Heterocyclic compounds as parp1 inhibitors

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• X is C or N;
• Y is C or N;
• is a single or double bond;
• m is 0, 1, 2, 3, 4, 5, or 6;
• p is 0, 1, 2, 3, 4, 5, or 6;
• q is 0, 1, 2, 3, 4, 5, or 6;
• Ring B is C5-10 cycloalkyl, phenyl, 5-10 membered heterocycloalkyl, or 5-6 membered heteroaryl;
• Ring C is 4-14 membered heterocycloalkyl;
• Ring D is C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl;
• L is selected from C1-4 alkylene, C1-4 haloalkylene, C3-7 cycloalkylene, 4-7 membered heterocycloalkylene, —C3-7 cycloalkylene-C1-4 alkyl-, -(4-7 membered heterocycloalkylene)-C1-4 alkyl-, —O—, —N(RL)—, —C(O)—, —C(O)N(RL)—, —N(RL)C(O)N(RL)—, —N(RL)C(O)O—, —S(O)2—, —N(RL)S(O)2—, and —N(RL)S(O)2N(RL)—, wherein the C1-4 alkylene, C1-4 haloalkylene, C3-7 cycloalkylene, 4-7 membered heterocycloalkylene, C3-7 cycloalkylene-C1-4 alkyl, and (4-7 membered heterocycloalkylene)-C1-4 alkyl of L are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• each RL is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;
• R1 is selected from H, halo, CN, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, and C1-3 haloalkoxy;
• R2 is selected from H, halo, CN, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, and C1-3 haloalkoxy;
• R3 is selected from H, halo, C1-3 alkyl, and C1-3 haloalkyl;
• R4 is selected from H, halo, C1-3 alkyl, and C1-3 haloalkyl;
• or, R3 and R4, together with the carbon atom to which they are attached, form a C3-7 cycloalkyl, or 4-7 membered heterocycloalkyl group, wherein the C3-7 cycloalkyl, and 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• R50 is selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, (5-6 membered heteroaryl)-C1-4 alkyl, —CN, —ORa50, —SRa50, —NRc50Rd50, —NO2, —C(O)Ra50, —C(O)ORa50, —C(O)NRc50Rd50, —C(O)NRc50 (ORa50), —OC(O)Ra50, —OC(O)NRc50Rd50, —OC(O)ORa50, —OS(O)2Rb50, —OS(O)2NRc50Rd50, —NRc50C(O)Ra50, —NRc50C(O)ORa50, —NRc50C(O)NRc50Rd50, —NRc50S(O)2Rb50, —NRc50S(O)2NRc50Rd50, —NRc50ORa50, —NRc50S(O)Rb50, —NRc50S(O)NRc50Rd50, —S(O)Rb50, —S(O)2Rb50, —S(O)NRc50Rd50, —S(O)2NRc50Rd50, —C(═NRc50)Ra50, —C(═NRe50)NRc50Rd50, —NRc50C(═NRe50)Ra50, —NRc50C(═NRe50)NRc50Rd50, —NRc50S(O)(═NRe50)Rb50, —NRc50S(O)(═NRe50)NRc50Rd50, —OS(O)(═NRe50)Rb50, —S(O)(═NRe50)Rb50, —S(O)(═NRe50)NRc50Rd50, —C(O)NRc50 S(O)2Rb50, —C(O)NRc50S(O)2NRc50Rd50, —S(O)2NRc50C(O)Rb50, —NRc50S(O)NRc50C(O)Rb5, and —P(O)Rf50Rg50, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl of R50 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Ra50, Rc50, and Rd50 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl of Ra50, Rc50 and Rd50 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• or, any Rc50 and Rd50 attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Rb50 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl of Rb50 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Re50 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl;
• each Rf50 and Rg50 are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl;
• each R6 is independently selected from oxo, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, (5-6 membered heteroaryl)-C1-4 alkyl, —CN, —ORa6, —SRa6, —NRc6Rd6, —NO2, —C(O)Ra6, —C(O)ORa6, —C(O)NRc6Rd6, —C(O)NRc6(ORa6), —OC(O)Ra6, —OC(O)NRc6Rd6, —OC(O)ORa6, —OS(O)2Rb6, —OS(O)2NRc6Rd6, —NRc6C(O)Ra6, —NRc6C(O)ORa6, —NRc6C(O)NRc6Rd6, —NRc6S(O)2Rb6, —NRc6S(O)2NRc6Rd6, —NRc6ORa6, —NRc6S(O)Rb6, —NRc6S(O)NRc6Rd6, —S(O)Rb6, —S(O)2R6, —S(O)NRc6Rd6, —S(O)2NRc6Rd6, —C(═NRe6)Ra6, —C(═NRe6)Rc6Rd6, —Rc6C(═NRe6)Ra6, —NRc6C(═Re6NRc6Rd6, —NRc6S(O)(═NRe6)Rb6, —NRc6S(O)(═NRe6)NRc6Rd6, —OS(O)(═NRe6)Rb6, —S(O)(═NRe6)Rb6, —S(O)(═NRe6)NRc6Rd6, —C(O)NRc6S(O)2Rb6, —C(O)NRc6S(O)2NRc6Rd6, —S(O)2NRc6C(O)Rb6, —NRc6S(O)NRc6C(O)Rb6, and —P(O)Rf6Rg6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl of R6 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Ra6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl of Ra6, Rc6, and Rd6 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• or, any Rc6 and Rd6 attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Rb6 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl of Rb6 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Re6 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl;
• each Rf6 and Rg6 are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl;
• each R7 is independently selected from oxo, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, (5-6 membered heteroaryl)-C1-4 alkyl, —CN, —ORa7, —SRa7, —NRc7Rd7, —NO2, —C(O)Ra7, —C(O)ORa7, —C(O)NRc7Rd7, —C(O)NRc7(ORa7), —OC(O)Ra7, —OC(O)NRc7Rd7, —OC(O)ORa7, —OS(O)2Rb7, —OS(O)2NRc7Rd7, —NRc7C(O)Ra7, —NRc7C(O)ORa7, —NR7C(O)NRc7Rd7, —NRc7S(O)2Rb7, —NRc7S(O)2NRc7Rd7, —NRc7ORa7, —NRc7S(O)Rb7, —Rc7S(O)NRc7Rd7, —S(O)Rb7, —S(O)2Rb7, —S(O)NRc7Rd7, —S(O)2NRc7Rd7, —C(═NRe7)Ra7, —C(═NRe7)NRc7Rd7, —NRc7C(═NRe7)Ra7, —NRc7C(═NRc7)NRc7Rd7, —NRc7S(O)(═NRe7)Rb7, —NRc7S(O)(═NRe7)NRc7Rd7, —OS(O)(═NRe7)Rb7, —S(O)(═NRe7)Rb7, —S(O)(═NRe7)NRc7Rd7, —C(O)NRc7S(O)2Rb7, —C(O)NRc7S(O)2NRc7Rd7, —S(O)2NRc7C(O)Rb7, —NR7S(O)NRc7C(O)Rb7 and —P(O)Rf7Rg7, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl of R7 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Ra7, Rc7, and Rd7 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl of Ra7, Rc7, and Rd7 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• or, any Rc7 and Rd7 attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Rb7 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl of Rb7 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Rc7 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl;
• each Rf7 and Rg7 are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, (4-7 membered heterocycloalkyl)-C1-4 alkyl, and (5-6 membered heteroaryl)-C1-4 alkyl;
• each R8 is independently selected from oxo, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, —CN, —ORa8, —SRa8, —NRc8Rd8, —NO2, —C(O)Ra8, —C(O)ORa8, —C(O)NRc8Rd8, —C(O)NRc8(ORa8), —OC(O)Ra8, —OC(O)NRc8Rd8, —OC(O)ORa8, —OS(O)2Rb8, —OS(O)2NRc8Rd8, —NRc8C(O)Ra8, —NRc8C(O)ORa8, —NRc8C(O)NRc8Rd8, —NRc8S(O)2Rb8, —NRc8S(O)2NRc8Rd8, —NRc8ORa8, —NRS(O)Rb8, NRc8S(O)NRc8Rd8, —S(O)Rb8, —S(O)2Rb8, —S(O)NRc8Rd8, —S(O)2NRc8Rd8, —C(═NRe8)Ra8, —C(═NRe8)NRc8Rd8, —NRc8C(═NRe8)Ra8, —NRc8C(═NRe8)NRc8Rd8, —NRc8S(O)(═NRe8)Rb8, —NRc8S(O)(NRe8)NRc8Rd8, —OS(O)(═NRe8)Rb8, —S(O)(═NRe8)Rb8, —S(O)(═NRe8)NRc8Rd8, —C(O)NRc8S(O)2Rb8, —C(O)NRc8S(O)2NRc8Rd8, —S(O)2NRc8C(O)Rb8, —NRc8S(O)NRc8C(O)Rb8 and —P(O)Rf8Rg8, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl of R8 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R8A substituents;
• or, a R7 and a R8, together with the atoms to which they are attached, form a C5-10 cycloalkyl, phenyl, 5-10 membered heterocycloalkyl, or 5-6 membered heteroaryl group, wherein the C5-10 cycloalkyl, phenyl, 5-10 membered heterocycloalkyl, or 5-6 membered heteroaryl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R8A substituents;
• each Ra8, Rc8, and Rd8 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl of Ra8, Rc8, and Rd8 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R8A substituents;
• or, any Rc8 and Rd8 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R8A substituents;
• each Rb8 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl of Rb8 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R8A substituents;
• each R8 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl;
• each Rf8 and Rg8 are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl;
• each R8A is independently selected from oxo, H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, —CN, —ORa8A, —SRa8A, —NRc8ARd8A, —NO2, —C(O)Ra8A, —C(O)ORa8A, —C(O)NRc8ARd8A, —C(O)NRc8A(ORa8A), —OC(O)Ra8A, —OC(O)NRe8ARd8A, —OC(O)ORa8A, —OS(O)2Rb8A, OS(O)2NRe8ARd8A, —NRe8AC(O)Ra8A, —NRe8AC(O)ORa8A, —NRc8AC(O)NRe8ARd8A, —NRe8AS(O)2Rb8A, —NRc8AS(O)2NRe8ARd8A, —NRe8AORa8A, —NRc8AS(O)Rb8A, —NRe8AS(O)NRe8ARd8A, —S(O)Rb8A, —S(O)2Rb8A, —S(O)NRe8ARd8A, —S(O)2NRe8ARd8A, —C(═NRe8A)Ra8A, —C(═NRe8A)NRe8ARd8A, —NRc8AC(═NRe8A)Ra8A, —NRe8AC(═NRe8A)NRe8ARd8A, —NRe8AS(O)(═NRe8A)Rb8A, —NRe8AS(O)(═NRe8A)NRe8ARd8A, —OS(O)(═NRe8A)Rb8A, —S(O)(═NRe8A)Rb8A, —S(O)(═NRe8A)NRe8ARd8A, —C(O)NRc8AS(O)2Rb8A, —C(O)NRc8AS(O)2NRe8ARd8A, —S(O)2NRe8AC(O)Rb8A, —NRc8AS(O)NRe8AC(O)Rb8A, and —P(O)Rf8ARg8A, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl of R8A are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Ra8A, Ra8A, and Rd8A is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl of Ra8A, Rc8A and Rd8A are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• or, any Rc8A and Rd8A attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Rb8A is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl of Rb8A are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Re8A is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl;
• each Rf8A and Rg8A are independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, C6-10 aryl-C1-4 alkyl, (4-10 membered heterocycloalkyl)-C1-4 alkyl, and (5-10 membered heteroaryl)-C1-4 alkyl;
• and
• each RG is independently selected from H, OH, CN, halo, oxo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-C1-4 alkyl, HO—C1-4 alkyl, C1-4 alkoxy-C1-4 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(C1-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(C1-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(C1-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(C1-3 alkyl)aminocarbonylamino.