Substituted pyrrolo[3,4-d]imidazoles as JAK inhibitors

A compound of formula (G),

• or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
• each R2 is independently H, halogen, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, or a bicyclic 7-11 membered heteroaryl;
• wherein each C1-6 alkyl, C2-6 alkenyl, OC1-6 alkyl, OC1-6 haloalkyl, and SC1-4 alkyl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-7 cycloalkyl;
• and
• wherein each C3-7 cycloalkyl, 4-10 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, and 7-11 membered heteroaryl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-7 cycloalkyl;
• L is a bond, —CH2—, —C(O)—, or —S(O)2—;
• R13 is H, halogen, CN, NO2, C1-6 alkyl, NR17R18, OH, OC1-6 alkyl, OC1-4 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, C5-11 bicycloalkyl, a 3-7 membered heterocycloalkyl, a bicyclic 5-11 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, a bicyclic 7-11 membered heteroaryl, or an 11-15 membered tricyclyl, wherein R13 is optionally substituted with 1, 2, 3, or 4 independently selected R1 substituents;
• each R1 is independently halogen, CN, NO2, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-8 alkyl, OC1-4 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, C5-11 bicycloalkyl, a 3-10 membered heterocycloalkyl, a bicyclic 5-11 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, a bicyclic 7-11 membered heteroaryl, or an 11-15 membered tricyclyl;
• wherein each C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, OC1-8 alkyl, and SC1-4 alkyl is optionally and independently substituted with 1, 2, 3, or 4 independently selected R3 substituents;
• and
• wherein each C3-7 cycloalkyl, 3-10 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, and 7-11 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 independently selected R4 substituents;
• and
• each R3 is independently halogen, CN, NO2, C(O)R12, C(O)NR7R8, C(O)OR12, NR5R6, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 3-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, or a bicyclic 7-11 membered heteroaryl;
• wherein each C3-7 cycloalkyl, 3-10 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, or 7-11 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl;
• each R4 is independently halogen, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)R12, C(O)NR7R8, C(O)OR12, NR5R6, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 3-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, or a bicyclic 7-11 membered heteroaryl;
• wherein each C1-6 alkyl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-4 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl;
• wherein each C3-7 cycloalkyl, 3-10 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, and 7-11 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substitutes substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-4haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl;
• each R5 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
• wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substitutes substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NH(CH3), N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• and
• wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substitutes substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NH(CH3), N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• each R6 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
• wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• and
• wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• each R7 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
• wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• and
• wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• each R8 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
• wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• and
• wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• X1 is CR14 or N;
• X2 is CR15 or N;
• X3 is CR16 or N;
• R14 is H, halogen, CN, NO2, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-4haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, or a monocyclic 5-7 membered heteroaryl, wherein the C1-6 alkyl, OC1-6 alkyl, or SC1-4 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, N(C1-4 alkyl)(C(O) C1-4 alkyl), OH, OC1-4 alkyl, OC1-4 haloalkyl, SC1-4 alkyl, and C3-7 cycloalkyl;
• and
• wherein the C3-7 cycloalkyl, or 3-7 membered heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, N(C1-4 alkyl)-C(O)C1-4 alkyl, OH, OC1-4 alkyl, OC1-4 haloalkyl, SC1-4 alkyl, and C3-7 cycloalkyl;
• R15 is H, halogen, CN, NO2, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, or a monocyclic 5-7 membered heteroaryl,
• wherein the C1-6 alkyl, OC1-6 alkyl, or SC1-4 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, N(C1-4 alkyl)(C(O) C1-4 alkyl), OH, OC1-4 alkyl, OC1-4 haloalkyl, SC1-4 alkyl, and C3-7 cycloalkyl;
• and
• wherein the C3-7 cycloalkyl, or 3-7 membered heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, N(C1-4 alkyl)-C(O)C1-4 alkyl, OH, OC1-4 alkyl, OC1-4 haloalkyl, SC1-4 alkyl, and C3-7 cycloalkyl;
• R16 is H, halogen, CN, NO2, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-4haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, or a monocyclic 5-7 membered heteroaryl,
• wherein the C1-6 alkyl, OC1-6 alkyl, or SC1-4 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, N(C1-4 alkyl)(C(O) C1-4 alkyl), OH, OC1-4 alkyl, OC1-4 haloalkyl, SC1-4 alkyl, C3-7 cycloalkyl;
• and
• wherein the C3-7 cycloalkyl, or 3-7 membered heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, N(C1-4 alkyl)-C(O)C1-4 alkyl, OH, OC1-4 alkyl, OC1-4 haloalkyl, SC114 alkyl, and C3-7 cycloalkyl;
• R17 is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OC1-6 alkyl, OC1-6 haloalkyl, C3-7 cycloalkyl, C5-11 bicycloalkyl, a 3-7 membered heterocycloalkyl, a bicyclic 5-11 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, a bicyclic 7-11 membered heteroaryl, or an 11-15 membered tricycyl;
• wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OC1-6 alkyl, or OC1-6 haloalkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, and a bicyclic 7-11 membered heteroaryl;
• wherein the C3-7 cycloalkyl, C5-11 bicycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, 7-11 membered heteroaryl, or 11-15 membered tricyclyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, and a bicyclic 7-11 membered heteroaryl;
• wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OC1-6 alkyl, OC1-6 haloalkyl and SC1-4 haloalkyl substituent is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl;
• and
• wherein each C3-7 cycloalkyl, 4-10 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, and 7-11 membered heteroaryl substituent is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl;
• R18 is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OC1-6 alkyl, OC1-6 haloalkyl, C3-7 cycloalkyl, C5-11 bicycloalkyl, a 3-7 membered heterocycloalkyl, a bicyclic 5-11 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, a bicyclic 7-11 membered heteroaryl, or an 11-15 membered tricycyl;
• wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OC1-6 alkyl, or OC1-6 haloalkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, and a bicyclic 7-11 membered heteroaryl;
• wherein the C3-7 cycloalkyl, C5-11 bicycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, 7-11 membered heteroaryl, or 11-15 membered tricyclyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, and a bicyclic 7-11 membered heteroaryl;
• wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OC1-6 alkyl, OC1-6 haloalkyl, and SC1-4 haloalkyl substituent is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl;
• and
• wherein each C3-7 cycloalkyl, 4-10 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, and 7-11 membered heteroaryl substituent is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl;
• or
• R17 and R18 together with the nitrogen atom to which they are attached, form a 3-14 membered heterocyclyl;
• each R9 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
• wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• and
• wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• each R10 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
• wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• and
• wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• each R11 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
• wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• and
• wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• and
• each R12 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
• wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
• and
• wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl.