SARM1 inhibitors

Abstract

This disclosure is drawn to SARM1 inhibitors, compositions thereof, and associated methods, useful for inhibition of SARM1 activity and / or for treating or preventing neurological disorders.

Description

SARM1 INHIBITORS CROSS-REFERENCE

[0001] This application claims benefit of U.S. Provisional Patent Application No.63 / 569,667 filed on March 25, 2024, and U.S. Provisional Patent Application No.63 / 768,788 filed on March 7, 2025, each of which is incorporated herein by reference in its entirety. FIELD OF THE INVENTION

[0002] Described herein are compounds and compositions, and associated methods, useful for inhibition of SARM1 activity and / or for treating or preventing a neurological disorder. BACKGROUND OF THE INVENTION

[0003] Aging constitutes the main risk factor for the development of neurodegenerative diseases. Axonal degeneration is an important pathological event in many neurodegenerative and neurological disorders, including peripheral neuropathy and traumatic brain injury (Gerdts, J. et al., Neuron, 2016, 89, 449–60). Axonal degeneration has also been implicated in, for example, Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis, where degeneration precedes symptom onset and widespread neuronal loss (Kurowska, Z. et al., J. Parkinson’s Dis., 2016, 6, 703–07). While these neurological conditions have unique underlying etiologies, inhibition of axonal degeneration in the conditions’ early stages may slow or prevent their progression by preventing the loss of functional synapses and maintaining neuronal connectivity (Essuman, K. et al., Neuron, 2017 Mar.22, 93(6), 1334-43).

[0004] Axonal degeneration after injury occurs both toward the proximal cell body (termed retrograde degeneration) and toward the distal axon terminal (termed Wallerian or orthograde degeneration) (Kanamori A. et al., Am. J. Pathol.2012 Jul; 181(1):62-73). Wallerian degeneration, which occurs in that section of the axon that is distal to the site of injury, occurs after axonal injury in both the peripheral nervous system (PNS) and the central nervous system (CNS). Wallerian degeneration usually begins within 24–36 hours of a lesion. Prior to degeneration, the distal section of the axon tends to remain electrically excitable, while after injury, the axonal skeleton disintegrates and the axonal membrane breaks apart.

[0005] The processes of death of the cell body and degeneration of the axon are independent events. As alluded to above, evidence exists indicating that the degeneration of axons precedes clinical symptoms in neurodegenerative diseases and occurs before cell body loss. Thus, axonal degeneration constitutes an early event in pathological processes and provides a potentialtherapeutic target to treat neurodegeneration prior to neuronal cell death (Salvadores, N. et al., Front. Neurosci., 2017, 11, 451).

[0006] In view of the above, new modalities are needed for the treatment of neurological disorders such as neurodegenerative disease by the prevention of axonal degeneration. SUMMARY OF THE INVENTION

[0007] In one aspect described herein is a compound of Formula (I’), or a pharmaceutically acceptable salt thereof:Formula (I’); wherein: A and G are independently selected from C(R2) and N; W, X, Y, and Z are independently selected from C(R2) and N, wherein at least one of W, X, Y, and Z is C(R2); J is C(R3)(R4), O, S, or N(R3a); each L is C(R4a)2; each L1is C(R4b)2; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; each R5is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; m is 0, 1, 2, or 3; n is 1 or 2; and p is 1, 2, or 3.

[0008] In another aspect described herein is a compound of Formula (I), or a pharmaceutically acceptable salt thereof:Formula (I); wherein: A and G are independently selected from C(R2) and N; W, X, Y, and Z are independently selected from C(R2) and N, wherein at least one of W, X, Y, and Z is C(R2); J is C(R3)(R4), O, S, or N(R3a); R1is selected from hydrogen and C1-6alkyl;each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R5is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; m is 0, 1, 2, or 3; n is 1 or 2; and p is 1, 2, or 3.

[0009] In some embodiments is a compound of Formula (I’) or (I), wherein A and G are C(R2). In some embodiments is a compound of Formula (I’) or (I), wherein A is C(R2) and G is N. In some embodiments is a compound of Formula (I’) or (I), wherein A is N and G is C(R2).

[0010] In some embodiments is a compound of Formula (I’) or (I), or a pharmaceutically acceptable salt thereof, having the structure of Formula (Ia):Formula (Ia).

[0011] In some embodiments is a compound of Formula (I’), (I), or (Ia), wherein W, X, Y, and Z are C(R2). In some embodiments is a compound of Formula (I’), (I), or (Ia), wherein W, X, and Y are C(R2) and Z is N. In some embodiments is a compound of Formula (I’), (I), or (Ia), wherein W, X, and Z are C(R2) and Y is N. In some embodiments is a compound of Formula (I’), (I), or (Ia), wherein W, Y, and Z are C(R2) and X is N. In some embodiments is a compound of Formula (I’), (I), or (Ia), wherein X, Y, and Z are C(R2) and W is N.

[0012] In another aspect described herein is a compound of Formula (II’), or a pharmaceutically acceptable salt thereof:Formula (II’); wherein: J is C(R3)(R4), O, S, or N(R3a); J1is C(R2) or N; J2is O, S, or N(R3b); each L is C(R4a)2; each L1is C(R4b)2; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one,two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3bis selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; each R5is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), -C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R6is independently selected from halogen, oxo, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or two R6attached to the same carbon atom are combined to form a C3-6cycloalkyl; each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2- C3haloalkyl;each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; m is 0, 1, 2, 3, 4, or 5; n is 1 or 2; p is 1, 2, or 3; q is 0, 1, or 2; v is 0, 1, 2, 3, or 4; and indicates a single or double bond such that all valences are satisfied.

[0013] In another aspect described herein is a compound of Formula (II), or a pharmaceutically acceptable salt thereof:Formula (II); wherein: J is C(R3)(R4), O, S, or N(R3a); J1is C(R2) or N; J2is O, S, or N(R3b); R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one,two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3bis selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R5is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R6is independently selected from halogen, oxo, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or two R6attached to the same carbon atom are combined to form a C3-6cycloalkyl; each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl;each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; m is 0, 1, 2, 3, 4, or 5; n is 1 or 2; p is 1, 2, or 3; q is 0, 1, or 2; v is 0, 1, 2, 3, or 4; and indicates a single or double bond such that all valences are satisfied.

[0014] In some embodiments is a compound of Formula (II’) or (II), wherein J1is C(R2). In some embodiments is a compound of Formula (II’) or (II), wherein J1is N. In some embodiments is a compound of Formula (II’) or (II), wherein J2is N(R3b). In some embodiments is a compound of Formula (II’) or (II), wherein R3bis selected from hydrogen and -C(O)R13. In some embodiments is a compound of Formula (II’) or (II), wherein R3bis hydrogen. In some embodiments is a compound of Formula (II’) or (II), wherein R3bis -C(O)R13and R13is independently selected from C1-6alkyl and C3-6cycloalkyl wherein C1-6alkyl and C3-6cycloalkyl are optionally substituted with hydroxy. In some embodiments is a compound of Formula (II’) or (II), wherein each R6is independently selected from oxo and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein v is 1, 2, or 3. In some embodiments is a compound of Formula (II’) or (II), wherein v is 0. In some embodiments is a compound of Formula (II), wherein q is 0. In some embodiments is a compound of Formula (II’) or (II), wherein q is 1. In some embodiments is a compound of Formula (II’) or (II), wherein q is 2. In some embodiments is a compound of Formula (II’) or (II), wherein indicates a single bond. In some embodiments is a compound of Formula (II’) or (II), wherein indicates a double bond.

[0015] In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein J is C(R3)(R4), O, or S. In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein J is C(R3)(R4). In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein R3is hydrogen and R4is selected from hydrogen, -CN, C1-6alkyl, and - C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein R3and R4are hydrogen. In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl,wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and - C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from C1-6alkyl, -C(O)OR10, and -C(O)R13. In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein J is O. In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein J is S. In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein J is N(R3a). In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein R3ais C1-6alkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and - N(R10)(R11). In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein R3ais -C(O)R13and R13is unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein each R5is independently selected from halogen, - CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein each R5is independently selected from halogen and C1-6alkyl. In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein m is 1 or 2. In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), or (II), wherein n is 1 and p is 1.

[0016] In another aspect described herein is a compound of Formula (III’), or a pharmaceutically acceptable salt thereof:Formula (III’); wherein: J1is C(R2) or N; each L is C(R4a)2; each L1is C(R4b)2; R1is selected from hydrogen and C1-6alkyl;each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; each R7is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substitutedwith one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; n is 1 or 2; p is 1, 2, or 3; and t is 1, 2, 3, 4, or 5.

[0017] In another aspect described herein is a compound of Formula (III), or a pharmaceutically acceptable salt thereof:Formula (III); wherein:J1is C(R2) or N; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R7is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substitutedwith one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; and t is 1, 2, 3, 4, or 5.

[0018] In some embodiments is a compound of Formula (III’) or (III), wherein J1is C(R2). In some embodiments is a compound of Formula (III’) or (III), wherein J1is N. In some embodiments is a compound of Formula (III’) or (III), wherein R3is hydrogen and R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are hydrogen. In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with -C(O)R13. In some embodiments is a compound of Formula (III’) or (III), wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein each R7is independently selected from halogen, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula(III’) or (III), wherein each R7is independently selected from halogen and C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein t is 1 or 2.

[0019] In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), (II), (III’), or (III), wherein each R2is independently selected from hydrogen, halogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), (II), (III’), or (III), wherein each R2is hydrogen. In some embodiments is a compound of Formula (I’), (I), (Ia), (II’), (II), (III’), or (III), wherein R1is hydrogen.

[0020] In another aspect described herein is a compound of Formula (IV’), or a pharmaceutically acceptable salt thereof:Formula (IV’); wherein: W, X, Y, and Z are independently selected from C(R2) and N, wherein at least one of Y and Z is C(R2); L is C(R6a)(R6b); each L1is C(R4a)2; each L2is C(R4b)2; J is C(R3)(R4), O, S, or N(R3a); R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl,wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3cis selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), and -C(O)N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; R6aand R6bare independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substitutedwith one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R8is selected from C6-10aryl and C1-9heteroaryl, wherein C6-10aryl and C1-9heteroaryl are optionally substituted with one, two, or three R9groups; each R9is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two,or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; n is 1 or 2; p is 1, 2, or 3; q is 0 or 1; and indicates a single or double bond such that all valences are satisfied; wherein the compound is not.

[0021] In another aspect described herein is a compound of Formula (IV), or a pharmaceutically acceptable salt thereof:Formula (IV); wherein: W, X, Y, and Z are independently selected from C(R2) and N, wherein at least one of Y and Z is C(R2); L is C(R6a)(R6b); J is C(R3)(R4), O, S, or N(R3a); R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl,wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3cis selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), and -C(O)N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); R6aand R6bare independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11);R8is selected from C6-10aryl and C1-9heteroaryl, wherein C6-10aryl and C1-9heteroaryl are optionally substituted with one, two, or three R9groups; each R9is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl;n is 1 or 2; p is 1, 2, or 3; q is 0 or 1; and indicates a single or double bond such that all valences are satisfied; wherein the compound is not.

[0022] In some embodiments is a compound of Formula (IV’) or (IV), wherein W, X, Y, and Z are C(R2). In some embodiments is a compound of Formula (IV’) or (IV), wherein W, X, and Y are C(R2) and Z is N. In some embodiments is a compound of Formula (IV’) or (IV), wherein W, X, and Z are C(R2) and Y is N. In some embodiments is a compound of Formula (IV’) or (IV), wherein W, Y, and Z are C(R2) and X is N. In some embodiments is a compound of Formula (IV’) or (IV), wherein X, Y, and Z are C(R2) and W is N. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3cis selected from C1-6alkyl and C3-6cycloalkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3cis -CH3. In some embodiments is a compound of Formula (IV’) or (IV), wherein R6aand R6bare hydrogen. In some embodiments is a compound of Formula (IV’) or (IV), wherein q is 1. In some embodiments is a compound of Formula (IV’) or (IV), wherein q is 0. In some embodiments is a compound of Formula (IV’) or (IV), whereinindicates a single bond. In some embodiments is a compound of Formula (IV’) or (IV), whereinindicates a double bond.

[0023] In another aspect described herein is a compound of Formula (V’), or a pharmaceutically acceptable salt thereof:Formula (V’); wherein: J is C(R3)(R4), O, S, or N(R3a); each L is C(R4a)2; each L1is C(R4b)2; X1is C(R2a) or N; R1is selected from hydrogen and C1-6alkyl;each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R2ais selected from hydrogen and C1-6alkyl; R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3dis selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), and -C(O)N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groupsselected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; R8is selected from C6-10aryl and C1-9heteroaryl, wherein C6-10aryl and C1-9heteroaryl are optionally substituted with one, two, or three R9groups; each R9is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl;each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; n is 1 or 2; and p is 1, 2, or 3.

[0024] In another aspect described herein is a compound of Formula (V), or a pharmaceutically acceptable salt thereof:wherein: J is C(R3)(R4), O, S, or N(R3a); X1is C(R2a) or N; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R2ais selected from hydrogen and C1-6alkyl; R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two,or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3dis selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), and -C(O)N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); R8is selected from C6-10aryl and C1-9heteroaryl, wherein C6-10aryl and C1-9heteroaryl are optionally substituted with one, two, or three R9groups; each R9is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substitutedwith one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; n is 1 or 2; and p is 1, 2, or 3.

[0025] In some embodiments is a compound of Formula (V’) or (V), wherein X1is C(R2a). In some embodiments is a compound of Formula (V’) or (V), wherein X1is C(R2a) and R2ais hydrogen. In some embodiments is a compound of Formula (V’) or (V), wherein X1is C(R2a) and R2ais C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein X1is N.

[0026] In some embodiments is a compound of Formula (V’) or (V), wherein R3dis selected from hydrogen and C1-6alkyl optionally substituted with one, two, or three groups selected from halogen, -OR10, -N(R10)(R11), and -C(O)N(R10)(R11). In some embodiments is a compound ofFormula (V’) or (V), wherein R3dis C1-6alkyl optionally substituted with one group selected from -OR10, -N(R10)(R11), and -C(O)N(R10)(R11) and wherein R10and R11are hydrogen.

[0027] In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein J is C(R3)(R4), O, or S. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein J is C(R3)(R4). In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein R3is hydrogen and R4is selected from hydrogen, -CN, C1-6alkyl, and - C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein R3and R4are hydrogen. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and - C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from C1-6alkyl, -C(O)OR10, and -C(O)R13. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein J is O. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein J is S. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein J is N(R3a). In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein R3ais hydrogen or C1-6alkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11). In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein R3ais -C(O)R13and R13is unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein R8is selected C6-10aryl optionally substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein R8is phenyl substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein each R9is independently selected from halogen, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein each R9is independently selected from halogen and C1-6alkyl. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein n is 1 and p is 1. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein each R2is independently selected from hydrogen, halogen, and C1-6alkyl. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein each R2is hydrogen. In some embodiments is a compound of Formula (IV’), (IV), (V’), or (V), wherein R1is hydrogen.

[0028] In another aspect is a pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and a compound described herein, or a pharmaceutically acceptable salt thereof.

[0029] In another aspect is a method of inhibiting SARM1 comprising contacting the SARM1 with a compound described herein, or a pharmaceutically acceptable salt thereof. In some embodiments is a method of inhibiting SARM1 comprising contacting the SARM1 with a compound described herein, or a pharmaceutically acceptable salt thereof, wherein the contacting is carried out in vitro. In some embodiments is a method of inhibiting SARM1 comprising contacting the SARM1 with a compound described herein, or a pharmaceutically acceptable salt thereof, wherein the contacting is carried out in vivo.

[0030] In another aspect is a method of inhibiting axonal degeneration in a patient in need thereof comprising administering to the patient an inhibiting amount of a compound described herein, or a pharmaceutically acceptable salt thereof. In some embodiments is a method of inhibiting axonal degeneration in a patient in need thereof comprising administering to the patient an inhibiting amount of a compound described herein, or a pharmaceutically acceptable salt thereof, wherein the axonal degeneration is caused by abnormal reduction or depletion of NAD+ in the axons.

[0031] In another aspect is a method of treating or preventing a neurological disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof. In some embodiments is a method of treating or preventing a neurological disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, wherein the neurological disorder is a neurodegenerative disease.

[0032] In some embodiments is a method of treating or preventing a neurological disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, in combination with a further pharmaceutically active agent.

[0033] In some embodiments is a use of a compound described herein, or a pharmaceutically acceptable salt thereof, in treating or preventing a neurological disorder in a patient in need thereof.

[0034] In some embodiments is a compound described herein, or a pharmaceutically acceptable salt thereof, for use in the preparation of a medicament for treating or preventing a neurological disorder in a patient in need thereof.DETAILED DESCRIPTION

[0035] Similar to programmed cell death pathways (e.g., apoptosis), axonal degeneration in response to injury or disease stimulates a local signaling cascade that causes destruction of the injured axon segment (Summers D. W., et al., PNAS USA, 2016 Oct 11, 113(41):E6271– E6280). Following injury, the axonal skeleton disintegrates, and the axonal membrane breaks apart. Subsequent to axonal degeneration, the myelin sheath degrades and infiltration by macrophages follows; the macrophages, along with Schwann cells, clear the cellular debris resulting from the degeneration (Coleman M.P., et al., PNAS USA, 1998 Aug, 95(17):9985-90).

[0036] SARM1 (sterile alpha and TIR motif-containing 1) protein (NP_055892) is a 724 amino acid protein involved in axon degeneration. It has also been implicated in infectious and inflammatory disorders. The SARM1 protein, also known as FLJ36296, KIAA0524, MyD88-5, SAM domain-containing protein 2, and SAMD2, comprises four domains, i) a mitochondrial localization signal, ii) an auto-inhibitory N-terminus region consisting of armadillo / HEAT motifs, iii) two sterile alpha motifs responsible for multimerization, and iv) a C-terminus Toll / Interleukin-1 receptor that possesses enzymatic activity (Essuman K., et al., Neuron 2017 Mar., 93(6):1334-43.e5).

[0037] SARM1 protein plays a critical role in the Wallerian degeneration pathway. Activation of SARM1 triggers a rapid collapse of NAD+levels in the distal section of the injured axon, which then undergoes degeneration (Gerdts J. et al., Science 2015 Apr.348(6233):453-57). Promoting dimerization of the Toll / interleukin receptor (TIR) domain of SARM1 has been shown to be sufficient to promote NAD+loss and axon degeneration.

[0038] SARM1’s activity is responsible for, at least in part, the protective nature of the survival factor NMNAT2, as NMKNAT enzymes have been found to prevent SARM1-mediated depletion of NAD+. Other pro-degeneration signaling pathways, including the MAP kinase pathway, have been linked to SARM1 activation. MAPK signaling has been shown to promote the loss of NMNAT2, which promotes SARM1 activation (See, e.g., Yang J. et al., Cell 2015 Jan 160(1-2):161-76).

[0039] SARM1 is involved in the innate immune response. It promotes neuronal cell death in response to stress and other stimuli. SARM1 acts as a negative regulator of TICAM1 / TRIF- dependent Toll-like receptor signaling by inhibiting induction of TLR3- and TLR4-dependent genes, which play a pivotal role in activating axonal degeneration following injury. In addition, SARM1 specifically blocks TICAM1 / TRIF-dependent transcription factor activation and gene induction, without affecting the MYD88- dependent pathway or non-TLR signaling. It is also a negative regulator of NF- kappa-B and IRF activation. (See, e.g., Summers, D.W. et al., J Neurosci., 2014 Jul 9, 34(28):9338-50).

[0040] In some embodiments described herein are inhibitors of SARM1. SARM1 activation can cause a rapid reduction in NAD+levels in injured axons, which then undergo degeneration. In particular embodiments, the compounds inhibit axonal degeneration, including axonal degeneration that results from reduction or depletion of NAD+(e.g., inhibition of SARM1 NADase).

[0041] Further described herein are active-site SARM1 NAD hydrolase inhibitors. In some aspects, the inhibitors described herein act in the catalytic pocket but do not directly compete with substrate binding. In some embodiments, the resulting small molecule-ADPR adducts confer knock-out like axon protection in vivo - reducing levels of the translatable biomarker neurofilament light and conferring functional protection. In some embodiments, described herein is a mode of pharmacologic inhibition that has implications not just for SARM1 but for a broader panel of related NAD hydrolases linked to age-related decline and disease. Compounds

[0042] Compounds described herein, including pharmaceutically acceptable salts, active metabolites and pharmaceutically acceptable solvates thereof, are inhibitors of SARM1.

[0043] In some embodiments is a compound of Formula (I’):Formula (I’); or a pharmaceutically acceptable salt thereof, wherein: A and G are independently selected from C(R2) and N; W, X, Y, and Z are independently selected from C(R2) and N, wherein at least one of W, X, Y, and Z is C(R2); J is C(R3)(R4), O, S, or N(R3a); each L is C(R4a)2; each L1is C(R4b)2; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; each R5is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; m is 0, 1, 2, or 3; n is 1 or 2; and p is 1, 2, or 3.

[0044] In some embodiments is a compound of Formula (I’), wherein each R4ais hydrogen. In some embodiments is a compound of Formula (I’), wherein each R4bis hydrogen.

[0045] In some embodiments is a compound of Formula (I):Formula (I); or a pharmaceutically acceptable salt thereof, wherein: A and G are independently selected from C(R2) and N; W, X, Y, and Z are independently selected from C(R2) and N, wherein at least one of W, X, Y, and Z is C(R2); J is C(R3)(R4), O, S, or N(R3a); R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one,two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R5is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl;each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; m is 0, 1, 2, or 3; n is 1 or 2; and p is 1, 2, or 3.

[0046] In some embodiments is a compound of Formula (I’) or (I), wherein A and G are C(R2). In some embodiments is a compound of Formula (I’) or (I), wherein A and G are C(H). In some embodiments is a compound of Formula (I’) or (I), wherein A is C(R2) and G is N. In some embodiments is a compound of Formula (I’) or (I), wherein A is C(H) and G is N. In some embodiments is a compound of Formula (I’) or (I), wherein A is N and G is C(R2). In some embodiments is a compound of Formula (I’) or (I), wherein A is N and G is C(H).

[0047] In some embodiments is a compound of Formula (I’) or (I), wherein W, X, Y, and Z are C(R2). In some embodiments is a compound of Formula (I’) or (I), wherein W, X, and Y are C(R2) and Z is N. In some embodiments is a compound of Formula (I’) or (I), wherein W, X, and Z are C(R2) and Y is N. In some embodiments is a compound of Formula (I’) or (I), wherein W, Y, and Z are C(R2) and X is N. In some embodiments is a compound of Formula (I’) or (I), wherein X, Y, and Z are C(R2) and W is N. In some embodiments is a compound of Formula (I’) or (I), wherein each R2is independently selected from hydrogen, halogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (I’) or (I), wherein each R2is independently selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (I’) or (I), wherein each R2is independently selected from hydrogen and halogen. In some embodiments is a compound of Formula (I’) or (I), wherein each R2is hydrogen.

[0048] In some embodiments is a compound of Formula (I’) or (I), wherein R1is hydrogen. In some embodiments is a compound of Formula (I’) or (I), wherein R1is C1-6alkyl. In some embodiments is a compound of Formula (I’) or (I), wherein R1is -CH3.

[0049] In some embodiments is a compound of Formula (I’) or (I), wherein J is C(R3)(R4), O, or S.

[0050] In some embodiments is a compound of Formula (I’) or (I), wherein J is C(R3)(R4).

[0051] In some embodiments is a compound of Formula (I’) or (I), wherein R3is selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (I’) or (I), wherein R3is hydrogen. In some embodiments is a compound of Formula (I’) or (I), wherein R3is C1-6alkyl. In some embodiments is a compound of Formula (I’) or (I), wherein R3is -CH3.

[0052] In some embodiments is a compound of Formula (I’) or (I), wherein R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’) or (I), wherein R4is hydrogen. In some embodiments is a compound of Formula (I’) or (I), wherein R4is -CN. In some embodiments is a compound of Formula (I’) or (I), wherein R4is C1-6alkyl. In some embodiments is a compound of Formula (I’) or (I), wherein R4is -CH3. In some embodiments is a compound of Formula (I’) or (I), wherein R4is C1-6alkyl. In some embodiments is a compound of Formula (I’) or (I), wherein R4is -C(O)N(R10)(R11).

[0053] In some embodiments is a compound of Formula (I’) or (I), wherein R3is hydrogen and R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’) or (I), wherein R3is hydrogen and R4is hydrogen. In some embodiments is a compound of Formula (I’) or (I), wherein R3is hydrogen and R4is -CN. In some embodiments is a compound of Formula (I’) or (I), wherein R3is C1-6alkyl and R4is -CN. In some embodiments is a compound of Formula (I’) or (I), wherein R3is -CH3and R4is -CN. In some embodiments is a compound of Formula (I’) or (I), wherein R3is hydrogen and R4is - C(O)N(R10)(R11).

[0054] In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, - OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from C1-6alkyl and -C(O)R13. In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments isa compound of Formula (I’) or (I), wherein R3and R4are combined to form an unsubstituted C2-9heterocycloalkyl.

[0055] In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form an azetidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), - C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13. In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form an unsubstituted azetidine ring.

[0056] In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form an unsubstituted pyrrolidine ring.

[0057] In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form a piperidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form a piperidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form a piperidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (I’) or (I), wherein R3and R4are combined to form an unsubstituted piperidine ring.

[0058] In some embodiments is a compound of Formula (I’) or (I), wherein J is O.

[0059] In some embodiments is a compound of Formula (I’) or (I), wherein J is S.

[0060] In some embodiments is a compound of Formula (I’) or (I), wherein J is N(R3a). In some embodiments is a compound of Formula (I’) or (I), wherein R3ais hydrogen or C1-6alkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and - N(R10)(R11). In some embodiments is a compound of Formula (I’) or (I), wherein R3ais selected from hydrogen, C1-6alkyl and -C(O)R13. In some embodiments is a compound of Formula (I’) or (I), wherein R3ais hydrogen. In some embodiments is a compound of Formula (I’) or (I), wherein R3ais C1-6alkyl. In some embodiments is a compound of Formula (I’) or (I), wherein R3ais -CH3. In some embodiments is a compound of Formula (I’) or (I), wherein R3ais -C(O)R13. In some embodiments is a compound of Formula (I’) or (I), wherein R3ais -C(O)R13and R13is unsubstituted C1-6alkyl.

[0061] In some embodiments is a compound of Formula (I’) or (I), wherein each R5is independently selected from halogen, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (I’) or (I), wherein each R5is independently selected from halogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (I’) or (I), wherein each R5is independently selected from halogen and C1-6alkyl. In some embodiments is a compound of Formula (I’) or (I), wherein each R5is independently selected from halogen and C1-6haloalkyl. In some embodiments is a compound of Formula (I’) or (I), wherein each R5is independently selected from halogen. In some embodiments is a compound of Formula (I’) or (I), wherein each R5is independently selected from C1-6alkyl. In some embodiments is a compound of Formula (I’) or (I), wherein each R5is independently selected from C1-6haloalkyl. In some embodiments is a compound of Formula (I’) or (I), wherein each R5is independently selected from -CN.

[0062] In some embodiments is a compound of Formula (I’) or (I), wherein m is 1 or 2. In some embodiments is a compound of Formula (I’) or (I), wherein m is 2. In some embodiments is a compound of Formula (I’) or (I), wherein m is 1. In some embodiments is a compound of Formula (I’) or (I), wherein m is 0. In some embodiments is a compound of Formula (I’) or (I), wherein m is 3.

[0063] In some embodiments is a compound of Formula (I’) or (I), wherein n is 1 and p is 1. In some embodiments is a compound of Formula (I’) or (I), wherein n is 1 and p is 2. In some embodiments is a compound of Formula (I’) or (I), wherein n is 2 and p is 2. In some embodiments is a compound of Formula (I’) or (I), wherein n is 1 and p is 3. In some embodiments is a compound of Formula (I’) or (I), wherein n is 2 and p is 3.

[0064] In some embodiments is a compound of Formula (Ia):Formula (Ia); or a pharmaceutically acceptable salt thereof, wherein: W, X, Y, and Z are independently selected from C(R2) and N, wherein at least one of W, X, Y, and Z is C(R2); J is C(R3)(R4), O, S, or N(R3a); R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), -C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R5is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclicnitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; m is 0, 1, 2, or 3; n is 1 or 2; and p is 1, 2, or 3.

[0065] In some embodiments is a compound of Formula (Ia), wherein W, X, Y, and Z are C(R2). In some embodiments is a compound of Formula (Ia), wherein W, X, and Y are C(R2) and Z is N. In some embodiments is a compound of Formula (Ia), wherein W, X, and Z are C(R2) and Y is N. In some embodiments is a compound of Formula (Ia), wherein W, Y, and Z are C(R2) and X is N. In some embodiments is a compound of Formula (Ia), wherein X, Y, and Z are C(R2) and W is N. In some embodiments is a compound of Formula (Ia), wherein each R2is independently selected from hydrogen, halogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (Ia), wherein each R2is independently selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein each R2is independently selected from hydrogen and halogen. In some embodiments is a compound of Formula (Ia), wherein each R2is hydrogen.

[0066] In some embodiments is a compound of Formula (Ia), wherein R1is hydrogen. In some embodiments is a compound of Formula (Ia), wherein R1is C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein R1is -CH3.

[0067] In some embodiments is a compound of Formula (Ia), wherein J is C(R3)(R4), O, or S.

[0068] In some embodiments is a compound of Formula (Ia), wherein J is C(R3)(R4).

[0069] In some embodiments is a compound of Formula (Ia), wherein R3is selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein R3is hydrogen. In some embodiments is a compound of Formula (Ia), wherein R3is C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein R3is -CH3.

[0070] In some embodiments is a compound of Formula (Ia), wherein R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound ofFormula (Ia), wherein R4is hydrogen. In some embodiments is a compound of Formula (Ia), wherein R4is -CN. In some embodiments is a compound of Formula (Ia), wherein R4is C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein R4is -CH3. In some embodiments is a compound of Formula (Ia), wherein R4is C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein R4is -C(O)N(R10)(R11).

[0071] In some embodiments is a compound of Formula (Ia), wherein R3is hydrogen and R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (Ia), wherein R3is hydrogen and R4is hydrogen. In some embodiments is a compound of Formula (Ia), wherein R3is hydrogen and R4is -CN. In some embodiments is a compound of Formula (Ia), wherein R3is C1-6alkyl and R4is -CN. In some embodiments is a compound of Formula (Ia), wherein R3is -CH3and R4is -CN. In some embodiments is a compound of Formula (Ia), wherein R3is hydrogen and R4is -C(O)N(R10)(R11).

[0072] In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one, two, or three groups selected from halogen, - CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, - OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, - C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form an unsubstituted C2-9heterocycloalkyl.

[0073] In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form an azetidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), - C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form an unsubstituted azetidine ring.

[0074] In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), - C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form an unsubstituted pyrrolidine ring.

[0075] In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form a piperidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form a piperidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), - C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form a piperidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein R3and R4are combined to form an unsubstituted piperidine ring.

[0076] In some embodiments is a compound of Formula (Ia), wherein J is O.

[0077] In some embodiments is a compound of Formula (Ia), wherein J is S.

[0078] In some embodiments is a compound of Formula (Ia), wherein J is N(R3a). In some embodiments is a compound of Formula (Ia), wherein R3ais hydrogen or C1-6alkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl,C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11). In some embodiments is a compound of Formula (Ia), wherein R3ais selected from hydrogen, C1-6alkyl and -C(O)R13. In some embodiments is a compound of Formula (Ia), wherein R3ais hydrogen. In some embodiments is a compound of Formula (Ia), wherein R3ais C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein R3ais -CH3. In some embodiments is a compound of Formula (Ia), wherein R3ais -C(O)R13. In some embodiments is a compound of Formula (Ia), wherein R3ais -C(O)R13and R13is unsubstituted C1-6alkyl.

[0079] In some embodiments is a compound of Formula (Ia), wherein each R5is independently selected from halogen, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (Ia), wherein each R5is independently selected from halogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (Ia), wherein each R5is independently selected from halogen and C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein each R5is independently selected from halogen and C1-6haloalkyl. In some embodiments is a compound of Formula (Ia), wherein each R5is independently selected from halogen. In some embodiments is a compound of Formula (Ia), wherein each R5is independently selected from C1-6alkyl. In some embodiments is a compound of Formula (Ia), wherein each R5is independently selected from C1-6haloalkyl. In some embodiments is a compound of Formula (Ia), wherein each R5is independently selected from -CN.

[0080] In some embodiments is a compound of Formula (Ia), wherein m is 1 or 2. In some embodiments is a compound of Formula (Ia), wherein m is 2. In some embodiments is a compound of Formula (Ia), wherein m is 1. In some embodiments is a compound of Formula (Ia), wherein m is 0. In some embodiments is a compound of Formula (Ia), wherein m is 3.

[0081] In some embodiments is a compound of Formula (Ia), wherein n is 1 and p is 1. In some embodiments is a compound of Formula (Ia), wherein n is 1 and p is 2. In some embodiments is a compound of Formula (Ia), wherein n is 2 and p is 2. In some embodiments is a compound of Formula (Ia), wherein n is 1 and p is 3. In some embodiments is a compound of Formula (Ia), wherein n is 2 and p is 3.

[0082] In some embodiments is a compound of Formula (II’):Formula (II’); or a pharmaceutically acceptable salt thereof, wherein:J is C(R3)(R4), O, S, or N(R3a); J1is C(R2) or N; J2is O, S, or N(R3b); each L is C(R4a)2; each L1is C(R4b)2; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3bis selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl,C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; each R5is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R6is independently selected from halogen, oxo, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or two R6attached to the same carbon atom are combined to form a C3-6cycloalkyl; each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; m is 0, 1, 2, 3, 4, or 5; n is 1 or 2; p is 1, 2, or 3; q is 0, 1, or 2; v is 0, 1, 2, 3, or 4; and indicates a single or double bond such that all valences are satisfied.

[0083] In some embodiments is a compound of Formula (II’), wherein each R4ais hydrogen. In some embodiments is a compound of Formula (II’), wherein each R4bis hydrogen.

[0084] In some embodiments is a compound of Formula (II):Formula (II);or a pharmaceutically acceptable salt thereof, wherein: J is C(R3)(R4), O, S, or N(R3a); J1is C(R2) or N; J2is O, S, or N(R3b); R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3bis selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one,two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R5is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R6is independently selected from halogen, oxo, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or two R6attached to the same carbon atom are combined to form a C3-6cycloalkyl; each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; m is 0, 1, 2, 3, 4, or 5; n is 1 or 2; p is 1, 2, or 3; q is 0, 1, or 2; v is 0, 1, 2, 3, or 4; and indicates a single or double bond such that all valences are satisfied.

[0085] In some embodiments is a compound of Formula (II’) or (II), wherein J1is C(R2).

[0086] In some embodiments is a compound of Formula (II’) or (II), wherein J1is N.

[0087] In some embodiments is a compound of Formula (II’) or (II), wherein J2is N(R3b). In some embodiments is a compound of Formula (II’) or (II), wherein J2is N(R3b) and R3bis selected from hydrogen, C1-6alkyl, and -C(O)R13. In some embodiments is a compound of Formula (II’) or (II), wherein J2is N(R3b) and R3bis hydrogen. In some embodiments is a compound of Formula (II’) or (II), wherein J2is N(R3b) and R3bis C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein J2is N(R3b) and R3bis -C(O)R13. In some embodiments is a compound of Formula (II’) or (II), wherein J2is N(R3b), R3bis - C(O)R13, and R13is independently selected from C1-6alkyl and C3-6cycloalkyl wherein C1-6alkyl and C3-6cycloalkyl are optionally substituted with hydroxy. In some embodiments is a compound of Formula (II’) or (II), wherein J2is N(R3b), R3bis -C(O)R13, and R13is unsubstituted C1-6alkyl.In some embodiments is a compound of Formula (II’) or (II), wherein J2is N(R3b), R3bis - C(O)R13, and R13is -CH3. In some embodiments is a compound of Formula (II’) or (II), wherein J2is N(R3b), R3bis -C(O)R13, and R13is C3-6cycloalkyl optionally substituted with hydroxy. In some embodiments is a compound of Formula (II’) or (II), wherein J2is N(R3b), R3bis -C(O)R13, and R13is C3-6cycloalkyl substituted with hydroxy.

[0088] In some embodiments is a compound of Formula (II’) or (II), wherein J2is O.

[0089] In some embodiments is a compound of Formula (II’) or (II), wherein J2is S.

[0090] In some embodiments is a compound of Formula (II’) or (II), wherein q is 0. In some embodiments is a compound of Formula (II’) or (II), wherein q is 1. In some embodiments is a compound of Formula (II’) or (II), wherein q is 2.

[0091] In some embodiments is a compound of Formula (II’) or (II), wherein each R6is independently selected from oxo and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein each R6is oxo. In some embodiments is a compound of Formula (II’) or (II), wherein each R6is unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein v is 1, 2, or 3. In some embodiments is a compound of Formula (II’) or (II), wherein v is 3. In some embodiments is a compound of Formula (II’) or (II), wherein v is 2. In some embodiments is a compound of Formula (II’) or (II), wherein v is 1. In some embodiments is a compound of Formula (II’) or (II), wherein v is 0.

[0092] In some embodiments is a compound of Formula (II’) or (II), wherein indicates a single bond. In some embodiments is a compound of Formula (II’) or (II), wherein indicates a double bond.

[0093] In some embodiments is a compound of Formula (II’) or (II), wherein each R2is independently selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein each R2is independently selected from hydrogen and halogen. In some embodiments is a compound of Formula (II’) or (II), wherein each R2is hydrogen.

[0094] In some embodiments is a compound of Formula (II’) or (II), wherein R1is hydrogen. In some embodiments is a compound of Formula (II’) or (II), wherein R1is C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein R1is -CH3.

[0095] In some embodiments is a compound of Formula (II’) or (II), wherein J is C(R3)(R4), O, or S.

[0096] In some embodiments is a compound of Formula (II’) or (II), wherein J is C(R3)(R4).

[0097] In some embodiments is a compound of Formula (II’) or (II), wherein R3is selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein R3is hydrogen. In some embodiments is a compound of Formula (II’) or (II), wherein R3is C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein R3is -CH3.

[0098] In some embodiments is a compound of Formula (II’) or (II), wherein R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (II’) or (II), wherein R4is hydrogen. In some embodiments is a compound of Formula (II’) or (II), wherein R4is -CN. In some embodiments is a compound of Formula (II’) or (II), wherein R4is C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein R4is -CH3. In some embodiments is a compound of Formula (II’) or (II), wherein R4is C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein R4is - C(O)N(R10)(R11).

[0099] In some embodiments is a compound of Formula (II’) or (II), wherein R3is hydrogen and R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (II’) or (II), wherein R3is hydrogen and R4is hydrogen. In some embodiments is a compound of Formula (II’) or (II), wherein R3is hydrogen and R4is -CN. In some embodiments is a compound of Formula (II’) or (II), wherein R3is C1-6alkyl and R4is - CN. In some embodiments is a compound of Formula (II’) or (II), wherein R3is -CH3and R4is - CN. In some embodiments is a compound of Formula (II’) or (II), wherein R3is hydrogen and R4is -C(O)N(R10)(R11).

[0100] In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, - OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form an unsubstituted C2-9heterocycloalkyl.

[0101] In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form an azetidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), - C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form an unsubstituted azetidine ring.

[0102] In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form an unsubstituted pyrrolidine ring.

[0103] In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form a piperidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form a piperidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), - C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form a piperidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogenand unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein R3and R4are combined to form an unsubstituted piperidine ring.

[0104] In some embodiments is a compound of Formula (II’) or (II), wherein J is O.

[0105] In some embodiments is a compound of Formula (II’) or (II), wherein J is S.

[0106] In some embodiments is a compound of Formula (II’) or (II), wherein J is N(R3a). In some embodiments is a compound of Formula (II’) or (II), wherein R3ais hydrogen or C1-6alkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and - N(R10)(R11). In some embodiments is a compound of Formula (II’) or (II), wherein R3ais selected from hydrogen, C1-6alkyl and -C(O)R13. In some embodiments is a compound of Formula (II’) or (II), wherein R3ais hydrogen. In some embodiments is a compound of Formula (II’) or (II), wherein R3ais C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein R3ais -CH3. In some embodiments is a compound of Formula (II’) or (II), wherein R3ais -C(O)R13. In some embodiments is a compound of Formula (II’) or (II), wherein R3ais - C(O)R13and R13is unsubstituted C1-6alkyl.

[0107] In some embodiments is a compound of Formula (II’) or (II), wherein each R5is independently selected from halogen, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (II’) or (II), wherein each R5is independently selected from halogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (II’) or (II), wherein each R5is independently selected from halogen and C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein each R5is independently selected from halogen and C1-6haloalkyl. In some embodiments is a compound of Formula (II’) or (II), wherein each R5is independently selected from halogen. In some embodiments is a compound of Formula (II’) or (II), wherein each R5is independently selected from C1-6alkyl. In some embodiments is a compound of Formula (II’) or (II), wherein each R5is independently selected from C1-6haloalkyl. In some embodiments is a compound of Formula (II’) or (II), wherein each R5is independently selected from -CN.

[0108] In some embodiments is a compound of Formula (II’) or (II), wherein m is 1 or 2. In some embodiments is a compound of Formula (II’) or (II), wherein m is 2. In some embodiments is a compound of Formula (II’) or (II), wherein m is 1. In some embodiments is a compound of Formula (II’) or (II), wherein m is 0. In some embodiments is a compound of Formula (II’) or (II), wherein m is 3.

[0109] In some embodiments is a compound of Formula (II’) or (II), wherein n is 1 and p is 1. In some embodiments is a compound of Formula (II’) or (II), wherein n is 1 and p is 2. In some embodiments is a compound of Formula (II’) or (II), wherein n is 2 and p is 2. In someembodiments is a compound of Formula (II’) or (II), wherein n is 1 and p is 3. In some embodiments is a compound of Formula (II’) or (II), wherein n is 2 and p is 3.

[0110] In some embodiments is a compound of Formula (III’):Formula (III’); or a pharmaceutically acceptable salt thereof, wherein: J1is C(R2) or N; each L is C(R4a)2; each L1is C(R4b)2; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; each R7is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two,or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; n is 1 or 2; p is 1, 2, or 3; and t is 1, 2, 3, 4, or 5.

[0111] In some embodiments is a compound of Formula (III’), wherein each R4ais hydrogen. In some embodiments is a compound of Formula (III’), wherein each R4bis hydrogen.

[0112] In some embodiments is a compound of Formula (III):Formula (III); or a pharmaceutically acceptable salt thereof, wherein: J1is C(R2) or N; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyland C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R7is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two,or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; and t is 1, 2, 3, 4, or 5.

[0113] In some embodiments is a compound of Formula (III’) or (III), wherein J1is C(R2).

[0114] In some embodiments is a compound of Formula (III’) or (III), wherein J1is N.

[0115] In some embodiments is a compound of Formula (III’) or (III), wherein each R2is independently selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein each R2is independently selected from hydrogen and halogen. In some embodiments is a compound of Formula (III’) or (III), wherein each R2is hydrogen.

[0116] In some embodiments is a compound of Formula (III’) or (III), wherein R1is hydrogen. In some embodiments is a compound of Formula (III’) or (III), wherein R1is C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein R1is -CH3.

[0117] In some embodiments is a compound of Formula (III’) or (III), wherein J is C(R3)(R4), O, or S.

[0118] In some embodiments is a compound of Formula (III’) or (III), wherein J is C(R3)(R4).

[0119] In some embodiments is a compound of Formula (III’) or (III), wherein R3is selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein R3is hydrogen. In some embodiments is a compound of Formula (III’) or (III), wherein R3is C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein R3is - CH3.

[0120] In some embodiments is a compound of Formula (III’) or (III), wherein R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (III’) or (III), wherein R4is hydrogen. In some embodiments is a compound of Formula (III’) or (III), wherein R4is -CN. In some embodiments is a compound of Formula (III’) or (III), wherein R4is C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein R4is -CH3. In some embodiments is a compound of Formula (III’) or (III), wherein R4is C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein R4is - C(O)N(R10)(R11).

[0121] In some embodiments is a compound of Formula (III’) or (III), wherein R3is hydrogen and R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (III’) or (III), wherein R3is hydrogen and R4is hydrogen. In some embodiments is a compound of Formula (III’) or (III), wherein R3is hydrogen and R4is -CN. In some embodiments is a compound of Formula (III’) or (III), wherein R3is C1-6alkyl and R4is - CN. In some embodiments is a compound of Formula (III’) or (III), wherein R3is -CH3and R4is -CN. In some embodiments is a compound of Formula (III’) or (III), wherein R3is hydrogen and R4is -C(O)N(R10)(R11).

[0122] In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form an unsubstituted C2-9heterocycloalkyl.

[0123] In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form an azetidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form an unsubstituted azetidine ring.

[0124] In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form an unsubstituted pyrrolidine ring.

[0125] In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form a piperidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form a piperidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form a piperidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein R3and R4are combined to form an unsubstituted piperidine ring.

[0126] In some embodiments is a compound of Formula (III’) or (III), wherein each R7is independently selected from halogen, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (III’) or (III), wherein each R7is independently selected from halogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (III’) or (III), wherein each R7is independently selected from halogen and C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein each R7is independently selected from halogen and C1-6haloalkyl. In some embodiments is a compound of Formula (III’) or (III), wherein each R7is independently selected from halogen. In some embodiments is a compound of Formula (III’) or (III), wherein each R7is independently selected from C1-6alkyl. In some embodiments is a compound of Formula (III’) or (III), wherein each R7is independently selected from C1-6haloalkyl. In some embodiments is a compound of Formula (III’) or (III), wherein each R7is independently selected from -CN.

[0127] In some embodiments is a compound of Formula (III’) or (III), wherein t is 1 or 2. In some embodiments is a compound of Formula (III’) or (III), wherein t is 2. In someembodiments is a compound of Formula (III’) or (III), wherein t is 1. In some embodiments is a compound of Formula (III’) or (III), wherein t is 0. In some embodiments is a compound of Formula (III’) or (III), wherein t is 3.

[0128] In some embodiments is a compound of Formula (IV’):Formula (IV’); or a pharmaceutically acceptable salt thereof, wherein: W, X, Y, and Z are independently selected from C(R2) and N, wherein at least one of Y and Z is C(R2); L is C(R6a)(R6b); each L1is C(R4a)2; each L2is C(R4b)2; J is C(R3)(R4), O, S, or N(R3a); R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11);R3cis selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), and -C(O)N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; R6aand R6bare independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R8is selected from C6-10aryl and C1-9heteroaryl, wherein C6-10aryl and C1-9heteroaryl are optionally substituted with one, two, or three R9groups;each R9is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; n is 1 or 2; p is 1, 2, or 3;q is 0 or 1; and indicates a single or double bond such that all valences are satisfied; wherein the compound is not.

[0129] In some embodiments is a compound of Formula (IV’), wherein each R4ais hydrogen. In some embodiments is a compound of Formula (IV’), wherein each R4bis hydrogen.

[0130] In some embodiments is a compound of Formula (IV):Formula (IV); or a pharmaceutically acceptable salt thereof, wherein: W, X, Y, and Z are independently selected from C(R2) and N, wherein at least one of Y and Z is C(R2); L is C(R6a)(R6b); J is C(R3)(R4), O, S, or N(R3a); R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two,or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3cis selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), and -C(O)N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); R6aand R6bare independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R8is selected from C6-10aryl and C1-9heteroaryl, wherein C6-10aryl and C1-9heteroaryl are optionally substituted with one, two, or three R9groups;each R9is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; n is 1 or 2; p is 1, 2, or 3;q is 0 or 1; and indicates a single or double bond such that all valences are satisfied; wherein the compound is not.

[0131] In some embodiments is a compound of Formula (IV’) or (IV), wherein W, X, Y, and Z are C(R2). In some embodiments is a compound of Formula (IV’) or (IV), wherein W, X, and Y are C(R2) and Z is N. In some embodiments is a compound of Formula (IV’) or (IV), wherein W, X, and Z are C(R2) and Y is N. In some embodiments is a compound of Formula (IV’) or (IV), wherein W, Y, and Z are C(R2) and X is N. In some embodiments is a compound of Formula (IV’) or (IV), wherein X, Y, and Z are C(R2) and W is N. In some embodiments is a compound of Formula (IV’) or (IV), wherein each R2is independently selected from hydrogen, halogen, C1-6alkyl, and C1-6haloalkyl.

[0132] In some embodiments is a compound of Formula (IV’) or (IV), wherein R3cis selected from C1-6alkyl and C3-6cycloalkyl, wherein C1-6alkyl and C3-6cycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), and - C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3cis selected from C1-6alkyl and C3-6cycloalkyl, wherein C1-6alkyl and C3-6cycloalkyl are optionally substituted with one C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3cis C1-6alkyl optionally substituted with one C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3cis C1-6alkyl substituted with one C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3cis C1-6alkyl substituted with one C(O)NH2. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3cis selected from unsubstituted C1-6alkyl and unsubstituted C3-6cycloalkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3cis unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3cis -CH3. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3cis unsubstituted C3-6cycloalkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3cis hydrogen.

[0133] In some embodiments is a compound of Formula (IV’) or (IV), wherein R6aand R6bare independently selected from hydrogen, halogen, and C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R6aand R6bare independently selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), whereinR6aand R6bare independently selected from hydrogen and halogen. In some embodiments is a compound of Formula (IV’) or (IV), wherein R6aand R6bare hydrogen.

[0134] In some embodiments is a compound of Formula (IV’) or (IV), wherein q is 1.

[0135] In some embodiments is a compound of Formula (IV’) or (IV), wherein q is 0.

[0136] In some embodiments is a compound of Formula (IV’) or (IV), wherein indicates a single bond. In some embodiments is a compound of Formula (IV’) or (IV), wherein indicates a double bond.

[0137] In some embodiments is a compound of Formula (IV’) or (IV), wherein each R2is independently selected from hydrogen, halogen, and C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein each R2is independently selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein each R2is independently selected from hydrogen and halogen. In some embodiments is a compound of Formula (IV’) or (IV), wherein each R2is hydrogen.

[0138] In some embodiments is a compound of Formula (IV’) or (IV), wherein R1is hydrogen. In some embodiments is a compound of Formula (IV’) or (IV), wherein R1is C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R1is -CH3.

[0139] In some embodiments is a compound of Formula (IV’) or (IV), wherein J is C(R3)(R4), O, or S.

[0140] In some embodiments is a compound of Formula (IV’) or (IV), wherein J is C(R3)(R4).

[0141] In some embodiments is a compound of Formula (IV’) or (IV), wherein R3is selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3is hydrogen. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3is C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3is - CH3.

[0142] In some embodiments is a compound of Formula (IV’) or (IV), wherein R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R4is hydrogen. In some embodiments is a compound of Formula (IV’) or (IV), wherein R4is -CN. In some embodiments is a compound of Formula (IV’) or (IV), wherein R4is C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R4is -CH3. In some embodiments is a compound of Formula (IV’) or (IV), wherein R4is C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R4is - C(O)N(R10)(R11).

[0143] In some embodiments is a compound of Formula (IV’) or (IV), wherein R3is hydrogen and R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3is hydrogen and R4is hydrogen. In someembodiments is a compound of Formula (IV’) or (IV), wherein R3is hydrogen and R4is -CN. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3is C1-6alkyl and R4is - CN. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3is -CH3and R4is -CN. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3is hydrogen and R4is -C(O)N(R10)(R11).

[0144] In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form an unsubstituted C2-9heterocycloalkyl.

[0145] In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form an azetidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form an unsubstituted azetidine ring.

[0146] In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form an unsubstituted pyrrolidine ring.

[0147] In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form a piperidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form a piperidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form a piperidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3and R4are combined to form an unsubstituted piperidine ring.

[0148] In some embodiments is a compound of Formula (IV’) or (IV), wherein J is O.

[0149] In some embodiments is a compound of Formula (IV’) or (IV), wherein J is S.

[0150] In some embodiments is a compound of Formula (IV’) or (IV), wherein J is N(R3a). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3ais hydrogen or C1-6alkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and - N(R10)(R11). In some embodiments is a compound of Formula (IV’) or (IV), wherein R3ais selected from hydrogen, C1-6alkyl and -C(O)R13. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3ais hydrogen. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3ais C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3ais -CH3. In some embodiments is a compound of Formula(IV’) or (IV), wherein R3ais -C(O)R13. In some embodiments is a compound of Formula (IV’) or (IV), wherein R3ais -C(O)R13and R13is unsubstituted C1-6alkyl.

[0151] In some embodiments is a compound of Formula (IV’) or (IV), wherein R8is C6-10aryl optionally substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (IV’) or (IV), wherein R8is phenyl optionally substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (IV’) or (IV), wherein R8is phenyl substituted with one, two, or three R9groups.

[0152] In some embodiments is a compound of Formula (IV’) or (IV), wherein R8is C1-9heteroaryl optionally substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (IV’) or (IV), wherein R8is C1-9heteroaryl substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (IV’) or (IV), wherein R8is pyridyl optionally substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (IV’) or (IV), wherein R8is pyridyl substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (IV’) or (IV), wherein R8is thiazolyl optionally substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (IV’) or (IV), wherein R8is thiazolyl substituted with one, two, or three R9groups.

[0153] In some embodiments is a compound of Formula (IV’) or (IV), wherein each R9is independently selected from halogen, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein each R9is independently selected from halogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein each R9is independently selected from halogen and C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein each R9is independently selected from halogen and C1-6haloalkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein each R9is independently selected from halogen. In some embodiments is a compound of Formula (IV’) or (IV), wherein each R9is independently selected from C1-6alkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein each R9is independently selected from C1-6haloalkyl. In some embodiments is a compound of Formula (IV’) or (IV), wherein each R9is independently selected from -CN.

[0154] In some embodiments is a compound of Formula (IV’) or (IV), wherein n is 1 and p is 1. In some embodiments is a compound of Formula (IV’) or (IV), wherein n is 1 and p is 2. In some embodiments is a compound of Formula (IV’) or (IV), wherein n is 2 and p is 2. In some embodiments is a compound of Formula (IV’) or (IV), wherein n is 1 and p is 3. In some embodiments is a compound of Formula (IV’) or (IV), wherein n is 2 and p is 3.

[0155] In some embodiments is a compound of Formula (V’):Formula (V’); or a pharmaceutically acceptable salt thereof, wherein: J is C(R3)(R4), O, S, or N(R3a); each L is C(R4a)2; each L1is C(R4b)2; X1is C(R2a) or N; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R2ais selected from hydrogen and C1-6alkyl; R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3dis selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), and -C(O)N(R10)(R11);R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; R8is selected from C6-10aryl and C1-9heteroaryl, wherein C6-10aryl and C1-9heteroaryl are optionally substituted with one, two, or three R9groups; each R9is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; n is 1 or 2; and p is 1, 2, or 3.

[0156] In some embodiments is a compound of Formula (V’), wherein each R4ais hydrogen. In some embodiments is a compound of Formula (V’), wherein each R4bis hydrogen.

[0157] In some embodiments is a compound of Formula (V):Formula (V); or a pharmaceutically acceptable salt thereof, wherein: J is C(R3)(R4), O, S, or N(R3a); X1is C(R2a) or N; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), -C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R2ais selected from hydrogen and C1-6alkyl; R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3dis selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), and -C(O)N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11);R8is selected from C6-10aryl and C1-9heteroaryl, wherein C6-10aryl and C1-9heteroaryl are optionally substituted with one, two, or three R9groups; each R9is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl;n is 1 or 2; and p is 1, 2, or 3.

[0158] In some embodiments is a compound of Formula (V’) or (V), wherein X1is C(R2a). In some embodiments is a compound of Formula (V’) or (V), wherein X1is C(R2a) and R2ais hydrogen. In some embodiments is a compound of Formula (V’) or (V), wherein X1is C(R2a) and R2ais C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein X1is N.

[0159] In some embodiments is a compound of Formula (V’) or (V), wherein R3dis selected from C1-6alkyl and C3-6cycloalkyl, wherein C1-6alkyl and C3-6cycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), and - C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3dis selected from C1-6alkyl and C3-6cycloalkyl, wherein C1-6alkyl and C3-6cycloalkyl are optionally substituted with one C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3dis C1-6alkyl optionally substituted with one C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3dis C1-6alkyl substituted with one C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3dis C1-6alkyl substituted with one C(O)NH2. In some embodiments is a compound of Formula (V’) or (V), wherein R3dis selected from unsubstituted C1-6alkyl and unsubstituted C3-6cycloalkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R3dis unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R3dis -CH3. In some embodiments is a compound of Formula (V’) or (V), wherein R3dis unsubstituted C3-6cycloalkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R3dis hydrogen.

[0160] In some embodiments is a compound of Formula (V’) or (V), wherein each R2is independently selected from hydrogen, halogen, and C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein each R2is independently selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein each R2is independently selected from hydrogen and halogen. In some embodiments is a compound of Formula (V’) or (V), wherein each R2is hydrogen.

[0161] In some embodiments is a compound of Formula (V’) or (V), wherein R1is hydrogen. In some embodiments is a compound of Formula (V’) or (V), wherein R1is C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R1is -CH3.

[0162] In some embodiments is a compound of Formula (V’) or (V), wherein J is C(R3)(R4), O, or S.

[0163] In some embodiments is a compound of Formula (V’) or (V), wherein J is C(R3)(R4).

[0164] In some embodiments is a compound of Formula (V’) or (V), wherein R3is selected from hydrogen and C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R3is hydrogen. In some embodiments is a compound of Formula (V’) or (V), wherein R3is C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R3is - CH3.

[0165] In some embodiments is a compound of Formula (V’) or (V), wherein R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R4is hydrogen. In some embodiments is a compound of Formula (V’) or (V), wherein R4is -CN. In some embodiments is a compound of Formula (V’) or (V), wherein R4is C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R4is -CH3. In some embodiments is a compound of Formula (V’) or (V), wherein R4is C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R4is - C(O)N(R10)(R11).

[0166] In some embodiments is a compound of Formula (V’) or (V), wherein R3is hydrogen and R4is selected from hydrogen, -CN, C1-6alkyl, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3is hydrogen and R4is hydrogen. In some embodiments is a compound of Formula (V’) or (V), wherein R3is hydrogen and R4is -CN. In some embodiments is a compound of Formula (V’) or (V), wherein R3is C1-6alkyl and R4is - CN. In some embodiments is a compound of Formula (V’) or (V), wherein R3is -CH3and R4is -CN. In some embodiments is a compound of Formula (V’) or (V), wherein R3is hydrogen and R4is -C(O)N(R10)(R11).

[0167] In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, - OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compoundof Formula (V’) or (V), wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form an unsubstituted C2-9heterocycloalkyl.

[0168] In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form an azetidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form an azetidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form an unsubstituted azetidine ring.

[0169] In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, - N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form a pyrrolidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form an unsubstituted pyrrolidine ring.

[0170] In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form a piperidine ring optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form a piperidine ring optionally substituted with one group selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), - C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form a piperidine ring optionally substituted with one group selected from C1-6alkyl and -C(O)R13, and wherein R13is selected from hydrogen and unsubstituted C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R3and R4are combined to form an unsubstituted piperidine ring.

[0171] In some embodiments is a compound of Formula (V’) or (V), wherein J is O.

[0172] In some embodiments is a compound of Formula (V’) or (V), wherein J is S.

[0173] In some embodiments is a compound of Formula (V’) or (V), wherein J is N(R3a). In some embodiments is a compound of Formula (V’) or (V), wherein R3ais hydrogen or C1-6alkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and - N(R10)(R11). In some embodiments is a compound of Formula (V’) or (V), wherein R3ais selected from hydrogen, C1-6alkyl and -C(O)R13. In some embodiments is a compound of Formula (V’) or (V), wherein R3ais hydrogen. In some embodiments is a compound of Formula (V’) or (V), wherein R3ais C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein R3ais -CH3. In some embodiments is a compound of Formula (V’) or (V), wherein R3ais -C(O)R13. In some embodiments is a compound of Formula (V’) or (V), wherein R3ais - C(O)R13and R13is unsubstituted C1-6alkyl.

[0174] In some embodiments is a compound of Formula (V’) or (V), wherein R8is C6-10aryl optionally substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (V’) or (V), wherein R8is phenyl optionally substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (V’) or (V), wherein R8is phenyl substituted with one, two, or three R9groups.

[0175] In some embodiments is a compound of Formula (V’) or (V), wherein R8is C1-9heteroaryl optionally substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (V’) or (V), wherein R8is C1-9heteroaryl substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (V’) or (V), wherein R8is pyridyl optionally substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (V’) or (V), wherein R8is pyridyl substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (V’) or (V), wherein R8is thiazolyl optionally substituted with one, two, or three R9groups. In some embodiments is a compound of Formula (V’) or (V), wherein R8is thiazolyl substituted with one, two, or three R9groups.

[0176] In some embodiments is a compound of Formula (V’) or (V), wherein each R9is independently selected from halogen, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments isa compound of Formula (V’) or (V), wherein each R9is independently selected from halogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments is a compound of Formula (V’) or (V), wherein each R9is independently selected from halogen and C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein each R9is independently selected from halogen and C1-6haloalkyl. In some embodiments is a compound of Formula (V’) or (V), wherein each R9is independently selected from halogen. In some embodiments is a compound of Formula (V’) or (V), wherein each R9is independently selected from C1-6alkyl. In some embodiments is a compound of Formula (V’) or (V), wherein each R9is independently selected from C1-6haloalkyl. In some embodiments is a compound of Formula (V’) or (V), wherein each R9is independently selected from -CN.

[0177] In some embodiments is a compound of Formula (V’) or (V), wherein n is 1 and p is 1. In some embodiments is a compound of Formula (V’) or (V), wherein n is 1 and p is 2. In some embodiments is a compound of Formula (V’) or (V), wherein n is 2 and p is 2. In some embodiments is a compound of Formula (V’) or (V), wherein n is 1 and p is 3. In some embodiments is a compound of Formula (V’) or (V), wherein n is 2 and p is 3.

[0178] In some embodiments is a compound selected from:,, , , ,; or a pharmaceutically acceptable salt thereof.

[0179] In some embodiments is a compound selected from:,, ,, , and; or a pharmaceutically acceptable salt thereof.

[0180] In some embodiments is a compound selected from:, ; or a pharmaceutically acceptable salt thereof.

[0181] In some embodiments is a compound selected from:; or a pharmaceutically acceptable salt thereof.

[0182] It is further appreciated that certain features of the disclosure described herein, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment. Conversely, various features of the disclosure described herein which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination.

[0183] At various places in the present specification, substituents of compounds described herein are disclosed in groups or in ranges. It is specifically intended that the groups or ranges include each and every individual subcombination of the members of such groups and ranges. For example, the term “C1-6alkyl” is specifically intended to individually disclose methyl, ethyl, C3alkyl, C4alkyl, C5alkyl, and C6alkyl.

[0184] At various places in the present specification various aryl, heteroaryl, cycloalkyl, and heterocycloalkyl rings are described. Unless otherwise specified, these rings can be attached to the rest of the molecule at any ring member as permitted by valency. For example, the term “pyridinyl,” “pyridyl,” or “a pyridine ring” may refer to a pyridin-2-yl, pyridin-3-yl, or pyridin- 4-yl ring.

[0185] At various places in the present specification a di-valent or linking group may be present. Each linking group is understood as linking in either direction. That is, if a linking group is described as -A-B-, then it is understood, unless otherwise specified, that the linking group is not directionally limited and can also be -B-A-. For example, when a linking group is written as -C(=O)-O-, it also means –O-C(=O)-.

[0186] The term “n-membered,” where “n” is an integer, typically describes the number of ring-forming atoms in a moiety where the number of ring-forming atoms is “n”. For example,piperidinyl is an example of a 6-membered heterocycloalkyl ring, pyrazolyl is an example of a 5-membered heteroaryl ring, pyridyl is an example of a 6-membered heteroaryl ring, and 1,2,3,4-tetrahydro-naphthalene is an example of a 10-membered cycloalkyl group.

[0187] For compounds described herein in which a variable appears more than once, each variable can be a different moiety independently selected from the group defining the variable. For example, where a structure is described having two R groups that are simultaneously present on the same compound, the two R groups can represent different moieties independently selected from the group defined for R.

[0188] As used herein, the phrase “optionally substituted” means unsubstituted or substituted.

[0189] As used herein, the term “substituted” means that a hydrogen atom is replaced by a non-hydrogen group. It is to be understood that substitution at a given atom is limited by valency. In some embodiments, an atom substituted by oxo (=O) has two hydrogen atoms replaced by the oxo substituent.

[0190] As used herein, the term “Ci-j,” where i and j are integers, employed in combination with a chemical group, designates a range of the number of carbon atoms in the chemical group with i-j defining the range. For example, C1-6alkyl refers to an alkyl group having 1, 2, 3, 4, 5, or 6 carbon atoms.

[0191] As used herein, the term “alkyl,” employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chain or branched. In some embodiments, the alkyl group contains 1 to 7, 1 to 6, 1 to 4, or 1 to 3 carbon atoms. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methyl-1-butyl, 3-pentyl, n-hexyl, 1,2,2-trimethylpropyl, n-heptyl, and the like. In some embodiments, the alkyl group is methyl, ethyl, or propyl. In some embodiments, the alkyl group is methyl.

[0192] As used herein, “halo” or “halogen”, employed alone or in combination with other terms, includes fluoro, chloro, bromo, and iodo. In some embodiments, halo is F or Cl.

[0193] As used herein, the term “haloalkyl,” employed alone or in combination with other terms, refers to an alkyl group having up to the full valency of halogen atom substituents, which may either be the same or different. In some embodiments, the halogen atoms are fluoro atoms. In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. Example haloalkyl groups include CF3, C2F5, CHF2, CCl3, CHCl2, C2Cl5, and the like.

[0194] As used herein, the term “alkoxy,” employed alone or in combination with other terms, refers to a group of formula -O-alkyl. Example alkoxy groups include methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), t-butoxy, and the like. In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms.

[0195] As used herein, “haloalkoxy,” employed alone or in combination with other terms, refers to a group of formula -O-(haloalkyl). In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. An example haloalkoxy group is -OCF3.

[0196] As used herein, “amino,” employed alone or in combination with other terms, refers to NH2.

[0197] As used herein, the term “cycloalkyl,” employed alone or in combination with other terms, refers to a non-aromatic cyclic hydrocarbon including cyclized alkyl and alkenyl groups. Cycloalkyl groups can include mono- or polycyclic (e.g., having 2, 3, or 4 fused, bridged, or spiro rings) ring systems. Also included in the definition of cycloalkyl are moieties that have one or more aromatic rings (e.g., aryl or heteroaryl rings) fused (i.e., having a bond in common with) to the cycloalkyl ring, for example, benzo derivatives of cyclopentane, cyclohexene, cyclohexane, and the like, or pyrido derivatives of cyclopentane or cyclohexane. Ring-forming carbon atoms of a cycloalkyl group can be optionally substituted by oxo. Cycloalkyl groups also include cycloalkylidenes. The term “cycloalkyl” also includes bridgehead cycloalkyl groups (e.g., non-aromatic cyclic hydrocarbon moieties containing at least one bridgehead carbon, such as admantan-1-yl) and spirocycloalkyl groups (e.g., non-aromatic hydrocarbon moieties containing at least two rings fused at a single carbon atom, such as spiro[2.5]octane and the like). In some embodiments, the cycloalkyl group has 3 to 10 ring members, or 3 to 7 ring members. In some embodiments, the cycloalkyl group is monocyclic or bicyclic. In some embodiments, the cycloalkyl group is monocyclic. In some embodiments, the cycloalkyl group is a C3-7monocyclic cycloalkyl group. Example cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptatrienyl, norbornyl, norpinyl, norcarnyl, tetrahydronaphthalenyl, octahydronaphthalenyl, indanyl, and the like. In some embodiments, the cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0198] As used herein, the term “heterocycloalkyl,” employed alone or in combination with other terms, refers to a non-aromatic ring or ring system, which may optionally contain one or more alkenylene or alkynylene groups as part of the ring structure, which has at least one heteroatom ring member independently selected from nitrogen, sulfur, oxygen, and phosphorus. Heterocycloalkyl groups can include mono- or polycyclic (e.g., having 2, 3 or 4 fused, bridged, or spiro rings) ring systems. In some embodiments, the heterocycloalkyl group is a monocyclic or bicyclic group having 1, 2, 3, or 4 heteroatoms independently selected from nitrogen, sulfur and oxygen. Also included in the definition of heterocycloalkyl are moieties that have one or more aromatic rings (e.g., aryl or heteroaryl rings) fused (i.e., having a bond in common with) to the non-aromatic heterocycloalkyl ring, for example, 1,2,3,4-tetrahydro-quinoline and the like.Heterocycloalkyl groups can also include bridgehead heterocycloalkyl groups (e.g., a heterocycloalkyl moiety containing at least one bridgehead atom, such as azaadmantan-1-yl and the like) and spiroheterocycloalkyl groups (e.g., a heterocycloalkyl moiety containing at least two rings fused at a single atom, such as [1,4-dioxa-8-aza-spiro[4.5]decan-N-yl] and the like). In some embodiments, the heterocycloalkyl group has 3 to 10 ring-forming atoms, 4 to 10 ring- forming atoms, or about 3 to 8 ring forming atoms. In some embodiments, the heterocycloalkyl group has 2 to 20 carbon atoms, 2 to 15 carbon atoms, 2 to 10 carbon atoms, or about 2 to 8 carbon atoms. In some embodiments, the heterocycloalkyl group has 1 to 5 heteroatoms, 1 to 4 heteroatoms, 1 to 3 heteroatoms, or 1 to 2 heteroatoms. The carbon atoms or heteroatoms in the ring(s) of the heterocycloalkyl group can be oxidized to form a carbonyl, an N-oxide, or a sulfonyl group (or other oxidized linkage) or a nitrogen atom can be quaternized. In some embodiments, the heterocycloalkyl portion is a C2-7monocyclic heterocycloalkyl group. In some embodiments, the heterocycloalkyl group is a morpholine ring, pyrrolidine ring, piperazine ring, piperidine ring, tetrahydropyran ring, tetrahydropyridine, azetidine ring, or tetrahydrofuran ring.

[0199] As used herein, the term “aryl,” employed alone or in combination with other terms, refers to a monocyclic or polycyclic (e.g., a fused ring system) aromatic hydrocarbon moiety, such as, but not limited to, phenyl, 1-naphthyl, 2-naphthyl, and the like. In some embodiments, aryl groups have from 6 to 10 carbon atoms or 6 carbon atoms. In some embodiments, the aryl group is a monocyclic or bicyclic group. In some embodiments, the aryl group is phenyl or naphthyl. In some embodiments, the aryl group is phenyl.

[0200] As used herein, the term “heteroaryl,” employed alone or in combination with other terms, refers to a monocyclic or polycyclic (e.g., a fused ring system) aromatic hydrocarbon moiety, having one or more heteroatom ring members independently selected from nitrogen, sulfur and oxygen. In some embodiments, the heteroaryl group is a monocyclic or a bicyclic group having 1, 2, 3, or 4 heteroatoms independently selected from nitrogen, sulfur and oxygen.

[0201] In some embodiments, the heteroaryl group is a 5-14 membered heteroaryl group. In some embodiments, the heteroaryl group is a 5-10 membered heteroaryl group. In some embodiments, the heteroaryl group is a 5-6 membered heteroaryl group. Example heteroaryl groups include, but are not limited to, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrryl, oxazolyl, benzofuryl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 1,2,4-thiadiazolyl, isothiazolyl, purinyl, carbazolyl, benzimidazolyl, indolinyl, pyrrolyl, azolyl, quinolinyl, isoquinolinyl, benzisoxazolyl, imidazo[1,2-b]thiazolyl or the like. The carbon atoms or heteroatoms in the ring(s) of the heteroaryl group can be oxidized to form a carbonyl, an N-oxide, or a sulfonyl group (or other oxidized linkage) or a nitrogen atom can be quaternized, provided the aromatic nature of the ring is preserved. In some embodiments, the heteroaryl group has from 3 to 10 carbon atoms, from 3 to 8 carbon atoms, from 3 to 5 carbon atoms, from 1 to 5 carbon atoms, or from 5 to 10 carbon atoms. In some embodiments, the heteroaryl group contains 3 to 14, 4 to 12, 4 to 8, 9 to 10, or 5 to 6 ring-forming atoms. In some embodiments, the heteroaryl group has 1 to 4, 1 to 3, or 1 to 2 heteroatoms.

[0202] The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers and diastereomers, are intended unless otherwise indicated. Compounds described herein that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated herein. Cis and trans geometric isomers of the compounds described herein may be isolated as a mixture of isomers or as separated isomeric forms.

[0203] Compounds described herein also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone – enol pairs, amide - imidic acid pairs, lactam – lactim pairs, enamine – imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1H- and 3H-imidazole, 1H-, 2H- and 4H- 1,2,4-triazole, 1H- and 2H- isoindole, and 1H- and 2H-pyrazole.

[0204] Compounds described herein also include all isotopes of atoms occurring in the intermediates or final compounds. Isotopes include those atoms having the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium. In some embodiments, the compounds described herein include at least one deuterium atom.

[0205] The term, “compound,” as used herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted, unless otherwise specified. The term “compound” is also not limited by the way in which it was made. Thus, a compound described herein includes molecules that were made by a synthetic process or by a biological process (such as through enzyme conversion or metabolism), or combinations thereof.

[0206] All compounds, and pharmaceutically acceptable salts thereof, can be found together with other substances such as water and solvents (e.g., in the form of hydrates and solvates) or can be isolated.

[0207] In some embodiments, the compounds described herein, or salts thereof, are substantially isolated. By “substantially isolated” is meant that the compound is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched in the compounds described herein. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of a compound described herein, or salt thereof. Methods for isolating compounds and their salts are routine in the art.

[0208] 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.

[0209] As used herein, "pharmaceutically acceptable salts" refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts of the compounds described herein include the non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the compounds described herein can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p.1418 and Journal of Pharmaceutical Science, 66, 2 (1977), each of which is incorporated herein by reference in its entirety. Synthesis of Compounds

[0210] Compounds described herein are synthesized using standard synthetic techniques or using methods known in the art in combination with methods described herein.

[0211] Unless otherwise indicated, conventional methods of mass spectroscopy, NMR, HPLC, protein chemistry, biochemistry, recombinant DNA techniques and pharmacology are employed.

[0212] Compounds are prepared using standard organic chemistry techniques such as those described in, for example, March’s Advanced Organic Chemistry, 6thEdition, John Wiley andSons, Inc. Alternative reaction conditions for the synthetic transformations described herein may be employed such as variation of solvent, reaction temperature, reaction time, as well as different chemical reagents and other reaction conditions. The starting materials are available from commercial sources or are readily prepared.

[0213] Suitable reference books and treatise that detail the synthesis of reactants useful in the preparation of compounds described herein, or provide references to articles that describe the preparation, include for example, "Synthetic Organic Chemistry", John Wiley & Sons, Inc., New York; S. R. Sandler et al., "Organic Functional Group Preparations," 2nd Ed., Academic Press, New York, 1983; H. O. House, "Modern Synthetic Reactions", 2nd Ed., W. A. Benjamin, Inc. Menlo Park, Calif.1972; T. L. Gilchrist, "Heterocyclic Chemistry", 2nd Ed., John Wiley & Sons, New York, 1992; J. March, "Advanced Organic Chemistry: Reactions, Mechanisms and Structure", 4th Ed., Wiley-Interscience, New York, 1992. Additional suitable reference books and treatise that detail the synthesis of reactants useful in the preparation of compounds described herein, or provide references to articles that describe the preparation, include for example, Fuhrhop, J. and Penzlin G. "Organic Synthesis: Concepts, Methods, Starting Materials", Second, Revised and Enlarged Edition (1994) John Wiley & Sons ISBN: 3-527-29074-5; Hoffman, R.V. "Organic Chemistry, An Intermediate Text" (1996) Oxford University Press, ISBN 0-19-509618-5; Larock, R. C. "Comprehensive Organic Transformations: A Guide to Functional Group Preparations" 2nd Edition (1999) Wiley-VCH, ISBN: 0-471-19031-4; March, J. "Advanced Organic Chemistry: Reactions, Mechanisms, and Structure" 4th Edition (1992) John Wiley & Sons, ISBN: 0-471-60180-2; Otera, J. (editor) "Modern Carbonyl Chemistry" (2000) Wiley- VCH, ISBN: 3-527-29871-1; Patai, S. "Patai's 1992 Guide to the Chemistry of Functional Groups" (1992) Interscience ISBN: 0-471-93022-9; Solomons, T. W. G. "Organic Chemistry" 7th Edition (2000) John Wiley & Sons, ISBN: 0-471-19095-0; Stowell, J.C., "Intermediate Organic Chemistry" 2nd Edition (1993) Wiley-Interscience, ISBN: 0-471-57456-2; "Industrial Organic Chemicals: Starting Materials and Intermediates: An Ullmann's Encyclopedia" (1999) John Wiley & Sons, ISBN: 3-527-29645-X, in 8 volumes; "Organic Reactions" (1942-2000) John Wiley & Sons, in over 55 volumes; and "Chemistry of Functional Groups" John Wiley & Sons, in 73 volumes.

[0214] In some embodiments, compounds are prepared as described in the Examples. Methods of Use

[0215] Compounds described herein can inhibit the activity of SARM1. For example, the compounds described herein can be used to inhibit activity or a function of SARM1 in a cell or in an individual or patient in need of inhibition of the enzyme by administering an inhibitingamount of a compound described herein to the cell, individual, or patient. As used herein, the term “in a cell” includes both inside the cell membrane and on the surface of the cell membrane.

[0216] Compounds described herein, as SARM1 inhibitors, can increase levels of NAD+ in a cell. Accordingly, the present disclosure is further directed to a method of increasing the level of NAD+ in a sample or in a patient, comprising contacting the sample or administering to the patient a compound described herein, or a pharmaceutically acceptable salt thereof, wherein the increased level of NAD+ is relative to the level of NAD+ prior to the contacting or administering.

[0217] Compounds described herein, as SARM1 inhibitors, can inhibit axonal degeneration. Accordingly, the present disclosure is further directed to a method of inhibiting axonal degeneration in a sample or in a patient, comprising contacting the sample or administering to the patient an inhibiting amount of a compound described herein, or a pharmaceutically acceptable salt thereof.

[0218] The compounds described herein are useful in the treatment and prevention of various diseases associated with abnormal expression or activity of SARM1. For example, the compounds described herein are useful in the treatment and prevention of neurological disorders. In some embodiments, the compounds described herein are useful in the treatment of neurological disorders. In some embodiments, the compounds described herein are useful in the prevention of neurological disorders. The term "neurological disorder" generally refers to a disorder affecting the nervous system, including the central nervous system or the peripheral nervous system. The term “neurological disorder” also includes ocular indications having a nexus to the nervous system.

[0219] In some embodiments, the neurological disorder treatable or preventable by administration of a compound described herein includes neurodegenerative diseases. In some embodiments, the compounds described herein are useful in the treatment of neurodegenerative diseases. In some embodiments, the compounds described herein are useful in the prevention of neurodegenerative diseases. Neurodegenerative diseases are characterized by damage to the central nervous system and can be identified by progressive dysfunction, degeneration and death of specific populations of neurons which are often synaptically interconnected. Examples of neurodegenerative diseases include Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), prion disease, motor neuron diseases (MND), spinocerebellar ataxia (SCA), spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and epilepsy.

[0220] Examples of neurological disorders treatable or preventable according to the methods described herein include spinal muscular atrophy (SMA), Chemotherapy Induced Peripheral Neuropathy (representative chemotherapeutic agents include vinca-alkaloids, taxols and platins),multiple sclerosis (MS), traumatic brain injury (TBI), spinal cord injury, stroke, Parkinson’ disease, glaucoma, Huntington’s disease, Alzheimer’s disease, Charcot-Marie-Tooth disease (CMT), retinitis pigmentosa (RP), age-related macular degeneration (AMD), small fiber neuropathies, peripheral neuropathy (e.g., viral neuropathy), spinocerebellar ataxias, cystic fibrosis, familial amyloidotic polyneuropathy, spongiform encephalopathies, spinal and bulbar muscular atrophy, hereditary dentatorubral-pallidoluysian atrophy, adrenoleukodystrophy, adrenomyeloneuropathy, Alexander’s disease, amyotrophic lateral sclerosis (ALS), Bassen- Kornzweig syndrome, Bell’s palsy, progressive supra nuclear palsy (PSP), central pontine myelolysis, cluster headache, congenital hypomyelination, corticobasal degeneration, Creutzfeldt-Jakob disease, epilepsy, dementia (e.g., frontotemporal dementia and Lewy body dementia), demyelination disorders (e.g., ischemic demyelination), encephalomyelitis, Friedrich’s ataxia, Gaucher’s disease, hereditary sensory and autonomic neuropathy (HSAN), Hurler syndrome, Krabbe’s disease, metachromatic leukodystrophy, migraine and tension headaches, mild cognitive impairment, motor spinoneuron disease, neuromyelitis optica, Niemann-Pick disease, optic neuritis, Pelizaeus Merzbacher disease, peripheral neuropathy, periventricular leukomalacia, post-herpetic neuralgia, prion disease, progressive supranuclear palsy, progressive multifocal leukoencephalopathy, Tay-Sacks disease, thoracic disc herniation, traverse myelitis, trigeminal neuralgia, Wallerian degeneration, cerebellar degeneration, chiari malformation, dystonia, encephalitis (e.g., pediatric viral encephalitis and La Crosse virus encephalitis), hyperekplexia, multifocal motor neuropathy, muscular dystrophy, myasthenia gravis, myopathy, neurofibromatosis, neuronal ceroid lipofuscinosis, neuropathies (e.g., peripheral neuropathy), pseudobulbar affect, restless legs syndrome, spina bifida, syringomyelia, thoracic outlet syndrome, and transverse myelitis.

[0221] In other embodiments, the neurological disorder treatable or preventable by administration of a compound described herein is a neuropathy. As used herein, the term “neuropathy” refers broadly to diseased conditions of the nervous system, including polyneuropathy; neuropathy, ataxia, and retinosa pigmentosa (NARP); familial amyloid neuropathies; diabetic neuropathy (peripheral neuropathy due to diabetes mellitus); peripheral neuropathy (e.g., chemotherapy-induced peripheral neuropathy (CIPN), including CIPN caused by vinca alkaloids, bortezomib, ixabepilone, thalidomide and its analogs, taxanes, and platinum- based agents); and cranial neuropathy (e.g., auditory neuropathy and optic neuropathy). The term also includes other neuropathies associated with genetic disorders (e.g., NMNAT2 genetic mutation disorders).

[0222] In still other embodiments, the neurological disorder treatable or preventable by administration of a compound described herein is an ocular neuropathy (e.g., optic neuropathy).The term “optic neuropathy” refers to damage to the optic nerve from a number of causes. Types of optic neuropathy include ischemic optic neuropathy (e.g., anterior and posterior ischemic optic neuropathy); optic neuritis (e.g., chronic relapsing inflammatory optic neuropathy (CRION), single isolated optic neuritis (SION), and relapsing isolated optic neuritis); compressive optic neuropathy; infiltrative optic neuropathy; traumatic optic neuropathy; mitochondrial optic neuropathies; and hereditary optic neuropathies (e.g., Leber’s hereditary optic neuropathy (LHON), hereditary neuropathy with liability to pressure palsy (HNPP), and dominant optic atrophy).

[0223] In still other embodiments, the neurological disorder treatable or preventable by administration of a compound described herein is multiple sclerosis (MS), chemotherapy- induced peripheral neuropathy (CIPN), amyotrophic lateral sclerosis (ALS), glaucoma, traumatic brain injury (TBI), or stroke.

[0224] As used herein, the term “cell” is meant to refer to a cell that is in vitro, ex vivo or in vivo. In some embodiments, an ex vivo cell can be part of a tissue sample excised from an organism such as a mammal. In some embodiments, an in vitro cell can be a cell in a cell culture. In some embodiments, an in vivo cell is a cell living in an organism such as a mammal.

[0225] As used herein, the term “contacting” refers to the bringing together of indicated moieties in an in vitro system or an in vivo system. For example, “contacting” SARM1 or “contacting” a cell with a compound described herein includes the administration of a compound described herein to an individual or patient, such as a human, having SARM1, as well as, for example, introducing a compound described herein into a sample containing a cellular or purified preparation containing SARM1.

[0226] As used herein, the term “individual” or “patient,” used interchangeably, refers to mammals, and particularly humans. The individual or patient can be in need of treatment.

[0227] As used herein, the phrase “therapeutically effective amount” refers to the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue, system, animal, individual or human that is being sought by a researcher, veterinarian, medical doctor or other clinician.

[0228] As used herein, the phrase “inhibiting amount” refers to the amount of active compound or pharmaceutical agent that elicits a measurable SARM1 inhibition or axonal degeneration in a tissue, system, animal, individual or human.

[0229] As used herein the term “treating” or “treatment” refers to 1) inhibiting the disease in an individual who is experiencing or displaying the pathology or symptomatology of the disease (i.e., arresting further development of the pathology and / or symptomatology), or 2) amelioratingthe disease in an individual who is experiencing or displaying the pathology or symptomatology of the disease (i.e., reversing the pathology and / or symptomatology).

[0230] As used herein the term “preventing” or “prevention” refers to preventing the disease in an individual who may be predisposed to the disease but does not yet experience or display the pathology or symptomatology of the disease. In some embodiments is a method of preventing a disease in a patient, by administering to the patient a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof. Combination Therapy

[0231] One or more additional pharmaceutically active agents or treatment methods can be used in combination with the compounds described herein. The agents can be combined with the present compounds in a single dosage form, or the agents can be administered simultaneously or sequentially as separate dosage forms. Examples of additional agents include acamprosate, agomelatine, almotriptan, amantadine, amisulpride, amitriptyline, apomorphine, aripiprazole, asenapine, atomoxetine, baclofen, botulinum toxin type A, bromocriptine, buccal midazolam, buprenorphine, buspirone, cabergoline, carbamazepine, chlordiazepoxide, chlorpromazine, citalopram, clobazam, clomethiazole, clomipramine, clonazepam, clozapine, denzapine, co- beneldopa, co-careldopa, dantrolene, dexamfetamine, diazepam, divalproex sodium, donepezil, doxepin, duloxetine, eletriptan, entacapone, epinephrine, escitalopram, eslicarbazepine, ethosuximide, fingolimod, fluoxetine, flupentixol, flupentixol, fluphenazine long-acting injection (modecate), fluvoxamine (Faverin), frovatriptan, gabapentin, galantamine, haloperidol, imipramine, lacosamide, lamotrigine, levetiracetam, levomepromazine, lisdexamfetamine, lithium, lofepramine, loprazolam, lorazepam, lormetazepam, lurasidone, melatonin, memantine, methylphenidate, mianserin, mirtazapine, moclobemide, modafinil, naratriptan, neostigmine, nitrazepam, nortriptyline, olanzapine, orlistat, orphenadrine, oxazepam, oxcarbazepine, paliperidone, paliperidone, paroxetine, perampanel, pergolide, pericyazine, phenobarbital, phenytoin, piracetam, pizotifen, pramipexole, pregabalin, primidone, prochlorperazine, procyclidine, pyridostigmine, quetiapine, rasagiline, reboxetine, risperidone, rivastigmine, rizatriptan, ropinirole, rotigotine, rufinamide, selegiline, sertraline, sodium oxybate, sodium valproate, sulpiride, sumatriptan, temazepam, tetrabenazine, tiagabine, tizanidine, tolcapone, topiramate, trazodone, trihexyphenidyl, trimipramine, valproate semisodium, venlafaxine, vigabatrin, vortioxetine, zolmitriptan, zolpidem, zonisamide, zopiclone, and zuclopenthixol.

[0232] In some embodiments, the one or more additional pharmaceutically active agent can include a neuroprotective agent. In some embodiments, the neuroprotective agent is a dual leucine-zipper kinase (DLK) inhibitor. In some embodiments, the neuroprotective agent is a nicotinamide phosphoribosyltransferase (NAMPT) inhibitor.

[0233] In some embodiments, the one or more additional pharmaceutically active agent can be NAD+ or an NAD+ precursor. NAD+ precursors include, for example, nicotinamide riboside (NR), nicotinic acid (NA), nicotinic acid riboside (NaR), nicotinamide (NAM), nicotinamide mononucleotide (NMN), nicotinic acid mononucleotide (NaMN), tryptophan, vitamin B3, and nicotinic acid adenine dinucleotide (NAAD). Pharmaceutical Formulations and Dosage Forms

[0234] When employed as pharmaceuticals, the compounds described herein can be administered in the form of pharmaceutical compositions. A pharmaceutical composition refers to a combination of a compound described herein, or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable carrier.

[0235] These compositions can be prepared in a manner well known in the pharmaceutical art, and can be administered by a variety of routes, depending upon whether local or systemic treatment is desired and upon the area to be treated. Pharmaceutical compositions may be formulated in a conventional manner using one or more physiologically acceptable carriers including excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. Additional details about suitable excipients for pharmaceutical compositions described herein may be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington’s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins1999), herein incorporated by reference for such disclosure.

[0236] Administration may be oral, topical (including ophthalmic and to mucous membranes including intranasal, vaginal and rectal delivery), pulmonary (e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal, intranasal, epidermal and transdermal), ocular (e.g., eye drops or intravitreal, subconjunctival, subtenon, or retrobulbar injection), or parenteral.

[0237] Also described herein are pharmaceutical compositions which contain, as the active ingredient, one or more of the compounds described herein above in combination with one or more pharmaceutically acceptable carriers. In making the compositions described herein, the active ingredient is typically mixed with an excipient, diluted by an excipient or enclosed within such a carrier in the form of, for example, a capsule, sachet, paper, or other container. When the excipient serves as a diluent, it can be a solid, semi-solid, or liquid material, which acts as avehicle, carrier or medium for the active ingredient. Thus, the compositions can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), ointments, soft and hard gelatin capsules, suppositories, sterile injectable solutions, and sterile packaged powders.

[0238] The compositions can be formulated in a unit dosage form. The term "unit dosage form" refers to a physically discrete unit suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient.

[0239] The active compound can be effective over a wide dosage range and is generally administered in a pharmaceutically effective amount. It will be understood, however, that the amount of the compound actually administered will usually be determined by a physician, according to the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, and the like.

[0240] For preparing solid compositions such as tablets, the principal active ingredient is mixed with a pharmaceutical excipient to form a solid pre-formulation composition containing a homogeneous mixture of a compound described herein. When referring to these pre-formulation compositions as homogeneous, the active ingredient is typically dispersed evenly throughout the composition so that the composition can be readily subdivided into equally effective unit dosage forms such as tablets, pills and capsules. This solid pre-formulation is then subdivided into unit dosage forms of the type described above.

[0241] The tablets or pills described herein can be coated or otherwise compounded to provide a dosage form affording the advantage of prolonged action. For example, the tablet or pill can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope over the former. The two components can be separated by an enteric layer which serves to resist disintegration in the stomach and permit the inner component to pass intact into the duodenum or to be delayed in release. A variety of materials can be used for such enteric layers or coatings, such materials including a number of polymeric acids and mixtures of polymeric acids with such materials as shellac, cetyl alcohol, and cellulose acetate.

[0242] The liquid forms in which the compounds and compositions described herein can be incorporated for administration orally or by injection include aqueous solutions, suitably flavored syrups, aqueous or oil suspensions, and flavored emulsions with edible oils such as cottonseed oil, sesame oil, coconut oil, or peanut oil, as well as elixirs and similar pharmaceutical vehicles.

[0243] Compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable, aqueous or organic solvents, or mixtures thereof, and powders. The liquid or solid compositions may contain suitable pharmaceutically acceptable excipients as described supra. In some embodiments, the compositions are administered by the oral or nasal respiratory route for local or systemic effect. Compositions can be nebulized by use of inert gases. Nebulized solutions may be breathed directly from the nebulizing device or the nebulizing device can be attached to a face masks tent, or intermittent positive pressure breathing machine. Solution, suspension, or powder compositions can be administered orally or nasally from devices which deliver the formulation in an appropriate manner.

[0244] The amount of compound or composition administered to a patient will vary depending upon what is being administered, the purpose of the administration, such as prophylaxis or therapy, the state of the patient, the manner of administration, and the like. In therapeutic applications, compositions can be administered to a patient already suffering from a disease in an amount sufficient to cure or at least partially arrest the symptoms of the disease and its complications. Effective doses will depend on the disease condition being treated as well as by the judgment of the attending clinician depending upon factors such as the severity of the disease, the age, weight and general condition of the patient, and the like.

[0245] The compositions administered to a patient can be in the form of pharmaceutical compositions described above. These compositions can be sterilized by conventional sterilization techniques, or may be sterile filtered. Aqueous solutions can be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile aqueous carrier prior to administration.

[0246] The therapeutic dosage of the compounds described herein can vary according to, for example, the particular use for which the treatment is made, the manner of administration of the compound, the health and condition of the patient, and the judgment of the prescribing physician. The proportion or concentration of a compound described herein in a pharmaceutical composition can vary depending upon a number of factors including dosage, chemical characteristics (e.g., hydrophobicity), and the route of administration. The dosage is likely to depend on such variables as the type and extent of progression of the disease or disorder, the overall health status of the particular patient, the relative biological efficacy of the compound selected, formulation of the excipient, and its route of administration. Effective doses can be extrapolated from dose-response curves derived from in vitro or animal model test systems.EXAMPLES General Experimental:

[0247] The following examples are offered for purposes of illustration and are not intended to limit the scope of the claims provided herein. Those of skill in the art will readily recognize a variety of non-critical parameters which can be changed or modified to yield essentially the same results. The compounds of the Examples were found to be inhibitors of SARM1 according to one or more of the assays provided herein.

[0248] All reactions sensitive to air or moisture were carried out in flame-dried glassware under an atmosphere of nitrogen. All commercially available reagents were purchased from suppliers such as Sigma-Aldrich (MilliporeSigma), Combi-Blocks, Enamine, Sinopharm Chemical Reagent Co. (SCRC), and Alfa Aesar and were used without purification unless otherwise noted. Proton nuclear magnetic resonance (1H NMR) spectra were recorded on Bruker AVⅢ 400 or Bruker AVⅢ 500 spectrometers. Samples were dissolved in deuterated chloroform (CDCl3), dimethyl sulfoxide (DMSO-d6), acetonitrile (CD3CN) or methanol (CD3OD). Chemical shifts are recorded in parts per million (ppm) and are referenced to the centerline of deuterochloroform (δ 7.26 ppm), of DMSO-d6(δ 2.50 ppm), of CD3CN (δ 1.94 ppm) or of CD3OD (δ 3.31 ppm). Data were recorded as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, qt = quintet, m = multiplet, br = broad). Coupling constants (J values) are given in Hertz (Hz). Low resolution ESI mass spectra were recorded on a either an Agilent 1200 HPLC / 6100 SQ system or an Agilent 1260 Infinity II HPLC / 6125 SQ system. LCMS measurements were recorded on Agilent 1200 HPLC / 6100 SQ System. List of Abbreviations: aq aqueous Boc tert-butyloxycarbonyl Boc2O Boc-anhydride or di-tert-butyl dicarbonate CDI 1,1’-carbonyl-diimidazole d day(s) D2H (deuterium) DABCO 1,4-diazabicyclo[2.2.2]octane dba dibenzylideneacetone DCM dichloromethane DMP Dess-Martin periodinane or 3-Oxo-1λ5,2-benziodoxole-1,1,1(3H)-triyl triacetate DEA diethylamineDHP 3,4-dihydropyran DIAD diisopropyl azodicarboxylate DIPEA N,N-diisopropylethylamine DMAP 4-(dimethylamino)pyridine DMF dimethylformamide DMSO dimethylsulfoxide DPPA diphenyl phosphoryl azide EDC.HCl N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride ESI-MS electrospray ionization – mass spectrometry Et ethyl EtOAc ethyl acetate EtOH ethanol equiv equivalent(s) FA formic acid (g) gaseous h hour(s) HATU 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3- oxide hexafluorophosphate HOBt 1-hydroxybenzotriazole LAH lithium aluminum hydride LCMS liquid chromatography mass spectrometry LiHMDS lithium bis(trimethylsilyl)amide MS mass spectrometry MeCN acetonitrile MeOH methanol MHz megahertz min minute(s) mg milligram(s) mL milliliter(s) mmol millimole(s) M molar MeCN acetonitrile mol mole(s) Ms methanesulfonyl MW microwaveN normal NBS N-bromosuccinimide NCS N-chlorosuccinimide OTf trifluoromethanesulfonate Pd / C palladium on carbon PE petroleum ether Ph phenyl PTSA p-toluenesulfonic acid1H NMR proton nuclear magnetic resonance RP-HPLC reverse-phase high performance liquid chromatography RT retention time rt room temperature sat saturated SEM 2-(trimethylsilyl)ethoxymethyl SFC supercritical fluid chromatography T3P propylphosphonic anhydride TBAF tetrabutylammonium fluoride TBPH tert-butyl hydroperoxide solution (Luperox®, TBH70X) TBUP tri-tert-butylphosphonium tetrafluoroborate t-BuOK potassium tert-butoxide TEA triethylamine TFA trifluoroacetic acid THF tetrahydrofuran THP tetrahydropyran TLC thin layer chromatography Tol toluene TosMIC p-toluenesulfonylmethyl isocyanide wt % weight percent v / v % volume by volume percent w / v % weight by volume percent XPhos 2-dicyclohexylphosphino-2’,4’,6’-triisopropylbiphenylExample 1

[0249] Int.1.1: 2-methyl-N-(3-phenyloxetan-3-yl)propane-2-sulfinamide. To a stirred solution of bromobenzene (300 mg, 1.9 mmol) in THF (6 mL) was added n-BuLi (0.92 mL, 2.29 mmol) dropwise at -70 °C and stirred for 1 h under a nitrogen atmosphere. Then 2-methyl-N- (oxetan-3-ylidene) propane-2-sulfinamide (334 mg, 1.9 mmol) was added dropwise at -70 °C and stirred for 1 h. The resulting mixture was poured into ice water (10 mL) slowly and extracted with EtOAc (2 x 20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by reverse phase flash to afford Int.1.1, 2-methyl-N-(3-phenyloxetan-3- yl)propane-2-sulfinamide (210 mg, 43.3%) as a brown oil.

[0250] Int.1.2: 3-phenyloxetan-3-amine. To a stirred solution of 2-methyl-N-(3- phenyloxetan-3-yl) propane-2-sulfinamide (200 mg, 0.79 mmol) in MeOH (4 mL) was added HCl / MeOH (1.97 mL, 7.89 mmol) at 0 °C. The resulting mixture was stirred 2 h at rt. The resulting mixture was concentrated under reduced pressure to yield light brown oil. The residue was dissolved in EtOAc (5 mL) and H2O (5 mL), then was extracted with EtOAc (1 x 5 mL). The aqueous phase was basified to pH 9-10 with sat. Na2CO3. The resulting mixture was extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by reverse phase flash to Int.1.2, afford 3-phenyloxetan-3-amine (87 mg, 73.8%) as a light oil.

[0251] Example 1: N-(3-phenyloxetan-3-yl)quinolin-7-amine. To a stirred solution of 3- phenyloxetan-3-amine (87 mg, 0.58 mmol), Cs2CO3(380 mg, 1.16 mmol) and 7- bromoquinoline (121 mg, 0.58 mmol) in dioxane (2 mL) was added Cphos (25.4 mg, 0.058 mmol) and Cphos Pd G3(47.9 mg, 0.058 mmol) at rt under a nitrogen atmosphere. The resulting mixture was heated to 100 °C and stirred for 12 h under a nitrogen atmosphere. The resulting mixture was cooled to rt, diluted with water (5 mL) and the organics were extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with brine (5 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by reverse phase flash and Prep-HPLC to afford Example 1, N-(3-phenyloxetan-3-yl)quinolin-7- amine (7.3 mg, 4.5%) as a light green solid.1H NMR (400 MHz, DMSO-d6, ppm) δ 8.52 (dd, J =4.3, 1.8 Hz, 1H), 8.04 (dd, J = 8.0, 1.8 Hz, 1H), 7.74 – 7.62 (m, 4H), 7.45 –7.26 (m, 3H), 7.14– 7.07 (m, 2H), 6.01 (d, J = 2.3 Hz, 1H), 4.99 – 4.88 (m, 4H). LCMS EI-MS m / z: = 277 [M+H]+. Example 2

[0252] Int.2.1: 2-methyl-N-[3-(2-methylphenyl)oxetan-3-yl]propane-2-sulfinamide. To a stirred solution of O-bromotoluene (1.00 g, 5.85 mmol, 1.0 eq.) in THF (20 mL) was added n- BuLi (2.81 mL, 7.02 mmol, 1.2 eq., 2.5 M) dropwise at -70 °C under a nitrogen atmosphere. The resulting mixture was stirred for 30 min at -70 °C. Then to the above mixture was added a solution of 2-methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide (1.02 g, 5.85 mmol, 1.0 eq.) in THF (5 mL) dropwise at -70 °C. The resulting mixture was stirred for 2 h at -70 °C and then warmed to 0 °C. The resulting mixture was quenched by sat. NH4Cl (aq.) (30 mL) at 0 °C and was extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated to yield Int.2.1, 2-methyl-N-[3-(2- methylphenyl)oxetan-3-yl]propane-2-sulfinamide (900 mg) as an off-white solid. The crude product was used in the next step directly without further purification. LCMS ESI-MS m / z: = 268 [M+H]+.

[0253] Int.2.2: 3-(2-methylphenyl)oxetan-3-amine. To a stirred solution of 2-methyl-N-[3- (2-methylphenyl)oxetan-3-yl]propane-2-sulfinamide (0.90 g, 3.37 mmol, 1 eq.) in MeOH (9 mL) was added HCl / MeOH (8.41 mL, 33.7 mmol, 10.0 eq., 4 M) dropwise at 0 °C. The resulting mixture was stirred for additional 3 h at 0 °C under a nitrogen atmosphere. The reaction was diluted by water (20 mL). The resulting mixture was basified to pH 9 with saturated Na2CO3(aq.). The resulting mixture was extracted with EtOAc (3 x 25 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated to yield an off-white solid. The crude product was purified by reverse phase flash with the following conditions (Column, WelFlash C18-Ⅰ, 20-40 μm, 330 g; Mobile Phase A: Water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Gradient: 25% B to 45% B in 20 min; Flow rate: 120 mL / min; Wave Length: 220 nm; RT1 (min): 10; Number of Runs: 2 times) to afford Int.2.2, 3-(2-methylphenyl)oxetan-3-amine (300.0 mg, 2 steps yield: 31.3%) as an off- white solid. LCMS EI-MS m / z: = 164 [M+H]+.

[0254] Example 2: N-[3-(2-methylphenyl)oxetan-3-yl]quinolin-7-amine. To a stirred solution of 3-(2-methylphenyl)oxetan-3-amine (300.0 mg, 1.84 mmol, 1.0 eq.) and 7- bromoquinoline (382.4 mg, 1.84 mmol, 1.0 eq.) in dioxane (30 mL) were added Cs2CO3(1497.2 mg, 4.60 mmol, 2.5 eq.) and Cphos (136.4 mg, 0.31 mmol, 0.17 eq.), Cphos Pd G3 (256.9 mg, 0.31 mmol, 0.17 eq.) at room temperature under a nitrogen atmosphere. The resulting mixture was stirred for 12 h at 100 °C. The mixture was cooled to room temperature. The reaction was diluted by water (10 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (15 mL), dried over Na2SO4, filtered, and concentrated to yield a light yellow solid. The crude product was purified by reverse phase flash with the following conditions (Column, WelFlash C18-Ⅰ, 20-40 μm, 330 g; Mobile Phase A: Water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Gradient: 40% B to 60% B in 20 min; Flow rate: 120 mL / min; Wave Length: 220 nm; RT1 (min): 12; Number of Runs: 1 time) to afford crude product (70 mg) as light yellow solid. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD Colum, 19*250 nm, 5 μm; Mobile Phase A: Water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 25 mL / min; Gradient: 5% B to 5% B in 2 min, 5% B to 43% B in 2.5 min, 43% B to 43% B in 10 min; Wave Length: 254 nm / 220 nm; RT1 (min): 12; Number Of Runs: 3 times) to afford Example 2, N-[3- (2-methylphenyl)oxetan-3-yl]quinolin-7-amine (42.5 mg, yield: 7.95%).1H NMR (400 MHz, DMSO-d6) δ 8.55 (dd, J = 4.3, 1.8 Hz, 1H), 7.98 (dd, J = 8.1, 1.8 Hz, 1H), 7.81 – 7.74 (m, 1H), 7.64 - 7.55 (m, 2H), 7.28 (td, J = 7.4, 1.8 Hz, 1H), 7.21 – 7.04 (m, 4H), 6.60 (d, J = 2.3 Hz, 1H), 5.24 (d, J = 6.5 Hz, 2H), 4.96 (d, J = 6.5 Hz, 2H), 2.24 (s, 3H). LCMS EI-MS m / z: = 291 [M+H]+. Example 3

[0255] Int.3.1: 2-methyl-N-[3-(3-methylphenyl)oxetan-3-yl]propane-2-sulfinamide. To a solution of M-bromotoluene (600 mg, 3.51 mmol) in THF (50 mL) was added n-BuLi (1.7 mL, 4.23 mmol, 2.5M in n-hexane) dropwise at -78 °C under a nitrogen atmosphere. The resulting mixture was stirred for 30 min at -78 °C. Then 2-methyl-N-(oxetan-3-ylidene) propane-2- sulfinamide (614 mg, 3.51 mmol) in THF (2 mL) was added dropwise at -78 °C and the resulting mixture was stirred for additional 2 h at -78 °C. The mixture was warmed to -30 °C and then quenched by NH4Cl (aq.) (50 mL). The mixture was warmed to rt and extracted withEtOAc (3 x 30 mL). The combined organic layers were washed with brine (70 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by reverse phase chromatography to afford Int.3.1, 2-methyl-N-[3-(3- methylphenyl)oxetan-3-yl]propane-2-sulfinamide (1.1 g, 76%) as a light yellow oil.

[0256] Int.3.2: 3-(3-methylphenyl)oxetan-3-amine. A solution of 2-methyl-N-[3-(3- methylphenyl)oxetan-3- yl]propane-2-sulfinamide (1.1 g, 4.11 mmol) in MeOH (11 mL) was treated with HCl / MeOH (10 mL, 4 M) at 0 °C under nitrogen atmosphere. The mixture was warmed to rt and stirred for 3 h. The mixture was concentrated under reduced pressure. The resulting mixture was diluted with water (10 mL), basified to pH 10 with NaOH (2 M) and extracted with EtOAc (3 x 10 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude mixture was purified by reverse phase chromatography to afford Int.3.2, 3-(3-methylphenyl)oxetan-3-amine (200 mg, 37%) as a yellow solid.

[0257] Example 3: N-[3-(3-methylphenyl)oxetan-3-yl]quinolin-7-amine. A solution of 3- (3-methylphenyl) oxetan-3-amine (165 mg, 1.01 mmol) in dioxane (4 mL) was treated with 7- bromoquinoline (210 mg, 1.01 mmol), RuPhos (47.2 mg, 0.101 mmol), RuPhos Pd G3 (84.5 mg, 0.101 mmol) and Cs2CO3(658 mg, 2.02 mmol) at rt under nitrogen atmosphere. The mixture was heated to 100 °C and stirred for 12 h. The mixture was cooled to rt, diluted with water (5 mL) and extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude mixture was purified by reverse phase chromatography to afford Example 3, N-[3-(3- methylphenyl)oxetan-3-yl]quinolin-7-amine (49.1 mg, 16%) as a light yellow solid.1H NMR (300 MHz, Methanol-d4, ppm) δ 8.47 (dd, J = 4.5, 1.7 Hz, 1H), 8.08 (dd, J = 8.1, 1.7 Hz, 1H), 7.69 (d, J = 8.9 Hz, 1H), 7.58 – 7.56 (m, 1H), 7.50 (d, J = 7.8 Hz, 1H), 7.27 (t, J = 7.7 Hz, 1H), 7.18 – 7.07 (m, 3H), 6.19 (d, J = 2.3 Hz, 1H), 5.09 – 4.98 (m, 4H), 2.34 (s, 3H). LCMS EI-MS m / z: = 291 [M+H]+. Example 4

[0258] Int.4.1: 2-methyl-N-[3-(4-methylphenyl)oxetan-3-yl]propane-2-sulfinamide. To a stirred solution of P-bromotoluene (500 mg, 2.92 mmol) in THF (10 mL) was added n-BuLi (1.4 mL, 3.51 mmol) dropwise at -70 °C under a nitrogen atmosphere. The resulting mixture was stirred for 30 min at -70 °C under a nitrogen atmosphere. Then to the above mixture was added2-methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide (512 mg, 2.92 mmol) in THF (2.5 mL) dropwise at -78 °C, warmed to rt and stirred for 2 h. The resulting mixture was poured into ice water (60 mL) and the organics were extracted with EtOAc (3 x 30 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford Int.4.1, 2-methyl-N-[3-(4-methylphenyl)oxetan-3-yl]propane-2-sulfinamide (500 mg) as a yellow solid. The crude product was used in the next step directly without further purification. LCMS ESI-MS m / z: = 268 [M+H]+.

[0259] Int.4.2: 3-(4-methylphenyl)oxetan-3-amine. To a stirred solution of 2-methyl-N-[3- (4-methylphenyl) oxetan-3-yl]propane-2-sulfinamide (500 mg, 1.87 mmol) in MeOH (5 mL) was added HCl / MeOH (4.7 mL, 18.7 mmol) dropwise at 0 °C under a nitrogen atmosphere, warmed to rt and stirred for 3 h. The resulting mixture was concentrated under reduced pressure. The residue was dissolved with water (10 mL). The mixture was basified to pH 8 with saturated NaHCO3(aq.) and the organics were extracted with EtOAc (3 x 15 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford a brown oil. The resulting mixture was purified by reversed-phase flash to afford Int.4.2, 3-(4-methylphenyl)oxetan-3-amine (120 mg, 25% (2 steps)) as a yellow oil. LCMS ESI-MS m / z: = 164 [M+H]+.

[0260] Example 4: N-[3-(4-methylphenyl)oxetan-3-yl]quinolin-7-amine. To a stirred solution of 3-(4-methylphenyl)oxetan-3-amine (120 mg, 0.74 mmol) and 7-bromoquinoline (153 mg, 0.74 mmol) in dioxane (12 mL) was added Cphos (32.1 mg, 0.07 mmol), Cs2CO3(479 mg, 1.47 mmol) and Cphos Pd G3 (60.5 mg, 0.07 mmol) at rt under a nitrogen atmosphere. The resulting mixture was heated to 100 °C and stirred for 12 h. The mixture was cooled to rt. The resulting mixture was poured into ice water (10 mL). The organics were extracted with EtOAc (3 x 10 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford a brown solid. The resulting mixture was purified by reversed-phase flash and Prep-HPLC to afford Example 4, N-[3-(4-methylphenyl)oxetan-3- yl]quinolin-7-amine (12.8 mg, 6%) as an off-white solid.1H NMR (300 MHz, Methanol-d4, ppm) δ 8.45 (dd, J = 4.5, 1.7 Hz, 1H), 8.07 (dd, J = 8.1, 1.7 Hz, 1H), 7.67 (d, J = 8.9 Hz, 1H), 7.61 – 7.54 (m, 2H), 7.24 – 7.07 (m, 4H), 6.17 (d, J = 2.3 Hz, 1H), 5.01 (d, J = 1.7 Hz, 4H), 2.30 (s, 3H). LCMS ESI-MS m / z: = 291 [M+H]+.Example 5

[0261] Int.5.1: N-[3-(3-chloro-2-methylphenyl)oxetan-3-yl]-2-methylpropane-2- sulfinamide. To a stirred solution of 3-bromochlorobenzene (1.0 g, 5.22 mmol, 1.0 eq.) in THF (25 mL) was added n-BuLi (2.5 mL, 6.27 mmol, 1.2 eq., 2.5 M) dropwise at -70 °C under a nitrogen atmosphere. The resulting mixture was stirred for 30 min at -70 °C under a nitrogen atmosphere. Then to the above mixture was added 2-methyl-N-(oxetan- 3-ylidene)propane-2- sulfinamide (0.9 g, 5.22 mmol, 1.0 eq.) in THF (2.5 mL) dropwise at -70 °C. The resulting mixture was stirred for additional 2 h at -70 °C. The resulting mixture warmed to 0 °C and quenched by sat. NH4Cl (aq.) (50 mL). The mixture was extracted with EtOAc (3 x 25 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated to afford Int.5.1, N-[3-(3-chloro-2-methylphenyl)oxetan-3-yl]-2-methylpropane-2- sulfinamide (850 mg) as a yellow oil. The crude product was used in the next step directly without further purification. LCMS ESI-MS m / z: = 288 [M+H]+.

[0262] Int.5.2: 3-(3-chlorophenyl)oxetan-3-amine. To a stirred solution of N-[3-(3- chlorophenyl)oxetan-3-yl]-2-methylpropane-2-sulfinamide (850 mg) in MeOH (8.5 mL) was added HCl / MeOH (7.38 mL, 29.5 mmol, 10.0 eq., 4 M) dropwise at 0 °C under a nitrogen atmosphere. The resulting mixture was stirred for additional 3 h at 0 °C under a nitrogen atmosphere. The reaction was concentrated, and the residue was dissolved with water (25 mL). The mixture was basified to pH 9 with saturated Na2CO3(aq.). The resulting mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine (25 mL), dried over Na2SO4, filtered, and concentrated to yield a yellow oil. The crude product was purified by reverse phase flash with the following conditions (Column, WelFlash C18-Ⅰ, 20-40 μm, 330 g; Mobile Phase A: Water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Gradient: 40% B to 60% B in 20 min; Flow rate: 120 mL / min; Wave Length: 220 nm; RT1 (min): 8; Number of Runs: 2 times) to afford Int.5.2, 3-(3-chlorophenyl)oxetan-3-amine (350 mg, 2 steps yield: 31.1%) as a yellow oil. LCMS EI-MS m / z: = 184 [M+H]+.

[0263] Example 5: N-[3-(3-chlorophenyl)oxetan-3-yl]quinoline-7-amine. To a stirred solution of 3-(3-chlorophenyl)oxetan-3-amine (300 mg, 1.63 mmol, 1.0 eq.) and 7- bromoquinoline (340 mg, 1.63 mmol, 1.0 eq.) in dioxane (30 mL) was added Cphos (121 mg, 0.278 mmol, 0.17 eq.), Cs2CO3(1.33 g, 4.085 mmol, 2.5 eq.) and Cphos Pd G3 (228 mg, 0.278mmol, 0.17 eq.) at room temperature under a nitrogen atmosphere. The resulting mixture was stirred for 12 h at 100 °C under a nitrogen atmosphere. The resulting mixture was cooled to room temperature. The reaction was quenched with water (10 mL) at 0 °C and extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated to yield a brown oil. The crude product was purified by reverse phase flash with the following conditions (Column, WelFlash C18-Ⅰ, 20-40 μm, 330 g; Mobile Phase A: Water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Gradient: 50% B to 70% B in 20 min; Flow rate: 120 mL / min; Wave Length: 220 nm; RT1 (min): 17; Number of Runs: 1 time) to afford Example 5, N-[3-(3-chlorophenyl)oxetan-3-yl]quinoline-7-amine (29.5 mg, yield: 5.71%) as a yellow solid.1H NMR (400 MHz, DMSO-d6,ppm): δ 8.54 (dd, J = 4.3, 1.8 Hz, 1H), 8.06 (dd, J = 8.2, 1.8 Hz, 1H), 7.75 – 7.62 (m, 4H), 7.46 (t, J = 7.8 Hz, 1H), 7.38 (dt, J = 8.1, 1.5 Hz, 1H), 7.16 – 7.06 (m, 2H), 6.01 (d, J = 2.3 Hz, 1H), 4.99 – 4.87 (m, 4H). LCMS EI-MS m / z: = 311 [M+H]+. Example 6

[0264] Int.6.1: N-[3-(2-fluorophenyl)oxetan-3-yl]-2-methylpropane-2-sulfinamide. To a stirred solution of 1-bromo-2-fluorobenzene (500 mg, 2.86 mmol, 1 eq.) in THF (12.5 mL) was added n-BuLi (1.37 mL, 3.43 mmol, 1.2 eq., 2.5 M) at -70 °C under a nitrogen atmosphere. The resulting mixture was stirred for 30 min at -70 °C under a nitrogen atmosphere. To the above mixture was added 2-methyl-N- (oxetan-3-ylidene)propane-2-sulfinamide (501 mg, 2.86 mmol, 1 eq.) at -70 °C. The resulting mixture was stirred for additional 2 h at -70 °C. The reaction was warmed to 0 °C and quenched with sat. NH4Cl (30 mL). The mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield a brown oil. The crude product was purified by reversed-phase flash chromatography with the following conditions: (Column, WelFlash C18-Ⅰ, 20-40 μm, 330 g; Mobile Phase A: water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Gradient: 30% B to 50% B in 20min; Flow rate: 120 mL / min; Wave Length: 220 nm; RT1 (min): 13; Number of Runs: 1 time) to afford Int.6.1, N-[3-(2-fluorophenyl)oxetan-3-yl]-2- methylpropane-2-sulfinamide (350 mg, yield: 44.9%) as a light yellow oil. LCMS ESI-MS m / z: = 272 [M+H]

[0265] Int.6.2: 3-(2-fluorophenyl)oxetan-3-amine. To a stirred solution of N-[3-(2- fluorophenyl)oxetan-3-yl]-2-methylpropane-2-sulfinamide (350 mg, 1.29 mmol, 1 eq.) in MeOH(3.5 mL) was added HCl (g) in MeOH (3.22 mL, 12.9 mmol, 10 eq., 4 M) at 0 °C under a nitrogen atmosphere. The resulting mixture was stirred for 3 h at rt under a nitrogen atmosphere. The mixture was concentrated under reduced pressure. The residue was dissolved with water and basified to pH 9 with saturated NaHCO3(aq.). The resulting mixture was extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by reversed-phase flash chromatography with the following conditions: (Column, WelFlash C18-Ⅰ, 20-40 μm, 120 g; Mobile Phase A: water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Gradient: 10% B to 30% B in 20 min; Flow rate: 80 mL / min; Wave Length: 220 nm; RT1 (min): 9; to afford 3-(2-fluorophenyl)oxetan-3-amine (120 mg, yield: 55.6%) as a yellow oil. LCMS ESI-MS m / z: = 168 [M+H]

[0266] Example 6: N-[3-(2-fluorophenyl)oxetan-3-yl]quinoline-7-amine. To a stirred solution of 3-(2-fluorophenyl)oxetan-3-amine (120 mg, 0.72 mmol, 1 eq.), 7-bromoquinoline (149 mg, 0.72 mmol, 1 eq.) and Cs2CO3(468 mg, 1.44 mmol, 2 eq.) in dioxane (12 mL) was added Cphos (31.3 mg, 0.07 mmol, 0.1 eq.) and Cphos Pd G3 (59 mg, 0.07 mmol, 0.1 eq.) at room temperature under a nitrogen atmosphere. The resulting mixture was stirred for 12 h at 100 °C under a nitrogen atmosphere. The reaction was cooled down to room temperature and dissolved with water (10 mL). The resulting mixture was extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: (Column, WelFlash C18-Ⅰ, 20-40 μm, 120 g; Mobile Phase A: Water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Gradient: 40% B to 60% B in 20 min; Flow rate: 80 mL / min; Wave Length: 220 nm; RT1 (min): 15; Number of Runs: 1 time) to afford N-[3-(2-fluorophenyl)oxetan-3-yl]quinoline-7-amine (50 mg) as a yellow solid. The product was further purified by Prep-HPLC with the following conditions: (Column: Xselect CSH Prep C18 OBD Colum, 19*250 nm, 5 μm; Mobile Phase A: Water (0.1%FA), Mobile Phase B: ACN; Flow rate: 25 mL / min mL / min; Gradient: 3% B to 3% B in 5 min, 8% B to 8% B in 10 min; Wave Length: 254 nm / 220 nm; RT1 (min): 8.5: Number of Runs: 2 times) to afford N-[3-(2-fluorophenyl)oxetan-3-yl]quinoline-7-amine (9.3 mg, 4.3%) as a yellow solid. LCMS ESI-MS m / z: = 295 [M+H]+.1H NMR (400 MHz, DMSO-d6, ppm) δ 8.57 (dd, J = 4.3, 1.8 Hz, 1H), 8.03 (dd, J = 8.1, 1.8 Hz, 1H), 7.70 – 7.59 (m, 3H), 7.34 (tdd, J = 7.4, 5.2, 1.7 Hz, 1H), 7.30 – 7.15 (m, 2H), 7.11 (ddd, J = 9.1, 5.6, 3.3 Hz, 2H), 6.35 (d, J = 2.3 Hz, 1H), 5.19 (dd, J = 6.5, 1.3 Hz, 2H), 4.88 (d, J = 6.7 Hz, 2H).19F NMR (376 MHz, DMSO- d6, ppm) δ -113.9498.Example 7

[0267] Int.7.1: N-[3-(3-fluorophenyl)oxetan-3-yl]-2-methylpropane-2-sulfinamide. To a stirred solution of M-bromofluorobenzene (500 mg, 2.86 mmol) in THF (12.5 mL) was added n- BuLi (1.37 mL, 3.43 mmol.2.5 M in THF) dropwise at -70 °C under a nitrogen atmosphere. The resulting mixture was stirred at -70 °C for 30 min under a nitrogen atmosphere. Then a solution of 2-methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide (501 mg, 2.86 mmol) in THF (2 mL) was added dropwise at -70 °C and stirred for 2 h at -70 °C under a nitrogen atmosphere. The reaction was quenched with sat. NH4Cl (aq.) (15 mL) at -70 °C. The resulting mixture was warmed up to rt. The resulting mixture was extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield light yellow oil. The crude product was purified by reverse phase flash to afford Int.7.1, N-[3-(3-fluorophenyl)oxetan-3-yl]-2-methylpropane-2- sulfinamide (420 mg, 54%) as a colorless oil.

[0268] Int.7.2: 3-(3-fluorophenyl)oxetan-3-amine. To a stirred solution of N-[3-(3- fluorophenyl)oxetan-3-yl]-2-methylpropane-2-sulfinamide (420 mg, 1.55 mmol) in MeOH (4.2 mL) was added HCl / MeOH (3.87 mL, 15.5 mmol) dropwise at 0 °C under a nitrogen atmosphere. The resulting mixture was stirred at rt for 3 h under a nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to yield a black solid. The residue was dissolved in H2O (2 mL) and EtOAc (2 mL), and then extracted with EtOAc (2 x 2 mL). The aqueous phase was basified to PH 9-10 with sat. Na2CO3(aq.) and extracted with EtOAc (3 x 3 mL). The combined organic layers were washed with brine (2 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure to yield a brown solid. The crude product was purified by reverse phase flash to afford Int.7.2, 3-(3- fluorophenyl)oxetan-3-amine (130 mg, 50%) as a white solid.

[0269] Example 7: N-[3-(3-fluorophenyl)oxetan-3-yl]quinoline-7-amine. To a stirred solution of 3-(3-fluorophenyl)oxetan-3-amine (115 mg, 0.69 mmol) and 7-bromoquinoline (143 mg, 0.69 mmol) in dioxane (1.1 mL) was added Cs2CO3(450 mg, 1.38 mmol), Cphos (30 mg, 0.07 mmol) and Cphos Pd G3 (56.6 mg, 0.07 mmol) at room temperature under a nitrogen atmosphere. Then the resulting mixture was heated to 95 °C and stirred for 12 h. The resulting mixture was cooled to room temperature. The resulting mixture was diluted with H2O (2 mL)and extracted with EtOAc (3 x 2 mL). The combined organic phase was washed with brine (5 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product (20 mg) was purified by Prep-HPLC to afford Example 7, N-[3-(3-fluorophenyl)oxetan-3-yl]quinoline-7-amine (3.2 mg, 1%) as a white solid.1H NMR (300 MHz, DMSO-d6, ppm) δ 8.54 (dd, J = 4.3, 1.8 Hz, 1H), 8.05 (dd, J = 8.2, 1.8 Hz, 1H), 7.75 – 7.64 (m, 2H), 7.58 – 7.36 (m, 3H), 7.20 – 7.04 (m, 3H), 6.02 (d, J = 2.3 Hz, 1H), 4.96 (d, J = 6.3 Hz, 2H), 4.90 (d, J = 6.3 Hz, 2H).19F NMR (282 MHz, DMSO-d6, ppm) δ -112.72. LCMS ESI-MS m / z: = 295 [M+H]+. Example 8

[0270] Int.8.1: N-[3-(4-fluorophenyl)oxetan-3-yl]-2-methylpropane-2-sulfinamide. To a stirred solution of 4-bromofluorobenzene (600 mg, 3.4 mmol) in THF (15 mL) was added n- BuLi (1.65 mL, 4.1 mmol) dropwise at -70 °C and stirred for 1 h under a nitrogen atmosphere. Then 2-methyl-N-(oxetan-3-ylidene) propane-2-sulfinamide (600 mg, 3.4 mmol) was added dropwise at -70 °C and stirred for 1 h. The resulting mixture was poured into ice water (15 mL) slowly and extracted with EtOAc (2 x 10 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by reverse phase flash to afford Int.8.1, N-[3-(4- fluorophenyl)oxetan-3-yl]-2-methylpropane-2-sulfinamide (370 mg, 40%) as a brown oil.

[0271] Int.8.2: 3-(4-fluorophenyl)oxetan-3-amine. To a stirred solution of N-[3-(4- fluorophenyl) oxetan-3-yl]-2-methylpropane-2-sulfinamide (370 mg, 1.36 mmol) in MeOH (3.7 mL) was added HCl / MeOH (3.4 mL, 13.6 mmol) at rt. The resulting mixture was cooled to 0 °C and stirred for 3 h. The resulting mixture was warmed to rt and concentrated under reduced pressure to yield light brown oil. The residue was dissolved in EtOAc (5 mL) and H2O (5 mL), then was extracted with EtOAc (1 x 5 mL). The aqueous phase was basified to pH 9-10 with sat. Na2CO3. The resulting mixture was extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by reverse phase flash to afford Int.8.2, 3-(4-fluorophenyl)oxetan-3-amine (120 mg, 53%) as a light oil.

[0272] Example 8: N-[3-(4-fluorophenyl)oxetan-3-yl]quinolin-7-amine. To a stirred solution of 3-(4-fluorophenyl)oxetan-3-amine (120 mg, 0.7 mmol), Cs2CO3(467 mg, 1.4 mmol) and 7-bromoquinoline (149 mg, 0.7 mmol) in dioxane (2 mL) was added Cphos (34 mg, 0.07mmol) and Cphos Pd G3 (59 mg, 0.07 mmol) at rt under a nitrogen atmosphere. The resulting mixture was heated to 100 °C and stirred for 6 h under a nitrogen atmosphere. The resulting mixture was cooled to rt, diluted with water (5 mL) and the organics were extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by reverse phase flash and Prep-HPLC to afford N-[3-(4-fluorophenyl)oxetan-3-yl]quinolin-7- amine (9.7 mg, 5%) as a white solid.1H NMR (400 MHz, DMSO-d6, ppm) δ 8.53 (dd, J = 4.3, 1.8 Hz, 1H), 8.05 (dd, J = 8.1, 1.8 Hz, 1H), 7.74 – 7.63 (m, 4H), 7.27 – 7.19 (m, 2H), 7.15 – 7.06 (m, 2H), 6.01 (d, J = 2.3 Hz, 1H), 4.99 – 4.87 (m, 4H). F NMR (300 MHz, DMSO-d6, ppm) δ-115.92. LCMS EI-MS m / z: = 295 [M+H]+.

[0273] Int.9.1, 2-methyl-N-{3-[2-(trifluoromethyl)phenyl]oxetan-3-yl}propane-2- sulfinamide. To a stirred solution of 1-bromo-2-(trifluoromethyl)benzene (500 mg, 2.2 mmol, 1 eq.) in THF (12.5 mL) was added n-BuLi (1.1 mL, 2.7 mmol, 1.2 eq.) at -70 °C under a nitrogen atmosphere. The resulting mixture was stirred for 30 min at -70 °C. To the above mixture was added 2-methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide (389.4 mg, 2.2 mmol, 1 eq.), and the resulting mixture was stirred for additional 2 h at -70 °C. The reaction was warmed to 0 °C and quenched with sat. NH4Cl (30 mL). The mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield a brown oil. The crude product was purified by reversed-phase flash chromatography with the following conditions: (Column, WelFlash C18-Ⅰ, 20-40 μm, 330 g; Mobile Phase A: water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Gradient: 30% B to 50% B in 20min; Flow rate: 120 mL / min; Wave Length: 220 nm; RT1 (min): 13; Number of Runs: 1 time) to afford 2-methyl-N-{3-[2- (trifluoromethyl)phenyl]oxetan-3-yl}propane-2- sulfinamide (260 mg, 36.3%) as a light yellow solid. LCMS ESI-MS m / z: = 322 [M+H]+.

[0274] Int.9.2, 3-[2-(trifluoromethyl)phenyl]oxetan-3-amine. To a stirred solution of 2- methyl-N-{3-[2-(trifluoromethyl)phenyl]oxetan-3-yl}propane-2-sulfinamide (260 mg, 0.8 mmol, 1 eq.) in MeOH (2.6 mL) was added HCl (g) in MeOH (3.7 mL, 14.9 mmol, 10 eq., 4 M) at 0 °C under a nitrogen atmosphere. The resulting mixture was stirred for 3 h at rt under a nitrogen atmosphere. The mixture was concentrated under reduced pressure. The residue was dissolved with water and basified to pH 9 with saturated NaHCO3(aq.). The resulting mixturewas extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by reversed-phase flash chromatography with the following conditions: (Column, WelFlash C18-Ⅰ, 20-40 μm, 120 g; Mobile Phase A: water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Gradient: 10% B to 30% B in 20 min; Flow rate: 80 mL / min; Wave Length: 220 nm; RT1 (min): 8; Number of Runs: 1) to afford 3-[2- (trifluoromethyl)phenyl]oxetan-3-amine (80.0 mg, yield: 45.5%) as a yellow oil. LCMS ESI-MS m / z: = 218 [M+H]+.

[0275] Example 9: N-{3-[2-(trifluoromethyl)phenyl]oxetan-3-yl}quinolin-7-amine. To a stirred solution of 3-[2-(trifluoromethyl)phenyl]oxetan-3-amine (80 mg, 0.37 mmol, 1 eq.), 7- bromoquinoline (76.6 mg, 0.37 mmol, 1 eq.) and Cs2CO3(240 mg, 0.74 mmol, 2 eq.) in dioxane (8 mL) was added Cphos (16.1 mg, 0.04 mmol, 0.1 eq.) and Cphos Pd G3 (30.3 mg, 0.04 mmol, 0.1 eq.) at room temperature under a nitrogen atmosphere. The resulting mixture was stirred for 12 h at 100 °C under a nitrogen atmosphere. The reaction was cooled down to room temperature and dissolved with water (10 mL). The resulting mixture was extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: (Column, WelFlash C18-Ⅰ, 20-40 μm, 120 g; Mobile Phase A: water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Gradient: 40% B to 60% B in 20 min; Flow rate: 80 mL / min; Wave Length: 220 nm; RT1 (min): 12; Number of Runs: 1 time) to afford N-[3-(pyridin-3-yl)oxetan-3-yl]quinolin-7-amine (50 mg) as a yellow solid. The product was further purified by Prep-HPLC with the following conditions: (Column: YMC-Actus Triart C18 ExRS Colum, 30*150 nm, 5 μm; Mobile Phase A: Water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: isocratic 30%-30%; Wave Length: 220 / 254 nm; RT1 (min): 12; Number of Runs: 3 times) to afford N-{3-[2-(trifluoromethyl)phenyl]oxetan-3-yl}quinolin-7-amine (5.9 mg, 4.2%) as a light yellow solid. LCMS ESI-MS m / z: = 345 [M+H]+.1H NMR (400 MHz, DMSO-d6, ppm) δ 8.52 (dd, J = 4.3, 1.8 Hz, 1H), 8.26 (d, J = 7.9 Hz, 1H), 7.98 (dd, J = 8.1, 1.8 Hz, 1H), 7.86 – 7.78 (m, 1H), 7.74 (dd, J = 8.0, 1.4 Hz, 1H), 7.65 – 7.58 (m, 2H), 7.54 (t, J = 7.6 Hz, 1H), 7.12 – 7.04 (m, 2H), 6.32 (d, J = 2.3 Hz, 1H), 5.33 – 5.27 (m, 2H), 4.88 (d, J = 6.8 Hz, 2H).19F NMR (376 MHz, DMSO-d6, ppm) δ -57.1690, -57.2004.Example 10

[0276] Int.10.1: 2-methyl-N-{3-[3-(trifluoromethyl)phenyl]oxetan-3-yl}propane-2- sulfinamide. To a stirred solution of 1-bromo-3-(trifluoromethyl)benzene (600 mg, 2.67 mmol, 1.0 eq.) in THF (15 mL) was added butyllithium (1.28 mL, 3.20 mmol, 1.2 eq., 2.5 M in THF) dropwise at -70 °C under a nitrogen atmosphere. The resulting mixture was stirred at -70 °C for 30 min under a nitrogen atmosphere. Then a solution of 2-methyl-N-(oxetan-3-ylidene)propane- 2-sulfinamide (467 mg, 2.67 mmol, 1 eq.) in THF (4 mL) was added dropwise at -70 °C and stirred for 2 h under a nitrogen atmosphere. The reaction was quenched with sat. NH4Cl (aq.) (15 mL) at -70 °C. The resulting mixture was warmed up to room temperature. The resulting mixture was extracted with EtOAc (3 x 10 mL). The combined organic phase was washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield light yellow oil. The crude product was purified by reverse phase flash with the following conditions (Column, WelFlash C18-Ⅰ, 20-40 μm, 330 g; Mobile Phase A: Water (10 mmol / L NH4HCO3), Mobile Phase B: ACN; Gradient: 55% B to 75% B in 20 min; Flow rate: 120 mL / min; Wave Length: 220 nm; RT1 (min): 13; Number of Runs: 2 times) to afford 2- methyl-N-{3-[3-(trifluoromethyl)phenyl]oxetan-3-yl}propane-2-sulfinamide (600 mg, 70.0%) as colorless oil. LCMS ESI-MS m / z: = 322 [M+H]+.

[0277] Int.10.2: 3-[3-(trifluoromethyl)phenyl]oxetan-3-amine. To a stirred solution of 2- methyl-N-{3-[3-(trifluoromethyl)phenyl]oxetan-3-yl}propane-2-sulfinamide (600 mg, 1.87 mmol, 1.0 eq.) in MeOH (6 mL) was added HCl / MeOH (4.67 mL, 18.7 mmol, 10.0 eq.) dropwise at 0 °C under a nitrogen atmosphere. The resulting mixture was stirred at room temperature for 3 h under a nitrogen a...

Claims

CLAIMS What is claimed is:

1. A compound of Formula (I’):Formula (I’); or a pharmaceutically acceptable salt thereof, wherein: A and G are independently selected from C(R2) and N; W, X, Y, and Z are independently selected from C(R2) and N, wherein at least one of W, X, Y, and Z is C(R2); J is C(R3)(R4), O, S, or N(R3a); each L is C(R4a)2; each L1is C(R4b)2; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; each R5is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclicring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; m is 0, 1, 2, or 3; n is 1 or 2; and p is 1, 2, or 3.

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, having the structure of Formula (I):Formula (I).

3. The compound of claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein A and G are C(R2).

4. The compound of claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein A is C(R2) and G is N.

5. The compound of claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, wherein A is N and G is C(R2).

6. The compound of claim 1 or claim 2, or a pharmaceutically acceptable salt thereof, having the structure of Formula (Ia):Formula (Ia).

7. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, wherein W, X, Y, and Z are C(R2).

8. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, wherein W, X, and Y are C(R2) and Z is N.

9. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, wherein W, X, and Z are C(R2) and Y is N.

10. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, wherein W, Y, and Z are C(R2) and X is N.

11. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, wherein X, Y, and Z are C(R2) and W is N.

12. A compound of Formula (II’):Formula (II’); or a pharmaceutically acceptable salt thereof, wherein: J is C(R3)(R4), O, S, or N(R3a); J1is C(R2) or N; J2is O, S, or N(R3b); each L is C(R4a)2; each L1is C(R4b)2; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11);R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3bis selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; each R5is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R6is independently selected from halogen, oxo, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or two R6attached to the same carbon atom are combined to form a C3-6cycloalkyl; each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl;each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; m is 0, 1, 2, 3, 4, or 5; n is 1 or 2; p is 1, 2, or 3; q is 0, 1, or 2; v is 0, 1, 2, 3, or 4; and indicates a single or double bond such that all valences are satisfied.

13. The compound of claim 12, or a pharmaceutically acceptable salt thereof, having the structure of Formula (II):Formula (II).

14. The compound of claim 12 or claim 13, or a pharmaceutically acceptable salt thereof, wherein J1is C(R2).

15. The compound of claim 12 or claim 13, or a pharmaceutically acceptable salt thereof, wherein J1is N.

16. The compound of any one of claims 12-15, or a pharmaceutically acceptable salt thereof, wherein J2is N(R3b).

17. The compound of any one of claims 12-16, or a pharmaceutically acceptable salt thereof, wherein R3bis selected from hydrogen and -C(O)R13.

18. The compound of any one of claims 12-17, or a pharmaceutically acceptable salt thereof, wherein R3bis hydrogen.

19. The compound of any one of claims 12-17, or a pharmaceutically acceptable salt thereof, wherein R3bis -C(O)R13and R13is independently selected from C1-6alkyl and C3-6cycloalkyl wherein C1-6alkyl and C3-6cycloalkyl are optionally substituted with hydroxy.

20. The compound of any one of claims 12-19, or a pharmaceutically acceptable salt thereof, wherein each R6is independently selected from oxo and unsubstituted C1-6alkyl.

21. The compound of any one of claims 12-20, or a pharmaceutically acceptable salt thereof, wherein v is 1, 2, or 3.

22. The compound of any one of claims 12-19, or a pharmaceutically acceptable salt thereof, wherein v is 0.

23. The compound of any one of claims 12-22, or a pharmaceutically acceptable salt thereof, wherein q is 0.

24. The compound of any one of claims 12-22, or a pharmaceutically acceptable salt thereof, wherein q is 1.

25. The compound of any one of claims 12-22, or a pharmaceutically acceptable salt thereof, wherein q is 2.

26. The compound of any one of claims 12-25, or a pharmaceutically acceptable salt thereof, wherein indicates a single bond.

27. The compound of any one of claims 12-25, or a pharmaceutically acceptable salt thereof, wherein indicates a double bond.

28. The compound of any one of claims 1-27, or a pharmaceutically acceptable salt thereof, wherein J is C(R3)(R4), O, or S.

29. The compound of any one of claims 1-28, or a pharmaceutically acceptable salt thereof, wherein J is C(R3)(R4).

30. The compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, wherein R3is hydrogen and R4is selected from hydrogen, -CN, C1-6alkyl, and - C(O)N(R10)(R11).

31. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt thereof, wherein R3and R4are hydrogen.

32. The compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, wherein R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and - C(O)N(R10)(R11).

33. The compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from C1-6alkyl, -C(O)OR10, and -C(O)R13.

34. The compound of claim 33, or a pharmaceutically acceptable salt thereof, wherein R13is selected from hydrogen and unsubstituted C1-6alkyl.

35. The compound of any one of claims 1-28, or a pharmaceutically acceptable salt thereof, wherein J is O.

36. The compound of any one of claims 1-28, or a pharmaceutically acceptable salt thereof, wherein J is S.

37. The compound of any one of claims 1-27, or a pharmaceutically acceptable salt thereof, wherein J is N(R3a).

38. The compound of claim 37, or a pharmaceutically acceptable salt thereof, wherein R3ais C1-6alkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11).

39. The compound of claim 38, or a pharmaceutically acceptable salt thereof, wherein R3ais - C(O)R13and R13is unsubstituted C1-6alkyl.

40. The compound of any one of claims 1-39, or a pharmaceutically acceptable salt thereof, wherein each R5is independently selected from halogen, -CN, C1-6alkyl, and C1-6haloalkyl.

41. The compound of any one of claims 1-40, or a pharmaceutically acceptable salt thereof, wherein each R5is independently selected from halogen and C1-6alkyl.

42. The compound of any one of claims 1-41, or a pharmaceutically acceptable salt thereof, wherein m is 1 or 2.

43. The compound of any one of claims 1-42, or a pharmaceutically acceptable salt thereof, wherein n is 1 and p is 1.

44. A compound of Formula (III’):Formula (III’); or a pharmaceutically acceptable salt thereof, wherein: J1is C(R2) or N; each L is C(R4a)2; each L1is C(R4b)2; R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), -C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; each R7is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; n is 1 or 2; p is 1, 2, or 3; and t is 1, 2, 3, 4, or 5.

45. The compound of claim 44, or a pharmaceutically acceptable salt thereof, having the structure of Formula (III):Formula (III).

46. The compound of claim 44 or claim 45, or a pharmaceutically acceptable salt thereof, wherein J1is C(R2).

47. The compound of claim 44 or claim 45, or a pharmaceutically acceptable salt thereof, wherein J1is N.

48. The compound of any one of claims 44-47, or a pharmaceutically acceptable salt thereof, wherein R3is hydrogen and R4is selected from hydrogen, -CN, C1-6alkyl, and - C(O)N(R10)(R11).

49. The compound of any one of claims 44-48, or a pharmaceutically acceptable salt thereof, wherein R3and R4are hydrogen.

50. The compound of any one of claims 44-47, or a pharmaceutically acceptable salt thereof, wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with - C(O)R13.

51. The compound of claim 50, or a pharmaceutically acceptable salt thereof, wherein R13is selected from hydrogen and unsubstituted C1-6alkyl.

52. The compound of any one of claims 44-51, or a pharmaceutically acceptable salt thereof, wherein each R7is independently selected from halogen, -CN, C1-6alkyl, and C1-6haloalkyl.

53. The compound of any one of claims 44-52, or a pharmaceutically acceptable salt thereof, wherein each R7is independently selected from halogen and C1-6alkyl.

54. The compound of any one of claims 44-53, or a pharmaceutically acceptable salt thereof, wherein t is 1 or 2.

55. The compound of any one of claims 1-54, or a pharmaceutically acceptable salt thereof, wherein each R2is independently selected from hydrogen, halogen, C1-6alkyl, and C1-6haloalkyl.

56. The compound of any one of claims 1-55, or a pharmaceutically acceptable salt thereof, wherein each R2is hydrogen.

57. The compound of any one of claims 1-56, or a pharmaceutically acceptable salt thereof, wherein R1is hydrogen.

58. A compound of Formula (IV’):Formula (IV’); or a pharmaceutically acceptable salt thereof, wherein: W, X, Y, and Z are independently selected from C(R2) and N, wherein at least one of Y and Z is C(R2); L is C(R6a)(R6b); each L1is C(R4a)2;each L2is C(R4b)2; J is C(R3)(R4), O, S, or N(R3a); R1is selected from hydrogen and C1-6alkyl; each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3cis selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), and -C(O)N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyland C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; R6aand R6bare independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R8is selected from C6-10aryl and C1-9heteroaryl, wherein C6-10aryl and C1-9heteroaryl are optionally substituted with one, two, or three R9groups; each R9is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; n is 1 or 2; p is 1, 2, or 3; q is 0 or 1; and indicates a single or double bond such that all valences are satisfied; wherein the compound is not.

59. The compound of claim 58, or a pharmaceutically acceptable salt thereof, having the structure of Formula (IV):Formula (IV).

60. The compound of claim 58 or claim 59, or a pharmaceutically acceptable salt thereof, wherein W, X, Y, and Z are C(R2).

61. The compound of claim 58 or claim 59, or a pharmaceutically acceptable salt thereof, wherein W, X, and Y are C(R2) and Z is N.

62. The compound of claim 58 or claim 59, or a pharmaceutically acceptable salt thereof, wherein W, X, and Z are C(R2) and Y is N.

63. The compound of claim 58 or claim 59, or a pharmaceutically acceptable salt thereof, wherein W, Y, and Z are C(R2) and X is N.

64. The compound of claim 58 or claim 59, or a pharmaceutically acceptable salt thereof, wherein X, Y, and Z are C(R2) and W is N.

65. The compound of any one of claims 58-64, or a pharmaceutically acceptable salt thereof, wherein R3cis selected from C1-6alkyl and C3-6cycloalkyl.

66. The compound of any one of claims 58-65, or a pharmaceutically acceptable salt thereof, wherein R3cis -CH3.

67. The compound of any one of claims 58-66, or a pharmaceutically acceptable salt thereof, wherein R6aand R6bare hydrogen.

68. The compound of any one of claims 58-67, or a pharmaceutically acceptable salt thereof, wherein q is 1.

69. The compound of any one of claims 58-68, or a pharmaceutically acceptable salt thereof, wherein q is 0.

70. The compound of any one of claims 58-69, or a pharmaceutically acceptable salt thereof, wherein indicates a single bond.

71. The compound of any one of claims 58-69, or a pharmaceutically acceptable salt thereof, wherein indicates a double bond.

72. A compound of Formula (V’):Formula (V’); or a pharmaceutically acceptable salt thereof, wherein: J is C(R3)(R4), O, S, or N(R3a); each L is C(R4a)2; each L1is C(R4b)2; X1is C(R2a) or N; R1is selected from hydrogen and C1-6alkyl;each R2is independently selected from hydrogen, halogen, -CN, -OR10, -SR10, -N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, oxo, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R2ais selected from hydrogen and C1-6alkyl; R3ais selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); R3dis selected from hydrogen, -C(O)OR10, -C(O)R13, -S(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), and -C(O)N(R10)(R11); R3and R4are independently selected from hydrogen, halogen, -CN, -OR10, -SR10, - N(R10)(R11), -C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), - N(R12)C(O)OR13, -N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); or R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groupsselected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and -C(O)N(R10)(R11); each R4ais independently selected from hydrogen and C1-6alkyl; each R4bis independently selected from hydrogen and C1-6alkyl; R8is selected from C6-10aryl and C1-9heteroaryl, wherein C6-10aryl and C1-9heteroaryl are optionally substituted with one, two, or three R9groups; each R9is independently selected from halogen, -CN, -OR10, -SR10, -N(R10)(R11), - C(O)OR10, -OC(O)N(R10)(R11), -N(R12)C(O)N(R10)(R11), -N(R12)C(O)OR13, - N(R12)S(O)2R13, -C(O)R13, -S(O)R13, -OC(O)R13, -C(O)N(R10)(R11), - C(O)C(O)N(R10)(R11), -N(R12)C(O)R13, -S(O)2R13, -S(O)2N(R10)(R11)-, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, -CH2-C3-6cycloalkyl, C2-9heterocycloalkyl, -CH2-C2-9heterocycloalkyl, C6-10aryl, -CH2-C6-10aryl, C1-9heteroaryl, and -CH2-C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11); each R10is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; each R11is independently selected from hydrogen, C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl; or R10and R11taken together with the nitrogen atom to which they are attached independently form a 4-to-7-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3alkyl, C3-C6cycloalkyl, or C2-C3haloalkyl; each R12is independently selected from C1-6haloalkyl C2-6heteroalkyl, C3-6cycloalkyl, and C2-9heterocycloalkyl;each R13is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C1-6haloalkyl, C2-6heteroalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, SF5, -CN, hydroxy, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl; n is 1 or 2; and p is 1, 2, or 3.

73. The compound of claim 72, or a pharmaceutically acceptable salt thereof, having the structure of Formula (V):Formula (V).

74. The compound of claim 72 or claim 73, or a pharmaceutically acceptable salt thereof, wherein X1is C(R2a).

75. The compound of any one of claims 72-74, or a pharmaceutically acceptable salt thereof, wherein R2ais hydrogen 76. The compound of claim 72 or claim 73, or a pharmaceutically acceptable salt thereof, wherein X1is N.

77. The compound of any one of claims 72-76, or a pharmaceutically acceptable salt thereof, wherein R3dis selected from hydrogen and C1-6alkyl optionally substituted with one, two, or three groups selected from halogen, -OR10, -N(R10)(R11), and -C(O)N(R10)(R11).

78. The compound of any one of claims 72-77, or a pharmaceutically acceptable salt thereof, wherein R3dis C1-6alkyl optionally substituted with one group selected from -OR10, - N(R10)(R11), and -C(O)N(R10)(R11), and wherein R10and R11are hydrogen.

79. The compound of any one of claims 58-78, or a pharmaceutically acceptable salt thereof, wherein J is C(R3)(R4), O, or S.

80. The compound of any one of claims 58-79, or a pharmaceutically acceptable salt thereof, wherein J is C(R3)(R4).

81. The compound of any one of claims 58-80, or a pharmaceutically acceptable salt thereof, wherein R3is hydrogen and R4is selected from hydrogen, -CN, C1-6alkyl, and - C(O)N(R10)(R11).

82. The compound of any one of claims 58-81, or a pharmaceutically acceptable salt thereof, wherein R3and R4are hydrogen.

83. The compound of any one of claims 58-80, or a pharmaceutically acceptable salt thereof, wherein R3and R4are combined to form a C3-6cycloalkyl or C2-9heterocycloalkyl, wherein the C3-6cycloalkyl and C2-9heterocycloalkyl are optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, -N(R10)(R11), -C(O)OR10, -C(O)R13, and - C(O)N(R10)(R11).

84. The compound of claim 83, or a pharmaceutically acceptable salt thereof, wherein R3and R4are combined to form a C2-9heterocycloalkyl optionally substituted with one group selected from C1-6alkyl, -C(O)OR10, and -C(O)R13.

85. The compound of claim 84, or a pharmaceutically acceptable salt thereof, wherein R13is selected from hydrogen and unsubstituted C1-6alkyl.

86. The compound of any one of claims 58-79, or a pharmaceutically acceptable salt thereof, wherein J is O.

87. The compound of any one of claims 58-79, or a pharmaceutically acceptable salt thereof, wherein J is S.

88. The compound of any one of claims 58-78, or a pharmaceutically acceptable salt thereof, wherein J is N(R3a).

89. The compound of claim 88, or a pharmaceutically acceptable salt thereof, wherein R3ais hydrogen or C1-6alkyl optionally substituted with one, two, or three groups selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, -OR10, and -N(R10)(R11).

90. The compound of claim 88, or a pharmaceutically acceptable salt thereof, wherein R3ais - C(O)R13and R13is unsubstituted C1-6alkyl.

91. The compound of any one of claims 58-90, or a pharmaceutically acceptable salt thereof, wherein R8is selected C6-10aryl optionally substituted with one, two, or three R9groups.

92. The compound of any one of claims 58-91, or a pharmaceutically acceptable salt thereof, wherein R8is phenyl substituted with one, two, or three R9groups.

93. The compound of any one of claims 58-92, or a pharmaceutically acceptable salt thereof, wherein each R9is independently selected from halogen, -CN, C1-6alkyl, and C1-6haloalkyl.

94. The compound of any one of claims 58-93, or a pharmaceutically acceptable salt thereof, wherein each R9is independently selected from halogen and C1-6alkyl.

95. The compound of any one of claims 58-94, or a pharmaceutically acceptable salt thereof, wherein n is 1 and p is 1.

96. The compound of any one of claims 58-95, or a pharmaceutically acceptable salt thereof, wherein each R2is independently selected from hydrogen, halogen, and C1-6alkyl.

97. The compound of any one of claims 58-96, or a pharmaceutically acceptable salt thereof, wherein each R2is hydrogen.

98. The compound of any one of claims 58-97, or a pharmaceutically acceptable salt thereof, wherein R1is hydrogen.

99. A compound, or a pharmaceutically acceptable salt thereof, selected from:, , , ,.

100. A compound, or a pharmaceutically acceptable salt thereof, selected from:.

101. A compound, or a pharmaceutically acceptable salt thereof, selected from:

102. A pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and a compound of any one of claims 1-101, or a pharmaceutically acceptable salt thereof.

103. A method of inhibiting SARM1 comprising contacting the SARM1 with a compound of any one of claims 1-101, or a pharmaceutically acceptable salt thereof.

104. A method of inhibiting axonal degeneration in a patient in need thereof comprising administering to the patient an inhibiting amount of a compound of any one of claims 1-101, or a pharmaceutically acceptable salt thereof.

105. The method of claim 104, wherein the axonal degeneration is caused by abnormal reduction or depletion of NAD+ in the axons.

106. A method of treating or preventing a neurological disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound of any one of claims 1-101, or a pharmaceutically acceptable salt thereof.

107. The method of claim 106 wherein the neurological disorder is a neurodegenerative disease.

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