRc61Rd61, S(O)2Rb61, and S(0)2NRo61Rd61, wherein said Ci-6alkyd, C2-6alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyd, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally7substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each Ra61, R°61, and Rd61is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl. C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alky l, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;or, any Rc61and Rd61attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl. 6-10 membered aryl, 4-10 membered heterocycloalkyl. 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each R6Bis independently selected from D, halo, CN, C1-6 alkyl, C1-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd, 5-6 membered heteroaryl-C 1.4 alkyl, ORa62, SRa62, C(O)Rb62, C(O)NRc62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRo62Rd62, NRc62Rd62, NRo62C(O)Rb62. NRo62C(O)ORa62, NRc62C(O)NRc62Rd62, NRc62S(O)2Rb62, NRo62S(O)2NRo62Rd62. S(O)2Rb62, and S(O)2NRc62Rd62, wherein said Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky I-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R6Csubstituents;each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyL 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;each Rb62is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl.phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;each R6Cis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1.4 alkyl. ORa63, SRa63. C(O)Rb63, C(O)NRc63Rd63. C(O)ORa63, OC(O)Rb63, OC(O)NRc63Rd63, NRc63Rd63, NRc63C(O)Rb63, NRc63C(O)ORa63, NRo63C(O)NRc63Rd63, NRo63S(O)2Rb63, NRc63S(O)2NRc63Rd63, S(O)2Rb63, and S(O)2NRo63Rd63, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ra63, Rc63, and Rd63is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected RGsubstituents; andeach Rb63is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaiyl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;R8is selected fromH, D, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents; andeach RGis independently selected from OH, NO2, CN, halo, C1-3 alkyl, C2-s alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Ci-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxy carbonyl, C1-3 alkylcarbonyloxy, C1-3alkylcarbonylamino, C1-3 alkoxy carbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1.3 alkylaminosulfonylamino, di (C 1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-3 alkylaminocarbonylamino, and di(Ci-s alkyl)aminocarbonylamino.

35. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: n is 0, 1, or 2;X is O, S(O)2, orN(-L-R4);L is S(O)2or S(O)2NRa;Rais selected from H, Ci-6 alkyl and C 1-6 haloalkyl;R1is selected from C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each R1Ais independently selected fromH, D, halo, CN, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl. 5-6 membered heteroaryl-C 1.4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRollRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRollC(O)NRcllRd11, NRollS(O)2Rb11, NRollS(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRc11Rd11, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Ral1, R011, and Rdl1is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1 or 2 independently selected R1Bsubstituents;each Rb11is independently selected from Ci-6 alkyl and Ci-6 haloalk l. which are each optionally substituted with 1 or 2 independently selected R1Bsubstituents;each R1Bis independently selected from H, D. halo, CN, Ci-6 alkyl, Ci-g haloalkyl, ORa12, SRa12, C(O)Rb12, C(O)NRcl2Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRcl2Rd12,NR°i2Rdi2, NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRcl2C(O)NRcl2Rd12, NRcl2S(O)2Rb12, NRol2S(O)2NRcl2Rd12, S(O)2Rb12, and S(O)2NRcl2Rd12;each Ra12, Rc12, and Rd12is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb12is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;R2A, R2B, and R2Care each independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, and ORa2;each Ra2is independently selected from H and Ci-6 alkyl;each R3is independently selected from halo, CN, C1-3 alkyl, C1-3 haloalkyl, ORa3, and NRc3Rd3, wherein said C1-3 alkyl and C1-3 haloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents.each Ra3, Rc3. and Rd3is independently selected from H, C1-6 alkyl, and Ci-6 haloalkyl; R4is selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl; wherein said C1-6 alkyl, C1-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;each R4Ais independently selected from D, halo, CN, NO2, C1-6 alky l, Ci-6 haloalkyl, ORa41, SRa41. C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rh41, OC(O)NRo41Rd41,NRC4iRd4i NRc41C(O)Rb41, NRo41C(O)ORa41, NRc41C(O)NRc41Rd41. NRo41S(O)2Rb41.NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;R5is selected from halo and CN;R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocy cloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents;R7is selected fromH, Ci-6 alkyl, and Ci-6 haloalky l;or, R6and R7, together with the nitrogen atom to which they are attached, form a 4-10 membered heterocy cloalkyl moiety or a 5-6 membered heteroaryl moiety, each of which is optionally substituted by' 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents;each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1.4 alkyl, 5-6 membered heteroaiy l-Ci-4 alkyl, ORa61, SRa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRo61Rd61, NRc61Rd61, NRo61C(O)Rb61, NRo61C(O)ORa61, NRo61C(O)NRc61Rd61, NRo61S(O)2Rb61, NRo61S(O)2NRo61Rd61. S(O)2Rb61, and S(O)2NRo61Rd61, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each Ra61, Rc61. and Rd61is independently selected from H, Ci-6 alkyl. C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alky l, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaiy 1-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each Rb61is independently selected from Ci-s alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaiy 1, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaiy I-C1.4 alkyl, ORa62, SRa62, C(O)Rb62, C(O)NRo62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRo62Rd62, NRc62Rd62, NRo62C(O)Rb62. NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, NRc62S(O)2Rb62, NRc62S(O)2NRo62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-Ci-4 alkyl, and 5-6 membered heteroary l-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, Ci-6 haloalky 1, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1.4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;each Rb62is independently selected from Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Csubstituents;each R6Cis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalky l, ORa63, SRa63, C(O)Rb63, C(O)NRo63Rd63, C(O)ORa63, OC(O)Rb63. OC(O)NRc63Rd63, NRo63Rd63, NRc63C(O)Rb63, NRc63C(O)ORa63, NRc63C(O)NRc63Rd63, NRc63S(O)2Rb63, NRc63S(O)2NRc63Rd63, S(O)2Rb63, and S(O)2NRc63Rd63;each Ra63, Rc63, and Rd63is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb63is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;R8is selected from H, D, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl; andeach RGis independently selected from OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl. C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino. thio, Ci-3 alkydthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1.3 alkydcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3alkylcarbonyl, C1-3 alkoxy carbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxy carbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C 1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-3 alkydaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.

36. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: n is 0 or 1;X is O, S(O)2, orN(-L-R4);L is S(0)2;R1is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each R1Ais independently selected fromH, D, halo, CN, Ci-6 alkyl, C1-6 haloalkyl, C3-5 cycloalkyl, 4-5 membered heterocycloalkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRc11C(O)NRc11Rd11, NRc11S(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRc11Rd11;each Ra11, R011, and Rdnis independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;each Rb11is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;R2A, R2B, and R2Care each independently selected from H, halo, CN, and ORa2; each Ra2is independently selected from H and Ci-6 alky l;each R3is independently selected from halo. CN, C1-3 alkyl. C1-3 haloalkyl, ORa3. and NRc3Rd3, wherein said C1-3 alkyl and C1-3 haloalkyl are each optionally substituted a substituent selected from OH, C1-3 alkoxy, amino, C1-3 alkylamino, and di(Ci-3 alkyl)amino;each Ra3, Rc3, and Rd3is independently selected from H, C1-3 alkyl, and C1-3 haloalky l; R4is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cl oalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl; wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocy cloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;each R4Ais independently selected from D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl, ORa41, SRa41, C(O)Rb41, C(O)NRo41Rd41, C(O)OR“41, OC(O)Rb41, OC(O)NRc41Rd41,NRc4iRd4iNRc4iC(O)Rb4i NRo41C(O)ORa41, NRc41C(O)NRo41Rd41. NRo41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb41is independently selected from Ci-s alkyl and Ci-6 haloalkyl;R5is selected from F, Cl, and CN;R6is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered and, 4-10 membered heterocycloalkyl, 5-10 membered heteroary l, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl; which are each optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents;R7is selected fromH, C1-6 alkyl, and Ci-6 haloalky l;or, R6and R7, together with the nitrogen atom to which they are attached, form a 4-10 membered heterocycloalkyd moiety or a 5-6 membered heteroaryl moiety7, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents;each R6Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd, 5-6 membered heteroaiyd-C 1.4 alkyl, ORa61, SRa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRo61Rd61, NRo61Rd61, NRo61C(O)Rb61, NRo61C(O)ORa61, NRo61C(O)NRc61Rd61, NRo61S(O)2Rb61, NRo61S(O)2NRo61Rd61. S(O)2Rb61, and S(O)2NRo61Rd61, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each Ra61, Rc61. and Rd61is independently selected from H, Ci-6 alkyl. Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alky l, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa62, SRa62, C(O)Rb62, C(O)NRc62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62,NRc62C(O)Rb62, NRo62C(O)ORa62, NRc62C(O)NRo62Rd62, NRc62S(O)2Rb62, NRc62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62;each Ra62, R°62, and Rd62is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb62is independently selected from Ci-6 alkyl and Ci-6 haloalky l; andR8is selected fromH, D. halo, CN, C1-3 alkyl, and C1-3 haloalkyl.

37. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: n is 0 or 1;X is O, S(O)2, orN(-L-R4);L is S(O)2;R1is selected from C1-6 alkyl, C1-6 haloalky l, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently-selected R1Asubstituents;each R1Ais independently selected from H, D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NR011Rd11, NRcllC(O)Rb11, NRollC(O)ORa11, NRG11C(O)NRollRd11, NRollS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11;each Ra11, Rc11, and Rd11is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;each Rb11is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;R2AR2BANC|R2Care each independentiy selected from H, halo, and ORa2; each Ra2is C 1-6 alkyl;each R3is independently7selected from -Ci-4alkylene-ORa3, -Ci-4alkylene-NRc3Rd3, ORa3, and NRc3Rd?;each Ra3is H;each Rc3and Rd3is independently selected from H and C1.3 alkyl;R4is selected from Ci-6 alkyl and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;each R4Ais independently selected from D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl. ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRo41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;R3is selected from F, Cl, and CN;R6is selected from Ci-6 alkyl, Ci-6 haloalky l, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted by 1, 2, 3, or 4 independently selected R6Asubstituents;R7is selected fromH, Ci-6 alkyl, and Ci-6 haloalky l;or, R6and R7, together with the nitrogen atom to which they are attached, form a 4-10 membered heterocycloalkyl moiety or a 5-6 membered heteroaryl moiety7, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R6Asubstituents;each R6Ais independently selected from D, halo, CN, C1-6 alkyl, Ci-6 haloalkyl, C3-5 cycloalkyl, 4-5 membered heterocycloalky7!. ORa61, SRa61, C(O)Rh61, C(O)NRo61Rd61.C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)2Rb61, NRc61S(O)2NRc61Rd61, S(O)2Rb61, and S(O)2NRc61Rd61, wherein said Ci-6 alky l, Ci-6 haloalkyl, C3-5 cycloalky l, and 4-5 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents; each Ra61, Rc61. and Rd61is independently selected from H, Ci-6 alkyl. Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl, wherein said Ci-6 alky l, Ci-6 haloalkyl, Ci-6 alkyl, Ci-6 haloalky7!, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl are each optionally substituted with 1 or 2 independently selected R6Bsubstituents;each Rb61is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkyl. Ci-6 haloalkyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl, which are each optionally substituted with 1 or 2 independently selected R6Bsubstituents;each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalky l, ORa62, SRa62, C(O)Rb62, C(O)NRo62Rd62, C(O)ORa62, OC(O)Rb62. OC(O)NRc62Rd62, NRo62Rd62, NRc62C(O)Rb62, NRc62C(O)ORa62, NRc62C(O)NRc62Rd62, NRc62S(O)2Rb62, NRc62S(O)2NRc62Rd62, S(O)2Rb62, and S(O)2NRc62Rd62;each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb62is independently selected from Ci-6 alkyl and Ci-6 haloalkyl; andR8is selected from H, C1-3 alkyl, and C1.3 haloalkyl.

38. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: n is 0 or 1;X is O or N(-L-R4);L is S(O)2;R1is selected from Ci-6 alkyl, Ci-6 haloalkyl, and C3-10 cycloalkyl;R2A, R2B, and R2Care each independently selected from H, halo, and ORa2; each Ra2is C1-6 alkyl;each R3is ORaa;each Ra3is H;R4is C1-6 alkyl;R5is selected from halo and CN;R6is selected from C1-6 alkyl and C3.10 cycloalkyl-Ci-4 alkyl; which are each optionally substituted by 1 or 2 independently selected R6Asubstituents;R7is selected from H and Ci-6 alkyl;or, R6and R7, together with the nitrogen atom to which they are attached, form a 4-15 membered heterocycloalkyl moiety, which is optionally substituted by 1, 2, 3, 4, or 5 independently selected R6Asubstituents;each R6Ais independently selected from halo, CN, Ci-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, ORa61, NRc61Rd61, and S(O)2Rb61. wherein said Ci-6 alkyl, C3-10 cycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 independently selected R6Bsubstituents;each Ra61, Rc61, and Rd61is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb61is independently selected from Ci-6 alkyl and C3-10 cycloalkyl;each R6Bis independently selected from D, halo, CN, Ci-6 alkyl, ORa62, andNRO62Rd62.each Ra62, Rc62, and Rd62is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; andR8is selected from H and Ci-6 alkyl.

39. The compound of claim 1, wherein the compound is a compound of Formula (la):or a pharmaceutically acceptable salt thereof.

40. The compound of claim 1, wherein the compound is a compound of Formula (lb):or a pharmaceutically acceptable salt thereof.

41. The compound of any one of claims 1-40, wherein the compound comprises from 1 to 6 deuterium atoms.

42. The compound of claim 1, selected from:4-fluoro-6-(5-fluoro-2-(((37?,47?)-3-hydroxy-l -(methylsulfonyl)piperidin-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-jV-methyl-177-indole-3-carboxamide;4-fluoro-6-(5-fluoro-2-(((3S',4i?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-JV-methyl-177-indole-3-carboxamide;4-fluoro-6-(5-fluoro-2-(((37?,4J?)-3-hydroxy-l-(methylsulfonyl)piperidin-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-jV-(2-(pyrimidin-2-yl)ethyl)-17f-indole-3-carboxamide;6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)- 4-fluoro- 1 -isopropy l-V-(( 1 -methyl- 1 / 7-i ndazol -6-y l)methy 1)- l / f-indole-3-carboxamide;6-(5-cyano-2-(((35,4 )-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-4-fluoro-l-isopropyl-jV-((l-methyl-17 / -indazol-6-yl)methyl)-17 / -indole-3-carboxamide;6-(5-chloro-2-(((3S,4A)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-4-fluoro-l -isopropyl-JV,2-dimethyl- 177-indole-3 -carboxamide;l-cyclopentyl-4,7-difluoro-6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-7V-methyl-l / f-indole-3-carboxamide;(4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-17 / -indol-3-yl)(3-(trifluoromethyl)azetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4J?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-17 / -indol-3-yl)((<S)-2-(hydroxymethyl)azetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2 / f-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-l / 7-indol-3-yl)((2S,3S)-2-(hydroxymethyl)-3-methylazetidin- 1 -y l)methanone;((2< S',47?)-4-fluoro-2-(hydroxymethyl)pyrrolidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((35.4J?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-l / f-indol-3-yl)methanone; and((S)-4,4-difluoro-2-(hydroxymethyl)pyrrolidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((35’,4J?)-3-hy droxy tetrahydro-2H-py ran-4-y I )amino)py rimidin-4-y I )- 1 -isopropy 1- 1 H-indol-3-yl)methanone;or a pharmaceutically acceptable salt thereof.

43. The compound of claim 1, selected from:(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((R)-4-(hy droxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone; and(4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-277-pyran-4-y l)amino)pyrimidin-4-yl)- 1 -isopropyl- 1 H-i ndol -3 -y l)((J?)-2-(hy droxy methy l)azetidin- 1 -yl)methanone;or a pharmaceutically acceptable salt thereof.

44. The compound of claim 1. selected from:(4-fluoro-6-(5-fluoro-2-(((3S,4J?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- l -indol-3-yl)((25,3S)-2-(hydroxymethyl-J2)-3-methyl azetidin- 1 -y l)methanone;((2R, 3S)-3-(difluoromethoxy)-2-(hydroxymethyl)azeti din-1 -yl)(4-fluoro-6-(5-fluoro-2-(((35,4J?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;or a pharmaceutically acceptable salt thereof.

45. The compound of claim 1, selected from:(6-(5-fluoro-2-(((35,47?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)- l-methyl-IH-mdol-3-yl)((25'.

3. S')-2-(hydroxymethyl-c / 2)-3-methylazetidiri-l -yljmethariorie;(l-ethyl-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyri mi din-4-yl)-17f-indol-3-yl)((2S,3< S)-2-(hydroxymethyl-ti2)-3-methylazeti din-1-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S',47?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-17f-indol-3-yl)(3-(trifluoromethyl)azetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- l / / -indol-3-yl)(3-(2-fluoropropan-2-yl)azetidin-l-yl)methanone;(5, -difluoro-2-azaspiro[3.3]heptan-2-yl)(4-fluoro-6-(5-fluoro-2-(((3<S',4J?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-l / 7-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-17f-indol-3-yl)((J?)-2-methylazetidin-l-yl)methanone;(1 J-difluoro-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4 )-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-l / / -indol-3-yl)methanone;(6-(5-chloro-2-(((3S,4J?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-4-fluoro-l-isopropyl-l / 7-indol-3-yl)((2S,3S)-2-(hydroxymethyl)-3-methylazetidin-l-yl)methanone;(6-(5-chloro-2-(((3i<?,47?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-4-Huoro- 1 -isopropyl- 1 H-mdol-3-yl)((25.

3. S')-2-(tiydroxymethyl-d2)-3-methyl azetidin- 1-yl)methanone;(l-ethyl-4-fluoro-6-(5-fluoro-2-(((3< S’,4 )-3-hydroxytetrahydro-2 / f-pyran-4-yl)amino)pyrimidin-4-yl)-17 / -indol-3-yl)((2S,3 )-2-(hydroxymethyl-rf2)-3-methylazeti din-1 -yl)methanone;((2J?,3S)-3-(difluoromethoxy)-2-(hydroxymethyl)azetidin-l-yl)(l-ethyl-4-fluoro-6-(5-nuoro-2-(((3, S'.4 / ?)-3-hydroxytctrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-l / / -indol-3-yl)methanone;-cyclopropyl-2-hydroxy ethyl)- l-ethyl-4-fluoro-6-(5-fluoro-2-(((35, 4 / )-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-l / / -indole-3-carboxamide;(l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,4J?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)- l / f-indol-3-yl)((5)-2-(trifluoromethyl)azetidin- 1 -y l)methanone;(l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-l / 7-indol-3-yl)methanone;(l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4J?)-3-hydroxy tetrahydro-2 / / -pyran -4-yl)amino)py rimidin-4-y I)- 1 -isopropyl- 1 / / -indol-3-yl)methanone;(l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-17f-indol-3-yl)((25',3< S’)-2-(hydroxymethyl)-3-(trifluoromethyl)azeti din-1 -yl)methanone;(l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-17 / -indol-3-yl)((2S.35)-2-(hydroxymethyl-r / 2)-3-(trifluoromethyl)azetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4J?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lJ / -indol-3-yl)((2< S',3S)-2-(hydroxymethyl)-3-(trifluoromethyl)azetidin- 1 -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-27 / -pyran-4-y l)annno)py rimidin-4-yl )- 1 -isopropyl- 1 / / -indol-3-yl)((2X.3, S')-2-(hydroxymethyl-6 / 2)-3-(trifluoromethyl)azetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- 17 / -indol-3-yl)((2S,3< S)-2-(hydroxymethyl)-3-(trifluoromethyl)azeti din-1 -yl)methanone;(l-ethyl-6-(5-fluoro-2-(((3S,4J / ?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-l / f-indol-3-yl)((2S',3S)-2-(hydroxymethyl)-3-(trifluoromethy l)azetidin- 1 -y l)methanone;(6-(5-fluoro-2-(((3<S',4J?)-3-hydroxytetrahydro-27 -pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-l / 7-indol-3-yl)((2S,35)-2-(hydroxymethyl)-3-(trifluoromethyl)azetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4J?)-3-hydroxytetrahydro-27f-pyran-4-yl)ammo)pyrimidm-4-yl)-l-isopropyl-l / / -indol-3-yl)((2 / ?.3 / )-2-(hydro\ymethyl)-3-methoxy -3 -methy lazetidin- 1 -yl)methanone;(l-ethyl-4-fluoro-6-(5-fluoro-2-(((3< S',4A)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-17f-indol-3-yl)((2J?,3i?)-2-(hydroxymethyl)-3-methoxy-3-methylazetidin- 1 -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-17 / -indol-3-yl)((2A.3J?)-2-(hydroxymethyl)-3-methoxy-3-methylazeti din-1 -yl)methanone;(6-(5-fluoro-2-(((31S',4i?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-17 / -indol-3-yl)((27?,3S)-2-(hydroxymethyl)-3-(trifluoromethoxy)azeti din-1-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- l / / -indol-3-yl)((2 / ?.3, S')-2-(hydro\ymethyl)-3-(trifluoromethoxy)azetidin- 1 -y l)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4A)-3-hydroxytetrahydro-2 / f-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-l / 7-indol-3-yl)((27?,35)-2-(hydroxymethyl)-3-(trifluoromethoxy)azetidin- 1 -y l)methanone;(6-(5-chloro-2-(((3S,4J?)-3-hydroxytetrahydro-2£Z-pyran-4-yl)amino)pyrimidin-4-yl)-4-fluoro-l-isopropyl-l -indol-3-yl)((27?,3S')-2-(hydroxymethyl)-3-(trifluoromethoxy)azetidin- 1 -yl)methanone;(l-ethyl-4-fluoro-6-(5-fluoro-2-(((35,47?)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-17f-indol-3-yl)((2J?,31S)-2-(hydroxymethyl)-3-(trifluoromethoxy)azetidin- 1 -yl)methanone;(6-(5-chloro-2-(((3S,4JR)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-1 -ethyl -4-fluoro-17 / -indol-3-yl)((2A,3iS)-2-(hydroxymethyl)-3-(trifluoromethoxy)azeti din- 1-yl)methanone;(l-(2,2-difluoroethyl)-4-fluoro-6-(5-fluoro-2-(((3S,4-K)-3-hydroxytetrahydro-27 / -pyran-4-yl)amino)pyrimidin-4-yl)-l / 7-indol-3-yl)(5-azaspiro[2.3]hexan-5-yl)methanone;(l-(2,2-difluoroethyl)-6-(5-fluoro-2-(((3S',47?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-17 / -indol-3-yl)((2S,3< S)-2-(hydroxymethyl-t / 2)-3-methylazeti din-1 -yl)methanone;(6-(5-chloro-2-(((35',4J?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-4-fluoro-177-indol-3-yl)((< S -4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;(6-(5-chloro-2-(((3X.4 / )-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-1 -ethyl -4-fluoro-17f-indol-3-yl)((7?)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;(3-(fe / 7-butyl)-3-hydroxyazetidin-l-yl)(6-(5-chloro-2-(((3S',4J?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)py rimidin-4-yl)- 1 -ethyl-4-fluoro- 17 / -indol-3-yl)methanone;(6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-1 -ethyl -4-fluoro-17f-indol-3-yl)(3-((difluoromethoxy)methyl)azetidin-l-yl)methanone;(6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-4-fluoro-17 / -indol-3-yl)((2S.3< S’)-2-(hydroxymethyl-J2)-3-methylazetidin-l-yl)methanone;(6-(5-chloro-2-(((3S,4J?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-4-fluoro-177-indol-3-yl)(3-(difluoromethyl)azetidin-l-yl)methanone;(6-(5-chloro-2-(((3S',47?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-1 -ethyl -4-fluoro-17 / -indol-3-yl)((2,3^-3-(difluoromethoxy)-2-(hydroxymethyl)azetidin-l-yl)methanone;(l-ethyl-6-(5-fluoro-2-(((35',4J?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-l / f-indol-3-yl)((S)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;(l-ethyl-6-(5-fluoro-2-(((3S,47?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-17f-indol-3-yl)((7?)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;(6-(5-fluoro-2-(((3S\47?)-3-hydroxytetrahydro-2 -pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-17 / -indol-3-yl)((S)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;(6-(5-fluoro-2-(((31S',4J?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-17 / -indol-3-yl)((J?)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;((4< S’)-l.l-dilluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(6-(5-lluoro-2-(((35,4?)-3-hydroxytetrahydro-2 / / -pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-17 / -indol-3-yl)methanone;((47?)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(6-(5-fluoro-2-(((35.47?)-3-hydroxytetrahydro-2#-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(6-(5-fluoro-2-(((31S',47?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-177-indol-3-yl)((iS)-l-(hydroxymethyl)-2-azaspiro[3.3]heptan-2-yl)methanone;(6-(5-fluoro-2-(((3,47?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-l / / -indol-3-yl)((^)-l-(hydroxymethyl)-2-azaspiro[3.3]heptan-2-yl)methanone;(6-(5-fluoro-2-(((31S',47?)-3-hydroxytetrahydro-27f-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-177-indol-3-yl)((2<S',3S)-2-(hydroxymethyl)-3-methylazetidin-l-yl)methanone;2-((S)-l-(6-(5-fluoro-2-(((3< S',47?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-17 / -indole-3-carbonyl)azetidin-2-yl)acetonitrile;((27?,3S)-3-(difluoromethoxy)-2-(hydroxymethyl)azetidin-l-yl)(l-ethyl-6-(5-fluoro-2-(((35,47?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)pyrimidin-4-yl)-177-indol-3-yl)methanone;(6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-2 / 7-pyran-4-yl)amino)pyrimidin-4-yl)-1 -ethyl-17 / -indol-3-yl)((2S,3l)-2-(hydroxymethyl-<72)-3-methylazetidin-l -yl)methanone; and (6-(5-chloro-2-(((3S,47?)-3-hydroxytetrahydro-2£f-pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-177-indol-3-yl)((2?,3S)-3-(difluoromethoxy)-2-(hydroxymethyl)azetidin-l-yl)methanone;or a pharmaceutically acceptable salt thereof.

46. The compound of claim 1, selected from:(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)(5-azaspiro[2.3]hexan-5-yl)methanone;(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)(3-(trifluoromethyl)azetidin-l-yl)methanone;(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((R)-2-methylazetidin-l-yl)methanone;(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((S)-2-(hydroxymethyl)azetidin-l-yl)methanone;(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-1 -methyl-1 H-indol-3-yl)((S)-2-((methylsulfonyl)methyl)azeti din-1 -yl)methanone;(5,5-difluoro-2-azaspiro[3.3]heptan-2-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;N-((S)-l-cyclopropyl-2-hydroxyethyl)-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indole-3-carboxamide;(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)(3-hydroxy-3-(trifluoromethyl)azetidin-l-yl)methanone;(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2R,3R)-3-hydroxy-2-methylazetidin-l-yl)methanone;(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2R,3S)-3-hydroxy-2-methylazetidin-l-yl)methanone;((2S,3S)-2-((cyclopropylsulfonyl)methyl)-3-methylazetidin-l-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;((2R,3S)-3-(difluoromethoxy)-2-(hydroxymethyl)azetidin-l-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;((2S,4R)-4-(difluoromethoxy)-2-(hydroxymethyl)pyrrolidin-l-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2S,4R)-2-(hydroxymethyl)-4-(trifluoromethoxy)pyrrolidin-l-yl)methanone;(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2S,4R)-2-(hydroxymethyl)-4-(trifluoromethyl)pyrrolidin-l-yl)methanone;((S)-4,4-difluoro-2-(hydroxymethyl)pyrrolidin-l-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((S)-2-(hydroxymethyl)-4,4-dimethylpyrrolidin-l-yl)methanone;(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)(3-(trifluoromethyl)azetidin-l-yl)methanone;((2S,4R)-4-(difluoromethoxy)-2-(hydroxymethyl)pyrrolidin-l-yl)(l-ethyl-6-(5-fluoro- 2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((2S,4R)-2-(hydroxymethyl)-4-(trifluoromethoxy)pyrrolidin- 1 -yl)methanone;(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((2S,4R)-2-(hydroxymethyl)-4-(trifluoromethyl)pyrrolidin- 1 -yl)methanone;(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((2S.4R)-4-fluoro-2-(hydroxymethyl)pyrrolidin-l-yl)methanone;(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((S)-2-(hydroxymethyl)-4,4-dimethylpyrrolidin-l-yl)methanone;(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((S)-6-(hydroxymethyl)-5-azaspiro[2.4]heptan-5-yl)methanone;((S)-4,4-difluoro-2-(hydroxymethyl)pyrrolidin-l-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)- 3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;((3S,6S)-l,l-difluoro-6-(hydroxymethyl)-5-azaspiro[2.4]heptan-5-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;2-((S)-l-(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indole-3-carbonyl)azetidin-2-yl)acetonitrile;(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((S)-2-((methylsulfonyl)methyl)azeti din-1 -yl)methanone;(l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;(5,5-difluoro-2-azaspiro[3.3]heptan-2-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)(3-(2-fluoropropan-2-yl)azetidin-l-yl)methanone;(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimi din-4-yl)-lH-indol-3-yl)((R)-3-(tri fluoromethoxy )pyrrolidin-l-yl)methanone;(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)(5-azaspiro[2.3]hexan-5-yl)methanone;N-((S)-1 -cyclopropyl-2 -hydroxy ethyl)-l-ethyl-6-(5-fluoro-2-(((3S, 4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indole-3-carboxamide;(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)(5-azaspiro[2.4]heptan-5-yl)methanone;(3-(difluoromethyl)-3-hydroxyazetidin-l-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyri mi din-4-yl)-lH-indol-3-yl)(3-hydroxy-3-(trifluoromethyl)azeti din-1 -yl)methanone;((4S)-l?l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;((4R)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;((2S,3S)-2-((cyclopropylsulfonyl)methyl)-3-methylazetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;2-((S)-l-(4-fluoro-6-(5-fluoro-2-(((3S.4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indole-3-carbonyl)azetidin-2-yl)acetonitrile;((2S,4R)-4-(difluoromethoxy)-2-(hydroxymethyl)pyrrolidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrirnidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2S,4R)-2-(hydroxymethyl)-4-(trifluoromethoxy)py rrolidin- 1 -y l)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2S,4R)-2-(hydroxymethyl)-4-(trifluoromethyl)pyrrolidin-l-yl)methanone;((3S,6S)-l,l-difluoro-6-(hydroxymethyl)-5-azaspiro[2.4]heptan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-mdol-3-yl)((2S,4S)-2-(hydroxymethyl)-4-methoxy-4-(trifluoromethyl)pyrrolidin- 1 -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)((2S,4S)-4-hydroxy-2-(hydroxymethyl)-4-(trifluoromethyl)pyrrolidin- 1 -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((R)-3-(trifluoromethoxy)pyrrolidin-l-yl)methanone;((R)-3-(difluoromethoxy)pyrrolidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)(5-azaspiro[2.3]hexan-5-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((2S.3S)-2-(hydroxymethyl-d2)-3-methylazetidin- 1 -y l)methanone;((2R,3S)-3-(difluoromethoxy)-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro- 2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol- 3-yl)methanone;((S)-2-(difluoromethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(S)-l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indole-3-carbonyl)azetidine-2-carbonitrile;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)(3-hy droxyazeti din-1 -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)(3-methylazetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)(3-methoxyazetidin-l -yl)methanone;(3-(l,l-difluoroethyl)-3-methylazetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(1,1 -difluoro-2,2-dimethyl -5 -azaspiro [2.3]hexan-5 -yl)(4-fluoro-6-(5 -fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(6-(5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-lH-indol-3-yl)(3-(trifluoromethyl)azetidin-l-yl)methanone;(6-(5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-lH-indol-3-yl)((R)-2-methylazetidin-l-yl)methanone;(6-(5-chloro-2-(((3S.4R)-3-hydroxytetraliydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-ethyl-lH-indol-3-yl)((2S,4R)-4-(difluoromethoxy)-2-(hydroxymethyl)pyrrolidin-l-yl)methanone;(6-(5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)- 1-ethyl-lH-indol-3-yl)((2S,4R)-4-fluoro-2-(hydroxymethyl)pyrrolidin-l-yl)methanone;(5,5 -difluoro-2-azaspiro [3.3]heptan-2-yl)( 1 -(2,2-difluoroethy l)-4-fluoro-6-(5 -fluoro- 2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;(l-(2,2-difluoroethyl)-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((2S,3S)-2-(hydroxymethyl-d2)-3-methylazeti din-1 -yl)methanone;(l-(2,2-difluoroethyl)-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)(3-(2-fluoropropan-2-yl)azetidin-l-yl)methanone;(l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(l-(2,2-difluoroethyl)-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;(6-(5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-4-fluoro-l-methyl-lH-indol-3-yl)(3-(2-lluoropropan-2-yl)azetidin-l-yl)methanone;(6-(5-chloro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-4-fluoro-l-methyl-lH-indol-3-yl)(l,l-difluoro-2,2-dimethyl-5-azaspiro[2.3]hexan-5-yl)methanone;(l-(2,2-difluoroethyl)-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((S)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;(l-(2,2-difluoroethyl)-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((R)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;((4S)-Ll-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(l-(2,2-difluoroethyl)-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;((4R)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(l-(2,2-difluoroethyl)-6-(5-fluoro-2-(((3S.4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;(l-(2,2-difluoroethyl)-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((S)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;(l-(2,2-difluoroethyl)-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((R)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)- 1 -methyl- lH-indol-3-yl)((S)- 1 -(hydroxymethy l)-2-azaspiro[3.3]heptan-2-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)((R)-l-(hydroxymethyl)-2-azaspiro[3.3]heptan-2-yl)methanone;((4S)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl-lH-indol-3-yl)methanone;((4R)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl-lH-indol-3-yl)methanone;((2S,3S)-3-(difluoromethyl)-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;((2R,3R)-3-(difluoromethyl)-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((lR,4S,5R)-5-(hydroxymethyl)-2-azabicyclo[2.1.0]pentan-2-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((lS,4R,5S)-5-(hydroxymethyl)-2-azabicyclo[2.1,0]pentan-2-yl)methanone;(2S,3S)-l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indole-3-carbonyl)-2-(hydroxymethyl)azetidine-3-carbonitrile;(2R,3R)-l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indole-3-carbonyl)-2-(hydroxymethyl)azetidine-3-carbonitrile;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((2R,3R)-2-(hydroxymethyl)-3-(methylsulfonyl)azetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)arrrino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((2S,3S)-2-(hydroxymethyl)-3-(methylsulfonyl)azetidin- 1 -y l)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((2R,3S)-2-(hydroxymethyl)-3-(methy lsulfonyl)azetidin- 1 -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((2S,3R)-2-(hydroxymethyl)-3-(methylsulfonyl)azetidin-l-yl)methanone;((4R)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;((4S)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(l-ethyl-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;((4R)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;((4S)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)mehthanone;(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((R)-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((2S,3S)-2-(hydroxymethyl)-3-((trifluoromethoxy)methyl)azetidin- 1 -y l)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((2R, 3R)-2-(hy droxymethyl)-3-((trifluoromethoxy)methyl)azetidin- 1 -yl)methanone;((2S,3S)-3-((difluoromethoxy)methyl)-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;((2R,3R)-3-((difluoromethoxy)methyl)-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;((4S)-1 J-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;((4R)-l,l-difluoro-4-(hydroxymethyl)-5-azaspiro[2.3]hexan-5-yl)(l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((R)-l-(hydroxymethyl)-2-azaspiro[3.3]heptan-2-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((S)-l-(hydroxymethyl)-2-azaspiro [ 3.3 ]heptan-2-y 1 )methanone;((R)-3,3-difluoro-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;((S)-3,3-difluoro-2-(hydroxymethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;4-fluoro-6-(5-fluoro-2-(((3A,4^)-3-hydroxy-l-(methylsulfonyl)piperidin-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-jV,jV-dimethyl-l / f-indole-3-carboxamide;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-2-(methoxymethyl)azetidin-l-yl)methanone;2-((S)-l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indole-3-carbonyl)azetidin-2-yl)acetonitrile;((S)-2-((dimethylamino)methyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S.4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;((S)-2-(2,2-difluoroethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(l,l-difluoro-5-azaspiro[2.4]heptan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(5,5-difluoro-2-azaspiro[3.3]heptan-2-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimi din -4-yl)- 1-isopropyl- lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-2-(hydroxymethyl)-2-methylazetidin- 1 -y l)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((2S,3R)-2-(hydroxymethyl)-3-methylazetidin- 1 -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((S)-2-(2-hydroxyethyl)azetidin-l -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((S)-2-(2-hydroxypropan-2-yl)azeti din-1 -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((2S,3S)-3-methyl-2-((methy Isulfony l)methyl)azetidin- 1 -y l)methanone;((S)-2-((cyclopropylsulfonyl)methyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)methanone;(l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-y l)amino)pyrimidin-4-yl)- 1 -isopropyl- lH-indol-3 -yl)(3-(py rrolidin- 1 -yl)azeti din- 1 -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)(6-oxa-2-azaspiro[3.4]octan-2-yl)methanone;(3-(dimethylamino)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-2-(fluoromethyl)azetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)(3-hydroxyazeti din- 1 -yl)methanone;(3-(difluoromethoxy)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3R,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)(3-(pyrrolidin-l-yl)azeti din-1-yl)methanone;azetidin-l-yl(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(3-aminoazetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(3-(difluoromethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-fluoroazetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-methylazetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((R)-2-methylazetidin-l-yl)methanone;((2R,4R)-2,4-dimethylazetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(5-azaspiro[2.3]hexan-5-yl)methanone;l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indole-3-carbonyl)azetidine-3-carbonitrile;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(pyrroli din-1 -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((R)-3-fluoropyrrolidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((R)-3-hydroxypyrrolidin-l -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-3-hydroxypyrrolidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)(3-hydroxy-3-(trifluoromethyl)azeti din-1 -yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((S)-2-(hydroxymethyl)pyrrolidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((R)-2-(hydroxymethyl)pyrroli din-1 -yl)methanone;(3,3-difluoropyrrolidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)((lR,2S,5S)-2-(hydroxymethyl)-3-azabicyclo[3.1,0]hexan-3-yl)methanone;(S)-l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indole-3-carbonyl)pyrrolidine-3-carbonitrile;(R)-l-(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indole-3-carbonyl)pyrrolidine-3-carbonitrile;(3-fluoro-3-(trifluoromethyl)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(5-azaspiro[2.4]heptan-5-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-methyl-3-(trifluoromethyl)azetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)(3-isopropoxyazetidin-l-yl)methanone:(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-(hydroxymethyl)azetidin-l-yl)methanone;(3-((difluoromethoxy)methyl)azetidin-1-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)(3-(2-(trifluoromethoxy)ethyl)azeti din-1 -yl)methanone;(l-ethyl-4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-lH-indol-3-yl)((S)-2-(hydroxymethyl)azetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)(3-(trifluoromethoxy)azetidin-l-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-isopropyl-lH-indol-3-yl)(3-((trifluoromethoxy)methyl)azetidin-l-yl)methanone;(3-(difluoromethoxy)azetidin-l-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -isopropyl- lH-indol-3-yl)((S)-2-(l-hy droxycy cl opropyl)azeti din-1 -yl)methanone;(4,7-difluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-y l)amino)pyrimidin-4-yl)- 1 -methy 1- lH-indol-3 -y 1)( 1, 1 -difluoro-5 -azaspiro[2.3]hexan-5 -yl)methanone;(l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(7-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(7-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)((2S,3S)-2-(hydroxymethyl-d2)-3-methylazetidin- 1 -y l)methanone;(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l,7-dimethyl-lH-indol-3-yl)((2S.3S)-2-(hydroxymethyl-d2)-3-methyl azetidin- 1 -y l)methanone;(l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l,7-dimethyl-lH-indol-3-yl)methanone;(4,5-difluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-y l)amino)pyrimidin-4-yl)- 1 -methy 1- lH-indol-3 -y 1)( 1, 1 -difluoro-5 -azaspiro[2.3]hexan-5 -yl)methanone;(l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(5-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l-methyl-lH-indol-3-yl)methanone;(5-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-l -methyl- lH-indol-3-yl)((2S,3S)-2-(hydroxymethyl-d2)-3-methylazetidin- 1 -yl)methanone; and(l,l-difluoro-5-azaspiro[2.3]hexan-5-yl)(4-fluoro-6-(5-fluoro-2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-5-methoxy-l -methyl- lH-indol-3-yl)methanone;or a pharmaceutically acceptable salt thereof.

47. A pharmaceutical composition comprising the compound of any one of claims 1-46, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

48. A method of inhibiting CDK4, comprising contacting the CDK4 w ith the compound of any one of claims 1-46, or a pharmaceutically acceptable salt thereof.

49. A method of inhibiting CDK4 in a patient, comprising administering to the patient a compound of any one of claims 1-46, or a pharmaceutically acceptable salt thereof.

50. A method of treating a disease or disorder associated with CDK4 in a patient, comprising administering to the patient a therapeutically effective amount of the compound of any one of claims 1-46, or pharmaceutically acceptable salt thereof.

51. The method of claim 50, wherein the disease or disorder is cancer.

52. The method of claim 51, wherein the cancer is selected from breast cancer, ovarian cancer, a gynecological cancer, a gastrointestinal cancer, prostate cancer, melanoma, colorectal cancer, endometrial cancer, esophageal cancer, gastric cancer, liposarcoma, Ewing sarcoma, or melanoma.

53. The method of any one of claims 49-52, wherein the administering further comprises administering one or more additional pharmaceutical agents.

54. The method of claim 53, wherein the one or more additional pharmaceutical agents is an aromatase inhibitor, luteinizing hormone-rel easing hormone (LHRH) agonist, an anti-androgen, therapy targeting the PI3K / AKT / mT0R (PAM) pathway, a selective estrogen receptor degrader (SERD). a CDK.2 inhibitor, a CDK4 / 6 inhibitor, a CDK4 inhibitor, or VEGF-A inhibitor, or a combination thereof.

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