HETEROCYCLIC COMPOUNDS AS PI3Ka INHIBITORS

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• X1 is NR1 or O;
• X2 is CR2 or N;
• X3 is CR3 or N;
• n is 0, 1, 2, 3, 4, 5, or 6;
• m is 0, 1, 2, 3, 4, 5, or 6;
• Ring A is C3-14 cycloalkyl or 4-14 membered heterocycloalkyl;
• Ring B is C3-10 cycloalkyl, C6-10 aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl;
• L1 is selected from bond, C1-6 alkylene, C1-6 haloalkylene, C3-7 cycloalkylene, 4-7 membered heterocycloalkylene, 5-6 membered heteroarylene, —C3-7 cycloalkylene-C1-4 alkyl-, -(4-7 membered heterocycloalkylene)—C1-4 alkyl-, -(5-6 membered heteroarylene)—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 C1-6 alkylene, C1-6 haloalkylene, C3-7 cycloalkylene, 4-7 membered heterocycloalkylene, 5-6 membered heteroarylene, C3-7 cycloalkylene-C1-4 alkyl, (4-7 membered heterocycloalkylene)—C1-4 alkyl, and (5-6 membered heteroarylene)—C1-4 alkyl of L1 are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• L2 is selected from bond, C1-6 alkylene, C1-6 haloalkylene, C3-7 cycloalkylene, 4-7 membered heterocycloalkylene, 5-6 membered heteroarylene, —C3-7 cycloalkylene-C1-4 alkyl-, -(4-7 membered heterocycloalkylene)—C1-4 alkyl-, -(5-6 membered heteroarylene)—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 C1-6 alkylene, C1-6 haloalkylene, C3-7 cycloalkylene, 4-7 membered heterocycloalkylene, 5-6 membered heteroarylene, C3-7 cycloalkylene-C1-4 alkyl, (4-7 membered heterocycloalkylene)—C1-4 alkyl, and (5-6 membered heteroarylene)—C1-4 alkyl of L2 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, 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, 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 R1 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• R2 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, —ORa2, —SRa2—NR2Rd2, —C(O)Ra2, —C(O)ORa2, —C(O)NRc2Rd2, —C(O)NRc2(ORa2), —OC(O)NR2Rd2—NRc2C(O)Ra2, —NRc2C(O)ORa2, —NRc2C(O)NRc2Rd2—NR2S(O)2Rb2-Rc2S(O)2NRc2Rd2—NRc20Ra2, —NRc2S(O)Rb2, —NRc2S(O)NRc2Rd2, —S(O)Rb2, —S(O)2Rb2, —S(O)NRc2Rd2, —S(O)2NRc2Rd2, —C(═NRc2)Ra2, —C(═NRc2)NRc2Rd2—NRc2C(═NRc2)Ra2—NR2C(═NRc2)NRc2Rd2-Rc2S(O)(═NRc2)Rb2—NRc2S(O)(═NRc2)NR2Rd2—S(O)(═NRc2)Rb2, and —S(O)(═NRc2)NRc2Rd2, 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 R2 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Ra2, Rb2, Rc2, and Rd2 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 Ra2, Rb2, Rc2, and Rd2 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• or, any Rc2 and Rd2 attached to the same N atom, together with the N atom to which they are attached, form a 4-7 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;
• and
• each Rc2 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;
• R3 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, —ORa3, —SRa3—NRc3Rd3—C(O)R3, —C(O)ORa3, —C(O)NRc3Rd3, —C(O)NRc3(ORa3), —OC(O)NRc3Rd3—NRc3C(O)Ra3, —NRc3C(O)ORa3, —NRc3C(O)NRc3Rd3—NRc3S(O)2Rb3, —NRc3S(O)2NR3Rd3—NRc3ORa3, —NRc3S(O)Rb3, —NRc3S(O)NRc3Rd3, —S(O)Rb3, —S(O)2R13, —S(O)NRc3Rd3, —S(O)2NRc3Rd3, —C(═NRc3)Ra3, —C(═NRc3)NRc3Rd3—NRc3C(═NRc3)Ra3, —NRc3C(═NRc3)NRc3Rd3, —NR3S(O)(═NRc3)Rb3, —NRc3S(O)(═NRc3)NR3Rd3—S(O)(═NRc3)Rb3, and —S(O)(═NRc3)NRc3Rd3, 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 R3 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Ra3, Rb3, Rc3, and Rd3 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 Ra3, Rb3, Rc3, and Rd3 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• or, any Rc3 and Rd3 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;
• and
• each Rc3 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;
• R4 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, —ORa4, —SRa4—NRc4Rd4—C(O)Ra4, —C(O)ORa4, —C(O)NRc4Rd4, —C(O)NRc4(ORa4), —OC(O)NRc4Rd4—NRc4C(O)Ra4, —NRc4C(O)ORa4, —NRc4C(O)NRc4Rd4, —NRc4S(O)2Rb4, —NRc4S(O)2NRc4Rd4, —NRc4ORa4, —NRc4S(O)Rb4, —NRc4S(O)NRc4Rd4, —S(O)Rb4, —S(O)2Rb4, —S(O)NRc4Rd4, —S(O)2NRc4Rd4, —C(═NRc4)Ra4, —C(═NRc4)NRc4Rd4—NRc4C(═NRc4)Ra4, —NRc4C(═NRc4)NRc4Rd4—NRc4S(O)(═NRc4)Rb4, —NRc4S(O)(═NRc4)NRc4Rd4—S(O)(═NRc4)Rb4, and —S(O)(═NRc4)NRc4Rd4, 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 R4 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Ra4, Rb4, Rc4, and Rd4 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 Ra4, Rb4, Rc4, and Rd4 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• or, any Rc4 and Rd4 attached to the same N atom, together with the N atom to which they are attached, form a 4-7 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;
• and
• each Rc4 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;
• R5 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, 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 R5 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• or, R4 and R5 taken 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 are each optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
• R6 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, —ORa6, —SRa6—NR6Rd6, —C(O)Ra6, —C(O)ORa6, —C(O)NR6Rd6, —C(O)NRc6(ORa6), —OC(O)NR6Rd6—NRc6C(O)Ra6, —NR6C(O)ORa6, —NRc6C(O)NR6Rd6—NR6S(O)2Rb6, —NRc6S(O)2NRc6Rd6—NRo60Ra6, —NRc6S(O)Rb6, —NRc6S(O)NRc6Rd6, —S(O)Rb6, —S(O)2R6, —S(O)NRc6Rd6, —S(O)2NRc6Rd6, —C(═NRc6)Ra6, —C(═NRc6)NRc6Rd6—NRc6C(═NRc6)Ra6—NR6C(═NRc6)NRc6Rd6-Rc6S(O)(═NRc6)Rb6, —NRc6S(O)(═NRc6)NR6Rd6—S(O)(═NRc6)Rb6, and —S(O)(═NRc6)NRc6Rd6, 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, Rb6, 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, Rb6, 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;
• and
• each Rc6 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 R7 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, —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—NRo70Ra7, —NRc7S(O)Rb7, —NRc7S(O)NRc7Rd7, —S(O)Rb7, —S(O)2Rb7, —S(O)NRc7Rd7, —S(O)2NRc7Rd7, —C(═NRc7)Ra7, —C(═NRc7)NRc7Rd7—NRc7C(═NRc7)Ra7, —NR7C(═NRc7)NRc7Rd7-Rc7S(O)(═NRc7)Rb7, —NRc7S(O)(═NRc7)NRc7Rd7—OS(O)(═NRc7)Rb7, —S(O)(═NRc7)Rb7, —S(O)(═NRc7)NRc7Rd7, —C(O)NRc7S(O)2Rb7, —C(O)NRc7S(O)2NRc7Rd7—S(O)2NRc7C(O)Rb7, —NRc7S(O)NRc7C(O)Rb7, and —P(O)R7Rg7, 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 R7 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R7A substituents;
• each Ra7, Rc7, and Rd7 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 Ra7, Rc7, and Rd7 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R7A substituents;
• or, any Rc7 and Rd7 attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R7A substituents;
• each Rb7 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 Rb7 are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R7A 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, C3-10 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 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, C3-10 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 R7A 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, —ORa7A, —SRa7A, —Nc7A, Rd7A, —NO2, —C(O)Ra7A, —C(O)ORa7A, —C(O)NRc7A, Rd7A, —C(O)NRc7A(ORa7A), —OC(O)Ra7A, —OC(O)NRc7A, Rd7A, —OC(O)ORa7A, —OS(O)2Rb7A, OS(O)2NR7A, Rd7A, —NRc7aC(O)Ra7A, —NRc7aC(O)ORa7A, —NRc7aC(O)NRc7A, Rd7A, —NRc7AS(O)2Rb7A NRc7AS(O)2NRc7A, Rd7A, —NRc7AORa7A, —NRc7AS(O)Rb7A, —NRc7AS(O)NRc7A, Rd7A, —S(O)Rb7A, —S(O)2Rb7A, —S(O)NRc7A, Rd7A, —S(O)2NRc7A, Rd7A, —C(═NRe7A)Ra7A, —C(═NRc7A)Rc7A, Rd7A, —NRc7aC(═NRc7A)Ra7A, —NRc7aC(═NRe7A)NRc7A, Rd7A Nc7AS(O)(═NRc7A)Rb7A, —NRc7AS(O)(═NRc7A)NRc7A, Rd7A, —OS(O)(═NRc7A)Rb7A, —S(O)(═NRc7A)Rb7A, —S(O)(═NRc7A)Rc7A, Rd7A, —C(O)NRc7AS(O)2Rb7A, —C(O)NRc7AS(O)2NRc7A, Rd7A, —S(O)2NRc7aC(O)Rb7A—NRc7AS(O)NRc7aC(O)Rb7A, and —P(O)Rf7ARg7A, 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 R7A are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Ra7A, Rc7A, and Rd7A 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 Ra7A, Rc7A and Rd7A are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• or, any Rc7A and Rd7A 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 Rb7A 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 Rb7A are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RG substituents;
• each Re7A 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 Rf7A and Rg7A 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 Rf7A 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)RV, —NRc8S(O)NR8Rd8, —S(O)Rb8, —S(O)2Rb8, —S(O)NRc8Rd8, —S(O)2NRc8Rd8, —C(═NRc8)Ra8, —C(═NRc8)NRc8Rd8—NRc8C(═NRc8)Ra8, —NRc8C(═NRc8)NRc8Rd8—NRc8S(O)(═NRc8)RV, —NRc8S(O)(NRe8)NRc8Rd8—OS(O)(═NRc8)Rb8, —S(O)(═NRc8)Rb8, —S(O)(═NRc8R)N 8Rd8, —C(O)NRc8S(O)2Rb, —C(O)NRc8S(O)2NRc8Rd8—S(O)2NRc8C(O)Rb8, —NRc8S(O)NRc8C(O)RV, and —P(O)Rb8, 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 Rf7A are each 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 Rb8 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 R and R98 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, 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, —NR8ARd8A, —NO2, —C(O)Ra8A, —C(O)ORa8A, —C(O)NRc8A, Rd8A, —C(O)NRc8A(ORa8A), —OC(O)Ra8A, —OC(O)NRc8A, Rd8A, —OC(O)ORa8A, —OS(O)2Rb8A, —OS(O)2NR8A, Rd8A, —NRc8aC(O)Ra8A, —NRc8aC(O)ORa8A, —NR8aC(O)NRc8A, Rd8A, —NR8AS(O)2Rb8A, —NRc8AS(O)2NRc8A, Rd8A, —NRc8AORa8A, —NRc8AS(O)Rb8A, —NR8AS(O)NRc8A, Rd8A, —S(O)Rb8A, —S(O)2Rb8A, —S(O)NRc8A, Rd8A, —S(O)2NRc8A, Rd8A, —C(═NRc8A)Ra8A, -C(═NRe8A)R8A, Rd8A, —NRc8aC(═NRc8A)Ra8A, —NRc8aC(═NRe8A)NR8A, Rd8A, —R8AS(O)(═NRc8A)Rb8A, —NRc8AS(O)(═NRc8A)NR8A, Rd8A, —OS(O)(═NRc8A)Rb8A, —S(O)(═NRc8A)Rb8A, —S(O)(═NRc8A)R8A, Rd8A, —C(O)NRc8AS(O)2Rb8A, —C(O)NRc8AS(O)2NRc8A, Rd8A, —S(O)2NRc8aC(O)Rb8A, —NRc8AS(O)NRc8aC(O)Rb8A, and —P(O)Rg8A, 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, Rb8A, 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, C60.1o 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 Rb8A 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 Rc8A 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;
• each RG is independently selected from 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.