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1. WO2020205560 - SULFONYLAMIDE COMPOUNDS AS CDK2 INHIBITORS

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

What is claimed is:

1. A compound of Formula (I):


or a pharmaceutically acceptable salt thereof, wherein:

X is N or CR9;

Y is N or CR10;

R1 is selected from Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl -C 1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl are each optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R4 substituents;

R2 and R3 are each independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 independently selected RG substituents;

or R2 and R3, together with the carbon atom to which they are attached, form Ring B;

Ring B is a 3-7 membered cycloalkyl ring or a 4-7 membered heterocycloalkyl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected RG substituents; each R4 is independently selected from H, D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered

heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl -C 1-4 alkyl,



wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4A substituents;

each Ra4, Rc4, and Rd4 is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl,

5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl -C 1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl -C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C 1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl,

6-10 membered aryl -C 1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4

independently selected R4A substituents;

or, any Rc4 and Rd4 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 R4A substituents;

each Rb4 is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4A substituents;

each Re4 is independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl -C 1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;

each Rf4 and Rg4 are independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;

each Rh4 and Rl4 is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;

each R'4 and Rk4 is independently selected from OH, Ci-6 alkoxy, and Ci-6 haloalkoxy; or any RJ4 and Rk4 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 Ci-6 alkyl and Ci-6 haloalkyl;

each R4A is independently selected from H, D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered

heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl -C 1-4 alkyl, ORa41, SRa41, NHORa41, C(0)Rb41, C(0)NRc41Rd41, C(0)NRc41(0Ra41), C(0)ORa41, 0C(0)Rb41, 0C(0)NRc41Rd41, NRc41Rd41, NRc41NRc41Rd41, NRc41C(0)Rb41, NRc41C(0)0Ra41, NRc41C(0)NRc41Rd41,

C(=NRe41)Rb41, C(=NRe41)NRc41Rd41, NRc41C(=NRe41)NRc41Rd41, NRc41C(=NRe41)RM1, NRc41S(0)NRc41Rd41, NRc41S(0)Rb41, NRc41S(0)2Rb41, NRc41S(0)(=NRe41)Rb41,

NRc41S(0)2NRc41Rd41, S(0)Rb41, S(0)NRc41Rd41, S(0)2RM1, S(0)2NRc41Rd41,

0S(0)(=NRe41)RM1, OS(0)2RM1, S(0)(=NRe41)RM1, SFs, P(0)Rf41Rg41,

0P(0)(0Rh41)(0Ri41), P(0)(0Rh41)(0Ri41), and B 41Rk41, wherein said Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4B substituents;

each Ra41, Rc41, and Rd41 is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered

heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered

heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4B substituents;

or, any Rc41 and Rd41 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 R4B substituents;

each Rb41 is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4B substituents;

each Re41 is independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each Rf41 and Rg41 are independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each Rh41 and Rl41 is independently selected from H, Ci-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each R>41 and Rk41 is independently selected from OH, Ci-6 alkoxy, and Ci-6 haloalkoxy;

or any R'41 and Rk41 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 Ci-6 alkyl and Ci-6 haloalkyl;

each R4B is independently selected from H, D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered

heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl -C 1-4 alkyl, ORa42, SRa42, NHORa42,


2Rd42,


Ci-e alkyl, C 2-e alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;

each Ra42, Rc42, and Rd42 is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered

heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered

heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;

or, any Rc42 and Rd42 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 Rb42 is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;

each Re42 is independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl;

each Rf42 and Rg42 are independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl;

each Rh42 and Rl42 is independently selected from H, Ci-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each R'42 and Rk42 is independently selected from OH, Ci-6 alkoxy, and Ci-6 haloalkoxy;

or any R42 and Rk42 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 Ci-6 alkyl and Ci-6 haloalkyl;

R5 is selected from H, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl -C 1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5A substituents;

each R5A is independently selected from H, D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered

heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl -C 1-4 alkyl, ORa51, SRa51, NHORa51, C(0)Rb51, C(0)NRc51Rd51, C(0)NRc51(0Ra51), C(0)ORa51, OC(0)Rb51, 0C(0)NRc51Rd51, NRc51Rd51, NRc51NRc51Rd51, NRc51C(0)Rb51, NRc51C(0)0Ra51, NRc51C(0)NRc51Rd51, C(=NRe51)Rb51, C(=NRe51)NRc51Rd51, NRc51C(=NRe51)NRc51Rd51, NRc51C(=NRe51)Rb51, NRc51S(0)NRc51Rd51, NRc51S(0)Rb51, NRc51S(0)2Rb51, NRc51S(0)(=NRe51)Rb51,

NRc51S(0)2NRc51Rd51, S(0)Rb51, S(0)NRc51Rd51, S(0)2Rb51, S(0)2NRc51Rd51,

0S(0)(=NRe51)Rb51, 0S(0)2Rb51, S(0)(=NRe51)Rb51, SFs, P(0)Rf51Rg51,

0P(0)(0Rh51)(0Ri51), P(0)(0Rh51)(0Ri51), and BRj51Rk51, wherein said Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5B substituents;

each Ra51, Rc51, and Rd51 is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6

membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered

heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5B substituents;

or, any Rc51 and Rd51 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 R5B substituents;

each Rb51 is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5B substituents;

each Re51 is independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each Rf51 and Rg51 are independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each R1151 and Rl51 is independently selected from H, Ci-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each R'5 1 and Rk51 is independently selected from OH, Ci-6 alkoxy, and Ci-6 haloalkoxy;

or any R'51 and Rk51 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 Ci-6 alkyl and Ci-6 haloalkyl;

each R5B is independently selected from H, D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl -C 1-4 alkyl, ORa52, SRa52, NHORa52, C(0)Rb52, C(0)NRc52Rd52, C(0)NRc52(0Ra52), C(0)0Ra52, 0C(0)Rb52, 0C(0)NRc52Rd52, NRc52Rd52, NRc52NRc52Rd52, NRc52C(0)Rb52, NRc52C(0)0Ra52, NRc52C(0)NRc52Rd52, C(=NRe52)Rb52, C(=NRe52)NRc52Rd52, NRc52C(=NRe52)NRc52Rd52, NRc52C(=NRe52)Rb52, NRc52S(0)NRc52Rd52, NRc52S(0)Rb52, NRc52S(0)2Rb52, NRc52S(0)(=NRe52)Rb52,

NRc52S(0)2NRc52Rd52, S(0)Rb52, S(0)NRc52Rd52, S(0)2Rb52, S(0)2NRc52Rd52,

0S(0)(=NRe52)Rb52, 0S(0)2Rb52, S(0)(=NRe52)Rb52, SFs, P(0)Rf52Rg52,

0P(0)(0Rh52)(0Ri52), P(0)(0Rh52)(0Ri52), and B 52Rk52, wherein said Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;

each Ra52, Rc52, and Rd52 is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered

heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered

heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;

or, any Rc52 and Rd52 attached to the same N atom, together with the N atom to which they are attached, form a 5 4-7 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;

each Rb52 is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;

each Re52 is independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each Rf52 and Rg52 are independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each R1152 and Rl52 is independently selected from H, Ci-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each R>52 and Rk52 is independently selected from OH, Ci-6 alkoxy, and Ci-6 haloalkoxy;

or any RJ52 and Rk52 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 Ci-6 alkyl and Ci-6 haloalkyl;

R6 is H, Ci-4 alkyl, Ci-4 haloalkyl, and C3-4 cycloalkyl;

R7 and R8 are each independently selected from H, D, OH, NO2, CN, halo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, cyano-Ci-6 alkyl, HO-Ci-6 alkyl, Ci-6 alkoxy-Ci-6 alkyl, C3-4 cycloalkyl, Ci-6 alkoxy, Ci-6 haloalkoxy, amino, Ci-6 alkylamino, and di(Ci-6 alkyl)amino;

R9 and R10 are each independently selected from H, D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl -C 1-4 alkyl, ORa9, SRa9, NHORa9, C(0)Rb9, C(0)NRc9Rd9, C(0)NRc9(0Ra9), C(0)0Ra9, 0C(0)Rb9, 0C(0)NRc9Rd9, NRc9Rd9, NRc9NRc9Rd9, NRc9C(0)Rb9, NRc9C(0)0Ra9, NRc9C(0)NRc9Rd9, C(=NRe9)Rb9,

C(=NRe9)NRc9Rd9, NRc9C(=NRe9)NRc9Rd9, NRc9C(=NRe9)Rb9, NRc9S(0)NRc9Rd9,

NRc9S(0)Rb9, NRc9S(0)2Rb9, NRc9S(0)(=NRe9)Rb9, NRc9S(0)2NRc9Rd9, S(0)Rb9,

S(0)NRc9Rd9, S(0)2Rb9, S(0)2NRc9Rd9, 0S(0)(=NRe9)Rb9, 0S(0)2Rb9, S(0)(=NRe9)Rb9, SFs, P(0)R®Rg9, 0P(0)(0Rh9)(0Ri9), P(0)(0Rh9)(0R'9), and BR|9Rky, wherein said Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered

heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;

Ra9, Rc9, and Rd9 is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C 1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered

heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;

or, any Rc9 and Rd9 attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;

each Rb9 is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;

each Re9 is independently selected from H, OH, CN, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each R® and Rg9 are independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each R and Rl9 is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

each R>9 and Rk9 is independently selected from OH, Ci-6 alkoxy, and Ci-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 Ci-6 alkyl and Ci-6 haloalkyl; and each RG is independently selected from H, D, OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-7 cycloalkyl, Ci-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Ci-3 alkylthio, C1-3 alkylsulfmyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkyl carbonyl, C 1-3 alkoxy carbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, C1-3 alkylaminocarbonyloxy, C1-3

alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from Ci-6 alkyl, C 1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-10 membered

heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, each of which is optionally substituted by 1, 2, or 3 independently selected R4 substituents.

3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from C 1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-10 membered heterocycloalkyl, and C3-7 cycloalkyl-Ci-4 alkyl, each of which is optionally substituted by 1 or 2 independently selected R4 substituents.

4. The compound of any one of claims 1-3, or a pharmaceutically acceptable salt thereof, wherein:

each R4 is independently selected from H, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl, C3-4 cycloalkyl, ORa4, SRa4, C(0)Rb4, C(0)NRc4Rd4, C(0)ORa4, 0C(0)Rb4, 0C(0)NRc4Rd4, NRc4Rd4, NRC4C(0)Rm, NRc4C(0)0Ra4, NRc4C(0)NRc4Rd4, NRc4S(0)2Rb4,

NRc4S(0)2NRc4Rd4, S(0)2Rm, and S(0)2NRc4Rd4;

each Ra4, Rc4, and Rd4 is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and

each Rb4 is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

5. The compound of any one of claims 1-3, or a pharmaceutically acceptable salt thereof, wherein:

each R4 is independently selected from H, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-4 cycloalkyl, ORa4, and NRc4Rd4; and

each Ra4, Rc4, and Rd4 is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl.

6. The compound of any one of claims 1-5, or a pharmaceutically acceptable salt thereof, wherein R6 is H.

7. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, wherein R7, R8, R9, and R10 are each independently selected from H, OH, CN, halo, Ci-3 alkyl, and C1-3 haloalkyl.

8. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, wherein R7, R8, R9, and R10 are each independently selected from H and halo.

9. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, wherein R7 is H or halo; and R8, R9, and R10 are each H.

10. The compound of any one of claims 1-9, or a pharmaceutically acceptable salt thereof, wherein R5 is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, each of which is optionally substituted with 1, 2, 3, or 4 independently selected R5A substituents.

11. The compound of any one of claims 1-9, or a pharmaceutically acceptable salt thereof, wherein R5 is selected from Ci-6 alkyl, Ci-6 haloalkyl, and 4-7 membered

heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 independently selected R5A substituents.

12. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt thereof, wherein:

each R5A is independently selected from H, D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl, C3-4 cycloalkyl, ORa51, C(0)Rb51, C(0)NRc51Rd51, C(0)ORa51, OC(0)Rb51,

0C(0)NRc51Rd51, NRc51Rd51, NRc51C(0)Rb51, NRc51S(0)2Rb51, S(0)2Rb51, and

S(0)2NRc51Rd51;

each Ra51, Rc51, and Rd51 is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and

each Rb51 is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

13. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt thereof, wherein:

each R5A is independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, OR851, NRc51Rd51; and

each Ra51, Rc51, and Rd51 is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl.

14. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt thereof, wherein each R5A is independently selected from D, Ci-6 alkyl, ORa51, and NRc51Rd51; and.

each Ra51, Rc51, and Rd51 is independently selected from H and Ci-6 alkyl.

15. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:

X is N or CR9;

Y is N or CR10;

R1 is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-10 membered heterocycloalkyl, C3-7 cycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl, each of which is optionally substituted by 1 or 2 independently selected R4 substituents;

R2 and R3 are independently selected from C1-3 alkyl and C1-3 haloalkyl;

or R2 and R3, together with the carbon atom to which they are attached, form Ring B;

Ring B is a 3-7 membered cycloalkyl ring;

each R4 is independently selected from H, D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered

heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl -C 1-4 alkyl, ORa4, SRa4, C(0)Rb4, C(0)NRc4Rd4, C(0)ORa4, OC(0)Rb4, 0C(0)NRc4Rd4, NRc4Rd4, NRc4C(0)Rb4,

NRc4C(0)0Ra4, NRc4C(0)NRc4Rd4, NRc4S(0)2Rb4, NRc4S(0)2NRc4Rd4, S(0)2Rb4, and S(0)2NRc4Rd4, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7

cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, are each optionally substituted with 1, 2, 3, or 4

independently selected R4A substituents;

each Ra4, Rc4, and Rd4 is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C 1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered

heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4A substituents;

each Rb4 is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4A substituents;

each R4A is independently selected from H, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl, ORa41, SRa41, C(0)Rb41, C(0)NRc41Rd41, C(0)0Ra41, 0C(0)Rb41, 0C(0)NRc41Rd41,

NRc41Rd41, NRc41C(0)RM1, NRc41C(0)0Ra41, NRc41C(0)NRc41Rd41, NRc41S(0)2Rb41,

NRc41S(0)2NRc41Rd41, S(0)2RM1, and S(0)2NRc41Rd41;

each Ra41, Rc41, and Rd41 is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

each Rb41 is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

R5 is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, each of which is optionally substituted with 1, 2, or 3 independently selected R5A substituents;

each R5A is independently selected from H, D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered

heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl -C 1-4 alkyl, ORa51, SRa51, C(0)Rb51, C(0)NRc51Rd51, C(0)0Ra51, 0C(0)Rb51, 0C(0)NRc51Rd51, NRc51Rd51, NRc51C(0)Rb51, NRc51C(0)0Ra51, NRc51C(0)NRc51Rd51, NRc51S(0)2Rb51, NRc51S(0)2NRc51Rd51, S(0)2Rb51, and S(0)2NRc51Rd51;

each Ra51, Rc51, and Rd51 is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

each Rb51 is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

R6 is H; and

R7, R8, R9, and R10 are each independently selected from H, OH, CN, halo, Ci-6 alkyl, and Ci-6 haloalkyl.

16. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:

X is N or CR9;

Y is N or CR10;

R1 is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-10 membered heterocycloalkyl, C3-7 cycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl, each of which is optionally substituted 1 or 2 independently selected R4 substituents;

R2 and R3 are independently selected from C1-3 alkyl and C1-3 haloalkyl;

or R2 and R3, together with the carbon atom to which they are attached, form Ring B;

Ring B is a 3-7 membered cycloalkyl ring;

each R4 is independently selected from H, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa4, and NRc4Rd4;

each Ra4, Rc4, and Rd4 is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; R5 is selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, each of which is optionally substituted with 1, 2, or 3 independently selected R5A substituents;

each R5A is independently selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, OR851, and NRc51Rd51;

each Ra51, Rc51, and Rd51 is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

R6 is H; and

R7, R8, R9, and R10 are each independently selected from H, CN, halo, C 1-3 alkyl, and Ci-3 haloalkyl.

17. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:

X is N or CR9;

Y is N or CR10;

R1 is Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-10 membered heterocycloalkyl or C3-7 cycloalkyl-Ci-4 alkyl, each of which is optionally substituted by 1 or 2 independently selected R4 substituents;

R2 and R3 are independently selected from C1-3 alkyl;

or R2 and R3, together with the carbon atom to which they are attached, form Ring B;

Ring B is a 3-4 membered cycloalkyl ring;

each R4 is independently selected from H, halo, CN, OH, Ci-4 alkyl, Ci-4 haloalkyl, and Ci-4 alkoxy;

each Ra4, Rc4, and Rd4 is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

R5 is selected from Ci-6 alkyl, Ci-6 haloalkyl, and monocyclic 4-6 membered heterocycloalkyl having one nitrogen ring member; each of which is optionally substituted with 1, 2, or 3 independently selected R5A substituents;

R5A is independently selected from D, Ci-6 alkyl, ORa51, and NRc51Rd51;

each Ra51, Rc51, and Rd51 is independently selected from H and Ci-6 alkyl;

R6 is H; and

R7, R8, R9, and R10 are each independently selected from H, F, and Cl.

18. The compound of any one of claims 1-17, having Formula (II):


or a pharmaceutically acceptable salt thereof.

19. The compound of any one of claims 1-18, wherein ring B is C3-7 cycloalkyl.

20. The compound of any one of claims 1-18, wherein ring B is cyclopropyl, cyclobutyl, or cyclopentyl.

21. The compound of any one of claims 1-20, having Formula (III):


or a pharmaceutically acceptable salt thereof.

22. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, wherein compound of Formula (Ilia):


or a pharmaceutically acceptable salt thereof.

23. The compound of any one of claims 18-22, or a pharmaceutically acceptable salt thereof, wherein R7 is H or halo; and R8 is H.

24. The compound of claim 1, selected from:

4-((7'-((czV)-2-hydroxy-2-methylcyclopentyl)-6'-oxo-6',7'-dihydrospiro[cyclopropane- 1 ,5'-pyrrolo[2,3-i/]pyrimidin]-2'-yl)amino)-/V-methylbenzenesulfonamide;

/V-methyl-4-((7'-((/m«5)-2-methylcyclopentyl)-6'-oxo-6',7'-dihydrospiro[cyclopropane-l,5'-pyrrolo[2,3-i/]pyrimidin]-2'-yl)amino)benzenesulfonamide;

4-((7'-((czA)-2-hydroxy-2-methylcyclopentyl)-6'-oxo-6',7'-dihydrospiro[cyclopropane-l,5'-pyrrolo[2,3-i/]pyrimidin]-2'-yl)amino)-/V-(3-methylazetidin-3-yl)benzenesulfonamide; and

(i?)-/V-methyl-4-((6'-oxo-7'-(l , 1 , 1 -trifluorobutan-2-yl)-6',7'-dihydrospiro[cyclopropane-l,5'-pyrrolo[2,3-i/]pyrimidin]-2'-yl)amino)benzenesulfonamide; or a pharmaceutically acceptable salt thereof.

25. The compound of claim 1, selected from:

4-((7'-(2-methylcyclopentyl)-6'-oxo-6',7'-dihydrospiro[cyclopropane-l,5'-pyrrolo[2,3- 6/]pyrimidin]-2'-yl)amino)-A -((/^)- l -methyl pi peri din-3-yl) benzenesulfonamide;

4-((7'-((li?,3i?)-3-hydroxycyclohexyl)-6'-oxo-6',7'-dihydrospiro [cyclopropane-1, 5'-pyrrolo[2,3-6/]pyrimidin]-2'-yl)amino)-A-methyl benzene sulfonamide;

4-((7'-((li?,3i?)-3-hydroxycyclohexyl)-6'-oxo-6',7'-dihydrospiro[cyclopro pane-1, 5'-pyrrolo[2,3-6/]pyrimidin]-2'-yl)amino)-A-( ethyl- )benzenesulfonamide;

(5)-4-((7'-(l-cyclopropylethyl)-6'-oxo-6',7'-dihydrospiro[cyclopropane-l,5'-pyrrolo[2,3-6/]pyrimidin]-2'-yl)amino)-A-( ethyl- )benzenesulfonamide;

4-((7l-((/ra//.s)-2-hydroxy-2-methylcyclopentyl)-6l-oxo-6l,7l-dihydrospiro

[cyclopropane- 1 ,5,-pyrrolo[2,3-6/]pyrimidin]-2'-yl)amino)-A-(methyl- )benzene

sulfonamide;

4-((7'-(2-hydroxy-2-methylcyclopentyl)-6'-oxo-6',7'-dihydrospiro [cyclopropane-1,51-pyrrolo[2,3-6/]pyrimidin]-2'-yl)amino)-A-(2-hydroxy-2- ethylpropyl)benzenesulfonamide;

3-fluoro-4-((7'-((/ra«5)-2-hydroxy-2-methylcyclopentyl)-6'-oxo-6',7'-dihydrospiro[cyclopropane- l ,5,-pyrrolo[2,3-6/]pyrimidin]-2,-yl)amino)-A-methylbenzenesulfonamide;

4-((7'-(2-chloro-5-fluorophenyl)-6'-oxo-6',7'-dihydrospiro[cyclopropane-l,5'-pyrrolo[2,3-6/]pyrimidin]-2'-yl)amino)-A-(2-(dimethylamino)ethyl)benzenesulfonamide;

4-((7'-(7-chloro-l,2,3,4-tetrahydroisoquinolin-6-yl)-6'-oxo-6',7'-dihydrospiro[cyclopropane- l ,5,-pyrrolo[2,3-6/]pyrimidin]-2,-yl)amino)-A-methylbenzenesulfonamide;

4-((7'-(5-fluoro-2-methylphenyl)-6'-oxo-6',7'-dihydrospiro[cyclopropane-l,5'-pyrrolo[2,3-6/]pyrimidin]-2'-yl)amino)-A-methyl benzenesulfonamide; and

4-((7'-(2-chloro-5-fluorophenyl)-6'-oxo-6',7'-dihydrospiro[cyclopropane-l,5'-pyrrolo[2,3-6/]pyrimidin]-2'-yl)amino)-A-methyl benzenesulfonamide;

or a pharmaceutically acceptable salt thereof.

26. A pharmaceutical composition comprising the compound of any one of claims 1-25, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

27. A method of inhibiting CDK2, comprising contacting the CDK2 with the compound of any one of claims 1-25, or a pharmaceutically acceptable salt thereof.

28. A method of inhibiting CDK2 in a patient, comprising administering to the patient the compound of any one of claims 1-25, or a pharmaceutically acceptable salt thereof.

29. A method of treating a disease or disorder associated with CDK2 in a patient, comprising administering to the patient a therapeutically effective amount of the compound of any one of claims 1-25, or a pharmaceutically acceptable salt thereof.

30. A method of treating a disease or disorder associated with CDK2 in a patient, comprising administering to the patient a therapeutically effective amount of the compound of any one of claims 1-25, or pharmaceutically acceptable salt thereof, wherein the disease or disorder is associated with an amplification of the cyclin El (CCNE1) gene and/or overexpression of CCNE1.

31. A method of treating a human subject having a disease or disorder associated with cyclin-dependent kinase 2 (CDK2), comprising administering to the human subject a compound of any one of claims 1-25, or a pharmaceutically acceptable salt thereof, wherein the human subject has been previously determined to:

(i)

(a) have a nucleotide sequence encoding a pl6 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;

(ϋ)

(a) have an amplification of the cyclin El (CCNEl) gene; and/or

(b) have an expression level of CCNEl in a biological sample obtained from the human subject that is higher than a control expression level of CCNEl.

32. A method of treating a human subject having a disease or disorder associated with cyclin-dependent kinase 2 (CDK2), comprising:

(i) identifying, in a biological sample obtained from the human subject:

(a) a nucleotide sequence encoding a pl6 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 El (CCNE1) gene; and/or

(b) an expression level of CCNE1 that is higher than a control expression level of CCNEl; and

(iii) administering a compound of any one of claims 1-25, or a pharmaceutically acceptable salt thereof, to the human subject.

33. The method of claim 32, comprising:

(i) identifying, in a biological sample obtained from the human subject:

(a) a nucleotide sequence encoding a pl6 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 CCNEl gene; and

(iii) administering the compound or the salt to the human subject.

34. A method of evaluating the response of a human subject having a disease or disorder associated with cyclin-dependent kinase 2 (CDK2) to a compound of any one of claims 1-25, 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 El (CCNEl) gene and/or an expression level of CCNEl that is higher than a control expression level of CCNEl;

(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.

35. The method of any one of claims 29-34, wherein the disease or disorder is cancer.