Bicyclic heteroaromatic compounds for treating neurological disorders

Abstract

This disclosure provides compounds and pharmaceutically acceptable salts thereof, that are useful, e.g., for treating neurological disorder in subject. This disclosure also provides compositions containing the same as well as methods of using and making the same.

Description

[0001] BICYCLIC HETEROAROMAT NEUROLOGICAL DISORDERS

[0002] TECHNICAL FIELD

[0003] This disclosure provides compounds and pharmaceutically acceptable salts thereof, that are useful, e.g., for treating neurological disorder in subject. This disclosure also provides compositions containing the same as well as methods of using and making the same.

[0004] SEQUENCE LISTING

[0005] This application contains a Sequence Listing that has been submitted electronically as an XML file named “50887-0043W01.XML.” The XML file, created on June 12, 2024, is 4,096 bytes in size. The material in the XML file is hereby incorporated by reference in its entirety.

[0006] PARTIES TO A JOINT RESEARCH AGREEMENT

[0007] The subject matter of the present disclosure was created pursuant to a joint research agreement between Prothena Biosciences Limited and V anderbilt University, that was in effect on or before the date the subject matter described herein was made, and the subject matter was made as a result of activities undertaken within the scope of the joint development agreement.

[0008] PRIORITY CLAIM

[0009] The application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 508,131 filed June 14, 2023, U.S. Provisional Patent Application Serial No. 63 / 508,137 filed June 14, 2023, U.S. Provisional Patent Application Serial No. 63 / 508,139 filed June 14, 2023, U.S. Provisional Patent Application Serial No. 63 / 510,695 filed June 28, 2023, U.S. Provisional Patent Application Serial No. 63 / 510,696 filed June 28, 2023, U.S. Provisional Patent Application Serial No. 63 / 510,711 filed June 28, 2023, U.S. Provisional Patent Application Serial No. 63 / 656,038 filed June 4, 2024, and U.S. Provisional Patent Application Serial No. 63 / 656,070 filed June 4, 2024, each of which is incorporated by reference herein in its entirety.

[0010] BACKGROUND

[0011] Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1 A) is a 763 amino acid, 85 kDa serme / threonine / tyrosme kinase located on chromosome 21 (21q22.2). DYRK1A possesses catalytic activity that is regulated by autophosphorylation of a tyrosine residue (Y321) which results in constitutively active serine / threonine kinase activity. See Abbassi, et al., Pharmacology & Therapeutics, 151, 87-98 (2015). Since DYRK1A is constitutively active, its activity is dosage dependent. Thus, both elevated levels and depressed levels of DYRK1A, (relative to wild-type levels) have been shown to lead to neurological impairment. See Duchon and Herault, Front Behav. Neurosci. 10, 104-104 (2016). DYRK1A is also a member of a large family of CMGC kinases, which include cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAPKs), glycogen synthase kinases (GSKs), and CDC-like kinases (CLKs). DYRK1A additionally has been shown to have a role in cell cycle regulation, at least in part by phosphorylating (and thus inhibiting) the nuclear factor of activated T cells (NFAT) family of transcription factors. Additionally, over 20 substrates of DYRK1A have been identified, including cell signaling, chromatin modulation, gene expression, alternative splicing, cytoskeletal, and synaptic function. See Abassi, et al, (2016). DYRK1A dysregulation is implicated in various disease states such as Alzheimer’s disease, autism, and Down syndrome. In some cases, novel mutations in DYRK1A have been associated with autism phenotypes. See e.g., Dang, et al., Molecular Psychiatry, 23, 747-758 (2018). DYRK1A is also known to play an important role in brain development. For example, reduced DYRK1A activity (such has having a single copy of loss of function mutation) during neural development results in intellectual disability phenotypes. Conversely, trisomy 21 in Down syndrome individuals is associated with a triplication of the DYRK1A gene, which results in elevated DYRK1A activity. DYRK1A is located on chromosome 21, specifically within the “Down syndrome critical region” a portion of chromosome 21 that includes genes particularly relevant for developing Down syndrome phenotypes. As a result, individuals with Down syndrome have three copies of DYRK1A, and since DYRK1A is dosage sensitive, the elevated levels of DYRK1A in such individuals markedly affects the localization and function of the DYRK1A protein. The expression of DYRK1A is also elevated in the CNS in individuals with neurodegenerative diseases, such as Parkinson’s disease, Pick’s disease, and Alzheimer’s disease. Moreover, approximately 50% of individuals with Down syndrome ultimately develop Alzheimer’s disease, with symptoms generally beginning between the ages of 40 and 60. DYRK1A phosphorylates amyloid precursor protein (APP) which promotes the production of pathogenic amyloid-ȕ peptide (Aȕ). Dyrk1A also phosphorylates tau both directly and indirectly (see Abassi, et al, (2016)). Both amyloid-P and tau pathologies are associated with Down syndrome phenotypes.

[0012] Normalization of DYRK1A gene dosage by crossing Ts65Dn mice (DS model) with DYRK1 A knockout mice mice reverses many Azlheimer’s-like phenotypes. See Garcia-Cerro et al., 2017. In individuals with Down Syndrome, DYRK1 A mRNA levels, protein levels, and kinase activity are increased by -50%, reflecting the number of gene copies. See Liu et al., 2008; see also Wegiel et al., 2011.

[0013] Because no treatment is available for these neurological disorders, the prognosis for individuals with, for example, Alzheimer’s disease is poor. This can be particularly devastating because Alzheimer’s disease is responsible for a sharp decline in survival in individuals with Down syndrome that are over 45 years old. Only about 25% of those with Down syndrome live more than 60 years, and most of those have developed Alzheimer’s disease.

[0014] Across all individuals, dementia remains a significant leading unmet medical need and a costly burden on public health. Currently, 1 in 3 seniors develops dementia, and about 70% of dementia cases are attributed to Alzheimer’s disease. Some 11% of Americans over age 65 has AD, which constitutes over 6.2 million in 2021, This figure is projected to exceed 12 million in 2050 (www.AIz.org).

[0015] Presently, no therapies have been approved to treat Alzheimer’s disease associated with Down syndrome, which represents a significant unmet medical need. Some DYRK1 A inhibitors have been tested in vitro or in animal preclinical models to treat Alzheimer’s disease or Down syndrome, however, since DYRK1A is a member of the highly conserved CMGC family of kinases, identifying compounds that selectively target DYRK1A has proved challenging. Thus, there remains a need to identify D YRK1 A inhibitors to treat Down syndrome, Alzheimer’s disease, Alzheimer’s disease associated with Down syndrome, and other neurodegenerative and neurological diseases.

[0016] SUMMARY

[0017] Some embodiments provide a compound represented by the structure of Formula (I):

[0018] (I), or a pharmaceutically acceptable salt thereof, wherein: each represents a single or a double bond, such that the bicyclic ring system comprising Y1, Y2, Y3, and Y4is an aromatic bicyclic ring system where (i) Y1is CR3, Y2is N, Y3is CR4, and Y4is CR3or N; (ii) Y1is S, Y2is C, Y3is CR4or N, and Y4is CR3; or (iii) Y1is N, Y2is N, Y3is CR4, and Y4is CR3; L is selected from , , and , wherein * denotes the point of attachment to Ring A, Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene, Z’ is selected from -NR1-, -S(O)-, -S(O)2-, C1-4alkylene, -NR1-C1-4alkylene, -S(O)-C1-4alkylene, and -S(O)2-C1-4alkylene; wherein each C1-4alkylene is optionally substituted with one or more halogen; Ring B is selected from (a), (b) and (c): (a) , X1is selected from N, CH, and CR5; (b) , X2is selected from S and NR7; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system, provided that when Ring B is (a), Y1is CR3, Y2is N, Y3is CR4, and Y4is N, then p is 0; R1is independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4haloalkyl, and –C(O)C3-6cycloalkyl optionally substituted with one or more halogen; R2is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, - OR10, -SR10, -N(R10)2, NO2, and -CN; R3and R4are each independently selected at each occurrence from hydrogen, halogen, C1- 4 alkyl, and C1-4 haloalkyl; Ring A is selected from: cyclopropyl substituted with one or more C1-6alkyl or -CN, C3-6carbocycle substituted with one or more halogen, 3- to 6-membered heterocycle substituted with one or more halogen, C5-6spirocyclic carbocycle, and 5- to 6-membered spirocyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; C7-12carbocycle and 7- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl, provided that when Ring B is selected from (b), then Ring A is not chromane; provided that when one or more of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) apply, then Ring A is further selected from C4-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl: (i) Ring B is (a) and RAis selected from halogen, C1-4 haloalkyl, C3-6 cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4 alkyl or C1-4 haloalkyl; (vi) Ring B is (c); and (vii) Y1is CR3, Y2is N, Y3is CR3, and Y4is N; (viii) Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c); provided that when Ring B is (a), X1is CH, RAis methyl, Y1is CR3, and Y2is N, then Ring A is further selected from tetrahydrofuranyl substituted with methyl; R5is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -N(R13)S(O)2(R13), -S(O)2R13, -S(O)2N(R13)2, -NO2, and -CN, provided that when RAis -OR11, then R5is not -OR13; R6is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)OR14, -OC(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2(R14), -S(O)2R14, -S(O)2N(R14)2, -NO2, =O, and -CN; R8is independently selected at each occurrence from halogen, C2-4alkyl, C1-4haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)OR14, -OC(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2(R14), -S(O)2R14, -S(O)2N(R14)2, -NO2, =O, and -CN; R7and R9are each independently selected from hydrogen, C1-4 alkyl, and C1-4 haloalkyl; R10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 cycloalkyl; m is selected from 0 and 1; p is selected from 0, 1, and 2; q is selected from 0, 1, and 2; and r is selected from 0, 1, and 2. Some embodiments provide a compound of Formula (II), (II); or a pharmaceutically acceptable salt thereof, wherein: each represents a single or a double bond, such that the bicyclic ring system comprising Y1, Y2, and Y3is an aromatic bicyclic ring system where (i) Y1is CR3and Y2is N, or (ii) Y1is S and Y2is C; Y3is selected from N and CR4; Ring B is selected from (a), (b) and (c): (a) , X1is selected from N, CH, and CR5; (b) , X2is selected from S and NR7; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system; R1is selected from hydrogen, C1-4 alkyl, and –C(O)C3-6 cycloalkyl optionally substituted with one or more halogen; R2is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -OR10, -SR10, -N(R10)2, NO2, and -CN; R3and R4are each independently selected from hydrogen, halogen, C1-4alkyl, and C1-4 haloalkyl; RAis selected from halogen, C1-4alkyl, C1-4haloalkyl, C1-4hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, -S(O)2C1-4 alkyl, C3-6 cycloalkyl, and 3- to 6-membered heterocycloalkyl, provided that: when Y1is CR3and Y2is N, then RAis further selected from -OR11, when Y1is CR3, Y2is N, Y3is CH, Ring B is (a), p is 0, X1is N, and Ring A is 1-fluoro- 1-tetrahydropyranyl, then RAis further selected from hydrogen, and when Y1is S, Y2is C, and X1is N, then RAis further selected from hydrogen; Ring A is selected from: C3-6carbocycle and 3- to 6-membered heterocycle, each of which is substituted with one or more halogen, and is optionally substituted with one or more substituents independently selected from: C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6- membered heterocycle optionally substituted with one or more C1-4alkyl; C7-12carbocycle and 7- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2,- C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl, provided that when Ring B is selected from (b), then Ring A is not chromane; provided that when one or more of (i), (ii), (ii), (iv), and (v) apply, then Ring A is further selected from C4-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2,-C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl: (i) Ring B is (a) and RAis selected from halogen, C1-4 haloalkyl, C3-6 cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis Ci-4 alkyl;

[0019] (iv) Ring B is (a), and p is 1, 2, or 3;

[0020] (v) R1is Ci -4 alkyl; and

[0021] (vi)Ring B is (c); provided that when Ring B is (a), Xi is CH, RAis methyl, Y1is CR’, and Y2is N, then Ring A is further selected from tetrahydrofuranyl substituted with methyl;

[0022] R5is independently selected at each occurrence from halogen, Ci-4 alkyl, Ct-i haloalkyl, -OR14, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -N(R! 3)S(O)2(R! 3), -S(O)2R1J, -S(O)2N(R1J)2, ~NO2, and -CN, provided that when RAis -OR11, then R' is not -OR13;

[0023] R6is independently selected at each occurrence from halogen, Ci-4 alkyl, Ci-4 haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)OR14, -OC(O)R14, -C(O)N(R14)2,

[0024] -N(R! 4)C(O)R14, -N(R14)S(O)2(R14), -S(O)2R14, -S(O)2N(R14)2, -NO2, =0, and -CN;

[0025] R8is independently selected at each occurrence from halogen, C2-4 alkyl, Ci-4 haloalkyl, -OR14, -SR14, -N(R14)2, -C(0)R14, -C(O)OR14, -OC(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2(R14), -S(O)2R14, -S(O)2N(R14)2, -NO2, =0, and -CN;

[0026] R / and R9are each independently selected from hydrogen, Ci-4 alkyl, and Ci-4 haloalkyl;

[0027] Rso, R11, Rl2, R13, and R14are each independently selected at each occurrence from hydrogen, Ci- 6 alkyl. Ci- 6 haloalkyl, and C3 -6 cycloalkyl; m is selected from 0, 1, and 2; p is selected from 0, 1 , and 2; q is selected from 0, 1, and 2; and r is selected from 0, 1 , and 2.

[0028] Some embodiments provide a compound of Formula (V):

[0029] (v), or a pharmaceutically acceptable salt thereof, wherein: Q!is N, S, O or CR3, Q2is N or C, Q3is N or CR4, Q4is N or CR3, Q3is C or N, and each represents a single or a double bond, such that the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is benzo [djthiazole, benzo[d]oxazole, imidazo[l,2-a]pyridine, thiazolo[5,4- bjpyridine, imidazofl ,2-b]pyridazine, pyrazolo[l,5-a]pyridine, [l,2,4]triazolo[l,5-a]pyridine, or [l,2,4]triazolo[l,5-b]pyridazine;

[0030] RAis selected from halogen, -OR10, -SR10, -N(R10)2, -CN, Ci-e alkyl optionally substituted with one or more halogen or -OR10, Cs-Ce saturated cycloalkyl, and 3- to 6-membered saturated heterocycloalkyl ;

[0031] Ring A is selected from a C3-C10 saturated cycloalkyl, a C3-C10 partially saturated carbocycle, a 3- to 10-membered saturated heterocycloalkyl, and a 3- to 10-membered partially saturated heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR”, -N(R”)2, -C(O)R”, -C(O)ORU, -OC(O)R”, -OC(O)N(R”)2, -C(0)N(R”)2, -N(R”)C(O)R”, -N(R11)C(O)OR11, -N(R11)C(O)N(R11)2, -MR^SCOXR11), -SIOJR11, -SlOyR A -S(O)2N(RU)2, -S(O)(NR11)R11, -NO2, and =0;

[0032] C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R! 1)2, -C(O)Rn, -C(0)0Rn, -OC(O)RU, -0C(0)N(Ru)2, -C(0)N(R! 1)2, -N(R:\)C(O)R A -N(R11)C(0)0R11, -N(R11)C(0)N(R11)2, -N(R11)S(0)2(R11), -S(O)R!1, -S(O)2R!1, -S(O)2N(RU)2, -S(0)(NR11)R11, -N02, =0, -CN; and

[0033] C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR11, -SR11, -N(Rii)2, -C(0)R”, -CfC^OR11, -OC(O)R”, -0C(0)N(Rn)2, -C(0)N(R11)2, -N(R11)C(())R11, -N(R11)C(0)0R11, -N(R11)C(())N(R11)2, -N(R11)S(())2(R11), -S(O)R”, -S(0) R A -S(O)2N(R11)2, -S(0)(NR11)Rii, -NO: 2, 0 and -CN;

[0034] Ring B is selected from a C3-C10 carbocycle and a 3 - to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR A -SR12, -N(R12)2, -C(())R12, -C(0)0R12, -0C(0)R12, -0C(0)N(Rl 2)2, -C(())N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), ■S(O)R A -S(O).-R A -S(O)2N(R12)2, -S(O)(NR12)R12, -NOZ, O. and -CN;

[0035] C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(0)0R12, -0C(0)R12, -OC(O)N(R12)2, -C(())N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)Z(R12), ■S(O)R . -Sf Oi.-R2, -S(0)2N(Ri 2)2, -S(O)(NR12)R12, -NO.-. O. ■( N; and

[0036] C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, Ci-e alkyl, Ci-e haloalkyl, -OR12, -SR12, -N(RI2)2, -C(O)R12, -C(())OR12, -OC(O)R12, ■O('{O)N( Ri 2) -C(O)N(R!2)2, -N(R12)C(())R12, -N(R12)C(O)OR12, -N(R12)C(())N(R12)2, -N(R12)S(())2(R12), -S(O)R12, -S(O) 2R12, -S(O) 2N(R! 2)2, -S(O)(NR12)R12, -NO: 2, O. and -CN;

[0037] R1is selected from hydrogen, Ci-4 alkyl, Cu4 haloalkyl, and -C(O)R1J;

[0038] R2is independently selected at each occurrence from halogen, Ci-4 alkyl, Ci-4 haloalkyl, -OR14, -SR14, -N(R14)2, -NO2, and -CN;

[0039] R3is independently selected at each occurrence from hydrogen, halogen, Ci -4 alkyl, and Ci-4 haloalkyl;

[0040] R4is selected from hydrogen, halogen, Ci -4 alkyl, and Ci-4 haloalkyl;

[0041] R10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen, Ci-4 alkyl, Ci-4 haloalkyl, and cycloalkyl optionally substituted with one or more halogen; and n is selected from 0, 1 , and 2; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl.

[0042] Some embodiments provide a compound of Formula (VI): or a pharmaceutically acceptable salt thereof, wherein:

[0043] Q1is S or CR3, Q2is N or C, QJis selected from N and CR4, and each represents a single or a double bond, such that the bicyclic ring system comprising Q1, Q2, and Q3is benzo[d]thiazole, imidazofl ,2-a]pyridine, thiazolo[5,4-b]pyridine, or imidazo[l,2-b]pyridazine;

[0044] RAis selected from halogen, -OR10, -SR10, -N(R10)2, -CN, C1-6 alkyl, C1-6 haloalkyl, C3-C6 saturated cycloalkyl, and 3- to 6-membered saturated heterocycloalkyl; Ring A is selected from a C3-C10 saturated cycloalkyl, a C3-C10 partially saturated carbocycle, a 3- to 10-membered saturated heterocycloalkyl, and a 3- to 10-membered partially saturated heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR! !, -N(Rll)2, -C(O)Rn, -C(O)ORn, -OC(O)RU, OC{O)X( Ri :} -C(0)N(R1 !)2, •X{ R: i)('(())()R: i. -N(R11)C(0)N(R11)2, -X-: R: :;-S(()) -: R.: :;-.

[0045] -S(O)Rn, -S(O)2Rn, -S(O)2N(R!1)2, -S(O)(NR11)R11, -NO2, and ();

[0046] C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, •N(R" r. -C(O)Rn, -C(O)OR! 1, -OC(O)R! !, -OC(O)N(R! 1)2, -C(O)N(R’! 1)2, -N(R11)C(O)R11, -N(RH)C(O)OR51, -N(Rn)C(O)N(Rn)2, -N(Rn)S(O)2(Rn), -S(O)Rn, -S(O)2Rn, -S(O)2N(R! !)2, -S(O)(NR”)Rn, -NO2, =0, -CN; and

[0047] C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR11, -SR11, -N(R!!)2, -C(0)R11, -C(0)0R! 1, -OC(O)R1!, -0C(0)N(RU)2, -C(0)N(Rn)2, -\iR KW -N^'^OR11, -N(R11)C(0)N(R11)2, -N(Rll)S(0)2(R11), -S(O)R!!, -S(O)2R! 1, -S(O)2N(RH)2, -S(0)(NRll)R!!, -NO2, =0, and -CN;

[0048] Ring B is selected from a C3-C10 carbocycle and a 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(0)R12, -C(0)0R12, -0C(0)R12, -OC(O)N(Ri2)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N( R12): 2, -S(())(NRi2)R12, -N02, O. and -CN;

[0049] C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(())0R12, -0C(0)R12, -OC(O)N( R12): 2, -C(())N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N( R12): 2, -S(())(NRi2)R12, -N02, O. -CN; and

[0050] C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, Ci-e alkyl, Ci-e haloalkyl, -OR12, -SR12, -N(R12)2, -C(())R12, -C(())0R12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(())R12, -N(R12)C(O)OR12, -N(R12)C(())N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(0) 2R12, -S(0) 2N(R12)2, -S(O)(NR12)R12, -NO: 2, O, and -CN;

[0051] R1is selected from hydrogen, C1-4 alkyl, and -C(O)R13; R2is independently selected at each occurrence from halogen, Ci-4 alkyl, Ci-4 haloalkyl, -OR14, -SR14, -N(R14)2, -NO2, and -CN;

[0052] R3and R4are each selected from hydrogen, halogen, Ci-4 alkyl, and Ci-4 haloalkyl;

[0053] R10, Ru, R12, R13, and R14are each independently selected at each occurrence from hydrogen, Ci-4 alkyl, C1-4 haloalkyl, and cycloalkyl optionally substituted with one or more halogen; and n is selected from 0, 1, and 2; provided that when Ring B is pyrazolyl, then Ring A is not A-Boc pyrrolidinyl.

[0054] Also provided herein is a pharmaceutical composition comprising a compound of Formula

[0055] (I), (II), (III), (IV), (V), or (VI), or any subformulae thereof, a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0056] Provided herein is a method for treating a neurological disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula (I), (II), (III), (IV), (V), or (VI), or any subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein.

[0057] Some embodiments provide a method for treating a neurological disorder in a subject in need thereof, the method comprising (a) determining that the neurological disorder is associated with a dysregulation of & DYRK1A gene, a DYRK1A protein, or expression or activity or level of any of the same; and (b) administering to the subject a therapeutically effective amount of a compound of Formula (I), (II), (III), (IV), (V), or (VI), or any subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein.

[0058] Also provided herein is a method for treating a neurological disorder in a subject in need thereof, the method comprising (a) determining that the neurological disorder is a DYRK1A- associated neurological disorder, and (b) administering to the subject a therapeutically effective amount of a compound of Formula (I), (II), (III), (IV), (V), or (VI), or any subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein.

[0059] Also provided herein is a method for treating a neurological disorder in a subject in need thereof, the method comprising (a) determining that the subject has a neurological disorder; and (b) administering to the subject a therapeutically effective amount of a compound of Formula (I),

[0060] (II), (III), (IV), (V), or (VI), or any subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. Provided herein is a method of treating a DYRKlA-associated disorder in a subject, the method comprising administering to a subject previously determined to have a DYRKlA- associated disorder a therapeutically effective amount of a compound of Formula (I), (II), (III), (IV), (V), or (VI), or any subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein.

[0061] Provided herein is a method of treating a subject, the method comprising administering a therapeutically effective amount of a compound of Formula (I), (II), (III), (IV), (V), or (VI), or any subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein, to a subject having a clinical record that indicates that the subject has a dysregulation of a DYRKIA gene, a DYRKIA protein, or expression or activity or level of any of the same.

[0062] This disclosure also provides a method for inhibiting DYRKIA activity in a mammalian cell, the method comprising contacting the mammalian cell with a therapeutically effective amount of a compound of Formula (I), (II), (III), (IV), (V), or (VI), or any subformulae thereof, sor a pharmaceutically acceptable salt thereof.

[0063] The details of one or more embodiments of this disclosure are set forth in the accompanying drawings and the description below. Other features and advantages of the present disclosure will be apparent from the description and the claims.

[0064] Additional Definitions

[0065] To facilitate understanding of the disclosure set forth herein, a number of additional terms are defined below. Generally, the nomenclature used herein and the laboratory procedures in organic chemistry, medicinal chemistry, and pharmacology described herein are those well-known and commonly employed in the art. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Each of the patents, applications, published applications, and other publications that are mentioned throughout the specification and the attached appendices are incorporated herein by reference in their entireties. In case of conflict, the present specification, including definitions, wall control.

[0066] The term “about” w'hen referring to a number or a numerical range means that the number or numerical range referred to is an approximation, for example, within experimental variability and / or statistical experimental error, and thus the number or numerical range may vary up to ±10% of the stated number or numerical range.

[0067] The term “acceptable” with respect to a formulation, composition or ingredient, as used herein, means having no persistent detrimental effect on the general health of the subject being treated.

[0068] The term “inhibit” or “inhibition of’ means to reduce by a measurable amount, or to prevent entirely (e.g., 100% inhibition).

[0069] The phrase “therapeutically effective amount” means an amount of compound that, when administered to a subject in need of such treatment, is sufficient to (i) treat a neurological disorder as described herein, (ii) attenuate, ameliorate, or eliminate one or more symptoms of the particular neurological disorder, or (iii) delay the onset of one or more symptoms of the particular neurological disorder described herein. In some embodiments, the therapeutically effective amount is an amount sufficient to inhibit DYRK1 A activity in brain tissue.

[0070] As used herein, terms “treat” or “treatment” refer to therapeutic or palliative measures. Beneficial or desired clinical results include, but are not limited to, alleviation, in whole or in part, of symptoms associated with a neurological disorder, diminishment of the extent of a neurological disorder, stabilized (i.e., not worsening) state of a neurological disorder, delay or slowing of disease progression, amelioration or palliation of the disease state (e.g., one or more symptoms of the neurological disorder), and remission (whether partial or total), whether detectable or undetectable and can be determined by various clinical assessments including clinical evaluation and self-reporting. “Treatment” can also mean prolonging survival as compared to expected survival if not receiving treatment.

[0071] The term “pharmaceutically acceptable excipient” means a. pharmaceutical! y-accep table material, composition, or vehicle, such as a liquid or solid filler, diluent, carrier, solvent, or encapsulating material. In one embodiment, each component is “pharmaceutically acceptable” in the sense of being compatible with the other ingredients of a pharmaceutical formulation, and suitable for use in contact with the tissue or organ of humans and animals without excessive toxicity, irritation, allergic response, immunogenicity, or other problems or complications, commensurate with a reasonable benefit / risk ratio. See, e.g., Remington: The Science and Practice of Pharmacy, 21st ed.: Lippincott Williams & Wilkins: Philadelphia, PA, 2005; Handbook of Pharmaceutical Excipients, 6th edg Rowe eta!., Eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009; Handbook of Pharmaceutical Additives, 3rd ed.\ Ash and Ash Eds.; Gower Publishing Company: 2007; Pharmaceutical Preformulation and Formulation, 2nd ed.. Gibson Ed.; CRC Press LLC: Boca Raton, FL, 2009.

[0072] The term “pharmaceutically acceptable salt” refers to a formulation of a compound that does not cause significant irritation to an organism to winch it is administered and does not abrogate the biological activity and properties of the compound. In certain instances, pharmaceutically acceptable salts are obtained by reacting a compound described herein, with acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like. In some instances, pharmaceutically acceptable salts are obtained by reacting a compound having acidic group described herein with a base to form a salt such as an ammonium salt, an alkali metal salt, such as a sodium or a potassium salt, an alkaline earth metal salt, such as a calcium or a magnesium salt, a salt of organic bases such as dicyclohexylamine, A-methyl-D-glucamine, tris(hydroxymethyl)methylaniine, and salts with amino acids such as arginine, lysine, and the like, or by other methods previously determined. The pharmacologically acceptable salt s not specifically limited as far as it can be used in medicaments. Examples of a salt that the compounds described heremform with a base include the following: salts thereof with inorganic bases such as sodium, potassium, magnesium, calcium, and aluminum; salts thereof with organic bases such as methylamine, ethylamine and ethanolamine; salts thereof with basic ammo acids such as lysine and ornithine; and ammonium salt. The salts may be acid addition salts, which are specifically- exemplified by acid addition salts with the following: mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid, and organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, and ethanesulfonic acid; acidic amino acids such as aspartic acid and glutamic acid.

[0073] The term “pharmaceutical composition” refers to a mixture of a compound described herein with other chemical components (referred to collectively herein as “pharmaceutically acceptable carriers”), such as stabilizers, diluents, dispersing agents, suspending agents, thickening agents, and / or other excipients. The pharmaceutical composition facilitates administration of the compound to an organism. The term “subject” refers to an animal, including, but not limited to, a primate (e.g., human), monkey, cow, pig, sheep, goat, horse, dog, cat, rabbit, rat, or mouse. The terms “subject” and “patient” are used interchangeably herein in reference, for example, to a mammalian subject, such as a human. The terms “halo” and “halogen” refers to fluoro (F), chloro (Cl), bromo (Br), or iodo (I). The term “oxo” refers to a divalent doubly bonded oxygen atom (i.e., “=O”). As used herein, oxo groups are attached to carbon atoms to form carbonyls. The term “hydroxyl” refers to an -OH radical. The term “nitro” refers to an –NO2radical. The term “cyano” refers to a -CN radical. The term “alkyl” refers to a saturated acyclic hydrocarbon radical that may be a straight chain or branched, containing the indicated number of carbon atoms. For example, C1-10 indicates that the group may have from 1 to 10 (inclusive) carbon atoms in it. Non-limiting examples include methyl, ethyl, iso-propyl, tert-butyl, n-hexyl. The term “saturated” as used in this context means only single bonds present between constituent carbon atoms and other available valences occupied by hydrogen and / or other substituents as defined herein. An “alkylene” group is a divalent alkyl group as described herein. The term “haloalkyl” refers to an alkyl, in which one or more hydrogen atoms is / are replaced with an independently selected halogen. The term “hydroxyalkyl” refers to an alkyl, in which one or more hydrogen atoms is / are replaced with a hydroxyl group, as described herein. The term “alkoxy” refers to an -O-alkyl radical (e.g., -OCH3). The terms “carbocycle” and “carbocyclyl” refer to a 3-20 carbon mono-, bi-, tri- or polycyclic group that can be fully saturated, partially unsaturated, aromatic, and (in multi-ring systems) any combination thereof. Carbocyclyl groups can include fused, bridged, and spiro ring systems. In some embodiments, a carbocyclyl is an aryl as defined herein. Examples of carbocyclyl groups include aryl and cycloalkyl groups as described herein. The term “aryl” refers to a 6-20 carbon mono-, bi-, tri- or polycyclic group wherein at least one ring in the system is aromatic (e.g., 6-carbon monocyclic, 10-carbon bicyclic, or 14-carbon tricyclic aromatic ring system. Examples of aryl groups include phenyl, naphthyl, tetrahydronaphthyl, and the like. The term “cycloalkyl” as used herein refers to cyclic saturated or partially unsaturated hydrocarbon groups having, e.g., 3 to 20 ring carbons, preferably 3 to 16 ring carbons, and more preferably 3 to 12 ring carbons or 3-10 ring carbons or 3-6 ring carbons. Examples of cycloalkyl groups include, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Cycloalkyl groups can include fused and bridged ring systems. Non-limiting examples of fused / bridged cycloalkyl includes: bicyclofl.1.0]butane, bicyclo[2. l.Ojpentane, bicyclofl.1.1 ]pentane, bicyclof 3.1.0] hexane, bicyclo[2.1.1 ]hexane, bicyclof3.2.0]heptane, bicyclo[4.1.0]heptane, bicyclof2.2. l]heptane, bicyclofS.1. Ijheptane, bicyclof4.2.0]octane, bicyclof3.2.1]octane, bicyclof2.2.2]octane, and the like. Cycloalkyl groups can also include spirocyclic rings (e.g., spirocyclic bicycle wherein two rings are connected through just one atom). Non-limiting examples of spirocyclic cycloalkyls include spirof2.2]pentane, spiro [2.5] octane, spiro [3.5] nonane, spiro[3.5]nonane, spiro[3.5]nonane, spirof4.4]nonane, spirof2.6]nonane, spiro[4.5]decane, spiro [3.6] decane, spiro[5.5]undecane, and the like.

[0074] The terms “heterocycle” and “heterocyclyl” refers to a mono-, bi-, tri-, or polycyclic saturated, partially unsaturated, or aromatic ring systems with 3-20 total ring atoms and having 1 - 4 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic or polycyclic. Exemplary heteroatoms include O, N, S, P, Si, and B. In some embodiments, for example, a heterocycle comprises 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, a heterocycle comprises 1, 2, or 3 (e.g., 1) heteroatoms selected from O, N, and S, In some embodiments, a heterocycle comprises one 0 atom. In some embodiments, a heterocycle comprises one S atom. In some embodiments, a heterocycle comprises one N atom. In some embodiments, for example, a heterocycle comprises 1 , 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, a heterocycle comprises 1 or 2 (e.g., 1) heteroatoms selected from O, N, and S. In some embodiments, a heterocycle comprises one 0 atom. In some embodiments, a heterocycle comprises one S atom. In some embodiments, a heterocycle comprises one N atom. Heterocyclic ring systems can also include 1 -3 ring atoms that are -C(())-, N-oxide, S-oxide, and / or S,S-dioxide groups, valence permitting. In some embodiments, a heterocyclyl is a heteroaryl as defined herein. Examples of heterocyclyl groups include heteroaryl groups, as described herein, as well as fully and partially saturated groups such as piperazinyl, pyrrolidinyl, pyrrolidonyl, pyrrolidonyl, tetrahydrothiophenyl 1,1 -dioxide, thiomorpholinyl 1,1 -dioxide, tetrahydrothiophenyl 1,1 -dioxide, thiomorpholinyl 1,1 -dioxide, dioxanyl, morpholinyl, tetrahydrofuranyl, tetrahydropyridyl, dihydropyrazinyl, dihydropyridyl, dihydropyrrolyl, dihy dr of uranyl, dihydrothiophenyl, and the like. Heterocyclyl groups can include multiple fused and bridged rings. Non-limiting examples of fused / bridged heteorocyclyl includes: 2- azabicyclo [1.1.0]butane, 2-azabicy clo[2.1.0]pentane, 2-azabicyclo[ 1.1.1 ]pentane, 3- aza bicyclo [3.1.0] hexane, 5-azabicyclo[2.1.1 ]hexane, 3 -azabicyclo [3.2.0 ]heptane, octahydrocyclopentalclpvrrole, 3-azabicyclol4.1.Olheptane, 7-azabicyclol2.2.1 lheptane, 6 azabicyclo[3.1. 1 ]heptane, 7-azabicyclo[4.2.0]octane, 2-azabicyclo[2.2.2]octane, 3- azabicyclo[3.2. l]octane, 2-oxabicyclo[ 1.1.0]butane, 2-oxabicyclo[2.1.01 pentane, 2- oxabicyclo[ 1.1.1 ]pentane, 3 -oxabicy clo[3.1.0]hexane, 5-oxabicyclo[2.1.1 ]hexane, 3- oxabicy clo[3.2.0] heptane, 3-oxabicyclo[4.1.0]heptane, 7-oxabicyclo[2.2.1 ]heptane, 6- oxabicy clo[3.1.1 ] heptane, 7-oxabicy clo[4.2.0] octane, 2-oxabicyclo[2.2.2]octane, 3- oxabicyclo[3.2.1]octane, and the like. Heterocyclyl groups can also include spirocyclic rings (e.g., spirocyclic bicycle wherein two rings are connected through just one atom). Non-limiting examples of spirocyclic heterocyclyls include 2-azaspiro[2.2]pentane, 4-azaspiro[2.5]octane, 1- azaspiro[3.5]nonane, 2-azaspiro[3.5]nonane, 7-azaspiro[3.5]nonane, 2 -azaspiro [4.4] nonane, 6- azaspiro[2.6]nonane, 1 ,7-diazaspiro[4.5]decane, 7-azaspiro[4.5]decane 2,5- diazaspiro[3.6]decane, 3 -azaspiro [5.5] undecane, 2-oxaspiro[2.2]pentane, 4-oxaspiro[2.5]octane, l-oxaspiro[3.5]nonane, 2-oxaspiro[3.5]nonane, 7-oxaspiro[3.5]nonane, 2-oxaspiro[4.4]nonane, 6- oxaspiro[2.6]nonane, l,7-dioxaspiro[4.5]decane, 2,5-dioxaspiro[3.6]decane, 1 - oxaspiro[5.5] undecane, 3-oxaspiro[5.5]undecane, 3-oxa-9-azaspiro[5.5jundecane and the like.

[0075] The term “heteroaryl”, as used herein, means a mono-, bi-, tri- or polycyclic aromatic group (i.e., the entire ring system is aromatic) having 5 to 20 ring atoms, alternatively 5, 6, 9, 10, or 14 ring atoms, wherein at least one ring in the system contains one or more heteroatoms independently selected from the group consisting of O, N, S, P, Si, and B. In some embodiments, for example, a heteroaryl comprises 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, a heteroaryl comprises 1 or 2 (e.g., 1) heteroatoms selected from 0, N, and S. In some embodiments, a heteroaryl comprises one 0 atom. In some embodiments, a heteroaryl comprises one S atom. In some embodiments, a heteroaryl comprises one N atom. In some embodiments, for example, a heteroaryl comprises 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, a heteroaryl comprises 1 or 2 (e.g., 1) heteroatoms selected from O, N, and S. In some embodiments, a heteroaryl comprises one O atom. In some embodiments, a heteroaryl comprises one S atom. In some embodiments, a heteroaryl comprises one N atom. Examples of heteroaryl include thienyl, pyridinyl, furyl, oxazolyl, oxadiazolyl, pyrrolyl, imidazolyl, triazolyl, thiodiazolyl, pyrazolyl, isoxazolyl, thiadiazolyl, pyranyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl benzothienyl, benzoxadiazolyl, benzofuranyl, benzimidazolyl, benzotriazolyl, cinnolinyl, indazolyl, indolyl, isoquinolinyl, isothiazolyl, naphthyridinyl, purinyl, thienopyridinyl, pyndo[2,3-r / ]pyrimidinyl, pyrrolo[2,3-£]pyridinyl, quinazoiinyl, quinolinyl, thieno[2,3- c[pyridinyl, pyrazolo[3,4-i?]pyridinyl, pyrazolo[3,4-c]pyridinyl, pyrazolo[4,3-c]pyridine, pyrazolo[4,3-6]pyridinyl, tetrazolyl, and the like.

[0076] The term “heterocycloalkyl” refers to a mono-, bi-, tri-, or polycyclic saturated or partially unsaturated ring system with 3-20 total ring atoms and having 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic or polycyclic. Exemplary heteroatoms include O, N, S, P, Si, and B. In some embodiments, for example, a heterocycloalkyl comprises 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, for example, a heterocycloalkyl comprises 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, a heterocycloalkyl comprises 1 or 2 (e.g., 1) heteroatoms selected from O, N, and S. In some embodiments, a heterocycloalkyl comprises one O atom. In some embodiments, a heterocycloalkyl comprises one S atom. In some embodiments, a heterocycloalkyl comprises one N atom. Heterocycloalkyl ring systems can also include 1-3 ring atoms that are -C(O)~, N-oxide, S-oxide, and / or S,S-dioxide groups, valence permitting. Examples of heterocycloalkyl groups include piperazinyl, pyrrolidinyl, pyrrolidonyl, tetrahydrothiophenyl 1,1 -dioxide, thiomorpholinyl 1,1-dioxide, dioxanyl, morpholinyl, tetrahydrofuranyl, tetrahydropyridyl, dihydropyrazinyl, dihydropyridyl, dihydropyrrolyl, dihydrofuranyl, dihydrothiophenyl, and the like. Heterocycloalkyl groups can include multiple fused and bridged rings. Non-limiting examples of fused / bridged heteorocyclyl includes: 2-azabicyclo[1.1.0]butane, 2-azabicyclo[2.1.0]pentane, 2- azabicy do [1.1.1 ]pentane, 3-azabicyclo[3.1 .0]hexane, 5-azabicyclo[2.1.1 jhexane, 3- azabi cyclo [3.2.0]heptane, octahydrocyclopenta[c]pyrrole, 3-azabicyc1o[4.1 .0]heptane;azabicyclo [2.2.1 ]heptane, 6-azabicyclo[3.1.1 [heptane, 7-azabicyclo[4.2.0]octane, aza bicyclo [2.2.2] octane, 3-azabicydo[3.2.1 [octane, 2-oxabicyclo[ 1.1.0] butane, 2- oxabicyclo[2.1.0]pentane, 2-oxabicy clo[ 1.1.1 ]pentane, 3-oxabicyclo[3.1.0]hexane, oxabicy clo[2.1.1 ]hexane, 3-oxabicyclo[3.2.0]heptane, 3 -oxabicy clo[4.1 ,0]heptane, 7- oxabicy clo[2.2.1 ]heptane, 6-oxabicyclo[3.1.1 [heptane, 7-oxabicyclo[4.2.0]octane, oxabicyclo[2.2,2]octane, 3-oxabicyclo[3.2.1]octane, and the like. Heterocycloalkyl groups can also include spirocyclic rings (e.g., spirocyclic bicycle wherein two rings are connected through just one atom). Non-limiting examples of spirocyclic heterocycloalkyls include 2- azaspiro[2.2]pentane, 4-azaspiro[2.5]octane, l-azaspiro[3.5]nonane, 2-azaspiro[3.5]nonane, 7- azaspiro[3.5]nonane, 2-azaspiro[4.4]nonane, 6-azaspiro[2.6]nonane, l,7-diazaspiro[4.5]decane, 7-azaspiro[4.5]decane 2,5-diazaspiro[3.6]decane, 3 -azaspiro [5.5] undecane, 2- oxaspiro[2.2]pentane, 4-oxaspiro[2.5]octane, l-oxaspiro[3.5]nonane, 2-oxaspiro[3.5]nonane, 7- oxaspiro[3.5]nonane, 2-oxaspiro[4.4]nonane, 6-oxaspiro[2.6]nonane, l,7-dioxaspiro[4.5]decane, 2,5-dioxaspiro[3.6]decane, l-oxaspiro[5.5]undecane, 3-oxaspiro[5.5]undecane, 3-oxa-9- azaspiro[5.5]undecane and the like.

[0077] The term “heterocycloalkyl” refers to a mono-, bi-, tri-, or polycyclic saturated or partially unsaturated ring system with 3-20 total ring atoms and having 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic or polycyclic. Exemplary heteroatoms include O, N, S, P, Si, and B. In some embodiments, for example, a heterocycloalkyl comprises 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, for example, a heterocycloalkyl comprises 1, 2, 3, or 4 heteroatoms selected from O, N, and S. In some embodiments, a heterocycloalkyl comprises 1 or 2 (e.g., 1) heteroatoms selected from O, N, and S. In some embodiments, a heterocycloalkyl comprises one O atom. In some embodiments, a heterocycloalkyl comprises one S atom. In some embodiments, a heterocycloalkyl comprises one N atom. Heterocycloalkyl ring systems can also include 1-3 ring atoms that are oxo, N-oxide, S- oxide, and / or S,S-dioxide groups, valence permitting. Examples of heterocycloalkyl groups include piperazinyl, pyrrolidinyl, pyrrolidonyl, tetrahydrothiophenyl 1,1 -dioxide, thiomorpholinyl 1,1-dioxide, dioxanyl, morpholinyl, tetrahydrofuranyl, tetrahydropyridyl, dihydropyrazinyl, dihydropyridyl, dihydropyrrolyl, dihydrofuranyl, dihydrothiophenyl, and the like. Heterocycloalkyl groups can include multiple fused and bridged rings. Non-limiting examples of fused / bridged heteorocyclyl includes: 2-azabicyclo[1.1.0]butane, 2-azabicyclo[2.1.0]pentane, 2- azabicy clo [1.1.1 [pentane, 3-azabicyclo[3.1.0]hexane, 5-azabicyclo[2.1.1 ]hexane, 3- azabicyclo [3.2.0] heptane, octahydrocyclopenta[c]pyrrole, 3-azabicyclo[4.1.0]heptane, azabicyclo [2.2.1 [heptane, 6-azabicyclo[3.1. l]heptane, 7-azabicyclo[4.2.0]octane, aza bicyclo [2.2.2] octane, 3-azabicyclo[3.2. l]octane, 2-oxabicyclo[ 1.1.0] butane, 2- oxabicyclo[2.1.0]pentane, 2-oxabicy clo[ 1.1.1 [pentane, 3-oxabicyclo[3.1.0]hexane, oxabicyclo[2.1.1 Jhexane, 3-oxabicyclo[3.2.0]heptane, 3-oxabicyclo[4.1.0]heptane, 7- oxabicyclo[2.2.1 ]heptane, 6-oxabicyclo[3.1.1 ]heptane, 7-oxabicyclo[4.2.0]octane, 2- oxabicyclo[2.2.2]octane, 3-oxabicyclo[3.2.1]octane, and the like. Heterocycloalkyl groups can also include spirocyclic rings (e.g., spirocyclic bicycle wherein two rings are connected through just one atom). Non-limiting examples of spirocyclic heterocycloalkyls include 2- azaspiro[2.2]pentane, 4-azaspiro[2.5]octane, l-azaspiro[3.5]nonane, 2-azaspiro[3.5]nonane, 7- azaspiro[3.5]nonane, 2-azaspiro[4.4]nonane, 6-azaspiro[2.6]nonane, l,7-diazaspiro[4.5]decane, 7-azaspiro[4.5]decane 2,5-diazaspiro[3.6]decane, 3 -azaspiro [5.5] undecane, 2- oxaspiro[2.2]pentane, 4-oxaspiro[2.5]octane, l-oxaspiro[3.5]nonane, 2-oxaspiro[3.5]nonane, 7- oxaspiro[3.5]nonane, 2-oxaspiro[4.4]nonane, 6-oxaspiro[2.6]nonane, l,7-dioxaspiro[4.5]decane, 2,5-dioxaspiro[3.6]decane, l-oxaspiro[5.5]undecane, 3-oxaspiro[5.5]undecane, 3-oxa-9- azaspiro[5.5]undecane and the like.

[0078] For purposes of clarification, heteroaryl also includes aromatic lactams, aromatic cyclic ureas, or vinylogous analogs thereof, in which each ring nitrogen adjacent to a carbonyl is tertiary (i.e., all three valences are occupied by non-hydrogen substituents), such as one or more of

[0079] | y O i ), and imidazolone (e.g., ’), wherein each ring nitrogen adjacent to a carbonyl is tertiary (i.e., the oxo group (i.e., “=O”) herein is a constituent part of the heteroaryl ring).

[0080] The term “saturated’1as used in this context means only single bonds present between constituent atoms.

[0081] As used herein, when a ring is described as being “partially unsaturated,” it means said ring has one or more additional degrees of unsaturation (in addition to the degree of unsaturation attributed to the ring itself; e.g., one or more double or triple bonds between constituent ring atoms), provided that the ring is not aromatic. Examples of such rings include: cyclopentene, cyclohexene, cycloheptene, dihydropyridine, tetrahydropyridine, dihydropyrrole, dihydrofuran, di hydrothiophene, and the like.

[0082] For the avoidance of doubt, and unless otherwise specified, for rings and cyclic groups (e.g., carbocycle, aryl, cycloalkyl, heterocyclyl, heteroaryl, and the like described herein) containing a sufficient number of ring atoms to form bicyclic or higher order ring systems (e.g., tricyclic, polycyclic ring systems), it is understood that such rings and cyclic groups encompass those having fused rings, including those in which the points of fusion are located (i) on adjacent ring atoms (e.g., [x.x.O] ring systems, in which 0 represents a zero atom bridge (e.g., ))•

[0083] J J

[0084] (ii) a single ring atom (spiro-fused ring systems) (e.g., , or ),or

[0085] (in) a contiguous array of ring atoms (bridged ring systems having all bridge lengths > 0) (e.g,,

[0086] In addition, any compound or structure given herein, is also intended to represent unlabeled forms as well as isotopically labeled forms of the compounds. These forms of compounds are referred to as “isotopically enriched.” Isotopically enriched compounds have structures depicted herein, except that one or more atoms are replaced by an atom having a selected atomic mass or mass number.

[0087] Examples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, chlorine and iodine, such as2H,13C,i4C,13N,15N,15O,17O,180,3iP,32P,35S,l8F,36C1 ,123I, and125I, respectively. Various isotopically enriched compounds of the present disclosure, for example those into which radioactive isotopes such as13C and!4C are incorporated. Such isotopically enriched compounds may be useful in metabolic studies, reaction kinetic studies, detection or imaging techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT) including drug or substrate tissue distribution assays or in radioactive treatment of patients. The term“isotopically enriched” compounds includes" deuterated” compounds described herein in which one or more hydrogens is / are replaced by deuterium, such as a hydrogen on a carbon atom. Such compounds exhibit increased resistance to metabolism and are thus useful for increasing the half-life of any compound when administered to a mammal, particularly a human. Such compounds are synthesized by means known in the art, for example by employing starting materials in which one or more hydrogens have been replaced by deuterium. Indeed, isotopically enriched compounds of this disclosure can generally be prepared by carrying out the procedures disclosed in the schemes or in the examples and preparations described below by substituting a readily available isotopically enriched reagent for a non-isotopically enriched reagent.

[0088] Deuterium enriched compounds of the present disclosure may have improved DMPK (drug metabolism and pharmacokinetics) properties, relating to distribution, metabolism and excretion (ADME). Substitution with heavier isotopes such as deuterium may afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life, reduced dosage requirements and / or an improvement in therapeutic index relative to the corresponding non-enriched compound.

[0089] The concentration of a heavier isotope, such as deuterium, may be defined by an isotopic enrichment factor. In some embodiments, the positions noted as “H” or “hydrogen” in the compounds described herein have hydrogen at its natural abundance isotopic composition. In some embodiments, the positions noted as “H” or “hydrogen” in the compounds described herein have hydrogen enriched in deuterium above its natural abundance isotopic composition, i.e., the compound is a deuterium enriched compound. Examples of deurated groups in the compounds described herein include, but are not limited to deuteromethine ( or monodeuteromethylene ) and dideuteromethylene °x ’D"''tyr trideuteromethyl (

[0090] CD,

[0091] Q tri deuteromethoxy (' ), and the like. Compounds of the present disclosure also include

[0092] O deuterium enriched compounds at the alpha position of an oxo group, such as D H; O o D o

[0093] D D , U?and Compounds of the present disclosure also include

[0094] D \ deuterium enriched compounds adjacent to a heteroatom, such as, for example and

[0095] N<- J-L J

[0096] In addition, the compounds generically or specifically disclosed herein are intended to include all tautomeric forms. Thus, by way of example, a compound containing the moiety: encompasses the tautomeric form containing the moiety:H $. Similarly, a pyridinyl or pyrimidinyl moiety that is described to be optionally substituted with hydroxyl encompasses pyridone or pyrimidone tautomeric forms.

[0097] The compounds provided herein may encompass various stereochemical forms. The compounds also encompass enantiomers (e.g., R and S isomers), diastereomers, as well as mixtures of enantiomers (e.g., R and S isomers) including racemic mixtures and mixtures of diastereomers, as well as individual enantiomers and diastereomers, which arise as a consequence of structural asymmetry in certain compounds. Unless otherwise indicated, when a disclosed compound is named or depicted by a structure without specifying the stereochemistry (e.g., a “flat” structure) and has one or more chiral centers, it is understood to represent all possible stereoisomers of the compound. Likewise, unless otherwise indicated, when a disclosed compound is named or depicted by a structure that specifies the stereochemistry (e.g., a structure with “wedge” and / or “dashed” bonds) and has one or more chiral centers, it is understood to represent the indicated stereoisomer of the compound.

[0098] The details of one or more embodiments of this disclosure are set forth in the accompanying drawings and the description below. Other features and advantages of the present disclosure wall be apparent from the description and from the claims. DETAILED DESCRIPTION

[0099] Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRKIA) is a member of the dual-specificity tyrosine phosphorylation regulated kinase (DYRK) family, which is also part of the larger CGMC family of kinases. DYRK 1 A is a 763 amino acid, 85 kDa serine / threonine kinase located on chromosome 21. DYRK1A contains a nuclear targeting signal sequence, a protein kinase domain, a leucine zipper motif, and a highly conservative 13-consecutive-histidine repeat. Alternative splicing DYRK 1 A generates several transcript variants differing from each other either in either the 5' untranslated region or in the 3' coding region resulting in at least five different isoforms.

[0100] DYRKIA possesses catalytic activity that is regulated by autophosphorylation of a tyrosine residue (¥321) which results in constitutively active serine / threonine kinase activity. Since DYRK 1 A is constitutively active, its activity is dosage dependent. Thus, both elevated levels and depressed levels of DYRKIA (relative to wild-type levels) have been shown to lead to neurological impairment.

[0101] DYRKIA displays a broad substrate spectrum (e.g., broad range of targets) including splicing factors, synaptic proteins, and transcription factors. It is ubiquitously expressed in all mammalian tissues and cells, although at different levels, with particularly high levels in embryonic and adult brain tissues. The human DYRKI A gene is a candidate gene to treat several Down syndrome characteristics, including intellectual impairment and Alzheimer’s disease associated with Down syndrome, due to its localization in the Down syndrome critical region on chromosome 21 and its role in brain function. Notably, Drosophila with deleterious mutations in the ortholog of DYRKIA (“Minibrain”) have a reduced number of neurons in their central nervous system. Likewise, mice heterozygous for a disrupted allele of the Dyrkla gene exhibit decreased viability, behavioral alterations, and delayed growth. Fotaki, et al., Mol Cell Biol., 22(18): 6636- 6647 (2014).

[0102] The identification of hundreds of genes deregulated by DYRKIA overexpression and numerous cytosolic, cytoskeletal and nuclear proteins, including transcription factors, phosphorylated by DYRKIA, indicates that DYRKIA over express! on is central for the deregulation of multiple pathways in the developing and aging brain of individuals with Down syndrome. Identifying DYRKIA cell signaling or transduction pathways can lead to a better understanding of how DYRKIA overexpression (or under expression) leads to the various disease states in which it is known to be involved. Specifically, DYRK1A is known to be active in activated PI3K / Akt signaling, a pathway largely involved in neuronal development, growth, and survival. DYRK1A is also known to be active in ASK1 / JNK1 activity and inhibitors of DYRK1A may induce neuronal death and apoptosis. DYRK1A is also known to phosphorylate p53 during embryonic brain development, and inhibitors of DYRK1A can prevent neuronal proliferation alteration. DYRK1A also phosphorylates synaptic proteins Amph 1, Dynamin 1, and Synaptojamn, which are involved in the regulation of endocytosis and inhibitors of DYRK1A can retain synaptic plasticity’ through preventing alteration of the number, size, and morphology of dendritic spines. DYRK1A also phosphorylates inhibit presenilm 1, the catalytic sub-unit of y- secretase. Ryu, et al., J Neurochem., 115(3): 574-84 (2010).

[0103] DYRK1A over expression leads to structural and functional alterations including intellectual disability’ and dementia, e.g., Alzheimer’s disease. In particular, genes involved in learning disorders, synaptic flexibility’ changes, memory loss, and abnormal cell cycles, result in neuropathological symptoms similar to dementia associated with Alzheimer’s disease. DYRK1A can also affect the proliferation and differentiation of neuronal progenitors, thus influencing neurogenesis and brain growth. It can also affect neurotransmission and dendritic spine formation through its interaction with synaptic proteins and the cytoskeleton.

[0104] One potential source of treatment are inhibitors of DYRK1 A, Inhibitors that can normalize DYRK1A levels in Down syndrome may improve synaptic plasticity' and delay the onset of Alzheimer’s disease pathology, including tau hyperphosphorylation. Therefore, inhibiting DYRK1 A activity in individuals with Down syndrome might counteract the phenotypic effects of its overexpression and is a potential avenue for the treatment of such developmental defects and prevention and / or mitigation of age-associated neurodegeneration, including Alzheimer’s disease associated with Down syndrome. Studies have shown that inhibition of overexpressed DYRK1 A resulted in normal DYRK1 A levels and been found to improve cognitive and behavioral deficits in transgenic models. See, e.g., Stringer, et al.. Mol Genet Genomic Med, 5, 451 -465 (2017) and Feki and Hibaoui, Brain Sci, 8, 187 (2018). However, despite promising results there is considerable variation across studies in terms of outcomes. Discrepancies were attributed to differences in model, dose, route of administration, the composition of the inhibitor, and timing of administration. Epigall ocatechin gallate (EGCG) is the primary flavonoid of green tea and has been investigated for its therapeutic effects, which include anti- oxi dative, anti-inflammatory, anticancer, anti -infective and neuroprotective activity. See, Bhat, et al. Towards the discovery of druglike epigallocatechin gallate analogs as Hsp90 inhibitors, Bioorg Med Chem Lett, 24, 2263-2266 (2014). EGCG is a non- ATP competitive DYRK1A inhibitor and studies have shown that green tea extract comprising 41% EGCG were able to alleviate cognitive decline seen in transgenic mice over expressing DYRK1A. ECGC has also been shown to improve memory recognition and working memory. However, ECGC is not significantly selective and has numerous off-target effects, thus reducing its potential long-term use.

[0105] SM07883 is an orally bioavailable (%F 92% in mice, 109% in monkey), BBB penetrant, DYRK1A inhibitor (IC50 1.6 nM) that also show's potent inhibition for DYRK1B, CLK4, and GSK3P in kinase assays. It was found to protect against tau hyperphosphorylation in mouse models. SM07883 wv.s tested for treatment of Alzheimer’s disease in a phase 1 study in Australia (ACTRN12619000327189). However, according to the study description page at www.anzctr.org.au, the date of last data collection was in May 2019 and no results have been published for the trial.

[0106] This disclosure provides compounds of Formula (I), (II), (III), (IV), (V), or (VI), or any subformulae thereof, and pharmaceutically acceptable salts thereof, that inhibit Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A). These chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) DYRK1A activation contributes to the pathology and / or symptoms and / or progression of the condition, disease or disorder (e.g., a neurological disorder in a subject (e.g., a human). This disclosure also provides compositions containing the same as well as methods of using and making the same.

[0107] Formulae (I), (II), (HI), and (IV) Compounds

[0108] Some embodiments provide a compound of Formula (I): (I), or a pharmaceutically acceptable salt thereof, wherein: each represents a single or a double bond, such that the bicyclic ring system comprising Y1, Y2, Y3, and Y4is an aromatic bicyclic ring system where (i) Y1is CR3, Y2is N, Y3is CR4, and Y4is CR3or N; (ii) Y1is S, Y2is C, Y3is CR4or N, and Y4is CR3; or (iii) Y1is N, Y2is N, Y3is CR4, and Y4is CR3; L is selected from , , and , wherein * denotes the point of attachment to Ring A, Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene, Z’ is selected from -NR1-, -S(O)-, -S(O)2-, C1-4alkylene, -NR1-C1-4alkylene, -S(O)-C1-4alkylene, and -S(O)2-C1-4alkylene; wherein each C1-4alkylene is optionally substituted with one or more halogen; Ring B is selected from (a), (b) and (c): (a) , X1is selected from N, CH, and CR5; (b) , X2is selected from S and NR7; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system, provided that when Ring B is (a), Y1is CR3, Y2is N, Y3is CR4, and Y4is N, then p is 0; R1is independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4haloalkyl, and –C(O)C3-6cycloalkyl optionally substituted with one or more halogen; R2is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, - OR10, -SR10, -N(R10)2, NO2, and -CN; R3and R4are each independently selected at each occurrence from hydrogen, halogen, C1- 4 alkyl, and C1-4 haloalkyl; RAis selected from halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, -S(O)2C1-4alkyl, C3-6cycloalkyl, and 3- to 6-membered heterocycloalkyl, provided that: when Y1is CR3, Y2is N, and Y4is CR3, or when Y1is CR3, Y2is N, and Y4is N, then RAis further selected from -OR11, when Y1is CR3, Y2is N, Y3is CH, Ring B is (a), p is 0, X1is N, and Ring A is 1- fluoro-1-tetrahydropyranyl, then RAis further selected from hydrogen, and when Y1is S, Y2is C, and X1is N, then RAis further selected from hydrogen; Ring A is selected from: cyclopropyl substituted with one or more C1-6alkyl or -CN, C3-6carbocycle substituted with one or more halogen, 3- to 6-membered heterocycle substituted with one or more halogen, C5-6spirocyclic carbocycle, and 5- to 6-membered spirocyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; C7-12carbocycle and 7- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-

[0109] 6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl, provided that when Ring B is 5 selected from (b), then Ring A is not chromane; provided that when one or more of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) apply, then Ring A is further selected from C4-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl: (i) Ring B is (a) and RAis selected from halogen, C1-4 haloalkyl, C3-6 cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4 alkyl or C1-4 haloalkyl; (vi) Ring B is (c); and (vii) Y1is CR3, Y2is N, Y3is CR3, and Y4is N; (viii) Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c); provided that when Ring B is (a), X1is CH, RAis methyl, Y1is CR3, and Y2is N, then Ring A is further selected from tetrahydrofuranyl substituted with methyl; R5is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -N(R13)S(O)2(R13), -S(O)2R13, -S(O)2N(R13)2, -NO2, and -CN, provided that when RAis -OR11, then R5is not -OR13; R6is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)OR14, -OC(O)R14, -C(O)N(R14)2, 30 -N(R14)C(O)R14, -N(R14)S(O)2(R14), -S(O)2R14, -S(O)2N(R14)2, -NO2, =O, and -CN; 31 R8is independently selected at each occurrence from halogen, C2-4alkyl, C1-4haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)OR14, -OC(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2(R14), -S(O)2R14, -S(O)2N(R14)2, -NO2, =O, and -CN; R7and R9are each independently selected from hydrogen, C1-4 alkyl, and C1-4 haloalkyl; R10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen, C1-6alkyl, C1-6haloalkyl, and C3-6cycloalkyl; m is selected from 0 and 1; p is selected from 0, 1, and 2; q is selected from 0, 1, and 2; and r is selected from 0, 1, and 2. In some embodiments, when a moiety or a list of moieties is optionally substituted or substituted with one or more substituents, the one or more substituents is 1-4 substituents (e.g., 1- 3, 2-4, 2-3, 1-2, 3-4, 1, 2, 3, or 4 substituents). For example, the one or more substituents is 1-4 substituents. For example, the one or more substituents is one substituent. In some embodiments, for the compound of Formula (I), Y1is CR3, Y2is N, Y3is CR4, and Y4is CR3or N. In some embodiments, Y1is CR3, Y2is N, Y3is CR4, and Y4is N. In some embodiments, Y1is CR3, Y2is N, Y3is CR4, and Y4is CR3. In some embodiments, Y1is S, Y2is C, Y3is CR4or N, and Y4is CR3. In some embodiments, Y1is S, Y2is C, Y3is CR4, and Y4is CR3. In some embodiments, Y1is S, Y2is C, Y3is N, and Y4is CR3. In some embodiments, Y1is N, Y2is N, Y3is CR4, and Y4is CR3. In some embodiments, for the compound of Formula (I), Y1is CH, Y2is N, Y3is CH, and Y4is CH or N. In some embodiments, Y1is CH, Y2is N, Y3is CH, and Y4is N. In some embodiments, Y1is CH, Y2is N, Y3is CH, and Y4is CH. In some embodiments, Y1is S, Y2is C, Y3is CH or N, and Y4is CH. In some embodiments, Y1is S, Y2is C, Y3is CH, and Y4is CH. In some embodiments, Y1is S, Y2is C, Y3is N, and Y4is CH. In some embodiments, Y1is N, Y2is N, Y3is CH, and Y4is CH. In some embodiments, the compound is of Formula (IA):

[0110] (IA), or a pharmaceutically acceptable salt thereof; wherein Y3is CH or N, and Y4is CH or N. In some embodiments, Y3is CH, and Y4is CH. In some embodiments, the compound is of Formula (IB): (IB), or a pharmaceutically acceptable salt thereof; the compound is of Formula (IC); wherein Y3is CH or N, and Y4is CH or N. (IC), or a pharmaceutically acceptable salt thereof; wherein Y3is CH or N. In some embodiments, the compound is of Formula (ID): 10 (ID), or a pharmaceutically acceptable salt thereof; wherein Y4is CH or N. 33 In some embodiments, for the compound of Formula (I), (IA), (IB), (IC), or (ID), L is or . In some embodiments, L is or . In some embodiments, L is or . In some embodiments, for the compound of Formula (I), (IA), (IB), (IC), or (ID), Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene, wherein each C1-4alkylene is optionally substituted with one or more halogen. In some embodiments, Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene, wherein each C1-4alkylene is optionally substituted with one or more halogen; and R1is independently selected at each occurrence from hydrogen, C1-4 alkyl, and C1-4 haloalkyl. In some embodiments, Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene, wherein each C1-4alkylene is optionally substituted with one or more halogen; and R1is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene, wherein each C1-4alkylene is optionally substituted with one or more halogen; and each R1is hydrogen. In some embodiments, Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene; and each R1is hydrogen. In some embodiments, for the compound of Formula (I), (IA), (IB), (IC), or (ID), Z is selected from -O-, -NR1-, C1-2alkylene, -O-C1-2alkylene, and -NR1-C1-2alkylene, wherein each C1- 2alkylene is optionally substituted with one or more halogen; and R1is independently selected at each occurrence from hydrogen and C1-4 alkyl. In some embodiments, Z is selected from -O-, -NR1-, C1-2alkylene, -O-C1-2alkylene, and -NR1-C1-2alkylene, wherein each C1-2alkylene is optionally substituted with one or more halogen; and each R1is hydrogen. In some embodiments, Z is selected from -O-, -NR1-, C1-2alkylene, -O-C1-2alkylene, and -NR1-C1-2alkylene; and each R1is hydrogen In some embodiments, for the compound of Formula (I), (IA), (IB), (IC), or (ID), Z’ is selected from -NR1-, -S(O)-, -S(O)2-, C1-4alkylene, -NR1-C1-4alkylene, -S(O)-C1-4alkylene, and - S(O)2-C1-4alkylene; wherein each C1-4alkylene is optionally substituted with one or more halogen; and R1is independently selected at each occurrene from hydrogen and C1-4 alkyl. In some embodiments, Z’ is selected from -NR1-, -S(O)-, -S(O)2-, C1-4alkylene, -NR1-C1-4alkylene, -S(O)- C1-4alkylene, and -S(O)2-C1-4alkylene; and each R1is hydrogen. In some embodiments, for the compound of Formula (I), (IA), (IB), (IC), or (ID), Z’ is selected from -S(O)2-, C1-4alkylene, and -S(O)2-C1-4alkylene; wherein each C1-4alkylene is optionally substituted with one or more halogen. In some embodiments, Z’ is selected from -S(O)2- , C1-4alkylene, and -S(O)2-C1-4alkylene. In some embodiments, Z’ is C1-4alkylene, optionally substituted with one or more halogen. In some embodiments, Z’ is C1-4alkylene. In some embodiments, Z’ is C1-4alkylene, optionally substituted with one or more halogen; and R1is hydrogen. In some embodiments, Z’ is C1-4alkylene; and R1is hydrogen. In some embodiments, for the compound of Formula (I), (IA), (IB), (IC), or (ID), Z’ is selected from -NR1-, -S(O)-, -S(O)2-, C1-2alkylene, -NR1-C1-2alkylene, -S(O)-C1-2alkylene, and - S(O)2-C1-2alkylene; wherein each C1-2alkylene is optionally substituted with one or more halogen; and each R1is hydrogen. In some embodiments, Z’ is selected from -S(O)2-, C1-2alkylene, and - S(O)2-C1-2alkylene; wherein each C1-2alkylene is optionally substituted with one or more halogen, and R1is hydrogen. In some embodiments, Z’ is C1-2alkylene optionally substituted with one or more halogen. In some embodiments, Z’ is C1-2alkylene. In some embodiments, Z’ is C1-2alkylene optionally substituted with one or more halogen; and R1is hydrogen. In some embodiments, Z’ is C1-2alkylene; and R1is hydrogen. In some embodiments, for the compound of Formula (I), (IA), (IB), (IC), or (ID), Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene; and Z’ is selected from -S(O)2-, C1-4alkylene, and -S(O)2-C1-4alkylene; wherein each C1-4alkylene is optionally substituted with one or more halogen; and R1is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene; and Z’ is selected from -NR1-, -S(O)-, -S(O)2- , C1-4alkylene, -NR1-C1-2alkylene, -S(O)-C1-4alkylene, and -S(O)2-C1-4alkylene, wherein each C1-4alkylene is optionally substituted with one or more halogen. In some embodiments, Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene; and Z’ is selected from - NR1-, -S(O)-, -S(O)2-, C1-4alkylene, -NR1-C1-4alkylene, -S(O)-C1-4alkylene, and -S(O)2-C1- 4alkylene, wherein each C1-4alkylene is optionally substituted with one or more halogen; and R1is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene; In some embodiments, Z’ is selected from -S(O)2-, C1-4alkylene, and -S(O)2-C1-4alkylene; wherein each C1-4alkylene is optionally substituted with one or more halogen; and R1is independently selected at each occurrence from hydrogen and C1-4 alkyl. In some embodiments, Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene; Z’ is C1- 4alkylene, optionally substituted with one or more halogen; wherein each C1-4alkylene is optionally substituted with one or more halogen; and each R1is hydrogen. In some embodiments, Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene; Z’ is C1-4alkylene; and each R1is hydrogen. In some embodiments, for the compound of Formula (I), (IA), (IB), (IC), or (ID), Z is selected from -O-, -NR1-, C1-2alkylene, -O-C1-2alkylene, and -NR1-C1-2alkylene; and Z’ is selected from -NR1-, -S(O)-, -S(O)2-, C1-2alkylene, -NR1-C1-2alkylene, -S(O)-C1-2alkylene, and -S(O)2-C1- 2alkylene, wherein each C1-2alkylene is optionally substituted with one or more halogen; and R1is independently selected at each occurrence from hydrogen, C1-4 alkyl, and C1-4 haloalkyl. In some embodiments, Z is selected from -O-, -NR1-, C1-2alkylene, -O-C1-2alkylene, and -NR1-C1-2alkylene; In some embodiments, Z’ is selected from -S(O)2-, C1-2alkylene, and -S(O)2-C1-2alkylene; wherein each C1-2alkylene is optionally substituted with one or more halogen; and R1is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, Z is selected from -O-, -NR1-, C1-2alkylene, -O-C1-2alkylene, and -NR1-C1-2alkylene; Z’ is C1- 2alkylene, optionally substituted with one or more halogen; wherein each C1-2alkylene is optionally substituted with one or more halogen; and each R1is hydrogen. In some embodiments, Z is selected from -O-, -NR1-, C1-2alkylene, -O-C1-2alkylene, and -NR1-C1-2alkylene; Z’ is C1-4alkylene; and each R1is hydrogen. In some embodiments, Z is selected from -O-, -NH-, -CH2-, -O-CH2-, and - NH-CH2-; and Z’ is -CH2-. In some embodiments, for the compound of Formula (I), (IA), (IB), (IC), or (ID), L is selected from , , , , , , , , , , , , , and . In some embodiments, for the compound of Formula (I), (IA), (IB), (IC), or (ID), L is . In some embodiments, L is ; Z is selected from -O-, -NR1-, C1- 4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene, wherein each C1-4alkylene is optionally substituted with 1-2 halogen; and R1is independently selected at each occurrence from hydrogen, C1-4 alkyl, and C1-4haloalkyl. In some embodiments, L is ; Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene, wherein each C1-4alkylene is optionally substituted with 1-2 halogen; and R1is independently selected at each occurrence fromhydrogen and C1-4alkyl. In some embodiments, L is ; Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene; and R1is independently selected at each occurrence from hydrogen and C1-4 alkyl. In some embodiments, L is ; Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene; and each R1is hydrogen. In some embodiments, L is ; Z is selected from -O-, -NR1-, C1-2alkylene, -O-C1-2alkylene, and -NR1-C1-2alkylene, wherein each C1-2alkylene is optionally substituted with 1-2 halogen; and R1is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, L is ; Z is selected from -O-, -NR1-, C1-2alkylene, -O-C1- 2alkylene, and -NR1-C1 lk l h i h C lk l i tionally substituted with 1-2 halogen; and each R1is hydrogen. In some embodiments, L is selected from, , , , , , , and . In some embodiments, for the compound of Formula (I), (IA), (IB), (IC), or (ID), L is . In some embodiments, L is ; Z’ is selected from C1-4alkylene optionally substituted with 1-2 halogen; and R1is selected from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, L is ; Z’ is selected from C1-4alkylene optionally substituted with 1-2 halogen; and R1is hydrogen. In some embodiments, L is ; Z’ is selected from C1- 4alkylene; and R1is hydrogen. In some embodiments, L is . In some embodiments, for the compound of Formula (I), (IA), (IB), (IC), or (ID), L is . In some embodiments, L is ; and R1is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, L is ; and R1is independently selected at each occurrence from hydrogen, C1-4 alkyl, C1-4 haloalkyl. In some embodiments, L is ; and R1is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, L is selected from , , , , , and . In some embodiments, L is . Some embodiments provide a compound of Formula (II): (II); or a pharmaceutically acceptable salt thereof, wherein: each represents a single or a double bond, such that the bicyclic ring system comprising Y1, Y2, and Y3is an aromatic bicyclic ring system where (i) Y1is CR3and Y2is N, or (ii) Y1is S and Y2is C; Y3is selected from N and CR4; Ring B is selected from (a), (b) and (c): (a) , X1is selected from N, CH, and CR5; (b) , X2is selected from S and NR7; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system; R1is selected from hydrogen, C1-4 alkyl, and –C(O)C3-6 cycloalkyl optionally substituted with one or more halogen; R2is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, - OR10, -SR10, -N(R10)2, NO2, and -CN; R3and R4are each independently selected from hydrogen, halogen, C1-4 alkyl, and C1- 4 haloalkyl; RAis selected from halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, -S(O)2C1-4alkyl, C3-6cycloalkyl, and 3- to 6-membered heterocycloalkyl, provided that: when Y1is CR3and Y2is N, then RAis further selected from -OR11, when Y1is CR3, Y2is N, Y3is CH, Ring B is (a), p is 0, X1is N, and Ring A is 1-fluoro- 1-tetrahydropyranyl, then RAis further selected from hydrogen, and when Y1is S, Y2is C, and X1is N, then RAis further selected from hydrogen; Ring A is selected from: C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is substituted with one or more halogen, and is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, - OC(O)N(R12)2,-C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, - N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6- membered heterocycle optionally substituted with one or more C1-4 alkyl; C7-12 carbocycle and 7- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1- 6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, - C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), - S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl, provided that when Ring B is selected from (b), then Ring A is not chromane; provided that when one or more of (i), (ii), (ii), (iv), and (v) apply, then Ring A is further selected from C4-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl: (i) Ring B is (a) and RAis selected from halogen, C1-4 haloalkyl, C3-6 cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4alkyl; and (vi) Ring B is (c); provided that when Ring B is (a), X1 is CH, RAis methyl, Y1is CR3, and Y2is N, then Ring A is further selected from tetrahydrofuranyl substituted with methyl; R5is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -N(R13)S(O)2(R13), -S(O)2R13, -S(O)2N(R13)2, -NO2, and -CN, provided that when RAis -OR11, then R5is not -OR13; R6is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)OR14, -OC(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2(R14), -S(O)2R14, -S(O)2N(R14)2, -NO2, =O, and -CN; R8is independently selected at each occurrence from halogen, C2-4 alkyl, C1-4 haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)OR14, -OC(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2(R14), -S(O)2R14, -S(O)2N(R14)2, -NO2, =O, and -CN; R7and R9are each independently selected from hydrogen, C1-4alkyl, and C1-4haloalkyl; R10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen, C1-6alkyl, C1-6haloalkyl, and C3-6cycloalkyl; m is selected from 0, 1, and 2; p is selected from 0, 1, and 2; q is selected from 0, 1, and 2; and r is selected from 0, 1, and 2. In some embodiments for the compound of Formula (II), Y1is CR3; Y2is N; and Y3is N. In some embodiments, Y1is CR3; Y2is N; and Y3is CR4. In some embodiments, Y1is CR3; Y2is N; and Y3is CH. In some embodiments, Y1is CR3, Y2is N, and Y4is CR3. In some embodiments, Y1is CR3; Y2is N; Y3is N; and Ring B is (a). In some embodiments, Y1is CR3; Y2is N; Y3is CR4; and Ring B is (a). In some embodiments, Y1is S and Y2is C. In some embodiments, Y1is S; Y2is C; and Y3is N. In some embodiments, Y1is S; Y2is C; and Y3is CR4. In some embodiments, Y1is S; Y2is C; and Y3is CH. In some embodiments, Y3is N. In some embodiments, Y3is CR4; and R4is selected from hydrogen and halogen. In some embodiments, Y3is CH.In some embodiments, Y1is S; Y2is C; and X1is N. In some embodiments, Y1is S; Y2is C; and RAis selected from C1-4alkyl. In some embodiments, Y1is CR3, Y2is N, Y3is CR4, and Y4is N. In some embodiments, Y1is CR3, Y2is N, Y3is CH, and Y4is N. In some embodiments, Y1is CR3, Y2is N, Y3is CR4, and Y4is N. In some embodiments, Y1is CH, Y2is N, Y3is CR4, and Y4is N; and R4is selected from hydrogen, halogen, and C1-4 alkyl. In some embodiments, the compound is of Formula (IIA): (IIA), or a pharmaceutically acceptable salt thereof; wherein Y3is CH or N, and Y4is CH or N. In some embodiments, the compound is of Formula (IIA-1): (IIA-1), or a pharmaceutically acceptable salt thereof; wherein Y3is CH or N.

[0111] In some embodiments, the compound is of Formula (IIB): (IIB), or a pharmaceutically acceptable salt thereof; wherein Y3is CH or N, and Y4is CH or N. In some embodiments, R3is selected from selected from hydrogen, halogen, and C1-4 alkyl. In some embodiments, the compound is of Formula (IIB-1): (IIB-1), or a pharmaceutically acceptable salt thereof; wherein Y3is CH or N. In some embodiments, R3is selected from selected from hydrogen, halogen, and C1-4 alkyl. In some embodiments, the compound is of Formula (IIC): (IIC), or a pharmaceutically acceptable salt thereof; wherein Y3is CH or N. In some embodiments, the compound is of Formula (IIC-1): (IIC-1), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IID): (IID), or a pharmaceutically acceptable salt thereof; wherein Y4is CH or N. In some embodiments, the compound is of Formula (IID-1): (IID-1), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), Formula (II), (IIA), (IIA-1), (IIB), (IIB-1), (IIC), (IIC-1), (IID), or (IID-1), each R3is selected from selected from hydrogen, halogen, and C1-4 alkyl. In some embodiments, each R3is selected from selected from hydrogen and halogen. In some embodiments, R3is hydrogen. In some embodiments, R3is halogen. In some embodiments, R3is fluoro. In some embodiments, R3is chloro. In some embodiments, R3is C1-4alkyl. In some embodiments, R3is methyl. In some embodiments, R3is C1-4 haloalkyl. In some embodiments, R3is trifluoromethyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), Formula (II), (IIA), (IIA-1), (IIB), (IIB-1), (IIC), (IIC-1), (IID), or (IID-1), R1is independently selected at each occurrence from hydrogen, C1-4 alkyl, and C1-4 haloalkyl. In some embodiments, R1is independently selected at each occurrence from hydrogen and C1-4 alkyl. R1is independently selected at each occurrence from hydrogen, -CH3, -CF3, -CH2CH3, , and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), Formula (II), (IIA), (IIA-1), (IIB), (IIB-1), (IIC), (IIC-1), (IID), or (IID-1), R1is selected from hydrogen, - CH3, -CH2CH3, d I b di R1is hydrogen In some embodiments, R1is C1-4alkyl. In some embodiments, R1is –C(O)C3-6cycloalkyl optionally substituted with one or more halogen. In some embodiments, R1is –C(O)C3-6 cycloalkyl substituted with one or more fluoro. In some embodiments, R1is -CH3. In some embodiments, R1is -CH2CH3. In some embodiments, R1is . In some embodiments, R1is . In some embodiments, each R1is hydrogen. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), Formula (II), (IIA), (IIA-1), (IIB), (IIB-1), (IIC), (IIC-1), (IID), or (IID-1), R2is independently selected at each occurrence from halogen and C1-4alkyl. In some embodiments, R2is halogen. In some embodiments, R2is C1-4alkyl. In some embodiments, R2is C1-4haloalkyl. In some embodiments, R2is -OR10. In some embodiments, R2is -SR10. In some embodiments, R2is -N(R10)2. In some embodiments, R2is NO2. In some embodiments, R2is –CN. In some embodiments, R2is independently selected at each occurrence from C1-4 alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), Formula (II), (IIA), (IIA-1), (IIB), (IIB-1), (IIC), (IIC-1), (IID), or (IID-1), m is 0 or 1. . In some embodiments, m is 1 or 2. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), Formula (II), (IIA), (IIA-1), (IIB), (IIB-1), (IIC), (IIC-1), (IID), or (IID-1), R3and R4are each independently selected at each occurrence from hydrogen, halogen, and C1-4 alkyl. In some embodiments, R3and R4are each independently selected at each occurrence from hydrogen and halogen. In some embodiments, R3and R4are each independently selected at each occurrence from hydrogen and C1-4 alkyl. In some embodiments, each R3is hydrogen. In some embodiments, each R4is hydrogen. In some embodiments, the compound is of Formula (IIA-2): (IIA-2), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IIB-2): (IIB-2), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IIC-2): (IIC-2), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IID-2): (IID-2), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of Formula (IIE-2): (IIE-2), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (a), (b) and (c): (a) , X1is selected from N, CH, and CR5; (b) , X2is selected from S and NR7; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system, provided that when Ring B is (a), Y1is CR3, Y2is N, Y3is CR4, and Y4is N, then p is 0. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (a) and (c): (a) , X1is selected from N, CH, and CR5; (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from: (b) , and X2is selected from S and NR7. In some embodiments, Ring B is selected from: (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system,. provided that when Ring B is (a), Y1is CR3, Y2is N, Y3is CR4, and Y4is N, then p is 0. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (a) and (c): (a) , X1is selected from N, CH, and CH; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; wherein: RAis selected from halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, C3-6cycloalkyl, and 3- to 6-membered heterocycloalkyl; and when Y1is CR3and Y2is N, then RAis further selected from -OR11; R11is selected from hydrogen, C1-4alkyl, C1-4haloalkyl, and C3-6cycloalkyl; R5is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, and -CN; R8is independently selected at each occurrence from halogen, C2-4 alkyl, C1-4 haloalkyl, and -CN; R9is selected from hydrogen and C1-4 alkyl; p is selected from 0 and 1; and r is selected from 0 and 1. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (a) and (c): (a) , X1is selected from N, CH, and CR5; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; wherein: RAis selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, , , , , and ; and when Y1is CR3and Y2is N, then RAis further selected from - OH, -OCH3, and ; R5is selected at each occurrence from -F, -Cl, and -CH3; R9is selected from hydrogen and -CH3; p is selected from 0 and 1; and r is 0. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from: (a) , and X1is selected from N, CH, and CR5; provided that when Y1is CR3, Y2is N, Y3is CR4, and Y4is N, then p is 0, In some embodiments, X1is selected from N and CH. In some embodiments, X1is N. In some embodiment, X1is CH. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), RAis selected from halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, -N(R11)2, -SR11, - N(R11)C(O)R11, -CN, -S(O)2C1-4 alkyl, C3-6 cycloalkyl, and 3- to 6-membered heterocycloalkyl, provided that: when Y1is CR3, Y2is N, and Y4is CR3, or when Y1is CR3, Y2is N, and Y4is N, then RAis further selected from -OR11, when Y1is CR3, Y2is N, Y3is CH, Ring B is (a), p is 0, X1is N, and Ring A is 1- fluoro-1-tetrahydropyranyl, then RAis further selected from hydrogen, and when Y1is S, Y2is C, and X1is N, then RAis further selected from hydrogen. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), RAis selected from halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, -S(O)2C1-4alkyl, C3-6cycloalkyl, and 3- to 6-membered heterocycloalkyl, provided that: when Y1is CR3, Y2is N, and Y4is CR3, or when Y1is CR3, Y2is N, and Y4is N, then RAis further selected from -OR11; and wherein R11is independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4 haloalkyl; and C3-6 cycloalkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), RAis selected from halogen, C1-4alkyl, C1-4haloalkyl, C1-4hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, C3-5cycloalkyl, and 5- to 6-membered heterocycloalkyl, provided that: when Y1is CR3, Y2is N, and Y4is CR3, or when Y1is CR3, Y2is N, and Y4is N, then RAis further selected from -OR11; and wherein R11is independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4 haloalkyl, and C3-6 cycloalkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), RAis selected from halogen, C1-4alkyl, C1-4haloalkyl, C1-4hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, C3-6cycloalkyl, and 3- to 6-membered heterocycloalkyl; and Y1is CR3, Y2 is N, and Y4is CR3or when Y1is CR3, Y2is N, and Y4is N, then RAis further selected from - OR11; R11is selected from hydrogen, C1-4 alkyl, C1-4 haloalkyl, and C3-6 cycloalkyl. In some embodiments, RAis selected from halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, C3-6 cycloalkyl, and 3- to 6-membered heterocycloalkyl; and when Y1is CR3and Y2is N, then RAis further selected from -OR11; R11is selected from hydrogen, C1-4alkyl, C1-4haloalkyl, and C3-6cycloalkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), RAis halogen. In some embodiments, RAis C1-4alkyl. In some embodiments, RAis methyl. In some embodiments, RAis ethyl. In some embodiments, RAis C1-4 haloalkyl. In some embodiments, RAis C1-4 hydroxyalkyl. In some embodiments, RAis -N(R11)2. In some embodiments, RAis -SR11. In some embodiments, RAis -N(R11)C(O)R11. In some embodiments, RAis -CN. In some embodiments, RAis C3-6 cycloalkyl. In some embodiments, RAis 3- to 6-membered heterocycloalkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Y1is CR3and Y2is N; and RAis further selected from -OR11, provided that when RAis -OR11, then R5is not -OR13. In some embodiments, Y1is CR3, Y2is N, and Y4is N, and RAis further selected from - OR11. In some embodiments, Y1is CR3, Y2is N, Y3is CH, Ring B is (a), p is 0, X1is N, and Ring A is 1-fluoro-1-tetrahydropyranyl; and RAis further selected from hydrogen. In some embodiments, Y1is S, Y2is C, and X1is N; and RAis further selected from hydrogen. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), RAis selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, , , , , and ; and when Y1is CR3and Y2is N, then RAis further selected from -OH, -OCH3, and . In some embodiments, RAis -F. In some embodiments, RAis -Cl. In some embodiments, RAis -CN. In some embodiments, RAis -NH2. In some embodiments, RAis -OH. In some embodiments, RAis -OCH3. In some embodiment, RAis . In some embodiments, RAis -CH3. In some embodiments, RAis -CF3. In some embodiments, RAis -CHF2. In some embodiments, RAis . In some embodiments, RAis . In some embodiments, RAis . In some embodiments, RAis . In some embodiments, RAis and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R5is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -OR13, -SR13, -N(R13)2, -C(O)OR13, -C(O)N(R13)2, -NO2, and -CN, provided that when RAis -OR11, then R5is not -OR13; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, R5is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -SR13, -N(R13)2, -C(O)OR13, -C(O)N(R13)2, -NO2, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4 haloalkyl. In some embodiments, R5is independently selected at each occurrence from halogen, C1-4 alkyl, C1- 4 haloalkyl, -OR13, -N(R13)2, and -CN, provided that when RAis -OR11, then R5is not -OR13; and R13is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, R5is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -N(R13)2, and -CN; and R13is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, R5is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, and -OR13, provided that when RAis -OR11, then R5is not -OR13; and R13is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, R5is independently selected at each occurrence from halogen, C1-4 alkyl, and C1- 4 haloalkyl. In some emb di R5i i d d l l d ach occurrence from halogen. In some embodiments, R5is independently selected at each occurrence from C1-4alkyl. In some embodiments, R5is independently selected at each occurrence from C1-4 haloalkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4 haloalkyl. In some embodiments, R13is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, each R13is hydrogen. In some embodiments, or the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (b) , and X2is selected from S and NR7. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), X2is S. In some embodiments, X2is NR7. In some embodiments, X2is S or NH. In some embodiments, X2is NH. In some embodiments, X2is S. In some embodiments, R7is selected from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, R7is selected from hydrogen, and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), q is 0 or 1. In some embodiments, q is 1. In some embodiments, q is 0. In some embodiments, q is 1 or 2. In some embodiments, q is 2. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R6is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)OR14, -OC(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2(R14), -S(O)2R14, -S(O)2N(R14)2, -NO2, and -CN; and R14is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, R6is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)OR14, -S(O)2N(R14)2, -NO2, and -CN; and R14is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4 haloalkyl. In some embodiments, R6is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -OR14, -SR14, -N(R14)2, and -CN; and R14is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, R6is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -OR14, and -N(R14)2, and R14is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, R6is independently selected at each occurrence from halogen, C1-4 alkyl, and C1-4haloalkyl. In some embodiments, R6is independently selected at each occurrence from halogen and C1-4alkyl. In some embodiments, R6is independently selected at each occurrence from halogen. In some embodiments, R6is independently selected at each occurrence from C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R6is halogen. In some embodiments, R6is C1-4 alkyl. In some embodiments, R6is C1-4 haloalkyl. In some embodiments, R6is -OR14. In some embodiments, R6is -SR14. In some embodiments, R6is -N(R14)2. In some embodiments, R6is -C(O)R14. In some embodiments, R6is -C(O)OR14. In some embodiments, R6is -OC(O)R14. In some embodiments, R6is -C(O)N(R14)2. In some embodiments, R6is -N(R14)C(O)R14. In some embodiments, R6is -N(R14)S(O)2(R14). In some embodiments, R6is -S(O)2R14. In some embodiments, R6is -S(O)2N(R14)2. In some embodiments, R6is -NO2. In some embodiments, R6is =O. In some embodiments, R6is -CN. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system. In some embodiments, Ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA),(IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), X3 isselected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan. In some embodiments, Ring B is an aromatic bicyclic ring system selected from benzothiazole, and benzofurazan. In some embodiments, Ring B is an aromatic bicyclic ring system selected from benzothiazole and benzimidazole. Ring B is an aromatic bicyclic ring system selected from benzimidazole and benzofurazan. In some embodiments, Ring B is a benzothiazole. In some embodiments, Ring B is abenzimidazole. In some embodiments, Ring B is a benzofurazan. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), X3is S. In some embodiments, X3is N. In some embodiments, X3is NH. In some embodiments, X4is O. In some embodiments, X4is CR9. In some embodiments, X3is S and X4is O. In some embodiments, X3is S and X4is CR9. In some embodiments, X3is N and X4is O. In some embodiments, X3is N and X4is CR9. In some embodiments, X3is NH and X4is O. In some embodiments, X3is NH and X4is CR9. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), r is 0 or 1. In some embodiments, r is 1. In some embodiments, r is 0. In some embodiments, r is 1 or 2. In some embodiments, r is 2. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R8is independently selected at each occurrence from halogen, C2-4 alkyl, C1-4 haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)OR14, -OC(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2(R14), - S(O)2R14, -S(O)2N(R14)2, -NO2, and -CN; R14is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, R8is independently selected at each occurrence from halogen, C2-4alkyl, C1-4haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)OR14, - C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2(R14), -S(O)2R14, -S(O)2N(R14)2, -NO2, and -CN; and R14is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4 haloalkyl. In some embodiments, R8is independently selected at each occurrence from halogen, C2-4 alkyl, C1- 4 haloalkyl, -OR14, -SR14, -N(R14)2, and -CN; and R14is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, R8is independently selected at each occurrence from halogen, C1-4haloalkyl, -OR14, -SR14, -N(R14)2, and -CN; and R14is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, R8 is independently selected at each occurrence from halogen, C2-4alkyl, C1-4haloalkyl, -OR14, and - N(R14)2; and R14is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, R8is independently selected at each occurrence from halogen, C1-4 haloalkyl, -OR14, and -N(R14)2, and R14is independently selected at each occurrence from hydrogen and C1- 4alkyl. In some embodiments, R8is independently selected at each occurrence from halogen, C2-4 alkyl, and C1-4haloalkyl. In some embodiments, R8is independently selected at each occurrence from halogen and C1-4haloalkyl. In some embodiments, R8is independently selected at each occurrence from halogen. In some embodiments, R8is independently selected at each occurrence from C2-4alkyl. In some embodiments, R8is independently selected at each occurrence from C1-4 haloalkyl. In some embodiments, R8is not methyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R9is selected from hydrogen, C1-4 alkyl, and C1-4 haloalkyl. In some embodiments, R9is selected from hydrogen, and C1-4alkyl. In some embodiments, R9is hydrogen. In some embodiments, R9is C1-4alkyl. . In some embodiments, R9is methyl. In some emboimdnets, R9is hydrogen. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), R5is independently selected at each occurrence from halogen and C1-4 alkyl. In some embodiments, R6and R8are each independently selected at each occurrence from halogen and C1-4 alkyl. In some embodiments, R7and R9are each independently selected from hydrogen, and C1-4 alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (a) and (c): (a) , X1is selected from N, CH, and CR5; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; wherein: RAis selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, , , , , and ; and when Y1is CR3and Y2is N, then RAis further selected from - OH, -OCH3, and ; R5is selected at each occurrence from -F, -Cl, and -CH3; R9is selected from hydrogen and -CH3; p is selected from 0 and 1; and r is 0; provided that when Ring B is (a), Y1is CR3, Y2is N, Y3is CR4, and Y4is N, then p is 0. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (a) and (c): (a) , X1is selected from N, CH, and CR5; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; wherein: RAis selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, , , , , and ; and when Y1is CR3and Y2is N, then RAis further selected from - OH, -OCH3, and ; R5is selected at each occurrence from -F, -Cl, and -CH3; R9is selected from hydrogen and -CH3; p is selected from 0 and 1; and r is 0; provided that when Ring B is (a), Y1is CR3, Y2is N, Y3is CR4, and Y4is N, then p is 0. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (a) and (c): (a) , X1is selected from N, CH, and CR5; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; wherein: RAis selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, , , , , and ; and when Y1is CR3and Y2is N, then RAis further selected from - OH, -OCH3, and ; R5is selected at each occurrence from -F, -Cl, and -CH3; R9is selected from hydrogen and -CH3; p is selected from 0 and 1; and r is 0; provided that when Ring B is (a), Y1is CR3, Y2is N, Y3is CR4, and Y4is N, then p is 0. In some embodiments, Y1is CR3and Y2is N, and RAis –OH. In some embodiments, Y1is CR3and Y2is N, and RAis -OCH3. In some embodiments, Y1is CR3and Y2is N, and RAis . In some embodiments, when RAis -OR11, then R5is not -OR13. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (a) ; RAis selected from halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, -N(R11)2, -N(R11)C(O)R11, -CN, C3-6 cycloalkyl, and 3- to 6-membered heterocycloalkyl, and when Y1is CR3and Y2is N, then RAis further selected from -OR11; R11is independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4haloalkyl, and C3-6cycloalkyl; p is 0 or 1, provided that when Y1is CR3, Y2is N, Y3is CR4, and Y4is N, then p is 0; X is selected from N, CH, and CR5; and R5is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl. In some embodiments, Ring B is selected from: (a) ; RAis selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, , , , , and ; and when Y1is CR3and Y2is N, then RAis further selected from -OH, -OCH3, and ; and X1is selected from N, CH, and CR5; R5 is selected from -F and -CH3; p is 0 or 1, provided that when Y1is CR3, Y2is N, Y3is CR4, and Y4is N, then p is 0. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from: , , , , , , , , , , , , , , , , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring H N O N B is . In some embodiments, Ring B is N . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (b) , and X2is selected from S and NR7; q is 0 or 1; R6is selected from halogen, C1-4 alkyl, and C1-4 haloalkyl; and R7is selected from hydrogen, C1-4 alkyl, and C1-4 haloalkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system; R8is selected from halogen, C2-4alkyl, and C1-4haloalkyl. R9is selected from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl.; and r is 0 or 1. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; R9is selected from hydrogen and -CH3; and r is 0. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is selected from: , , , and . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), at least one of the (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) applies: (i) Ring B is (a) and RAis selected from halogen, C1-4haloalkyl, C3-6cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4 alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4 alkyl or C1-4 haloalkyl; (vi) Ring B is (c); (vii) Y1is CR3, Y2is N, Y3is CR3, and Y4is N; and (viii) Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c). In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), Ring B is (a) and RAis selected from halogen, C1-4 haloalkyl, C3-6 cycloalkyl, -NR11, and -OR11. In some embodiments, Y1is S, Y2is C, Ring B is (a), and X1is N. In some embodiments, Y1is S, Y2is C, Ring B is (a), and RAis C1-4 alkyl. In some embodiments, Ring B is (a), and p is 1, 2, or 3. In some embodiments, R1is C1-4alkyl or C1-4haloalkyl. In some embodiments, Ring B is (c). In some embodiments, Y1is CR3, Y2is N, Y3is CR3, and Y4is N. In some embodiments, Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c). In some embodiments, one or more (e.g., 1-3 (e.g., 1-2 (e.g., 1))) of (i), (ii), (ii), (iv), and (v) apply: (vii) Ring B is (a) and RAis selected from halogen, C1-4 haloalkyl, C3-6 cycloalkyl, -NR11, and -OR11; (viii) Y1is S, Y2is C, Ring B is (a), and X1is N; (ix) Y1is S, Y2is C, Ring B is (a), and RAis C1-4alkyl; (x) Ring B is (a), and p is 1, 2, or 3; (xi) R1is C1-4alkyl; and (xii) Ring B is (c). In some embodiments, Ring B is: , wherein X3is selected from S and N, X4is selected from O and CR9, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; wherein: R8is independently selected at each occurrence from halogen, C2-4 alkyl, C1-4 haloalkyl, and -CN; R9is selected from hydrogen and C1-4alkyl; p is selected from 0 and 1; and r is selected from 0 and 1. In some embodiments, Ring B is , wherein X1is selected from N, CH, and CR5. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), when at least one of the (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) applies: (i) Ring B is (a) and RAis selected from halogen, C1-4haloalkyl, C3-6 cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4 alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4alkyl or C1-4haloalkyl; (vi) Ring B is (c); (vii) Y1is CR3, Y2is N, Y3is CR3, and Y4is N; and (viii) Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c); Ring A is selected from cyclopropyl substituted with one or more halogen, C1-6 alkyl, or -CN; C4-12 carbocycle; and 3- to 12-membered heterocycle; any of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, C1-6haloalkyl, and C3-6cycloalkyl; and provided that when Ring B is (a), X1 is CH, RAis methyl, Y1is CR3, and Y2is N, then Ring A is further selected from tetrahydrofuranyl substituted with methyl; and when Ring B is selected from (b), then Ring A is not chromane. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), when at least one of the (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) applies: (i) Ring B is (a) and RAis selected from halogen, C1-4haloalkyl, C3-6 cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4 alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4alkyl or C1-4haloalkyl; (vi) Ring B is (c); (vii) Y1is CR3, Y2is N, Y3is CR3, and Y4is N; and (viii) Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c); Ring A is selected from: cyclopropyl substituted with one or more halogen, C1-6 alkyl or -CN, C4-12 carbocycle, and 3- to 12-membered heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; and R12is independently selected at each occurrence from hydrogen and C1-6alkyl; provided that when Ring B is (a), X1is CH, RAis methyl, Y1is CR3, and Y2is N, then Ring A is further selected from tetrahydrofuranyl substituted with methyl; and when Ring B is selected from (b), then Ring A is not chromane. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), when at least one of the (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) applies: (i) Ring B is (a) and RAis selected from halogen, C1-4haloalkyl, C3-6cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4 alkyl or C1-4 haloalkyl; (vi) Ring B is (c); (vii) Y1is CR3, Y2is N, Y3is CR3, and Y4is N; and (viii) Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c); Ring A is selected from: cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, sulfolanyl, azetidinyl, pyrrolidinyl, piperidinyl, spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2-oxabicyclo[2.2.1]heptanyl, 8- oxabicyclo[3.2.1]octanyl, 1-Oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and phenyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), when at least one of the (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) applies: (ix) Ring B is (a) and RAis selected from halogen, C1-4 haloalkyl, C3- 6 cycloalkyl, -NR11, and -OR11; (x) Y1is S, Y2is C, Ring B is (a), and X1is N; (xi) Y1is S, Y2is C, Ring B is (a), and RAis C1-4alkyl; (xii) Ring B is (a), and p is 1, 2, or 3; (xiii) R1is C1-4 alkyl or C1-4 haloalkyl; (xiv) Ring B is (c); (xv) Y1is CR3, Y2is N, Y3is CR3, and Y4is N; and (xvi) Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c); and Ring A is selected from: cyclopropyl substituted with one or more -CH3or -CN, cyclobutyl, cyclohexyl, phenyl, oxepanyl, sulfolanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6- oxaspiro[2.5]octanyl, 2-Oxabicyclo[2.2.1]heptanyl, 8-Oxabicyclo[3.2.1]octanyl, 1- Oxaspiro[5.5]undecanyl, adamantanyl, 2-Azaspiro[3.3]heptanyl, and 1,9- dioxaspiro[5.5]undecanyl, each of which is optionally substituted with one or more substituents independently selected from: -F, -OH, -OCH3, -CH3, -CF3, =O, -CN, , , , , , , and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIB), (IIB-1), (IIB-2), (IIC), (IIC-1), (IIC-2), (IID), (IID-1), or (IID-2), m is selected from 0 and 1. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, p is selected from 0 and 1. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, q is selected from 0 and 1. In some embodiments, q is 0. In some embodiments, q is 1. In some embodiments, r is selected from 0 and 1. In some embodiments, r is 0. In some embodiments, r is 1. In some embodiments, the compound is of Formula (IIA-3): O A N HN R5p S Y3X1N RA(IIA-3), or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, the compound is of Formula (IIB-3): (IIB-3), or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, the compound is of Formula (IIB-3): (IIB-3), or a pharmaceutically acceptable salt thereof; wherein Ring A is C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is substituted with one or more halogen, and is optionally substituted with one or more substituents independently selected from: C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl. In some embodiments, the compound is of Formula (IIB-4): (IIB-4), or a pharmaceutically acceptable salt thereof, wherein X1is selected from N, CH, and CR5. In some embodiments, the compound is of Formula (IIC-3): (IIC-3),or a pharmaceutically acceptable salt thereof, wherein X1is selected from N, CH, and CR5. In some embodiments, the compound is of Formula (ID-3): (ID-3), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IIB-5): (IIB-5), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IIB-6) (IIB-6), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: cyclopropyl substituted with one or more C1-6 alkyl or -CN, C3-6 carbocycle substituted with one or more halogen, 3- to 6-membered heterocycle substituted with one or more halogen, C5-6 spirocyclic carbocycle, and 5- to 6-membered spirocyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from: C1-6 alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; C7-12 carbocycle and 7- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1- 6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl, provided that when Ring B is selected from (b), then Ring A is not chromane; provided that when one or more of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) apply, then Ring A is further selected from C4-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: C1-6 alkyl, C1- 6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl: (i) Ring B is (a) and RAis selected from halogen, C1-4haloalkyl, C3-6cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4 alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4alkyl or C1-4haloalkyl; (vi) Ring B is (c); and (vii) Y1is CR3, Y2is N, Y3is CR3, and Y4is N; (viii) Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c); provided that when Ring B is (a), X1 is CH, RAis methyl, Y1is CR3, and Y2is N, then Ring A is further selected from tetrahydrofuranyl substituted with methyl; and R12is independently selected at each occurrence from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 cycloalkyl. In some embodiments, In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB- 6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: C4-12 carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl, provided that when Ring B is selected from (b), then Ring A is not chromane; and R12is independently selected at each occurrence from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 cycloalkyl. In some embodiments, In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB- 6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: C4-12carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl, provided that when Ring B is selected from (b), then Ring A is not chromane; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, C1-6haloalkyl, and C3-6cycloalkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: C4-12 carbocycle and 3- to 12- membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; and R12is independently selected at each occurrence from hydrogen and C1-6alkyl, provided that when Ring B is selected from (b), then Ring A is not chromane. In some embodiments, Ring A is selected from: C4-12 carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1- 6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6-membered heterocycle optionally substituted with 1-4 C1-4 alkyl; and R12is independently selected at each occurrence from hydrogen and C1-6alkyl, provided that when Ring B is selected from (b), then Ring A is not chromane. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: C4-6 carbocycle and 3- to 6-membered heterocycle, each of which is substituted with one or more -F, and is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; 7- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN, provided that when Ring B is selected from (b), then Ring A is not chromane; and R12is independently selected at each occurrence from hydrogen and C1-6 alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: C4-6carbocycle and 3- to 6-membered heterocycle, each of which is substituted with one or more -F, and is optionally substituted with 1-4 substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6- membered heterocycle optionally substituted with one or more C1-4 alkyl; 7- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, provided that when Ring B is selected from (b), then Ring A is not chromane; and R12is independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is saturated C3-6 carbocycle or saturated 3- to 6- membered heterocycle, each of which is substituted with one or more halogen, and is optionally substituted with one or more substituents independently selected from: C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2,-C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl. In some embodiments, Ring A is saturated C3-6carbocycle or saturated 3- to 6-membered heterocycle comprising one O ring member, each of which is substituted with one or more halogen, and is optionally substituted with one or more substituents independently selected from: C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is C3-6 carbocycle substituted with one or more halogen, and optionally substituted with one or more substituents independently selected from: C1- 6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2,-C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6- membered heterocycle optionally substituted with one or more C1-4alkyl. In some embodiments, Ring A is C3-5carbocycle substituted with one -F, and optionally substituted with one or more substituents independently selected from: C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl. In some embodiments, Ring A is 5- to 6-membered heterocycle substituted with one -F, and optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2,-C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl. In some embodiments, Ring A is selected from: C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is substituted with one or more halogen, and is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2,-C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), the Ring A heterocycle comprises 1-4 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A heterocycle comprises 1-3 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A heterocycle comprises 1-2 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A heterocycle comprises 2-3 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A heterocycle comprises 1 heteroatom selected from O, N, and S. In some embodiments, the Ring A heterocycle comprises 2 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A heterocycle comprises 3 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A heterocycle comprises 4 heteroatoms independently selected from O, N, and S. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), the Ring A heterocycle comprises 1-4 heteroatoms independently selected from O and N. In some embodiments, the Ring A heterocycle comprises 1-3 heteroatoms independently selected from O and N. In some embodiments, the Ring A heterocycle comprises 1-2 heteroatoms independently selected from O and N. In some embodiments, the Ring A heterocycle comprises 2-3 heteroatoms independently selected from O and N. In some embodiments, the Ring A heterocycle comprises 1 heteroatom selected from O and N. In some embodiments, the Ring A heterocycle comprises 2 heteroatoms independently selected from O and N. In some embodiments, the Ring A heterocycle comprises 3 heteroatoms independently selected from O and N. In some embodiments, the Ring A heterocycle comprises 4 heteroatoms independently selected from O and N. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), the Ring A heterocycle comprises 4 N heteroatoms. In some embodiments, the Ring A heterocycle comprises 3 N heteroatoms. In some embodiments, the Ring A heterocycle comprises 3 N heteroatoms and 1 O heteroatom. In some embodiments, the Ring A heterocycle comprises 2 N heteroatoms and 1 O heteroatom. In some embodiments, the Ring A heterocycle comprises 2 N heteroatoms and 1 S heteroatom. In some embodiments, the Ring A heterocycle comprises 1 O heteroatom and 1 N heteroatom. In some embodiments, the Ring A heterocycle comprises 1 O heteroatom and 1 S heteroatom. In some embodiments, the Ring A heterocycle comprises 1 S heteroatom and 1 N heteroatom. In some embodiments, the Ring A heterocycle comprises 2 N heteroatoms. In some embodiments, the Ring A heterocycle comprises 1 heteroatom that is O. In some embodiments, the Ring A heterocycle comprises 1 heteroatom that is N. In some embodiments, the Ring A heterocycle comprises 1 heteroatom that is S. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3),, Ring A as described herein is substituted with 1-4 substituents as described herein. In some embodiments, Ring A as described herein is unsubstituted. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: cyclopropyl substituted with one or more -CH3 or -CN, optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl pyrrolidinyl, and piperidinyl, each of which is substituted with one or more -F, and is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; and spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2- oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-Oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl, any of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; and provided that when one or more of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) apply, then Ring A is further selected from cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, sulfolanyl, azetidinyl, pyrrolidinyl, piperidinyl, spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2-Oxabicyclo[2.2.1]heptanyl, 8- Oxabicyclo[3.2.1]octanyl, 1-Oxaspiro[5.5]undecanyl, adamantanyl, 2-Azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, -C(O)OR12, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; (i) Ring B is (a) and RAis selected from halogen, C1-4 haloalkyl, C3-6 cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4 alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4alkyl or C1-4haloalkyl; (vi) Ring B is (c); and (vii) Y1is CR3, Y2is N, Y3is CR3, and Y4is N; (viii) Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c); provided that when Ring B is (a), X1 is CH, RAis methyl, Y1is CR3, and Y2is N, then Ring A is further selected from tetrahydrofuranyl substituted with methyl; and R12is independently selected at each occurrence from hydrogen and C1-6 alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: cyclopropyl substituted with one or more -CH3 or -CN; cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl pyrrolidinyl, and piperidinyl, each of which is substituted with one or more -F, and is optionally substituted with one or more substituents independently selected from: -F, -OH, -OCH3, -CH3, , , , , , and ;and spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2- oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-Oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl, any of which is optionally substituted with one or more substituents independently selected from: -F, -OH, and -CH3, and provided that when one or more of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) apply, then Ring A is further selected from cyclobutyl, cyclohexyl, phenyl, oxepanyl, sulfolanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2-Oxabicyclo[2.2.1]heptanyl, 8- Oxabicyclo[3.2.1]octanyl, 1-Oxaspiro[5.5]undecanyl, adamantanyl, 2-Azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is optionally substituted with one or more substituents independently selected from: -F, -OH, -OCH3, -CH3, -CF3, =O, , and ; (i) Ring B is (a) and RAis selected from halogen, C1-4haloalkyl, C3-6cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4alkyl or C1-4haloalkyl; (vi) Ring B is (c); and (vii) Y1is CR3, Y2is N, Y3is CR3, and Y4is N; (viii) Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c); provided that Ring A is selected from tetrahydrofuranyl substituted with methyl only when Ring B is (a), X1is CH, RAis methyl, Y1is CR3, and Y2is N. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: phenyl, tetrahydrofuanyl, tetrahydropyranyl, azetidinyl; pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6- membered heterocycle optionally substituted with one or more C1-4 alkyl; and R12is independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, Ring A is selected from: phenyl, tetrahydrofuanyl, tetrahydropyranyl, azetidinyl; pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; and R12is independently selected at each occurrence from hydrogen and C1-6 alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, -C(O)OR12, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; and R12is independently selected at each occurrence from hydrogen and C1-6 alkyl. In some embodiments, Ring A is selected from: phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, C1-6alkyl, -C(O)OR12, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; and R12is independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), the halogen substituent on Ring A is bonded to the ring member of Ring A that is bonded to –L-. In some embodiments, the -F substituent on Ring A is bonded to the ring member of Ring A that is bonded to –L-. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: cyclopropyl, phenyl, tetrahydrofuanyl, tetrahydropyranyl, azetidinyl pyrrolidinyl, and piperidinyl, each of which is substituted with one or more -F, and is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; and 1,9-dioxaspiro[5.5]undecanyl optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN; and R12is independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: cyclopropyl, phenyl, tetrahydrofuanyl, tetrahydropyranyl, azetidinyl pyrrolidinyl, and piperidinyl, each of which is substituted with 1-4 -F, and is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; and 1,9-dioxaspiro[5.5]undecanyl optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN; and R12is independently selected at each occurrence from hydrogen and C1-6 alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl; pyrrolidinyl, piperidinyl, and 1,9- dioxaspiro[5.5]undecanyl, each of which is optionally substituted with one or more substituents independently selected from: -F, -OH, -CH3, , , , , and . In some embodiments, Ring A is selected from: cyclopropyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl; pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is optionally substituted with one or more substituents independently selected from: -F, - CH3, , , , , and . In some embodiments, Ring A is selected from: cyclopropyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl; pyrrolidinyl, piperidinyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is optionally substituted with 1-4 substituents independently selected from: -F, -CH3, , , , , and . In some embodiments, Ring A is cyclopropyl optionally substituted with 1-4 substituents independently selected from: -F, -CH3, , , , , and . In some embodiments, Ring A is cyclopropyl optionally substituted with 1-4 substituents independently selected from: -F and -CH3. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is phenyl optionally substituted with 1-4 substituents independently selected from: -F, -CH3, , , , , and . In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with 1-4 substituents independently selected from: -F, -CH3, , , , , and . In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with 1-4 substituents independently selected from: -F and -CH3. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with 1-4 substituents independently selected from: -F, -CH3, , , , , and . In some embodiments, Ring A is tetrahydropyranyl optionally substituted with 1- 4 substituents independently selected from: -F and -CH3. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is azetidinyl optionally substituted with 1-4 substituents independently selected from: -F, -CH3, , , , , and . In some embodiments, Ring A is pyrrolidinyl optionally substituted with 1-4 substituents independently selected from: -F, -CH3, , , , , and . In some embodiments, Ring A is piperidinyl optionally substituted with 1-4 substituents independently selected from: -F, -CH3, , , , , and . In some embodiments, Ring A is 1,9-dioxaspiro[5.5]undecanyl optionally substituted with 1-4 substituents independently selected from: -F, -CH3, , , , , and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: F , , , , , ,HO, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: cyclopropyl substituted with one or more C1-6 alkyl or -CN, C3-6 carbocycle substituted with one or more halogen, 3- to 6-membered heterocycle substituted with one or more halogen, C5-6 spirocyclic carbocycle, and 5- to 6-membered spirocyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; C7-12carbocycle and 7- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl, provided that when Ring B is selected from (b), then Ring A is not chromane; and R12is independently selected at each occurrence from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6cycloalkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: cyclopropyl substituted with one or more -halogen, C1-6 alkyl or -CN; cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl pyrrolidinyl, and piperidinyl, each of which is substituted with one or more halogen; and spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2- oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-Oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl; any of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; and R12is independently selected at each occurrence from hydrogen and C1-6 alkyl. In some embodiments, for the compound of any of the preceding Formulae, when Ring B is selected from (b), then Ring A is not chromane. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: cyclopropyl substituted with one or more -F, -CH3, or -CN; cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl pyrrolidinyl, and piperidinyl, each of which is substituted with one or more -F; and spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2- oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-Oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl; any of which is optionally substituted with one or more substituents independently selected from: -F, -OH, -OCH3, -CH3, -CF3, =O, -CN, , , , , , , , and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: F , , , ,HO, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: , , , , , , , , and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: , , , , , , , , , , , , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is selected from: , , , , , , , , , , , , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is tetrahydropyranyl optionally substituted with 1-4 halogen. In some embodiments, Ring A is tetrahydropyranyl substituted with 1-4 halogen. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with 1-4 fluorine. In some embodiments, Ring A is tetrahydropyranyl substituted with 1-4 fluorine. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with one halogen. In some embodiments, Ring A is tetrahydropyranyl substituted with one halogen. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with one fluorine. In some embodiments, Ring A is tetrahydropyranyl substituted with one fluorine. In some embodiments, Ring A is unsubstituted tetrahydropyranyl. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with 1-4 C1-6alkyl. In some embodiments, Ring A is tetrahydropyranyl substituted with 1-4 C1-6alkyl. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with 1-4 methyl. In 20 some embodiments, Ring A is tetrahydropyranyl substituted with 1-4 methyl. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with one C1-6alkyl. In some embodiments, Ring A is tetrahydropyranyl substituted with one C1-6 alkyl. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with one methyl. In some embodiments, Ring A is tetrahydropyranyl substituted with one methyl. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with four C1-6 alkyl. In some embodiments, Ring A is tetrahydropyranyl substituted with four C1-6alkyl. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with four methyl. In some embodiments, Ring A is tetrahydropyranyl substituted with four methyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is unsubstituted tetrahydrofuranyl. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with 1-4 C1-6 alkyl. In some embodiments, Ring A is tetrahydrofuranyl substituted with 1-4 C1-6 alkyl. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with 1-4 methyl. In some embodiments, Ring A is tetrahydrofuranyl substituted with 1-4 methyl. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with one C1-6alkyl. In some embodiments, Ring A is tetrahydrofuranyl substituted with one C1-6alkyl. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with one methyl. In some embodiments, Ring A is tetrahydrofuranyl substituted with one methyl. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with four C1-6 alkyl. In some embodiments, Ring A is tetrahydrofuranyl substituted with four C1-6 alkyl. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with four methyl. In some embodiments, Ring A is tetrahydrofuranyl substituted with four methyl. In some embodiments, the compound is of Formula (IIIA): (IIIA), or a pharmaceutically acceptable salt thereof; wherein R5is selected from hydrogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR12; and R16 is selected from halogen, -OR12, and C1-6alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, the compound is of Formula (IIIB) (IIIB), or a pharmaceutically acceptable salt thereof; wherein R16is selected from halogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR12; and Q is O, NH, or S. In some embodiments, Q is O. In some embodiments, the compound is of Formula (IIIA-1): (III-A1), or a pharmaceutically acceptable salt thereof; wherein R5is selected from hydrogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR12; and R16is selected from halogen, -OR12, and C1-6alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, the compound is of Formula (IIIB-1): (IIIB-1), or a pharmaceutically acceptable salt thereof; wherein R16is selected from halogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR12; and Q is O, NH, or S. In some embodiments, Q is O. In some embodiments, p is 0. In some embodiments, the compound is of Formula (IIIC-1): (IIIC-1), or a pharmaceutically acceptable salt thereof; wherein R16is selected from halogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR12; and Q is O, NH, or S. In some embodiments, Q is O. In some embodiments, the compound is of Formula (IIIA-2): (IIIA-2), or a pharmaceutically acceptable salt thereof; wherein R5is selected from hydrogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR12; and R16is selected from halogen, -OR12, and C1-6alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, the compound is of Formula (IIIA-3): (IIIA-3), or a pharmaceutically acceptable salt thereof; wherein R5is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and -C(O)OR12; and R16is selected from halogen, -OR12, and C1-6alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, the compound is of Formula (IIIA-4): (IIIA-4), or a pharmaceutically acceptable salt thereof; wherein R5is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and -C(O)OR12; and R16is selected from halogen, -OR12, and C1-6alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, the compound is of Formula (IIIA-5): (IIIA-5), or a pharmaceutically acceptable salt thereof; wherein R5is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and -C(O)OR12; and R16is selected from halogen, -OR12, and C1-6 alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, for the compound of Formulae (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), or (IIIC-1), RAis selected from halogen, C1-4alkyl, C1-4haloalkyl, C1-4hydroxyalkyl, -OR11, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, C3-6cycloalkyl, and 3- to 6-membered heterocycloalkyl; and R11is selected from hydrogen, C1-4 alkyl, C1-4 haloalkyl, and C3-6 cycloalkyl. In some embodiments, RAis selected from halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, C3-6 cycloalkyl, and 3- to 6-membered heterocycloalkyl; and R11is selected from hydrogen, C1-4 alkyl, C1-4 haloalkyl, and C3-6 cycloalkyl. In some embodiments, RAis selected from halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, and -CN, and R11is selected from hydrogen, C1-4alkyl, C1-4haloalkyl, and C3-6cycloalkyl. In some embodiments, RAis selected from halogen, C1-4alkyl, C1-4haloalkyl, C1-4hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, and -CN, and R11is selected from hydrogen, and C1-4 alkyl. In some embodiments, RAis selected from halogen, C1-4 alkyl, C1- 4 haloalkyl, and C1-4 hydroxyalkyl. In some embodiments, RAis selected from halogen, C1-4 alkyl, and C1-4 haloalkyl. In some embodiments, RAis selected from halogen and C1-4 alkyl. . In some embodiments, RAis selected from C1-4 alkyl. In some embodiments, for the compound of Formulae (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), or (IIIC-1), RAis selected from -F, -Cl, -CN, -NH2, -OH, - OCH3, , -CH3, -CF3, -CHF2, , , , , and . In some embodiments, RAis selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, , , , , and . In some embodiments, RAis selected from -F, - Cl, -CN, -NH2, -CH3, -CF3, and -CHF2. In some embodiments, RAis selected from -F, -Cl, -CH3, -CF3, and -CHF2. In some embodiments, RAis selected from -F and -Cl. In some embodiments, RAis selected from -CH3, -CF3, and -CHF2. In some embodiments, RAis selected from -CH3. In some embodiments, for the compound of Formulae (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), or (IIIC-1), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, for the compound of Formulae (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), or (IIIC-1), R5is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, - C(O)N(R13)2, -N(R13)C(O)R13, -N(R13)S(O)2(R13), -S(O)2R13, -S(O)2N(R13)2, -NO2, and -CN. In some embodiments, R5is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -SR13, -N(R13)2, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, and -CN. In some embodiments, R5is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -SR13, -N(R13)2, and -CN. In some embodiments, R5is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, and -CN. In some embodiments, R5is halogen. In some embodiments, R5is C1-4 alkyl. In some embodiments, R5is C1-4 haloalkyl. In some embodiments, R5is -OR13. In some embodiments, R5is -SR13. In some embodiments, R5is -N(R13)2. In some embodiments, R5is -C(O)R13. In some embodiments, R5is -C(O)OR13. In some embodiments, R5is -OC(O)R13. In some embodiments, R5is -C(O)N(R13)2. In some embodiments, R5is -N(R13)C(O)R13. In some embodiments, R5is -N(R13)S(O)2(R13). In some embodiments, R5is -S(O)2R13. In some embodiments, R5is -S(O)2N(R13)2. In some embodiments, R5is -NO2. In some embodiments, R5is -CN. In some embodiments, the compound is of Formula (IIIB-2): (IIIB-2), or a pharmaceutically acceptable salt thereof; wherein R16is selected from halogen, C1-4alkyl, and C1-4haloalkyl; and Q is O, NH, or S. In some embodiments, Q is O. In some embodiments, R16is selected from -F and -CH3; Q is O; and X1is CH or N. In some embodiments, the compound is of Formula (IIIB-3): (IIIB-3), or a pharmaceutically acceptable salt thereof; wherein R16is selected from halogen, C1-4alkyl, and C1-4haloalkyl; and Q is O, NH, or S. In some embodiments, Q is O. In some embodiments, R16is selected from -F and -CH3; Q is O; and X1is CH or N. In some embodiments, for the compound of Formulae (IIIA), (IIIA-1), (IIIB), (IIIB-1), (IIIB-2), (IIIB-3), or (IIIC-1), X1is selected from N, CH, and CR5. In some embodiments, X1is selected from N and CH. In some embodiments, X1is selected from CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, X1is CR5. In some embodiments, for the compound of Formulae (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), (IIIB-2), (IIIB-3), or (IIIC-1), Q is O, NH, or S. In some embodiments, Q is O. In some embodiments, for the compound of Formulae (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), (IIIB-2), (IIIB-3), or (IIIC-1), each R16is independently selected from halogen, C1-4 alkyl, and C1-4 haloalkyl. In some embodiments, each R16is independently selected from halogen and C1-4 alkyl. In some embodiments, each R16is independently selected from halogen and C1-4 alkyl. In some embodiments, each R16is independently selected from -F and C1-4alkyl. In some embodiments, each R16is independently selected from -F and -CH3. In some embodiments, each R16is independently selected from C1-4alkyl. In some embodiments, each R16is -CH3. In some embodiments, each R16is independently selected from halogen. In some embodiments, each R16is -F. In some embodiments, for the compound of Formulae (IIIA), (IIIA-1), (IIIA-2), (IIIA-3), (IIIA-4), (IIIA-5), (IIIB), (IIIB-1), (IIIB-2), (IIIB-3), or (IIIC-1), the compound has 0, 1, 2, 3, or 4 R16groups. In some embodiments, the compound has 0, 1, 2, or 3 R16groups. In some embodiments, the compound has 0, 1, or 2 R16groups. In some embodiments, the compound has 0 or 1 R16groups. In some embodiments, the compound has 1, 2, 3, or 4 R16groups. In some embodiments, the compound has 1, 2, or 3 R16groups. In some embodiments, the compound has 1 or 2 R16groups. In some embodiments, the compound has 0 R16groups. In some embodiments, the compound has 1 R16groups. In some embodiments, the compound has 2 R16groups. In some embodiments, the compound has 3 R16groups. In some embodiments, the compound has 4 R16groups. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (II), (IIA), (IIA-1), (IIA-2) (IIA-3), (IIB), (IIB-1), (IIB-2), (IIB-3), (IIB-5), (IIB-6), (IIC), (IIC-1), (IIC-2), (IIC-3), (IID), (IID-1), (IID-2), or (IID-3), Ring A is cyclopropyl optionally substituted with 1-4 halogen. In some embodiments, Ring A is cyclopropyl substituted with 1-4 halogen. In some embodiments, Ring A is cyclopropyl optionally substituted with 1-4 fluorine. In some embodiments, Ring A is cyclopropyl substituted with 1-4 fluorine. In some embodiments, Ring A is cyclopropyl optionally substituted with one halogen. In some embodiments, Ring A is cyclopropyl substituted with one halogen. In some embodiments, Ring A is cyclopropyl optionally substituted with one fluorine. In some embodiments, Ring A is cyclopropyl substituted with one fluorine. In some embodiments, Ring A is not chromane. In some embodiments, the compound is of Formula (IVA): (IVA), or a pharmaceutically acceptable salt thereof; wherein R15is selected from hydrogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR12. In some embodiments, the compound is of Formula (IVA-1): (IVA-1), or a pharmaceutically acceptable salt thereof; wherein R15is selected from hydrogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR12. In some embodiments, the compound is of Formula (IVB-1): (IVB-1), or a pharmaceutically acceptable salt thereof; wherein R15is selected from hydrogen, halogen, C1-6alkyl, C1-6haloalkyl, and - C(O)OR12. In some embodiments, the compound is of Formula (IVA-2): (IVA-2), or a pharmaceutically acceptable salt thereof; wherein R15is selected from hydrogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR12. In some embodiments, the compound is of Formula (IVA-3): (IVA-3), or a pharmaceutically acceptable salt thereof; wherein R15is selected from hydrogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR12. In some embodiments, for the compound of Formulae (IVA), (IVA-1), (IVA-2), (IVA-3), or (IVB-1), RAis selected from halogen, C1-4alkyl, C1-4haloalkyl, C1-4hydroxyalkyl, -OR11, - N(R11)2, -SR11, -N(R11)C(O)R11, -CN, C3-6 cycloalkyl, and 3- to 6-membered heterocycloalkyl; and R11is selected from hydrogen, C1-4 alkyl, C1-4 haloalkyl, and C3-6 cycloalkyl. In some embodiments, RAis selected from halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, C3-6 cycloalkyl, and 3- to 6-membered heterocycloalkyl; and R11is selected from hydrogen, C1-4 alkyl, C1-4 haloalkyl, and C3-6 cycloalkyl. In some embodiments, RAis selected from halogen, C1-4alkyl, C1-4haloalkyl, C1-4hydroxyalkyl, -N(R11)2, -SR11, - N(R11)C(O)R11, and -CN, and R11is selected from hydrogen, C1-4alkyl, C1-4haloalkyl, and C3-6cycloalkyl. In some embodiments, RAis selected from halogen, C1-4alkyl, C1-4haloalkyl, C1-4 hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, and -CN, and R11is selected from hydrogen, and C1-4 alkyl. In some embodiments, RAis selected from halogen, C1-4 alkyl, C1-4 haloalkyl, and C1- 4 hydroxyalkyl. In some embodiments, RAis selected from halogen, C1-4 alkyl, and C1-4 haloalkyl. In some embodiments, RAis selected from halogen and C1-4 alkyl. . In some embodiments, RAis selected from C1-4 alkyl. In some embodiments, for the compound of Formulae (IVA), (IVA-1), (IVA-2), (IVA-3), or (IVB-1), RAis selected from -F, -Cl, -CN, -NH2, -OH, -OCH3, , -CH3, -CF3, -CHF2, , , , , and . In some embodiments, RAis selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, , , , , and . In some embodiments, RAis selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, and -CHF2. In some embodiments, RAis selected from -F, -Cl, -CH3, -CF3, and -CHF2. In some embodiments, RAis selected from -F and -Cl. In some embodiments, RAis selected from -CH3, -CF3, and -CHF2. In some embodiments, RAis selected from -CH3. In some embodiments, for the compound of Formulae (IVA), (IVA-1), (IVA-2), (IVA-3), or (IVB-1), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, for the compound of Formulae (IVA), (IVA-1), (IVA-2), (IVA-3), or (IVB-1), R5is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -N(R13)S(O)2(R13), -S(O)2R13, -S(O)2N(R13)2, -NO2, and -CN. In some embodiments, R5is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -SR13, -N(R13)2, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, and -CN. In some embodiments, R5is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -SR13, -N(R13)2, and -CN. In some embodiments, R5is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, and -CN. In some embodiments, R5is halogen. In some embodiments, R5is C1-4alkyl. In some embodiments, R5is C1-4haloalkyl. In some embodiments, R5is -OR13. In some embodiments, R5is -SR13. In some embodiments, R5is -N(R13)2. In some embodiments, R5is -C(O)R13. In some embodiments, R5is -C(O)OR13. In some embodiments, R5is -OC(O)R13. In some embodiments, R5is -C(O)N(R13)2. In some embodiments, R5is -N(R13)C(O)R13. In some embodiments, R5is -N(R13)S(O)2(R13). In some embodiments, R5is -S(O)2R13. In some embodiments, R5is -S(O)2N(R13)2. In some embodiments, R5is -NO2. In some embodiments, R5is -CN. In some embodiments, RAis C1-4alkyl. In some embodiments, R16is selected from -F and -CH3; Q is O; and X1is CH or N. In some embodiments, p is 0. In some embodiments, the compound is of Formula (IVA-4): (IVA-4), or a pharmaceutically acceptable salt thereof; wherein R15is selected from hydrogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR12. In some embodiments, the compound is of Formula (IVB-2): (IVB-2), or a pharmaceutically acceptable salt thereof; wherein R15is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and -C(O)OR12. In some embodiments, the compound is of Formula (IVB-3): R150-4 F O N 1-4NHN N X1N (IVB-3), or a pharmaceutically acceptable salt thereof; wherein X1is CH or N, and R15is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and -C(O)OR12. In some embodiments, the compound is of Formula (IVB-4): R15 0-4FO NNHN N X1N (IVB-4), or a pharmaceutically acceptable salt thereof; wherein X1is CH or N, and R15is selected from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and -C(O)OR12. In some embodiments, for the compound of Formulae (IVA), (IVA-1), (IVA-2), (IVA-3), (IVA-4), (IVB-1), (IVB-2), (IVB-3), or (IVB-4), X1is selected from N, CH, and CR5. In some embodiments, X1is selected from N and CH. In some embodiments, X1is selected from CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, X1is CR5. In some embodiments, for the compound of Formulae (IVA), (IVA-1), (IVA-2), (IVA-3), (IVA-4), (IVB-1), (IVB-2), (IVB-3), or (IVB-4), X1is CR5, and R5is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -SR13, -N(R13)2, and -CN. In some embodiments, X1is CR5, and R5is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, and -CN. In some embodiments, X1is CR5, and R5is halogen. In some embodiments, X1is CR5, and R5is C1-4 alkyl. In some embodiments, X1is CR5, and R5is C1-4haloalkyl. In some embodiments, the compound is of Formula (IVA-5): (IVA-5), or a pharmaceutically acceptable salt thereof; wherein R15is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and -C(O)OR12. In some embodiments, for the compound of Formulae (IVA), (IVA-1), (IVA-2), (IVA-3), (IVA-4), (IVA-5), (IVB-1), (IVB-2), (IVB-3), or (IVB-4), each R15is independently selected from halogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, each R15is independently selected from halogen and C1-4alkyl. In some embodiments, each R15is independently selected from halogen and C1-4 alkyl. In some embodiments, each R15is independently selected from -F and C1- 4 alkyl. In some embodiments, each R15is independently selected from -F and -CH3. In some embodiments, each R15is independently selected from C1-4 alkyl. In some embodiments, each R15is -CH3. In some embodiments, each R15is independently selected from halogen. In some embodiments, each R15is -F. In some embodiments, R15is hydrogen. In some embodiments, R15 is C1-6alkyl. In some embodiments, R15is C1-6haloalkyl. In some embodiments, R15is -C(O)OR12. In some embodiments, for the compound of Formulae (IVA), (IVA-1), (IVA-2), (IVA-3), (IVA-4), (IVA-5), (IVB-1), (IVB-2), (IVB-3), or (IVB-4), the compound has 0, 1, 2, 3, or 4 R15groups. In some embodiments, the compound has 0, 1, 2, or 3 R15groups. In some embodiments, the compound has 0, 1, or 2 R15groups. In some embodiments, the compound has 0 or 1 R15groups. In some embodiments, the compound has 1, 2, 3, or 4 R15groups. In some embodiments, the compound has 1, 2, or 3 R15groups. In some embodiments, the compound has 1 or 2 R15groups. In some embodiments, the compound has 0 R15groups. In some embodiments, the compound has 1 R15groups. In some embodiments, the compound has 2 R15groups. In some embodiments, the compound has 3 R15groups. In some embodiments, the compound has 4 R15groups. In some embodiments, for the compound of any of the preceding FormulaeR10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen and C1-6alkyl. In some embodiments, R10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, each R10is independently selected from hydrogen and C1-6alkyl. In some embodiments, each R10is independently hydrogen. In some embodiments, each R10is independently C1-6 alkyl. In some embodiments, each R11is independently selected from hydrogen and C1-6 alkyl. In some embodiments, each R11is independently hydrogen. In some embodiments, each R11is independently C1-6 alkyl. In some embodiments, each R12is independently selected from hydrogen and C1-6 alkyl. In some embodiments, each R12is independently hydrogen. In some embodiments, each R12is independently C1-6alkyl. In some embodiments, each R13is independently selected from hydrogen and C1-6alkyl. In some embodiments, each R13is independently hydrogen. In some embodiments, each R13is independently C1-6alkyl. In some embodiments, each R14is independently selected from hydrogen and C1-6 alkyl. In some embodiments, each R14is independently hydrogen. In some embodiments, each R14is independently C1-6 alkyl. In some embodiments, the compound is of Formula (IVA-6): (IVA-6), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IVA-7): (IVA-7), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IVA-8): (IVA-8), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IIC-10): (IIC-10), or a pharmaceutically acceptable salt thereof, wherein: Ring B is selected from (a), (b) and (c): (a) , X1is selected from N, CH, and CR5; (b) , X2is selected from S and NR7; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system; R1is selected from hydrogen, C1-4 alkyl, and –C(O)C3-6 cycloalkyl optionally substituted with one or more halogen; R2is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -OR10, -SR10, -N(R10)2, NO2, and -CN; R3and R4are each independently selected at each occurrence from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; RAis selected from hydrogen, halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, -S(O)2C1-4alkyl, C3-6cycloalkyl, and 3- to 6-membered heterocycloalkyl; Ring A is selected from: cyclopropyl substituted with one or more halogen, C4-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; R5,R6, andR8are each independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -N(R13)S(O)2(R13), -S(O)2R13, -S(O)2N(R13)2, -NO2, and -CN; R7and R9are each independently selected from hydrogen, C1-4 alkyl, and C1-4 haloalkyl; R10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 cycloalkyl; m is selected from 0, 1, and 2; p is selected from 0, 1, and 2; q is selected from 0, 1, and 2; and r is selected from 0, 1, and 2. In some embodiments, for the compound of Formula (IIC-10), RAis selected from halogen, C1-4alkyl, C1-4haloalkyl, C1-4hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, C3-6cycloalkyl, and 3- to 6-membered heterocycloalkyl; and when Y1is CR3and Y2is N, then RAis further selected from -OR11; R11is selected from hydrogen, C1-4 alkyl, C1-4 haloalkyl, and C3-6 cycloalkyl; R5is independently selected at each occurrence from halogen, and C1-4 alkyl; and p is selected from 0 and 1. In some embodiments, for the compound of Formula (IIC-10), RAis selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, , , , , and ; and when Y1is CR3and Y2is N, then RAis further selected from - OH, -OCH3, and ; R5is selected at each occurrence from -F, -Cl, and -CH3; p is selected from 0 and 1. In some embodiments, the compound of Formula (II) is a compound of: (II), or a pharmaceutically acceptable salt thereof, wherein: each represents a single or a double bond, such that the bicyclic ring system comprising Y1, Y2, and Y3is an aromatic bicyclic ring system where (i) Y1is CR3and Y2is N, or (ii) Y1is S and Y2is C; Y3is selected from N and CR4; Ring B is selected from (a), (b) and (c): (a) , X1is selected from N, CH, and CR5; (b) , X2is selected from S and NR7; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system; R1is selected from hydrogen, C1-4alkyl, C1-4haloalkyl, and –C(O)C3-6cycloalkyl optionally substituted with one or more halogen; R2is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -OR10, -N(R10)2,, and -CN; R3and R4are each independently selected from hydrogen, halogen, C1-4 alkyl, and C1- 4 haloalkyl; RAis selected from halogen, C1-4alkyl, C1-4haloalkyl, C1-4hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, -S(O)2C1-4alkyl, C3-6cycloalkyl, and 3- to 6-membered heterocycloalkyl, provided that: when Y1is CR3, Y2is N, and Y4is CR3, or when Y1is CR3, Y2is N, and Y4is N, then RAis further selected from -OR11, when Y1is CR3, Y2is N, Y3is CH, Ring B is (a), p is 0, X1is N, and Ring A is 1- fluoro-1-tetrahydropyranyl, then RAis further selected from hydrogen, and when Y1is S, Y2is C, and X1is N, then RAis further selected from hydrogen; Ring A is selected from cyclopropyl substituted with one or more C1-6alkyl or -CN, C3-6carbocycle substituted with one or more halogen, 3- to 6-membered heterocycle substituted with one or more halogen, C5-6 spirocyclic carbocycle, and 5- to 6-membered spirocyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; C7-12carbocycle and 7- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; provided that when Ring B is selected from (b), then Ring A is not chromane; provided that when one or more of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) apply, then Ring A is further selected from C4-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl;, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl: (i) Ring B is (a) and RAis selected from halogen, C1-4 haloalkyl, C3-6 cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4 alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4alkyl or C1-4haloalkyl; (vi) Ring B is (c); and (vii) Y1is CR3, Y2is N, Y3is CR3, and Y4is N; (viii) Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c); provided that when Ring B is (a), X1 is CH, RAis methyl, Y1is CR3, and Y2is N, then Ring A is further selected from tetrahydrofuranyl substituted with methyl; and R5is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, and -OR13, provided that when RAis -OR11, then R5is not -OR13; R6is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -OR14, and -N(R14)2; R7is selected from hydrogen and C1-4 alkyl; R8is independently selected at each occurrence from halogen, C2-4 alkyl, C1-4 haloalkyl, -OR14, and -N(R14)2; R9is selected from hydrogen, C1-4alkyl, and C1-4haloalkyl; R10, R11, R12, R13, R14are each independently selected at each occurrence from hydrogen and C1-4alkyl; m, p, q, and r are each independently selected from 0, and 1. In some embodiments, for the compound of Formulae (I), (II), or sub-formulae thereof, when Y1is CR3and Y2is N, then RAis further selected from -OR11. In some embodiments, Y1is CR3and Y2is N; and RAis further selected from -OR11, provided that when RAis -OR11, then R5is not -OR13;. In some embodiments, for the compound of Formulae (I), (II), or sub-formulae thereof, when Y1is CR3, Y2is N, Y3is CH, Ring B is (a), p is 0, X1is N, and Ring A is 1-fluoro-1- tetrahydropyranyl, then RAis further selected from hydrogen. In some embodiments, Y1is CR3, Y2is N, Y3is CH, Ring B is (a), p is 0, X1is N, and Ring A is 1-fluoro-1-tetrahydropyranyl; and RAis further selected from hydrogen. In some embodiments, for the compound of Formulae (I), (II), or sub-formulae thereof, when Y1is S, Y2is C, and X1is N, then RAis further selected from hydrogen. In some embodiments, Y1is S, Y2is C, and X1is N; and RAis further selected from hydrogen. In some embodiments, for the compound of Formulae (I), (II), or sub-formulae thereof, when one or more of (i), (ii), (ii), (iv), and (v) apply, then Ring A is further selected from C4-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl: (i) Ring B is (a) and RAis selected from halogen, C1-4haloalkyl, C3-6cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4 alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4 alkyl; and (vi) Ring B is (c). In some embodiments, for the compound of Formulae (I), (II), or sub-formulae thereof, one or more of (i), (ii), (ii), (iv), and (v) apply; and Ring A is further selected from C4-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl: (i) Ring B is (a) and RAis selected from halogen, C1-4haloalkyl, C3-6cycloalkyl, -NR11, and -OR11; (ii) Y1is S, Y2is C, Ring B is (a), and X1is N; (iii) Y1is S, Y2is C, Ring B is (a), and RAis C1-4alkyl; (iv) Ring B is (a), and p is 1, 2, or 3; (v) R1is C1-4 alkyl; and (vi) Ring B is (c). In some embodiments, for the compound of Formulae (I), (II), or sub-formulae thereof, when Ring B is (a), X1is CH, RAis methyl, Y1is CR3, and Y2is N, then Ring A is further selected from tetrahydrofuranyl substituted with methyl. In some embodiments, Ring B is (a), X1is CH, RAis methyl, Y1is CR3, and Y2is N; and Ring A is further selected from tetrahydrofuranyl substituted with methyl. In some embodiments, for the compound of Formulae (I), (II), or sub-formulae thereof, when RAis -OR11, then R5is chloro. In some embodiments, RAis -OR11; and R5is chloro. Formulae (V) and (VI) Compounds Some embodiments provide a compound of Formula (V): (V), or a pharmaceutically acceptable salt thereof, wherein: Q1is N, S, O or CR3, Q2is N or C, Q3is N or CR4, Q4is N or CR3, Q5is C or N, and each represents a single or a double bond, such that the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is benzo[d]thiazole, benzo[d]oxazole, imidazo[1,2-a]pyridine, thiazolo[5,4- b]pyridine, imidazo[1,2-b]pyridazine, pyrazolo[1,5-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, or [1,2,4]triazolo[1,5-b]pyridazine, RAis selected from halogen, -OR10, -SR10, -N(R10)2, -CN, C1-6alkyl optionally substituted with one or more halogen or -OR10, C3-C6 saturated cycloalkyl, and 3- to 6-membered saturated heterocycloalkyl; Ring A is selected from a C3-C10 saturated cycloalkyl, a C3-C10 partially saturated carbocycle, a 3- to 10-membered saturated heterocycloalkyl, and a 3- to 10-membered partially saturated heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -OC(O)N(R11)2,-C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)C(O)N(R11)2, -N(R11)S(O)2(R11), -S(O)R11, -S(O)2R11, -S(O)2N(R11)2, -S(O)(NR11)R11, -NO2, and =O; C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -OC(O)N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)C(O)N(R11)2, -N(R11)S(O)2(R11), -S(O)R11, -S(O)2R11, -S(O)2N(R11)2, -S(O)(NR11)R11, -NO2, =O, -CN; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -OC(O)N(R11)2,-C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)C(O)N(R11)2, -N(R11)S(O)2(R11), -S(O)R11, -S(O)2R11, -S(O)2N(R11)2, -S(O)(NR11)R11, -NO2, =O, and -CN; Ring B is selected from a C3-C10 carbocycle and a 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2,-C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; R1is selected from hydrogen, C1-4alkyl, C1-4haloalkyl, and -C(O)R13; R2is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -OR14, -SR14, -N(R14)2, -NO2, and -CN; R3is independently selected at each occurrence from hydrogen, halogen, C1-4 alkyl, and C1-4 haloalkyl; R4is selected from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; R10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4haloalkyl, and cycloalkyl optionally substituted with one or more halogen; and n is selected from 0, 1, and 2; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl. In some embodiments, for the compound of Formula (V), Q1is CR3. In some emboidments, Q1is N. In some emboidments, Q1is S. In some emboidments, Q1is O. In some embodiments, Q2is C. In some emboidments, Q2is N. In some embodiments, Q3is CR4. In some emboidments, Q3 is N. In some embodiments, Q4is CR3. In some emboidments, Q4is N. In some embodiments, Q5is C. In some embodiments, for the compound of Formula (V), the the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is benzo[d]thiazole, benzo[d]oxazole, or thiazolo[5,4- b]pyridine. In some embodiments, the the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is imidazo[1,2-a]pyridine, imidazo[1,2-b]pyridazine, or pyrazolo[1,5-a]pyridine. In some embodiments, the the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is [1,2,4]triazolo[1,5- a]pyridine or [1,2,4]triazolo[1,5-b]pyridazine. In some embodiments, for the compound of Formula (V), the the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is benzo[d]thiazole. In some embodiments, the the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is benzo[d]oxazole. In some embodiments, the the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is imidazo[1,2-a]pyridine. In some embodiments, the the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is thiazolo[5,4- b]pyridine. In some embodiments, the the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is imidazo[1,2-b]pyridazine. In some embodiments, the the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is pyrazolo[1,5-a]pyridine. In some embodiments, the the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is [1,2,4]triazolo[1,5-a]pyridine. In some embodiments, the the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is [1,2,4]triazolo[1,5-b]pyridazine. Some embodiments provide a compound of Formula (VA): (VA), or a pharmaceutically acceptable salt thereof. In some embodiments, Q3is CR4. In some emboidments, Q3is N. In some embodiments, Q4is CR3. In some emboidments, Q4is N. In some embodiments, Q3is CR4and Q4is N. In some embodiments, Q3is CR4and Q4is CR3. In some embodiments, Q3is N and Q4is CR3. Some embodiments provide a compound of Formula (VB): (VB), or a pharmaceutically acceptable salt thereof. In some embodiments, Q3is CR4. In some emboidments, Q3is N. Some embodiments provide a compound of Formula (VC): (VC), or a pharmaceutically acceptable salt thereof. In some embodiments, Q4is CR3. In some emboidments, Q4is N. Some embodiments provide a compound of Formula (VD): (VD), or a pharmaceutically acceptable salt thereof. In some embodiments, Q3is CR4. In some emboidments, Q3is N. Some embodiments provide a compound of Formula (VE): (VE), or a pharmaceutically acceptable salt thereof. In some embodiments, Q3is CR4. In some emboidments, Q3is N. Some embodiments provide a compound of Formula (VF): (VF), or a pharmaceutically acceptable salt thereof In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), or (VF), R1is selected from hydrogen, C1-4alkyl, C1-4haloalkyl, and -C(O)R13; and R13is selected at from C1-4alkyl and cycloalkyl. In some embodiments, R1is selected from hydrogen and C1-4alkyl. In some embodiments, R1is selected from hydrogen, C1-4alkyl, C1-4haloalkyl, and -C(O)R13; and R13is selected from C1-4alkyl and cyclopropyl optionally substituted with one or more -F. In some embodiments, R1is selected from hydrogen, C1-4 alkyl, and C1-4 haloalkyl. In some embodiments, R1is selected from hydrogen and C1-4 alkyl. In some embodiments, R1is selected from hydrogen, -CH3, -CF3, and . In some embodiments, R1is hydrogen. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), or (VF), R2is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, and -CN. In some embodiments, R2is independently selected at each occurrence from halogen and C1-4 alkyl. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), or (VF), R3is independently selected at each occurrence from hydrogen, halogen, and C1-4 alkyl. In some embodiments, R3is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, each R3is independently hydrogen. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), or (VF), R4is selected from hydrogen, halogen, and C1-4alkyl. In some embodiments, R4is selected from hydrogen and C1-4 alkyl. R4is selected from hydrogen and -CH3. In some embodiments, R4is hydrogen. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), or (VF), n is 0 or 1. In some embodiments, n is 0. Some embodiments provide a compound of Formula (VI): (VI), or a pharmaceutically acceptable salt thereof, wherein: Q1is S or CR3, Q2is N or C, Q3is selected from N and CR4, and each represents a single or a double bond, such that the bicyclic ring system comprising Q1, Q2, and Q3is benzo[d]thiazole, imidazo[1,2-a]pyridine, thiazolo[5,4-b]pyridine, or imidazo[1,2-b]pyridazine; RAis selected from halogen, -OR10, -SR10, -N(R10)2, -CN, C1-6alkyl, C1-6haloalkyl, C3-C6saturated cycloalkyl, and 3- to 6-membered saturated heterocycloalkyl; Ring A is selected from a C3-C10 saturated cycloalkyl, a C3-C10 partially saturated carbocycle, a 3- to 10-membered saturated heterocycloalkyl, and a 3- to 10-membered partially saturated heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -OC(O)N(R11)2,-C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)C(O)N(R11)2, -N(R11)S(O)2(R11), -S(O)R11, -S(O)2R11, -S(O)2N(R11)2, -S(O)(NR11)R11, -NO2, and =O; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -OC(O)N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)C(O)N(R11)2, -N(R11)S(O)2(R11), -S(O)R11, -S(O)2R11, -S(O)2N(R11)2, -S(O)(NR11)R11, -NO2, =O, -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -OC(O)N(R11)2,-C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)C(O)N(R11)2, -N(R11)S(O)2(R11), -S(O)R11, -S(O)2R11, -S(O)2N(R11)2, -S(O)(NR11)R11, -NO2, =O, and -CN; Ring B is selected from a C3-C10carbocycle and a 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; R1is selected from hydrogen, C1-4alkyl, and -C(O)R13; R2is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -OR14, -SR14, -N(R14)2, -NO2, and -CN; R3and R4are each selected from hydrogen, halogen, C1-4 alkyl, and C1-4 haloalkyl; R10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen, C1-4 alkyl, C1-4 haloalkyl, and cycloalkyl optionally substituted with one or more halogen; and n is selected from 0, 1, and 2; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl. For purposes of clarification, when Ring A is substituted with one or more substituents, the one or more substituents do not include and are in addition to the RAgroup. In some embodiments, when a moiety or a list of moieties is optionally substituted or substituted with one or more substituents, the one or more substituents is 1-4 substituents (e.g., 1- 3, 2-4, 2-3, 1-2, 3-4, 1, 2, 3, or 4 substituents). For example, in some embodiments, the one or more substituents is 1-4 substituents. In some embodiments, the one or more substituents is one substituent. In some embodiments, for the compound of Formula (VI), Q1is CR3and Q2is N. In some embodiments, Q1is CR3; Q2is N; and Q3is N. In some embodiments, Q1is CR3; Q2is N; and Q3is CR4. In some embodiments, Q1is CR3; Q2is N; and Q3is CH. In some embodiments, Q1is S and Q2is C. In some embodiments, Q1is S; Q2is C; and Q3is N. In some embodiments, Q1is S; Q2is C; and Q3is CR4. In some embodiments, Q1is S; Q2is C; and Q3is CH. In some embodiments, Q3is N. In some embodiments, Q3is CR4. In some embodiments, Q3is CR4; and R4is selected from hydrogen and halogen. In some embodiments, R4is selected from hydrogen and C1-4alkyl. In some embodiments, R4is selected from hydrogen and -CH3. In some embodiments, Q3is CH. In some embodiments, Q4is CR3. In some embodiments, Q4is N. In some embodiments, Q4is CR3.and R3is selected from hydrogen and halogen. In some embodiments, R3is selected from hydrogen and C1-4 alkyl. In some embodiments, R3is selected from hydrogen and -CH3. In some embodiments, Q4is CH. In some embodiments, for the compound of Formula (VI), Q1is CR3; Q2is N; Q3is N; and Q4is CR3. In some embodiments, Q1is CR3; Q2is N; Q3is CR4; and Q4is CR3. In some embodiments, Q1is CR3; Q2is N; and Q3is CR4; and Q4is CR3. In some embodiments, Q1is CR3; Q2is N; and Q3is CR4; and Q4is N. In some embodiments, Q1is CH; Q2is N; and Q3is CH; and Q4is N. In some embodiments, the compound is of Formula (VIA): (VIA), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIA-1): (VIA-1), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIB): (VIB), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIC): (VIC), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIC-1): (VIC-1), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIC-2): (VIC-2), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIB), (VIC), (VIC-1), or (VIC-2), R1is selected from hydrogen, C1-4alkyl, and -C(O)R13.In some embodiments, R1is selected from hydrogen and C1-4alkyl. In some embodiments, R1is hydrogen. In some embodiments, R1is C1-4alkyl. In some embodiments, R1is -C(O)R13. In some embodiments, R1is selected from hydrogen, -CH3, and . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIB), (VIC), (VIC-1), or (VIC-2), n is 0 or 1. In some embodiments, n is 1 or 2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIB), (VIC), (VIC-1), or (VIC-2), R2is independently selected at each occurrence from halogen and C1-4 alkyl. In some embodiments. In some embodiments, R2is halogen. In some embodiments, R2is C1-4 alkyl. In some embodiments, R2is C1-4 haloalkyl. In some embodiments, R2is -OR14. In some embodiments, R2is -SR14. In some embodiments, R2is -N(R14)2. In some embodiments, R2is NO2. In some embodiments, R2is –CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIB), (VIC), (VIC-1), or (VIC-2), R3is hydrogen. In some embodiments, R3is halogen. In some embodiments, R3is fluoro. In some embodiments, R3is chloro. In some embodiments, R3is C1-4 alkyl. In some embodiments, R3is methyl. In some embodiments, R3is C1-4 haloalkyl. In some embodiments, R3is trifluoromethyl. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIB), (VIC), (VIC-1), or (VIC-2), R2is independently selected at each occurrence from halogen and C1-4alkyl. In some embodiments. In some embodiments, R2is halogen. In some embodiments, R2is C1-4alkyl. In some embodiments, R2is C1-4haloalkyl. In some embodiments, R2is -OR14. In some embodiments, R2is -SR14. In some embodiments, R2is -N(R14)2. In some embodiments, R2is NO2. In some embodiments, R2is –CN. In some embodiments, the compound is of Formula (VIA-2): (VIA-2), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIA-3): (VIA-3), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIB-1): RAO A N HN S B (VIB-1), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIB-2): (VIB-2), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIC-3): (VIC-3), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VID-1): (VID-1); or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (ID-2): (VID-2); or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIE-1): (VIE-1), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIE-2): (VIE-2), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIF): (VIF), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is selected from a C3-C10 carbocycle and a 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, - N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, =O, -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, =O, and -CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), the Ring B heterocycle comprises 1-4 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring B heterocycle comprises 1-3 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring B heterocycle comprises 1-2 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring B heterocycle comprises 2-3 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring B heterocycle comprises 1 heteroatom selected from O, N, and S. In some embodiments, the Ring B heterocycle comprises 2 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring B heterocycle comprises 3 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring B heterocycle comprises 4 heteroatoms independently selected from O, N, and S. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), the Ring B heterocycle comprises 1-4 heteroatoms independently selected from O and N. In some embodiments, the Ring B heterocycle comprises 1-3 heteroatoms independently selected from O and N. In some embodiments, the Ring B heterocycle comprises 1-2 heteroatoms independently selected from O and N. In some embodiments, the Ring B heterocycle comprises 2-3 heteroatoms independently selected from O and N. In some embodiments, the Ring B heterocycle comprises 1 heteroatom selected from O and N. In some embodiments, the Ring B heterocycle comprises 2 heteroatoms independently selected from O and N. In some embodiments, the Ring B heterocycle comprises 3 heteroatoms independently selected from O and N. In some embodiments, the Ring B heterocycle comprises 4 heteroatoms independently selected from O and N. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), the Ring B heterocycle comprises 4 N heteroatoms. In some embodiments, the Ring B heterocycle comprises 3 N heteroatoms. In some embodiments, the Ring B heterocycle comprises 3 N heteroatoms and 1 O heteroatom. In some embodiments, the Ring B heterocycle comprises 2 N heteroatoms and 1 O heteroatom. In some embodiments, the Ring B heterocycle comprises 2 N heteroatoms and 1 S heteroatom. In some embodiments, the Ring B heterocycle comprises 1 O heteroatom and 1 N heteroatom. In some embodiments, the Ring B heterocycle comprises 1 O heteroatom and 1 S heteroatom. In some embodiments, the Ring B heterocycle comprises 1 S heteroatom and 1 N heteroatom. In some embodiments, the Ring B heterocycle comprises 2 N heteroatoms. In some embodiments, the Ring B heterocycle comprises 1 heteroatom that is O. In some embodiments, the Ring B heterocycle comprises 1 heteroatom that is N. In some embodiments, the Ring B heterocycle comprises 1 heteroatom that is S. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is C3-C10carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, - N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, =O, -CN; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, =O, and -CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is 3- to 12-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, - N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, =O, -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, =O, and -CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is selected from a C3-C10carbocycle and a 3- to 12-membered heterocycle, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, - N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, =O, -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, =O, and -CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is selected from a C6-C10aryl and a 3- to 12-membered heteroaryl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, - N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, =O, and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, =O, and -CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is selected from a C6-C10 aryl and a 3- to 12-membered heteroaryl, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, - N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; C1-6 alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, =O, and -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, =O, and -CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is selected from a C6-C10 aryl and a 3- to 12-membered heteroaryl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, - N(R12)S(O)2(R12), -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, =O, -CN, C3-6carbocycle and 3- to 6-membered heterocycle, and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen and -OR12. In some embodiments, Ring B is selected from a C6-C10aryl and a 3- to 12-membered heteroaryl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -N(R12)2, -C(O)N(R12)2, - N(R12)C(O)R12, -N(R12)S(O)2(R12), -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, =O, -CN, C3-6 carbocycle and 3- to 6-membered heterocycle, and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen and -OR12; and R12is selected from hydrogen, C1-4alkyl, C1-4haloalkyl, and C3-6cycloalkyl. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is selected from a C6-C10aryl and a 3- to 12-membered heteroaryl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2(R12), -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, =O, -CN, C3-6 carbocycle and 3- to 6-membered heterocycle, and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen and -OR12; and R12is selected from hydrogen, -CH3, -CH2CH2CH3, -CH2CH(CH3)2, -CH2CF3, and cyclopropyl. In some embodiments, Ring B is selected from a C6-C10aryl and a 3- to 12-membered heteroaryl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2(R12), -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, =O, -CN, C3-6 carbocycle and 3- to 6-membered heterocycle, and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen and -OR12. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is selected from a C6-C10aryl and a 3- to 12-membered heteroaryl, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, -N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2(R12), -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, =O, -CN, C3-6 carbocycle and 3- to 6-membered heterocycle, and C1-6 alkyl optionally substituted with 1-4 substituents independently selected from halogen and -OR12. In some embodiments, Ring B is selected from phenyl, pyridinyl, pyridazinyl, pyrimidinyl, benzthiazolyl, benzimidazolyl, and benzfurazanyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2(R12), -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, =O, -CN, C3-6carbocycle and 3- to 6-membered heterocycle, and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen and - OR12. In some embodiments, Ring B is not pyrazolyl. In some embodiments, Ring B is selected from phenyl, pyridinyl, pyridazinyl, pyrimidinyl, benzthiazolyl, benzimidazolyl, and benzfurazanyl, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, -N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2(R12), -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, =O, -CN, C3-6carbocycle and 3- to 6-membered heterocycle, and C1-6alkyl optionally substituted with 1-4 substituents independently selected from halogen and -OR12. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is selected from phenyl, pyridinyl, pyridazinyl, pyrimidinyl, indolyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, 2,1,3- benzoxadiazolyl benzfurazanyl, thiazolo[4,5-b]pyridinyl, pyrrolo[2,3-b]pyridinyl, imidazo[1,5- a]pyridinyl, quinolinyl, isoquinolinyl, quinazolinyl, and quinoxalinyl, each of which is optionally substituted with one or more substituents independently selected from: -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, , , , , , , , , , , , , , , , , and . In some embodiments, Ring B is selected from phenyl, pyridinyl, pyridazinyl, pyrimidinyl, benzthiazolyl, benzimidazolyl, and benzfurazanyl, each of which is optionally substituted with one or more substituents independently selected from: -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, , , , , , , , , , , , , and . In some embodiments, Ring B is selected from phenyl, pyridinyl, pyridazinyl, pyrimidinyl, benzthiazolyl, benzimidazolyl, and benzfurazanyl, each of which is optionally substituted with 1- 4 substituents independently selected from: -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, - CHF2, , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is phenyl optionally substituted with 1- 4 substituents independently selected from: -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, , , , , , , , , , , , , and . In some embodiments, Ring B is pyridinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, , , , , , , , , , , , , and . In some embodiments, Ring B is pyridazinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, , , , , , , , , , , , , and . In some embodiments, Ring B is pyrimidinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, , , , , , , , , , , , , and . In some embodiments, Ring B is benzthiazolyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, , , , , , , , , , , , , and . In some embodiments, Ring B is benzimidazolyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, - CHF2, , , , , , , , , , , , , and . In some embodiments, Ring B is benzfurazanyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is selected from: , , , , , , , , , , , , , , , , , , , , , , , O S O , , , , , , , , , , , , , , , , , , , , , , , , F N , , , , , , , , , , , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is O S O . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, F Ring B is . In some embodiments, Ring B isN. In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is selected from (a), (b) and (c): (a) , wherein X1is selected from N, CH, and CR5; (b) , wherein X2is selected from S and NR7; and (c) , wherein X3is selected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system; and each occurrence of R5, R6, and R8are halogen, C1- 6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, - N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and –CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 1 or 2. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), q is 0, 1, or 2. In some embodiments, q is 0 or 1. In some embodiments, q is 1 or 2. In some embodiments, q is 0. In some embodiments, p is 1. In some embodiments, q is 2. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), r is 0, 1, or 2. In some embodiments, r is 0 or 1. In some embodiments, r is 1 or 2. In some embodiments, r is 0. In some embodiments, r is 1. In some embodiments, r is 2. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), X1is N. In some embodiments, X1is CH. In some embodiments, X1is CH. In some embodiments, X2is S. In some embodiments, X2is NR7. In some embodiments, X2is NH. In some embodiments, X3is S. In some embodiments, X3is N. In some embodiments, X3is NH. In some embodiments, X4is O. In some embodiments, X4is CR9. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), X3is S and X4is O. In some embodiments, X3is S and X4is CR9. In some embodiments, X3is N and X4is O. In some embodiments, X3is N and X4is CR9. In some embodiments, X3is NH and X4is O. In some embodiments, X3is NH and X4is CR9. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R9is hydrogen. In some embodiments, R9is C1-4alkyl. In some embodiments, R9is methyl. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- X1N 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B isRB. In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, Ring B is . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), RBis selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, - N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN. In some embodiments, RBis selected from halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2(R12), -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, =O, and -CN. In some embodiments, RBis selected from halogen, C1-6 alkyl, C1-6 haloalkyl, and -OR12. In some embodiments, RBis selected from halogen, methyl, C1-6haloalkyl, and -OR12. In some embodiments, RBis halogen. In some embodiments, RBis C1-4alkyl. In some embodiments, RBis methyl. In some embodiments, RBis C1-4haloalkyl. In some embodiments, RBis -OR12. In some embodiments, RBis -SR12. In some embodiments, RBis -N(R12)2. In some embodiments, RBis -C(O)R12. In some embodiments, RBis -C(O)OR12. In some embodiments, RBis -OC(O)R12. In some embodiments, RBis -C(O)N(R12)2. In some embodiments, RBis -N(R12)C(O)R12. In some embodiments, RBis -N(R12)S(O)2(R12). In some embodiments, RBis -S(O)2R12. In some embodiments, RBis -S(O)2N(R12)2. In some embodiments, RBis -NO2. In some embodiments, RBis -CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is , wherein X1is selected from N, CH, and CR5. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is , and X2is selected from S and NR7. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), Ring B is , and X3is selected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R7and R9are each independently selected from hydrogen, and C1-4alkyl. In some embodiments, R7is hydrogen. In some embodiments, R7is C1-4alkyl. In some embodiments, R7is C1-4 haloalkyl. In some embodiments, R9is hydrogen. In some embodiments, R9is C1-4 alkyl. In some embodiments, R9is C1-4 haloalkyl. In some embodiments,, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R6and R8are each independently selected at each occurrence from halogen and C1-4alkyl. In some embodiments,, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R5is independently selected at each occurrence from halogen and C1-4 alkyl. In some embodiments, R5is halogen. In some embodiments, R5is C1-4alkyl. In some embodiments, R5is C1-4haloalkyl. In some embodiments, R5is -OR12. In some embodiments, R5is -SR12. In some embodiments, R5is -N(R12)2. In some embodiments, R5is -C(O)R12. In some embodiments, R5is -C(O)OR12. In some embodiments, R5is -OC(O)R12. In some embodiments, R5is -C(O)N(R12)2. In some embodiments, R5is -N(R12)C(O)R12. In some embodiments, R5is -N(R12)S(O)2(R12). In some embodiments, R5is -S(O)2R12. In some embodiments, R5is -S(O)2N(R12)2. In some embodiments, R5is -NO2. In some embodiments, R5is -CN. In some embodiments,, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R6is halogen. In some embodiments, R6is C1-4 alkyl. In some embodiments, R6is C1-4 haloalkyl. In some embodiments, R6is -OR12. In some embodiments, R6is -SR12. In some embodiments, R6is -N(R12)2. In some embodiments, R6is -C(O)R12. In some embodiments, R6is -C(O)OR12. In some embodiments, R6is -OC(O)R12. In some embodiments, R6is -C(O)N(R12)2. In some embodiments, R6is -N(R12)C(O)R12. In some embodiments, R6is -N(R12)S(O)2(R12). In some embodiments, R6is -S(O)2R12. In some embodiments, R6is -S(O)2N(R12)2. In some embodiments, R6is -NO2. In some embodiments, R6is -CN. In some embodiments,, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R8is halogen. In some embodiments, R8is C1-4 alkyl. In some embodiments, R8is C1-4 haloalkyl. In some embodiments, R8is -OR12. In some embodiments, R8is -SR12. In some embodiments, R8is -N(R12)2. In some embodiments, R8is - C(O)R12. In some embodiments, R8is -C(O)OR12. In some embodiments, R8is -OC(O)R12. In some embodiments, R8is -C(O)N(R12)2. In some embodiments, R8is -N(R12)C(O)R12. In some embodiments, R8is -N(R12)S(O)2(R12). In some embodiments, R8is -S(O)2R12. In some embodiments, R8is -S(O)2N(R12)2. In some embodiments, R8is -NO2. In some embodiments, R8is -CN. In some embodiments,, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R10is hydrogen. In some embodiments, R10is C1-6alkyl. In some embodiments, R10is C1-4haloalkyl. In some embodiments, R10is cycloalkyl optionally substituted with one or more halogen. In some embodiments, R10is hydrogen. In some embodiments, R10is C1-6 alkyl. In some embodiments, R10is C1-4 haloalkyl. In some embodiments, R10is cycloalkyl optionally substituted with 1-4 halogen. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R11is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, R11is hydrogen. In some embodiments, R11is C1-6alkyl. In some embodiments, R11is C1-4haloalkyl. In some embodiments, R11is cycloalkyl optionally substituted with one or more halogen. In some embodiments, R11is independently selected at each occurrence from hydrogen, and C1-4 alkyl. In some embodiments, R11is hydrogen. In some embodiments, R11is C1-6 alkyl. In some embodiments, R11is C1-4 haloalkyl. In some embodiments, R11is cycloalkyl optionally substituted with 1-4 halogen. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R12is hydrogen. In some embodiments, R12is C1-6alkyl. In some embodiments, R12is C1-4haloalkyl. In some embodiments, R12is cycloalkyl optionally substituted with one or more halogen. In some embodiments, R12is -CH3. In some embodiments, R12is CH2CF3. In some embodiments, R12is cyclopropyl. In some embodiments, R12is independently selected at each occurrence from hydrogen, -CH3, -CH2CH2CH3, -CH2CH(CH3)2, -CH2CF3, and cyclopropyl. In some embodiments, R12is hydrogen. In some embodiments, R12is C1-6 alkyl. In some embodiments, R12is C1-4 haloalkyl. In some embodiments, R12is cycloalkyl optionally substituted with 1-4 halogen. In some embodiments, R12is -CH3. In some embodiments, R12is CH2CF3. In some embodiments, R12is cyclopropyl. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R13is selected from C1-4 alkyl and cyclopropyl optionally substituted with one or more -F. In some embodiments, R13is hydrogen. In some embodiments, R13is C1-6 alkyl. In some embodiments, R13is C1-4 haloalkyl. In some embodiments, R13is cycloalkyl optionally substituted with one or more halogen. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIB), (VIB-1), (VIB-2), (VIC), (VIC-1), (VIC-2), (VIC- 3), (VID-1), (VID-2), (VIE-1), (VIE-2), or (VIF), R14is hydrogen. In some embodiments, R14is C1-6 alkyl. In some embodiments, R14is C1-4 haloalkyl. In some embodiments, R14is cycloalkyl optionally substituted with one or more halogen. In some embodiments, the compound is of Formula (VIA-4): (VIA-4), or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VIA-5): (VIA-5), or a pharmaceutically acceptablesalt thereof; wherein X1 is selected from N, CH, and CR5.In some embodiments, the compound is of Formula (VIA-6): (VIA-6), or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VIA-7): (VIA-7), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIB-3): (VIB-3), or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VIC-4): (VIC-4), or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VID-3): (VID-3); or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VID-4): (VID-4); or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, for the compound of Formulae (VIA-4), (VIA-5), (VIA-6), (VIA- 7), (VIB-3), (VIC-4), (VID-3), or (VID-4), R5is independently selected at each occurrence from halogen and C1-4alkyl. In some embodiments, R5is halogen. In some embodiments, R5is C1-4alkyl. In some embodiments, R5is C1-4haloalkyl. In some embodiments, R5is -OR12. In some embodiments, R5is -SR12. In some embodiments, R5is -N(R12)2. In some embodiments, R5is - C(O)R12. In some embodiments, R5is -C(O)OR12. In some embodiments, R5is -OC(O)R12. In some embodiments, R5is -C(O)N(R12)2. In some embodiments, R5is -N(R12)C(O)R12. In some embodiments, R5is -N(R12)S(O)2(R12). In some embodiments, R5is -S(O)2R12. In some embodiments, R5is -S(O)2N(R12)2. In some embodiments, R5is -NO2. In some embodiments, R5is -CN. In some embodiments, for the compound of Formulae (VIA-4), (VIA-5), (VIA-6), (VIA- 7), (VIB-3), (VIC-4), (VID-3), or (VID-4), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 1 or 2. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, the compound is of Formula (VIC-5): (VIC-5), or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VIA-8): (VIA-8), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (VIA-4), (VIA-5), (VIA-6), (VIA- 7), (VIA-8), (VIB-3), (VIC-4), (VIC-5), (VID-3), or (VID-4), RBis selected from halogen, C1- 6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2,-C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, - N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN. In some embodiments, RBis selected from halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2(R12), -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, =O, and -CN. In some embodiments, RBis selected from halogen, C1-6alkyl, C1-6haloalkyl, and - OR12. In some embodiments, RBis selected from halogen, methyl, C1-6 haloalkyl, and -OR12. In some embodiments, RBis halogen. In some embodiments, RBis C1-4 alkyl. In some embodiments, RBis methyl. In some embodiments, RBis C1-4 haloalkyl. In some embodiments, RBis -OR12. In some embodiments, RBis -SR12. In some embodiments, RBis -N(R12)2. In some embodiments, RB is -C(O)R12. In some embodiments, RBis -C(O)OR12. In some embodiments, RBis -OC(O)R12. In some embodiments, RBis -C(O)N(R12)2. In some embodiments, RBis -N(R12)C(O)R12. In some embodiments, RBis -N(R12)S(O)2(R12). In some embodiments, RBis -S(O)2R12. In some embodiments, RBis -S(O)2N(R12)2. In some embodiments, RBis -NO2. In some embodiments, RBis -CN. In some embodiments, the compound is of Formula (VIC-6): (VIC-6), or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VIC-7): (VIC-7), or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VID-5): (VID-5); or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VID-6): (VID-6); or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VIE-3): (VIE-3); or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VIE-4): (VIE-4); or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VIE-5): (VIE-5); or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VIE-6): (VIE-6); or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VIF-1): (V1F-1); or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VIF-2): (VIF-2), or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), the Ring A saturated heterocycloalkyl comprises 1- 4 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A saturated heterocycloalkyl comprises 1-3 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A saturated heterocycloalkyl comprises 1-2 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A saturated heterocycloalkyl comprises 2-3 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A saturated heterocycloalkyl comprises 1 heteroatom selected from O, N, and S. In some embodiments, the Ring A saturated heterocycloalkyl comprises 2 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A saturated heterocycloalkyl comprises 3 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A saturated heterocycloalkyl comprises 4 heteroatoms independently selected from O, N, and S. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), the Ring A saturated heterocycloalkyl comprises 1- 4 heteroatoms independently selected from O and N. In some embodiments, the Ring A saturated heterocycloalkyl comprises 1-3 heteroatoms independently selected from O and N. In some embodiments, the Ring A saturated heterocycloalkyl comprises 1-2 heteroatoms independently selected from O and N. In some embodiments, the Ring A saturated heterocycloalkyl comprises 2-3 heteroatoms independently selected from O and N. In some embodiments, the Ring A saturated heterocycloalkyl comprises 1 heteroatom selected from O and N. In some embodiments, the Ring A saturated heterocycloalkyl comprises 2 heteroatoms independently selected from O and N. In some embodiments, the Ring A saturated heterocycloalkyl comprises 3 heteroatoms independently selected from O and N. In some embodiments, the Ring A saturated heterocycloalkyl comprises 4 heteroatoms independently selected from O and N. In some embodiments, t for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), he Ring A saturated heterocycloalkyl comprises 4 N heteroatoms. In some embodiments, the Ring A saturated heterocycloalkyl comprises 3 N heteroatoms. In some embodiments, the Ring A saturated heterocycloalkyl comprises 3 N heteroatoms and 1 O heteroatom. In some embodiments, the Ring A saturated heterocycloalkyl comprises 2 N heteroatoms and 1 O heteroatom. In some embodiments, the Ring A saturated heterocycloalkyl comprises 2 N heteroatoms and 1 S heteroatom. In some embodiments, the Ring A saturated heterocycloalkyl comprises 1 O heteroatom and 1 N heteroatom. In some embodiments, the Ring A saturated heterocycloalkyl comprises 1 O heteroatom and 1 S heteroatom. In some embodiments, the Ring A saturated heterocycloalkyl comprises 1 S heteroatom and 1 N heteroatom. In some embodiments, the Ring A saturated heterocycloalkyl comprises 2 N heteroatoms. In some embodiments, the Ring A saturated heterocycloalkyl comprises 1 heteroatom that is O. In some embodiments, the Ring A saturated heterocycloalkyl comprises 1 heteroatom that is N. In some embodiments, the Ring A saturated heterocycloalkyl comprises 1 heteroatom that is S. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), the Ring A partially saturated heterocycle comprises 1-4 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A partially saturated heterocycle comprises 1-3 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A partially saturated heterocycle comprises 1-2 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A partially saturated heterocycle comprises 2-3 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A partially saturated heterocycle comprises 1 heteroatom selected from O, N, and S. In some embodiments, the Ring A partially saturated heterocycle comprises 2 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A partially saturated heterocycle comprises 3 heteroatoms independently selected from O, N, and S. In some embodiments, the Ring A partially saturated heterocycle comprises 4 heteroatoms independently selected from O, N, and S. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), the Ring A partially saturated heterocycle comprises 1-4 heteroatoms independently selected from O and N. In some embodiments, the Ring A partially saturated heterocycle comprises 1-3 heteroatoms independently selected from O and N. In some embodiments, the Ring A partially saturated heterocycle comprises 1-2 heteroatoms independently selected from O and N. In some embodiments, the Ring A partially saturated heterocycle comprises 2-3 heteroatoms independently selected from O and N. In some embodiments, the Ring A partially saturated heterocycle comprises 1 heteroatom selected from O and N. In some embodiments, the Ring A partially saturated heterocycle comprises 2 heteroatoms independently selected from O and N. In some embodiments, the Ring A partially saturated heterocycle comprises 3 heteroatoms independently selected from O and N. In some embodiments, the Ring A partially saturated heterocycle comprises 4 heteroatoms independently selected from O and N. In some embodiments, t for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), he Ring A partially saturated heterocycle comprises 4 N heteroatoms. In some embodiments, the Ring A partially saturated heterocycle comprises 3 N heteroatoms. In some embodiments, the Ring A partially saturated heterocycle comprises 3 N heteroatoms and 1 O heteroatom. In some embodiments, the Ring A partially saturated heterocycle comprises 2 N heteroatoms and 1 O heteroatom. In some embodiments, the Ring A partially saturated heterocycle comprises 2 N heteroatoms and 1 S heteroatom. In some embodiments, the Ring A partially saturated heterocycle comprises 1 O heteroatom and 1 N heteroatom. In some embodiments, the Ring A partially saturated heterocycle comprises 1 O heteroatom and 1 S heteroatom. In some embodiments, the Ring A partially saturated heterocycle comprises 1 S heteroatom and 1 N heteroatom. In some embodiments, the Ring A partially saturated heterocycle comprises 2 N heteroatoms. In some embodiments, the Ring A partially saturated heterocycle comprises 1 heteroatom that is O. In some embodiments, the Ring A partially saturated heterocycle comprises 1 heteroatom that is N. In some embodiments, the Ring A partially saturated heterocycle comprises 1 heteroatom that is S. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), Ring A is selected from C3-C10 saturated cycloalkyl, and 3- to 10-membered saturated heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -C(O)N(R11)2, -N(R11)C(O)R11, -NO2, and =O; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, and =O, -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, C1- 6 alkyl, C1-6 haloalkyl, =O, and -CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), Ring A is selected from C3-C10 saturated cycloalkyl, and 3- to 10-membered saturated heterocycloalkyl, each of which is optionally substituted with 1- 4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -C(O)N(R11)2, -N(R11)C(O)R11, -NO2, and =O; C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, and =O, -CN; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, C1-6 alkyl, C1- 6 haloalkyl, =O, and -CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), Ring A is C3-C10saturated cycloalkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -C(O)N(R11)2, -N(R11)C(O)R11, -NO2, and =O; C1-6 alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, and =O, -CN; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, C1-6alkyl, C1-6haloalkyl, =O, and -CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), Ring A is 3- to 10-membered saturated heterocycloalkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -C(O)N(R11)2, -N(R11)C(O)R11, -NO2, and =O; C1-6 alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, and =O, -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, C1-6alkyl, C1-6haloalkyl, =O, and -CN. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), Ring A is selected from C3-C6 saturated cycloalkyl, and 3- to 6-membered saturated heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -C(O)OR11, C1-6alkyl, C1-6haloalkyl, and 3- to 6-membered heterocycloalkyl, optionally substituted with one or more C1-6alkyl. In some embodiments, Ring A is selected from C3-C6saturated cycloalkyl, and 3- to 6-membered saturated heterocycloalkyl, each of which is optionally substituted with 1-4 substituents independently selected from halogen, -C(O)OR11, C1-6 alkyl, C1-6 haloalkyl, and 3- to 6-membered heterocycloalkyl, optionally substituted with 1-4 C1-6 alkyl. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), Ring A is selected from: cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -C(O)OR11, C1-6 alkyl, C1-6 haloalkyl, and 3- to 6-membered heterocycloalkyl, optionally substituted with one or more C1-6 alkyl; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl. In some embodiments, Ring A is selected from: cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -C(O)OR11, C1-6alkyl, C1-6haloalkyl, and 3- to 6-membered heterocycloalkyl, optionally substituted with one or more C1-6 alkyl; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl; and R11is independently selected at each occurrence from hydrogen, and C1-4 alkyl. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), Ring A is selected from: cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - C(O)OR11, C1-6 alkyl, C1-6 haloalkyl, and 3- to 6-membered heterocycloalkyl, optionally substituted with one or more C1-6 alkyl. In some embodiments, Ring A is selected from: cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is optionally substituted with 1-4 substituents independently selected from halogen, -C(O)OR11, C1-6alkyl, C1-6haloalkyl, and 3- to 6-membered heterocycloalkyl, optionally substituted with 1-4 C1-6alkyl; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), Ring A is selected from: cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is optionally substituted with one or more substituents independently selected from -F, -CH3, O O ,O,O, , and ; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl. In some embodiments, Ring A is selected from: cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is optionally substituted with 1-4 substituents independently selected from -F, -CH3, O O ,O,O, , and ; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), wherein Ring A is selected from: cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is optionally substituted with one or more substituents independently selected from -F, -CH3, , , , , and ; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl. In some embodiments, wherein Ring A is selected from: cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is optionally substituted with 1-4 substituents independently selected from -F, -CH3, , , , , and ; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl; RAis selected from -F, -CN, -CH3, -CHF2, -CF3, -CH2OCH3, -OCH3, and . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), wherein Ring A is selected from: cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is optionally substituted with one or more substituents independently selected from -F, - CH3, , , , , and ; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl. In some embodiments, wherein Ring A is selected from: cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is optionally substituted with 1-4 substituents independently selected from -F, -CH3, , , , , and ; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl; RAis selected from -F, -CN, -CH3, -CHF2, -CF3, -CH2OCH3, -OCH3, and . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), RAis selected from halogen, -CN, C1-6alkyl, C1-6haloalkyl, and C3-C6saturated cycloalkyl. In some embodiments, RAis halogen. In some embodiments, RAis fluoro. In some embodiments, RAis -OR10. In some embodiments, RAis -SR10. In some embodiments, RAis -N(R10)2. In some embodiments, RAis -CN. In some embodiments, RAis C1-6 alkyl. In some embodiments, RAis C1-6 haloalkyl. In some embodiments, RAis C3-C6 saturated cycloalkyl. In some embodiments, RAis 3- to 6-membered saturated heterocycloalkyl.In some embodiments, RAis selected from -F, -CN, -CH3, -CHF2, -CF3, -CH2OCH3, -OCH3, and . In some embodiments, RAis selected from -F, CN, -CH3, -CHF2, -CF3, and . In some embodiments, RAis selected from -F. In some embodiments, RAis CN. In some embodiments, RAis -CH3. In some embodiments, RAis -CHF2. In some embodiments, RAis -CF3. In some embodiments, RAis . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), is selected from: O O F , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), is selected from: O O F , , , , , , , , , , , , , , , , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), is selected from: O O F , , , , , , , , , , , , , , , , , , , , , , , , , , and . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), O F (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), is . In some embodiments, is . In some embodiments, is . In some O embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, F N is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some embodiments, is . In some F embodiments, is and . In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), R10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen and C1-6 alkyl. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), Ring A is unsubstituted tetrahydropyranyl. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with 1-4 C1-6 alkyl. In some embodiments, Ring A is tetrahydropyranyl substituted with 1-4 C1-6 alkyl. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with 1-4 methyl. In some embodiments, Ring A is tetrahydropyranyl substituted with 1-4 methyl. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with one C1-6alkyl. In some embodiments, Ring A is tetrahydropyranyl substituted with one C1-6alkyl. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with one methyl. In some embodiments, Ring A is tetrahydropyranyl substituted with one methyl. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with four C1-6 alkyl. In some embodiments, Ring A is tetrahydropyranyl substituted with four C1-6 alkyl. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with four methyl. In some embodiments, Ring A is tetrahydropyranyl substituted with four methyl In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), Ring A is unsubstituted tetrahydrofuranyl. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with 1-4 C1-6alkyl. In some embodiments, Ring A is tetrahydrofuranyl substituted with 1-4 C1-6alkyl. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with 1-4 methyl. In some embodiments, Ring A is tetrahydrofuranyl substituted with 1-4 methyl. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with one C1-6 alkyl. In some embodiments, Ring A is tetrahydrofuranyl substituted with one C1-6 alkyl. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with one methyl. In some embodiments, Ring A is tetrahydrofuranyl substituted with one methyl. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with four C1-6alkyl. In some embodiments, Ring A is tetrahydrofuranyl substituted with four C1-6alkyl. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with four methyl. In some embodiments, Ring A is tetrahydrofuranyl substituted with four methyl. In some embodiments, Ring A is not N-Boc pyrrolidinyl. In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC- 7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), Ring A is tetrahydropyranyl optionally substituted with 1-4 halogen. In some embodiments, Ring A is tetrahydropyranyl substituted with 1-4 halogen. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with 1-4 fluorine. In some embodiments, Ring A is tetrahydropyranyl substituted with 1-4 fluorine. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with one halogen. In some embodiments, Ring A is tetrahydropyranyl substituted with one halogen. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with one fluorine. In some embodiments, Ring A is tetrahydropyranyl substituted with one fluorine. In some embodiments, the compound is of Formula (VIA-9): (VIA-9), or a pharmaceutically acceptable salt thereof; wherein R5is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and -C(O)OR11; and R16is selected from halogen, -OR11, and C1-6 alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, the compound is of Formula (VIA-10): (VIA-10), or a pharmaceutically acceptable salt thereof; wherein R5is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and -C(O)OR11; and R16is selected from halogen, -OR11, and C1-6alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, the compound is of Formula (VIA-11): (VIA-11), or a pharmaceutically acceptable salt thereof; wherein R5is selected from hydrogen C1 6 alkyl C1 6 haloalkyl and -C(O)OR11; and R16 is selected from halogen, -OR11, and C1-6alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, the compound is of Formula (VIA-12): (VIA-12), or a pharmaceutically acceptable salt thereof; wherein R5is selected from hydrogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR11; and R16is selected from halogen, -OR11, and C1-6alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, for the compound of Formulae (VIA-9), (VIA-10), ), (VIA-11), or (VIA-12), R5is independently selected at each occurrence from halogen and C1-4alkyl. In some embodiments, R5is halogen. In some embodiments, R5is C1-4 alkyl. In some embodiments, R5is C1-4 haloalkyl. In some embodiments, R5is -CN. In some embodiments, for the compound of Formulae (VIA-9), (VIA-10), ), (VIA-11), or (VIA-12), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 1 or 2. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, the compound is of Formula (VIA-13): (VIA-13), or a pharmaceutically acceptable salt thereof; wherein R5is selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and -C(O)OR11; and R16is selected from halogen, -OR11, and C1-6 alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, for the compound of Formulae (VIA-9), (VIA-10), ), (VIA-11), (VIA-12), ir (VIA-13), RBis selected from halogen, C1-6 alkyl, C1-6 haloalkyl, and -CN. In some embodiments, RBis selected from halogen, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, RBis selected from halogen, methyl, and halomethyl. In some embodiments, RBis halogen. In some embodiments, RBis C1-4 alkyl. In some embodiments, RBis methyl. In some embodiments, RBis C1-4haloalkyl. In some embodiments, RBis -CN. In some embodiments, for the compound of Formulae (VIA-9), (VIA-10), ), (VIA-11), (VIA-12), ir (VIA-13), each R16is independently selected from halogen, C1-6alkyl, C1-6haloalkyl, and -C(O)OR11; and R11is selected from hydrogen and C1-4alkyl. In some embodiments, each R16is independently is selected from halogen, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, each R16is independently is selected from halogen, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, each R16is independently is selected from halogen, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, each R16is independently is selected from hydrogen and C1-6 alkyl. In some embodiments, each R16is independently is selected from -F, C1-4alkyl, and C1-4fluroalkyl. In some embodiments, R16is hydrogen. In some embodiments, R16is C1-6alkyl. In some embodiments, R16is C1-6haloalkyl. In some embodiments, R16is -C(O)OR11. In some embodiments, each R16is independently is selected from -F and methyl. In some embodiments, each R16is independently is selected from halogen. In some embodiments, each R16is -F. In some embodiments, each R16is independently is selected from C1-6 alkyl. In some embodiments, each R16is independently is selected from methyl. In some embodiments, for the compound of Formulae (VIA-9), (VIA-10), ), (VIA-11), (VIA-12), ir (VIA-13), the compound has 0, 1, 2, or 3 R16groups. In some embodiments, the compound has 0, 1, or 2, R16groups. In some embodiments, the compound has 0 or 1 R16groups. In some embodiments, the compound has 0 R16groups. In some embodiments, the compound has 1, 2, or 3 R16groups. In some embodiments, the compound has 1 or 2, R16groups. In some embodiments, the compound has 1 R16groups. In some embodiments, the compound has 2 R16groups. In some embodiments, In some embodiments, for the compound of Formulae (V), (VA), (VB), (VC), (VD), (VE), (VI), (VIA), (VIA-1), (VIA-2), (VIA-3), (VIA-4), (VIA-5), (VIA-6), (VIA-7), (VIA-8), (VIB), (VIB-1), (VIB-2), (VIB-3), (VIC), (VIC-1), (VIC-2), (VIC-3), (VIC-4), (VIC-5), (VIC-6), (VIC-7), (VID-1), (VID-2), (VID-3), (VID-4), (VID-5), (VID-6), (VIE-1), (VIE-2), (VIE-3), (VIE-4), (VIE-5), (VIE-6), (VIF), (VIF-1), or (VIF-2), Ring A is cyclopropyl optionally substituted with 1-4 halogen. In some embodiments, Ring A is cyclopropyl substituted with 1-4 halogen. In some embodiments, Ring A is cyclopropyl optionally substituted with 1-4 fluorine. In some embodiments, Ring A is cyclopropyl substituted with 1-4 fluorine. In some embodiments, Ring A is cyclopropyl optionally substituted with one halogen. In some embodiments, Ring A is cyclopropyl substituted with one halogen. In some embodiments, Ring A is cyclopropyl optionally substituted with one fluorine. In some embodiments, Ring A is cyclopropyl substituted with one fluorine. In some embodiments, the compound is of Formula (VIA-14): (VIA-14), or a pharmaceutically acceptable salt thereof; wherein Q3is selected from N and CH; and X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, the compound is of Formula (VIA-15): (VIA-15), or a pharmaceutically acceptable salt thereof; wherein Q3is selected from N and CH; X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, for the compound of Formulae (VIA-14) or (VIA-15), R5is independently selected at each occurrence from halogen and C1-4alkyl. In some embodiments, R5is halogen. In some embodiments, R5is C1-4 alkyl. In some embodiments, R5is C1-4 haloalkyl. In some embodiments, R5is -CN. In some embodiments, for the compound of Formulae (VIA-14) or (VIA-15), p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 1 or 2. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, the compound is of Formula (VIA-16): (VIA-16), or a pharmaceutically acceptable salt thereof; wherein Q3is selected from N and CH; and X1is selected from N, CH, and CR5. In some embodiments, for the compound of Formulae (VIA-14), (VIA-15), or (VIA-16), RBis selected from halogen, C1-6alkyl, C1-6haloalkyl, and -CN. In some embodiments, RBis selected from halogen, C1-6 alkyl, and C1-6 haloalkyl. In some embodiments, RBis selected from halogen, methyl, and halomethyl. In some embodiments, RBis halogen. In some embodiments, RBis C1-4 alkyl. In some embodiments, RBis methyl. In some embodiments, RBis C1-4 haloalkyl. In some embodiments, RBis -CN. In some embodiments, the compound is of Formula (VIA-17): (VIA-17), or a pharmaceutically acceptable salt thereof; wherein Q3is selected from N and CH; X1is selected from N, CH, and CR5. In some embodiments, X1is N. In some embodiments, X1is CH. In some embodiments, for the compound of Formulae (VIA-14), (VIA-15), (VIA-16), or (VIA-17), each R15is independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, and - C(O)OR11; and R11is selected from hydrogen and C1-4 alkyl. In some embodiments, each R15is independently is selected from halogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, each R15is independently is selected from halogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, each R15is independently is selected from halogen C1 6alkyl, and C1-6haloalkyl. In some embodiments, each R15is independently is selected from hydrogen and C1-6alkyl. In some embodiments, each R15is independently is selected from -F, C1-4 alkyl, and C1-4 fluroalkyl. In some embodiments, R15is hydrogen. In some embodiments, R15is C1-6 alkyl. In some embodiments, R15is C1-6 haloalkyl. In some embodiments, R15is -C(O)OR11. In some embodiments, each R15is independently is selected from -F and methyl. In some embodiments, each R15is independently is selected from halogen. In some embodiments, each R15is -F. In some embodiments, each R15is independently is selected from C1-6alkyl. In some embodiments, each R15is independently is selected from methyl. In some embodiments, for the compound of Formulae (VIA-14), (VIA-15), (VIA-16), or (VIA-17), the compound has 0, 1, 2, or 3 R15groups. In some embodiments, the compound has 0, 1, or 2, R15groups. In some embodiments, the compound has 0 or 1 R15groups. In some embodiments, the compound has 0 R15groups. In some embodiments, the compound has 1, 2, or 3 R15groups. In some embodiments, the compound has 1 or 2, R15groups. In some embodiments, the compound has 1 R15groups. In some embodiments, the compound has 2 R15groups. In In some embodiments, the compound is of Formula (VIA-18): (VIA-18), or a pharmaceutically acceptable salt thereof; wherein Q3is selected from N and CH. In some embodiments, the compound is of Formula (VIA-19): (VIA-19), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (VIA-20): (VIA-20), or a pharmaceutically acceptable salt thereof. Non-Limiting Exemplary Compounds In some embodiments, the compound is selected from the group consisting of the compounds in Examples 1-11 (e.g., Compounds 1-152), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is selected from the group consisting of the compounds delineated in Table 1, or a pharmaceutically acceptable salt thereof.

[0112] 1OW3400-78371

[0113] 471 1OW3400-78 1OW3400-78

[0114]

[0115] 1OW3400-78

[0116] 181

[0117]

[0118] 481

[0119] 58

[0120]

[0121] 1OW3400-78 1OW3400-78

[0122]

[0123]

[0124]

[0125] 1OW3400-78

[0126]

[0127]

[0128] 1OW3400-78

[0129]

[0130]

[0131]

[0132] :03

[0133]

[0134] O

[0135]

[0136] :06

[0137]

[0138] O

[0139] C-f

[0140]

[0141]

[0142] 1 0

[0143]

[0144] 1 1

[0145] ri

[0146] Fl

[0147]

[0148] 

[0149] cl

[0150] Pharmaceutical Compositions

[0151] Some embodiments provide a pharmaceutical composition comprising a compound of Formula (I), (II), (III), (IV), (V), or (VI), or any subformulae thereof, or any pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0152] Methods of Treatment

[0153] Provided herein are methods for inhibiting dual specificity tyrosine-phosphorylation- regulated kinase 1 A, encoded by the DYRK1A gene. For example, provided herein are inhibitors of DYRK1A useful for treating disorders associated with dysregulation of a DYRKL4 gene, a DYRK1A protein, or the expression or activity or level of any of the same (i.e., a DYRK1A- associated disorder), such as a DYRK1 A-associated neurological disorder.

[0154] A “DYRK1A inhibitor” as used herein includes any compound exhibiting DYRK1A inactivation activity (e.g., inhibiting or decreasing).

[0155] Indications

[0156] Compounds disclosed herein, including those of Formula (I), (II), (III), (IV), (V), or (VI), or any subformulae thereof, or pharmaceutically acceptable salts thereof, are useful for treating disorders which can be treated with a DYRK1 A inhibitor, such as DYRK1 A-associated disorders, e.g., neurological disorders such as those described herein.

[0157] Provided herein is a method for treating a neurological disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein.

[0158] The term “neurological disorder” refers to any disorder of the nervous system and / or visual system. “Neurological disease” or “neurological disorder” are used interchangeably herein, and include diseases or disorders that involve the central nervous system (CNS; e.g., brain, brainstem and cerebellum), the peripheral nervous system (PNS; including cranial nerves), and the autonomic nervous system (parts of which are located in both the CN S and PNS), including both structural and / or functional disorders (e.g., neurological syndrome).

[0159] Examples of neurological disorders include, but are not limited to, headache, stupor and coma, dementia, seizure, sleep disorders, trauma, infections, neoplasms, neuroopthalmology, movement disorders, demyelinating diseases, spinal cord disorders, tauopathies, synucleinopathies, and disorders of peripherai nerves, muscle and neuromuscular junctions. Addiction and mental illness, include, but are not limited to, bipolar disorder and schizophrenia, are also included in the definition of neurological disorder. The following is a list of several neurological disorders, symptoms, signs and syndromes that can be treated using compositions and methods according to the present invention: acquired epileptiform aphasia; acute disseminated encephalomyelitis; adrenoleukodystrophy; agenesis of the corpus callosum; agnosia: Aicardi syndrome; Alexander disease; Alpers’ disease; alternating hemiplegia; vascular dementia; amyotrophic lateral sclerosis; anencephaly; Angelman syndrome; angiomatosis; anoxia; aphasia; apraxia; arachnoid cysts; arachnoiditis; Anronl-Chiari malformation; arteriovenous malformation; Asperger syndrome; ataxia telegiectasia; attention deficit hyperactivity disorder; autism; autonomic dysfunction; back pain; Batten disease; Behcet's disease; Bell's palsy; benign essential blepharospasm; benign focal; amyotrophy; benign intracranial hypertension; Binswanger's disease; blepharospasm: Bloch Sulzberger syndrome; brachial plexus injury; brain abscess; brain injury; Brown-Sequard syndrome; Cana van disease; carpal tunnel syndrome; causalgia; central pain syndrome; central pontine myelinolysis: cephalic disorder; cerebral aneurysm; cerebral arteriosclerosis: cerebral atrophy; cerebral gigantism; cerebral palsy; Charcot-Marie-Tooth disease; Chiari malformation; chorea; chronic inflammatory demyelinating polyneuropathy; chronic pain; chronic regional pain syndrome; Coffin Lowry syndrome; coma, including persistent vegetative state; congenital facial diplegia; corticobasal degeneration: cranial arteritis; craniosynostosis, Creutzfeldt- Jakob disease; cumulative trauma disorders; Cushing's syndrome; cytomegalic inclusion body disease, cytomegalovirus infection; dancing eyes-dancing feet syndrome, Dandy Walker syndrome, Dawson disease; De Moisier’s syndrome, Dejerine-Klumke palsy; dementia, dermatomyositis; diabetic neuropathy; diffuse sclerosis; dysautonomia; dysgraphia; dyslexia; dystonias, early infantile epileptic encephalopathy; empty sella syndrome; encephalitis; encephaloceles, encephalotrigeminal angiomatosis; epilepsy; Erb's palsy; essential tremor, Fabry's disease, Fahr's syndrome; fainting; familial spastic paralysis, febrile seizures; Fisher syndrome; Friedreich's ataxia; fronto-temporal dementia; Gaucher's disease; Gerstmann's syndrome; giant cell arteritis; giant cell inclusion disease; globoid cell leukodystrophy; Guillain- Barre syndrome; HTLV-1 -associated myelopathy; Hallervorden-Spatz disease; head injury; headache; ...

Claims

WHAT IS CLAIMED IS:

1. A compound represented by the structure of Formula (I): (I), or a pharmaceutically acceptable salt thereof, wherein: each represents a single or a double bond, such that the bicyclic ring system comprising Y1, Y2, Y3, and Y4is an aromatic bicyclic ring system where (i) Y1is CR3, Y2is N, Y3is CR4, and Y4is CR3or N; (ii) Y1is S, Y2is C, Y3is CR4or N, and Y4is CR3; or (iii) Y1is N, Y2is N, Y3is CR4, and Y4is CR3; L is selected from , , and , wherein * denotes the point of attachment to Ring A, Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene, Z’ is selected from -NR1-, -S(O)-, -S(O)2-, C1-4alkylene, -NR1-C1-4alkylene, -S(O)-C1-4alkylene, and -S(O)2-C1-4alkylene; wherein each C1-4alkylene is optionally substituted with one or more halogen; Ring B is selected from (a), (b) and (c): (a) , X1is selected from N, CH, and CR5; (b) , X2is selected from S and NR7; and(c) , X3is selected from S, N, and NH, X4is selected from O and CR9, X5is N or CH, X6is N or CH, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system, provided that when Ring B is (a), Y1is CR3, Y2is N, Y3is CR4, and Y4is N, then p is 0; R1is independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4haloalkyl, and –C(O)C3-6cycloalkyl optionally substituted with one or more halogen; R2is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, - OR10, -SR10, -N(R10)2, NO2, and -CN; R3and R4are each independently selected at each occurrence from hydrogen, halogen, C1- 4 alkyl, and C1-4 haloalkyl; Ring A is selected from: cyclopropyl substituted with one or more C1-6alkyl or -CN, C3-6carbocycle substituted with one or more halogen, 3- to 6-membered heterocycle substituted with one or more halogen, C5-6spirocyclic carbocycle, and 5- to 6-membered spirocyclic heterocycle, any of which is optionally substituted with one or more substituents independently selected from: C1-6 alkyl, C1- 6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; C7-12carbocycle and 7- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl, provided that when Ring B is selected from (b), then Ring A is not chromane; provided that when one or more of (i), (ii), (ii), (iv), (v), (vi), (vii), and (viii) apply, then Ring A is further selected from C4-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl: (ix) Ring B is (a) and RAis selected from halogen, C1-4 haloalkyl, C3-6 cycloalkyl, -NR11, and -OR11; (x) Y1is S, Y2is C, Ring B is (a), and X1is N; (xi) Y1is S, Y2is C, Ring B is (a), and RAis C1-4alkyl; (xii) Ring B is (a), and p is 1, 2, or 3; (xiii) R1is C1-4 alkyl or C1-4 haloalkyl; (xiv) Ring B is (c); and (xv) Y1is CR3, Y2is N, Y3is CR3, and Y4is N; (xvi) Y1is N, Y2is N, Y3is CR4, Y4is CR3, and Ring B is (a) or (c); provided that when Ring B is (a), X1is CH, RAis methyl, Y1is CR3, and Y2is N, then Ring A is further selected from tetrahydrofuranyl substituted with methyl; R5is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -N(R13)S(O)2(R13), -S(O)2R13, -S(O)2N(R13)2, -NO2, and -CN, provided that when RAis -OR11, then R5is not -OR13; R6is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)OR14, -OC(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2(R14), -S(O)2R14, -S(O)2N(R14)2, -NO2, =O, and -CN; R8is independently selected at each occurrence from halogen, C2-4alkyl, C1-4haloalkyl, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)OR14, -OC(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -N(R14)S(O)2(R14), -S(O)2R14, -S(O)2N(R14)2, -NO2, =O, and -CN; R7and R9are each independently selected from hydrogen, C1-4 alkyl, and C1-4 haloalkyl; R10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 cycloalkyl; m is selected from 0 and 1; p is selected from 0, 1, and 2; q is selected from 0, 1 and 2; andr is selected from 0, 1, and 2.

2. The compound or salt of claim 1, wherein Y1is CR3, Y2is N, Y3is CR4, and Y4is CR3or N.

3. The compound or salt of claim 1, wherein Y1is S, Y2is C, Y3is CR4or N, and Y4is CR3.

4. The compound or salt of claim 1, wherein Y1is N, Y2is N, Y3is CR4, and Y4is CR3.

5. The compound or salt of claim 1, wherein Y1is CR3, Y2is N, Y3is CR4, and Y4is N.

6. The compound or salt of any one of claims 1 to 5, wherein L is .

7. The compound or salt of claim 6, wherein Z is selected from -O-, -NR1-, C1-4alkylene, -O-C1-4alkylene, and -NR1-C1-4alkylene.

8. The compound or salt of any one of claims 1 to 5, wherein L is .

9. The compound or salt of claim 8, wherein Z’ is selected from C1-4alkylene.

10. The compound or salt of any one of claims 1 to 5, wherein L is selected from: , , , , , , , , , , , , , and .

11. The compound or salt of any one of claims 1 to 5, wherein L is .

12. The compound or salt of claim 1, wherein the compound or salt is a compound of Formula (IIA-1):(IIA-1), or a pharmaceutically acceptable salt thereof.

13. The compound or salt of claim 1, wherein the compound or salt is a compound of Formula (IIB): (IIB-1), or a pharmaceutically acceptable salt thereof; wherein R3is selected from selected from hydrogen, halogen, and C1-4 alkyl.

14. The compound or salt of claim 1, wherein the compound or salt is a compound of Formula (IID-1): (IID-1), or a pharmaceutically acceptable salt thereof; wherein R3is selected from selected from hydrogen, halogen, and C1-4 alkyl.

15. The compound or salt of claim 1, wherein the compound or salt is a compound of Formula (IIC-1): (IIC-1),or a pharmaceutically acceptable salt thereof; wherein R3is independently selected at each occurrence from selected from hydrogen, halogen, and C1-4 alkyl.

16. The compound or salt of any one of claims 1 to 15, wherein each R3is hydrogen.

17. The compound or salt of any one of claims 1 to 16, wherein R1is independently selected at each occurrence from hydrogen, -CH3, -CF3, -CH2CH3, , and .

18. The compound or salt of any one of claims 1 to 17, wherein each R1is hydrogen.

19. The compound or salt of any one of claims 1 to 18, wherein m is 0.

20. The compound or salt of any one of claims 1 and 16 to 19, wherein the compound or salt is a compound of Formula (IA-1): (IIA-2), or a pharmaceutically acceptable salt thereof.

21. The compound or salt of any one of claims 1 and 16 to 19, wherein the compound or salt is a compound of Formula (IIB-2): (IIB-2), or a pharmaceutically acceptable salt thereof.

22. The compound or salt of claim 1 and 16 to 19, wherein the compound or salt is a compound of Formula (IC-1): (IIC-2), or a pharmaceutically acceptable salt thereof23. The compound or salt of any one of claims 1 to 22, wherein Ring B is selected from (a) and (c): (a) , X1is selected from N, CH, and CR5; and (c) , X3is selected from S, N, and NH, X4is selected from O and CR9, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; wherein: RAis selected from halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, C3-6cycloalkyl, and 3- to 6-membered heterocycloalkyl; and when Y1is CR3and Y2is N, then RAis further selected from -OR11; R11is selected from hydrogen, C1-4alkyl, C1-4haloalkyl, and C3-6cycloalkyl; R5is independently selected at each occurrence from halogen, C1-4alkyl, C1-4haloalkyl, and -CN; R8is independently selected at each occurrence from halogen, C2-4 alkyl, C1-4 haloalkyl, and -CN; R9is selected from hydrogen and C1-4 alkyl; p is selected from 0 and 1; and r is selected from 0 and 1.

24. The compound or salt of any one of claims 1 to 23, wherein X2is S.

25. The compound or salt of any one of claims 1 to 24, wherein Ring B is selected from (a) and (c): (a) , X1is selected from N, CH, and CR5; andĨc) , X3is selected from S, N, and NH, X4is selected from O and CR9, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; wherein: RAis selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, , , , , and ; and when Y1is CR3and Y2is N, then RAis further selected from - OH, -OCH3, and ; R5is selected at each occurrence from -F, -Cl, and -CH3; R9is selected from hydrogen and -CH3; p is selected from 0 and 1; and r is 0.

26. The compound or salt of any one of claims 1 to 25, wherein Ring B is selected from: , , , , , , , , , , , , , , , , , , , , , ,, , , , , , , , , and .

27. The compound or salt of any one of claims 1 to 22, wherein Ring B is selected from: , wherein X3is selected from S and N, X4is selected from O and CR9, and each represents a single or a double bond, such that Ring B is an aromatic bicyclic ring system selected from benzothiazole, benzimidazole, and benzofurazan; wherein: R8is independently selected at each occurrence from halogen, C2-4alkyl, C1-4haloalkyl, and -CN; R9is selected from hydrogen and C1-4 alkyl; p is selected from 0 and 1; and r is selected from 0 and 1.

28. The compound or salt of any one of claims 1 to 22, wherein Ring B is selected from , wherein X1is selected from N, CH, and CR5.

29. The compound or salt of claim 28, wherein the compound or salt is a compound of Formula (IIA-3): (IIA-3)or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5.

30. The compound or salt of claim 28, wherein the compound or salt is a compound of Formula (IIB-3): (IIB-3), or a pharmaceutically acceptable salt thereof; wherein X1is selected from N, CH, and CR5.

31. The compound or salt of any one of claims 1 to 30, wherein Y3is N.

32. The compound or salt of any one of claims 1 to 30, wherein Y3is CR4; and R4is selected from hydrogen and halogen.

33. The compound or salt of any one of claims 1 to 30, wherein Y3is CH.

34. The compound or salt of claim 1, wherein the compound or salt is a compound of Formula (IIC-3): (IIC-3), or a pharmaceutically acceptable salt thereof.

35. The compound or salt of any one of claims 1 to 34, wherein: RAis selected from halogen, C1-4alkyl, C1-4haloalkyl, C1-4hydroxyalkyl, -N(R11)2, -SR11, -N(R11)C(O)R11, -CN, C3-6 cycloalkyl, and 3- to 6-membered heterocycloalkyl; and Y1is CR3, Y2is N, and Y4is CR3or when Y1is CR3, Y2is N, and Y4is N, then RAis further selected from - OR11; R11is selected from hydrogen, C1-4 alkyl, C1-4 haloalkyl, and C3-6 cycloalkyl; R5is independently selected at each occurrence from halogen and C1-4 alkyl; and p is selected from 0 and 1.

36. The compound or salt of any one of claims 1 to 35, whereinRAis selected from -F, -Cl, -CN, -NH2, -CH3, -CF3, -CHF2, , , , , and ; and when Y1is CR3, Y2is N, and Y4is CR3or when Y1is CR3, Y2is N, and Y4is N, then RAis further selected from -OH, -OCH3, and ; R5is selected at each occurrence from -F, -Cl, and -CH3; p is selected from 0 and 1.

37. The compound or salt of claim 1 to 36, wherein Ring B is selected from: , , , , , , , , , , , , , , , F , , ,N, , , , , , , , and .

38. The compound or salt of any one of claim 1 to 19, 23 to 28, 35, 36, and 37, wherein R1is C1-4 alkyl.

39. The compound or salt of any one of claims 1 to 22 and 28 to 38, wherein RAis selected from halogen, C1-4haloalkyl, C3-6cycloalkyl, -NR11, and -OR11.

40. The compound or salt of any one of claims 1 to 22 and 28 to 39, wherein p is 1, 2, or 3.

41. The compound or salt of any one of claims 1 to 22 and 28 to 40, wherein Y1is S; Y2is C; and X1is N.

42. The compound or salt of any one of claims 1 to 22 and 28 to 41, wherein Y1is S; Y2is C; and RAis selected from C1-4 alkyl.

43. The compound or salt of any one of claims 1 to 42, wherein Ring A is selected from: cyclopropyl substituted with one or more C1-6 alkyl or -CN, C4-12 carbocycle, and 3- to 12- membered heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2,-C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl, provided that when Ring B is selected from (b), then Ring A is not chromane; and R12is independently selected at each occurrence from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and C3-6 cycloalkyl.

44. The compound or salt of any one of claims 1 to 43, wherein Ring A is selected from: cyclopropyl substituted with one or more C1-6alkyl or -CN, C4-12carbocycle, and 3- to 12- membered heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl, provided that when Ring B is selected from (b), then Ring A is not chromane; and R12is independently selected at each occurrence from hydrogen and C1-6 alkyl.

45. The compound or salt of any one of claims 1 to 44, wherein Ring A is selected from: cyclopropyl substituted with one or more C1-4alkyl or -CN, cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, sulfolanyl, azetidinyl, pyrrolidinyl, piperidinyl, spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2- oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-Oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, - OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and phenyl.

46. The compound or salt of any one of claims 1 to 45, wherein Ring A is selected from: cyclopropyl substituted with one or more C1-4 alkyl or -CN, cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, sulfolanyl, azetidinyl, pyrrolidinyl, piperidinyl, spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2- Oxabicyclo[2.2.1]heptanyl, 8-Oxabicyclo[3.2.1]octanyl, 1-Oxaspiro[5.5]undecanyl, adamantanyl, 2-Azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, - C(O)OR12, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; and R12is independently selected at each occurrence from hydrogen and C1-6alkyl.

47. The compound or salt of any one of claims 1 to 46, wherein Ring A is selected from: cyclopropyl substituted with one or more -CH3 or -CN, cyclobutyl, cyclohexyl, phenyl, oxepanyl, sulfolanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2- Oxabicyclo[2.2.1]heptanyl, 8-Oxabicyclo[3.2.1]octanyl, 1-Oxaspiro[5.5]undecanyl, adamantanyl, 2-Azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl, each of which is optionally substituted with one or more substituents independently selected from: -F, -OH, -OCH3, -CH3, -CF3, =O, -CN, , , , , , , , and .

48. The compound or salt of any one of claims 1 to 47, wherein Ring A is selected from: , , , , , , , , , , , , ,, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,, , , , , , , , , , , and .

49. The compound or salt of any one of claims 1 to 42, wherein Ring A is selected from: cyclopropyl substituted with one or more C1-6 alkyl or -CN, C3-6 carbocycle substituted with one or more -F, and 3- to 6-membered heterocycle substituted with one or more -F, any of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4alkyl; 7- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN, provided that when Ring B is selected from (b), then Ring A is not chromane; and R12is independently selected at each occurrence from hydrogen and C1-6alkyl.

50. The compound or salt of any one of claims 1 to 42, wherein Ring A is selected from: cyclopropyl, cyclobutyl, cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl pyrrolidinyl, and piperidinyl, each of which is substituted with one or more -F, and is optionally substituted with one or more substituents independently selected from: halogen, C1- 6 alkyl, C1-6 haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, and 3- to 6-membered heterocycle optionally substituted with one or more C1-4 alkyl; and spiro[2.2]pentanyl, spiro[3.2]hexanyl, spiro[4.2]heptanyl, 6-oxaspiro[2.5]octanyl, 2- oxabicyclo[2.2.1]heptanyl, 8-oxabicyclo[3.2.1]octanyl, 1-Oxaspiro[5.5]undecanyl, adamantanyl, 2-azaspiro[3.3]heptanyl, and 1,9-dioxaspiro[5.5]undecanyl, any of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl,-OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, =O, -CN, and 3- to 6-membered heterocycleoptionally substituted with oR12is independently selected at each occurrence from hydrogen and C1-6alkyl.

51. The compound or salt of any one of claims 1 to 42, wherein Ring A is selected from: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 0 , and .

52. The compound or salt of any one of claims 1 to 51, wherein p is selected from 0 and 1, provided that when RAis -OR11, then p is 0; q is selected from 0 and 1; and r is 0.

53. The compound or salt of any one of claims 1 to 52, wherein R10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen and C1-6 alkyl.

54. A compound represented by the structure of Formula (V): (V), or a pharmaceutically acceptable salt thereof, wherein: Q1is N, S, O or CR3, Q2is N or C, Q3is N or CR4, Q4is N or CR3, Q5is C or N, and each represents a single or a double bond, such that the bicyclic ring system comprising Q1, Q2, Q3, Q4, and Q5is benzo[d]thiazole, benzo[d]oxazole, imidazo[1,2-a]pyridine, thiazolo[5,4- b]pyridine, imidazo[1,2-b]pyridazine, pyrazolo[1,5-a]pyridine, [1,2,4]triazolo[1,5-a]pyridine, or [1,2,4]triazolo[1,5-b]pyridazine; RAis selected from halogen, -OR10, -SR10, -N(R10)2, -CN, C1-6alkyl optionally substituted with one or more halogen or -OR10, C3-C6saturated cycloalkyl, and 3- to 6-membered saturated heterocycloalkyl; Ring A is selected from a C3-C10 saturated cycloalkyl, a C3-C10 partially saturated carbocycle, a 3- to 10-membered saturated heterocycloalkyl, and a 3- to 10-membered partially saturated heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -OC(O)N(R11)2,-C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)C(O)N(R11)2, -N(R11)S(O)2(R11), -S(O)R11, -S(O)2R11, -S(O)2N(R11)2, -S(O)(NR11)R11, -NO2, and =O; C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -OC(O)N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)C(O)N(R11)2, -N(R11)S(O)2(R11), -S(O)R11, -S(O)2R11, -S(O)2N(R11)2, -S(O)(NR11)R11, -NO2, =O, -CN; andC3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -OC(O)N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)C(O)N(R11)2, -N(R11)S(O)2(R11), -S(O)R11, -S(O)2R11, -S(O)2N(R11)2, -S(O)(NR11)R11, -NO2, =O, and -CN; Ring B is selected from a C3-C10carbocycle and a 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2,-C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, -CN; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -OC(O)N(R12)2,-C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)C(O)OR12, -N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, -NO2, =O, and -CN; R1is selected from hydrogen, C1-4 alkyl, C1-4 haloalkyl, and -C(O)R13; R2is independently selected at each occurrence from halogen, C1-4 alkyl, C1-4 haloalkyl, -OR14, -SR14, -N(R14)2, -NO2, and -CN; R3is independently selected at each occurrence from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; R4is selected from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; R10, R11, R12, R13, and R14are each independently selected at each occurrence from hydrogen, C1-4 alkyl, C1-4 haloalkyl, and cycloalkyl optionally substituted with one or more halogen; and n is selected from 0, 1, and 2; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl.

55. The compound or salt of claim 54 wherein the compound or salt is a compound ofFormula (VA): (VA), or a pharmaceutically acceptable salt thereof.

56. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VB): (VB), or a pharmaceutically acceptable salt thereof.

57. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VC): (VC), or a pharmaceutically acceptable salt thereof.

58. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VD): (VD),or a pharmaceutically acceptable salt thereof.

59. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VE): (VE), or a pharmaceutically acceptable salt thereof.

60. The compound or salt of any one of claims 54 to 56, 58, and 59, wherein Q3is CR4.

61. The compound or salt of any one of claims 54 to 56, 58, and 59, wherein Q3is N.

62. The compound or salt of any one of claims 54, 55, 57, 60 and 61, wherein Q4is CR3.

63. The compound or salt of any one of claims 54, 55, 57, 60 and 61, wherein Q4is N.

64. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VF): (VF), or a pharmaceutically acceptable salt thereof.

65. The compound or salt of any one of claims 54 to 64, wherein each R3is independently hydrogen.

66. The compound or salt of any one of claims 54 to 65, wherein R4is selected from hydrogen and C1-4alkyl.

67. The compound or salt of any one of claims 54 to 66, wherein R4is selected from hydrogen and -CH3.

68. The compound or salt of any one of claims 54 to 67, wherein R1is selected from hydrogen, C1-4 alkyl, C1-4 haloalkyl and -C(O)R1369. The compound or salt of any one of claims 54 to 68, wherein R13is selected from C1-4 alkyl and cyclopropyl optionally substituted with one or more -F.

70. The compound or salt of any one of claims 54 to 69, wherein R1is selected from F hydrogen, -CH3, -CF3, andO.

71. The compound or salt of any one of claims 54 to 70, wherein n is 0.

72. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VIA-1): (VIA-1), or a pharmaceutically acceptable salt thereof.

73. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VIA-2): (VIA-2), or a pharmaceutically acceptable salt thereof.

74. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VIB-1): RAO A N HN S B (VIB-1), or a pharmaceutically acceptable salt thereof75. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VIB-2): (VIB-2), or a pharmaceutically acceptable salt thereof.

76. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VIC-3): (VIC-3), or a pharmaceutically acceptable salt thereof.

77. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VID-1): (VID-1); or a pharmaceutically acceptable salt thereof.

78. The compound or salt of claim 54, wherein the compound or salt is a compound ofFormula (VID-2): (VID-2); or a pharmaceutically acceptable salt thereof.

79. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VIE-1): (VIE-1), or a pharmaceutically acceptable salt thereof.

80. The compound or salt of claim 54, wherein the compound or salt is a compound of Formula (VIE-2): (VIE-2), or a pharmaceutically acceptable salt thereof.

81. The compound or salt of claim 54, wherein the compound or salt is a compound ofFormula (VIF): (VIF), or a pharmaceutically acceptable salt thereof.

82. The compound or salt of any one of claims 54 to 81, wherein Ring A is selected from C3-C10 saturated cycloalkyl, and 3- to 10-membered saturated heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -C(O)N(R11)2, -N(R11)C(O)R11, -NO2, and =O; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, and =O, -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, C1- 6 alkyl, C1-6 haloalkyl, =O, and -CN; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl.

83. The compound or salt of any one of claims 54 to 82, wherein Ring A is selected from C3-C6saturated cycloalkyl, and 3- to 6-membered saturated heterocycloalkyl, each of which is optionally substituted with one or more substituents independently selected from halogen, - C(O)OR11, C1-6alkyl, C1-6haloalkyl, and 3- to 6-membered heterocycloalkyl, optionally substituted with one or more C1-6 alkyl.

84. The compound or salt of any one of claims 54 to 83, wherein Ring A is selected from: cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -C(O)OR11, C1-6alkyl, C1-6haloalkyl, and 3- to 6-membered heterocycloalkyl, optionally substituted with one or more C1-6alkyl; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl.

85. The compound or salt of any one of claims 54 to 84, wherein R11is independently selected at each occurrence86. The compound or salt of any one of claims 54 to 85, wherein Ring A is selected from: cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, and tetrahydrofuranyl, each of which is optionally substituted with one or more substituents independently selected from -F, -CH3, , , , , and ; provided that when Ring B is pyrazolyl, then Ring A is not N-Boc pyrrolidinyl.

87. The compound or salt of any one of claims 54 to 86, wherein RAis selected from - F, -CN, -CH3, -CHF2, -CF3, -CH2OCH3, -OCH3, and .

88. The compound or salt of any one of claims 54 to 87, wherein is selected from: , , , , , , , , , , , , , , , , , , , , , , , , , ,, , , , , , F , , , , and .

89. The compound or salt of any one of claims 54 to 88, wherein Ring B is selected from a C3-C10carbocycle and a 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -C(O)N(R12)2, -N(R12)C(O)R12, - N(R12)C(O)OR12, - N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, - S(O)(NR12)R12, -NO2, =O, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, =O, -CN; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, - OR12, -SR12, -N(R12)2, -C(O)R12, =O, and -CN.

90. The compound or salt of any one of claims 54 to 89, wherein Ring B is selected from a C6-C10 aryl and a 3- to 12-membered heteroaryl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -C(O)N(R12)2, -N(R12)C(O)R12, - N(R12)C(O)OR12, - N(R12)C(O)N(R12)2, -N(R12)S(O)2(R12), -S(O)R12, -S(O)2R12, -S(O)2N(R12)2, - S(O)(NR12)R12, -NO2, =O, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, =O, and -CN; and C3-6 carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6 alkyl, C1-6 haloalkyl, - OR12, -SR12, -N(R12)2, -C(O)R12, =O, and -CN.

91. The compound or salt of any one of claims 54 to 90, wherein Ring B is selected from a C6-C10aryl and a 3- to 12-membered heteroaryl, each of which is optionally substitutedwith one or more substituents independently selected from: halogen, -OR12, -N(R12)2, - C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2(R12), -S(O)2R12, -S(O)2N(R12)2, -S(O)(NR12)R12, =O, -CN, C3-6 carbocycle and 3- to 6-membered heterocycle, and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen and -OR12.

92. The compound or salt of any one of claim 54 to 91, wherein Ring B is selected from phenyl, pyridinyl, pyridazinyl, pyrimidinyl, indolyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, 2,1,3-benzoxadiazolyl, benzfurazanyl, thiazolo[4,5-b]pyridinyl, pyrrolo[2,3-b]pyridinyl, imidazo[1,5-a]pyridinyl, quinolinyl, isoquinolinyl, quinazolinyl, and quinoxalinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, - OR12, -N(R12)2, -C(O)N(R12)2, -N(R12)C(O)R12, -N(R12)S(O)2(R12), -S(O)2R12, -S(O)2N(R12)2, - S(O)(NR12)R12, =O, -CN, C3-6 carbocycle and 3- to 6-membered heterocycle, and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen and - OR12.

93. The compound or salt of any one of claims 54 to 92, wherein R12is selected from hydrogen, -CH3, -CH2CH2CH3, -CH2CH(CH3)2, -CH2CF3, and cyclopropyl.

94. The compound or salt of any one of claims 54 to 93, wherein Ring B is selected from phenyl, pyridinyl, pyridazinyl, pyrimidinyl, indolyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, 2,1,3-benzoxadiazolyl benzfurazanyl, thiazolo[4,5-b]pyridinyl, pyrrolo[2,3- b]pyridinyl, imidazo[1,5-a]pyridinyl, quinolinyl, isoquinolinyl, quinazolinyl, and quinoxalinyl, each of which is optionally substituted with one or more substituents independently selected from: -F, -Cl, -CN, -OH, -NH2, =O, -CH3, -OCH3, -CF3, -CHF2, , , , , , , , , , , , , N N , , , , and .

95. The compound or salt of any one of claims 54 to 94, wherein Ring B is selected from:, , , , , , , , , , , , , , , , , , , , , , , O S O , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 10 , , ,, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

96. A compound selected from a compound in Table 1, or a pharmaceutically acceptable salt thereof.

97. A pharmaceutical composition comprising a compound of any one of claims 1 to 96, or a pharmaceutically acceptable salt thereof, and pharmaceutically acceptable diluent or carrier.

98. A method for treating a neurological disorder in a subject in need thereof, themethod comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 96, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 97.

99. The method of claim 98, wherein the neurological disorder is selected from the group consisting of Down Syndrome, Alzheimer’s disease, and Alzheimer’s disease associated with Down Syndrome.

100. The method of claim 98 or 99, wherein the neurological disorder is selected Alzheimer’s disease associated with Down syndrome.

101. A method for treating a metabolic disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 96, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 97.

102. The method of claim 101, wherein the metabolic disorder is diabetes.

103. A method for treating a cardiovascular disease or disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 96, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 97.

104. A method for treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 96, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 97.

105. A method of inhibiting DYRK1A activity in a mammalian cell comprising a DYRK1A protein, the method comprising contacting the mammalian cell with a compound of any one of claims 1 to 96, or a pharmaceutically acceptable salt thereof.

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