2-azabicyclo[2.2.1]heptane kras inhibitors

Abstract

Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting KRAS activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with KRAS activity such as cancer.

Description

Abstract: (I) A compound, a method of using the compound that inhibits KRAS activity, and a pharmaceutical composition comprising the compound. The compound may be used to treat, prevent, or improve diseases or conditions associated with KRAS activity, such as cancer.

Claims

What is claimed is:1 . A compound having Formula (I):or a pharmaceutically acceptable salt thereof, wherein:Cy1is phenyl optionally substituted with 1 , 2, 3, or 4 substituents each selected from D, C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, halo, OH, C1-3 alkoxy, and C1-3 haloalkoxy;R1is halogen;R2is selected from H, D, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, C3-5 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, Cs-e cycloalkyl- C1-3 alkylene, 4-6 membered heterocycloalkyl-Ci-3 alkylene, phenyl-Ci-3 alkylene, 5-6 membered heteroaryl-Ci-3 alkylene, halo, CN, ORa2, C(O)Rb2, C(O)NRc2Rd2, NRc2Re2, and NRc2C(O)Rb2; wherein the C3-5 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, C3-6 cycloalkyl-Ci-3 alkylene, 4-6 membered heterocycloalkyl-Ci-3 alkylene, phenyl-Ci-3 alkylene, and 5-6 membered heteroaryl-Ci-3 alkylene forming R2are each optionally substituted with 1 , 2, or 3 substituents independently selected from R2A; wherein the ring-forming atoms of the 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl-Ci-3 alkylene, and 4-6 membered heterocycloalkyl-Ci-3 alkylene forming R2consist of at least one carbon atom and 1 , 2, 3, or 4 heteroatoms selected from O, N, and S; wherein a ring-forming carbon atom of the 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-6 cycloalkyl-Ci-3 alkylene, and 4-6 membered heterocycloalkyl-Ci-3 alkylene forming R2is optionally substituted by oxo to form a carbonyl group; and wherein the C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl forming R2are each optionally substituted with 1 , 2, or 3 substituents independently selected from R2B; each Ra2is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl; wherein the C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl forming Ra2are each optionally substituted with 1 , 2, or 3 substituents independently selected from R2A; wherein the ring-forming atoms of the 4-6 membered heterocycloalkyl and 5-6 membered heteroaryl forming Ra2consist of at least one carbonatom and 1 , 2, 3, or 4 heteroatoms selected from O, N, and S; wherein a ring-forming carbon atom of the 4-6 membered heterocycloalkyl and 5-6 membered heteroaryl forming Ra2is optionally substituted by oxo to form a carbonyl group; and wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl forming Ra2are each optionally substituted with 1 , 2, or 3 substituents independently selected from R2B; each Rb2, Rc2, and Rd2is independently selected from H, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl; wherein the C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl forming Rb2, Rc2, and Rd2are each optionally substituted with 1 , 2, or 3 substituents independently selected from R2A; the ring-forming atoms of the 4-6 membered heterocycloalkyl and 5-6 membered heteroaryl forming Rb2, Rc2, and Rd2consist of at least one carbon atom and 1 , 2, 3, or 4 heteroatoms selected from O, N, and S; wherein a ring-forming carbon atom of the 4-6 membered heterocycloalkyl and 5-6 membered heteroaryl forming Rb2, Rc2, and Rd2is optionally substituted by oxo to form a carbonyl group; and wherein the C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl forming Rb2, Rc2, and Rd2are each optionally substituted with 1 , 2, or 3 substituents independently selected from R2B; or any Rc2and Rd2attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 , 2, or 3 substituents independently selected from R2B; each Re2is independently selected from C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; wherein the C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl forming Re2are each optionally substituted with 1 , 2, or 3 substituents independently selected from R2A; wherein the ring-forming atoms of the 4-6 membered heterocycloalkyl and 5-6 membered heteroaryl forming Re2consist of at least one carbon atom and 1 , 2, 3, or 4 heteroatoms selected from O, N, and S; wherein a ring-forming carbon atom of the 4-6 membered heterocycloalkyl and 5-6 membered heteroaryl forming Re2is optionally substituted by oxo to form a carbonyl group; and wherein the C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, forming Re2are each optionally substituted with 1 , 2, or 3 substituents independently selected from R2B; orRc2and Re2attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, or 6-membered heterocycloalkyl group optionally substituted with 1 , 2, or 3 substituents independently selected from R2B; each R2Ais independently selected from C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, and R2B, wherein the C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, forming R2Aare each optionally substituted with 1 , 2 or 3 substituents independently selected from R2B;each R2Bis independently selected from C3-6 cycloalkyl, 4-10 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, ORa2B, C(O)Rb2B, C(O)NRc2BRd2B, C(O)ORa2B, NRc2BRd2B, and S(O)2Rb2B; wherein the C1.3 alkyl, C3-6cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted with 1 , 2, or 3 substituents independently selected from R2C; each R2Cis independently selected from C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, ORa2C, C(O)Rb2C, C(O)NRc2CRd2C, C(O)ORa2C, NRc2CRd2C, and S(O)2Rb2C; each Ra2B, Rb2B, Rc2Band Rd2Bis independently selected from H, C1-3 alkyl, and C1-3 haloalkyl; each Ra2C, Rb2C, Rc2Cand Rd2Cis independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;R3is selected from C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, Ce-w aryl, 5-10 membered heteroaryl, OR3A, and NR3BR3C; wherein the C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, Ce- aryl, and 5-10 membered heteroaryl C1-3 alkyl forming R3are each optionally substituted with 1 , 2, or 3 substituents independently selected from R3D; wherein the ring-forming atoms of the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl forming R3consist of at least one carbon atom and 1 , 2, 3, or 4 heteroatoms selected from O, N, and S; wherein a ring-forming carbon atom of the 4-10 membered heterocycloalkyl or 5-10 membered heteroaryl forming R3is optionally substituted by oxo to form a carbonyl group; and wherein the C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl forming R3are each optionally substituted with 1 , 2, or 3 substituents independently selected from R3E;R3Ais selected from C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, Ce-w aryl, and 5-10 membered heteroaryl; wherein the C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, Ce- aryl, and 5-10 membered heteroaryl C1-3 alkyl forming R3Aare each optionally substituted with 1 , 2, or 3 substituents independently selected from R3D; wherein the ring-forming atoms of the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl forming R3Aconsist of at least one carbon atom and 1 , 2, 3, or 4 heteroatoms selected from O, N, and S; wherein a ring-forming carbon atom of the 4-10 membered heterocycloalkyl or 5-10 membered heteroaryl forming R3Ais optionally substituted by oxo to form a carbonyl group; and wherein the C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl forming R3Aare each optionally substituted with 1 , 2, or 3 substituents independently selected from R3E;R3Bis selected from H, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, Ce-w aryl, and 5-10 membered heteroaryl; wherein the C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, Ce- aryl, and 5-10 membered heteroarylforming R3Bare each optionally substituted with 1 , 2, or 3 substituents independently selected from R3D; wherein the ring-forming atoms of the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl forming R3Bconsist of at least one carbon atom and 1 , 2, 3, or 4 heteroatoms selected from O, N, and S; wherein a ring-forming carbon atom of the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl forming R3Bis optionally substituted by oxo to form a carbonyl group; and wherein the C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl forming R3Bare each optionally substituted with 1 , 2, or 3 substituents independently selected from R3E;R3Band R3C, together with the N atom to which they are both attached, optionally form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group that is optionally substituted with 1 , 2, or 3 substituents independently selected from independently selected from R3D;R3Cis selected from H, C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl; wherein the C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl forming R3Care each optionally substituted with 1 , 2, or 3 substituents independently selected from R3E; each R3Dis independently selected from C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, and R3E; wherein each of the C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl forming R3Dis optionally substituted with 1 , 2, or 3 substituents independently selected from R3E; each R3Eis independently selected from D, halo, CN, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)NRc3Rd3, NRc3C(O)ORa3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, NRc3S(O)2Rb3, and S(O)2NRc3Rd3;Ra3, Rb3, Rc3, and Rd3are each independently selected from H, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, Ce- aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, Ce-w ary l-C 1-3 alkyl, 5-10 membered heteroaryl-Ci-3 alkyl, C3-7 cycloalkyl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl; wherein the Ce- aryl-Ci-3 alkyl, 5-10 membered heteroaryl-Ci-3 alkyl, C3-7 cycloalkyl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl forming Ra3, Rb3, Rc3, and Rd3are each optionally substituted with 1 , 2, 3, 4, or 5 substituents independently selected from C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, halo, CN, ORa3A, SRa3A, C(O)Rb3A, C(O)NRc3ARd3A, C(O)ORa3A, OC(O)Rb3A, OC(O)NRc3ARd3A, NRc3ARd3A, NRc3AC(O)Rb3A, NRc3AC(O)NRc3ARd3A, NRc3AC(O)ORa3A, C(=NRe3A)NRc3ARd3A, NRc3AC(=NRe3A)NRc3ARd3A, S(O)Rb3A, S(O)NRc3ARd3A, S(O)2Rb3A, NRc3AS(O)2Rb3A, and S(O)2NRc3ARd3A; wherein the ring-forming atoms of the 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, 5-10 membered heteroaryl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl forming Ra3, Rb3, Rc3, and Rd3consist of at least one carbon atom and 1 , 2, 3, or 4 heteroatoms selected from O, N, and S; wherein a ring-forming carbon atom of the 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, 5-10membered heteroaryl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl forming Ra3, Rb3, Rc3, and Rd3is optionally substituted by oxo to form a carbonyl group; orRc3and Rd3attached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group or 5-membered heteroaryl group, each optionally substituted with 1 , 2, or 3 substituents independently selected from C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, halo, CN, ORa3A, SRa3A, C(O)Rb3A, C(O)NRc3ARd3A, C(O)ORa3A, OC(O)Rb3A, OC(O)NRc3ARd3A, NRc3ARd3A, NRc3AC(O)Rb3A, NRc3AC(O)NRc3ARd3A, NRc3AC(O)ORa3A, C(=NRe3A)NRc3ARd3A, NRc3AC(=NRe3A)NRc3ARd3A, S(O)Rb3A, S(O)NRc3ARd3A, S(O)2Rb3A, NRc3AS(O)2Rb3A, and S(O)2NRc3ARd3A;Ra3A, Rb3A, Rc3A, and Rd3Aare each independently selected from H, C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, aryl, Ce- aryl-Ci-s alkyl, 5-10 membered heteroaryl-Ci-3 alkyl, C3-7 cycloalkyl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl; wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl Ce- aryl-Ci-s alkyl, 5-10 membered heteroaryl-Ci-3 alkyl, C3-7 cycloalkyl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl forming Ra3A, Rb3A, Rc3A, and Rd3Aare each optionally substituted with 1 , 2, or 3 substituents independently selected from OH, CN, amino, NH(CI-6 alkyl), N(CI-6 alkyl)2, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy; wherein the ring-forming atoms of the 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, 5-10 membered heteroaryl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl forming Ra3A, Rb3A, Rc3A, and Rd3Aconsist of at least one carbon atom, and 1 , 2, 3, or 4 heteroatoms selected from O, N, and S; and wherein a ring-forming carbon atom of the 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, 5-10 membered heteroaryl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl forming Ra3A, Rb3A, Rc3A, and Rd3Ais optionally substituted by oxo to form a carbonyl group; orRc3Aand Rd3Aattached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group or 5-membered heteroaryl group, each optionally substituted with 1 , 2, or 3 substituents independently selected from OH, CN, amino, NH(CI-6 alkyl), N(CI-6 alkyl)2, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy; Re3, and Re3Aare each, independently, H, CN or NO2; each R4is independently selected from H, D, C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, halo, and ORa4; each Ra4is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl; one R5is R5A; and each other R5is independently selected from H, D, halo, C1-3 alkyl, ORa5, C1-3 haloalkyl, C2-3 alkenyl, and C2-3 alkynyl; or, optionally, two other R5attached to the same carbon atom, together with the carbon atom to which they are both attached, form a spiro C3-6 cycloalkyl ring that is optionally substituted with 1 , 2, 3, or 4 substituents eachselected from D, C1-3 alkyl, and halo; or, optionally, two other R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused C3-6 cycloalkyl ring that is optionally substituted with 1 , 2, 3, or 4 substituents each selected from D, C1-3 alkyl, and halo;R5Ais H, D, C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, halo, ORa5A, CN, or Cy2; wherein the C1-3 alkyl forming R5Ais optionally substituted with 1 , 2, 3 or 4 substituents each selected from R5Band also optionally substituted with Cy2, or, optionally, R5Aand R5attached to the same carbon atom, together with the carbon atom to which they are both attached, form a spiro C3-6 cycloalkyl ring that is optionally substituted with 1 , 2, 3, or 4 substituents each selected from D, C1-3 alkyl, and halo; or, optionally, R5Aand R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused C3-6 cycloalkyl ring that is optionally substituted with 1 , 2, 3, or 4 substituents each selected from D, C1-3 alkyl, and halo; each R5Bis independently selected from D and halo; each Ra5is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;Ra5Ais selected from H, C1-3 alkyl, C1-3 haloalkyl, and Cy2, wherein the C1-3 alkyl forming Ra5Ais optionally substituted with 1 , 2, 3 or 4 substituents each selected from R5Band also optionally substituted with Cy2;Cy2is selected from C3-7 cycloalkyl, 4-10 membered heterocycloalkyl, Ce- aryl, and 5-10 membered heteroaryl; wherein the C3-7 cycloalkyl, 4-10 membered heterocycloalkyl, Ce-w aryl, 5-10 membered heteroaryl, Ce- aryl, and 5-10 membered heteroaryl forming Cy2is optionally substituted with 1 , 2, 3, or 4 substituents independently selected from RCy2; wherein the ring-forming atoms of the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl forming Cy2consist of at least one carbon atom and 1 , 2, 3, or 4 heteroatoms independently selected from N, O, and S; and wherein a ring-forming carbon atom of the 4- 10 membered heterocycloalkyl and 5-10 membered heteroaryl forming Cy2is optionally substituted by oxo to form a carbonyl group; each RCy2is independently selected from D, C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, C3-6 cycloalkyl, 4-10 membered heterocycloalkyl, Ce- aryl, 5-10 membered heteroaryl, halo, CN, ORaCy21, SRaCy21, C(O)RbCy21, C(O)NRcCy21RdCy21, C(O)ORaCy21, OC(O)RbCy21, OC(O)NRcCy21RdCy21, NRcCy21RdCy21, NRcCy21C(O)RbCy21, NRcCy21C(O)NRcCy21RdCy21, NRcCy21C(O)ORaCy21, C(=NReCy21)NRcCy21RdCy21, NRcCy21C(=NReCy21)NRcCy21RdCy21, S(O)RbCy21, S(O)NRcCy21RdCy21, S(O)2RbCy21, NRcCy21S(O)2RbCy21, and S(O)2NRcCy21RdCy21; wherein the C3-6 cycloalkyl, 4-10 membered heterocycloalkyl, Ce- aryl, and 5-10 membered heteroaryl forming RCy2are each optionally substituted by 1 , 2, 3, or 4 substituents independently selected from RCy2A; wherein the ringforming atoms of the 4-10 membered heterocycloalkyl and 5-10 membered heteroarylforming RCy2consist of at least one carbon atom and 1 , 2, 3, or 4 heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of the 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl forming RCy2is optionally substituted by oxo to form a carbonyl group; and wherein the C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl forming RCy2are each optionally substituted by 1 , 2, or 3 substituents independently selected from RCy2B- each R°y2Ais independently selected from C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, and RCy2B; wherein the C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl forming RCy2Aare each optionally substituted by 1 , 2, or 3 substituents independently selected from R0''26, each R0''26is independently selected from D, halo, CN, ORaCy21, SRaCy21, C(O)RbCy21,C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, Ce- aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl,4-10 membered heterocycloalkyl, Ce-w aryl-Ci-3 alkyl, 5-10 membered heteroaryl-Ci-3 alkyl,C3-7 cycloalkyl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl; wherein the Ce- aryl-Ci-3 alkyl, 5-10 membered heteroaryl-Ci-3 alkyl, C3-7 cycloalkyl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl forming RaCy21, RbCy21, RCCY2Ianc| Rdcy2iare eac|1optionally substituted with 1 , 2, or 3 substituents independently selected from C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, halo, CN, ORaCy22, SRaCy22, C(O)RbCy22,C(O)NRcCy22RdCy22, C(O)ORaCy22, OC(O)RbCy22, OC(O)NRcCy22RdCy22, NRcCy22RdCy22,NRcCy22C(O)RbCy22, NRcCy22C(O)NRcCy22RdCy22, NRcCy22C(O)ORaCy22, C(=NReCy22)NRcCy22RdCy22,NRcCy22C(=NReCy22)NRcCy22RdCy22, S(O)RbCy22, S(O)NRcCy22RdCy22, S(O)2RbCy22,NRcCy22s(O)2RbCy22, and S(O)2NRcCy22RdCy22; wherein the ring-forming atoms each of the 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl forming RaCy21, RbCv21, RCCY2I ,anc| Rdcy2i consist of at least one carbon atom and 1 , 2, 3, or 4 heteroatoms independently selected from N, O, and S; and wherein a ring-forming carbon atom of the 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl forming RaCy21, RbCv21, RCCY2I ,anc| Rdcy2i jSoptionally substituted by oxo to form a carbonyl group; or RCCV21and RdCy21attached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group or 5- membered heteroaryl group, each optionally substituted with 1 , 2, or 3 substituents independently selected from C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, halo, CN,Ci-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, aryl, Ce- aryl-Ci-3 alkyl, 5-10 membered heteroaryl- C1-3 alkyl, C3-7 cycloalkyl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl; wherein the C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, Ce- aryl-Ci-3 alkyl, 5-10 membered heteroaryl-Ci-3 alkyl, C3-7 cycloalkyl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl forming RaCy22, RbCy22, Rccy22optionally substituted with 1 , 2, or 3 substituents independently selected from OH, CN, amino, NH(CI-3 alkyl), N(CI-3 alkyl)2, halo, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, and C1-3 haloalkoxy; wherein the ring-forming atoms each of the 5- 10 membered heteroaryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl forming RaCy22, RbCy22, RCCY22,anc| Rdcy22 consist of at least one carbon atom and 1 , 2, 3, or 4 heteroatoms independently selected from N, O, and S; and wherein a ring-forming carbon atom of the 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl-Ci-3 alkyl, and 4-10 membered heterocycloalkyl-Ci-3 alkyl forming RaCy22, RbCy22, RCCY22,anc| Rdcy22 jSoptionally substituted by oxo to form a carbonyl group; orRcCy22and RdCy22attached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group or 5- membered heteroaryl group, each optionally substituted with 1 , 2, or 3 substituents independently selected from OH, CN, amino, NH(CI-6 alkyl), N(CI-6 alkyl)2, halo, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, and C1-3 haloalkoxy; andReCy21and ReCy22are each, independently, H, CN or NO2.

2. A compound or pharmaceutically acceptable salt thereof according to claim 1 having any one of the Formulae (l-A), (l-B), (l-C), (l-D), (l-E), (l-F), (l-G), (l-H), (l-l), (l-J), (l-K), (l-L),3. A compound or pharmaceutically acceptable salt thereof according to claim 1 or 2, whereinCy1is phenyl optionally substituted with 1 or 2 substituents each selected from D, C1-3 alkyl, C1-3 haloalkyl, halo, OH, and C1-3 alkoxy;R1is halo;R2is C1-3 alkyl optionally substituted with OH;R3is C3-10 cycloalkyl optionally substituted with halo; each R4is H; one R5is R5A; and each other R5is independently selected from H, D, halo, C1-3 alkyl, OC1-3 alkyl, C1-3 haloalkyl; or, optionally, two other R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused C3-6 cycloalkyl ring that is optionally substituted with 1 or 2 substituents each selected from D, C1-3 alkyl, and halo; andR5Ais H, halo, or ORa5A;Ra5Ais selected from C1-3 alkyl, C1-3 haloalkyl, and Cy2, wherein the C1-3 alkyl forming Ra5Ais optionally substituted with 1 , 2, or 3 D, and also optionally substituted with Cy2; andCy2is selected from Ce-io aryl and 5-10 membered heteroaryl.

4. A compound or pharmaceutically acceptable salt thereof according to claim 1 or 2, whereinCy1is phenyl optionally substituted with 1 or 2 substituents each selected from D, C1-3 alkyl, C1-3 haloalkyl, halo, OH, and C1-3 alkoxy;R1is halo;R2is C1-3 alkyl optionally substituted with OH;R3is C3-10 cycloalkyl optionally substituted with halo; each R4is H; one R5is R5A; and each other R5is independently selected from H, D, halo, C1-3 alkyl, OC1-3 alkyl, C1-3 haloalkyl; or, optionally, two other R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused C3-6 cycloalkylring that is optionally substituted with 1 or 2 substituents each selected from D, C1-3 alkyl, and halo; andR5Ais H, halo, or ORa5A;Ra5Ais selected from C1-3 alkyl, C1-3 haloalkyl, and Cy2, wherein the C1-3 alkyl forming Ra5Ais optionally substituted with 1 , 2, or 3 D, and also optionally substituted with Cy2; andCy2is selected from C3-7 cycloalkyl, Ce- aryl, and 5-10 membered heteroaryl.

5. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, whereinCy1is phenyl optionally substituted with 2 substituents each selected from halo;R1is halo;R2is C1-3 alkyl optionally substituted with OH;R3is cyclopropyl optionally substituted with halo; each R4is H; one R5is R5A; and each other R5is independently selected from H, halo, C1-3 alkyl, OC1-3 alkyl, C1-3 haloalkyl; or, optionally, two other R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused cyclopropyl ring that is optionally substituted with 1 or 2 substituents each selected from D, C1-3 alkyl, and halo; andR5Ais H, halo, or ORa5A;Ra5Ais selected from C1-3 alkyl, C1-3 haloalkyl, and Cy2, wherein the C1-3 alkyl forming Ra5Ais optionally substituted with 1 , 2, or 3 D, and also optionally substituted with Cy2; andCy2is selected from phenyl and pyridinyl.

6. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, whereinCy1is 2,3-dichlorophenyl;R1is halo;R2is methyl or 1 -hydroxyethyl;R3is cyclopropyl optionally substituted with fluoro; each R4is H; one R5is R5A; and each other R5is independently selected from H, halo, C1-3 alkyl, OC1-3 alkyl, C1-3 haloalkyl; or, optionally, two other R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused cyclopropyl ring that is optionally substituted with 1 or 2 substituents each selected from D, C1-3 alkyl, and halo; andR5Ais H, halo, OC1-3 alkyl, OC1-3 haloalkyl, OCD3, O-pyridinyl, and O-benzyl.

7. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, whereinCy1is 2,3-dichlorophenyl;R1is halo;R2is methyl or 1 -hydroxyethyl;R3is cyclopropyl optionally substituted with fluoro; each R4is H; one R5is R5A; and each other R5is independently selected from H, halo, C1-3 alkyl, OC1-3 alkyl, C1-3 haloalkyl; or, optionally, two other R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused cyclopropyl ring that is optionally substituted with 1 or 2 substituents each selected from D, C1-3 alkyl, and halo; andR5Ais H, halo, OC1-3 alkyl, OC1-3 haloalkyl, OCD3, O-cyclopropyl, O-pyridinyl, and O- benzyl.

8. A compound or pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein Cy1is phenyl optionally substituted with 1 , 2, or 3 substituents, (or 1 or 2 substituents, or 1 substituent) independently selected from C1-3 alkyl (such as methyl), C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, halo (such as fluoro or such as chloro), OH, C1-3 alkoxy, and C1-3 haloalkoxy.

9. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8, wherein Cy1is phenyl optionally substituted with 1 , 2, or 3 substituents, (or 1 or 2 substituents, or 1 substituent) independently selected from C1-3 alkyl (such as methyl) and halo (such as fluoro or such as chloro).

10. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, 8, and 9, wherein Cy1is 2-chloro-3-methylphenyl.

11. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, 8, and 9, wherein Cy1is 2,3-dichlorophenyl12. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 11 , wherein R1is halo.

13. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 12, wherein R1is fluoro.

14. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1, 2, and 8 to 13, wherein R4is H.

15. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1, 2, and 8 to 14, wherein R2is C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, wherein the C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl forming R2are each optionally substituted with 1, 2, or 3 substituents (or 1 or 2 substituents, or 1 substituent) independently selected from R2B.

16. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1, 2, and 8 to 15, wherein R2is C1-3 alkyl (e.g., methyl or ethyl) optionally substituted with 1 , 2, or 3 substituents (or 1 or 2 substituents, or 1 substituent) independently selected from R2B.

17. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1, 2, and 8 to 16, wherein R2is methyl optionally substituted with 1, 2, or 3 substituents (or 1 or 2 substituents, or 1 substituent) independently selected from R2B.

18. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 17, wherein R2is methyl.

19. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 5 and 8 to 16, wherein R2is ethyl optionally substituted with 1, 2, or 3 substituents (or 1 or 2 substituents, or 1 substituent) independently selected from R2B.

20. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, 8 to 16, and 19, wherein R2is ethyl.

21. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, 8 to 16, and 19, wherein R2is 1 -hydroxyethyl.

22. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1, 2, and 8 to 14, wherein R2is 4-6 membered heterocycloalkyl (or 4-membered, or 5- membered-, or 6-membered heterocycloalkyl) optionally substituted with 1 , 2, or 3 substituents (or 1 or 2 substituents, or 1 substituent) independently selected from R2A.

23. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1, 2, 8 to 14, and 22, wherein R2is azetidin-1-yl optionally substituted with 1, 2, or 3 substituents (or 1 or 2 substituents, or 1 substituent) independently selected from R2A.

24. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 14, 22, and 23, wherein R2is 2-methyl-2-( / V, / V-dimethylamino)-2- methylazetidin-1-yl.

25. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 14, wherein R2is 5-6 membered heteroaryl (or 5-membered or 6- membered heteroaryl) optionally substituted with 1 , 2, or 3 substituents (or 1 or 2 substituents, or 1 substituent) independently selected from R2A.

26. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 14, and 25, wherein R2is 6 membered heteroaryl (e.g., pyridyl, such as 2- pyridyl, 3-pyridyl, or 4-pyridyl) optionally substituted with 1 , 2, or 3 substituents (or 1 or 2 substituents, or 1 substituent) independently selected from R2A.

27. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 14, 25, and 26, wherein R2is 6 membered heteroaryl (e.g., pyridyl, such as 2-pyridyl, 3-pyridyl, or 4-pyridyl) optionally substituted with 2-hydroxypropyl or with C(O)NRc2BRc2D(such as C(O)NH2, C(O)NHMe, or C(O)NMe2).

28. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 14, wherein R2is ORa2.

29. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 14, 22, 23, 25, and 26, wherein each R2Ais independently selected from C1-3 alkyl, NRc2BRc2D(such as NH2, NHMe, or NMe2), or C(O)NRc2BRc2D(such as C(O)NH2, C(O)NHMe, or C(O)NMe2), wherein the C1-3 alkyl forming R2Ais optionally substituted with 1 , 2, or 3 substituents (or 1 or 2 substituents, or 1 substituent) each independently selected from R2B.

30. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 14, 22, 23, 25, 26, and 29, wherein each R2Ais independently selected from C1-3 alkyl optionally substituted with 1 , 2, or 3 substituents (or 1 or 2 substituents, or 1 substituent) each independently selected from R2B.

31. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 14, 22, 23, 25, and 26, wherein each R2Ais R2B.

32. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 31 , wherein R3is C1-3 alkyl (such as methyl or ethyl) optionallysubstituted with 1 , 2, or 3 substituents (or 1 or 2 substituents or 1 substituent) independently selected from R3E.

33. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 31 , wherein R3is C3-10 cycloalkyl optionally substituted with 1 , 2, or 3 substituents (or 1 or 2 substituents or 1 substituent) independently selected from R3E.

34. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 31 , and 33, wherein R3is C3-7 cycloalkyl optionally substituted with 1 , 2, or 3 substituents (or 1 or 2 substituents or 1 substituent) independently selected from R3E.

35. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 31 , 33, and 34, wherein R3is C3-6 cycloalkyl (such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl) optionally substituted with 1 , 2, or 3 substituents (or 1 or 2 substituents or 1 substituent) independently selected from R3E.

36. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 31 , and 33 to 35, wherein R3is cyclobutyl optionally substituted with 1 , 2, or 3 substituents (or 1 or 2 substituents or 1 substituent) independently selected from R3E.

37. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 31 , and 33 to 35, wherein R3is cyclopropyl optionally substituted with 1 , 2, or 3 substituents (or 1 or 2 substituents or 1 substituent) independently selected from R3E.

38. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 31 and 33 to 37, wherein R3is cyclopropyl.

39. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 31 and 33 to 377, wherein R3is 1-fluorocycloprop-1-yl.

40. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 31 and 33 to 37, wherein R3is 1-methylcycloprop-1-yl.

41. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 31 , wherein R3is Ce- aryl (such as phenyl) optionally substituted with 1 , 2, or 3 substituents (or 1 or 2 substituents or 1 substituent) independently selected from R3E.

42. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 31 , wherein R3is 5-10 membered heteroaryl optionally substituted with1 , 2, or 3 substituents (or 1 or 2 substituents or 1 substituent) independently selected from R3E.

43. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 31 , wherein R3is OR3A.

44. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 31 , wherein R3is NR3BR3C.

45. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 12, and 14 to 44, wherein each R4is independently selected from H, D, C1-3 alkyl (such as methyl or ethyl), C1-3 haloalkyl (such as trifluoroalkyl), and halo (such as fluoro).

46. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 12, and 14 to 45, wherein each R4is independently selected from H, D, C1-3 alkyl (such as methyl or ethyl), and halo (such as fluoro).

47. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 12, and 14 to 46, wherein each R4is independently selected from H, methyl, and fluoro.

48. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 12, and 14 to 47, wherein each R4is independently selected from H and methyl.

49. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 12, and 14 to 48, wherein one R4is H and one R4is methyl.

50. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 12, and 14 to 48, wherein each R4is H.

51. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 12, and 14 to 48, wherein each R4is methyl.

52. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8to 51 , wherein one R5is R5A; and each other R5is independently selected from H, methyl, and fluoro, or, optionally, two other R5attached to the same carbon atom, together with the carbon atom to which they are both attached, form a spiro C3-6 cycloalkyl ring (such as cyclopropyl) that is optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2,or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from methyl and fluoro; or, optionally, two other R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused C3-6 cycloalkyl ring (such as cyclopropyl) that is optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from methyl and fluoro.

53. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 52, wherein one R5is R5A; and each other R5is independently selected from H, methyl, and fluoro.

54. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 52, wherein one R5is R5A; and each other R5is independently selected from H and methyl, or, optionally, two other R5attached to the same carbon atom, together with the carbon atom to which they are both attached, form a spiro C3-6 cycloalkyl ring (such as cyclopropyl) that is optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from methyl; or, optionally, two other R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused C3-6 cycloalkyl ring (such as cyclopropyl) that is optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from methyl.

55. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 54, wherein one R5is R5A; and each other R5is independently selected from H and methyl.

56. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 54, wherein one R5is R5A; and each other R5is H, or, optionally, two other R5attached to the same carbon atom, together with the carbon atom to which they are both attached, form a spiro C3-6 cycloalkyl ring (such as cyclopropyl) that is optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from methyl; or, optionally, two other R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused C3-6 cycloalkyl ring (such as cyclopropyl) that is optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from methyl.

57. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 56, wherein one R5is R5A; and each other R5is H.

58. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 57, whereinR5Ais H, D, C1-3 alkyl (such as methyl), C1-3 haloalkyl (such as trifluoromethyl), C2-3 alkenyl, C2-3 alkynyl, halo (such as fluoro), ORa5A, and CN; or, optionally, R5Aand R5attached to the same carbon atom, together with the carbon atom to which they are both attached, form a spiro C3-6 cycloalkyl ring, such as cyclopropyl, that is optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from D, C1-3 alkyl (such as methyl), and halo (such as fluoro); or, optionally, R5Aand R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused C3-6 cycloalkyl ring (such as cyclopropyl) that is optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from D, C1-3 alkyl (such as methyl), and halo (such as fluoro); andRa5Ais selected from H, C1-3 alkyl, and C1-3 haloalkyl, and Cy2, wherein the C1-3 alkyl forming Ra5Ais optionally substituted with 1 , 2, 3 or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from R5B.

59. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 58, wherein R5Ais H, C1-3 alkyl (such as methyl), or halo (such as fluoro); or, optionally, R5Aand R5attached to the same carbon atom, together with the carbon atom to which they are both attached, form a spiro C3-6 cycloalkyl ring, such as cyclopropyl, that is optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from C1-3 alkyl (such as methyl) and halo (such as fluoro); or, optionally, R5Aand R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused C3-6 cycloalkyl ring (such as cyclopropyl) that is optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from C1-3 alkyl (such as methyl), and halo.

60. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 59, wherein R5Ais H or C1-3 alkyl (such as methyl); or, optionally, R5Aand R5attached to the same carbon atom, together with the carbon atom to which they are both attached, form a spiro C3-6 cycloalkyl ring, such as cyclopropyl, that is optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from C1-3 alkyl (such as methyl); or, optionally, R5Aand R5attached to adjacent carbon atoms, together with the carbon atoms to which they are each attached, form a fused C3-6 cycloalkyl ring (such as cyclopropyl) that is optionally substitutedwith 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from C1-3 alkyl (such as methyl).

61. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 58, whereinR5Ais H, D, C1-3 alkyl (such as methyl), C1-3 haloalkyl (such as trifluoromethyl), C2-3 alkenyl, C2-3 alkynyl, halo (such as fluoro), ORa5A, and CN; andRa5Ais selected from H, C1-3 alkyl, and C1-3 haloalkyl, and Cy2, wherein the C1-3 alkyl forming Ra5Ais optionally substituted with 1 , 2, 3 or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from R5B.

62. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 61 , wherein R5Ais H, C1-3 alkyl (such as methyl), or halo (such as fluoro).

63. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 62, wherein R5Ais H or C1-3 alkyl (such as methyl).

64. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 63, wherein R5Ais H.

65. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 57, wherein R5Ais Cy2.

66. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 57, wherein R5Ais C1-3 alkyl (such as methyl or ethyl) wherein the C1-3 alkyl (or methyl or ethyl) forming R5Ais substituted with Cy2and also optionally substituted with 1 , 2, 3 or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from R5B.

67. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 57, wherein R5Ais C1-3 alkyl (such as methyl or ethyl) wherein the C1-3 alkyl (or methyl or ethyl) forming R5Ais substituted with Cy2.

68. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 57, and 67, wherein R5Ais CH2Cy2.

69. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 57, and 67, wherein R5Ais CH2CH2Cy2.

70. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 57, wherein R5Ais ORa5A; and Ra5Ais Cy2.

71. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 57, wherein R5Ais C1-3 alkyl (such as methyl or ethyl), wherein the C1-3 alkyl forming Ra5Ais substituted with Cy2and also optionally substituted with 1 , 2, 3 or 4 substituents or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) each selected from R5B.

72. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 57, wherein R5Ais OCH2Cy2.

73. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 57, wherein R5Ais OCH2CH2Cy2.

74. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 73, wherein Cy2is Ce- aryl (such as phenyl) optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) independently selected from RCy2.

75. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 74, wherein Cy2is phenyl optionally substituted with 1 , 2, 3, or 4 substituents independently selected from RCy2.

76. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 75, wherein Cy2is Ce- aryl.

77. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 76, wherein Cy2is phenyl.

78. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 73, wherein Cy2is 5-10 membered heteroaryl optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) independently selected from RCy2.

79. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 73, and 78, wherein Cy2is 6 membered heteroaryl optionally substituted with 1 , 2, 3, or 4 substituents independently selected from RCy2.

80. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 73, 78, and 79, wherein Cy2is 6 membered heteroaryl.

81. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 73, and 78 to 80, wherein Cy2is pyridinyl optionally substituted with 1 , 2, 3, or 4 substituents independently selected from R0''2.

82. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 73, and 78 to 81 , wherein Cy2is pyridinyl.

83. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 73, wherein Cy2is C3-7 cycloalkyl optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) independently selected from R0''2.

84. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, and 8 to 73, wherein Cy2is 4-10 membered heterocycloalkyl optionally substituted with 1 , 2, 3, or 4 substituents (or 1 , 2, or 3 substituents, or 1 or 2 substituents, or 1 substituent) independently selected from R0''2.

85. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 75, 78, 79, 81 , 83 and 84, wherein each RCy2is independently selected from D, C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, and halo.

86. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1 , 2, 8 to 75, 78, 79, 81 , and 83 to 85, wherein each RCy2is independently halo.

87. A compound selected from the compounds listed in Tables 1 and 2, and pharmaceutically acceptable salts thereof.

88. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 87, and at least one pharmaceutically acceptable carrier or excipient.

89. A method of inhibiting KRAS activity, the method comprising contacting the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 87, or the pharmaceutical composition of claim 88, with KRAS.

90. The method of claim 89, wherein the contacting comprises administering the compound to a patient.

91. The method of claim 89 or 90, wherein KRAS is characterized as having a somatic mutation of G12C.

92. The method of claim 89 or 90, wherein KRAS is characterized as having a somatic mutation of G12D.

93. The method of claim 89 or 90, wherein KRAS is characterized as having a somatic mutation of G12V.

94. A method of treating a disease or disorder associated with activity of KRAS, the method comprising administering to a patient in need thereof a therapeutically effective amount of the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 87, or the pharmaceutical composition of claim 88.

95. A method of treating a disease or disorder associated with activity of a KRAS protein harboring a G12C mutation, the method comprising administering to a patient in need thereof a therapeutically effective amount of the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 87, or the pharmaceutical composition of claim 88.

96. A method of treating a disease or disorder associated with activity of a KRAS protein harboring a G12D mutation, the method comprising administering to a patient in need thereof a therapeutically effective amount of the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 87, or the pharmaceutical composition of claim 88.

97. A method of treating a disease or disorder associated with activity of a KRAS protein harboring a G12V mutation, the method comprising administering to a patient in need thereof a therapeutically effective amount of the compound or pharmaceutically acceptable salt thereof according any one of claims 1 to 87, or the pharmaceutical composition of claim 88.

98. A method for treating a cancer in a patient, the method comprising administering to the patient a therapeutically effective amount of the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 87, or the pharmaceutical composition of claim 88.

99. The method of claim 98, wherein the cancer is selected from carcinomas, hematological cancers, sarcomas, and glioblastoma.

100. The method of claim 98, wherein the cancer is a hematological cancer selected from myeloproliferative neoplasms, myelodysplastic syndrome, chronic and juvenilemyelomonocytic leukemia, acute myeloid leukemia, acute lymphocytic leukemia, and multiple myeloma.

101. The method of claim 98, wherein the cancer is a carcinoma selected from pancreatic, colorectal, lung, bladder, gastric, esophageal, breast, head and neck, cervical, skin, and thyroid cancers.

102. The method of any one of claims 98 to 101 , wherein abnormally proliferating cells of the cancer comprise KRAS having a G12C mutation.

103. The method of any one of claims 98 to 101 , wherein abnormally proliferating cells of the cancer comprise KRAS having a G12D mutation.

104. The method of any one of claims 98 to 101 , wherein abnormally proliferating cells of the cancer comprise KRAS having a G12V mutation.

105. A method of treating an immunological or inflammatory disorder comprising administering to a patient in need thereof a therapeutically effective amount of the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 87, or the pharmaceutical composition of claim 88.

106. The method of claim 105, wherein the immunological or inflammatory disorder is associated with activity of KRAS.

107. The method of claim 105, wherein the immunological or inflammatory disorder is associated with activity of KRAS having a G12C mutation.

108. The method of claim 105, wherein the immunological or inflammatory disorder is associated with activity of KRAS having a G12D mutation.

109. The method of claim 105, wherein the immunological or inflammatory disorder is associated with activity of KRAS having a G12V mutation.

110. The method of claim 105, wherein the immunological or inflammatory disorder is Ras-associated lymphoproliferative disorder or juvenile myelomonocytic leukemia caused by a somatic mutation of KRAS.

111. The method of claim 110, wherein the somatic mutation of KRAS is G12C.

112. The method of claim 110, wherein the somatic mutation of KRAS is G12D.

113. The method of claim 110, wherein the somatic mutation of KRAS is G12V.

114. A method of treating a cancer in a patient comprising: identifying that the patient is in need of treatment of a cancer and that abnormally proliferating cells of the cancer comprise KRAS having a G12C mutation;administering to the patient a therapeutically effective amount of t the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 87, or the pharmaceutical composition of claim 88.

115. A method of treating a cancer in a patient comprising: identifying that the patient is in need of treatment of a cancer and that abnormally proliferating cells of the cancer comprise KRAS having a G12D mutation; administering to the patient a therapeutically effective amount of the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 87, or the pharmaceutical composition of claim 88.

116. A method of treating a cancer in a patient comprising: identifying that the patient is in need of treatment of a cancer and that abnormally proliferating cells of the cancer comprise KRAS having a G12V mutation; administering to the patient a therapeutically effective amount of the compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 87, or the pharmaceutical composition of claim 88.