Tricyclic pyridone compounds as JAK2 V617F inhibitors

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R1 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RM substituents;
• R2 is selected from H, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa2, SRa2, NHORa2, C(O)Rb2, C(O)NRc2Rd2, C(O)NR2(ORa2), C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, C(═NRe2)Rb2, C(═NRe2)NRc2Rd2, NRc2C(═NRe2)NRc2Rd2, NRe2C(═NRe2)Rb2, NRc2S(O)Rb2, NRc2S(O)NRc2Rd2, NRe2S(O)2Rb2, NRc2S(O)(═NRe2)Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2, OS(O)(═NRe2)Rb2, and OS(O)2Rb2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R2 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2A substituents;
• each Ra2, Re2, and Rd21s independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra2, Rc2 and Rd2 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2A substituents;
• or, any Rc2 and Rd2 attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected R2A substituents;
• each Rb2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Rb2 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2A substituents;
• each Re2 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, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;
• each R2A is independently selected from halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa21, SRa21, NHORa21, C(O)Rb21, C(O)NRc21Rd21, C(O)NRc21(ORa21) C(O)ORa21, OC(O)Rb21, OC(O)NRc21Rd21, NRc21Rd21, NRc21Rd21, NRe21C(O)Rb21, NR21C(O)ORa21NRc21C(O)NRc21Rd21, C(═NRe21)Rb21, C(═NRe21)NRc21Rd21, NRc21C(═NRe21)NRc21Rd21, NRc21C(═NRe21)Rb21, NRc21S(O)Rb21, NRc21S(O)NRc21Rd21, NRc21S(O)2Rb21, NRc21S(O)(═NRe21)Rb21, NRc21S(O)2NRe21Rd21, S(O)Rb21, S(O)NRc21Rd21, S(O)2Rb21, S(O)2NRc2Rd21, OS(O)(═NRe21)Rb21, and OS(O)2Rb21, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R2A are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2B substituents;
• each Ra21, Rc21, and Rd21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra21, Rc21 and Rd21 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2B substituents;
• or, any Rc21 and Rd21 attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected R2B substituents;
• each Rb21 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Rb21 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2B substituents;
• each Re21 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, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;
• each R2B is independently selected from halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa22, SRa22, NHORa22, C(O)Rb22, C(O)NRc22Rd22, C(O)NRc22(ORa22), C(O)ORa22, OC(O)Rb22, OC(O)NRc22Rd22, NRc22Rd22, NRc22NRd22, NRc22C(O)Rb22, NRc22C(O)ORa22, NRc22C(O)NRc22Rd22, C(═NRe22)Rb22, C(═NRe22)NRc22Rd2, NR22C(═NRe22)NRc22Rd22, NRc22C(═NRe22)Rb22, NRc22S(O)Rb22, NRc22S(O)NRc22Rd22, NRc22S(O)2Rb22, NRc22S(O)(═NRe22)Rb22, NRc22S(O)2NRc22Rd22, S(O)Rb22, S(O)NRc22Rd22, S(O)2Rb22, S(O)2NRc22Rd22, OS(O)(═NRe22)Rb22, and OS(O)2Rb22, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R2B are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2C substituents;
• each Ra22, Rc22, and Rd22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra22, Rc22 and Rd22 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2C substituents;
• or, any Rc22 and Rd22 attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected R2C substituents;
• each Rb22 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Rb22 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R2C substituents;
• each Re22 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, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;
• each R2C is independently selected from halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, (4-7 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa23, SRa23, NHORa23, C(O)Rb23, C(O)NRc23Rd23, C(O)NR23(ORa23), C(O)ORa23, OC(O)Rb23, OC(O)NRc23Rd23, NRc23Rd23, NRc23NRc23Rd23, NRc23C(O)Rb23, NRc23C(O)ORa23, NRc23C(O)NRc23R23, C(═NRe23)Rb23, C(═NRe23)R23Rd23, NRc23C(═NRe23)NRc23Rd23, NRc23C(═NRe23)Rb23, NRc23S(O)Rb23, NRc23S(O)NRc23R23, NRe23S(O)2Rb23, NRe23S(O)(═NRe23)Rb23, NRc23S(O)2NRc23Rd23, S(O)Rb23, S(O)NRc23Rd23, S(O)2Rb23, S(O)2NRc23Rd23, OS(O)(═NRe23)Rb23, and OS(O)2Rb23, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of R2C are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• each Ra23, Rc23, and Rd23 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Ra23, Re23 and Rd23 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• or, any Rc23 and Rd23 attached to the same N atom, together with the N atom to which they are attached, form a 5-6 membered heteroaryl or a 4-7 membered heterocycloalkyl group, wherein the 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• each Rb23 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Rb23 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• each Re23 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, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-;
• R3 is selected from H, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa3, SRa3, NHORa3, C(O)Rb3, C(O)NRc3Rd3, C(O)NRc3(ORa3), C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(═NRe3)Rb3, C(═NRe3)NRc3Rd3, NRc3C(NRe3)NRc3Rd3, NRc3C(═NRe3)Rb3, NRc3S(O)Rb3, NRc3S(O)NRc3Rd3, NRc3S(O)2Rb3, NRc3S(O)(═NRe3)Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3, OS(O)(═NRe3)Rb3, and OS(O)2Rb3, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R3 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3A substituents;
• each Ra3, Rc3, and Rd3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra3, Rc3 and Rd3 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3A substituents;
• or, any Rc3 and Rd3 attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected R3A substituents;
• each Rb3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Rb3 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3A substituents;
• each Re3 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, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;
• each R3A is independently selected from halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa31, SRa31, NHORa31, C(O)Rb31, C(O)NRc31Rd31, C(O)NRc31(ORa31), C(O)ORa31, OC(O)Rb31, OC(O)NRc31Rd31, NRb31Rd31, NRc3NRc31Rd31, NRc31C(O)Rb31, NRc31C(O)ORa31, NRc31C(O)NRc31Rd31, C(═NRe31)Rb31, C(═NRe31)NRc31Rd31, NRc31C(═NRe31NRc31Rd31, NRc31C(═NRe31)Rb31, NRc31S(O)Rb31, NRc31S(O)NRb31Rd31, NRc31S(O)2Rb31, NRc31S(O)(═NRe31)Rb31 NRc31S(O)2NRc31Rd31, S(O)Rb31, S(O)NRc31Rd31, S(O)2Rb31, S(O)2NRc31Rd31, OS(O)(═NRe31)Rb31, and OS(O)2Rb31, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R3A are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3B substituents;
• each Ra31, Rc31, and Rd31 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra3, Rc31 and Rd31 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3B substituents;
• or, any Rc31 and Rd31 attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected R3B substituents;
• each Rb31 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Rb31 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3B substituents;
• each Re31 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, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;
• each R3B is independently selected from halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa32, SRa32, NHORa32C(O)Rb32, C(O)NRc32Rd32, C(O)NR32(ORa32), C(O)ORa32, OC(O)Rb32, OC(O)NRc32Rd32 NRc32Rd32, NRc32NRc32Rd32, NRb32C(O)Rb32, NR62C(O)ORa32, NR32C(O)NRc32Rd32, C(═NRe32)Rb32, C(═NRe32)NRc32Rd32, NRc32C(═NRe32NRc32Rd32, NRe32C(═NRe32)Rb32, NRe32S(O)Rb32, NRe32S(O)NRe32Rd32, NRe32S(O)2Rb32, NRc32S(O)(═NRe32)Rb32, NRc32S(O)2NRc32Rd32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, S(O)2NRe32Rd32, OS(O)(═NRe32)Rb32, and OS(O)2Rb32, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R3B are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3C substituents;
• each Ra32, R32, and Rd32 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra32, Rc32 and Rd32 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3C substituents;
• or, any Rc32 and Rd32 attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected R3C substituents;
• each Rb32 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Rb32 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R3C substituents;
• each Re32 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, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;
• each R3C is independently selected from halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, (4-7 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa33, SRa33, NHORa33, C(O)Rb33, C(O)NRc33Rd33, C(O)NRc33(ORa33), C(O)ORa33, OC(O)Rb33, OC(O)NRc33Rd33, NRc33Rd33, NRc33NRc33Rd33, NRc33C(O)Rb33, NRc33C(O)ORa33, NRc33C(O)NRc33Rd33, C(═NRe33)Rb33, C(═NRe33)NRc33Rd33, NRc33C(═NRe33)NRc33Rd33, NRb33C(═NRe33)Rb33, NRc33S(O)Rb33, NRc33S(O)NRb33Rd33, NRc33S(O)2Rb33, NRc33S(O)(═NRe33)Rb33, NRc33S(O)2NRc33Rd33, S(O)Rb33, S(O)NRc33Rd33, S(O)2Rb33, S(O)2NRc33Rd33, OS(O)(═NRe33)Rb33, and OS(O)2Rb33, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of R3C are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• each Ra33, Rc33, and Rd33 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Ra33, Rc33 and Rd33 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• or, any Rc33 and Rd33 attached to the same N atom, together with the N atom to which they are attached, form a 5-6 membered heteroaryl or a 4-7 membered heterocycloalkyl group, wherein the 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• each Rb33 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Rb33 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• each Re33 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, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-;
• R4 is selected from H, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa4, SRa4, NHORa4, C(O)Rb4, C(O)NRc4Rd4, C(O)NRc4(ORa4), C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, C(═NRe4)Rb4, C(═NRe4)NRc4Rd4, NRc4C(═NRe4)NRc4Rd4, NRc4C(═NRe4)Rb4, NRc4S(O)Rb4, NRc4S(O)NRc4Rd4, NRc4S(O)2Rb4, NRc4S(O)(═NRe4)Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, S(O)2NRc4Rd4, OS(O)(═NRe4)Rb4, and OS(O)2Rb4, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R4A substituents;
• each Ra4, Rc4, and Rd4 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra4, Rc4 and Rd4 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R4A substituents;
• or, any Rc4 and Rd4 attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected R4A substituents;
• each Rb4 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Rb4 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R4A substituents;
• each Re4 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, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;
• each R4A is independently selected from halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa41, SRa41, NHORa41, C(O)Rb41, C(O)NRc41Rd41, C(O)NRc41(ORa41), C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41NRc41Rd41, NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, C(═NRe41)Rb41, C(═NRe41)NRc41Rd41, NRc41C(═NRe41)NRc41Rd41, NRc41C(═NRe41)Rb41, NRc41S(O)Rb41, NRc41S(O)NRc4Rd41, NRc41S(O)2R41, NRc41S(O)(═NRe41)R41, NRc41S(O)2NRc41Rd41, S(O)Rb41, S(O)NRc41Rd41, S(O)2Rb41, S(O)2NRc41Rd41, OS(O)(═NRe41)R41, and OS(O)2Rb41, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4A are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R4B substituents;
• each Ra41, Rc41, and Rd41 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra41, Rc41 and Rd41 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R4B substituents;
• or, any Rc41 and Rd41 attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected R4B substituents;
• each Rb41 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Rb41 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R4B substituents;
• each Re41 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, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;
• each R4B is independently selected from halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa42, SRa42, NHORa42, C(O)Rb42, C(O)NRc42Rd42, C(O)NRc42(ORa42), C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42NRc42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, C(═NRe42)Rb42, C(═NRe42)NRc42Rd42, NR42C(═NRe42)NRc42Rd42, NRc42C(═NRe42)Rb42, NRc42S(O)Rb42, NRc42S(O)NRe42Rd42, NRc42S(O)2Rb42, NRc42S(O)(═NRe42)Rb42, NRc42S(O)2NRc42Rd42, S(O)Rb42, S(O)NRc42Rd42, S(O)2Rb42, S(O)2NRc42Rd42, OS(O)(═NRe42)Rb42, and OS(O)2Rb42, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R4B are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R4C substituents;
• each Ra42, R42, and Rd42 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra42, Rc42 and Ra42 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R4C substituents;
• or, any Rc42 and Rd42 attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected R4C substituents;
• each Rb42 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Rb42 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R4C substituents;
• each Re42 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, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;
• each R4C is independently selected from halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, (4-7 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa43, SRa43, NHORa43, C(O)Rb43, C(O)NRc43Rd43, C(O)NRc43(ORa43), C(O)ORa43, OC(O)Rb43, OC(O)NRc43Rd43, NRc43Rd43 NRc43NRc43Rd43, NRc43C(O)Rb43, NRc43C(O)ORa43, NRc43C(O)NRc43Rd43, C(═NRe43)Rb43, C(═NRe43)NRc43Rd43, NRc43C(═NRe43)NRc43Rd43, NRc43C(═NRe43)Rb43, NRc43S(O)Rb43, NRc43S(O)NRc43Rd43, NRc43S(O)2Rb43, NRc43S(O)(═NRe43)Rb43, NRc43S(O)2NRc43Rd43, S(O)Rb43, S(O)NRc43Rd43, S(O)2Rb43, S(O)2NRc43Rd43, OS(O)(═NRe43)Rb43, and OS(O)2Rb43, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of R4C are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• each Ra43, Rc43, and Rd43 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Ra43, Rc43 and Rd43 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• or, any Rc43 and Rd43 attached to the same N atom, together with the N atom to which they are attached, form a 5-6 membered heteroaryl or a 4-7 membered heterocycloalkyl group, wherein the 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• each Rb43 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of R43 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• each Re43 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, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-;
• R5 is selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R5 are each optionally substituted with 1, 2, 3, or 4 independently selected R5A substituents;
• each R5A is independently selected from halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa51, SRa51, NHORa51, C(O)Rb51, C(O)NRc51Rd51, C(O)NRc51(ORa51), C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, C(═NRe51)Rb51, C(═NRe51)NRc51Rd51, NRc51C(═NRe51)NRc51Rd51, NRc51C(═NRe51)Rb51, NRc51S(O)Rb51, NRc51S(O)NRc51Rd51, NRc51S(O)2Rb51, NRc51S(O)(═NRe51)Rb51, NRc51S(O)2NRc51Rd51, S(O)Rb51, S(O)NRc51Rd51, S(O)2Rb51, S(O)2NRc51Rd51, OS(O)(═NRe51)Rb51, and OS(O)2Rb51, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R5A are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R5B substituents;
• each Ra51, Rc51, and Rd51 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra51, Rc51 and Rd51 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R5B substituents;
• or, any Rc51 and Rd51 attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected R5B substituents;
• each Rb51 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Rb51 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R5B substituents;
• each Re51 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, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;
• each R5B is independently selected from halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa52, SRa52, NHORa52, C(O)Rb52, C(O)NRc52Rd52, C(O)NRc52(ORa52), C(O)ORa52, OC(O)Rb52, OC(O)NRc52Rd52, NRc52Rd52 NRc52NRc52Rd52 NRc52C(O)Rb52, NRc52C(O)ORa52, NRc52C(O)NRc52Rd52, C(═NRe52)Rb52, C(═NRe52)NRc52Rd52, NRc52C(═NRe52)NRc52Rd52 NRc52C(═NRe52)Rb52, NRc52S(O)Rb52, NRc52S(O)NRc52Rd52, NRc52S(O)2Rb52, NRc52S(O)(═NRe52)Rb52, NRc52S(O)2NRc52Rd52, S(O)Rb52, S(O)NRc52Rd52, S(O)2Rb52, S(O)2NRc52Rd52, OS(O)(═NRe52)Rb52, and OS(O)2Rb52, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R5B are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R5C substituents;
• each Ra52, Rc52, and Rd52 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra52, Rc52 and Rd52 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R5C substituents;
• or, any Re52 and Rd52 attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected R5C substituents;
• each Rb52 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Rb52 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R5C substituents;
• each Re52 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, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-;
• each R5C is independently selected from halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, (4-7 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa53, SRa53, NHORa53, C(O)Rb53, C(O)NRc53Rd53, C(O)NRc53(ORa53), C(O)ORa53, OC(O)Rb53, OC(O)NRc53Rd53, NRc53Rd53, NRc53NRc53Rd53, NRc53C(O)Rb53, NRc53C(O)ORa53, NRc53C(O)NRc53Rd53, C(═NRe53)Rb53, C(═NRe53)NRc53Rd53, NRc53C(═NRe53NRc53Rd53, NRc53C(═NRe53)Rb53, NRc53S(O)Rb53, NRc53S(O)NRc53Rd53, NRc53S(O)2Rb53, NRc53S(O)(═NRe53)R53, NRc53S(O)2NRc53Rd53, S(O)Rb53, S(O)NRc53Rd53, S(O)2Rb53, S(O)2NRc53Rd53, OS(O)(═NRe53)Rb53, and OS(O)2Rb53, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of R5C are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• each Ra53, Rc53, and Rd53 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Ra53, Rc53 and Rd53 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• or, any Rc53 and Rd53 attached to the same N atom, together with the N atom to which they are attached, form a 5-6 membered heteroaryl or a 4-7 membered heterocycloalkyl group, wherein the 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl group are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• each Rb53 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Rb53 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
• each Re53 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, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-;
• and
• each RM is independently selected from H, OH, halo, oxo, CN, C(O)OH, NH2, NO2, SF5, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-.