# US 11,440,914 B2 · Tricyclic amine compounds as CDK2 inhibitors

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- Number: US 11,440,914 B2
- Document ID: US11440914B2
- Status: Granted
- Kind: B2
- Application number: 16/863,770
- Filed: 2020-04-30
- Published: 2020-11-05
- Granted: 2022-09-13
- Earliest claimed: 2019-05-01
- Assignees: Incyte Corporation
- Applicants: Incyte Corporation
- Inventors: Qinda Ye; Neil Lajkiewicz; Ken Mukai; Liangxing Wu; Wenqing Yao
- Web page: https://patentgrep.com/patent/US11440914B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61P 35/00: Antineoplastic agents
- C07D 491/14: Ortho-condensed systems
- C07D 491/147: the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present application provides tricyclic amine compounds, which are inhibitors of cyclin-dependent kinase 2 (CDK2), as well as pharmaceutical compositions thereof, and methods of treating cancer using the same.

## Claims

### Claim 1

A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
n is 0, 1, 2, 3, 4, 5, or 6;
Z1 is CR4R5; and Z2 is NR6z, O, or S; or
Z1 is CR4R5, NR6, O, or S; and Z2 is CR4zR5z;
Y is CR7 or N;
X1 is NR1x, CR1, N, or O;
X2 is NR2x, CR2, N, or O;
X3 is N or C;
wherein Ring
is an aromatic ring selected from:
Ring moiety A is selected from (1) C3-14 cycloalkyl, wherein 1, 2, 3, or 4 ring-forming carbon atoms of said C3-14 cycloalkyl can be optionally substituted by one or more oxo or sulfido, and (2) 4-14 membered 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 by one or more oxo or sulfido; wherein Ring moiety A is attached to the —NH— group of Formula (I) at a ring member of a saturated or partially saturated ring of said C3-14 cycloalkyl or said 4-14 membered heterocycloalkyl;
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 said 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;
R1x 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, 5-10 membered heteroaryl-C1-4 alkyl, C(O)Rb1, C(O)NRc1Rd1, C(O)NRc1(ORa1), C(O)ORa1, C(═NRe1)Rb1, C(═NRe1)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said 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;
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 said 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 said 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;
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 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, which 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, which 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;
R6 and R6z are each independently selected from H, C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, C2-4 alkynyl, cyano-C1-3 alkyl, HO—C1-3 alkyl, C1-3 alkoxy-C1-3 alkyl, and C3-4 cycloalkyl;
R7 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, cyano-C1-3 alkyl, HO—C1-3 alkyl, C1-3 alkoxy-C1-3 alkyl, and C3-4 cycloalkyl;
each R8 is 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, 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), P(O)(ORh8)(ORi8), and BRj8Rk8; wherein said 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 R8A substituents;
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 said 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 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)Rb12, NRc12S(O)NRc12Rd12, 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 said 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 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, NRc21NRc21Rd21, 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 said 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 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 said 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 R8A is 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, ORa81, SRa81, NHORa81, C(O)Rb81, C(O)NRc81Rd81, C(O)NRc81(ORa81), C(O)ORa81, OC(O)Rb81, OC(O)NRc81Rd81, NRc81Rd81, NRc81NRc81Rd81, NRc81C(O)Rb81, NRc81C(O)ORa81, NRc81C(O)NRc81Rd81, C(═NRe81)Rb81, C(═NRe81)NRc81Rd81, NRc81C(═NRe81)NRc81Rd81, NRc81C(═NRe81)Rb81, NRc81S(O)NRc81Rd81, NRc81S(O)Rb81, NRc81S(O)2Rb81, NRc81S(O)(═NRe81)Rb81, NRc81S(O)2NRc81Rd81, S(O)Rb81, S(O)NRc81Rd81, S(O)2Rb81, S(O)2NRc81Rd81, OS(O)(═NRe81)Rb81, OS(O)2Rb81, S(O)(═NRe81)Rb81, SF5, P(O)Rf81Rg81, OP(O)(ORh81)(ORi81), P(O)(ORh81)(ORi81), and BRj81Rk81; wherein said 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 R8B substituents;
each R8B 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, ORa82, SRa82, NHORa82, C(O)Rb82, C(O)NRc82Rd82, C(O)NRc82(ORa82), C(O)ORa82, OC(O)Rb82, OC(O)NRc82Rd82, NRc82Rd82, NRc82NRc82Rd82, NRc82C(O)Rb82, NRc82C(O)ORa82, NRc82C(O)NRc82Rd82, C(═NRe82)Rb82, C(═NRe82)NRc82Rd82, NRc82C(═NRe82)NRc82Rd82, NRc82C(═NRe82)Rb82, NRc82S(O)NRc82Rd82, NRc82S(O)Rb82, NRc82S(O)2Rb82, NRc82S(O)(═NRe82)Rb82, NRc82S(O)2NRc82Rd82, S(O)Rb82, S(O)NRc82Rd82, S(O)2Rb82, S(O)2NRc82Rd82, OS(O)(═NRe82)Rb82, OS(O)2Rb82, S(O)(═NRe82)Rb82, SF5, P(O)Rf82Rg82, OP(O)(ORh82)(ORi82), P(O)(ORh82)(ORi82), and BRj82Rk82; 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 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 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 said 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, which 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 are 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 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 said 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, which 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 are 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 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 said 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, which 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 are 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;
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 said 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, which 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 are 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 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 said 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, which 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-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 Rf21 and Rg21 are 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 Ri21 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 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 said 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, which 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 are 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;
each Ra8, Rc8, and Rd8 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 said 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 R8A substituents;
or, any Rc8 and Rd8 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R8A substituents;
each Rb8 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, which are each optionally substituted with 1, 2, 3, or 4 independently selected R8A 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, C3-10 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 Rf8 and Rg8 are 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 Rh8 and Ri8 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 Rj8 and Rk8 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
or any Rj8 and Rk8 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 Ra81, Rc81, and Rd81 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 said 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 R8B substituents;
or, any Rc81 and Rd81 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 R8B substituents;
each Rb81 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, which are each optionally substituted with 1, 2, 3, or 4 independently selected R8B substituents;
each Re81 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 Rf81 and Rg81 are 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 Rh81 and Ri81 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 Rj81 and Rk81 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
or any Rj81 and Rk81 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 Ra82, Rc82, and Rd82 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 said 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 Rc82 and Rd82 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 Rb82 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, which are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
each Re82 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 Rf82 and Rg82 are 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 Rh82 and Ri82 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 Rj82 and Rk82 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
or any Rj82 and Rk82 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, 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, 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
wherein “cycloalkyl” refers to a non-aromatic monocyclic or bicyclic hydrocarbon, including cyclized alkyl and alkenyl groups, which may be fused, spirocyclic, or bridged, which may contain one or more fused aromatic rings, wherein the ring-forming carbon atoms of a cycloalkyl group can be optionally substituted by oxo or sulfido (C(O) or C(S));
wherein “heterocycloalkyl” refers to monocyclic or bicyclic heterocycle, having at least one non-aromatic ring (saturated or partially unsaturated ring), which may contain a fused aromatic ring, wherein the ring-forming carbon atoms and heteroatoms of the heterocycloalkyl group can be optionally substituted by one or more oxo or sulfido (C(O), S(O), C(S), or S(O)2, and wherein 1, 2, 3, or 4 of the ring-forming atoms are independently selected from N, O, S, and B; and
wherein “heteroaryl” refers to a monocyclic or bicyclic aromatic heterocycle, wherein 1, 2, 3, or 4 of the ring-forming atoms are independently selected from N, O, S, and B, and wherein any ring-forming N in a heteroaryl moiety can be an N-oxide.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring

### Claim 3 (depends on 2)

The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from H, halo, CN, C1-6 alkyl, 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; wherein said C1-6 alkyl, 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 R1A substituents.

### Claim 4 (depends on 2)

The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from H, halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl; wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 independently selected R1A substituents.

### Claim 5 (depends on 2)

The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from H, halo, C1-6 alkyl, phenyl, and 5-6 membered heteroaryl, wherein said C1-6 alkyl, phenyl and 5-6 membered heteroaryl are each optionally substituted by 1 or 2 independently selected R1A substituents.

### Claim 6 (depends on 2)

The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R2x is selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 independently selected R2A substituents.

### Claim 7 (depends on 2)

The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R2x is selected from H, C1-6 alkyl, C3-7 cycloalkyl, and phenyl-C1-3 alkyl.

### Claim 8 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring

### Claim 9 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R1x is selected from H, C1-6 alkyl, 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; wherein said C1-6 alkyl, 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, or 3 independently selected R1A substituents.

### Claim 10 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R1x is selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl; wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 independently selected R1A substituents.

### Claim 11 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R1x is selected from H, C1-6 alkyl, C3-7 cycloalkyl, phenyl, and 4-7 membered heterocycloalkyl, wherein said C1-6 alkyl, C3-7 cycloalkyl, phenyl, and 4-7 membered heterocycloalkyl are each optionally substituted by 1 or 2 independently selected R1A substituents.

### Claim 12 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, halo, CN, C1-6 alkyl, 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; wherein said C1-6 alkyl, 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 R2A substituents.

### Claim 13 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl; wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 independently selected R2A substituents.

### Claim 14 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R2 is selected from H, C1-6 alkyl, and C3-7 cycloalkyl.

### Claim 15 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3 is H.

### Claim 16 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y is N.

### Claim 17 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z1 is CR4R5; and Z2 is CR4zR5z or O.

### Claim 18 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R4, R4z, R5 and R5z are each independently selected from H and C1-3 alkyl.

### Claim 19 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring moiety A is piperidin-4-yl.

### Claim 20 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2.

### Claim 21 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein one R8 is halo or C1-6 alkyl and one R8 is S(O)2Rb8, wherein Rb8 is selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R8A substituents.

### Claim 22 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
n is 1, 2, 3, or 4;
Z1 is CR4R5; and Z2 is NR6z, O, or S; or
Z1 is CR4R5, NR6, O, or S; and Z2 is CR4zR5z;
Y is CR7 or N;
X1 is NR1x or CR1;
X2 is NR2x or CR2;
X3 is N or C;
wherein Ring
is an aromatic ring selected from:
Ring moiety A is monocyclic or bicyclic 4-10 membered 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 by one or more oxo or sulfido, wherein said heterocycloalkyl does not comprise an aromatic ring;
R1 is selected from H, halo, CN, C1-6 alkyl, 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, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1; wherein said C1-6 alkyl, 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 R1A substituents;
R1x is selected from H, C1-6 alkyl, 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; wherein said C1-6 alkyl, 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, or 3 independently selected R1A substituents;
R2 is selected from H, halo, CN, C1-6 alkyl, 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, 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 C1-6 alkyl, 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 R2A substituents;
R2x is selected from H, C1-6 alkyl, 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, wherein said C1-6 alkyl, 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, or 3 independently selected R2A substituents;
R3 is selected from H, halo, CN, C1-3 alkyl, and C1-3 haloalkyl;
R4, R4z, R5 and R5z are independently selected from H, halo, CN, C1-3 alkyl, and C1-3 haloalkyl;
or R4 and R5, together with the carbon atom to which they are attached, form a cyclopropyl or cyclobutyl ring;
or R4z and R5z, together with the carbon atom to which they are attached, form a 3 cyclopropyl or cyclobutyl ring;
R7 is selected from H, halo, CN, C1-3 alkyl, and C1-3 haloalkyl;
R8 is selected from H, halo, CN, C1-6 alkyl, 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, C(O)Rb8, C(O)NRc8Rd8, C(O)ORa8, OC(O)Rb8, OC(O)NRc8Rd8, NRc8Rd8, NRc8C(O)Rb8, NRc8C(O)ORa8, NRc8C(O)NRc8Rd8, NRc8S(O)2Rb8, NRc8S(O)2NRc8Rd8, S(O)2Rb8, and S(O)2NRc8Rd8; wherein said C1-6 alkyl, 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 R8A substituents;
each Ra1, Rc1, and Rd1 is 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-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 R1A substituents;
each Rb1 is independently selected from C1-6 alkyl, 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, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1A substituents;
each R1A is independently selected from halo, CN, NO2, C1-6 alkyl, 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, 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, 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 R1B substituents;
each Ra11, Rc11, and Rd11 is 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-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 R1B substituents;
each Rb11 is independently selected from C1-6 alkyl, 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, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1B substituents;
each R1B is independently selected from halo, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, 4-5 membered heterocycloalkyl, ORa12, and NRc12Rd12;
each Ra12, Rc12, and Rd12 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;
each Ra2, Rc2, and Rd2 is 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-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 R2A substituents;
each Rb2 is independently selected from C1-6 alkyl, 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, which are each optionally substituted with 1, 2, 3, or 4 independently selected R2A substituents;
each R2A is independently selected from halo, CN, NO2, C1-6 alkyl, 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, ORa21, SRa21, C(O)Rb21, C(O)NRc21Rd21, C(O)ORa21, OC(O)Rb21, OC(O)NRc21Rd21, NRc21Rd21, NRc21C(O)Rb21, NRc21C(O)ORa21, NRc21C(O)NRc21Rd21, NRc21S(O)2Rb21, NRc21S(O)2NRc21Rd21, S(O)2Rb21, and S(O)2NRc21Rd21, wherein said C1-6 alkyl, 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 R2B substituents;
each Ra21, Rc21, and Rd21 is 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-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 R2B substituents;
each Rb21 is independently selected from C1-6 alkyl, 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, which are each optionally substituted with 1, 2, 3, or 4 independently selected R2B substituents;
each R2B is independently selected from halo, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, 4-5 membered heterocycloalkyl, ORa22, and NRc22Rd22;
each Ra22, Rc22, and Rd22 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;
each Ra8, Rc8, and Rd8 is 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-C14 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-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 R8A substituents;
each Rb8 is independently selected from C1-6 alkyl, 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, which are each optionally substituted with 1, 2, 3, or 4 independently selected R8A substituents;
each R8A is independently selected from halo, CN, NO2, C1-6 alkyl, 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, ORa81, SRa81, C(O)Rb81, C(O)NRc81Rd81, C(O)ORa81, OC(O)Rb81, OC(O)NRc81Rd81, NRc81Rd81, NRc81C(O)Rb81, NRc81C(O)ORa81, NRc81C(O)NRc81Rd81, NRc81S(O)2Rb81, NRc81S(O)2NRc81Rd81, S(O)2Rb81, and S(O)2NRc81Rd81, wherein said C1-6 alkyl, 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 R8B substituents;
each Ra81, Rc81, and Rd81 is 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-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 R8B substituents;
each Rb81 is independently selected from C1-6 alkyl, 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, which are each optionally substituted with 1, 2, 3, or 4 independently selected R8B substituents;
each R8B is independently selected from 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, ORa82, SRa82, C(O)Rb82, C(O)NRc82Rd82, C(O)ORa82, OC(O)Rb82, OC(O)NRc82Rd82, NRc82Rd82, NRc82C(O)Rb82, NRc82C(O)ORa82, NRc82C(O)NRc82Rd82, NRc82S(O)2Rb82, NRc82S(O)2NRc82Rd82, S(O)2Rb82, and S(O)2NRc82Rd82;
each Ra82, Rc82, and Rd82 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; and
each Rb82 is independently selected from C1-6 alkyl and C1-6 haloalkyl.

### Claim 23 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
n is 1 or 2;
Z1 is CR4R5; and Z2 is O; or
Z1 is CR4R5; and Z2 is CR4zR5z;
R4 and R5 are each independently selected from H and C1-3 alkyl;
or R4 and R5, together with the carbon atom to which they are attached, form a cyclopropyl or cyclobutyl ring;
R4z and R5z are each H;
Y is N;
X1 is NR1x or CR1;
X2 is NR2x or CR2;
X3 is C;
wherein Ring
is an aromatic ring selected from:
Ring moiety A is azetinidin-3-yl, pyrrolidin-3-yl, piperidin-3-yl, or piperidin-4-yl;
R1 is selected from H, halo, C1-6 alkyl, 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; wherein said C1-6 alkyl, 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, or 3 independently selected R1A substituents;
R1x is selected from H, C1-6 alkyl, 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; wherein said C1-6 alkyl, 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, or 3 independently selected R1A substituents;
each R1A is independently selected from halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa11, and NRc11Rd11;
each Ra11, Rc11, and Rd11 is independently selected from H and C1-6 alkyl;
R2 is selected from H, halo, CN, C1-6 alkyl, 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; wherein said C1-6 alkyl, 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, or 3 independently selected R2A substituents;
R2x is selected from C1-6 alkyl, 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; wherein said C1-6 alkyl, 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, or 3 independently selected R2A substituents;
each R2A is independently selected from halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa21, and NRc21Rd21;
each Ra21, Rc21, and Rd21 is independently selected from H and C1-6 alkyl;
one R8 is S(O)2Rb8;
the remaining R8 is selected from halo or C1-3 alkyl;
each Rb8 is independently selected from C1-6 alkyl, 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, which are each optionally substituted with 1, 2, or 3 independently selected R8A substituents;
each R8A is independently selected from halo, CN, NO2, C1-6 alkyl, 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, ORa81, SRa81, C(O)Rb81, C(O)NRc81Rd81, C(O)ORa81, OC(O)Rb81, OC(O)NRc81Rd81, NRc81Rd81, NRc81C(O)Rb81, NRc81C(O)ORa81, NRc81C(O)NRc81Rd81, NRc81S(O)2Rb81, NRc81S(O)2NRc81Rd81, S(O)2Rb81, and S(O)2NRc81Rd81, wherein said C1-6 alkyl, 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 R8B substituents;
each Ra81, Rc81, and Rd81 is 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-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-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 R8B substituents;
each Rb81 is independently selected from C1-6 alkyl, 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, which are each optionally substituted with 1, 2, 3, or 4 independently selected R8B substituents;
each R8B is independently selected from halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa82, SRa82, C(O)Rb82, C(O)NRc82Rd82, C(O)ORa82, OC(O)Rb82, OC(O)NRc82Rd82, NRc82Rd82, NRc82C(O)Rb82, NRc82C(O)ORa82, NRc82C(O)NRc82Rd82, NRc82S(O)2Rb82, NRc82S(O)2NRc82Rd82, S(O)2Rb82, and S(O)2NRc82Rd82;
each Ra82, Rc82, and Rd82 is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; and
each Rb82 is independently selected from C1-6 alkyl and C1-6 haloalkyl.

### Claim 24 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
n is 1 or 2;
Z1 is CR4R5; and Z2 is O; or
Z1 is CR4R5; and Z2 is CH2;
R4 and R5 are each independently selected from H and methyl;
R4z and R5z are each H;
Y is N;
X1 is NR1x or CR1;
X2 is NR2x or CR2;
X3 is C;
wherein Ring
is an aromatic ring selected from:
R1 is selected from H, halo, C1-6 alkyl, phenyl, and 5-6 membered heteroaryl, wherein said C1-6 alkyl, phenyl and 5-6 membered heteroaryl are each optionally substituted by 1 or 2 independently selected R1A substituents;
R1x is selected from H, C1-6 alkyl, C3-7 cycloalkyl, phenyl, and 4-7 membered heterocycloalkyl, wherein said C1-6 alkyl, C3-7 cycloalkyl, phenyl, and 4-7 membered heterocycloalkyl are each optionally substituted by 1 or 2 independently selected R1A substituents;
each R1A is independently selected from halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa11, and NRc11Rd11;
each Ra11, Rc11, and Rd11 is independently selected from H and C1-6 alkyl;
R2 is selected from H, halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl;
R2x is selected from H, C1-6 alkyl, C3-7 cycloalkyl, and phenyl-C1-3 alkyl;
R8 is C1-3 alkyl;
each Rb8 is independently selected from C1-6 alkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, which are each optionally substituted with 1 or 2 independently selected R8A substituents;
each R8A is independently selected from halo, CN, C1-6 alkyl, C1-6 haloalkyl, and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl, C1-6 haloalkyl, and 4-7 membered heterocycloalkyl are each optionally substituted by 1 or 2 independently selected R8B substituents;
each R8B is selected from C1-6 alkyl and ORa82; and
each Ra82 is independently selected from H and C1-6 alkyl.

### Claim 25 (depends on 1)

The compound of claim 1, having Formula (IVa):
or a pharmaceutically acceptable salt thereof, wherein k is n−1.

### Claim 26 (depends on 1)

The compound of claim 1, having Formula (IVb):
or a pharmaceutically acceptable salt thereof, wherein k is n−1.

### Claim 27 (depends on 1)

The compound of claim 1, having Formula (IVc):
or a pharmaceutically acceptable salt thereof, wherein k is n−1.

### Claim 28 (depends on 1)

The compound of claim 1, having Formula (IVd):
or a pharmaceutically acceptable salt thereof, wherein k is n−1.

### Claim 29 (depends on 1)

The compound of claim 1, selected from:
N-(1-(Ethylsulfonyl)piperidin-4-yl)-1,2-dimethyl-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
N-(1-(Cyclopropylsulfonyl)piperidin-4-yl)-1,2-dimethyl-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
1,2-Dimethyl-N-(1-((1-methyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
N-(1-((1H-Pyrazol-4-yl)sulfonyl)piperidin-4-yl)-1,2-dimethyl-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
3-((4-((1,2-Dimethyl-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-yl)amino)piperidin-1-yl)sulfonyl)benzonitrile;
N-(1-((1,2-Dimethyl-1H-imidazol-4-yl)sulfonyl)piperidin-4-yl)-1,2-dimethyl-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
2-Methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
1-Benzyl-2-methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
8-Methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-6,8-dihydro-5H-pyrazolo[3,4-h]quinazolin-2-amine;
8-Methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-6,8-dihydropyrazolo[4′,3′: 4,5]pyrano[3,2-d]pyrimidin-2-amine;
8-(2,6-Difluorophenyl)-9-methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-6,8-dihydro-5H-pyrazolo[3,4-h]quinazolin-2-amine;
9-Cyclopropyl-8-methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-6,8-dihydro-5H-pyrazolo[3,4-h]quinazolin-2-amine;
9-Isopropyl-8-methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-6,8-dihydro-5H-pyrazolo[3,4-h]quinazolin-2-amine;
9-Cyclopropyl-N-(1-(methylsulfonyl)piperidin-4-yl)-8-(tetrahydrofuran-3-yl)-6,8-dihydro-5H-pyrazolo[3,4-h]quinazolin-2-amine;
2-(9-Cyclopropyl-2-((1-(methylsulfonyl)piperidin-4-yl)amino)-5,6-dihydro-8H-pyrazolo[3,4-h]quinazolin-8-yl)ethan-1-ol;
8,9-Dicyclopropyl-N-(1-(methylsulfonyl)piperidin-4-yl)-6,8-dihydro-5H-pyrazolo[3,4-h]quinazolin-2-amine;
1,2-Dimethyl-N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
2-Isopropyl-1-methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
1-Cyclopropyl-2-methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
1-Cyclopropyl-N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
2-Bromo-1-cyclopropyl-N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
1-Cyclopropyl-N-(1-(methylsulfonyl)piperidin-4-yl)-2-phenyl-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
1-Cyclopropyl-2-(2-fluorophenyl)-N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
1-Cyclopropyl-2-(1,3-dimethyl-1H-pyrazol-4-yl)-N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
1-Cyclopropyl-2,4,4-trimethyl-N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine; and
1-Cyclopropyl-N-(1-(methylsulfonyl)piperidin-4-yl)-1,4-dihydroimidazo[4′,5′:4,5]pyrano[3,2-d]pyrimidin-8-amine,
or a pharmaceutically acceptable salt thereof.

### Claim 30 (depends on 1)

The compound of claim 1, selected from:
1-Isopropyl-2-methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
1,2-Dimethyl-N-((3R,4S)-3-methyl-1-((1-methyl-1H-imidazol-4-yl)sulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
1,2-Dimethyl-N-((3R,4S)-3-methyl-1-((6-(4-methylpiperazin-1-yl)pyridin-2-yl)sulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine;
(R)-1-(5-(((3R,4S)-4-((1,2-Dimethyl-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-yl)amino)-3-methylpiperidin-1-yl)sulfonyl)pyridin-2-yl)pyrrolidin-3-ol;
1-Cyclopropyl-2-methyl-N-((3R,4S)-3-methyl-1-((1-methyl-1H-imidazol-4-yl)sulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine; and
1-Cyclopropyl-2-methyl-N-((3R,4S)-3-methyl-1-((1-methyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-yl)-4,5-dihydro-1H-imidazo[4,5-h]quinazolin-8-amine,
or a pharmaceutically acceptable salt thereof.

### Claim 31 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

### Claim 32 (depends on 1)

A method of treating a cancer associated with CDK2 in a patient, comprising administering to the patient a therapeutically effective amount of the compound of claim 1, or pharmaceutically acceptable salt thereof, wherein the cancer is selected from the group consisting of ovarian, endometrial, esophagus, adenocarcinoma, adenocarcinoma of the esophagus, urothelial, gynecological, ovarian serous cystadenocarcinoma, uterine carcinoma, cervical carcinoma, endocervical adenocarcinoma, stomach (gastric), esophageal, breast, triple negative breast cancer, lung, non-small cell lung cancer, lung squamous cell carcinoma, bile duct, and bone.

### Claim 33 (depends on 32)

The method of claim 32, wherein the cancer is associated with an amplification of the cyclin E1 (CCNE1) gene and/or overexpression of CCNE1.

### Claim 34 (depends on 32)

The method of claim 32, wherein the human subject has been previously determined to:
(i)
(a) have a nucleotide sequence encoding a p16 protein comprising the amino acid sequence of SEQ ID NO:1; and/or
(b) have a cyclin dependent kinase inhibitor 2A (CDKN2A) gene lacking one or more inactivating nucleic acid substitutions and/or deletions;
(ii)
(a) have an amplification of the cyclin E1 (CCNE1) gene; and/or
(b) have an expression level of CCNE1 in a biological sample obtained from the human subject that is higher than a control expression level of CCNE1.

### Claim 35 (depends on 1, 32)

The method of claim 32, comprising:
(i) identifying, in a biological sample obtained from the human subject:
(a) a nucleotide sequence encoding a p16 protein comprising the amino acid sequence of SEQ ID NO:1; and/or
(b) a cyclin dependent kinase inhibitor 2A (CDKN2A) gene lacking one or more inactivating nucleic acid substitutions;
(ii) identifying, in a biological sample obtained from the human subject:
(a) an amplification of the cyclin E1 (CCNE1) gene; and/or
(b) an expression level of CCNE1 that is higher than a control expression level of CCNE1; and
(iii) administering the compound of claim 1, or a pharmaceutically acceptable salt thereof, to the human subject.

### Claim 36 (depends on 35)

The method of claim 35, comprising:
(i) identifying, in a biological sample obtained from the human subject:
(a) a nucleotide sequence encoding a p16 protein comprising the amino acid sequence of SEQ ID NO:1; and/or
(b) a CDKN2A gene lacking one or more inactivating nucleic acid substitutions and/or deletions;
(ii) identifying, in a biological sample obtained from the human subject:
(a) an amplification of the CCNE1 gene; and
(iii) administering the compound or the salt to the human subject.

### Claim 37 (depends on 1)

A method of evaluating the response of a human subject having a cancer associated with cyclin-dependent kinase 2 (CDK2) to a compound of claim 1, or a pharmaceutically acceptable salt thereof, comprising:
(a) administering the compound or the salt, to the human subject, wherein the human subject has been previously determined to have an amplification of the cyclin E1 (CCNE1) gene and/or an expression level of CCNE1 that is higher than a control expression level of CCNE1;
(b) measuring, in a biological sample of obtained from the subject subsequent to the administering of step (a), the level of retinoblastoma (Rb) protein phosphorylation at the serine corresponding to amino acid position 780 of SEQ ID NO:3,
wherein a reduced level of Rb phosphorylation at the serine corresponding to amino acid position 780 of SEQ ID NO:3, as compared to a control level of Rb phosphorylation at the serine corresponding to amino acid position 780 of SEQ ID NO:3, is indicative that the human subject responds to the compound or the salt,
wherein the cancer is selected from the group consisting of ovarian, endometrial, esophagus, adenocarcinoma, adenocarcinoma of the esophagus, urothelial, gynecological, ovarian serous cystadenocarcinoma, uterine carcinoma, cervical carcinoma, endocervical adenocarcinoma, stomach (gastric), esophageal, breast, triple negative breast cancer, lung, non-small cell lung cancer, lung squamous cell carcinoma, bile duct, and bone.