Tricyclic amine compounds as CDK2 inhibitors

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• n is 0, 1, or 2;
• m is 0, 1, 2, 3, or 4;
• X1 is N;
• X2 is CR2;
• Y is N;
• Z1 is CR4R5;
• and Z2 is O;
• or
• X1 is N;
• X2 is CR2;
• Y is N;
• Z1 is CR4R5;
• and Z2 is CR4zR5z;
• or
• X1 is C;
• X2 is NR2x;
• Y is N;
• Z1 is CR4R5;
• and Z2 is CR4zR5z;
• Ring moiety A is selected from (1) C6-10 aryl;
• (2) 5-10 membered monocyclic or bicyclic heteroaryl, wherein the 5-10 membered monocyclic or bicyclic heteroaryl has 1, 2, 3, or 4 ring heteroatoms independently selected from N, O, and S;
• and (3) a fused bicyclic moiety of formula:
• wherein Ring B is (a) phenyl or (b) a 5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl has 1, 2, or 3 ring heteroatoms independently selected from N, O, and S;
• and Ring B″ is (a) C5-7 membered cycloalkyl, wherein 1 or 2 ring carbon atoms of the C5-7 cycloalkyl are optionally substituted by 1 or 2 substituents independently selected from oxo and sulfido groups;
• or (b) 4-7 membered heterocycloalkyl, wherein the 4-7 membered heterocycloalkyl has 1, 2 or 3 ring heteroatoms independently selected from N, O, and S, and wherein 1 or 2 ring carbon atoms or heteroatoms are optionally substituted by 1 or 2 substituents independently selected from oxo and sulfido groups;
• R1 is selected from H, 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, ORa1, SRa1, NHORa1, C(O)Rb1, C(O)NRc1Rd1, C(O)NRc1(ORa1), C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, C(═NRe1)Rb1, C(═NRe1)NRc1Rd1, NRc1C(═NRe1)NRc1Rd1 NRc1C(═NRe1)Rb1, NRc1S(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)(═NRe1)Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Rd1, OS(O)(═NRe1)Rb1, OS(O)2Rb1, S(O)(═NRe1)Rb1, SF5, P(O)Rf1Rg1, OP(O)(ORh1)(ORi1), P(O)(ORh1)(ORi1), and BRj1Rk1;
• wherein the 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R1A substituents;
• each Ra1, Rc1, and Rd1 is independently selected from H, C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, wherein the 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1A substituents;
• or, any Rc1 and Rd1 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R1A substituents;
• each Rb1 is independently selected from C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1A substituents;
• each Re1 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rf1 and Rg1 is independently selected from H, 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 heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rh1 and Ri1 is independently selected from H, C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rj1 and Rk1 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
• or any Rj1 and Rk1 attached 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 C1-6 alkyl and C1-6 haloalkyl;
• each R1A is 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, ORa11, SRa11, NHORa11, C(O)Rb11, C(O)NRc11Rd11, C(O)NRc11(ORa11), C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)ORa11, NRc11C(O)NRc11Rd11, C(═NRe11)Rb11, C(═NRe11)NRc11Rd11, NRc11C(═NRe11)NRc11Rd11, NRc11C(═NRe11)Rb11, NRc11S(O)NRc11Rd11, NRc11S(O)Rb11 NRc11S(O)2Rb11, NRc11S(O)(═NRe11)Rb11, NRc11S(O)2NRc11Rd11, S(O)Rb11, S(O)NRc11Rd11, S(O)2Rb11, S(O)2NRc11Rd11, OS(O)(═NRe11)Rb11, OS(O)2Rb11, S(O)(═NRe11)Rb11, SF5, P(O)Rf11Rg11, OP(O)(ORh11)(ORi11), P(O)(ORh11)(ORi11) and BRj11Rk11, wherein the 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1B substituents;
• each Ra11, Rc11, and Rd11 is independently selected from H, C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, wherein the 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1B substituents;
• or, any Rc11 and Rd11 attached 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 R1B substituents;
• each Rb11 is independently selected from C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1B substituents;
• each Re11 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rf11 and Rg11 is independently selected from H, 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 heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rh11 and Ri11 is independently selected from H, C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rj11 and Rk11 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
• or any Rj11 and Rk11 attached 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 C1-6 alkyl and C1-6 haloalkyl;
• each R1B is independently selected from D, halo, CN, NO2, C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-C1-4 alkyl, ORa12, SRa12, NHORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)NRc12(ORa12), C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRc12Rd12, NRc12NRc12Rd12, NRc12C(O)Rb12, NRc12C(O)ORa12, NRc12C(O)NRc12Rd12, C(═NRe12)Rb12, C(═NRe12)NRc12Rd12, NRc12C(═NRe12)NRc12Rd12, NRc12C(═NRe12)Rb2, NRc12S(O)NRc12Rd2, NRc12S(O)Rb12, NRc12S(O)2Rb12, NRc12S(O)(═NRe12)Rb12, NRc12S(O)2NRc12Rd12, S(O)Rb12, S(O)NRc12Rd12, S(O)2Rb12, S(O)2NRc12Rd12, OS(O)(═NRe12)Rb12, OS(O)2Rb12, S(O)(═NRe12)Rb12, SF5, P(O)Rf12Rg12, OP(O)(ORh12)(ORi12), P(O)(ORh12)(ORi12), and BRj12Rk12, wherein the C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• each Ra12, Rc12, and Rd12 is independently selected from H, C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• or, any Rc12 and Rd12 attached 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 RG substituents;
• each Rb12 is independently selected from C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• each Re12 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;
• each Rf12 and Rg12 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;
• each Rh12 and Ri12 is independently selected from H, C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;
• each Rj12 and Rk12 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
• or any Rj12 and Rk12 attached 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 C1-6 alkyl and C1-6 haloalkyl;
• R2 is selected from H, D, halo, NO2, 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, ORa2, SRa2, NHORa2, C(O)Rb2, C(O)NRc2Rd2, C(O)NRc2(ORa2), C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, C(═NRe2)Rb2, C(═NRe2)NRc2Rd2, NRc2C(═NRe2)NRc2Rd2, NRc2C(═NRe2)Rb2, NRc2S(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)(═NRe2)Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2, OS(O)(═NRe2)Rb2, OS(O)2Rb2, S(O)(═NRe2)Rb2, SF5, P(O)Rf2Rg2, OP(O)(ORh2)(ORi2), P(O)(ORh2)(ORi2), and BRj2Rk2;
• wherein the 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R2A substituents;
• R2x is selected from H, C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, C(O)Rb2, C(O)NRc2Rd2, C(O)NRc2(ORa2), C(O)ORa2, C(═NRe2)Rb2, C(═NRe2)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• wherein the C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R2A substituents;
• each Ra2, Rc2, and Rd2 is independently selected from H, C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, wherein the 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R2A substituents;
• or, any Rc2 and Rd2 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R2A substituents;
• each Rb2 is independently selected from C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R2A substituents;
• each Re2 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rf2 and Rg2 is independently selected from H, 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 heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rh2 and Ri2 is independently selected from H, C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rj2 and Rk2 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
• or any Rj2 and Rk2 attached 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 C1-6 alkyl and C1-6 haloalkyl;
• each R2A is 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, ORa21, SRa21, NHORa21, C(O)Rb21, C(O)NRc21Rd21, C(O)NRc21(ORa21), C(O)ORa21, OC(O)Rb21, OC(O)NRc21Rd21, NRc21Rd21, NRc21Rd21, NRc21C(O)Rb21, NRc21C(O)ORa21, NRc21C(O)NRc21Rd21, C(═NRe21)Rb21, C(═NRe21)NRc21Rd21, NRc21C(═NRe21)NRc21Rd21, NRc21C(═NRe21)Rb21, NRc21S(O)NRc21Rd21, NRc21S(O)Rb21, NRc21S(O)2Rb21, NRc21S(O)(═NRe21)Rb21, NRc21S(O)2NRc21Rd21, S(O)Rb21, S(O)NRc21Rd21, S(O)2Rb21, S(O)2NRc21Rd21, OS(O)(═NRe21)Rb21, OS(O)2Rb21, S(O)(═NRe21)Rb21, SF5, P(O)Rf21Rg21, OP(O)(ORh21)(ORi21), P(O)(ORh21)(ORi21), and BRj21Rk21, wherein the 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R2B substituents;
• each Ra21, Rc21, and Rd21 is independently selected from H, C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, wherein the 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R2B substituents;
• or, any Rc21 and Rd21 attached 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 R2B substituents;
• each Rb21 is independently selected from C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R2B substituents;
• each Re21 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C14 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rf21 and Rg21 is independently selected from H, 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 heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rh21 and Ri12 is independently selected from H, C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rj21 and Rk21 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
• or any Rj21 and Rk21 attached 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 C1-6 alkyl and C1-6 haloalkyl;
• each R2B is independently selected from D, halo, CN, NO2, C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-C1-4 alkyl, ORa22, SRa22, NHORa22, C(O)Rb22, C(O)NRc22Rd22, C(O)NRc22(ORa22), C(O)ORa22, OC(O)Rb22, OC(O)NRc22Rd22, NRc22Rd22, NRc22NRc22Rd22, NRc22C(O)Rb22, NRc22C(O)ORa22, NRc22C(O)NRc22Rd22, C(═NRe22)Rb22, C(═NRe22)NRc22Rd22, NRc22C(═NRe22)NRc22Rd22, NRc22C(═NRe22)Rb22, NRc22S(O)NRc22Rd22, NRc22S(O)Rb22, NRc22S(O)2Rb22, NRc22S(O)(═NRe22)Rb22, NRc22S(O)2NRc22Rd22, S(O)Rb22, S(O)NRc22Rd22, S(O)2Rb22, S(O)2NRc22Rd22, OS(O)(═NRe22)Rb22, OS(O)2Rb22, S(O)(═NRe22)Rb22, SF5, P(O)Rf22Rg22, OP(O)(ORh22)(ORi22), P(O)(ORh22)(ORi22), and BRj22Rk22, wherein the C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• each Ra22, Rc22, and Rd22 is independently selected from H, C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• or, any Rc22 and Rd22 attached 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 RG substituents;
• each Rb22 is independently selected from C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• each Re22 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;
• each Rf22 and Rg22 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;
• each Rh22 and Ri22 is independently selected from H, C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;
• each Rj22 and Rk22 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
• or any Rj22 and Rk22 attached 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 C1-6 alkyl and C1-6 haloalkyl;
• R3 is selected from H, D, halo, CN, C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, C2-4 alkynyl, OH, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, and C3-4 cycloalkyl;
• R4, R4z, R5 and R5z are each independently selected from H, D, halo, CN, C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, C2-4 alkynyl, OH, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, cyano-C1-3 alkyl, HO—C1-3 alkyl, C1-3 alkoxy-C1-3 alkyl, and C3-4 cycloalkyl;
• or R4 and R5, together with the carbon atom to which they are attached, form a 3-7 membered cycloalkyl ring or a 4-7 membered heterocycloalkyl ring, wherein the 3-7 membered cycloalkyl ring and 4-7 membered heterocycloalkyl ring are each optionally substituted by 1, 2, 3, or 4 substituents independently selected from D, halo, CN, C1-3 alkyl, C1-3 haloalkyl, OH, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, cyano-C1-3 alkyl, HO—C1-3 alkyl, and C1-3 alkoxy-C1-3 alkyl;
• or R4z and R5z, together with the carbon atom to which they are attached, form a 3-7 membered cycloalkyl ring or a 4-7 membered heterocycloalkyl ring, wherein the 3-7 membered cycloalkyl ring and 4-7 membered heterocycloalkyl ring are each optionally substituted by 1, 2, 3, or 4 substituents independently selected from D, halo, CN, C1-3 alkyl, C1-3 haloalkyl, OH, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, cyano-C1-3 alkyl, HO—C1-3 alkyl, and C1-3 alkoxy-C1-3 alkyl;
• each R8 is independently selected from H, D, halo, CN, NO2, C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-C1-4 alkyl, 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, S(O)2NRc8Rd8, OS(O)(═NRe8)Rb8, OS(O)2Rb8, S(O)(═NRe8)Rb8, SF5, P(O)Rf8Rg8, OP(O)(ORh8)(ORi8), and P(O)(ORh8)(ORi8);
• wherein the C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected RG substituents;
• each Ra8, Rc8, and Rd8 is independently selected from H, C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• or, any Rc8 and Rd8 attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl, which is optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• each Rb8 is independently selected from C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• each Re8 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;
• each Rf8 and Rg8 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;
• each Rh8 and Ri8 is independently selected from H, C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;
• each R8″ is selected from H, D, OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-C1-3 alkyl, HO—C1-3 alkyl, C1-3 alkoxy-C1-3 alkyl, C3-7 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(C1-3 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(C1-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(C1-3 alkyl)aminocarbonylamino;
• RA is NR9R10 or R11;
• R9 is selected from H, 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, wherein the 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R9A substituents;
• R10 is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and C3-4 cycloalkyl;
• R11 is 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, wherein the 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R9A substituents;
• each R9A is 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, ORa9, SRa9, NHORa9, C(O)Rb9, C(O)NRc9Rd9, C(O)NRc9 (ORa9), C(O)ORa9, OC(O)Rb9, OC(O)NRc9Rd9, NRc9Rd9, NRc9NRc9Rd9, NRc9C(O)Rb9, NRc9C(O)ORa9, NRc9C(O)NRc9Rd9, C(═NRe9)Rb9, C(═NRe9)NRc9Rd9, NRc9C(═NRe9)NRc9Rd9, NRc9C(═NRe9)Rb9, NRc9S(O)NRc9Rd9, NRc9S(O)Rb9, NRc9S(O)2Rb9, NRc9S(O)(═NRe9)Rb9, NRc9S(O)2NRc9Rd9, S(O)Rb9, S(O)NRc9Rd9, S(O)2Rb9, S(O)2NRc9Rd9, OS(O)(═NRe9)Rb9, OS(O)2Rb9, S(O)(═NRe9)Rb9, SF5, P(O)Rf9Rg9, OP(O)(ORh9)(ORi9), P(O)(ORh9)(ORi9), and BRj9Rk9;
• wherein the 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R9B substituents;
• each Ra9, Rc9, and Rd9 is independently selected from H, C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, wherein the 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-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R9B substituents;
• or, any Rc9 and Rd9 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R9B substituents;
• each Rb9 is independently selected from C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R9B substituents;
• each Rc9 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rf9 and Rg9 is independently selected from H, 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 heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rh9 and Ri9 is independently selected from H, C1-6 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, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl;
• each Rj9 and Rk9 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
• or any Rj9 and Rk9 attached 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 C1-6 alkyl and C1-6 haloalkyl;
• each R9B is selected from D, halo, CN, NO2, C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-C1-4 alkyl, ORa91, SRa91, NHORa91, C(O)Rb91, C(O)NRc91Rd91, C(O)NRc91(ORa91), C(O)ORa91, OC(O)Rb91, OC(O)NRc91Rd91, NRc91Rd91, NRc91NRc91Rd91, NRc91C(O)Rb91, NRc91C(O)ORa91, NRc91C(O)NRc91Rd91, C(═NRe91)Rb91, C(═NRe91)NRc91Rd91, NRc91C(═NRe91)NRc91Rd91, NRc91C(═NRe91)Rb91, NRc91S(O)NRc91Rd91, NRc91S(O)Rb91, NRc91S(O)2Rb91, NRc91S(O)(═NRe91)Rb91, NRc91S(O)2NRc91Rd91, S(O)Rb91, S(O)NRc91Rd91, S(O)2Rb91, S(O)2NRc91Rd91, OS(O)(═NRe91)Rb91, OS(O)2Rb91, S(O)(═NRe91)Rb91, SF5, P(O)Rf91Rg91, OP(O)(ORh91)(ORi91), P(O)(ORh91)(OR91), and BRj91Rk91;
• wherein the C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected RG substituents;
• each Ra91, Rc91, and Rd91 is independently selected from H, C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• or, any Rc91 and Rd91 attached 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 RG substituents;
• each Rb91 is independently selected from C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein the C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• each Re91 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;
• each Rf91 and Rg91 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;
• each Rh91 and Ri91 is independently selected from H, C1-6 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;
• each Rj91 and Rk91 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
• or any Rj91 and Rk91 attached 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 C1-6 alkyl and C1-6 haloalkyl;
• and
• each RG is independently selected from OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-C1-3 alkyl, HO—C1-3 alkyl, C1-3 alkoxy-C1-3 alkyl, C3-7 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, alkylamino, di(C1-3 alkyl)amino, thio, alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(C1-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, C1-3 alkylaminocarbonyloxy, di(C1-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(C1-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(C1-3 alkyl)aminocarbonylamino.