Alpha 4 beta 7 integrin modulators and uses thereof

Abstract

The application relates to small molecule compounds of the general Formula (I) and pharmaceutical compositions comprising them for the modulation of alpha 4 beta 7 integrin, useful for the treatment of inflammatory conditions such as inflammatory bowel disease, including ulcerative colitis and Crohn's disease.

Description

ALPHA 4 BETA 7 INTEGRIN MODULATORS AND USES THEREOFBACKGROUND OF THE INVENTION

[0001] Alpha 4 beta 7 integrin (α4β7), also known as Lymphocyte Peyer patch adhesion molecule (LPAM) is a powerful signaling molecule embedded in the cell membranes of immune cells. α4β7is responsible for T-cell homing into gut-associated lymphoid tissues by binding to mucosal vascular addressin cell adhesion molecule (MAdCAM) located on high endothelial venules of mucosal lymphoid organs. It has been demonstrated that α4β7is implicated in several immune system disorders, including inflammatory bowel disease (IBD) (including, e.g., Crohn’s disease (CD) and ulcerative colitis (UC)) and graft-versus-host disease (GVHD)).

[0002] α4β7is a clinically-validated target for IBD, with ENTYVIO (vedolizumab), an injectable anti -α4β7mAb, approved for the treatment of UC and CD. However, the accessibility of ENTYVIO is limited by the need for parenteral administration. Further, ENTYVIO causes a range of side effects (including nausea, vomiting, severe diarrhea, stomach cramps, weight loss, and pain), which can be difficult to manage due to ENTYVIO ’s long half-life. Therefore, there is a need for highly active and / or selective α4β7small molecule inhibitors that are orally bioavailable and have reduced side effects.SUMMARY OF THE INVENTION

[0003] In one aspect, provided herein is a compound having the structure of Formula (I):or a pharmaceutically acceptable salt thereof, wherein:X1, X2, X3, and X4are each independently selected from N and C(R1), wherein at least one of X1, X2, and X3is C(R1);R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -OC(O)N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)C(O)N(R11)2-N(R11)C(S)N(R11)2, -N(R11)S(O)2(R11) , -S(O)R11, -S(O)2R11, -NO2,N(R11)2, -NO2, and -CN;C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN;R2is hydrogen or C1-6alkyl;R3aand R3bare each independently selected from hydrogen, halogen, -OR12, -SR12, -N(R12)2, -C(0)R12, -NO2, -CN, and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, -SR12, -N(R12)2, -C(0)R12, -NO2, and -CN;R4is hydrogen or C1-6alkyl;Y1is selected from -L1-, and -X5-L2-, wherein:L1is selected from C1-6alkylene, C2-6 alkenylene, and C1-6carbocyclene, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(0)R13, -N02, and -CN;X5is -0-, -N(R14)-, or -S-;L2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(0)R15, -NO2, and -CN;C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7- 10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -SR16, -N(R16)(R18), -C(0)R16, -C(0)0R18, -0C(0)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, =0, =S, =NR16, -N3, and -CN;C1 alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, =s, =NR16, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl;C4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, =0, =S, =NR16, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1- 4 haloalkyl; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected fromhalogen, C1-6alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(O)R16, -NO2, =0, =S, =NR16, -N3, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10- membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10- membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2;Y2is selected from a bond, -0-, -S-, -N(R19)-, and C1-6alkylene;Z is selected from a bond, -C(0)-, -C(R20)2-, -C(O)C(R20)2-, -C(=N-CN)-, -C(0)0-, -C(O)O-Ci- 3 alkylene-, -C(O)N(R20)-, -C(S)-, -C(S)N(R20)-, -S(0)-, and -8(0)2-;B is selected from C3-14 carbocycle and 3- to 14-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -NO2, =0, =S, =NR21, -N3, and -CN;R11, R12, R13, R14, R15, R16, R19, and R20are each independently selected at each occurrence from hydrogen, C1-6alkyl, C3-6 carbocycle, and 3- to 6-memebred heterocycle, wherein each of the C1-6alkyl, C3-6 carbocycle, and 3- to 6-memebred heterocycle are optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R17is independently selected at each occurrence from: hydrogen;Ci alkyl substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN; andC2-6 alkyl, and C3-6carbocycle, wherein each of the C2-6 alkyl and C3-6carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R18is independently selected at each occurrence from C1-6alkyl and C3-6carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R21is independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC<O)N(R22)2, -C(O)N(R22)2, -N(R22)C(O)R22, -N(R22)C(O)OR22, -N(R22)C(O)N(R22)2, -N(R22)C:(S)N(R22)2, -N(R22)S(O)2(R22), -S<O)R22, -S(O)2R22, -S(O)2N(R22)2, -NO2,=0, =S, =NR22, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC(O)N(R22)2, -C(O)N(R22)2, -N(R22)C(O)R22, -N(R22)C(0)0R22, -N(R22)C(O)N(R22)2, -N(R22)C:(S)N(R22)2, -N(R22)S(O)2(R22), -S<O)R22, -S(O)2R22, -S(O)2N(R22)2, -NO2,=0, =S, =NR22, -N3, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle; andR22is independently selected at each occurrence from hydrogen, C1-6alkyl, C1-6haloalkyl, Ci- 6 hydroxyalkyl, and C1-6aminoalkyl.

[0004] In another aspect, provided herein is a compound having the structure of Formula (I-a):or a pharmaceutically acceptable salt thereof, wherein:X1, X2, X3, and X4are each independently selected from N and C(R1), wherein at least one of X1, X2, and X3is C(R1);R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -0C(0)N(R11)2, -C(0)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11,-N(R11)C(O)N(R11)2, -N(R11)C(S)N(R11)2, -N(R11)S(O)2(R11), -S(O)R11, -S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN;R2is hydrogen or C1-6alkyl;R3aand R3bare each independently selected from hydrogen, halogen, -OR12, -SR12, -N(R12)2, -C(0)R12, -NO2, -CN, and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -NO2, and -CN;R4is hydrogen or C1-6alkyl;Y1is selected from -L1- and -X5-L2-, wherein:L1is C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(0)R13, -NO2, and -CN;X5is -0-, -N(R14)-, or -S-;L2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(0)R15, -N02, and -CN;C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7- 10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -SR16, -N(R16)(R18), -C(0)R16, -C(0)0R18, -0C(0)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16,-N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, =0, =S, =NR16, -N3, and -CN;C1 alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -N3,and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl;C2-3alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, =S, =NR16, -N3, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1- 4 haloalkyl;C4-6 alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -NCR16)2, -C(0)R16, -C(O)OR16, -OC(O)R16, -0C(0)N(R16)2, -C(0)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2NCR16)2, -NO2, =O, =S, =NR16, -N3, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1- 4 haloalkyl; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(O)R16, -NO2, =0, =S, =NR16, -N3, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10- membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10- membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2;Y2is selected from a bond, -0-, -S-, -N(R19)-, and C1-6alkylene;Z is selected from a bond, -C(0)-, -C(R20)2-, -C(O)C(R20)2-, -C(=N-CN)-, -C(0)0-, -C(O)N(R20)-, -C(S)-, -C(S)N(R20)-, -S(0)-, and -8(0)2-;B is selected from C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21,-N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -NO2, =0, =S, =NR21, -N3, and -CN;R11, R12, R13, R14, R15, R16, R19, and R20are each independently selected at each occurrence from hydrogen, C1-6alkyl, and C3-6 carbocycle, wherein each of the C1-6alkyl and C3- 6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R17is independently selected at each occurrence from: hydrogen;Ci alkyl substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN; andC2-6 alkyl, and C3-6carbocycle, wherein each of the C2-6 alkyl and C3-6carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R18is independently selected at each occurrence from C1-6alkyl and C3-6carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R21is independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC<O)N(R22)2, -C(O)N(R22)2, -N(R22)C(O)R22, -N(R22)C(O)OR22, -N(R22)C(O)N(R22)2, -N(R22X:(S)N(R22)2, -N(R22)S(O)2(R22), -S<O)R22, -S(O)2R22, -S(O)2N(R22)2, -NO2,=0, =S, =NR22, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC(O)N(R22)2, -C(O)N(R22)2, -N(R22)C(O)R22, -N(R22)C(O)OR22, -N(R22)C(O)N(R22)2, -N(R22)C(S)N(R22)2, -N(R22)S(O)2(R22), -S(O)R22, -S(O)2R22, -S(O)2N(R22)2, -NO2,=0, =S, =NR22, -N3, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle; andR22is independently selected at each occurrence from hydrogen, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, and C1-6aminoalkyl.

[0005] In another aspect, provided herein is a pharmaceutical composition comprising a compound or salt of Formula (I) and a pharmaceutically acceptable excipient.

[0006] In another aspect, provided herein is a method of modulating alpha 4 beta 7 integrin in a subject in need thereof, comprising administering to the subject a compound or salt of Formula (I) or a pharmaceutical composition comprising a compound or salt of Formula (I) and a pharmaceutically acceptable excipient.

[0007] In another aspect, provided herein is a method of treating an inflammatory disease or condition in a subject in need thereof, comprising administering to the subject a compound or salt of Formula (I) or a pharmaceutical composition comprising a compound or salt of Formula (I) and a pharmaceutically acceptable excipient.

[0008] In some embodiments, the inflammatory disease or condition is selected from: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, graft-versus-host disease, type1 diabetes, immune-mediated colitis, checkpoint inhibitor induced colitis, and primary sclerosing cholangitis.

[0009] In another aspect, provided herein is a method of evaluating a test molecule comprising:(a) contacting the test molecule with a genetically modified cell comprising a mutation in the ITGB7 gene, the genetically modified cell expressing a functional alpha 4 beta 1 integrin; and(b) determining whether the test molecule binds to the functional alpha 4 beta 1 integrin; wherein the mutation in the ITGB7 gene prevents expression of a functional alpha 4 beta 7 integrin.

[0010] In another aspect, provided herein is a method of evaluating a test molecule comprising:(a) contacting the test molecule with a genetically modified cell comprising a mutation in the ITGB7 gene, the genetically modified cell expressing a functional alpha 4 beta 1 integrin; and(b) determining whether the test molecule inhibits the functional alpha 4 beta 1 integrin; wherein the mutation in the ITGB7 gene prevents expression of a functional alpha 4 beta 7 integrin.

[0011] In some embodiments, the method further comprises(c) contacting the test molecule with a second genetically modified cell comprising a mutation in the ITGB1 gene, the genetically modified cell expressing a functional alpha 4 beta 7 integrin; and(d) determining whether the test molecule binds to the functional alpha 4 beta 7 integrin; wherein the mutation in the ITGB1 gene prevents expression of a functional alpha 4 beta 1 integrin

[0012] In another aspect, provided herein is a method of evaluating a test molecule comprising:(a) contacting the test molecule with a genetically modified cell comprising a mutation in the ITGB1 gene, the genetically modified cell expressing a functional alpha 4 beta 7 integrin; and(b) determining whether the test molecule binds to the functional alpha 4 beta 7 integrin; wherein the mutation in the ITGB1 gene prevents expression of a functional alpha 4 beta 1 integrin.

[0013] In another aspect, provided herein is a method of evaluating a test molecule comprising: (a) contacting the test molecule with a genetically modified cell comprising a mutation in the ITGB7 gene, the genetically modified cell expressing a functional alpha 4 beta 1 integrin; and(b) determining whether the test molecule inhibits the functional alpha 4 beta 1 integrin; wherein the mutation in the ITGB7 gene prevents expression of a functional alpha 4 beta 7 integrin.

[0014] In another aspect, provided herein is a method of evaluating a test molecule comprising:(a) contacting the test molecule with a genetically modified cell comprising a mutation in the ITGB1 gene, the genetically modified cell expressing a functional alpha 4 beta 7 integrin; and(b) determining whether the test molecule binds to the functional alpha 4 beta 7 integrin; wherein the mutation in the ITGB1 gene prevents expression of a functional alpha 4 beta 1 integrin.

[0015] In another aspect, provided herein is a method of evaluating a test molecule comprising:(a) contacting the test molecule with a genetically modified cell comprising a mutation in the ITGB1 gene, the genetically modified cell expressing a functional alpha 4 beta 7 integrin; and(b) determining whether the test molecule inhibits the functional alpha 4 beta 7 integrin; wherein the mutation in the ITGB7 gene prevents expression of a functional alpha 4 beta 1 integrin.

[0016] In some embodiments, the method further comprises(c) contacting the test molecule with a second genetically modified cell comprising a mutation in the ITGB7 gene, the genetically modified cell expressing a functional alpha 4 beta 1 integrin; and(d) determining whether the test molecule binds to the functional alpha 4 beta 1 integrin; wherein the mutation in the ITGB7 gene prevents expression of a functional alpha 4 beta 7 integrin.

[0017] In some embodiments, the genetically modified cell comprises a stable ITGB7 genetic knockout. In some embodiments, the genetically modified cell does not comprise a natural alpha 4 beta 7 integrin or a modified alpha 4 beta 7 integrin. In some embodiments, the genetically modified cell does not comprise a modified alpha 4 beta 7 integrin. In some embodiments, the method does not comprise a transient knock-down of the ITGB7 gene. In some embodiments, expression of the HGB7 gene is not knocked down by use of an oligonucleotide. In some embodiments, the mutation in the ITGB7 gene comprises a nucleotide insertion or a nucleotide deletion. In some embodiments, the mutation in the HGB7 gene comprises a nucleotide insertion. In some embodiments, the mutation in the ITGB7 gene comprises a nucleotide deletion. In some embodiments, the mutation in the ITGB7 genecomprises a nucleotide insertion and a nucleotide deletion. In some embodiments, the mutation in the ITGB7 gene comprises a nucleotide substitution. In some embodiments, the mutation in the ITGB7 gene was generated using CRISPR-Cas9. In some embodiments, the genetically modified cell expresses a wild-type alpha 4 beta 1 integrin. In some embodiments, the method further comprises determining whether the test molecule binds to the functional alpha 4 beta 1 integrin.

[0018] In some embodiments, the genetically modified cell is derived from a lymphocyte. In some embodiments, the genetically modified cell is derived from a B lymphocyte. In some embodiments, the genetically modified cell is derived from a RPMI 8866 cell. In some embodiments, the mutation in the ITGB7 gene was generated using CRISPR-Cas9. In some embodiments, the test molecule is a small molecule. In some embodiments, the test molecule comprises an RGB mimic. In some embodiments, the test molecule binds to alpha 4 beta 1 integrin selectively over alpha 4 beta 7 integrin. In some embodiments, the test molecule binds to alpha 4 beta 7 integrin selectively over alpha 4 beta 1 integrin.INCORPORATION BY REFERENCE

[0019] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.DETAILED DESCRIPTION OF THE INVENTION

[0020] Integrin alpha 4 beta 7 is an integrin family adhesion receptor that shares subunits with alpha 4 beta 1 (VLA4) and the E-Cadherin receptor, alpha E beta 7. α4β7is critical for directing immune cells to intestinal mucosa, and is induced during T cell activation in Peyer’s patches or mesenteric lymph nodes. α4β7is a clinically-validated target for IBD, with selective α4β7inhibition resulting in significant anti-inflammatory effects and reduction in symptoms. However, off-target binding to α4β1can result in significant dose-limiting side effects. For example, TYSABRI (natalizumab), binds to both α4β7and α4β1, and the binding of α4β1has been linked to progressive multifocal leukoencephalopathy, which resulted in the FDA restricting the use of TYSABRI in IBD.

[0021] In some aspects, the present disclosure provides an orally-available α4β7integrin antagonist designed in a manner designed to mimic the anti-inflammatory actions of ENTYVIO, specifically its high selectivity for α4β7over α4β1. For example, in some embodiments, the present disclosure provides compounds having over 100-fold selectivity for(I4B7 over 0461. In some embodiments, the present disclosure provides compounds having over 1,000-fold selectivity for (I4B7 over 0461.Ulcerative Colitis Disease

[0022] UC is a form of IBD characterized by inflammation and ulcers in the large intestine. The clinical symptoms of UC are diarrhea and bloody stool. Its clinical course is marked by exacerbations and remissions, which may occur spontaneously or in response to dietary changes, alterations in treatment regimens, other illnesses, or stress.

[0023] UC can be debilitating and can sometimes lead to life-threatening complications. Frequent diarrhea and bloody stools can lead to weight loss, dehydration and anemia. Persistent UC is associated with an increased risk of developing colon cancer. The Centers for Disease Control estimates that there are three million individuals in the United States with IBD, of which roughly half have UC. A similar number of individuals in Europe are estimated to have UC.

[0024] UC is typically treated with anti-inflammatory drugs starting with more moderate and locally-delivered drugs, and progressing to systemic immunosuppressive drugs for patients with refractory disease. First line therapy for patients with mild disease consists of 5- aminosalicylates such as mesalamine and sulfasalazine. Patients with more severe disease are treated with systemic corticosteroids, with the intent of inducing remission and transitioning patients to better-tolerated drugs such as 5-aminosalicylates for maintenance. Some patients may be treated with systemic immunomodulatory drugs such as azathioprine, cyclosporine and XELJANZ (tofacitinib). Anti-inflammatory biologies such as TNFa antagonists REMICADE (infliximab), HUMIRA (adalimumab) and SIMPONI (golimumab) and the IL-12 / IL-23 antagonist STELARA (ustekinumab) are effective in inducing remission in patients with moderate to severe UC.

[0025] ENTYVIO (vedolizumab), a monoclonal antibody that selectively targets α4β7, was first approved by the FDA to treat UC and CD in 2014. In clinical trials, approximately 30% of patients receiving ENTYVIO achieved remission at the end of one year of treatment.ENTYVIO is administered as a 30-minute intravenous infusion at zero, two and six weeks, then every eight weeks thereafter. Long term therapy is generally well-tolerated in patients, but frequent dose adjustments have been reported to be required to maintain efficacy.Crohn’s Disease

[0026] CD is a chronic inflammatory disease that most commonly affects the end of the small intestine and the beginning of the large intestine, although it may involve any part of the gastrointestinal tract. Both CD and UC are types of IBD and many of the symptoms and demographics overlap. In addition to the potential of CD developing in other segments of the intestine, CD differs from UC in that there can be normal healthy tissue in between patches of diseased tissue in CD, unlike UC where the inflammation is continuous. CD can also occur in all layers of the intestinal wall unlike UC which is limited to the inner most layer. It is estimated that there are 1.5 million individuals in the United States and 1.1 million individuals in Europe with CD.

[0027] The treatment paradigm for CD is very similar to that of UC with currently approved therapies focused on anti-inflammatory agents. Nearly 60% of CD patients will require surgery within twenty years of diagnosis to treat complications such as fistulas, or abnormal connections between body parts, life-threatening bleeding and intestinal obstructions.

[0028] While there are numerous approved therapeutics for UC and CD, there remains a significant unmet medical need for patients and clinicians to effectively and conveniently manage these chronic diseases, which could be facilitated by effective oral therapies.

[0029] In some aspects, the compounds of the present disclosure are used for the treatment and / or prevention of IBD. In some aspects of the present disclosure, the compounds provided herein are used for the treatment and / or prevention of UC. In some aspects of the present disclosure, the compounds provided herein are used for the treatment and / or prevention of CD.Definitions

[0030] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference.

[0031] As used in the specification and claims, the singular form “a”, “an” and “the” includes plural references unless the context clearly dictates otherwise.

[0032] “Alkyl” refers to a straight or branched hydrocarbon chain monovalent radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, and preferably having from one to twelve carbon atoms (i.e., C1-C12 alkyl). The alkyl is attached to the remainder of the molecule through a single bond. In certain embodiments, an alkyl comprises one to twelve carbon atoms (i.e., C1-C12 alkyl). In certain embodiments, an alkyl comprises one to eight carbon atoms (i.e., C1-C8 alkyl). In other embodiments, an alkyl comprises one to fivecarbon atoms (i.e., C1-C5 alkyl). In other embodiments, an alkyl comprises one to four carbon atoms (i.e., C1-C4 alkyl). In other embodiments, an alkyl comprises one to three carbon atoms (i.e., C1-C3 alkyl). In other embodiments, an alkyl comprises one to two carbon atoms (i.e., C1- C2 alkyl). In other embodiments, an alkyl comprises one carbon atom (i.e., Ci alkyl). In other embodiments, an alkyl comprises five to fifteen carbon atoms (i.e., C5-C15 alkyl). In other embodiments, an alkyl comprises five to eight carbon atoms (i.e., Cs-Cs alkyl). In other embodiments, an alkyl comprises two to five carbon atoms (i.e., C2-C5 alkyl). In other embodiments, an alkyl comprises three to five carbon atoms (i.e., C3-C5 alkyl). For example, the alkyl group may be attached to the rest of the molecule by a single bind, such as, methyl, ethyl, 1 -propyl (zz-propyl), 1 -methylethyl (iso-propyl), 1 -butyl (n-butyl), 1 -methylpropyl (sec- butyl), 2-methylpropyl (iso-butyl), 1,1 -dimethylethyl (tert-butyl), 1 -pentyl (w-pentyl), and the like.

[0033] “Alkenyl” refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having from two to twelve carbon atoms (i.e., C2-C12 alkenyl). In certain embodiments, an alkenyl comprises two to eight carbon atoms (i.e., C2-C8 alkenyl). In certain embodiments, an alkenyl comprises two to six carbon atoms (i.e., C1-C6 alkenyl). In other embodiments, an alkenyl comprises two to four carbon atoms (i.e., C2-C4 alkenyl). The alkenyl is attached to the rest of the molecule by a single bond, for example, ethenyl (i.e., vinyl), prop-l-enyl (i.e., allyl), but-l-enyl, pent-l-enyl, penta- 1,4-dienyl, and the like.

[0034] “Alkynyl” refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having from two to twelve carbon atoms (i.e., C2-C12 alkynyl). In certain embodiments, an alkynyl comprises two to eight carbon atoms (i.e., C2-C8 alkynyl). In other embodiments, an alkynyl comprises two to six carbon atoms (i.e., C1-C6 alkynyl). In other embodiments, an alkynyl comprises two to four carbon atoms (i.e., C2-C4 alkynyl). The alkynyl is attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

[0035] “Alkylene” refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturation, and preferably having from one to twelve carbon atoms, for example, methylene, (methyl)methylene, ethylene, propylene, butylene, and the like. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. Alkylene chain may be optionally substituted by one or more substituents such as thosesubstituents described herein. In certain embodiments, an alkylene comprises one to ten carbon atoms (i.e., C1-C10 alkylene). In certain embodiments, an alkylene comprises one to eight carbon atoms (i.e., C1-C8 alkylene). In other embodiments, an alkylene comprises one to five carbon atoms (i.e., C1-C5 alkylene). In other embodiments, an alkylene comprises one to four carbon atoms (i.e., C1-C4 alkylene). In other embodiments, an alkylene comprises one to three carbon atoms (i.e., C1-C3 alkylene). In other embodiments, an alkylene comprises one to two carbon atoms (i.e., C1-C2 alkylene). In other embodiments, an alkylene comprises one carbon atom (i.e., Ci alkylene). In other embodiments, an alkylene comprises five to eight carbon atoms (i.e., C5-C8 alkylene). In other embodiments, an alkylene comprises two to five carbon atoms (i.e., C2-C5 alkylene). In other embodiments, an alkylene comprises three to five carbon atoms (i.e., C3-C5 alkylene).

[0036] “Alkenylene” refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having from two to twelve carbon atoms. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. Alkenylene chain may be optionally substituted by one or more substituents such as those substituents described herein. In certain embodiments, an alkenylene comprises two to ten carbon atoms (i.e., C2-C10 alkenylene). In certain embodiments, an alkenylene comprises two to eight carbon atoms (i.e., C2-C8 alkenylene). In other embodiments, an alkenylene comprises two to five carbon atoms (i.e., C2-C5 alkenylene). In other embodiments, an alkenylene comprises two to four carbon atoms (i.e., C2-C4 alkenylene). In other embodiments, an alkenylene comprises two to three carbon atoms (i.e., C2-C3 alkenylene). In other embodiments, an alkenylene comprises two carbon atom (i.e., C2 alkenylene). In other embodiments, an alkenylene comprises five to eight carbon atoms (i.e., C5-C8 alkenylene). In other embodiments, an alkenylene comprises three to five carbon atoms (i.e., C3-C5 alkenylene).

[0037] “Alkynylene” refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having from two to twelve carbon atoms. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. Alkynylene chain may be optionally substituted by one or more substituents such as those substituents described herein. In certain embodiments, an alkynylene comprises two to ten carbon atoms (i.e., C2-C10 alkynylene). In certain embodiments, an alkynylene comprises two to eight carbon atoms (i.e., C2-C8 alkynylene). In other embodiments,an alkynylene comprises two to five carbon atoms (i.e., C2-C5 alkynylene). In other embodiments, an alkynylene comprises two to four carbon atoms (i.e., C2-C4 alkynylene). In other embodiments, an alkynylene comprises two to three carbon atoms (i.e., C2-C3 alkynylene). In other embodiments, an alkynylene comprises two carbon atoms (i.e., C2 alkynylene). In other embodiments, an alkynylene comprises five to eight carbon atoms (i.e., C5-C8 alkynylene). In other embodiments, an alkynylene comprises three to five carbon atoms (i.e., C3-C5 alkynylene).

[0038] The term “Cx.y” when used in conjunction with a chemical moiety, such as alkyl, alkenyl, or alkynyl is meant to include groups that contain from x to y carbons in the chain. For example, the term “C1-6alkyl” refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain alkyl and branched-chain alkyl groups that contain from 1 to 6 carbons. The term -Cx.yalkylene- refers to a substituted or unsubstituted alkylene chain with from x to y carbons in the alkylene chain. For example, -C1-6alkylene- may be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any one of which is optionally substituted.

[0039] The terms “Cx.yalkenyl” and “Cx.yalkynyl” refer to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond, respectively. The term -Cx.yalkenylene- refers to a substituted or unsubstituted alkenylene chain with from x to y carbons in the alkenylene chain. For example, -C2-6 alkenylene- may be selected from ethenylene, propenylene, butenylene, pentenylene, and hexenylene, any one of which is optionally substituted. An alkenylene chain may have one double bond or more than one double bond in the alkenylene chain. The term -Cx.yalkynylene- refers to a substituted or unsubstituted alkynylene chain with from x to y carbons in the alkynylene chain. For example, -C2-6 alkynylene- may be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, any one of which is optionally substituted. An alkynylene chain may have one triple bond or more than one triple bond in the alkynylene chain.

[0040] The term “carbocycle” as used herein refers to a saturated, unsaturated or aromatic ring in which each atom of the ring is carbon. Carbocycle include 3- to 10-membered monocyclic rings and 6- to 12-membered bicyclic rings. Each ring of a bicyclic carbocycle may be selected from saturated, unsaturated, and aromatic rings. Bicyclic carbocycles may be fused, bridged or spiro-ring systems. In some embodiments, the carbocycle is an aryl. In some embodiments, the carbocycle is a cycloalkyl. In some embodiments, the carbocycle is a cycloalkenyl. In an exemplary embodiment, an aromatic ring, e.g., phenyl, may be fused to a saturated orunsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated and aromatic bicyclic rings, as valence permits, are included in the definition of carbocyclic. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Carbocycle may be optionally substituted by one or more substituents such as those substituents described herein.

[0041] “Cycloalkyl” refers to a stable fully saturated monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, and preferably having from three to twelve carbon atoms (i.e., C3-12 cycloalkyl). In certain embodiments, a cycloalkyl comprises three to ten carbon atoms (i.e., C3-10 cycloalkyl). In other embodiments, a cycloalkyl comprises five to seven carbon atoms (i.e., C5-7 cycloalkyl). The cycloalkyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkyls include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl radicals include, for example, adamantyl, norbomyl (i.e., bicyclo[2.2.1]heptanyl), norbomenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. Cycloalkyl may be optionally substituted by one or more substituents such as those substituents described herein.

[0042] “Cycloalkenyl” refers to a stable unsaturated non-aromatic monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, preferably having from three to twelve carbon atoms and comprising at least one double bond (i.e., C3-12 cycloalkenyl). In certain embodiments, a cycloalkenyl comprises three to ten carbon atoms (i.e., C3-10 cycloalkenyl). In other embodiments, a cycloalkenyl comprises five to seven carbon atoms (i.e., C5-7 cycloalkenyl). The cycloalkenyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyls include, e.g., cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Cycloalkenyl may be optionally substituted by one or more substituents such as those substituents described herein.

[0043] “Aryl” refers to a radical derived from an aromatic monocyclic or aromatic multicyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or aromatic multicyclic hydrocarbon ring system contains only hydrogen and carbon and from five to eighteen carbon atoms, where at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic, delocalized (4n+2) p-electron system in accordance with the Huckel theory. The ring system from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin and naphthalene. Aryl maybe optionally substituted by one or more substituents such as those substituents described herein.

[0044] A “Cx-y carbocycle” is meant to include groups that contain from x to y carbons in a ring. For example, the term “C3-6 carbocycle” can be a saturated, unsaturated or aromatic ring system that contains from 3 to 6 carbon atoms — any of which is optionally substituted as provided herein.

[0045] The term “heterocycle” as used herein refers to a saturated, unsaturated, non-aromatic or aromatic ring comprising one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3- to 10-membered monocyclic rings and 6- to 12- membered bicyclic rings. Each ring of a bicyclic heterocycle may be selected from saturated, unsaturated, and aromatic rings. In some embodiments, the heterocycle comprises at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocycle comprises at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocycle comprises at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heterocycle comprises at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. The heterocycle may be attached to the rest of the molecule through any atom of the heterocycle, valence permitting, such as a carbon or nitrogen atom of the heterocycle. In some embodiments, the heterocycle is a heteroaryl. In some embodiments, the heterocycle is a heterocycloalkyl. Exemplary heterocycles include pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiophenyl, oxazolyl, thiazolyl, morpholinyl, indazolyl, indolyl, and quinolinyl. Heterocycle may be optionally substituted by one or more substituents such as those substituents described herein. Bicyclic heterocycles may be fused, bridged or spiro-ring systems. In an exemplary embodiment, a heterocycle, e.g., pyridyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Heterocycle may be optionally substituted by one or more substituents such as those substituents described herein.

[0046] “Heterocycloalkyl” refers to a stable 3 to 12 membered non-aromatic ring radical that comprises two to twelve carbon atoms and at least one heteroatom wherein each heteroatom may be selected from N, O, Si, P, B, and S atoms. In some embodiments, the heterocycloalkyl comprises at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocycloalkyl comprises at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocycloalkyl comprises at least one heteroatom selected from oxygen, sulfur, or any combination thereof. Insome embodiments, the heterocycloalkyl comprises at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. The heterocycloalkyl may be selected from monocyclic or bicyclic, and fused or bridged ring systems. The heteroatoms in the heterocycloalkyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quatemized. The heterocycloalkyl radical is partially or fully saturated. The heterocycloalkyl is attached to the rest of the molecule through any atom of the heterocycloalkyl, valence permitting, such as any carbon or nitrogen atoms of the heterocycloalkyl. Examples of heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thienyl[l,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2- oxopiperazinyl, 2oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4- piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxothiomorpholinyl, and 1,1- dioxothiomorpholinyl. Heterocycloalkyl may be optionally substituted by one or more substituents such as those substituents described herein.

[0047] The term “heteroaryl” refers to a radical derived from a 3- to 12-membered aromatic ring radical that comprises one to eleven carbon atoms and at least one heteroatom wherein each heteroatom may be selected from N, O, and S. In some embodiments, the heteroaryl comprises at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heteroaryl comprises at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heteroaryl comprises at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heteroaryl comprises at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. As used herein, the heteroaryl ring may be selected from monocyclic or bicyclic and fused or bridged ring systems rings wherein at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic, delocalized (4n+2) p-electron system in accordance with the Huckel theory. The heteroatom(s) in the heteroaryl radical may be optionally oxidized. One or more nitrogen atoms, if present, are optionally quatemized. The heteroaryl may be attached to the rest of the molecule through any atom of the heteroaryl, valence permitting, such as a carbon or nitrogen atom of the heteroaryl. Heteroaryl includes aromatic single ring structures, preferably 5- to 6-membered rings, whose ring structures include at least one heteroatom, preferably one to four heteroatoms, more preferably one or two heteroatoms. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine, and the like.Heteroaryl may be optionally substituted by one or more substituents such as those substituents described herein. Heteroaryl also includes polycyclic ring systems having two or more rings in which two or more atoms are common to two adjoining rings wherein at least one of the rings is heteroaromatic, e.g., the other rings can be aromatic or non-aromatic carbocyclic, or heterocyclic. Heteroaryl may be optionally substituted by one or more substituents such as those substituents described herein.

[0048] An “X-membered heterocycle” refers to the number of endocylic atoms, i.e., X, in the ring. For example, a 5-membered heteroaryl ring or 5-membered aromatic heterocycle has 5 endocyclic atoms, e.g., triazole, oxazole, thiophene, etc.

[0049] “Alkoxy” refers to a radical bonded through an oxygen atom of the formula -O-alkyl, where alkyl is an alkyl chain as defined above.

[0050] “Halo” or “halogen” refers to halogen substituents such as bromo, chloro, fluoro and iodo substituents.

[0051] As used herein, the term “haloalkyl” or “haloalkane” refers to an alkyl radical, as defined above, that is substituted by one or more halogen radicals, for example, trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, l-fluoromethyl-2-fluoroethyl, and the like. In some embodiments, the alkyl part of the fluoroalkyl radical is optionally further substituted. Examples of halogen substituted alkanes (“haloalkanes”) include halomethane (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), di-and trihalomethane (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2- haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combinations of alkanes (or substituted alkanes) and halogens (e.g., Cl, Br, F, and I). When an alkyl group is substituted with more than one halogen radicals, each halogen may be independently selected for example, 1 -chloro, 2-fluoroethane.

[0052] The term “substituted” refers to moieties having substituents replacing a hydrogen on one or more carbons or substitutable heteroatoms, e.g., an NH or NH2 of a compound. It will be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, i.e., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. In certain embodiments, substituted refers to moieties having substituents replacing two hydrogen atoms on the same carbon atom, such as substituting the two hydrogen atoms on a single carbon with an oxo, imino or thioxo group. As used herein, the term “substituted” iscontemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds.

[0053] In some embodiments, substituents may include any substituents described herein, for example: halogen, hydroxy, oxo (=0), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-0H), hydrazino(=N-NH2), -Rb-0Ra, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(0)N(Ra)2, -Rb-0-Rc-C(0)N(Ra)2, -Rb-N(Ra)C(O) ORa, -Rb-N(Ra)C(0)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2), and -Rb-S(O)tN(Ra)2(where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl any of which may be optionally substituted by alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=0), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo(=N-OH), hydrazine(=N- NH2), -Rb-0Ra, -Rb-OC(O)-Ra, -Rb-0C(0)-0Ra, -Rb-0C(0)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(0)Ra, - Rb-C(0)0Ra, -Rb-C(0)N(Ra)2, -Rb-0-Rc-C(0)N(Ra)2, -Rb-N(Ra)C(0)0Ra, -Rb-N(Ra)C(0)Ra, - Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(O)tN(Ra)2(where t is 1 or 2); wherein each Rais independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each Ra, valence permitting, may be optionally substituted with alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=0), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-0H), hydrazme(=N-NH2), -Rb-0Ra, -Rb-0C(0)-Ra, -Rb-0C(0)-0Ra, -Rb-0C(0)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(0)Ra, -Rb-C(0)0Ra, -Rb-C(0)N(Ra)2, - Rb-0-Rc-C(0)N(Ra)2, -Rb-N(Ra)C(0)0Ra, -Rb-N(Ra)C(0)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(0)tN(Ra)2(where t is 1 or 2); and wherein each Rbis independently selected from a direct bond or a straight or branched alkylene, alkenylene, or alkynylene chain, and each Rcis a straight or branched alkylene, alkenylene or alkynylene chain. It will be understood by those skilled in the art that substituents can themselves be substituted, if appropriate.

[0054] The term “salt” or “pharmaceutically acceptable salt” refers to salts derived from a variety of organic and inorganic counter ions well known in the art. Pharmaceuticallyacceptable acid addition salts can be formed with inorganic acids and organic acids. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases.

[0055] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0056] The phrase “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier” as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient.

[0057] The terms “subject,” “individual,” and “patient” may be used interchangeably and refer to humans, the as well as non-human mammals (e.g., non-human primates, canines, equines, felines, porcines, bovines, ungulates, lagomorphs, and the like). In various embodiments, the subject can be a human (e.g., adult male, adult female, adolescent male, adolescent female, male child, female child) under the care of a physician or other health worker in a hospital, as an outpatient, or other clinical context. In certain embodiments, the subject may not be under the care or prescription of a physician or other health worker.

[0058] As used herein, the phrase “a subject in need thereof’ refers to a subject, as described infra, that suffers from, or is at risk for, a pathology to be prophylactically or therapeutically treated with a compound or salt described herein.

[0059] The terms “administer”, “administered”, “administers” and “administering” are defined as providing a composition to a subject via a route known in the art, including but not limited to intravenous, intraarterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal routes of administration. In certain embodiments, oral routes of administering a composition can be used. The terms ““administer”, “administered”, “administers” and “administering” a compound should be understood to mean providing a compound of the invention or a prodrug of a compound of the invention to the individual in need.

[0060] As used herein, “treatment” or “treating” refers to an approach for obtaining beneficial or desired results with respect to a disease, disorder, or medical condition including, but not limited to, a therapeutic benefit and / or a prophylactic benefit. In certain embodiments,treatment or treating involves administering a compound or composition disclosed herein to a subject. A therapeutic benefit may include the eradication or amelioration of the underlying disorder being treated. Also, a therapeutic benefit may be achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder, such as observing an improvement in the subject, notwithstanding that the subject may still be afflicted with the underlying disorder. In certain embodiments, for prophylactic benefit, the compositions are administered to a subject at risk of developing a particular disease, or to a subject reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease may not have been made. Treating can include, for example, reducing, delaying or alleviating the severity of one or more symptoms of the disease or condition, or it can include reducing the frequency with which symptoms of a disease, defect, disorder, or adverse condition, and the like, are experienced by a patient. Treating can be used herein to refer to a method that results in some level of treatment or amelioration of the disease or condition, and can contemplate a range of results directed to that end, including but not restricted to prevention of the condition entirely.

[0061] In certain embodiments, the term “prevent” or “preventing” as related to a disease or disorder may refer to a compound that, in a statistical sample, reduces the occurrence of the disorder or condition in the treated sample relative to an untreated control sample, or delays the onset or reduces the severity of one or more symptoms of the disorder or condition relative to the untreated control sample.

[0062] A “therapeutic effect,” as that term is used herein, encompasses a therapeutic benefit and / or a prophylactic benefit as described above. A prophylactic effect includes delaying or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof.Compounds

[0063] In one aspect, the present disclosure provides compounds represented by the structure of Formula (I):or a pharmaceutically acceptable salt thereof, wherein:X1, X2, X3, and X4are each independently selected from N and C(R1), wherein at least one of X1, X2, and X3is C(R1);R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -0C(0)N(R11)2, -C(0)N(R11)2, -N(R11)C(0)R11, -N(R11)C(0)0R11, -N(R11)C(0)N(R11)2, -N(R11)C(S)N(R11)2, -N^S^CR11), -S(O)R11, -SCO)2R11, -SCO)2NCR11)2, -NO2, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; and C1-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN;R2is hydrogen or C1-6alkyl;R3aand R3bare each independently selected from hydrogen, halogen, -OR12, -SR12, -N(R12)2, -C(0)R12, -NO2, -CN, and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, -SR12, -N(R12)2, -C(0)R12, -N02, and -CN;R4is hydrogen or C1-6alkyl;Y1is selected from -L1- and -X5-L2-, wherein:L1is selected from C1-6alkylene, C2-6 alkenylene, and C3-6 caibocyclene, each of which is optionally substituted with halogen, -OR13, -SR13, -N(R13)2, -C(0)R13, -NO2, and -CN;X5is -O-, -N(R14)-, or -S-;L2is selected from a bond and C1-6alkylene optionally substituted with halogen, -OR15, -SR15, -N(R15)2, -C(0)R15, -NO2, and -CN;C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl;wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -SR16, -N(R16)(R18), -C(O)R16, -C(O)OR18, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, =0, =S, =NR16, -Ns, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -Ns, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, =S, =NR16, -Ns, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl;C4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2,=0, =S, =NR16, -N3, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl; andC3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(0)R16, -NO2, =0, =S, =NR16, -N3, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2;Y2is selected from a bond, -O-, -S-, -N(R19)-, and C1-6alkylene;Z is selected from: a bond, -C(0)-, -C(R20)2-, -C(O)C(R20)2-, -C(=N-CN)-, -C(O)O-, -C(O)O-Ci-3alkylene-, -C(O)N(R20)-, -C(S)-, -C(S)N(R20)-, -S(0)-, and -S(0)2-;B is selected from C3-i4 carbocycle and 3- to 14-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2,-NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(0)0R21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -NO2, =0, =S, =NR21, -N3, and -CN;R11, R12, R13, R14, R15, R16, R19, and R20are each independently selected at each occurrence from hydrogen, C1-6alkyl, C3-6 carbocycle, and 3- to 6-memebred heterocycle, whereineach of the Ci-6 alkyl, C3-6 carbocycle, and 3- to 6-memebred heterocycle, are optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R17is independently selected at each occurrence from: hydrogen;Ci alkyl substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN; andC2-6 alkyl, and C3-6 carbocycle, wherein each of the C2-6 alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R18is independently selected at each occurrence from C1-6alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R21is independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC<O)N(R22)2, -C<O)N(R22)2, -N(R22)C(O)R22, -N(R22)C(O)OR22, -N(R22)C(O)N(R22)2, -N(R22)C(S)N(R22)2, -N(R22)S(O)2(R22), -S(O)R22, -S(O)2R22, -S(O)2N(R22)2, -NO2,=0, =S, =NR22, -Ns, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC(O)N(R22)2, -C(O)N(R22)2, -NCR^XXOJR22, -N(R22)C(O)OR22, -N(R22)C(O)N(R22)2, -N(R22K^(S)N(R22)2, -N(R22)S(O)2(R22), -S(O)R22, -S(O)2R22, -S(O)2N(R22)2, -NO2,=0, =S, =NR22, -Ns, -CN, C3-6 carbocycle, and 3- to 6-membered heterocycle; andR22is independently selected at each occurrence from hydrogen, C1-6alkyl, C1-6haloalkyl, Ci- 6 hydroxyalkyl, and C1-6aminoalkyl.

[0064] In some embodiments, for the compound or salt of Formula (I), Y1is -L1-, and L1is selected from C1-6alkylene, C2-6 alkenylene, and C3-6 carbocyclene, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(0)R13, -NO2,and -CN.

[0065] In some embodiments, for the compound or salt of Formula (I), Y1is -L1-; and L1is selected from C2-6 alkenylene and C3-6 carbocyclene, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -NO2, and -CN. In some embodiments, Y1is -L1-; and L1is selected from C2- 6 alkenylene and C3-6 carbocyclene, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR13, -N(R13)2, and -C(O)R13. In some embodiments, Y1is -L1-; and L1is selected from C2-6 alkenylene and C3-6 carbocyclene, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR13, and -N(R13)2. In some embodiments, Y1is -L1-; and L1is selected from C2- 6 alkenylene and C3-6 carbocyclene.

[0066] In some embodiments, for the compound or salt of Formula (I), Y1is -L1-; and L1is C2- 6 alkenylene optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -NO2, and -CN. In some embodiments, Y1is -L1-; and L1is C2-6 alkenylene optionally substituted with one or more substituents independently selected from: halogen, -OR13, -N(R13)2, and -C(O)R13. In some embodiments, Y1is -L1-; and L1is C2-6 alkenylene optionally substituted with one or more substituents independently selected from: halogen, -OR13, and -N(R13)2. In some embodiments, Y1is -L1-; and L1is C2- 6 alkenylene. In some embodiments, Y1is -L1-; and L1is C2.4 alkenylene. In some embodiments,

[0067] In some embodiments, for the compound or salt of Formula (I), Y1is -L1-; and L1is C3-6 carbocyclene optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -NO2, and -CN. In some embodiments, Y1is -L1-; and L1is C3-6 carbocyclene optionally substituted with one or more substituents independently selected from: halogen, -OR13, -N(R13)2, and -C(O)R13. In some embodiments, Y1is -L1-; and L1is C3-6 carbocyclene optionally substituted with one or more substituents independently selected from: halogen, -OR13, and -N(R13)2. In some embodiments, Y1is -L1-; and L1is C3-6 carbocyclene. In some embodiments, Y1is -L1-; and L1is

[0068] In some embodiments, for the compound or salt of Formula (I), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from =0, methyl, Ci haloalkyl; andC2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2,=S, =NR16, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, Ci- 4 alkyl, and C1-4haloalkyl.

[0069] In some embodiments, for the compound or salt of Formula (I), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 caibocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10- membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from =0, methyl, Ci haloalkyl; andC2-3 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -SR16, -N(R16)2, -C(0)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -NO2, and -CN.

[0070] In some embodiments, for the compound or salt of Formula (I), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 caibocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 caibocycle, 3- to 10- membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from =0, methyl, Ci haloalkyl; andC2-3 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -NO2, and -CN.

[0071] In some embodiments, for the compound or salt of Formula (I), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 caibocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 caibocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from =0, methyl, Ci haloalkyl; andC2-3 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -N(R16)2, -C(O)R16, and -OC(O)R16.

[0072] In some embodiments, for the compound or salt of Formula (I), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10- membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from =0, methyl, Ci haloalkyl; and C2-3 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -N(R16)2, -C(O)R16, and -OC(O)R16.

[0073] In some embodiments, for the compound or salt of Formula (I), C is

[0074] In some embodiments, for the compound or salt of Formula (I), Z is selected from a bond, -C(O)-, -C(R20)2-, -C(O)C(R20)2-, -C(O)O-, -C(O)O-CI-3 alkylene-, -C(O)N(R20)-, -S(O)-, and -S(O)2-. In some embodiments, Z is selected from a bond, -C(O)-, -C(O)O-, -C(O)O-(Ci-3 alkylene)-, -S(O)-, and -S(O)2-. In some embodiments, Z is selected from a bond, -C(O)-, -C(O)O-, and -C(O)O-(Ci-3 alkylene)-. In some embodiments, Z is selected from a bond, -C(O)-, and -C(O)O-(Ci-3 alkylene)-. In some embodiments, Z is -C(O)O-(Ci-3 alkylene)-. In some embodiments, Z is -C(O)O-(CH2)-.

[0075] In some embodiments, for the compound or salt of Formula (I), B is selected from C3- 14 carbocycle and 3- to 14-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2J=0, =S, =NR21, -N3, and -CN;C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -NO2, =0, =S, =NR21, -N3, and -CN.

[0076] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3-i4 carbocycle and 3- to 14-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), and -S(O)R21;C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -N(R21)2, and -N(R21)C(O)R21; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0077] In some embodiments, for the compound or salt of Formula (I), B is selected from C3- 14 carbocycle and 3- to 14-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; and3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, Ci- 6 haloalkyl, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0078] In some embodiments, for the compound or salt of Formula (I), B is selected from C3- 14 carbocycle and 3- to 14-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -N(R21)2, and 3- to 10-membered heterocycle; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from:halogen, =0, Ci-6 alkyl, and Ci-6 haloalkyl.

[0079] In some embodiments, for the compound or salt of Formula (I), B is selected from C3- 14 carbocycle and 3- to 14-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl Ci-ehaloalkyl, C3- 10 carbocycle and 3- to 10-membered heterocycle.

[0080] In some embodiments, for the compound or salt of Formula (I), B is C3-14 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2J=0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2,-N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2J=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -NO2, =0, =S, =NR21, -N3, and -CN.

[0081] In some embodiments, for the compound or salt of Formula (I), B is C3-i4 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -N(R21)2, and -N(R21)C(O)R21; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0082] In some embodiments, for the compound or salt of Formula (I), B is C3-i4 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; and3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, Ci- 6 haloalkyl, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0083] In some embodiments, for the compound or salt of Formula (I), B is C3-14 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -N(R21)2, and 3- to 10-membered heterocycle; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, =0, C1-6alkyl, and C1-6haloalkyl.

[0084] In some embodiments, for the compound or salt of Formula (I), B is C3-14 carbocycle optionally substituted with one or more substituents independently selected from: halogen, Ci- 6 alkyl Ci-ehaloalkyl, C3-10 carbocycle and 3- to 10-membered heterocycle.

[0085] In some embodiments, for the compound or salt of Formula

[0086] In another aspect, the present disclosure provides compounds represented by the structure of Formula (I-a):or a pharmaceutically acceptable salt thereof, wherein:X1, X2, X3, and X4are each independently selected from N and C(R1), wherein at least one of X1, X2, and X3is CCR1);R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -0C(0)N(R11)2, -C(0)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)C(0)N(R11)2, -N(R11)C(S)N(R11)2, -N^S^CR11), -S(O)R11, -SCO)2R11, -SCO)2NCR11)2, -NO2, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN;R2is hydrogen or C1-6alkyl;R3aand R3bare each independently selected from hydrogen, halogen, -OR12, -SR12, -N(R12)2, -C(0)R12, -NO2, -CN, and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, -SR12, -N(R12)2, -C(0)R12, -NO2, and -CN;R4is hydrogen or C1-6alkyl;Y1is selected from -L1- and -X5-L2-, wherein:L1is C1-6alkylene optionally substituted with halogen, -OR13, -SR13, -N(R13)2, -C(0)R13, -NO2, and -CN;X5is -O-, -N(R14)-, or -S-;L2is selected from a bond and C1-6alkylene optionally substituted with halogen, -OR15, -SR15, -N(R15)2, -C(0)R15, -NO2, and -CN;C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -SR16, -N(R16)(R18), -C(0)R16, -C(0)0R18, -0C(0)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, =0, =S, =NR16, -N3, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(0)R16, -C(0)0R16, -0C(0)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2,—Ns, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, =S, =NR16, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl;C4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, =0, =S, =NR16, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(O)R16, -NO2, =0, =S, =NR16, -N3, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro;wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2;Y2is selected from a bond, -O-, -S-,-N(R19)-, and C1-6alkylene;Z is selected from: a bond, -C(O)-, -C(R20)2-, -C(O)C(R20)2-, -C(=N-CN)-, -C(O)O-, -C(O)N(R20)-, -C(S)-, -C(S)N(R20)-, -S(O)-, and -S(O)2-;B is selected from C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2J=0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21,-C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2J=0, =S, =NR21, -N3, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -NO2, =0, =S, =NR21, -N3, and -CN;R11, R12, R13, R14, R15, R16, R19, and R20are each independently selected at each occurrence from hydrogen, C1-6alkyl, and C3-6 carbocycle, wherein each of the C1-6alkyl and C3- 6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R17is independently selected at each occurrence from: hydrogen;Ci alkyl substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN; andC2-6 alkyl, and C3-6 carbocycle, wherein each of the C2-6 alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R18is independently selected at each occurrence from Ci-6 alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R21is independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC<O)N(R22)2, -C<O)N(R22)2, -N(R22)C(O)R22, -N(R22)C(O)OR22, -N(R22)C(O)N(R22)2, -N(R22)C(S)N(R22)2, -N(R22)S(O)2(R22), -S(O)R22, -S(O)2R22, -S(O)2N(R22)2, -NO2,=0, =S, =NR22, -Ns, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC(O)N(R22)2, -C(O)N(R22)2, -NCR^XXOJR22, -N(R22)C(O)OR22, -N(R22)C(O)N(R22)2, -N(R22)C(S)N(R22)2, -N(R22)S(O)2(R22), -S(O)R22, -S(O)2R22, -S(O)2N(R22)2, -NO2,=0, =S, =NR22, -Ns, -CN, C3-6 carbocycle, and 3- to 6-membered heterocycle; andR22is independently selected at each occurrence from hydrogen, C1-6alkyl, C1-6haloalkyl, Ci- 6 hydroxyalkyl, and C1-6aminoalkyl.

[0087] In some embodiments, for the compound or salt of Formula (I) or (I-a), X1, X2, X3, and X4are each independently selected from N and C(R1), further wherein at least one of X1, X2, and X3is C(R1). In some embodiments, X1is C(R1). In some embodiments, X2is C(R1). In some embodiments, X3is C(R1). In some embodiments, X4is C(R1). In some embodiments, X1and X2are each C(R1). In some embodiments, X1and X3are each CCR1). In some embodiments, X1and X4are each CCR1). In some embodiments, X2and X3are each CCR1). In some embodiments, X2and X4are each CCR1). In some embodiments, X3and X4are each CCR1). In some embodiments, X1, X2, and X3are each C(R1). In some embodiments, X1, X2, and X4are each C(R1). In some embodiments, X1, X3, and X4are each C(R1). In some embodiments, X2, X3, and X4are each C(R1). In some embodiments, X1, X2, X3, and X4are each C(R1).

[0088] In some embodiments, for the compound or salt of Formula (I) or (I-a), X1, X2, and X3are each N. In some embodiments, X1, X2, and X4are each N. In some embodiments, X1, X3, and X4are each N. In some embodiments, X2, X3, and X4are each N. In some embodiments, no more than two of X1, X2, X3, and X4are N. In some embodiments, X1and X2are each N. In some embodiments, X1and X3are each N. In some embodiments, X1and X4are each N. Insome embodiments, X2and X3are each N. In some embodiments, X2and X4are each N. In some embodiments, X3and X4are each N. In some embodiments, no more than one of X1, X2, X3, and X4is N. In some embodiments, X1is N. In some embodiments, X2is N. In some embodiments, X3is N. In some embodiments, X4is N.

[0089] In some embodiments, for the compound or salt of Formula (I) or (I-a), X1is C(RX), X2is QR1), X3is QR1), and X4is QR1); X1is N, X2is QR1), X3is QR1), and X4is QR1); X1is QR1), X2is N, X3is QR1), and X4is QR1); X1is QR1), X2is QR1), X3is N, and X4is QR1); X1is QR1), X2is QR1), X3is QR1), and X4is N; or X1is N, X2is QR1), X3is N, and X4is C(R1). In some embodiments, X1is QR1), X2is QR1), X3is QR1), and X4is QR1); X1is N, X2is QR1), X3is QR1), and X4is QR1); X1is QR1), X2is N, X3is QR1), and X4is QR1); X1is QR1), X2is QR1), X3is N, and X4is QR1); or X1is QR1), X2is QR1), X3is QR1), and X4is N. In some embodiments, X1is QR1), X2is C(RX), X3is C(RX), and X4is QR1); or X1is N, X2is C(RX), X3is N, and X4is C(R1). In some embodiments, X1is N, X2is C(RX), X3is C(RX), and X4is QR1); X1is QR1), X2is N, X3is QR1), and X4is QR1); X1is QR1), X2is QR1), X3is N, and X4is QR1); X1is QR1), X2is QR1), X3is QR1), and X4is N; or X1is N, X2is C(RX), X3is N, and X4is QR1). In some embodiments, X1is QR1), X2is QR1), X3is QR1), and X4is QR1). In some embodiments, X1is N, X2is QR1), X3is C(RX), and X4is QR1). In some embodiments, X1is C(RX), X2is N, X3is QR1), and X4is C(R1). In some embodiments, X1is C(RX), X2is C(RX), X3is N, and X4is QR1). In some embodiments, X1is C(RX), X2is C(RX), X3is QR1), and X4is N. In some embodiments, X1is N, X2is C(RX), X3is N, and X4is QR1).

[0090] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -OC(O)N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)C(O)N(R11)2, -N(R11)C(S)N(R11)2, -N(R11)S(O)2(R11), -S(O)R11, -S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN;Ci-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4 alkyl, C1-4 haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted withone or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN.

[0091] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -N(R11)2, -C(O)R11, -C(OX>R11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(0)R11, -NO2, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from: halogen, -OR11, -N(R11)2, =0, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -N(R11)2, =0, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -N(R11)2, =0, and -CN.

[0092] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -0C(0)N(R11)2, -C(0)N(R11)2, -NCRHJCCOJR11, -N^XXO^R11, -N^XWXR11^ -N(R11)C(S)N(R11)2, -N^^S^CR11), -S(O)R11, -S^R11, -SCO)2NCR11)2, -NO2, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN.

[0093] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -N(R11)2, -C(O)R11, -C(OX>R11, -OC(O)R11, -C(0)N(R11)2, -N(R11)C(0)R11, -NO2, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from: halogen, -OR11, -N(R11)2, =0, and -CN; andC1-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -N(R11)2, =0, and -CN.

[0094] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -N(R11)2, -C(O)N(R11)2, -N^XXOJR11, and -CN; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR11, -N(R11)2, =0, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, and =0.

[0095] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -N(R11)2, -C(O)N(R11)2, and -N(R11)C(O)R11; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR11, =0, and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, and

[0096] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from hydrogen, halogen, and C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR11, =0, and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, and =0. In some embodiments, R1is independently selected at each occurrence from: hydrogen, halogen, and C1-6alkyl optionally substituted by one or more substituents independently selected from halogen and 3- to 6-membered heterocycle. In some embodiments, R1is independently selected at each occurrence from: hydrogen, halogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, R1is independently selected at each occurrence from: hydrogen, halogen, and C1-6alkyl. In some embodiments, R1is independently selected at each occurrence from: hydrogen and halogen. In some embodiments, R1is independently selected at each occurrence from: hydrogen and Ci- 6 alkyl. In some embodiments, each R1is hydrogen.

[0097] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -NO2, and -CN. In someembodiments, R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -N(R11)2, -C(O)N(R11)2, and -N(R11)C(O)R11. In some embodiments, R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, and -N(R11)2. In some embodiments, R1is independently selected at each occurrence from: hydrogen, halogen, and -OR11. In some embodiments, R1is independently selected at each occurrence from: hydrogen, halogen, and -N(R11)2. In some embodiments, R1is independently selected at each occurrence from: hydrogen and halogen. In some embodiments, R1is independently selected at each occurrence from: hydrogen and fluoro.

[0098] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from: C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR11, =0, and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, and =0. In some embodiments, R1is independently selected at each occurrence from: C1-4alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR11, =0, and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, and =0. In some embodiments, R1is independently selected at each occurrence from: C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR11, =0, and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen and C1-4alkyl. In some embodiments, R1is independently selected at each occurrence from: C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR11, =0, and 3- to 6-membered heterocycle. In some embodiments, R1is independently selected at each occurrence from: Ci- 6 alkyl optionally substituted by one or more substituents independently selected from: halogen, =0, and 3- to 6-membered heterocycle. In some embodiments, R1is independently selected at each occurrence from: C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR11, and 3- to 6-membered heterocycle. In some embodiments, R1is independently selected at each occurrence from: C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen and 3- to 6-membered heterocycle.

[0099] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from: hydrogen, fluoro, trifluoromethyl, morpholino(methyl), and azetidinyl(methyl). In some embodiments, R1is independentlyselected at each occurrence from: hydrogen, fluoro, methyl, trifluoromethyl,

[0100] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from hydrogen, halogen, -OR11, -N(R11)2,-CN, and C1-6alkyl optionally substituted by one or more substituents independently selected from halogen, -OR11, -N(R11)2, =O,-CN, C3-6 carbocycle, and 3- to 6-membered heterocycle.

[0101] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from hydrogen, halogen, -OR11, -N(R11)2, -CN, and C1-6alkyl optionally substituted by one or more substituents independently selected from halogen, -OR11, -N(R11)2, =0, and -CN.

[0102] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is independently selected at each occurrence from halogen, -OR11, and C1-6alkyl optionally substituted by one or more substituents independently selected from halogen, -OR11, -N(R11)2, =0, and -CN.

[0103] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is selected from halogen and C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR11, -N(R11)2, =0, and -CN.

[0104] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is selected from halogen and C1.3 alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR11, -N(R11)2, =0, and -CN. In some embodiments, R1is selected from halogen and C1.3 alkyl optionally substituted by one or more substituents independently selected from halogen and -N(R11)2. In some embodiments, R1is selected from halogen and Ci. 3 alkyl optionally substituted by one or more substituents independently selected from halogen and -N(R11)2. In some embodiments, R1is selected from halogen and C1.3 alkyl optionally substituted by one or more -N(R11)2.

[0105] In some embodiments, for the compound or salt of Formula (I) or (I-a), R1is selected from Cl and

[0106] In some embodiments, for the compound or salt of Formula (I) or (I-a), R2is hydrogen or C1-6alkyl. In some embodiments, R2is hydrogen or C1.3 alkyl. In some embodiments, R2is hydrogen, methyl, ethyl, n-propyl, or isopropyl. In some embodiments, R2is hydrogen or methyl. In some embodiments, R2is hydrogen. In some embodiments, R2is C1-6alkyl. In someembodiments, R2is C1.3 alkyl. In some embodiments, R2is methyl, ethyl, n-propyl, or isopropyl. In some embodiments, R2is methyl. In some embodiments, R2is selected from hydrogen and methyl. In some embodiments, R2is hydrogen or methyl.

[0107] In some embodiments, for the compound or salt of Formula (I) or (I-a), R3aand R3bare each independently selected from hydrogen, halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -NO2, -CN, and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -NO2, and -CN. In some embodiments, R3aand R3bare each independently selected from hydrogen, halogen, -OR12, -N(R12)2, -C(O)R12, -NO2, -CN, and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, -N(R12)2, -C(O)R12, -NO2, and -CN. In some embodiments, R3aand R3bare each independently selected from hydrogen, halogen, -OR12, -N(R12)2, -C(O)R12, and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, -N(R12)2, and -C(O)R12. In some embodiments, R3aand R3bare each independently selected from hydrogen, halogen, -OR12, -N(R12)2, and Ci- 6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, and -N(R12)2. In some embodiments, R3aand R3bare each independently selected from hydrogen, halogen, -OR12, -N(R12)2, and C1-6alkyl. In some embodiments, R3aand R3bare each independently selected from hydrogen, halogen, and C1-6alkyl. In some embodiments, R3aand R3bare each independently selected from hydrogen and C1-6alkyl. In some embodiments, R3aand R3bare each independently selected from hydrogen and halogen. In some embodiments, R3aand R3bare each hydrogen.

[0108] In some embodiments, for the compound or salt of Formula (I) or (I-a), R4is hydrogen or C1-6alkyl. In some embodiments, R4is hydrogen or C1.3 alkyl. In some embodiments, R4is hydrogen, methyl, ethyl, n-propyl, or isopropyl. In some embodiments, R4is hydrogen, methyl, ethyl, or n-propyl. In some embodiments, R4is hydrogen, methyl, or ethyl. In some embodiments, R4is hydrogen or methyl. In some embodiments, R4is hydrogen.

[0109] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y2is selected from a bond, -O-, -S-, -N(R19)-, and C1-6alkylene. In some embodiments, Y2is selected from a bond, -O-, -N(R19)-, and C1-6alkylene. In some embodiments, Y2is selected from a bond, C1-3 alkylene, -O-, and -N(R19)-. In some embodiments, Y2is selected from a bond, C1-3 alkylene, -O-, and -N(CH3)-.

[0110] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y2is selected from a bond, -O-, and -N(R19)-. In some embodiments, Y2is selected from a bond, -O-, and -N(CH3)-. In some embodiments, Y2is selected from a bond and -O-. In some embodiments,Y2is selected from a bond and -N(R19)-. In some embodiments, Y2is selected from a bond and -N(CH3)-. In some embodiments, Y2is selected from -O- and -N(R19)-. In some embodiments, Y2is selected from -O- and -N(CH3)-. In some embodiments, Y2is a bond. In some embodiments, Y2is -O-. In some embodiments, Y2is -N(R19)-. In some embodiments, Y2is -N(CH3)-.

[0111] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y2is selected from a bond and Ci-6 alkylene. In some embodiments, Y2is a bond. In some embodiments, Y2is selected from a bond and C1-3 alkylene. In some embodiments, Y2is C1-3 alkylene. In some embodiments, Y2is methylene.

[0112] In some embodiments, for the compound or salt of Formula (I) or (I-a), R19is selected from hydrogen, C1-6alkyl, and C3-6 carbocycle, wherein each of the C1-6alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN. In some embodiments, R19is selected from hydrogen and C1-6alkyl. In some embodiments, R19is selected from hydrogen and C1-6alkyl. In some embodiments, R19is selected from hydrogen and C1.3 alkyl. In some embodiments, R19is selected from hydrogen, methyl, ethyl, n-propyl, and isopropyl. In some embodiments, R19is selected from hydrogen and methyl. In some embodiments, R19is methyl.

[0113] In some embodiments, for the compound or salt of Formula (I) or (I-a), Z is selected from: a bond, -C(O)-, -C^20)2-, -QO^tR20)2-, -C(=N-CN)-, -C(O)O-, -C(O)N(R20)-, — C(S)~ , -C(S)N(R20)-, — S(O)— , and -S(O)2-. In some embodiments, Z is selected from: a bond, -C(O)-, -C(R20)2-, -C(O)C(R20)2-, -C(O)O-, -C(O)N(R20)-, and -S(O)2-. hi some embodiments, Z is selected from: a bond, -C(O)-, -CfR20)?-, -^(OJCfR20)?-, -C(O)O-, and -C(O)N(R20)-. In some embodiments, Z is selected from: a bond, -C(O)-, and -C(R20)2-. In some embodiments, Z is selected from a bond and -C(O)-. In some embodiments, Z is a bond. In some embodiments, Z is -C(O)-.

[0114] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y1is selected from -L1- and -X5-L2-, wherein:L1is C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -NO2, and -CN;X5is -O-, -N(R14)-, or -S-;L2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from:halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -NO2, and -ON.

[0115] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y1is selected from -L1- and -X5-L2-, wherein:L1is C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR13, -N(R13)2, and -C(O)R13;X5is -O- or -N(R14)-;L2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, -N(R15)2, and -C(O)R15.

[0116] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y1is selected from -L1- and -X5-L2-, wherein:L1is C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR13, and -N(R13)2;X5is -O- or -N(R14)-;L2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, and -N(R15)2.

[0117] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y1is selected from -L1- and -X5-L2-, wherein:L1is C1-6alkylene optionally substituted with one or more substituents independently selected from halogen, -OR13, and -NQt13}?;X5is -O- or -N(R14)-;L2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from halogen, -OR15, and -N(R15)2.

[0118] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y1is selected from -L1- and -X5-L2-, wherein:L1is C1-6alkylene;X5is -O- or -N(R14)-;L2is selected from a bond and C1-6alkylene.

[0119] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y1is selected from -L1- and -X5-L2-, wherein:L1is C1-6alkylene;X5is -O- or -N(R14)-;L2is a bond.

[0120] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y1is -L1-, wherein L1is Ci-6 alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -NO2, and -CN. In some embodiments, L1is C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR13, -N(R13)2, and -C(O)R13. In some embodiments, L1is C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR13, and -N(R13)2.

[0121] In some embodiments, for the compound or salt of Formula (I) or (I-a), L1is Ci-6 alkylene. In some embodiments, L1is C1.3 alkylene. In some embodiments, L1is selected from methylene, methyl(methylene), ethylene, and propylene. In some embodiments, L1is (methyl)methylene. In some embodiments, L1is methylene.

[0122] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y1is -X5-L2-, wherein:X5is — O— , -N(R14)-, or -S-; andL2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -NO2, and -CN.

[0123] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y1is -X5-L2-, wherein:X5is -O- or -N(R14)-; andL2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, -N(R15)2, and -C(O)R15.

[0124] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y1is -X5-L2-, wherein:X5is -O- or -N(R14)-; andL2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, and -N(R15)2.

[0125] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y1is -X5-L2-, wherein:X5is -O- or -N(R14)-; andL2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, and -N(R15)2.

[0126] In some embodiments, for the compound or salt of Formula (I) or (I-a), Y1is -X5-L2-, wherein: X5is -O- or -N(R14)-; and L2is selected from a bond and C1-6alkylene. In someembodiments, X5is -O- or -N(R14)-; and L2is selected from a bond. In some embodiments, X5is — O— and L2is selected from a bond. In some embodiments, X5is -N(R14)- and L2is selected from a bond. In some embodiments, X5is -N(CH3)- and L2is selected from a bond.

[0127] In some embodiments, for the compound or salt of Formula (I) or (I-a), X5is -O- or -N(R14)-. In some embodiments, X5is -O-. In some embodiments, X5is -N(R14)-. In some embodiments, X5is -O- or -N(CH3)-. In some embodiments, X5is -N(CH3)-.

[0128] In some embodiments, for the compound or salt of Formula (I) or (I-a), L2is selected from a bond and Ci-6 alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -NO2, and -CN. In some embodiments, L2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, -N(R15)2, and -C(O)R15. In some embodiments, L2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, and -N(R15)2. In some embodiments, L2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, and -N(R15)2. In some embodiments, L2is selected from a bond and C1-6alkylene. In some embodiments, L2is selected from a bond and C1.3 alkylene. In some embodiments, L2is a bond.

[0129] In some embodiments, for the compound or salt of Formula (I) or (I-a), R11, R12, R13, R14, R15, R16, R19, and R20are each independently selected at each occurrence from hydrogen, C1-6alkyl, and C3-6 carbocycle, wherein each of the C1-6alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN. In some embodiments, R11, R12, R13, R14, R15, R16, R19, and R20are each independently selected at each occurrence from hydrogen and Ci- 6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN. In some embodiments, R11, R12, R13, R14, R15, R16, R19, and R20are each independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, R11, R12, R13, R14, R15, R16, R19, and R20are each independently selected at each occurrence from hydrogen and C1.3 alkyl. In some embodiments, R11, R12, R13, R14, R15, R16, R19, and R20are each independently selected at each occurrence from hydrogen and methyl. In some embodiments, R11, R12, R13, R14, R15, R16, R19, and R20are at each occurrence hydrogen. In some embodiments, R11, R12, R13, R14, R15, R16, R19, and R20are at each occurrence methyl.

[0130] In some embodiments, for the compound or salt of Formula (I) or (I-a), R11is independently selected at each occurrence from hydrogen, C1-6alkyl, and C3-6 carbocycle,wherein each of the Ci-6 alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-Ci- 6 haloalkyl, =0, and -CN. In some embodiments, R11is independently selected at each occurrence from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN. In some embodiments, R11is independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, R11is independently selected at each occurrence from hydrogen and C1.3 alkyl. In some embodiments, R11is independently selected at each occurrence from hydrogen and methyl. In some embodiments, each R11is hydrogen. In some embodiments, each R11is methyl.

[0131] In some embodiments, for the compound or salt of Formula (I) or (I-a), R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and C3-6 carbocycle, wherein each of the C1-6alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-Ci- 6 haloalkyl, =0, and -CN. In some embodiments, R12is independently selected at each occurrence from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN. In some embodiments, R12is independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, R12is independently selected at each occurrence from hydrogen and C1.3 alkyl. In some embodiments, R12is independently selected at each occurrence from hydrogen and methyl. In some embodiments, each R12is hydrogen. In some embodiments, each R12is methyl.

[0132] In some embodiments, for the compound or salt of Formula (I) or (I-a), R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C3-6 carbocycle, wherein each of the C1-6alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-Ci- 6 haloalkyl, =0, and -CN. In some embodiments, R13is independently selected at each occurrence from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN. In some embodiments, R13is independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, R13is independently selected at each occurrence from hydrogen and C1.3 alkyl. In some embodiments, R13is independently selected at each occurrence from hydrogen and methyl. In some embodiments, each R13is hydrogen. In some embodiments, each R13is methyl.

[0133] In some embodiments, for the compound or salt of Formula (I) or (I-a), R14is independently selected at each occurrence from hydrogen, Ci-6 alkyl, and C3-6 carbocycle, wherein each of the C1-6alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-Ci- 6 haloalkyl, =0, and -CN. In some embodiments, R14is independently selected at each occurrence from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN. In some embodiments, R14is independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, R14is independently selected at each occurrence from hydrogen and C1.3 alkyl. In some embodiments, R14is independently selected at each occurrence from hydrogen and methyl. In some embodiments, each R14is hydrogen. In some embodiments, each R14is methyl.

[0134] In some embodiments, for the compound or salt of Formula (I) or (I-a), R15is independently selected at each occurrence from hydrogen, C1-6alkyl, and C3-6 carbocycle, wherein each of the C1-6alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-Ci- 6 haloalkyl, =0, and -CN. In some embodiments, R15is independently selected at each occurrence from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN. In some embodiments, R15is independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, R15is independently selected at each occurrence from hydrogen and C1.3 alkyl. In some embodiments, R15is independently selected at each occurrence from hydrogen and methyl. In some embodiments, each R15is hydrogen. In some embodiments, each R15is methyl.

[0135] In some embodiments, for the compound or salt of Formula (I) or (I-a), R19is independently selected at each occurrence from hydrogen, C1-6alkyl, and C3-6 carbocycle, wherein each of the C1-6alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-Ci- 6 haloalkyl, =0, and -CN. In some embodiments, R19is independently selected at each occurrence from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN. In some embodiments, R19is independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, R19is independently selected at each occurrence from hydrogen and C1.3 alkyl. In some embodiments, R19is independently selected at eachoccurrence from hydrogen and methyl. In some embodiments, each R19is hydrogen. In some embodiments, each R19is methyl.

[0136] In some embodiments, for the compound or salt of Formula (I) or (I-a), R20is independently selected at each occurrence from hydrogen, Ci-6 alkyl, and C3-6 carbocycle, wherein each of the C1-6alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-Ci- 6 haloalkyl, =0, and -CN. In some embodiments, R20is independently selected at each occurrence from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN. In some embodiments, R20is independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, R20is independently selected at each occurrence from hydrogen and C1.3 alkyl. In some embodiments, R20is independently selected at each occurrence from hydrogen and methyl. In some embodiments, each R20is hydrogen. In some embodiments, each R20is methyl.

[0137] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3-10 caibocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21,-S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2J=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -N02, =0, =S, =NR21, -N3, and -CN.

[0138] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3-io carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, -NO2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,=0, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21,-C(O)N(R21)2, -N(R21)C(O)R21, -NO2Jand -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(O)R21, -NO2, =0, and -CN.

[0139] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21,-S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21,-S(O)2R21, -S(O)2N(R21)2, -NO2J=0, =S, =NR21, -Ns, and -CN.

[0140] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, -NO2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2, =0, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2, and -CN.

[0141] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, -NO2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2J=0, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN.

[0142] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, and C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0143] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0144] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; and3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0145] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -N(R21)2, and 3- to 10-membered heterocycle; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, =0, C1-6alkyl, and C1-6haloalkyl.

[0146] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: fluoro, chloro, methyl, — o trifluoromethyl, -CH2N(CH3)2, -NHCH2CF3, -NHS(O)2CH3,F3

[0147] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3-10 caibocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: fluoro, chloro, methyl, trifluoromethyl, -CH2N(CH3)2, -NHCH2CF3, -NHS(O)2CH3,

[0148] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -SCO)2NCR21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -SCO)2NCR21)2, -NO2J=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21,-S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -N02, =0, =S, =NR21, -N3, and -CN.

[0149] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, -NO2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen,C1-6alkyl, Ci-6 haloalkyl, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2, =0, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(0)R21, -N02, =0, and -CN.

[0150] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21,-S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2J=0, =S, =NR21, -N3, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN.

[0151] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, -NO2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,=0, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN.

[0152] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl,indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, -NO2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2,-N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, - O2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,=0, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN.

[0153] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, and C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from:halogen, -OR21, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0154] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0155] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; and3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0156] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -N(R21)2, and 3- to 10-membered heterocycle; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, =0, C1-6alkyl, and C1-6haloalkyl.

[0157] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: fluoro, chloro, methyl, trifluoromethyl, -

[0158] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: fluoro, chloro, methyl, trifluoromethyl, -CH2N(CH3)2, -NHCH2CF3, -NHS(O)2CH3

[0159] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from cyclohexyl, bicyclo[l.l.l]pentyl, phenyl, pyrrolidinyl, piperidinyl, pyridyl, 1H- benzo[d]imidazolyl, indolinyl, pyrazolo[l,5-a]pyridinyl, indazolyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21,-S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andCs-io carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN;C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -N02, =0, =S, =NR21, -N3, and -CN.

[0160] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from cyclohexyl, bicyclo[l.l.l]pentyl, phenyl, pyrrolidinyl, piperidinyl, pyridyl, 1H- benzo[d]imidazolyl, indolinyl, pyrazolo[l,5-a]pyridinyl, indazolyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21,-N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, Ci-6 haloalkyl, -OR21, -N(R21)2, -C(O)R21, =0, and -CN.

[0161] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from cyclohexyl, bicyclo[l.l.l]pentyl, phenyl, pyrrolidinyl, piperidinyl, pyridyl, 1H- benzo[d]imidazolyl, indolinyl, pyrazolo[l,5-a]pyridinyl, indazolyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, -NO2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,=0, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN.

[0162] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from cyclohexyl, bicyclo[l.l.l]pentyl, phenyl, pyrrolidinyl, piperidinyl, pyridyl, 1H- benzo[d]imidazolyl, indolinyl, pyrazolo[l,5-a]pyridinyl, indazolyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, and C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionallysubstituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0163] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from cyclohexyl, bicyclo[l.l.l]pentyl, phenyl, pyrrolidinyl, piperidinyl, pyridyl, 1H- benzo[d]imidazolyl, indolinyl, pyrazolo[l,5-a]pyridinyl, indazolyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0164] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from cyclohexyl, bicyclo[l.l.l]pentyl, phenyl, pyrrolidinyl, piperidinyl, pyridyl, 1H- benzo[d]imidazolyl, indolinyl, pyrazolo[l,5-a]pyridinyl, indazolyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; and3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0165] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from cyclohexyl, bicyclo[l.l.l]pentyl, phenyl, pyrrolidinyl, piperidinyl, pyridyl, 1H- benzo[d]imidazolyl, indolinyl, pyrazolo[l,5-a]pyridinyl, indazolyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -N(R21)2, and 3- to 10-membered heterocycle; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, =0, C1-6alkyl, and C1-6haloalkyl.

[0166] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is C3-10 carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2xC(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21,-S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2J=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -N02, =0, =S, =NR21, -N3, and -CN.

[0167] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from C3.s carbocycle, cyclohexyl, and C7-10 carbocycle, each of which is optionally substituted, and substituted phenyl; wherein substituents on the C3.s carbocycle, C7-10 carbocycle, 3- to 9-membered heterocycle, and substituted phenyl of B are each independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)2R21, S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(OX)R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21,-N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21,-S(O)2N(R21)2, -NO2J=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -N02, =0, =S, =NR21, -N3, and -CN.

[0168] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, and phenyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andCa-io carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(OX)R21,-OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21,-S(O)2N(R21)2, -NO2J=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -N02, =0, =S, =NR21, -N3, and -CN.

[0169] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, and phenyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, -NO2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from:halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2J=0, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(0)R21, -N02, =0, and -CN.

[0170] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, and phenyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C<O)OR21, -N(R21X:(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S<O)R21, -S(O)2R21, -SCO)2NCR21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -SCO)2NCR21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -SCO^^-SCO)2NCR21)2, -NO2, =0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -SCO)2NCR21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN.

[0171] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, and phenyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, -NO2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,=0, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN.

[0172] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, and phenyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, -NO2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2, =0, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2, and -CN.

[0173] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, and phenyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, and C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0174] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, and phenyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from:halogen, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0175] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, and phenyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; and3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0176] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, and phenyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -N(R21)2, and 3- to 10-membered heterocycle; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, =0, C1-6alkyl, and C1-6haloalkyl.

[0177] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, and phenyl, each of which is optionally substituted withone or more substituents independently selected from: fluoro, chloro, methyl, trifluoromethyl,

[0178] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from bicyclo[l.l.l]pentyl, cyclohexyl, and phenyl, each of which is optionally substituted with one or more substituents independently selected from: fluoro, chloro, methyl, trifluoromethyl,-CH2N(CH3)2, -NHCH2CF3, -NHS(O)2CH3,

[0179] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from:halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21,-S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -N02, =0, =S, =NR21, -N3, and -CN.

[0180] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from 3- to 9-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)2R21, S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one ormore substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21,-S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(0)R21, -N02, =0, =S, =NR21, -N3, and -CN.

[0181] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21,-S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -N02, =0, =S, =NR21, -N3, and -CN.

[0182] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(OX>R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21,-N(R21)S(O)2(R21), -S(O)R21, -NO2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,=0, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(0)R21, -N02, =0, and -CN.

[0183] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionallysubstituted with one or more substituents independently selected from: halogen, C1-6alkyl, Ci-6 haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2,-N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21),-S(O)R21, -S(O)2R21,-S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(0)R21, -C(O)OR21, -0C(0)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN.

[0184] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, -NO2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2,-N(R21)C(O)R21, -NO2, =0, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(0)0R21, -0C(0)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -NO2,and -CN.

[0185] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21, and C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0186] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0187] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from pyrrolidin-2-yl, pyrid-3-yl, lH-benzo[d]imidazol-5-yl, indolin-5-yl, and pyrazolo[l,5- a]pyridine-2-yl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and -N(R21)C(O)R21; and3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, Ci-6 alkyl, Ci-6 haloalkyl, -N(R21)2, and -N(R21)C(O)R21; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, and =0; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -C(O)N(R21)2, and -N(R21)C(O)R21.

[0188] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)S(O)2(R21), and -S(O)R21; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -N(R21)2, and 3- to 10-membered heterocycle; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, =0, C1-6alkyl, and C1-6haloalkyl.

[0189] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: fluoro, chloro, methyl, trifluoromethyl, -CH2N(CH3)2, -NHCH2CF3, -NHS(O)2CH.3,

[0190] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, and pyrazolo[l,5-a]pyridinyl, each of which is optionally substituted with one or more substituents independently selected from: fluoro, chloro, methyl, trifluoromethyl, -CH2N(CH3)2, -NHCH2CF3, -NHS(O)2CH3,

[0191] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected

[0192] In some embodiments, for the compound or salt of Formula (I) or (I-a), B is selected from

[0193] In some embodiments, for the compound or salt of Formula (I) or (I-a), R21is independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC(O)N(R22)2,C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, Ci--S(O)2N(R22)2, -NO2, =0, =S, =NR22, -Ns, -CN, C3-6 carbocycle, and 3- to 6-membered heterocycle.

[0194] In some embodiments, for the compound or salt of Formula (I) or (I-a), R21is independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR22, -N(R22}z, -C(O)R22, -C(O)OR22, -OC(O)R22, -C(O)N(R22)2, -NCR^XXOJR22, =0, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, Ci-6haloalkyl, -OR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -C(O)N(R22)2, -N(R22XXO)R22, -NO2, =0, -CN, C3-6 carbocycle, and 3- to 6-membered heterocycle.

[0195] In some embodiments, for the compound or salt of Formula (I) or (I-a), R21is independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR22, -N(R22}z, -C(O)N(R22)2, -N(R22)C(O)R22, =0, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, Ci- 6 haloalkyl,6 carbocycle, and 3- to 6-membered heterocycle.

[0196] In some embodiments, for the compound or salt of Formula (I) or (I-a), R21is independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR22, and =0; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, Ci- 6 haloalkyl, -OR22, -N(R22)2, -N^K^^R22, and =0.

[0197] In some embodiments, for the compound or salt of Formula (I) or (I-a), R21is independently selected at each occurrence from: hydrogen, C1-6alkyl, and C1-6haloalkyl; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, Ci- 6 haloalkyl, -N(R22)C(O)R22, and =0.

[0198] In some embodiments, for the compound or salt of Formula (I) or (I-a), R21is independently selected at each occurrence from: hydrogen, C1-6alkyl, and C1-6haloalkyl; and phenyl and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -N^^XXOJR22, and =0.

[0199] In some embodiments, for the compound or salt of Formula (I) or (I-a), R21is independently selected at each occurrence from: hydrogen, C1-6alkyl, and C1-6haloalkyl; andphenyl and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6haloalkyl, -N(R22)C(O)R22, and =0.

[0200] In some embodiments, for the compound or salt of Formula (I) or (I-a), R22is independently selected at each occurrence from: hydrogen, C1-6alkyl, C1-6haloalkyl, Ci- 6 hydroxyalkyl, and C1-6aminoalkyl. In some embodiments, R22is independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, R22is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, R22is independently selected at each occurrence from hydrogen, methyl, ethyl, n-propyl, isopropyl, n- butyl, s-butyl, and t-butyl. In some embodiments, R22is independently selected at each occurrence from hydrogen and t-butyl. In some embodiments, R22is independently selected at each occurrence from C1-6alkyl. In some embodiments, R22is independently selected at each occurrence from C1-4alkyl. In some embodiments, R22is independently selected at each occurrence from methyl, ethyl, n-propyl, isopropyl, n-butyl, s-butyl, and t-butyl. In some embodiments, each R22is hydrogen. In some embodiments, each R22is t-butyl.

[0201] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -SR16, -N(R16)(R18), -C(O)R16, -C(O)OR18, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, =0, =s, =NR16, -N3, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from:halogen-NO2, =S, =NR16, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2J=0, =S, =NR16, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(0)R16, -NO2, =0, =S, =NR16, -N3, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-memberedheterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0202] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, =0, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -C(0)R16, -NO2, =0, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro;wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0203] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -C(O)R16, -NO2J=0, and -CN; and wherein when R2is selected from hydrogen and C2-6alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -N02.

[0204] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(0)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;CM alkyl optionally substituted with one or more substituents independently selected from:halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -C(O)R16, -NO2, =0, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0205] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2,-N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen-NO2J=S, =NR16, -Na, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(O)R16, -NO2, =0, =S, =NR16, -N3, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0206] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-NO2, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen-NO2J=S, =NR16, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(O)R16, -NO2, =0, =S, =NR16, -Ns, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl;wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0207] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(0)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -C(O)N(R16)2, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -C(O)R16, -NO2, =0, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro;wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0208] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -C(O)N(R16)2, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -C(O)R16, -NO2, =0, and -CN; andwherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0209] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;CM alkyl optionally substituted with one or more substituents independently selected from: halogen-NO2, =S, =NR16, -N3, and -CN; andC4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2J=0, =S, =NR16, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(O)R16, -NO2,=0, =S, =NR16, -N3, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0210] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, =0, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -C(0)R16, -NO2, =0, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle,substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0211] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)N(R16)2, -N(R16)C(O)R16, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -0C(0)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -0C(0)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -NO2J=0, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle,substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0212] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -N(R16)C(O)R16, and =0;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -0C(0)R16, and -N(R16)C(O)R16; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -0C(0)R16, and -N(R16)C(O)R16; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -NO2Jand =0; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle,substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0213] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -N(R16)C(O)R16, and =0;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -0C(0)R16, and -N(R16)C(O)R16; and3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -0C(0)R16, and -N(R16)C(O)R16; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -NO2Jand =0; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl;wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0214] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-N(R16)(R18) and =0;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, and -N(R16)2; and3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen;C2-3 alkyl optionally substituted with one or more substituents independently selected from -N(R16)2; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen and C1-6alkyl; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-memberedheterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0215] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-N(R16)(R18) and =0;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, and -N(R16)2; and3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen;C2-3 alkyl optionally substituted with one or more substituents independently selected from -N(R16)2; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen and C1-6alkyl; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0216] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independentlyselected from: trifluoromethyl, =0,wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0217] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from: trifluoromethyl, =0, -CH2OCH2CH3, -N(CH.3)2, -CH2N(CH3)2,wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0218] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independentlyselected from: trifluoromethyl, =0, -CH2CH2N(CH3)2, V xwherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0219] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from: trifluoromethyl -CH2CH2N(CH3)2,wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; and wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy.

[0220] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from: trifluoromethyl, =0, -CH2OCH2CH3, -N(CH3)2, -CH2N(CH3)2,wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle,substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0221] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from: trifluoromethyl, =0, -CH2OCH2CHa, -N(CHa)2, -CH2N(CHa)2,wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro.

[0222] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from: trifluoromethyl, =0, -CH2OCH2CHa, -N(CHa)2, -CH2N(CH3)2, -C^CH^CHa)2,wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy.

[0223] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from: trifluoromethyl, =0,-CH2CH2N(CH3)2

[0224] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -SR16, -N(R16)(R18), -C(O)R16, -C(O)OR18, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, =0, =s, =NR16, -N3, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0225] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, =0, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy;wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0226] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and =0; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0227] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -OC(O)R16, -N(R16)C(O)R16, and =0; andwherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0228] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), and =0; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0229] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are eachindependently selected from:-OR17, -N(R16)(R18), and =0; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0230] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-OR17, -N(R16)(R18), and =0; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy.

[0231] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-N(R16)(R18) and =0; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro;wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy.

[0232] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from -N(CHa)2and =0; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; and wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy.

[0233] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from -N(CHJ)2and =0; and wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy.

[0234] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from -N(CHa)2and =0; wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro.

[0235] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from -N(CH3)2and =0.

[0236] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2J=S, =NR16, -Na, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andC4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2J=0, =S, =NR16, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle,substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0237] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2J=S, =NR16, -Na, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0238] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2J=S, =NR16, -Na, and -CN; andC4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2J=0, =S, =NR16, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0239] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2,-C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andC2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2J=S, =NR16, -Na, and -CN; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0240] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andC2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, and -CN; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0241] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, and -N(R16)C(O)R16; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andC2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)OR17, and -OC(O)R16; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0242] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, and -N(R16)2; and C3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen; andC2-3 alkyl optionally substituted with one or more substituents independently selected from -N(R16)2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle,substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0243] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, and -N(R16)2; and3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen; andC2-3 alkyl optionally substituted with one or more substituents independently selected from -N(R16)2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0244] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from: trifluoromethyl, -CH2OCH2CH3, -CH2N(CH3)2, -CH2CH2N(CH3)2,wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

[0245] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-memberedheterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from: trifluoromethyl, -CH2OCH2CH3, -CH2N(CH3)2, -CH2CH2N(CH3)2,

[0246] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(O)R16, -NO2, =0, =S, =NR16, -N3, and -CN.

[0247] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from: C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -C(O)R16, =0, and -CN.

[0248] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from: C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, and =0.

[0249] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl;wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen and C1-4alkyl.

[0250] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:

[0251] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from 3- to 10-membered heterocycle, which is optionally substituted, and substituted phenyl; wherein substituents on the 3- to 10-membered heterocycle and substituted phenyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -SR16, -N(R16)(R18), -C(O)R16, -C(O)OR18, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, =0, =s, =NR16, -N3, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2J=S, =NR16, -N3, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2J=0, =S, =NR16, -N3, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andC3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(O)R16, -NO2,=0, =S, =NR16, -N3, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0252] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from chromanyl, 2,3 -dihydrobenzofuranyl, pyridinyl, pyrazinyl, pyridin-2(lH)-on-yl, pyrimidine-2,4(lH,3H)-dion-yl, pyridazin-3(2H)-on-yl, quinolin-2(lH)-on-yl, 1,6-naphthyridin-2(lH)-on-yl, l,7-naphthyridin-2(lH)-on-yl, quinazoline-2,4(lH,3H)-dion-yl, pyrido[3,4-d]pyrimidine-2,4(lH,3H)-dion-yl, 5,6,7,8-tetrahydro-l,6-naphthyridin-2(lH)-on-yl, pyrido[4,3-d]pyrimidine-2,4(lH,3H)-dion-yl, l,3-dihydro-2H-benzo[d]imidazol-2-on-yl, isoquinolinyl, 2,7-naphthyridinyl, 2,6-naphthyridinyl, 1,6-naphthyridinyl, quinazolinyl, phthalazinyl, pyrazolo[l,5-a]pyrazinyl, imidazo[l,2-a]pyrazinyl, [l,2,4]triazolo[l,5- a]pyrazinyl, [l,2,4]triazolo[l,5-a]pyridinyl, each of which is optionally substituted, and substituted phenyl; wherein substituents on the chromanyl, 2,3-dihydrobenzofuranyl, pyridinyl, pyrazinyl, pyridin- 2(lH)-on-yl, pyrimidine-2,4(lH,3H)-dion-yl, pyridazin-3(2H)-on-yl, quinolin-2(lH)- on-yl, l,6-naphthyridin-2(lH)-on-yl, l,7-naphthyridin-2(lH)-on-yl, quinazoline- 2,4(lH,3H)-dion-yl, pyrido[3,4-d]pyrimidine-2,4(lH,3H)-dion-yl, 5,6,7,8-tetrahydro- l,6-naphthyridin-2(lH)-on-yl, pyrido[4,3-d]pyrimidine-2,4(lH,3H)-dion-yl, 1,3- dihydro-2H-benzo[d]imidazol-2-on-yl, isoquinolinyl, 2,7-naphthyridinyl, 2,6- naphthyridinyl, 1,6-naphthyridinyl, quinazolinyl, phthalazinyl, pyrazolo[l,5- a]pyrazinyl, imidazo[l,2-a]pyrazinyl, [l,2,4]triazolo[l,5-a]pyrazinyl, [l,2,4]triazolo[l,5-a]pyridinyl, and substituted phenyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -SR16, -N(R16)(R18), -C(O)R16, -C(O)OR18, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, =0, =s, =NR16, -N3, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -N3, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2,=S, =NR16, -N3, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16),-S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2J=0, =S, =NR16, -N3, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andC3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(O)R16, -NO2,=0, =S, =NR16, -N3, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0253] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from chromanyl, 2,3 -dihydrobenzofuranyl, pyridinyl, pyrazinyl, pyridin-2(lH)-on-yl, pyrimidine-2,4(lH,3H)-dion-yl, pyridazin-3(2H)-on-yl, quinolin-2(lH)-on-yl, 1,6-naphthyridin-2(lH)-on-yl, l,7-naphthyridin-2(lH)-on-yl, quinazoline-2,4(lH,3H)-dion-yl, pyrido[3,4-d]pyrimidine-2,4(lH,3H)-dion-yl, 5,6,7,8-tetrahydro-l,6-naphthyridin-2(lH)-on-yl, pyrido[4,3-d]pyrimidine-2,4(lH,3H)-dion-yl, l,3-dihydro-2H-benzo[d]imidazol-2-on-yl, isoquinolinyl, 2,7-naphthyridinyl, 2,6-naphthyridinyl, 1,6-naphthyridinyl, quinazolinyl, phthalazinyl, pyrazolo[l,5-a]pyrazinyl, imidazo[l,2-a]pyrazinyl, [l,2,4]triazolo[l,5- a]pyrazinyl, [l,2,4Jtriazolo[l,5-a]pyridinyl, each of which is optionally substituted, and substituted phenyl; wherein substituents or optional substituents of C are each independently selected from: -Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, =0, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -C(O)R16, -NO2,=0, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro;wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0254] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from chromanyl, 2,3 -dihydrobenzofuranyl, pyridinyl, pyrazinyl, pyridin-2(lH)-on-yl, pyrimidine-2,4(lH,3H)-dion-yl, pyridazin-3(2H)-on-yl, quinolin-2(lH)-on-yl, 1,6- naphthyridin-2(lH)-on-yl, l,7-naphthyridin-2(lH)-on-yl, quinazoline-2,4(lH,3H)-dion-yl, pyrido[3,4-d]pyrimidine-2,4(lH,3H)-dion-yl, 5,6,7,8-tetrahydro-l,6-naphthyridin-2(lH)-on-yl, pyrido[4,3-d]pyrimidine-2,4(lH,3H)-dion-yl, l,3-dihydro-2H-benzo[d]imidazol-2-on-yl, isoquinolinyl, 2,7-naphthyridinyl, 2,6-naphthyridinyl, 1,6-naphthyridinyl, quinazolinyl, phthalazinyl, pyrazolo[l,5-a]pyrazinyl, imidazo[l,2-a]pyrazinyl, [l,2,4]triazolo[l,5- a]pyrazinyl, [l,2,4]triazolo[l,5-a]pyridinyl, each of which is optionally substituted, and substituted phenyl; wherein substituents or optional substituents of C are each independently selected from: -Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from:halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -C(O)R16, -NO2, =0, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

[0255] In some embodiments, for the compound or salt of Formula (I) or (I-a), C is selected from chromanyl, 2,3 -dihydrobenzofuranyl, pyridinyl, pyrazinyl, pyridin-2(lH)-on-yl, pyrimidine-2,4(lH,3H)-dion-yl, pyridazin-3(2H)-on-yl, quinolin-2(lH)-on-yl, 1,6- naphthyridin-2(lH)-on-yl, l,7-naphthyridin-2(lH)-on-yl, quinazoline-2,4(lH,3H)-dion-yl, pyrido[3,4-d]pyrimidine-2,4(lH,3H)-dion-yl, 5,6,7,8-tetrahydro-l,6-naphthyridin-2(lH)-on-yl, pyrido[4,3-d]pyrimidine-2,4(lH,3H)-dion-yl, l,3-dihydro-2H-benzo[d]imidazol-2-on-yl, isoquinolinyl, 2,7-naphthyridinyl, 2,6-naphthyridinyl, 1,6-naphthyridinyl, quinazolinyl, phthalazinyl, pyrazolo[l,5-a]pyrazinyl, imidazo[l,2-a]pyrazinyl, [l,2,4]triazolo[l,5- a]pyrazinyl, [l,2,4]triazolo[l,5-a]pyridinyl, each of which is optionally substituted, and substituted phenyl;wherein substituents or optional substituents of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocy...

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A compound represented by the structure of Formula (I):or a pharmaceutically acceptable salt thereof, wherein:X1, X2, X3, and X4are each independently selected from N and C(R1), wherein at least one of X1, X2, and X3is CCR1);R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -OC(O)N(R11)2, -C(O)N(R11)2, -N(R11)C(0)R11, -N(R11)C(0)0R11, -N^^COJNCR11)2, -N(R11K:(S)N(R11)2, -NCRHJSCOXR11), -S(O)R11, -SCO)2R11, -SCO)2NCR11)2, -NO2, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C2-6alkyl, C2-6haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C2-6alkyl, C2-6haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN;R2is hydrogen or C1-6alkyl;R3aand R3bare each independently selected from hydrogen, halogen, -OR12, -SR12, -N(R12)2, -C(0)R12, -NO2, -CN, and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR12, -SR12, -N(R12)2, -C(0)R12, -NO2, and -CN;R4is hydrogen or C1-6alkyl;Y1is selected from -L1-, and -X5-L2-, wherein:L1is selected from C1-6alkylene, C2-6 alkenylene, and C3-6 carbocyclene, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -NO2, and -CN;X5is -O-, -N(R14)-, or -S-;L2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -NO2, and -CN;C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7- 10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -SR16, -N(R16)(R18), -C(O)R16, -C(O)OR18, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, =0, =S, =NR16, -Ns, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -Ns, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, =s, =NR16, -Ns, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl;C4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, =0, =S, =NR16, -N3, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl; andC3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, CM alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(O)R16, -NO2, =0, =S, =NR16, -N3, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10- membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2;Y2is selected from a bond, -O-, -S-, -N(R19)-, and C1-6alkylene;Z is selected from a bond, -C(O)-, -C(R20)2-, -C(O)C(R20)2-, -C(=N-CN)-, -C(O)O-, -C(O)O- C1.3 alkylene-, -C(O)N(R20)-, -C(S)-, -C(S)N(R20)-, -S(O)-, and -S(O)2-;B is selected from Ca-ucarbocycle and 3- to 14-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2J=0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(OX)R21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21,-N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -NO2, =0, =S, =NR21, -N3, and -CN;R11, R12, R13, R14, R15, R16, R19, and R20are each independently selected at each occurrence from hydrogen, C1-6alkyl, C3-6 carbocycle, and 3- to 6-memebred heterocycle, wherein each of the C1-6alkyl, C3-6 carbocycle, and 3- to 6-memebred heterocycle are optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R17is independently selected at each occurrence from: hydrogen;Ci alkyl substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN; andC2-6 alkyl, and C3-6 carbocycle, wherein each of the C2-6 alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R18is independently selected at each occurrence from C1-6alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R21is independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC<O)N(R22)2, -C(O)N(R22)2, -N(R22)C(O)R22, -N(R22)C(O)OR22, -N(R22)C(O)N(R22)2, -N(R22X:(S)N(R22)2, -N(R22)S(O)2(R22), -S<O)R22, -S(O)2R22, -S(O)2N(R22)2, -NO2,=0, =S, =NR22, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC(O)N(R22)2, -C(O)N(R22)2, -N(R22)C(O)R22, -N(R22)C(O)OR22,-N(R22)C(O)N(R22)2, -N(R22X:(S)N(R22)2, -N(R22)S(O)2(R22), -S<O)R22, -S(O)2R22, -S(O)2N(R22)2, -NO2, =0, =S, =NR22, -Ns, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle; andR22is independently selected at each occurrence from hydrogen, C1-6alkyl, C1-6haloalkyl, Ci- 6 hydroxyalkyl, and C1-6aminoalkyl.

2. The compound or salt of claim 1, wherein Y1is -L1-; and L1is selected from C2-6 alkenylene and C3-6 carbocyclene, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -NO2, and -CN.

3. The compound or salt of claim 2, wherein L1is C2-6 alkenylene optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -N02, and -CN.

4. The compound or salt of claim 3, wherein L1is5. The compound or salt of claim 2, wherein L1is C3-6 carbocyclene optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -NO2, and -CN.

6. The compound or salt of claim 5, wherein L1is7. The compound or salt of any one of claims 1-6, wherein C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from =0, methyl, Ci haloalkyl; and C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(0)R16, -C(0)0R17, -0C(0)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2,=S, =NR16, -Ns, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, Ci- 4 alkyl, and C1-4haloalkyl.

8. The compound or salt of claim 7, wherein C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 caibocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 caibocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from =0, methyl, Ci haloalkyl; and C2-3 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -NO2, and -CN.

9. The compound or salt of claim 8 wherein C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 caibocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 caibocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from =0, methyl, Ci haloalkyl; and C2-3 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -N(R16)2, -C(0)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -NO2, and -CN; and R16selected at each occurrence from hydrogen, Ci-6 alkyl, C3-6 caibocycle, and 3- to 6-memebred heterocycle, wherein each of the C1-6alkyl, C3-6 caibocycle, and 3- to 6-memebred heterocycle are optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-Ci- 6 haloalkyl, =0, and -CN. F10. The compound or salt of claim 9, wherein C is11. The compound or salt of any one of claims 1-10, wherein Z is selected from a bond, -C(O)-, -C(R20)2-, -C(O)C(R20)2-, -C(O)O-, -C(O)O-CI.3 alkylene-, -C(O)N(R20)-, -S(O)-, and -S(O)2-.

12. The compound or salt of claim 11, wherein Z is selected from a bond, -C(O)-, -C(O)O-, -C(O)O-(Ci-3 alkylene)-, -S(O)-, and -S(O)2-.

13. The compound or salt of claim 12, wherein Z is -C(O)O-(Ci-3 alkylene)-.

14. The compound or salt of any one of claims 1-13, wherein B is C3-14 caibocycle optionally substituted with one or more substituents independently selected from:halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andCs-io carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -N02, =0, =S, =NR21, -N3, and -CN.

15. The compound or salt of clam 14, wherein16. The compound or salt of claim 1, wherein the structure of Formula (I) is represented by the structure of Formula (I-a):or a pharmaceutically acceptable salt thereof, wherein:X1, X2, X3, and X4are each independently selected from N and C(R1), wherein at least one of X1, X2, and X3is CCR1);R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -0C(0)N(R11)2, -C(0)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N^^COJNCR11)2, -N(R11)C(S)N(R11)2, -NCRHJSCOXR11), -S(O)R11, -SCO)2R11, -SCO)2NCR11)2, -NO2, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, =0, =S, and -CN;R2is hydrogen or C1-6alkyl;R3aand R3bare each independently selected from hydrogen, halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -NO2, -CN, and C1-6alkyl optionally substituted with one or moresubstituents independently selected from halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -NO2, and -CN;R4is hydrogen or C1-6alkyl;Y1is selected from -L1- and -X5-L2-, wherein:L1is C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -NO2, and -CN;X5is -O-, -N(R14)-, or -S-;L2is selected from a bond and C1-6alkylene optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -NO2, and -CN;C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7- 10 carbocycle, 3- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -SR16, -N(R16)(R18), -C(O)R16, -C(O)OR18, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, =0, =S, =NR16, -Ns, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, -Ns, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16,-N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, =s, =NR16, -N3, and -CN; andCM carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl;C4-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -OC(O)N(R16)2, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)C(O)OR16, -N(R16)C(O)N(R16)2, -N(R16)C(S)N(R16)2, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, -NO2, =0, =S, =NR16, -N3, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and Ci- 4 haloalkyl; andC3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -SR16, -N(R16)2, -C(O)R16, -NO2, =0, =S, =NR16, -N3, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10- membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2;Y2is selected from a bond, -O-, -S-, -N(R19)-, and C1-6alkylene;Z is selected from a bond, -C(O)-, -C(R20)2-, -C(O)C(R20)2-, -C(=N-CN)-, -C(O)O-, -C(O)N(R20)-, -C(S)-, -C(S)N(R20)-, -S(O)-, and -S(O)2-;B is selected from C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2J=0, =S, =NR21, -N3, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21,-N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2,=0, =S, =NR21, -N3, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)N(R21)2, -N(R21)C(S)N(R21)2, -N(R21)S(O)2(R21), -S(O)R21, -S(O)2R21, -S(O)2N(R21)2, -NO2, =0, =s, =NR21, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -SR21, -N(R21)2, -C(O)R21, -NO2, =0, =S, =NR21, -N3, and -CN;R11, R12, R13, R14, R15, R16, R19, and R20are each independently selected at each occurrence from hydrogen, C1-6alkyl, and C3-6 carbocycle, wherein each of the C1-6alkyl and C3- 6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R17is independently selected at each occurrence from: hydrogen;Ci alkyl substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN; andC2-6 alkyl, and C3-6 carbocycle, wherein each of the C2-6 alkyl and C3-6 carbocycle is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R18is independently selected at each occurrence from C1-6alkyl and C3-6 carbocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN;R21is independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC<O)N(R22)2, -C(O)N(R22)2, -N(R22)C(O)R22, -N(R22)C(O)OR22, -N(R22)C(O)N(R22)2, -N(R22X:(S)N(R22)2, -N(R22)S(O)2(R22), -S<O)R22, -S(O)2R22, -S(O)2N(R22)2, -NO2,=0, =S, =NR22, -N3, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR22, -SR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -OC(O)N(R22)2, -C(O)N(R22)2, -N(R22)C(O)R22, -N(R22)C(0)0R22, -N(R22)C(O)N(R22)2, -N(R22X:(S)N(R22)2, -N(R22)S(O)2(R22), -S<O)R22, -S(O)2R22, -S(O)2N(R22)2, -NO2, =0, =S, =NR22, -N3, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle; andR22is independently selected at each occurrence from hydrogen, C1-6alkyl, C1-6haloalkyl, Ci- 6 hydroxyalkyl, and C1-6aminoalkyl.

17. The compound or salt of claim 16, wherein no more than two of X1, X2, X3, and X4are N.

18. The compound or salt of either claim 16 or claim 17, wherein:X1is CCR1), X2is CCR1), X3is CCR1), and X4is CCR1);X1is N, X2is CCR1), X3is CCR1), and X4is CCR1);X1is CCR1), X2is N, X3is CCR1), and X4is CCR1);X1is CCR1), X2is CCR1), X3is N, and X4is CCR1);X1is CCR1), X2is CCR1), X3is CCR1), and X4is N; orX1is N, X2is CCR1), X3is N, and X4is CCR1).

19. The compound or salt according to any one of claims 16-18, wherein R1is independently selected at each occurrence from: hydrogen, halogen, -OR11, -N(R11)2, -C(O)R11, -C(OX)R11, -OC(O)R11, -C(0)N(R11)2, -N(R11)C(0)R11, -N02, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted by one or more substituents independently selected from: halogen, -OR11, -N(R11)2, =0, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -N(R11)2, =0, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -N(R11)2, =0, and -CN.

20. The compound or salt according to any one of claims 16-19, wherein R1is independently selected at each occurrence from: hydrogen, halogen, and C1-6alkyl optionally substitutedby one or more substituents independently selected from halogen and 3- to 6-membered heterocycle.

21. The compound or salt according to any one of claims 16-20, wherein R1is independently selected at each occurrence from: hydrogen, fluoro, methyl, trifluoromethyl,and22. The compound or salt of claim 19, wherein R1is selected from halogen and Ci-6 alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR11, -N(R11)2, =0, and -CN.

23. The compound or salt of claim 22, wherein R1is selected from Cl and24. The compound or salt according to any one of claims 16-21, wherein R2is selected from hydrogen and methyl.

25. The compound or salt according to any one of claims 16-24, wherein R2is hydrogen.

26. The compound or salt according to any one of claims 16-25, wherein R3aand R3bare each hydrogen.

27. The compound or salt according to any one of claims 16-26, wherein R4is hydrogen.

28. The compound or salt according to any one of claims 16-27, wherein Y2is selected from a bond, Ci.3 alkylene, -0-, and -N(CH3)29. The compound or salt according to any one of claims 16-27, wherein Y2is selected from a bond, -0-, and -N(CH3)-.

30. The compound or salt according to any one of claims 16-29, wherein Y2is selected from a bond.

31. The compound or salt of claim 29, wherein Y2is methylene.

32. The compound or salt according to any one of claims 16-30, wherein Z is selected from a bond and -C(O)-.

33. The compound or salt according to any one of claims 16-32, wherein Z is -C(O)-.

34. The compound or salt according to any one of claims 16-33, wherein Y1is selected from -L1- and -X5-L2-, wherein:L1is Ci-6 alkylene;X5is -O- or -N(R14)-; andL2is a bond.

35. The compound or salt according to any one of claims 16-34, wherein Y1is-L1-.

36. The compound or salt according to any one of claims 16-35, wherein L1is C1.3 alkylene.

37. The compound or salt according to any one of claims 16-36, wherein L1is methylene or(methyl)methylene.

38. The compound or salt according to any one of claims 16-36, wherein L1is methylene, (methyl)methylene, ethylene, or propylene.

39. The compound or salt according to any one of claims 16-34, wherein Y1is -X5-L2-.

40. The compound or salt according to any one of claims 16-34 and 39, wherein X5is -O- or -N(CH3)-.

41. The compound or salt according to any one of claims 16-34, 39, and 40, wherein L2is a bond.

42. The compound or salt according to any one of claims 16-41, wherein B is selected from C3- 10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21,-N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(0)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from:halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(O)R21, =0, and -CN.

43. The compound or salt according to any one of claims 16-42, wherein B is selected from C3- 10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, -N(R21)S(O)2(R21), and -S(O)2R21; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and 3- to 10-membered heterocycle; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, =0, C1-6alkyl, and C1-6haloalkyl.

44. The compound or salt according to any one of claims 16-43, wherein B is selected from C3- 10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: hydrogen, fluoro, chloro, methyl, trifluoromethyl, -CH2N(CH3)2, -NHCH2CF3, -NHS^CEb,45. The compound or salt according to any one of claims 16-44, wherein B is selected from cyclohexyl, bicyclo[l.l.l]pentyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, pyrazolo[l,5-a]pyridine, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21,-N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, Ci-6 alkyl, Ci-6 haloalkyl, -OR21, -N(R21)2, -C(O)R21, =0, and -CN.

46. The compound or salt according to any one of claims 16-45, wherein B is selected from cyclohexyl, bicyclo[l.l.l]pentyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, pyrazolo[l,5-a]pyridine, each of which is optionally substituted with one or more substituents independently selected from: halogen, -NCR21)2, -N(R21)S(O)2(R21), and -SCO)2R21; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -N(R21)2, and 3- to 10-membered heterocycle; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, =0, C1-6alkyl, and C1-6haloalkyl.

47. The compound or salt according to any one of claims 16-46, wherein B is selected from cyclohexyl, bicyclo[l.l.l]pentyl, phenyl, pyrrolidinyl, pyridyl, lH-benzo[d]imidazolyl, indolinyl, pyrazolo[l,5-a]pyridine, each of which is optionally substituted with one or more substituents independently selected from: hydrogen, fluoro, chloro, methyl, trifluoromethyl,48. The compound or salt according to any one of claims 16-44, wherein B is selected from cyclohexyl, bicyclo[l.l.l]pentyl, phenyl, pyrrolidinyl, piperidinyl, pyridyl, 1H-benzo[d]imidazolyl, indolinyl, pyrazolo[l,5-a]pyridinyl, indazolyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21,-N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -OC(O)N(R21)2, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)OR21, -OC(O)R21, -C(O)N(R21)2, -N(R21)C(O)R21, -N(R21)S(O)2(R21), -S(O)2R21, -S(O)2N(R21)2, =0, and -CN; and C3-10 carbocycle and 3- to 10-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR21, -N(R21)2, -C(O)R21, =0, and -CN.

49. The compound or salt according to any one of claims 16-43 and 45-47, wherein R20is independently selected at each occurrence from hydrogen and C1-6alkyl, wherein each of the C1-6alkyl is optionally substituted with one or more substituents independently selected from halogen, -OH, -NH2, -O-C1-6alkyl, -O-C1-6haloalkyl, =0, and -CN.

50. The compound or salt according to any one of claims 16-49, wherein R21is independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted by one or more substituents independently selected from: halogen, -OR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -C(O)N(R22)2, =0, and -CN; andC3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR22, -N(R22)2, -C(O)R22, -C(O)OR22, -OC(O)R22, -C(O)N(R22)2, -N(R22)C(O)R22, =0, and -CN.

51. The compound or salt according to any one of claims 16-50, wherein R21is independently selected at each occurrence from: hydrogen, Ci-6 alkyl, and Ci-6 haloalkyl; and phenyl and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, Ci-6 alkyl, Ci-6 haloalkyl, -N(R22)C(0)R22, and =0.

52. The compound or salt according to any one of claims 16-51, wherein R22is independently selected at each occurrence from hydrogen and Ci-6 alkyl.

53. The compound or salt according to any one of claims 16-52, wherein B is selected from:

54. The compound or salt according to any one of claims 16-52, wherein B is selected from:

55. The compound or salt according to any one of claims 16-53, wherein C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 caibocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10- membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)S(O)2(R16), -S(O)2R16, -S(O)2N(R16)2, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(0)0R16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)S(O)2(R16), -S(O)2R16, -S(O)2N(R16)2, and -CN; andC3-6 caibocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(0)0R17, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, and -CN; andC3-6 caibocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;CM alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, and -CN; andCM carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andCM carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, CM alkyl, CM haloalkyl, -OR16, -N(R16)2, -C(O)R16, -NO2, =0, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and CM alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl; wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from -NH2; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heterocycloalkyl, 7- to 10-membered heterocycle, and substituted cyclopentyl, any substituents on C are further selected from -NO2.

56. The compound or salt according to any one of claims 16-53, wherein C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl;wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10- membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from: -N(R16XR18) and =0;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, and -N(R16)2; and3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen;CM alkyl optionally substituted with one or more substituents independently selected from -N(R16)2;C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen and C1-6alkyl; and wherein when R2is selected from hydrogen and C1-6alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and CM alkyl, any substituents on C are further selected from methoxy; and wherein when C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 5-membered heterocycle, 6-membered heteroaryl, 7- to 10-membered heterocycle, substituted phenyl, and substituted cyclopentyl, any substituents on C are further selected from methyl.

57. The compound or salt according to any one of claims 16-56, wherein C is selected from cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10-membered heterocycle, each of which is optionally substituted, substituted phenyl, and substituted cyclopentyl; wherein substituents on the cyclopropyl, cyclobutyl, cyclohexyl, C7-10 carbocycle, 3- to 10- membered heterocycle, substituted phenyl, and substituted cyclopentyl of C are each independently selected from: -CH2CH2N(CH3)2,58. The compound or salt according to any one of claims 16-57, wherein C is selected from optionally substituted 3- to 10-membered heterocycle and substituted phenyl.

59. The compound or salt according to any one of claims 16-58, wherein C is selected from optionally substituted 3- to 10-membered heterocycle and substituted phenyl; wherein substituents on 3- to 10-membered heterocycle and substituted phenyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)S(O)2(R16), -S(O)2R16, -S(O)2N(R16)2, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)S(O)2(R16), -S(O)2R16, -S(O)2N(R16)2, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR17, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, and -CN; andC3-6carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -C(0)R16, -N02, =0, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from 6-membered heteroaryl, 7- to 10-membered heterocycle, and substituted phenyl, any substituents on C are further selected from methyl.

60. The compound or salt according to any one of claims 16-59, wherein C is selected from optionally substituted 3- to 10-membered heterocycle and substituted phenyl; wherein substituents on the 3- to 10-membered heterocycle and substituted phenyl of C are each independently selected from: -N(R16XR18) and =0;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, and -N(R16)2; and3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen;C2-3 alkyl optionally substituted with one or more substituents independently selected from -NQt16}?;C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen and C1-6alkyl; and wherein when R2is selected from hydrogen, any substituents on C are further selected from fluoro and methoxy; and wherein when C is selected from 6-membered heteroaryl, 7- to 10-membered heterocycle, and substituted phenyl, any substituents on C are further selected from methyl.

61. The compound or salt according to any one of claims 16-60, wherein C is selected from chromanyl, 2,3-dihydrobenzofuranyl, pyridinyl, pyrazinyl, pyridin-2(lH)-on-yl, pyrimidine- 2,4(lH,3H)-dion-yl, pyridazin-3(2H)-on-yl, quinolin-2(lH)-on-yl, l,6-naphthyridin-2(lH)- on-yl, l,7-naphthyridin-2(lH)-on-yl, quinazoline-2,4(lH,3H)-dion-yl, pyrido[3,4- d]pyrimidine-2,4(lH,3H)-dion-yl, 5,6,7,8-tetrahydro-l,6-naphthyridin-2(lH)-on-yl, pyrido[4,3-d]pyrimidine-2,4(lH,3H)-dion-yl, l,3-dihydro-2H-benzo[d]imidazol-2-on-yl, isoquinolinyl, 2,7-naphthyridinyl, 2,6-naphthyridinyl, 1,6-naphthyridinyl, quinazolinyl, phthalazinyl, pyrazolo[l,5-a]pyrazinyl, imidazo[l,2-a]pyrazinyl, [l,2,4]triazolo[l,5- a]pyrazinyl, [l,2,4Jtriazolo[l,5-a]pyridinyl, each of which is optionally substituted, and substituted phenyl.

62. The compound or salt according to any one of claims 16-60, wherein C is selected from chromanyl, 2,3-dihydrobenzofuranyl, pyridinyl, pyrazinyl, pyridin-2(lH)-on-yl, pyrimidine- 2,4(lH,3H)-dion-yl, pyridazin-3(2H)-on-yl, quinolin-2(lH)-on-yl, l,6-naphthyridin-2(lH)- on-yl, l,7-naphthyridin-2(lH)-on-yl, quinazoline-2,4(lH,3H)-dion-yl, pyrido[3,4- d]pyrimidine-2,4(lH,3H)-dion-yl, 5,6,7,8-tetrahydro-l,6-naphthyridin-2(lH)-on-yl,pyrido[4,3-d]pyrimidine-2,4(lH,3H)-dion-yl, l,3-dihydro-2H-benzo[d]imidazol-2-on-yl, isoquinolinyl, 2,7-naphthyridinyl, 2,6-naphthyridinyl, 1,6-naphthyridinyl, quinazolinyl, phthalazinyl, pyrazolo[l,5-a]pyrazinyl, imidazo[l,2-a]pyrazinyl, [l,2,4]triazolo[l,5- a]pyrazinyl, [l,2,4]triazolo[l,5-a]pyridinyl, each of which is optionally substituted, and substituted phenyl; wherein substituents on chromanyl, 2,3-dihydrobenzofuranyl, pyridinyl, pyrazinyl, pyridin- 2(lH)-on-yl, pyrimidine-2,4(lH,3H)-dion-yl, pyridazin-3(2H)-on-yl, quinolin- 2(lH)-on-yl, l,6-naphthyridin-2(lH)-on-yl, l,7-naphthyridin-2(lH)-on-yl, quinazoline-2,4(lH,3H)-dion-yl, pyrido[3,4-d]pyrimidine-2,4(lH,3H)-dion-yl, 5,6,7,8-tetrahydro-l,6-naphthyridin-2(lH)-on-yl, pyrido[4,3-d]pyrimidine- 2,4(lH,3H)-dion-yl, l,3-dihydro-2H-benzo[d]imidazol-2-on-yl, isoquinolinyl, 2,7- naphthyridinyl, 2,6-naphthyridinyl, 1,6-naphthyridinyl, quinazolinyl, phthalazinyl, pyrazolo[ 1 ,5-a]pyrazinyl, imidazo[ 1 ,2-a]pyrazinyl, [1 ,2,4]triazolo[ 1 ,5-a]pyrazinyl, [l,2,4]triazolo[l,5-a]pyridinyl, and substituted phenyl of C are each independently selected from:-Cl, -Br, -I, -OR17, -N(R16XR18), -C(O)R16, -C(O)OR18, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)S(O)2(R16), -S(O)2R16, -S(O)2N(R16)2, =0, and -CN;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)S(O)2(R16), -S(O)2R16, -S(O)2N(R16)2, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl;C2-3 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR16, -N(R16)2, -C(O)R16, -C(0)0R17, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -N(R16)S(O)2(R16), -S(O)R16, -S(O)2R16, -S(O)2N(R16)2, and -CN; andC3-6 carbocycle and 3- to 6-membered heterocycle each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-4alkyl, and C1-4haloalkyl; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR16, -N(R16)2, -C(O)R16, -NO2, =0, and -CN; and wherein when R2is selected from hydrogen and C2-6 alkyl, any substituents on C are further selected from fluoro; wherein when R2is selected from hydrogen, methyl, and C3-6 alkyl, any substituents on C are further selected from methoxy; wherein when C is selected from 6-membered heteroaryl, 7- to 10-membered heterocycle, and substituted phenyl, any substituents on C are further selected from methyl.

63. The compound or salt according to any one of claims 16-62, wherein C is selected from chromanyl, 2,3-dihydrobenzofuranyl, pyridinyl, pyrazinyl, pyridin-2(lH)-on-yl, pyrimidine- 2,4(lH,3H)-dion-yl, pyridazin-3(2H)-on-yl, quinolin-2(lH)-on-yl, l,6-naphthyridin-2(lH)- on-yl, l,7-naphthyridin-2(lH)-on-yl, quinazoline-2,4(lH,3H)-dion-yl, pyrido[3,4- d]pyrimidine-2,4(lH,3H)-dion-yl, 5,6,7,8-tetrahydro-l,6-naphthyridin-2(lH)-on-yl, pyrido[4,3-d]pyrimidine-2,4(lH,3H)-dion-yl, l,3-dihydro-2H-benzo[d]imidazol-2-on-yl, isoquinolinyl, 2,7-naphthyridinyl, 2,6-naphthyridinyl, 1,6-naphthyridinyl, quinazolinyl, phthalazinyl, pyrazolo[l,5-a]pyrazinyl, imidazo[l,2-a]pyrazinyl, [l,2,4]triazolo[l,5- a]pyrazinyl, [l,2,4Jtriazolo[l,5-a]pyridinyl, each of which is optionally substituted, and substituted phenyl; wherein substituents on chromanyl, 2,3-dihydrobenzofuranyl, pyridinyl, pyrazinyl, pyridin- 2(lH)-on-yl, pyrimidine-2,4(lH,3H)-dion-yl, pyridazin-3(2H)-on-yl, quinolin- 2(lH)-on-yl, l,6-naphthyridin-2(lH)-on-yl, l,7-naphthyridin-2(lH)-on-yl, quinazoline-2,4(lH,3H)-dion-yl, pyrido[3,4-d]pyrimidine-2,4(lH,3H)-dion-yl, 5,6,7,8-tetrahydro-l,6-naphthyridin-2(lH)-on-yl, pyrido[4,3-d]pyrimidine- 2,4(lH,3H)-dion-yl, l,3-dihydro-2H-benzo[d]imidazol-2-on-yl, isoquinolinyl, 2,7- naphthyridinyl, 2,6-naphthyridinyl, 1,6-naphthyridinyl, quinazolinyl, phthalazinyl, pyrazolo[ 1 ,5-a]pyrazinyl, imidazo[ 1 ,2-a]pyrazinyl, [1 ,2,4]triazolo[ 1 ,5-a]pyrazinyl, [l,2,4]triazolo[l,5-a]pyridinyl, and substituted phenyl of C are each independently selected from:-N(R16XR18) and =0;Ci alkyl substituted with one or more substituents independently selected from: halogen, -OR16, and -N(R16)2; and3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen;C2-3 alkyl optionally substituted with one or more substituents independently selected from -NQt16}?; andC3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen and C1-6alkyl; wherein when R2is selected from hydrogen, any substituents on C are further selected from fluoro and methoxy; and wherein when C is selected from 6-membered heteroaryl, 7- to 10-membered heterocycle, and substituted phenyl, any substituents on C are further selected from methyl.

64. The compound or salt according to any one of claims 16-63, wherein C is selected from chromanyl, 2,3-dihydrobenzofuranyl, pyridinyl, pyrazinyl, pyridin-2(lH)-on-yl, pyrimidine- 2,4(lH,3H)-dion-yl, pyridazin-3(2H)-on-yl, quinolin-2(lH)-on-yl, l,6-naphthyridin-2(lH)- on-yl, l,7-naphthyridin-2(lH)-on-yl, quinazoline-2,4(lH,3H)-dion-yl, pyrido[3,4- d]pyrimidine-2,4(lH,3H)-dion-yl, 5,6,7,8-tetrahydro-l,6-naphthyridin-2(lH)-on-yl, pyrido[4,3-d]pyrimidine-2,4(lH,3H)-dion-yl, l,3-dihydro-2H-benzo[d]imidazol-2-on-yl, isoquinolinyl, 2,7-naphthyridinyl, 2,6-naphthyridinyl, 1,6-naphthyridinyl, quinazolinyl, phthalazinyl, pyrazolo[l,5-a]pyrazinyl, imidazo[l,2-a]pyrazinyl, [l,2,4]triazolo[l,5- a]pyrazinyl, [l,2,4Jtriazolo[l,5-a]pyridinyl, each of which is optionally substituted, and substituted phenyl; wherein substituents on chromanyl, 2,3-dihydrobenzofuranyl, pyridinyl, pyrazinyl, pyridin- 2(lH)-on-yl, pyrimidine-2,4(lH,3H)-dion-yl, pyridazin-3(2H)-on-yl, quinolin- 2(lH)-on-yl, l,6-naphthyridin-2(lH)-on-yl, l,7-naphthyridin-2(lH)-on-yl, quinazoline-2,4(lH,3H)-dion-yl, pyrido[3,4-d]pyrimidine-2,4(lH,3H)-dion-yl, 5,6,7,8-tetrahydro-l,6-naphthyridin-2(lH)-on-yl, pyrido[4,3-d]pyrimidine- 2,4(lH,3H)-dion-yl, l,3-dihydro-2H-benzo[d]imidazol-2-on-yl, isoquinolinyl, 2,7- naphthyridinyl, 2,6-naphthyridinyl, 1,6-naphthyridinyl, quinazolinyl, phthalazinyl, pyrazolo[ 1 ,5-a]pyrazinyl, imidazo[ 1 ,2-a]pyrazinyl, [1 ,2,4]triazolo[ 1 ,5-a]pyrazinyl, [l,2,4]triazolo[l,5-a]pyridinyl, and substituted phenyl of C are each independently selected from: -CF3, =0, -CH2OCH2CH3, -N(CH3)2, -CH2N(CH3)2, -wherein when R2is selected from hydrogen, any substituents on C are further selected from fluoro and methoxy; and wherein when C is selected from 6-membered heteroaryl, 7- to 10-membered heterocycle, and substituted phenyl, any substituents on C are further selected from methyl.

65. The compound or salt according to any one of claims 16-64, wherein R16is selected from hydrogen and C1-6alkyl.

66. The compound or salt according to any one of claims 16-65, wherein R18is selected from C1-6alkyl.

67. The compound or salt according to any one of claims 16-66, wherein C is selected from:

68. The compound or salt according to any one of claims 16-66, wherein C is selected from:

69. The compound or salt according to any one of claims 16-68, wherein R11, R12, R13, R14, R15, R16, R19, and R20are each independently selected at each occurrence from hydrogen and methyl.

70. The compound or salt according to any one of claims 16-69, wherein R16is independently selected at each occurrence from hydrogen and methyl.

71. The compound or salt according to any one of claims 16-70, wherein R16is hydrogen.

72. The compound or salt according to any one of claims 16-71, wherein R14, R16, or R19is methyl.

73. The compound or salt of claim 16, wherein the compound is selected from:

74. The compound or salt of claim 1 or claim 16, wherein the compound is selected from a compound of Table 1.

75. A pharmaceutical composition comprising pharmaceutically acceptable excipient and a compound or salt of any one of claims 1-74.

76. A method of modulating alpha 4 beta 7 integrin in a subject in need thereof, comprising administering to the subject a compound or salt of any one of claims 1-74 or a pharmaceutical composition of claim 74.

77. A method of treating an inflammatory disease or condition comprising administering to a subject in need thereof a compound or salt of any one of claims 1- or a pharmaceutical composition of claim 75.

78. The method of claim 77, wherein the inflammatory disease or condition is selected from: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, graft-versus-host disease, type 1 diabetes, immune-mediated colitis, checkpoint inhibitor induced colitis, and primary sclerosing cholangitis.

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