5-(cinnolin-6-yl)thiazole 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] 5-(CINNOLIN-6-YL)THIAZOLE COMPOUNDS FOR TREATING NEUROLOGICAL DISORDERS TECHNICAL FIELD 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. SEQUENCE LISTING This application contains a Sequence Listing that has been submitted electronically as an XML file named “50887-0042WO1.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. RELATED APPLICATIONS The application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 508,120 filed June 14, 2023, U.S. Provisional Patent Application Serial No. 63 / 508,121 filed June 14, 2023, U.S. Provisional Patent Application Serial No.63 / 508,126 filed June 14, 2023, U.S. Provisional Patent Application Serial No.63 / 510,689 filed June 28, 2023, U.S. Provisional Patent Application Serial No.63 / 510,692 filed June 28, 2023, U.S. Provisional Patent Application Serial No. 63 / 510,694 filed June 28, 2023, U.S. Provisional Patent Application Serial No. 63 / 656,006 filed June 4, 2024, and U.S. Provisional Patent Application Serial No. 63 / 656,025 filed June 4, 2024, each of which is incorporated by reference herein in its entirety. PARTIES TO A JOINT RESEARCH AGREEMENT The subject matter of the present disclosure was created pursuant to a joint research agreement between Prothena Biosciences Limited and Vanderbilt 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. BACKGROUND Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a 763 amino acid, 85 kDa serine / threonine / tyrosine 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-β peptide (Aβ). Dyrk1A also phosphorylates tau both directly and indirectly (see Abassi, et al, (2016)). Both amyloid-β and tau pathologies are associated with Down syndrome phenotypes. Normalization of DYRK1A gene dosage by crossing Ts65Dn mice (DS model) with DYRK1A knockout mice mice reverses many Azlheimer’s-like phenotypes. See García-Cerro et al., 2017. In individuals with Down Syndrome, DYRK1A 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. 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. 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.Alz.org). Presently, no therapies have been approved to treat Alzheimer’s disease associated with Down syndrome, which represents a significant unmet medical need. Some DYRK1A 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 DYRK1A inhibitors to treat Down syndrome, Alzheimer’s disease, Alzheimer’s disease associated with Down syndrome, and other neurodegenerative and neurological diseases. SUMMARY Some embodiments provide a compound of Formula (I): or a pharmaceutically acceptable salt thereof, wherein: D is selected from -N(R1)C(O)-L-, -X-, and -X-C1-6alkylene; X is selected from -O-, -S-, and -N(R6)-, L is absent or L is selected from -O-, -S-, -N(R6)-, C1-6alkylene, -N(R6)-C1-6alkylene, -O- C1-6alkylene, and -S- C1-6alkylene, wherein each C1-6alkylene of D or L is optionally substituted with one or more substituent independently selected from halogen, -OR7, and -CN; Ring A is selected from C3-C12carbocycle and 3- to 12-membered 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, =O, and -CN; and 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, and -CN; C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R1is selected from hydrogen, C1-4alkyl, C1-4haloalkyl; R2is selected from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; and R3and R4are each independently selected from: hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, -OR13, -SR13, -N(R13)2, and -CN; or R3and R4come together to form a 3- to 7-membered heterocycle optionally substituted with one or more substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R5is selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)OR15, -OC(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl; R6and R7are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; R11and R15are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; R13is independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4haloalkyl, C3-6carbocycle, and 3-to-6 membered heterocycle optionally substituted with one or more substituent selected from halogen, C1-4alkyl, and C1-4haloalkyl; and n is selected from 0, 1, and 2; provided that: (A) if D is -N(R1)C(O)-L-, L is absent and R3and R4are both hydrogen, Ring A is selected from (i), (ii), (iii), (iv), (v), (vi), or (vii): (i) bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2- oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane; (ii) phenyl and monocyclic heteroaryl, provided that Ring A is not 2-methylpyridine or 1-methyl-2-pyridone; (iii) monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur; (iv) monocyclic heterocycloalkyl substituted with two or more halogen; and (v) monocyclic heterocycloalkyl substituted with one or more substituents selected from C1-6haloalkyl, -OR11, C3-C6carbocycle, and 3- to 6-membered heterocycle; (vi) monocyclic C3-C4cycloalkyl substituted with 1-3 substituents independently selected from –OH, fluoro, C1-6alkyl, and C1-6haloalkyl; (vii) cyclohexyl substituted with -OH, 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, =O, and -CN; 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, and -CN; and C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, =O, -CN, C1-6alkyl, and C1-6haloalkyl;(B) if D is -N(R1)C(O)-L-, L is methylene and Ring A is tetrahydropyran, then at least one of R3and R4is not hydrogen; (C) if D is -N(R1)C(O)-L-, L is absent and R3and R4are each methyl, then Ring A is not 2,2,5,5-tetramethyltetrahydrofuranyl, 2,2-dimethyltetrahydropyranyl, or 2,2,6,6- tetramethyltetrahydropyranyl; (D) if D is -N(R1)C(O)-L-, L is absent, R3is 3-methylmorpholinyl, and R4is hydrogen, then Ring A is not 2,2,5,5-tetramethyltetrahydrofuranyl; and (E) if D is -N(R1)C(O)-L-, L is absent, R3is OH, and R4is hydrogen, then Ring A is not 4- fluorotetrahydropyranyl. Some embodiments provide a compound of Formula (II): or a pharmaceutically acceptable salt thereof, wherein: L is absent or L is selected from -O-, -N(R6)-, C1-4alkylene, -N(R6)-C1-4alkylene, -O-C1-4alkylene, wherein the C1-4alkylene is optionally substituted with one or more halogen; Ring A is selected from C3-C12carbocycle and 3- to 12-membered 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, =O, and -CN; and 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, and -CN; R1is selected from hydrogen and C1-4alkyl; R2is selected from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; and R3and R4are each independently selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, - C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, - OR13, -SR13, -N(R13)2, and -CN; or R3and R4come together to form a 3- to 7-membered heterocycle optionally substituted with one or more substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, - C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R5is selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)OR15, -OC(O)R15, - C(O)N(R15)2, -N(R15)C(O)R15, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl; R6is selected from hydrogen and C1-4alkyl; R11and R15are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; R13is independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4haloalkyl, C3-6carbocycle, and 3-to-6 membered heterocycle optionally substituted with one or more substituent selected from halogen, C1-4alkyl, and C1-4haloalkyl; and n is selected from 0, 1, and 2; provided that: (A) if L is absent and R3and R4are both hydrogen, Ring A is selected from (i), (ii), (iii), (iv), (v), (vi), or (vii): (i) bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2- oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane; (ii) phenyl and monocyclic heteroaryl, provided that Ring A is not 2-methylpyridine or 1-methyl-2-pyridone; (iii) monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur; (iv) monocyclic heterocycloalkyl substituted with two or more halogen; (v) monocyclic heterocycloalkyl substituted with one or more substituents selected from C1-6haloalkyl, -OR11, C3-C6carbocycle, and 3- to 6-membered heterocycle; (vi) monocyclic C3-C4cycloalkyl substituted with 1-3 substituents independently selected from –OH, fluoro, C1-6alkyl, and C1-6haloalkyl; (vii) cyclohexyl substituted with -OH, 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, =O, and -CN; and 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; (B) if L is methylene and Ring A is tetrahydropyran, then at least one of R3and R4is not hydrogen; (C) if L is absent and R3and R4are each methyl, then Ring A is not 2,2,5,5- tetramethyltetrahydrofuranyl, 2,2-dimethyltetrahydropyranyl, or 2,2,6,6- tetramethyltetrahydropyranyl; (D) if L is absent, R3is 3-methylmorpholinyl, and R4is hydrogen, then Ring A is not 2,2,5,5-tetramethyltetrahydrofuranyl; and (E) if L is absent, R3is OH, and R4is hydrogen, then Ring A is not 4- fluorotetrahydropyranyl. Some embodiments provide a compound of Formula (III): or a pharmaceutically acceptable salt thereof, wherein: RAis selected from: halogen, -OR10, -SR10, -N(R10)2, -CN, C1-6alkyl, C1-6alkoxy, and C1-6haloalkyl; and C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more halogen; Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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, =O, and -CN; 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, C3-C6carbocycle, and 3- to 6-membered heterocycle; and C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, -C(O)R11, =O, and -CN; Ring B is selected from a polycyclic C7-C12carbocycle, a polycyclic 7- to 14-membered heterocycle and a monocyclic heterocycle selected from thiazole and thiophene, any 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 3- to 6-membered heterocycle; 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, C1-4alkyl, and C1-4haloalkyl; R2is independently selected at each occurrence from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; and R10, R11, and R12are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; provided that if RAis methyl or ethyl and Ring B is cinnoline, 3-chloroisoquinoline, or 2- methylquinazolinyl, then Ring A is not tetrahydrofuran, tetrahydropyran, 2- methyltetrahydrofuran, or 2,6-dimethyltetrahydropyran; provided that if (i) RAis fluoro and Ring B is 4-hydroxycinnoline, or (ii) RAis methyl and Ring B is isoquinoline or 3-fluoroisoquinoline, then Ring A is not tetrahydropyran; provided that if RAis fluoro and Ring B is indazole, Ring A is not selected from N- cyanopyrrolidine; and provided that if RAis methyl and Ring A is 6,7-dihydroindolizin-8(5H)-one, then Ring B is not methylenedioxyphenyl substituted with two fluoro. Some embodiments provide a compound of Formula (III): or a pharmaceutically acceptable salt thereof, wherein: RAis selected from: halogen, -OR10, -SR10, -N(R10)2, -CN, C1-6alkyl, C1-6alkoxy, and C1-6haloalkyl; and C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more halogen; Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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, =O, and -CN; and 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; Ring B is selected from a polycyclic C7-C12carbocycle, a polycyclic 7- to 14-membered heterocycle, and a monocyclic heterocycle selected from thiazole and thiophene,any 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 3- to 6-membered heterocycle; 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 and C1-4alkyl; R2is independently selected at each occurrence from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; and R10, R11, and R12are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; provided that if RAis methyl or ethyl and Ring B is cinnoline, 3-chloroisoquinoline, or 2- methylquinazolinyl, then Ring A is not tetrahydrofuran, tetrahydropyran, 2- methyltetrahydrofuran, or 2,6-dimethyltetrahydropyran; provided that if (i) RAis fluoro and Ring B is 4-hydroxycinnoline, or (ii) RAis methyl and Ring B is isoquinoline or 3-fluoroisoquinoline, then Ring A is not tetrahydropyran; provided that if RAis fluoro and Ring B is indazole, Ring A is not selected from N- cyanopyrrolidine; and provided that if RAis methyl and Ring A is 6,7-dihydroindolizin-8(5H)-one, then Ring B is not methylenedioxyphenyl substituted with two fluoro. Some embodiments provide a compound of Formula (IV): or a pharmaceutically acceptable salt thereof; wherein X is N or CR6; R3and R4are each independently selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, - C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, - OR13, -SR13, -N(R13)2, and -CN; or R3and R4come together to form a 3- to 6-membered heterocycle optionally substituted with one or more substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, - C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R5is selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)OR15, -OC(O)R15, - C(O)N(R15)2, -N(R15)C(O)R15, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl; R6is selected from hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, - OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl; R13, R15, R16are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; and n is selected from 0, 1, and 2. Also provided herein is a pharmaceutical composition comprising a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 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), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. Some embodiments provide a method for treating a neurological disorder in a subject in need thereof, the method comprising (a) determining or having determined that the neurological disorder is associated with a dysregulation of a 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), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. Also provided herein is a method for treating a neurological disorder in a subject in need thereof, the method comprising (a) determining or having determined 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), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. Also provided herein is a method for treating a neurological disorder in a subject in need thereof, the method comprising (a) determining or having determined that the subject has a neurological disorder; and (b) administering to the subject a therapeutically effective amount of a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. Provided herein is a method of treating a DYRK1A-associated disorder in a subject, the method comprising administering to a subject previously determined to have a DYRK1A- associated disorder a therapeutically effective amount of a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. 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), or (IV), or a 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 DYRK1A gene, a DYRK1A protein, or expression or activity or level of any of the same. This disclosure also provides a method for inhibiting DYRK1A 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), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof. 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. DETAILED DESCRIPTION Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a member of the dual-specificity tyrosine phosphorylation regulated kinase (DYRK) family, which is also part of the larger CGMC family of kinases. DYRK1A 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 DYRK1A generates several transcript variants differing from each other either in either the 5ƍ untranslated region or in the 3ƍ coding region resulting in at least five different isoforms. DYRK1A possesses catalytic activity that is regulated by autophosphorylation of a tyrosine residue (Y321) which results in constitutively active serine / threonine kinase activity. 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. 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 DYRKIA 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 Dyrk1a gene exhibit decreased viability, behavioral alterations, and delayed growth. Fotaki, et al., Mol Cell Biol., 22(18): 6636- 6647 (2014). The identification of hundreds of genes deregulated by DYRK1A overexpression and numerous cytosolic, cytoskeletal and nuclear proteins, including transcription factors, phosphorylated by DYRK1A, indicates that DYRK1A overexpression is central for the deregulation of multiple pathways in the developing and aging brain of individuals with Down syndrome. Identifying DYRK1A cell signaling or transduction pathways can lead to a better understanding of how DYRK1A 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 Synaptojanin, 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 presenilin 1, the catalytic sub-unit of Ȗ- secretase. Ryu, et al., J Neurochem., 115(3): 574-84 (2010). DYRK1A overexpression 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. One potential source of treatment are inhibitors of DYRK1A. 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 DYRK1A 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 DYRK1A resulted in normal DYRK1A 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. Epigallocatechin gallate (EGCG) is the primary flavonoid of green tea and has been investigated for its therapeutic effects, which include anti-oxidative, anti-inflammatory, anti- cancer, anti-infective and neuroprotective activity. See, Bhat, et al. Towards the discovery of drug- like epigallocatechin gallate analogs as Hsp90 inhibitors, Bioorg Med Chem Lett, 24, 2263-2266 (2014). EGCG is a non-ATP competitive DYRKlA inhibitor and studies have shown that green tea extract comprising 41% EGCG were able to alleviate cognitive decline seen in transgenic mice over expressing DYRKlA. 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. SM07883 is an orally bioavailable (%F 92% in mice, 109% in monkey), BBB penetrant, DYRK1A inhibitor (IC50 1.6 nM) that also shows potent inhibition for DYRK1B, CLK4, and GSK3β in kinase assays. It was found to protect against tau hyperphosphorylation in mouse models. SM07883 was 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. This disclosure provides compounds of Formula (I), (II), (III), and (IV), and subformulae thereof, as well as 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. Additional Definitions 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, will control. The term “about” when 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. 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. The term “inhibit” or “inhibition of” means to reduce by a measurable amount, or to prevent entirely (e.g., 100% inhibition). 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 DYRK1A activity in brain tissue. 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. The term “pharmaceutically acceptable excipient” means a pharmaceutically-acceptable 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 ed.; Rowe et al., 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. The term “pharmaceutically acceptable salt” refers to a formulation of a compound that does not cause significant irritation to an organism to which 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, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, 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 hereinform 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 amino 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. 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, C1-10indicates 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: bicyclo[1.1.0]butane, bicyclo[2.1.0]pentane, bicyclo[1.1.1]pentane, bicyclo[3.1.0]hexane, bicyclo[2.1.1]hexane, bicyclo[3.2.0]heptane, bicyclo[4.1.0]heptane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[4.2.0]octane, bicyclo[3.2.1]octane, bicyclo[2.2.2]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 spiro[2.2]pentane, spiro[2.5]octane, spiro[3.5]nonane, spiro[3.5]nonane, spiro[3.5]nonane, spiro[4.4]nonane, spiro[2.6]nonane, spiro[4.5]decane, spiro[3.6]decane, spiro[5.5]undecane, and the like. A “cycloalkylene” group is a divalent cycloalkyl group as described herein. The terms “heterocycle” and “heterocyclyl” refer 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 O 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(O)-, 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, tetrahydrothiophenyl 1,1-dioxide, thiomorpholinyl 1,1-dioxide, dioxanyl, morpholinyl, tetrahydrofuranyl, tetrahydropyridyl, dihydropyrazinyl, dihydropyridyl, dihydropyrrolyl, dihydrofuranyl, 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- azabicyclo[2.1.0]pentane, 2-azabicyclo[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, 7-azabicyclo[2.2.1]heptane, 6-azabicyclo[3.1.1]heptane, 7- azabicyclo[4.2.0]octane, 2-azabicyclo[2.2.2]octane, 3-azabicyclo[3.2.1]octane, 2- oxabicyclo[1.1.0]butane, 2-oxabicyclo[2.1.0]pentane, 2-oxabicyclo[1.1.1]pentane, 3- oxabicyclo[3.1.0]hexane, 5-oxabicyclo[2.1.1]hexane, 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. 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, 1-oxaspiro[3.5]nonane, 2-oxaspiro[3.5]nonane, 7- oxaspiro[3.5]nonane, 2-oxaspiro[4.4]nonane, 6-oxaspiro[2.6]nonane, 1,7-dioxaspiro[4.5]decane, 2,5-dioxaspiro[3.6]decane, 1-oxaspiro[5.5]undecane, 3-oxaspiro[5.5]undecane, 3-oxa-9- azaspiro[5.5]undecane and the like. 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 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, pyrido[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyridinyl, quinazolinyl, quinolinyl, thieno[2,3- c]pyridinyl, pyrazolo[3,4-b]pyridinyl, pyrazolo[3,4-c]pyridinyl, pyrazolo[4,3-c]pyridine, pyrazolo[4,3-b]pyridinyl, tetrazolyl, and the like. 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- azabicyclo[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, 7- azabicyclo[2.2.1]heptane, 6-azabicyclo[3.1.1]heptane, 7-azabicyclo[4.2.0]octane, 2- azabicyclo[2.2.2]octane, 3-azabicyclo[3.2.1]octane, 2-oxabicyclo[1.1.0]butane, 2- oxabicyclo[2.1.0]pentane, 2-oxabicyclo[1.1.1]pentane, 3-oxabicyclo[3.1.0]hexane, 5- oxabicyclo[2.1.1]hexane, 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, 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, 1-oxaspiro[3.5]nonane, 2-oxaspiro[3.5]nonane, 7- oxaspiro[3.5]nonane, 2-oxaspiro[4.4]nonane, 6-oxaspiro[2.6]nonane, 1,7-dioxaspiro[4.5]decane, 2,5-dioxaspiro[3.6]decane, 1-oxaspiro[5.5]undecane, 3-oxaspiro[5.5]undecane, 3-oxa-9- azaspiro[5.5]undecane and the like. 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 pyridone (e.g., , , , or ), pyrimidone (e.g., or ), pyridazinone (e.g., or ), pyrazinone (e.g., or ), 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). The term “saturated” as used in this context means only single bonds present between constituent atoms. 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, dihydrothiophene, and the like. 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.0] ring systems, in which 0 represents a zero atom bridge (e.g., )); (ii) a single ring atom (spiro-fused ring systems) (e.g., , , or ), or (iii) a contiguous array of ring atoms (bridged ring systems having all bridge lengths > 0) (e.g., , , or ). 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. 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,14C,13N,15N,15O,17O,18O,31P,32P,35S,18F,36C1,123I, and125I, respectively. Various isotopically enriched compounds of the present disclosure, for example those into which radioactive isotopes such as13C and14C 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. 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. 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 ( ), trideuteromethyl ( ), trideuteromethoxy ( ), and the like. Compounds of the present disclosure also include deuterium enriched compounds at the alpha position of an oxo group, such as , , , and . Compounds of the present disclosure also include deuterium enriched compounds at the position of attachment of a ring to the remainder of a molecule, such as, for example . Compounds of the present disclosure also include deuterium enriched compounds adjacent to a heteroatom, such as, for example and . 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: . Similarly, a pyridinyl or pyrimidinyl moiety that is described to be optionally substituted with hydroxyl encompasses pyridone or pyrimidone tautomeric forms. 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. Formulae (I) and (II) Compounds Some embodiments provide a compound of Formula (I): (I); or a pharmaceutically acceptable salt thereof, wherein: D is selected from -N(R1)C(O)-L-, -X-, and -X-C1-6alkylene; X is selected from -O-, -S-, and -N(R6)-, L is absent or L is selected from -O-, -S-, -N(R6)-, C1-6alkylene, -N(R6)-C1-6alkylene, -O-C1-6alkylene, and -S- C1-6alkylene, wherein each C1-6alkylene of D or L is optionally substituted with one or more substituent independently selected from halogen, -OR7, and -CN; Ring A is selected from C3-C12carbocycle and 3- to 12-membered 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, =O, and -CN; and 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, and -CN; C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R1is selected from hydrogen, C1-4alkyl, C1-4haloalkyl; R2is selected from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; and R3and R4are each independently selected from: hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, -OR13, -SR13, -N(R13)2, and -CN; or R3and R4come together to form a 3- to 7-membered heterocycle optionally substituted with one or more substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R5is selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)OR15, -OC(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl; R6and R7are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; R11and R15are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; R13is independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4haloalkyl, C3-6carbocycle, and 3-to-6 membered heterocycle optionally substituted with one or more substituent selected from halogen, C1-4alkyl, and C1-4haloalkyl; and n is selected from 0, 1, and 2; provided that: (B) if D is -N(R1)C(O)-L-, L is absent and R3and R4are both hydrogen, Ring A is selected from (i), (ii), (iii), (iv), (v), (vi), or (vii): (i) bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2- oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane; (ii) phenyl and monocyclic heteroaryl, provided that Ring A is not 2-methylpyridine or 1-methyl-2-pyridone; (iii) monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur; (iv) monocyclic heterocycloalkyl substituted with two or more halogen; and (v) monocyclic heterocycloalkyl substituted with one or more substituents selected from C1-6haloalkyl, -OR11, C3-C6carbocycle, and 3- to 6-membered heterocycle (vi) monocyclic C3-C4cycloalkyl substituted with 1-3 substituents independently selected from –OH, fluoro, C1-6alkyl, and C1-6haloalkyl; (vii) cyclohexyl substituted with -OH, 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, =O, and -CN; 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, and -CN; and C3-C6carbocycle 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, -C(O)R11, -C(O)OR11, =O, -CN, C1-6alkyl, and C1-6haloalkyl;(B) if D is -N(R1)C(O)-L- , L is methylene and Ring A is tetrahydropyran, then at least one of R3and R4is not hydrogen; (C) if D is -N(R1)C(O)-L-, L is absent and R3and R4are each methyl, then Ring A is not 2,2,5,5-tetramethyltetrahydrofuranyl, 2,2-dimethyltetrahydropyranyl, or 2,2,6,6- tetramethyltetrahydropyranyl; (D) if D is -N(R1)C(O)-L-, L is absent, R3is 3-methylmorpholinyl, and R4is hydrogen, then Ring A is not 2,2,5,5-tetramethyltetrahydrofuranyl; and (E) if D is -N(R1)C(O)-L-, L is absent, R3is OH, and R4is hydrogen, then Ring A is not 4- fluorotetrahydropyranyl. In some embodiments for the compound of Formula (I), D is selected from -N(R1)C(O)-L-, -X-, and -X-C1-6alkylene; X is selected from -O-, -S-, and -N(R6)-, L is absent or L is selected from -O-, -S-, -N(R6)-, C1-6alkylene, -N(R6)-C1-6alkylene, -O-C1-6alkylene, and -S- C1-6alkylene, wherein each C1-6alkylene of D or L is optionally substituted with one or more substituent independently selected from halogen, -OR7, and -CN; Ring A is selected from C3-C12carbocycle and 3- to 12-membered 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, =O, and -CN; and 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, and -CN; C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R1is selected from hydrogen, C1-4alkyl, C1-4haloalkyl; R2is selected from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; and R3and R4are each independently selected from: hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, -OR13, -SR13, -N(R13)2, and -CN; or R3and R4come together to form a 3- to 7-membered heterocycle optionally substituted with one or more substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R5is selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)OR15, -OC(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl; R6and R7are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; R11and R15are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; R13is independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4haloalkyl, C3-6carbocycle, and 3-to-6 membered heterocycle optionally substituted with one or more substituent selected from halogen, C1-4alkyl, and C1-4haloalkyl; and n is selected from 0, 1, and 2; provided that: (A) if D is -N(R1)C(O)-L-, L is absent and R3and R4are both hydrogen, Ring A is selected from (i), (ii), and (iii): (i) bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2- oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane; (ii) phenyl and monocyclic heteroaryl, provided that Ring A is not 2-methylpyridine or 1-methyl-2-pyridone; (iii) monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur; 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, =O, and -CN; 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, and -CN; and C3-C6carbocycle 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, -C(O)R11, -C(O)OR11, =O, -CN, C1-6alkyl, and C1-6haloalkyl; (B) if D is -N(R1)C(O)-L-, L is methylene and Ring A is tetrahydropyran, then at least one of R3and R4is not hydrogen; (C) if D is -N(R1)C(O)-L-, L is absent and R3and R4are each methyl, then Ring A is not 2,2,5,5-tetramethyltetrahydrofuranyl, 2,2-dimethyltetrahydropyranyl, or 2,2,6,6- tetramethyltetrahydropyranyl; (D) if D is -N(R1)C(O)-L-, L is absent, R3is 3-methylmorpholinyl, and R4is hydrogen, then Ring A is not 2,2,5,5-tetramethyltetrahydrofuranyl; and (E) if D is -N(R1)C(O)-L-, L is absent, R3is OH, and R4is hydrogen, then Ring A is not 4- fluorotetrahydropyranyl. In some embodiments, for the compound of Formula (I), D is selected from -N(R1)C(O)-L-, -X-, and -X-C1-6alkylene; X is selected from -O-, -S-, and -N(R6)-, L is absent or L is selected from -O-, -S-, -N(R6)-, C1-6alkylene, -N(R6)-C1-6alkylene, and -O-C1-6alkylene, wherein each C1-6alkylene of D or L is optionally substituted with one or more substituent independently selected from halogen and -OR7; R6is selected from hydrogen and C1-4alkyl; and R7is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formula (I), D is selected from -N(R1)C(O)-L-, -X-, and -X-C1-6alkylene; X is selected from -S-, and -N(R6)-, L is absent or L is selected from -O-, -N(R6)-, C1-6alkylene, -N(R6)-C1-6alkylene, - O-C1-6alkylene, each C1-6alkylene of D or L is optionally substituted with one or more -OR7; R6is selected from hydrogen and methyl; and R7is independently selected at each occurrence from hydrogen and methyl. In some embodiments, D is selected from -N(R1)C(O)-L-, -X-, and -X-C1-4alkylene; X is selected from -S-, and -N(R6)-, L is absent or L is selected from -O-, -N(R6)-, C1-4alkylene, -N(R6)-C1-4alkylene, - O-C1-4alkylene, each C1-6alkylene of D or L is optionally substituted with one or more -OR7; R6is selected from hydrogen and methyl; and R7is independently selected at each occurrence from hydrogen and methyl. In some embodiments, for the compound of Formula (I), D is selected from In some embodiments, for the compound of Formula (I), D is selected from -X- and - N(R1)C(O)-L-. In some embodiments, D is selected from -N(R1)C(O)-L- and -X-C1-6alkylene. In some embodiments, D is selected from -N(R1)C(O)-L-. In some embodiments, for the compound of Formula (I), L is absent or L is selected from - O-, -S-, -N(R6)-, C1-6alkylene, -N(R6)-C1-6alkylene, and -O-C1-6alkylene, wherein each C1-6alkylene of D or L is optionally substituted with one or more substituent independently selected from halogen and -OR7; R6is selected from hydrogen and C1-4alkyl; and R7is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, L is absent or L is selected from C1-6alkylene, -N(R6)-C1-6alkylene, and -O-C1-6alkylene, wherein each C1-6alkylene of D or L is optionally substituted with one or more -OR7; R6is selected from hydrogen and methyl; and R7is independently selected at each occurrence from hydrogen and methyl. In some embodiments, L is absent or L is selected from -O-, -N(R6)-, C1-6alkylene, -N(R6)-C1-6alkylene, and -O-C1-6alkylene, wherein each C1-6alkylene of D or L is optionally substituted with one or more -OR7; R6is selected from hydrogen and methyl; and R7is independently selected at each occurrence from hydrogen and methyl. In some embodiments, for the compound of Formula (I), L is absent or L is selected from - O-, -S-, -N(R6)-, C1-6alkylene, -N(R6)-C1-6alkylene, -S-C1-6alkylene, and -O-C1-6alkylene. In some embodiments, L is absent or L is selected from -O-, -S-, and -N(R6)-. In some embodiments, L is absent or L is selected from -O- and -N(R6)-. In some embodiments, L is absent or -N(R6)-. In some embodiments, L is absent or -O-. In some embodiments, L is absent or L is selected from C1-6alkylene, -N(R6)-C1-6alkylene, -S-C1-6alkylene, and -O-C1-6alkylene. In some embodiments, L is absent or L is selected from C1-6alkylene, -N(R6)-C1-6alkylene, and -O-C1-6alkylene. In some embodiments, L is absent or L is selected from -N(R6)-C1-6alkylene, -S-C1-6alkylene, and -O-C1-6alkylene. In some embodiments, L is absent or L is selected from -N(R6)-C1-6alkylene and -O- C1-6alkylene. In some embodiments, L is absent or -O-C1-6alkylene. In some embodiments, L is absent or -N(R6)-C1-6alkylene. In some embodiments, L is absent or C1-6alkylene. In some embodiments, each C1-6alkylene of D or L is optionally substituted with one or more -OR7; R6is selected from hydrogen and methyl; and R7is independently selected at each occurrence from hydrogen and methyl. In some embodiments, for the compound of Formula (I), L is selected from -O-, -S-, -N(R6)- , C1-6alkylene, -N(R6)-C1-6alkylene, and -O-C1-6alkylene, wherein each C1-6alkylene of D or L is optionally substituted with one or more substituent independently selected from halogen and -OR7; R6is selected from hydrogen and C1-4alkyl; and R7is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, L is selected from C1-6alkylene, -N(R6)-C1-6alkylene, and -O-C1-6alkylene, wherein each C1-6alkylene of D or L is optionally substituted with one or more -OR7; R6is selected from hydrogen and methyl; and R7is independently selected at each occurrence from hydrogen and methyl. In some embodiments, L is selected from -O-, -N(R6)- , C1-6alkylene, -N(R6)-C1-6alkylene, and -O-C1-6alkylene, wherein each C1-6alkylene of D or L is optionally substituted with one or more -OR7; R6is selected from hydrogen and methyl; and R7is independently selected at each occurrence from hydrogen and methyl. In some embodiments, for the compound of Formula (I), L is selected from -O-, -S-, -N(R6)- , C1-6alkylene, -N(R6)-C1-6alkylene, -S-C1-6alkylene, and -O-C1-6alkylene. In some embodiments, L is selected from -O-, -S-, and -N(R6)-. In some embodiments, L is selected from -O- and -N(R6)- . In some embodiments, L is -N(R6)-. In some embodiments, L is -O-. In some embodiments, L is selected from C1-6alkylene, -N(R6)-C1-6alkylene, -S-C1-6alkylene, and -O-C1-6alkylene. In some embodiments, L is selected from C1-6alkylene, -N(R6)-C1-6alkylene, and -O-C1-6alkylene. In some embodiments, L is selected from -N(R6)-C1-6alkylene, -S-C1-6alkylene, and -O-C1-6alkylene. In some embodiments, L is selected from -N(R6)-C1-6alkylene and -O-C1-6alkylene. In some embodiments, -O-C1-6alkylene. In some embodiments, L is -N(R6)-C1-6alkylene. In some embodiments, L is C1-6alkylene. In some embodiments, each C1-6alkylene of D or L is optionally substituted with one or more -OR7; R6is selected from hydrogen and methyl; and R7is independently selected at each occurrence from hydrogen and methyl. In some embodiments, for the compound of Formula (I), L is absent. In some embodiments, for the compound of Formula (I), D is selected from In some embodiments, for the compound of Formula (I), D is selected from -X- and -X- C1-6alkylene; and X is selected from -S-, and -N(R6)-. In some embodiments, D is selected from - X- and -X-C1-4alkylene; and X is selected from -S-, and -N(R6)-. In some embodiments, each alkylene of D or L is optionally substituted with one or more -OR7. In some embodiments, R6is selected from hydrogen and methyl. In some embodiemnts, R7is independently selected at each occurrence from hydrogen and methyl. In some embodiments, for the compound of Formula (I), D is selected from In some embodiments, for the compound of Formula (I), D is -N(R1)C(O)-L-. In some embodiments, D is *-N(R1)C(O)-L-, wherein the * indicates the point of attachment to the thiazole of Formula (I). Some embodiments provide a compound of Formula (II): or a pharmaceutically acceptable salt thereof, wherein: L is absent or L is selected from -O-, -N(R6)-, C1-4alkylene, -N(R6)-C1-4alkylene, -O-C1-4alkylene, wherein the C1-4alkylene is optionally substituted with one or more halogen; Ring A is selected from C3-C12carbocycle and 3- to 12-membered 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, =O, and -CN; and 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, and -CN; R1is selected from hydrogen and C1-4alkyl; R2is selected from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; and R3and R4are each independently selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, -OR13, -SR13, -N(R13)2, and -CN; or R3and R4come together to form a 3- to 7-membered heterocycle optionally substituted with one or more substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R5is selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)OR15, -OC(O)R15, - C(O)N(R15)2, -N(R15)C(O)R15, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl; R6is selected from hydrogen and C1-4alkyl; R11and R15are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; R13is independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4haloalkyl, C3-6carbocycle, and 3-to-6 membered heterocycle optionally substituted with one or more substituent selected from halogen, C1-4alkyl, and C1-4haloalkyl; and n is selected from 0, 1, and 2; provided that: (A) if L is absent and R3and R4are both hydrogen, Ring A is selected from (i), (ii), (iii), (iv), (v), (vi), or (vii): (i) bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2- oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane; (ii) phenyl and monocyclic heteroaryl, provided that Ring A is not 2-methylpyridine or 1-methyl-2-pyridone; (iii) monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur; (iv) monocyclic heterocycloalkyl substituted with two or more halogen; (v) monocyclic heterocycloalkyl substituted with one or more substituents selected from C1-6haloalkyl, -OR11, C3-C6carbocycle, and 3- to 6-membered heterocycle; (vi) monocyclic C3-C4carbocycle substituted with at least one –OH or 1-2 fluorine; and (vii) cyclohexyl substituted with -OH, 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, =O, and -CN; and 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, and -CN; (B) if L is methylene and Ring A is tetrahydropyran, then at least one of R3and R4is not hydrogen; (C) if L is absent and R3and R4are each methyl, then Ring A is not 2,2,5,5- tetramethyltetrahydrofuranyl, 2,2-dimethyltetrahydropyranyl, or 2,2,6,6- tetramethyltetrahydropyranyl; (D) if L is absent, R3is 3-methylmorpholinyl, and R4is hydrogen, then Ring A is not 2,2,5,5-tetramethyltetrahydrofuranyl; and (E) if L is absent, R3is OH, and R4is hydrogen, then Ring A is not 4- fluorotetrahydropyranyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), 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 Formulae (I) or (II), R1is hydrogen or -CH3. In some embodiments, R1is hydrogen. In some embodiments, R1is C1-4alkyl. In some embodiments, R1is -CH3. In some embodiments, for the compound of Formulae (I) or (II), R2is hydrogen. In some embodiments, R2is halogen. In some embodiments, R2is fluoro. In some embodiments, R2is chloro. In some embodiments, R2is C1-4alkyl. In some embodiments, R2is methyl. In some embodiments, R2is ethyl. In some embodiments, R2is C1-4haloalkyl. In some embodiments, R2is trifluoromethyl. In some embodiments, R2is trifluoroethyl. In some embodiments, for the compound of Formulae (I) or (II), L is absent or L is selected from -O-, C1-2alkylene, and -N(R6)-C1-2alkylene, wherein the C1-2alkylene is optionally substituted with one or more -F. In some embodiments, L is absent or L is selected from -O-, C1-2alkylene, and -N(R6)-C1-2alkylene, wherein the C1-2alkylene is optionally substituted with 1-4 -F. In some embodiments, L is absent, or L is selected from -O-, -CH2-, -CFH-, -CF2-, and -N(H)CH2- . In some embodiments, L is selected from -O-, -CH2-, -CFH-, and -N(H)CH2-. In some embodiments, L is absent. In some embodiments, L is -O-. In some embodiments, L is -CH2-. In some embodiments, -CFH-. In some embodiments, -CF2-. In some embodiments, -N(H)CH2-. In some embodiments, C1-2alkylene. In some embodiments, L is -N(R6)-C1-2alkylene optionally substituted with 1-4 -F. In some embodiments, for the compound of Formulae (I) or (II), R6is hydrogen. In some embodiments, R6is -C1-6alkyl. In some embodiments, R6is methyl. In some embodiments, the compound is of Formula (IA): (IA), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IB): (IB), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IIA): (IIA), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IIB): (IIB), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), or (IIB), n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), or (IIB), R5is independently selected at each occurrence from halogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), or (IIB), R5is independently selected at each occurrence from halogen and C1-4alkyl, In some embodiments, the compound is of Formula (IIC): (IIC), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are each independently selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, -OR13, -SR13, -N(R13)2, and -CN. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are each independently selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR13, -SR13, -N(R13)2, and -CN. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are each independently selected from: hydrogen, halogen, -OR13, C1-6alkyl optionally substituted with one or more substituents independently selected from halogen and morpholinyl, and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more C1-6alkyl. In some embodiments, R3and R4are each independently selected from: hydrogen, halogen, -OR13, C1-6alkyl optionally substituted with 1-4 substituents independently selected from halogen and morpholinyl, and 3- to 6-membered heterocycle, each of which is optionally substituted with 1-4 C1-6alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are each independently selected from: hydrogen, halogen, -OR13, -N(R13)2, and -C(O)N(R13)2; C1-6alkyl optionally substituted with one or more substituents independently selected from -F and morpholinyl; and 3- to 6- membered heterocycle optionally substituted with one or more C1-6alkyl; or R3and R4come together to form a 5- to 7-membered heterocycle optionally substituted with one or more C1-4alkyl; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and 3-to-6 membered heterocycle. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are each independently selected from: hydrogen, halogen, -OR13, -N(R13)2, and -C(O)N(R13)2; C1-6alkyl optionally substituted with 1-4 substituents independently selected from -F and morpholinyl; and 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6alkyl; or R3and R4come together to form a 5- to 7-membered heterocycle optionally substituted with 1-4 C1-4alkyl; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and 3-to-6 membered heterocycle. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4come together to form a 3- to 7-membered heterocycle optionally substituted with one or more substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, - OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments, R3and R4come together to form a 3- to 7-membered heterocycle optionally substituted with 1-4 substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, - C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments, R3and R4come together to form a 3- to 7-membered heterocycle optionally substituted with 1-4 substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4come together to form a 3- to 7-membered heterocycle optionally substituted with 1-4 substituents selected from: -C(O)OR13and C1-6alkyl. In some embodiments, R3and R4come together to form a 3- to 7-membered heterocycle optionally substituted with 1-4 substituents selected from C1-6alkyl. In some embodiments, R3and R4come together to form a 3- to 6- membered heterocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, R3and R4come together to form a 5- to 7-membered heterocycle optionally substituted with one or more C1-4 alkyl. In some embodiments, R3and R4come together to form a 5- to 7-membered heterocycle optionally substituted with 1-4 C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4come together to form a 5- to 7-membered heterocycle selected from In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are each independently selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, - OR13, -SR13, -N(R13)2, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and 3-to-6 membered heterocycle. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are each independently selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR13, -SR13, -N(R13)2, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and 3-to-6 membered heterocycle. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are each independently selected from hydrogen, halogen, -OR13, -N(R13)2, and -C(O)N(R13)2; C1-6alkyl optionally substituted with one or more substituents independently selected from -F and morpholinyl; and 3- to 6-membered heterocycle optionally substituted with one or more C1-6alkyl; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and 3-to-6 membered heterocycle. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are each independently selected from hydrogen, halogen, -OR13, -N(R13)2, and -C(O)N(R13)2; C1-6alkyl optionally substituted with 1-4 substituents independently selected from -F and morpholinyl; and 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6alkyl; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and 3-to-6 membered heterocycle. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are each independently selected from C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6- membered heterocycle. In some embodiments, R3and R4are each independently selected from C1-6alkyl optionally substituted with 1-4 substituents independently selected from halogen, -OR13, - SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are each independently selected from C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3is halogen. In some embodiments, R3is fluoro. In some embodiments, R3is chloro. In some embodiments, R3is -OR13. In some embodiments, R3is –OH. In some embodiments, R3is methoxy.In some embodiments, R3is C1-6alkyl optionally substituted with 1-4 substituents independently selected from halogen and morpholinyl. In some embodiments, R3is unsubstituted C1-6alkyl. In some embodiments, R3is methyl. In some embodiments, R3is ethyl. In some embodiments, R3is isopropyl. In some embodiments, R3is 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R4is halogen. In some embodiments, R4is fluoro. In some embodiments, R4is chloro. In some embodiments, R4is -OR13. In some embodiments, R4is –OH. In some embodiments, R4is methoxy. In some embodiments, R4is C1-6alkyl optionally substituted with 1-4 substituents independently selected from halogen and morpholinyl. In some embodiments, R4is unsubstituted C1-6alkyl. In some embodiments, R4is methyl. In some embodiments, R4is ethyl. In some embodiments, R4is isopropyl. In some embodiments, R4is 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3is hydrogen. In some embodiments, R4is hydrogen. In some embodiments, at least one of R3and R4is not hydrogen. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3is hydrogen and R4is unsubstituted C1-6alkyl. In some embodiments, R3is hydrogen and R4is methyl. In some embodiments, R3is hydrogen and R4is ethyl. In some embodiments, R3is hydrogen and R4is isopropyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are each independently selected from: hydrogen, halogen, -OR13, C1-6alkyl optionally substituted with one or more substituents independently selected from halogen and morpholinyl, and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more C1-6alkyl. In some embodiments,, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC),R3is selected from hydrogen, -Cl, -OH, -CH3, In some embodiments,, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3is selected from hydrogen, -OH, -CH3, In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R4is selected from hydrogen, -Cl, -CH3, -CHF2, and . In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3is hydrogen and R4is selected from halogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, R3is hydrogen and R4is selected from halogen, C1-2alkyl, and C1-2haloalkyl. In some embodiments, R3is hydrogen and R4is selected from halogen, methyl, and C1 haloalkyl. In some embodiments, R3is hydrogen and R4is selected from -F, -Cl, C1-4alkyl, and C1-4haloalkyl. In some embodiments, R3is hydrogen and R4is selected from -F, -Cl, C1-2alkyl, and C1-2haloalkyl. In some embodiments, R3is hydrogen and R4is selected from -F, -Cl, methyl, and C1haloalkyl. In some embodiments, R3is hydrogen and R4is selected from halogen and C1-2alkyl. In some embodiments, R3is hydrogen and R4is selected from halogen and methyl. In some embodiments, R3is hydrogen and R4is selected from -F, -Cl, and methyl. In some embodiments, R3is hydrogen and R4is selected from -Cl, and methyl. In some embodiments, R3is hydrogen and R4is -Cl. In some embodiments, R3is hydrogen and R4is methyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (II), (IIA), (IIB), or (IIC), R3and R4are the same. In some embodiments, R3and R4are each hydrogen. In some embodiments, R3and R4are each methyl. In some embodiments, R3and R4are different. In some embodiments, one of R3and R4is hydrogen and the other of R3and R4is methyl. In some embodiments, R3is hydrogen and R4is methyl. In some embodiments, R3is methyl and R4is hydrogen. In some embodiments, the compound is of Formula (IC): (IC), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (ID): (ID), or a pharmaceutically acceptable salt thereof; wherein R14is 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 (IE): (IE), or a pharmaceutically acceptable salt thereof; wherein R14is selected from halogen, -OR11, and C1-6alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, R14is selected from halogen and C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, R14is selected from halogen and C1-6alky. In some embodiments, R14is selected from C1-6alkyl. In some embodiments, Q is O, NH, or S. In some embodiments, Q is O. In some embodiments, the compound is of Formula (IID): (IID), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IIE): (IIE), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IIE-2): (IIE-2), or a pharmaceutically acceptable salt thereof; wherein R14is selected from halogen, -OR11, and C1-6alkyl optionally substituted with 1- 4 halogen; and Q is O, NH, or S; and R11is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, the compound is of Formula (IIE-3): (IIE-3), or a pharmaceutically acceptable salt thereof; wherein R14is selected from halogen, -OR11, and C1-6alkyl optionally substituted with 1- 4 halogen; and Q is O, NH, or S; and R11is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, the compound is of Formula (IIE-3a): (IIE-3a), or a pharmaceutically acceptable salt thereof; wherein R14is selected from halogen, -OR11, and C1-6alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S; and R11is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, the compound is of Formula (IIE-3b): (IIE-3b), or a pharmaceutically acceptable salt thereof; wherein R14is selected from halogen, -OR11, and C1-6alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S; and and R11is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, the compound is of Formula (IIE-4): (IIE-4), or a pharmaceutically acceptable salt thereof; wherein R14is selected from halogen, -OR11, and C1-6alkyl optionally substituted with 1- 4 halogen; and Q is O, NH, or S; and R11is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, the compound is of Formula (IIE-5): (IIE-5), or a pharmaceutically acceptable salt thereof; wherein R14is selected from halogen, -OR11, and C1-6alkyl optionally substituted with 1- 4 halogen; and R11is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, the compound is of Formula (IIE-5a): (IIE-5a), or a pharmaceutically acceptable salt thereof; wherein R14is selected from halogen, -OR11, and C1-6alkyl optionally substituted with 1- 4 halogen; and R11is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, the compound is of Formula (IIE-5b): (IIE-5b), or a pharmaceutically acceptable salt thereof; wherein R14is selected from halogen, -OR11, and C1-6alkyl optionally substituted with 1- 4 halogen; and R11is independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl. In some embodiments, the compound is of Formula (IIE-6): (IIE-6), or a pharmaceutically acceptable salt thereof; wherein R14is C1-6alkyl optionally substituted with 1-4 halogen.

[0002] In some embodiments, the compound is of Formula (IIE-7): (IIE-7), or a pharmaceutically acceptable salt thereof; wherein R14is C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, the compound is of Formula (IIE-10): (IIE-10), or a pharmaceutically acceptable salt thereof; wherein R14is C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, the compound is of Formula (IIE-10a): (IIE-10a), or a pharmaceutically acceptable salt thereof; wherein R14is C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, the compound is of Formula (IIE-10b): (IIE-10b), or a pharmaceutically acceptable salt thereof; wherein R14is C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, the compound is of Formula (IIF): (IIF), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IG): (IIG), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IIH): (IIH), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE-5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), R4is selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR13, -SR13, -N(R13)2, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and 3-to-6 membered heterocycle. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE-5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), R4is selected from hydrogen, halogen, -OR13, -N(R13)2, and -C(O)N(R13)2; C1-6alkyl optionally substituted with 1-4 substituents independently selected from -F and morpholinyl; and 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6alkyl; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and 3-to-6 membered heterocycle. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE-5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), R4is selected from C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle. In some embodiments, R4is selected from C1-6alkyl optionally substituted with 1-4 substituents independently selected from halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE-5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), R4is halogen. In some embodiments, R4is fluoro. In some embodiments, R4is chloro. In some embodiments, R4is -OR13and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and 3-to-6 membered heterocycle. In some embodiments, R4is –OH. In some embodiments, R4is methoxy. In some embodiments, R4is C1-6alkyl optionally substituted with 1-4 substituents independently selected from halogen and morpholinyl.. In some embodiments, R4is C1-6alkyl or R4is C1-6haloalkyl. In some embodiments, R4is unsubstituted C1-6alkyl. In some embodiments, R4is methyl. In some embodiments, R4is ethyl. In some embodiments, R4is isopropyl. In some embodiments, R4is 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE-5a), (IIE-5b), (IIE-6), (IIE- 7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), R4is selected from hydrogen, -Cl, -CH3, - CHF2, and . In some embodiments, the compound is of Formula (ID): (ID), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IE): (IE), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IIE-1): (IIE-1), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from C3-C12carbocycle and 3- to 12-membered 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, =O, and -CN; and 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, and -CN; and C3-C6carbocycle 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, -C(O)R11, -C(O)OR11, =O, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from C3-C12carbocycle and 3- to 12-membered 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, -C(O)N(R11)2, -S(O)R11, -S(O)2R11, -S(O)2N(R11)2, =O, and -CN; and C1-6alkyl 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, -S(O)R11, - S(O)2R11, -S(O)2N(R11)2, =O, and -CN; and C3-C6carbocycle 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, =O, -CN, C1-6alkyl, and C1-6haloalkyl; and wherein R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodimetns, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from C3-C12carbocycle and 3- to 12-membered 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, -C(O)N(R11)2, -N(R11)C(O)R11, S(O)2R11, =O, and -CN; 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, -C(O)N(R11)2, -N(R11)C(O)R11, S(O)2R11, and -CN; and phenyl and 6-membered heterocycle, each of which is optionally substituted with one or more substituent independently selected from halogen, -OR11, C1-4alkyl, and C1-4haloalkyl; and R11is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodimetns, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from C3-C12carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with 1 to 4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, S(O)2R11, =O, and -CN; C1-6alkyl optionally substituted with 1 to 4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, S(O)2R11, and -CN; and phenyl and 6-membered heterocycle, each of which is optionally substituted with 1 to 4 substituent independently selected from halogen, -OR11, C1-4alkyl, and C1-4haloalkyl; and R11is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from C3-C12carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with 1 to 4 substituents independently selected from: halogen, -OR11, -SR11, -C(O)R11, -C(O)OR11, -S(O)2R11, and, =O; and C1-6alkyl optionally substituted with 1 to 4 substituents independently selected from: halogen and -OR11; and C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with 1 to 4 C1-6alkyl; and and wherein R11is selected at each occurrence from hydrogen and C1-4alkyl.In some embodiments, Ring A is selected from C3-C12carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with 1 to 4 substituents independently selected from: halogen, -OR11, -SR11, -C(O)R11, -C(O)OR11, -S(O)2R11, and, =O; and C1-6alkyl optionally substituted with 1 to 4 substituents independently selected from: halogen and -OR11; and phenyl and 6-membered heterocycle, each of which is optionally substituted with 1 to 4 C1-6alkyl; and and wherein R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from C3-C12carbocycle and 3- to 12-membered heterocycle comprising 1 to 4 heteroatoms selected from O, S, and N, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -C(O)R11, S(O)2R11, -CN, =O; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen and - OR11; phenyl; and 6-membered heteroaryl; and wherein R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from C3-C12carbocycle and 3- to 12-membered heterocycle comprising 1 to 4 heteroatoms selected from O, S, and N, each of which is optionally substituted with 1 to 4 substituents independently selected from: halogen, -OR11, -SR11, -C(O)R11, S(O)2R11, -CN, =O; C1-6alkyl optionally substituted with 1 to 4 substituents independently selected from halogen and -OR11; phenyl; and 6-membered heteroaryl; and wherein R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from C3-C12carbocycle and 3- to 12-membered 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, -C(O)N(R11)2, - N(R11)C(O)R11, =O, and -CN; and 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, -C(O)N(R11)2, - N(R11)C(O)R11, and -CN; and R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), 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, 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), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), 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), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from C3-C12carbocycle and 3- to 12-membered heterocycle, 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, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN; and R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is C3- C12carbocycle optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN; and R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is 3- to 12-membered heterocycle optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN; and R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from C3-C12carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -CN; and C1-6alkyl optionally substituted with one or more halogen; and R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, Ring A is selected from C3-C12carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -CN; and C1-6alkyl optionally substituted with 1-4 halogen; and R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, Ring A is C3-C12carbocycle is optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -CN; and C1-6alkyl optionally substituted with 1-4 halogen; and R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is 3- to 12-membered heterocycle optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -CN; and C1-6alkyl optionally substituted with 1-4 halogen; and R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, Ring A is 5- to 6-membered heterocycle optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -CN; and C1-6alkyl optionally substituted with 1-4 halogen; and R11is selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and 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, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), 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, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN. In some embodiments, Ring A is C3-C10saturated partially saturated carbocycle optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), 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, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is optionally substituted with one or more substituents independently selected from: halogen, -CN, and C1-6alkyl. In some embodiments, Ring A is optionally substituted with 1-4 substituents independently selected from: halogen, -CN, and C1-6alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially saturated carbocycle, and a 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, -CN; and C1-6alkyl. In some embodiments, Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially saturated carbocycle, and a 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, -CN; and C1-6alkyl. In some embodiments, Ring A is C3-C10saturated cycloalkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -CN; and C1-6alkyl.In some embodiments, Ring A is C3-C10partially saturated carbocycle optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -CN; and C1-6alkyl. In some embodiments, Ring A is 3- to 10-membered saturated heterocycloalkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -CN; and C1-6alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially saturated carbocycle, and a 3- to 10- membered saturated heterocycloalkyl, each of which is optionally substituted with one or more C1-6alkyl. In some embodiments, Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially saturated carbocycle, and a 3- to 10-membered saturated heterocycloalkyl, each of which is optionally substituted with 1-4 C1-6alkyl. In some embodiments, Ring A is selected from a C3- C10saturated cycloalkyl optionally substituted with 1-4 C1-6alkyl. In some embodiments, Ring A is selected from a C3-C10partially saturated carbocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, Ring A is selected from a 3- to 10-membered saturated heterocycloalkyl optionally substituted with 1-4 C1-6alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from cyclopropyl, cyclobutyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, oxazolidinyl, tetrahydropyranyl, 1,4,-dioxanyl, pyrrolidinyl, piperidinyl, morpholinyl, quinuclidinyl, spiro[2.2]pentanyl, 2-oxa-5-azabicyclo[2.2.1]heptane, 3-bicyclo[1.1.1]pentyl, 3- oxabicyclo[3.1.0]hexanyl, 2-oxabicyclo[3.1.0]hexanyl, hexahydro-2,5-dioxaindenyl, 2- oxabicyclo[2.1.1]hexanyl, 7-oxabicyclo[2.2.1]heptanyl, 2-oxabicyclo[2.2.1]heptanyl, 2- oxabicyclo[2.2.2]octanyl, 8-oxabicyclo[3.2.1]octanyl, 2-oxaspiro[3.3]heptanyl, 5- oxaspiro[2.4]heptanyl, 4-oxaspiro[2.5]octanyl, 6-oxaspiro[2.5]octanyl, 6-oxaspiro[4.5]decanyl, 5- oxaspiro[3.5]nonanyl, 2-oxaspiro[3.5]nonanyl, 1-oxaspiro[5.5]undecanyl, 1,9- dioxaspiro[5.5]undecanyl, 4,5,6,7-tetrahydroindazolyl, 2-oxaindazolyl, chromanyl, isochromanyl, phenyl, pyrimidinyl, pyrrolyl, pyridinyl, 2-pyridonyl, and pyrazolyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - C(O)R11, S(O)2R11, -CN, =O; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen and -OR11; phenyl; and 6-membered heterocycle optionally substituted with one or more C1-4alkyl; and wherein R11is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from cyclopropyl, cyclobutyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, oxazolidinyl, tetrahydropyranyl, 1,4,-dioxanyl, pyrrolidinyl, piperidinyl, morpholinyl, quinuclidinyl, spiro[2.2]pentanyl, 2-oxa-5-azabicyclo[2.2.1]heptane, 3-bicyclo[1.1.1]pentyl, 3- oxabicyclo[3.1.0]hexanyl, 2-oxabicyclo[3.1.0]hexanyl, hexahydro-2,5-dioxaindenyl, 2- oxabicyclo[2.1.1]hexanyl, 7-oxabicyclo[2.2.1]heptanyl, 2-oxabicyclo[2.2.1]heptanyl, 2- oxabicyclo[2.2.2]octanyl, 8-oxabicyclo[3.2.1]octanyl, 2-oxaspiro[3.3]heptanyl, 5- oxaspiro[2.4]heptanyl, 4-oxaspiro[2.5]octanyl, 6-oxaspiro[2.5]octanyl, 6-oxaspiro[4.5]decanyl, 5- oxaspiro[3.5]nonanyl, 2-oxaspiro[3.5]nonanyl, 1-oxaspiro[5.5]undecanyl, 1,9- dioxaspiro[5.5]undecanyl, 4,5,6,7-tetrahydroindazolyl, 2-oxaindazolyl, chromanyl, isochromanyl, phenyl, pyrimidinyl, pyrrolyl, pyridinyl, 2-pyridonyl, and pyrazolyl, each of which is optionally substituted with 1 to 4 substituents independently selected from: halogen, -OR11, -SR11, -C(O)R11, S(O)2R11, -CN, =O; C1-6alkyl optionally substituted with 1 to 4 substituents independently selected from halogen and -OR11; phenyl; and 6-membered heterocycle optionally substituted with 1 to 4 C1-4alkyl; and wherein R11is independently selected at each occurrence from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from: cyclopropyl, cyclobutyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, oxazolidinyl, tetrahydropyranyl, 1,4,-dioxanyl, pyrrolidinyl, piperidinyl, morpholinyl, quinuclidinyl, spiro[2.2]pentanyl, 2-oxa-5-azabicyclo[2.2.1]heptane, 3-bicyclo[1.1.1]pentyl, 3- oxabicyclo[3.1.0]hexanyl, 2-oxabicyclo[3.1.0]hexanyl, hexahydro-2,5-dioxaindenyl, 2- oxabicyclo[2.1.1]hexanyl, 7-oxabicyclo[2.2.1]heptanyl, 2-oxabicyclo[2.2.1]heptanyl, 2- oxabicyclo[2.2.2]octanyl, 8-oxabicyclo[3.2.1]octanyl, 2-oxaspiro[3.3]heptanyl, 5- oxaspiro[2.4]heptanyl, 4-oxaspiro[2.5]octanyl, 6-oxaspiro[2.5]octanyl, 6-oxaspiro[4.5]decanyl, 5- oxaspiro[3.5]nonanyl, 2-oxaspiro[3.5]nonanyl, 1-oxaspiro[5.5]undecanyl, 1,9- dioxaspiro[5.5]undecanyl, 4,5,6,7-tetrahydroindazolyl, 2-oxaindazolyl, chromanyl, isochromanyl, phenyl, pyrimidinyl, pyrrolyl, pyridinyl, 2-pyridonyl, and pyrazolyl, each of which is optionally substituted with one or more substituents independently selected from: -F, -CH3, ethyl, isopropyl, isobutyl, tert-butyl, -C(CH3)2OH, -CF3, -CHF2, -OH, -OCH3, -SCH3, -S(O)2CH3, =O, -CN, - C(O)CH3, -C(O)-tert-butyl, phenyl, N-methylpiperidinyl, and pyridinyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from: cyclopropyl, cyclobutyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, oxazolidinyl, tetrahydropyranyl, 1,4,-dioxanyl, pyrrolidinyl, piperidinyl, morpholinyl, quinuclidinyl, spiro[2.2]pentanyl, 2-oxa-5-azabicyclo[2.2.1]heptane, 3-bicyclo[1.1.1]pentyl, 3- oxabicyclo[3.1.0]hexanyl, 2-oxabicyclo[3.1.0]hexanyl, hexahydro-2,5-dioxaindenyl, 2- oxabicyclo[2.1.1]hexanyl, 7-oxabicyclo[2.2.1]heptanyl, 2-oxabicyclo[2.2.1]heptanyl, 2- oxabicyclo[2.2.2]octanyl, 8-oxabicyclo[3.2.1]octanyl, 2-oxaspiro[3.3]heptanyl, 5- oxaspiro[2.4]heptanyl, 4-oxaspiro[2.5]octanyl, 6-oxaspiro[2.5]octanyl, 6-oxaspiro[4.5]decanyl, 5- oxaspiro[3.5]nonanyl, 2-oxaspiro[3.5]nonanyl, 1-oxaspiro[5.5]undecanyl, 1,9- dioxaspiro[5.5]undecanyl, 4,5,6,7-tetrahydroindazolyl, 2-oxaindazolyl, chromanyl, isochromanyl, phenyl, pyrimidinyl, pyrrolyl, pyridinyl, 2-pyridonyl, and pyrazolyl, each of which is optionally substituted with 1 to 4 substituents independently selected from: -F, -CH3, ethyl, isopropyl, isobutyl, tert-butyl, -C(CH3)2OH, -CF3, -CHF2, -OH, -OCH3, -SCH3, -S(O)2CH3, =O, -CN, - C(O)CH3, -C(O)-tert-butyl, phenyl, N-methylpiperidinyl, and pyridinyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from:

[0003] In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -CN; and C1-6alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), R11is selected from hydrogen and C1-4alkyl. In some embodiments, R11is selected from hydrogen and methyl. In some embodiments, R11is hydrogen. In some embodiments, R11is C1-4alkyl. In some embodiments, R11is methyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is optionally substituted with one or more -CH3. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is ; wherein the asterisk indicates the point of connection to L; R14is selected from halogen, - OR11, and C1-6alkyl optionally substituted with 1-4 halogen; and Q is O, NH, or S. In some embodiments, R14is halogen. In some embodiments, R14is -OR11. In some embodiments, R14is C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, R14is C1-6alkyl. In some embodiments, R14is methyl. In some embodiments, Q is O. In some embodiments, Q is NH. In some embodiments, Q is S. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is optionally substituted with 1-4 -CH3. In some embodiments, Ring A is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is optionally substituted with one -CH3. In some embodiments, Ring A is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is substituted with 1-4 -CH3. In some embodiments, Ring A is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is substituted with one -CH3. In some embodiments, Ring A is selected from: unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, unsubstituted cyclohexyl, unsubstituted oxetanyl, unsubstituted tetrahydrofuranyl, unsubstituted tetrahydropyranyl, unsubstituted piperidinyl, unsubstituted and unsubstituted tetrahydronaphthyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from cyclopropyl, cyclobutyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholinyl, 3-oxabicyclo[3.1.0]hexane, hexahydro-2,5-dioxaindene, 2- oxabicyclo[2.1.1]hexane, 7-oxabicyclo[2.2.1]heptane, 2-oxabicyclo[2.2.1]heptane, 2- oxabicyclo[2.2.2]octane, 8-oxabicyclo[3.2.1]octane, 2-oxaspiro[3.3]heptane, 5- oxaspiro[2.4]heptane, 6-oxaspiro[2.5]octane, 6-oxaspiro[4.5]decane, 5-oxaspiro[3.5]nonane, 2- oxaspiro[3.5]nonane, 1-oxaspiro[5.5]undecane, 1,9-dioxaspiro[5.5]undecane, phenyl, pyridinyl, and pyrazole, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from cyclopropyl, cyclobutyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholinyl, 3-oxabicyclo[3.1.0]hexane, hexahydro-2,5-dioxaindene, 2- oxabicyclo[2.1.1]hexane, 7-oxabicyclo[2.2.1]heptane, 2-oxabicyclo[2.2.1]heptane, 2- oxabicyclo[2.2.2]octane, 8-oxabicyclo[3.2.1]octane, 2-oxaspiro[3.3]heptane, 5- oxaspiro[2.4]heptane, 6-oxaspiro[2.5]octane, 6-oxaspiro[4.5]decane, 5-oxaspiro[3.5]nonane, 2- oxaspiro[3.5]nonane, 1-oxaspiro[5.5]undecane, 1,9-dioxaspiro[5.5]undecane, phenyl, pyridinyl, and pyrazole, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is cyclopropyl optionally substituted with 1-4 substituents independently selected from: halogen, - OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is cyclobutyl optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is cyclohexyl optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is tetrahydrofuranyl optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is tetrahydropyranyl optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is piperidinyl optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is morpholinyl optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is 3- oxabicyclo[3.1.0]hexane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is hexahydro-2,5-dioxaindene optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is 2- oxabicyclo[2.1.1]hexane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is 7-oxabicyclo[2.2.1]heptane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is 2-oxabicyclo[2.2.1]heptane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is 2- oxabicyclo[2.2.2]octane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is 8-oxabicyclo[3.2.1]octane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is 2-oxaspiro[3.3]heptane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is 5- oxaspiro[2.4]heptane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is 6- oxaspiro[2.5]octane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is 6-oxaspiro[4.5]decane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is 5-oxaspiro[3.5]nonane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is 2- oxaspiro[3.5]nonane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is 1-oxaspiro[5.5]undecane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is 1,9- dioxaspiro[5.5]undecane optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is phenyl optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is pyridinyl optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, Ring A is pyrazole optionally substituted with 1-4 substituents independently selected from: halogen, -OCH3, -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from cyclopropyl, cyclobutyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, oxazolidine, tetrahydropyranyl, 1,4,-dioxanyl, piperidinyl, morpholinyl, 3-oxabicyclo[3.1.0]hexane, hexahydro-2,5-dioxaindene, 2-oxabicyclo[2.1.1]hexane, 7-oxabicyclo[2.2.1]heptane, 2- oxabicyclo[2.2.1]heptane, 2-oxabicyclo[2.2.2]octane, 8-oxabicyclo[3.2.1]octane, 2- oxaspiro[3.3]heptane, 5-oxaspiro[2.4]heptane, 6-oxaspiro[2.5]octane, 6-oxaspiro[4.5]decane, 5- oxaspiro[3.5]nonane, 2-oxaspiro[3.5]nonane, 1-oxaspiro[5.5]undecane, 1,9- dioxaspiro[5.5]undecane, phenyl, pyridinyl, and pyrazolyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OH, -OCH3, -CN, =O; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from: cyclopropyl, cyclobutyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholinyl, 3-oxabicyclo[3.1.0]hexane, hexahydro-2,5-dioxaindene, 2- oxabicyclo[2.1.1]hexane, 7-oxabicyclo[2.2.1]heptane, 2-oxabicyclo[2.2.1]heptane, 2- oxabicyclo[2.2.2]octane, 8-oxabicyclo[3.2.1]octane, 2-oxaspiro[3.3]heptane, 5- oxaspiro[2.4]heptane, 6-oxaspiro[2.5]octane, 6-oxaspiro[4.5]decane, 5-oxaspiro[3.5]nonane, 2- oxaspiro[3.5]nonane, 1-oxaspiro[5.5]undecane, 1,9-dioxaspiro[5.5]undecane, phenyl, pyridinyl, and pyrazole, each of which is optionally substituted with one or more substituents independently selected from: -F, -CH3, tert-butyl, -CF3, -CHF2, -OCH3, and -CN. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from: cyclopropyl, cyclobutyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, oxazolidine, tetrahydropyranyl, 1,4,-dioxanyl, piperidinyl, morpholinyl, 3-oxabicyclo[3.1.0]hexane, hexahydro-2,5-dioxaindene, 2-oxabicyclo[2.1.1]hexane, 7-oxabicyclo[2.2.1]heptane, 2- oxabicyclo[2.2.1]heptane, 2-oxabicyclo[2.2.2]octane, 8-oxabicyclo[3.2.1]octane, 2- oxaspiro[3.3]heptane, 5-oxaspiro[2.4]heptane, 6-oxaspiro[2.5]octane, 6-oxaspiro[4.5]decane, 5- oxaspiro[3.5]nonane, 2-oxaspiro[3.5]nonane, 1-oxaspiro[5.5]undecane, 1,9- dioxaspiro[5.5]undecane, phenyl, pyridinyl, and pyrazolyl, each of which is optionally substituted with one or more substituents independently selected from: -F, -CH3, tert-butyl, -CF3, -CHF2, - OH, -OCH3, =O, and -CN. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from: cyclopropyl, cyclobutyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholinyl, 3-oxabicyclo[3.1.0]hexane, hexahydro-2,5-dioxaindene, 2- oxabicyclo[2.1.1]hexane, 7-oxabicyclo[2.2.1]heptane, 2-oxabicyclo[2.2.1]heptane, 2- oxabicyclo[2.2.2]octane, 8-oxabicyclo[3.2.1]octane, 2-oxaspiro[3.3]heptane, 5- oxaspiro[2.4]heptane, 6-oxaspiro[2.5]octane, 6-oxaspiro[4.5]decane, 5-oxaspiro[3.5]nonane, 2- oxaspiro[3.5]nonane, 1-oxaspiro[5.5]undecane, 1,9-dioxaspiro[5.5]undecane, phenyl, pyridinyl, and pyrazole, each of which is optionally substituted with 1-4 substituents independently selected from: -F, -CH3, tert-butyl, -CF3, -CHF2, -OCH3, and -CN. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from:

[0004] In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from: In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from: In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), 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, 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), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), 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 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 C1-6alkyl. 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), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), 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 C1-6alkyl. 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 C1-6alkyl. 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, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), 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, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), when Ring A is optionally substituted with 1-4 substituents, one of the 1-4 substituents is attached to the ring member of Ring A that is attached to –L-. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), R10is selected from hydrogen and C1-4alkyl. In some embodiments, R10is selected from hydrogen and methyl. In some embodiments, R10is hydrogen. In some embodiments, R10is methyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from: In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is selected from: In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, Ring A is . In some embodiments, the compound is of Formula (IIE-8): (IIE-8), or a pharmaceutically acceptable salt thereof; wherein each R14is independently selected from hydrogen and C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, each R14is independently selected from C1-6alkyl. In some embodiments, the compound is of Formula (IIE-9): (IIE-9), or a pharmaceutically acceptable salt thereof; wherein each R14is independently selected from hydrogen and C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, each R14is independently selected from C1-6alkyl. In some embodiments, the compound is of Formula (IIE-9a): (IIE-9a), or a pharmaceutically acceptable salt thereof; wherein each R14is independently selected from hydrogen and C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, each R14is independently selected from C1-6alkyl. In some embodiments, the compound is of Formula (IIE-9b): (IIE-9b), or a pharmaceutically acceptable salt thereof; wherein each R14is independently selected from hydrogen and C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, each R14is independently selected from C1-6alkyl. In some embodiments, the compound is of Formula (IIE-11): (IIE-11), or a pharmaceutically acceptable salt thereof; wherein each R14is independently selected from hydrogen and C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, each R14is independently selected from C1-6alkyl. In some embodiments, the compound is of Formula (IIE-11a): (IIE-11a), or a pharmaceutically acceptable salt thereof; wherein R14is C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, the compound is of Formula (IIE-11b): (IIE-11b), or a pharmaceutically acceptable salt thereof; wherein each R14is independently selected from hydrogen and C1-6alkyl optionally substituted with 1-4 halogen. In some embodiments, each R14is independently selected from C1-6alkyl. In some embodiments, for the compound of for the compound of Formulae (I), (IA), (IB), (IC), (ID), or (IE), D is -N(R1)C(O)-L-; L is absent, R3and R4are both hydrogen, and Ring A is selected from (i), (ii), (iii): (i) bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2- oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane; (ii) phenyl and monocyclic heteroaryl, provided that Ring A is not 2-methylpyridine or 1-methyl-2-pyridone; (iii) monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur; and (iv) monocyclic heterocycloalkyl substituted with two or more halogen; 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, =O, and -CN; and 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, and -CN. In some embodiments, for the compound of for the compound of Formulae (I), (IA), (IB), (IC), (ID), or (IE), D is -N(R1)C(O)-L-; L is absent, R3and R4are both hydrogen, and Ring A is selected from (i), (ii), and (iii): Ring A is selected from (i), (ii), and (iii): (v) bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2- oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane; (vi) phenyl and monocyclic heteroaryl, provided that Ring A is not 2-methylpyridine or 1-methyl-2-pyridone; (vii) monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur; and (viii) monocyclic heterocycloalkyl substituted with two or more halogen; each of which is optionally substituted with one or more substituents independently selected from: halogen, -CN, -OR11, C(O)R11, C(O)OR11, C1-6alkyl, C1-4haloalkyl, and 6- membered heterocycle optionally substituted with C1-4alkyl; and wherein R11is selected from hydrogen and C1-4alkyl. In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), L is absent; R3and R4are both hydrogen, and Ring A is selected from (i), (ii), and (iii): (i) bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2- oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane; (ii) phenyl and monocyclic heteroaryl, provided that Ring A is not 2-methylpyridine or 1-methyl-2-pyridone; and (iii) monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur; 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, =O, and -CN; and 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, and -CN. In some embodiments,, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), L is absent; R3and R4are both hydrogen, and Ring A is selected from (i), (ii), and (iii): (i) bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2- oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane; (ii) phenyl and monocyclic heteroaryl, provided that Ring A is not 2-methylpyridine or 1-methyl-2-pyridone; and (iii) monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur; 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, -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; and C1-6alkyl optionally substituted with 1-4 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, and -CN. In some embodiments,, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), if L is absent and R3and R4are both hydrogen, Ring A is selected from (i), (ii), and (iii): (i) bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2- oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane; (ii) phenyl and monocyclic heteroaryl, provided that Ring A is not 2-methylpyridine or 1-methyl-2-pyridone; and (iii) monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur; 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, =O, and -CN; and 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, and -CN. In some embodiments,, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), if L is absent and R3and R4are both hydrogen, Ring A is selected from:

[0005] In some embodiments, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), L is absent, R3and R4are both hydrogen, and Ring A is selected from an optionally substituted bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2-oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane. In some embodiments,, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), L is absent, R3and R4are both hydrogen, and Ring A is selected from optionally substituted phenyl and optionally substituted monocyclic heteroaryl, provided that Ring A is not 2-methylpyridine or 1-methyl-2- pyridone. In some embodiments, L is absent, R3and R4are both hydrogen, and Ring A is selected from optionally substituted monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, L is absent, R3and R4are both hydrogen, and Ring A is selected from monocyclic heterocycloalkyl substituted with two or more halogens, which is further optionally substituted. In some embodiments,, for the compound of Formulae (I), (IA), (IB), (IC), (ID), (IE), (II), (IIA), (IIB), (IIC), (IID), (IIE), (IIE-1), (IIE-2), (IIE-3), (IIE-3a), (IIE-3b), (IIE-4), (IIE-5), (IIE- 5a), (IIE-5b), (IIE-6), (IIE-7), (IIE-10), (IIE-10a), (IIE-10b), (IIF), (IIG), or (IIH), if L is methylene and Ring A is tetrahydropyran, then at least one of R3and R4is not hydrogen. In some embodiments, if L is absent and R3and R4are each methyl, then Ring A is not 2,2,5,5- tetramethyltetrahydrofuranyl, 2,2-dimethyltetrahydropyranyl, or 2,2,6,6- tetramethyltetrahydropyranyl. In some embodiments, if L is absent, R3is 3-methylmorpholinyl, and R4is hydrogen, then Ring A is not 2,2,5,5-tetramethyltetrahydrofuranyl. In some embodiments, if L is absent, R3is OH, and R4is hydrogen, then Ring A is not 4- fluorotetrahydropyranyl. Formulae (III) and (IV) Compounds Some embodiments, provide a compound of Formula (III): or a pharmaceutically acceptable salt thereof, wherein: RAis selected from: halogen, -OR10, -SR10, -N(R10)2, -CN, C1-6alkyl, C1-6alkoxy, and C1-6haloalkyl; and C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more halogen; Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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, =O, and -CN; 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, C3-C6carbocycle, and 3- to 6-membered heterocycle; and C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, -C(O)R11, =O, and -CN; Ring B is selected from a polycyclic C7-C12carbocycle, a polycyclic 7- to 14-membered heterocycle and a monocyclic heterocycle selected from thiazole and thiophene, any 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 3- to 6-membered heterocycle; 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, C1-4alkyl, and C1-4haloalkyl; R2is independently selected at each occurrence from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; and R10, R11, and R12are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; provided that if RAis methyl or ethyl and Ring B is cinnoline, 3-chloroisoquinoline, or 2- methylquinazolinyl, then Ring A is not tetrahydrofuran, tetrahydropyran, 2- methyltetrahydrofuran, or 2,6-dimethyltetrahydropyran; provided that if (i) RAis fluoro and Ring B is 4-hydroxycinnoline, or (ii) RAis methyl and Ring B is isoquinoline or 3-fluoroisoquinoline, then Ring A is not tetrahydropyran; provided that if RAis fluoro and Ring B is indazole, Ring A is not selected from N- cyanopyrrolidine; and provided that if RAis methyl and Ring A is 6,7-dihydroindolizin-8(5H)-one, then Ring B is not methylenedioxyphenyl substituted with two fluoro. For purposes of clarification, for each Formulae of (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) and (IVJ), when Ring A is substituted with one or more substituents, the one or more substituents do not include but are in addition to the RAgroup. In various embodiments of Formulae of (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) and (IVJ), 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 (III), RAis selected from: halogen, -OR10, -SR10, -N(R10)2, -CN, C1-6alkyl, C1-6alkoxy, and C1-6haloalkyl; and C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more halogen; Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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, =O, and -CN; and 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; Ring B is selected from a polycyclic C7-C12carbocycle, a polycyclic 7- to 14-membered heterocycle, and a monocyclic heterocyclyl selected from thiazole and thiophene, any 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 3- to 6-membered heterocycle; 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 and C1-4alkyl; R2is independently selected at each occurrence from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; and R10, R11, and R12are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; provided that if RAis methyl or ethyl and Ring B is cinnoline, 3-chloroisoquinoline, or 2- methylquinazolinyl, then Ring A is not tetrahydrofuran, tetrahydropyran, 2- methyltetrahydrofuran, or 2,6-dimethyltetrahydropyran; provided that if (i) RAis fluoro and Ring B is 4-hydroxycinnoline, or (ii) RAis methyl and Ring B is isoquinoline or 3-fluoroisoquinoline, then Ring A is not tetrahydropyran; provided that if RAis fluoro and Ring B is indazole, Ring A is not selected from N- cyanopyrrolidine; provided that if RAis methyl and Ring A is 6,7-dihydroindolizin-8(5H)-one, then Ring B is not methylenedioxyphenyl substituted with two fluoro. In some embodiments, for the compound of Formula (III), R1is hydrogen or -CH3. In some embodiments, R1is hydrogen. In some embodiments, R1is C1-4alkyl. In some embodiments, R1is -CH3. In some embodiments, R1is hydrogen or -CF3. In some embodiments, R1is -CF3. In some embodiments, for the compound of Formula (III), R2is hydrogen. In some embodiments, R2is halogen. In some embodiments, R2is fluoro. In some embodiments, R2is chloro. In some embodiments, R2is C1-4alkyl. In some embodiments, R2is methyl. In some embodiments, R2is ethyl. In some embodiments, R2is C1-4haloalkyl. In some embodiments, R2is trifluoromethyl. In some embodiments, R2is trifluoroethyl. In some embodiments, for the compound of Formula (III), Ring B is a polycyclic 7- to 12- membered heterocycle, and a monocyclic heterocycle selected from thiazole and thiophene, any 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, -C(O)N(R12)2, -N(R12)C(O)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, -C(O)N(R12)2, -N(R12)C(O)R12, -CN, and 6-membered heterocycloalkyl; 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, -C(O)N(R12)2, -N(R12)C(O)R12, =O, and -CN. In some embodiments, for the compound of Formula (III), Ring B is a polycyclic 7- 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, -OC(O)R12, -C(O)N(R12)2, -N(R12)C(O)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, -C(O)N(R12)2, -N(R12)C(O)R12, -CN, and 6-membered heterocycloalkyl; 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, -C(O)N(R12)2, -N(R12)C(O)R12, =O, and -CN. In some embodiments, for the compound of Formula (III), 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 Formula (III), 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, 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, for the compound of Formula (III), 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 Formula (III), Ring B is a polycyclic C7-C10carbocycle optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -NO2, =O, and -CN; C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -CN, and 6-membered heterocycloalkyl; and C3-6carbocycle 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, -C(O)OR12, -OC(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, =O, and -CN. In some embodiments, for the compound of Formula (III), Ring B is selected from a polycyclic 7- to 12-membered heterocycle and a monocyclic heterocycle selected from thiazole and thiophene, any of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -NO2, =O, and -CN; C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -CN, and 6-membered heterocycloalkyl; and C3-6carbocycle 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, -C(O)OR12, -OC(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, =O, and -CN. In some embodiments, for the compound of Formula (III), Ring B is a polycyclic 7- to 12- membered heterocycle optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -NO2, =O, and -CN; C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, -SR12, -N(R12)2, -C(O)R12, -C(O)OR12, -OC(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, -CN, and 6-membered heterocycloalkyl; and C3-6carbocycle 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, -C(O)OR12, -OC(O)R12, -C(O)N(R12)2, -N(R12)C(O)R12, =O, and -CN. In some embodiments, for the compound of Formula (III), Ring B is a polycyclic 7- to 12- membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR12, =O, -CN, C1-6alkyl optionally substituted with one or more halogen or morpholinyl, and 3- to 6-membered heterocycle optionally substituted with one or more C1-6alkyl. In some embodiments, for the compound of Formula (III), Ring B is a polycyclic 7- to 12- membered heterocycle optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, =O, -CN, C1-6alkyl optionally substituted with 1-4 halogen or morpholinyl, and 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, for the compound of Formula (III), Ring B is selected from 3,4- dihydrothieno[3,2-d]pyrimidinyl, thiophenyl, thiazolyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, isoquinolinyl, quinazolinyl, phthalazinyl, cinnolinyl, 2,3- dihydropyrrolo[2,1-b]quinazolin-9(1H)-one, tetrahydropyrrolo[2,1-b]quinazolinyl, pyrido[3,2- d]pyrimidinyl, pyrido[1,2-a]pyrimidinyl, 2H-pyrazolo[3,4-c]isoquinolinyl, 1,2- dihydroquinazolinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, =O, -CN, C1-6alkyl optionally substituted with one or more halogen or morpholinyl, and 3- to 6-membered heterocycle optionally substituted with one or more C1-6alkyl. In some embodiments, for the compound of Formula (III), Ring B is selected from 3,4- dihydrothieno[3,2-d]pyrimidinyl, thiophenyl, thiazolyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, isoquinolinyl, quinazolinyl, phthalazinyl, cinnolinyl, 2,3- dihydropyrrolo[2,1-b]quinazolin-9(1H)-one, tetrahydropyrrolo[2,1-b]quinazolinyl, pyrido[3,2- d]pyrimidinyl, pyrido[1,2-a]pyrimidinyl, 2H-pyrazolo[3,4-c]isoquinolinyl, 1,2- dihydroquinazolinyl, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, =O, -CN, C1-6alkyl optionally substituted with 1-4 halogen or morpholinyl, and 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, Ring B is not indazole. In some embodiments, for the compound of Formula (III), R12is selected from hydrogen and C1-4alkyl. In some embodiments, R12is selected from hydrogen and -CH3. In some embodiments, R12is hydrogen. In some embodiments, R12is C1-4alkyl. In some embodiments, R12is -CH3. In some embodiments, for the compound of Formula (III), Ring B is selected from 3,4- dihydrothieno[3,2-d]pyrimidinyl, thiophenyl, thiazolyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, isoquinolinyl, quinazolinyl, phthalazinyl, cinnolinyl, 2,3- dihydropyrrolo[2,1-b]quinazolin-9(1H)-one, tetrahydropyrrolo[2,1-b]quinazolinyl, pyrido[3,2- d]pyrimidinyl, pyrido[1,2-a]pyrimidinyl, 2H-pyrazolo[3,4-c]isoquinolinyl, 1,2- dihydroquinazolinyl, each of which is optionally substituted with one or more substituents independently selected from: -F, -Cl, -CN, -OH, =O, -CH3, -CF3, -CHF2, , , In some embodiments, for the compound of Formula (III), Ring B is 3,4-dihydrothieno[3,2- d]pyrimidinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, - CN, -OH, =O, -CH3, -CF3, -CHF2, In some embodiments, for the compound of Formula (III), Ring B is thiophenyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, =O, -CH3, -CF3,

[0006] In some embodiments, for the compound of Formula (III), Ring B is thiazolyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, =O, -CH3, -CF3, In some embodiments, for the compound of Formula (III), Ring B is tetrazolo[1,5- a]pyridinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, In some embodiments, for the compound of Formula (III), Ring B is [1,2,4]triazolo[4,3- a]pyridinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, In some embodiments, for the compound of Formula (III), Ring B is [1,2,4]triazolo[1,5- a]pyridinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, In some embodiments, for the compound of Formula (III), Ring B is imidazo[1,2- a]pyridinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, In some embodiments, for the compound of Formula (III), Ring B is imidazo[1,5- a]pyridinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, In some embodiments, for the compound of Formula (III), Ring B is isoquinolinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, =O, - In some embodiments, for the compound of Formula (III), Ring B is quinazolinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, =O, - In some embodiments, for the compound of Formula (III), Ring B is phthalazinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, =O, - In some embodiments, for the compound of Formula (III), Ring B is cinnolinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, =O, -CH3, -CF3, In some embodiments, for the compound of Formula (III), Ring B is 2,3- dihydropyrrolo[2,1-b]quinazolin-9(1H)-one optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -CN, -OH, =O, -CH3, -CF3, -CHF2, In some embodiments, for the compound of Formula (III), Ring B is tetrahydropyrrolo[2,1- b]quinazolinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, - In some embodiments, for the compound of Formula (III), Ring B is pyrido[3,2- d]pyrimidinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, - In some embodiments, for the compound of Formula (III), Ring B is pyrido[1,2- a]pyrimidinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, - In some embodiments, for the compound of Formula (III), Ring B is 2H-pyrazolo[3,4- c]isoquinolinyl optionally substituted with 1-4 substituents independently selected from: -F, -Cl, -

[0007] dihydroquinazolinyl optionally substituted with 1-4 substituents independently selected from: -F, In some embodiments, for the compound of Formula (III), Ring B is cinnolinyl optionally substituted with C1-6alkyl. In some embodiments, Ring B is cinnolinyl substituted with C1-6alkyl. In some embodiments, Ring B is cinnolinyl optionally substituted with methyl. In some embodiments, Ring B is cinnolinyl substituted with methyl. In some embodiments, Ring B is unsubstituted cinnolinyl. In some embodiments, the Ring B cinnolinyl is 6-cinnolinyl. In some embodiments, when cinnolinyl is substituted with C1-6alkyl, the C1-6alkyl is bonded to the 3- position of the cinnolinyl. In some embodiments, when cinnolinyl is substituted with methyl, the methyl is bonded to the 3-position of the cinnolinyl. In some embodiments, for the compound of Formula (III), Ring B is selected from:

[0008] In some embodiments, for the compound of Formula (III), Ring B is selected from:

[0009] In some embodiments, for the compound of Formula (III), 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 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 Formula (III), R1is hydrogen; R2is hydrogen; Ring A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -CN; and C1-6alkyl; RAis selected from -F, -CN, -CH3, -CH2CH3, -CH2F, -CHF2, -CF3, -OCH3, and ; and Ring B is selected from 3,4-dihydrothieno[3,2-d]pyrimidinyl, thiophenyl, thiazolyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, isoquinolinyl, quinazolinyl, phthalazinyl, cinnolinyl, 2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one, tetrahydropyrrolo[2,1- b]quinazolinyl, pyrido[3,2-d]pyrimidinyl, pyrido[1,2-a]pyrimidinyl, 2H-pyrazolo[3,4- c]isoquinolinyl, 1,2-dihydroquinazolinyl, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, =O, -CN, C1-6alkyl optionally substituted with 1-4 halogen or morpholinyl, and 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, for the compound of Formula (III), R1is hydrogen; R2is hydrogen; Ring A is a 5-6 saturated heterocycloalkyl optionally substituted with 1-4 substituents independently selected from: halogen and C1-6alkyl; RAis selected from -F, -CN, -CH3, -CH2CH3, -CH2F, -CHF2, -CF3, -OCH3; and Ring B is selected from cinnolinyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR12, =O, -CN, C1-6alkyl optionally substituted with 1-4 halogen or morpholinyl, and 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6 alkyl. In some embodiments, the compound is of Formula (IV): (IV), or a pharmaceutically acceptable salt thereof; wherein X is N or CR6; R3and R4are each independently selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, -OR13, -SR13, -N(R13)2, and -CN; or R3and R4come together to form a 3- to 6-membered heterocycle optionally substituted with one or more substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R5is selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)OR15, -OC(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl; R6is selected from hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl; R13, R15, R16are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; and n is selected from 0, 1, and 2. In some embodiments, for the compound of Formulae (III) or (IV), n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, for the compound of Formulae (III) or (IV), X is N. In some embodiments, for the compound of Formulae (III) or (IV), X is CR6; and R6is selected from hydrogen, halogen, -C1-6alkyl, and C1-6haloalkyl. In some embodiments, X is CH. In some embodiments, for the compound of Formulae (III) or (IV), R6is hydrogen. In some embodiments, R6is halogen. In some embodiments, R6is -C1-6alkyl. In some embodiments, R6is C1-6haloalkyl. In some embodiments, the compound is of Formula (IVB): (IVB), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IVC): (IVC), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IVD): (IVD), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC) or (IVD), R3and R4are each independently selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, - C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, - OR13, -SR13, -N(R13)2, and -CN. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC) or (IVD), R3and R4are each independently selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, - C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR13, - SR13, -N(R13)2, and -CN. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC) or (IVD), R3and R4are each independently selected from: hydrogen, halogen, -OR13, C1-6alkyl optionally substituted with one or more substituents independently selected from halogen and morpholinyl, and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more C1-6 alkyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC) or (IVD), R3and R4are each independently selected from: hydrogen, halogen, -OR13, C1-6alkyl optionally substituted with 1-4 substituents independently selected from halogen and morpholinyl, and 3- to 6-membered heterocycle, each of which is optionally substituted with 1-4 C1-6alkyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC) or (IVD), R3is halogen. In some embodiments, R3is fluoro. In some embodiments, R3is chloro. In some embodiments, R3is -OR13. In some embodiments, R3is –OH. In some embodiments, R3is methoxy. In some embodiments, R3is C1-6alkyl optionally substituted with 1-4 substituents independently selected from halogen and morpholinyl. In some embodiments, R3is unsubstituted C1-6alkyl. In some embodiments, R3is methyl. In some embodiments, R3is ethyl. In some embodiments, R3is isopropyl. In some embodiments, R3is 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC) or (IVD), R4is halogen. In some embodiments, R4is fluoro. In some embodiments, R4is chloro. In some embodiments, R4is -OR13. In some embodiments, R4is –OH. In some embodiments, R4is methoxy. In some embodiments, R4is C1-6alkyl optionally substituted with 1-4 substituents independently selected from halogen and morpholinyl. In some embodiments, R4is unsubstituted C1-6alkyl. In some embodiments, R4is methyl. In some embodiments, R4is ethyl. In some embodiments, R4is isopropyl. In some embodiments, R4is hydrogen, -Cl, or -CH3. In some embodiments, R4is -Cl. In some embodiments, R4is -CH3. In some embodiments, R4is 3- to 6- membered heterocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC) or (IVD), R3is hydrogen. In some embodiments, R4is hydrogen. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC) or (IVD), R3is hydrogen and R4is unsubstituted C1-6alkyl. In some embodiments, R3is hydrogen and R4is methyl. In some embodiments, R3is hydrogen and R4is ethyl. In some embodiments, R3is hydrogen and R4is isopropyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC) or (IVD), R3and R4are each independently selected from: hydrogen, halogen, -OR13, C1-6alkyl optionally substituted with one or more substituents independently selected from halogen and morpholinyl, and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more C1-6 alkyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC) or (IVD), R3and R4come together to form a 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, the compound is of Formula (IVE): (IVE), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IVE-1): (IVE-1), or a pharmaceutically acceptable salt thereof.

[0010] In some embodiments, the compound is of Formula (IVE-2): (IVE-2), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IVF): (IVF), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), or (IVF), R4is selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, - C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, - OR13, -SR13, -N(R13)2, and -CN. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), or (IVF), R4is halogen. In some embodiments, R4is fluoro. In some embodiments, R4is chloro. In some embodiments, R4is -OR13. In some embodiments, R4is –OH. In some embodiments, R4is methoxy. In some embodiments, R4is C1-6alkyl optionally substituted with 1-4 substituents independently selected from halogen and morpholinyl. In some embodiments, R4is unsubstituted C1-6alkyl. In some embodiments, R4is methyl. In some embodiments, R4is ethyl. In some embodiments, R4is isopropyl. In some embodiments, R4is hydrogen, -Cl, or -CH3. In some embodiments, R4is -Cl. In some embodiments, R4is -CH3. In some embodiments, R4is 3- to 6-membered heterocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, the compound is of Formula (IVG): (IVG), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IVG-1): (IVG-1), or a pharmaceutically acceptable salt thereof.

[0011] In some embodiments, the compound is of Formula (IVG-2): (IVG-2), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IH): (IVH), or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (IVJ): (IVJ), or a pharmaceutically acceptable salt thereof. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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, -C(O)N(R11)2, -N(R11)C(O)R11, -S(O)2R11, -S(O)2N(R11)2, and -CN; and 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, -C(O)N(R11)2, -N(R11)C(O)R11, -CN, and C3-C6carbocycle; and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, =O, and -CN.In some embodiments, Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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, -S(O)2R11, and -CN; C1-6alkyl optionally substituted with C3-C6carbocycle; and 3- to 6-membered heterocycle. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially saturated carbocycle, a 3- to 10-membered saturated heterocycloalkyl, and 3- to 10-membered partially saturated heterocycle, each of which is optionally substituted with one or more C1-6alkyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and 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, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), 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 (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), 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, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), the 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 (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), 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, 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, the 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 (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), 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, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is C3-C10saturated partially saturated carbocycle optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), 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, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, =O, and -CN; and C1-6alkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, -OC(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, and -CN. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially saturated carbocycle, and a 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, -CN; and C1-6alkyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially saturated carbocycle, and a 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, -CN; and C1-6alkyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is C3-C10saturated cycloalkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -CN; and C1-6alkyl. In some embodiments, Ring A is C3-C10partially saturated carbocycle optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -CN; and C1-6alkyl. In some embodiments, Ring A is 3- to 10-membered saturated heterocycloalkyl optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -CN; and C1-6alkyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially saturated carbocycle, and a 3- to 10-membered saturated heterocycloalkyl, each of which is optionally substituted with one or more C1-6alkyl. In some embodiments, Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially saturated carbocycle, and a 3- to 10-membered saturated heterocycloalkyl, each of which is optionally substituted with 1-4 C1-6alkyl. In some embodiments, Ring A is selected from a C3-C10saturated cycloalkyl optionally substituted with 1-4 C1-6alkyl. In some embodiments, Ring A is selected from a C3-C10partially saturated carbocycle optionally substituted with 1-4 C1-6alkyl. In some embodiments, Ring A is selected from a 3- to 10-membered saturated heterocycloalkyl optionally substituted with 1-4 C1-6alkyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, dihydrobenzopyranyl, and tetrahydronaphthyl, any of which is optionally substituted. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, dihydrobenzopyranyl, and tetrahydronaphthyl, 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, -S(O)2R11, and -CN; C1-6alkyl optionally substituted with cyclopyropyl; and oxetanyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, dihydrobenzopyranyl, and tetrahydronaphthyl, 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, -S(O)2R11, and -CN; C1-6alkyl optionally substituted with cyclopyropyl; and oxetanyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydronaphthyl, and dihydrobenzopyranyl, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -CN; and C1-6alkyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydronaphthyl, and dihydrobenzopyranyl, each of which is optionally substituted with 1-4 or more -CH3. In some embodiments, the dihydrobenzopyranyl is isochromanyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is optionally substituted with 1-4 substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -CN; and C1-6alkyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), R11is selected from hydrogen and C1-4alkyl. In some embodiments, R11is selected from hydrogen and methyl. In some embodiments, R11is hydrogen. In some embodiments, R11is C1-4alkyl. In some embodiments, R11is methyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is optionally substituted with one or more - CH3. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is optionally substituted with 1-4 -CH3. In some embodiments, Ring A is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is optionally substituted with one -CH3. In some embodiments, Ring A is not selected from N- cyanopyrrolidine. In some embodiments, Ring A is not selected from pyrrolidine. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is substituted with 1-4 -CH3. In some embodiments, Ring A is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, and tetrahydronaphthyl, each of which is substituted with one -CH3. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is selected from: unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, unsubstituted cyclohexyl, unsubstituted oxetanyl, unsubstituted tetrahydrofuranyl, unsubstituted tetrahydropyranyl, unsubstituted piperidinyl, unsubstituted and unsubstituted tetrahydronaphthyl. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), 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 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 C1-6alkyl. 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 (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), 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 C1-6alkyl. 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 C1-6alkyl. 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, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), RAis selected from -F, -CN, -CH3, -CH2CH3, -CH2F, -CHF2, -CF3, -CH2CH2F, -OCH3, and . In some embodiments, RAis selected from halogen, -OR10, -CN, C1-6alkyl, and C1-6haloalkyl; and C3-C6carbocycle and phenyl substituted with halogen. In some embodiments, RAis halogen. In some embodiments, RAis fluoro. In some embodiments, RAis -OR10. In some embodiments, RAis hydroxyl. In some embodiments, RAis methoxy. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), R10is selected from hydrogen and C1-4alkyl. In some embodiments, R10is selected from hydrogen and methyl. In some embodiments, R10is hydrogen. In some embodiments, R10is methyl. In some embodiments, RAis –CN. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), RAis C1-6alkyl. In some embodiments, RAis methyl. In some embodiments, RAis ethyl. In some embodiments, RAis C1-6haloalkyl. In some embodiments, RAis trifluoromethyl. In some embodiments, RAis - CH2F. In some embodiments, RAis -CHF2. In some embodiments, RAis C3-C6carbocycle optionally substituted with halogen. In some embodiments, RAis C3-C6carbocycle substituted with halogen. In some embodiments, RAis C3-C6carbocycle substituted with fluoro or chloro. In some embodiments, RAis . In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), RAis selected from -F, -CN, -CH3, -CH2CH3, -CH2F, -CHF2, -CF3, -OCH3, and. In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), is selected from:

[0012] In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), In some embodiments, is In some embodiments, for the compound of Formulae (III), (IVA), (IVB), (IVC), (IVD), (IVE), (IVE-1), (IVE-2), (IVF), (IVG), (IVG-1), (IVG-2), (IVH) or (IVJ), Ring A is tetrahydrofuran optionally substituted with one to four methyl. In some embodiments, if RAis methyl or ethyl and Ring B is cinnoline, 3- chloroisoquinoline, or 2-methylquinazolinyl, then Ring A is not tetrahydrofuran, tetrahydropyran, 2-methyltetrahydrofuran, or 2,6-dimethyltetrahydropyran. In some embodiments, if (i) RAis fluoro and Ring B is 4-hydroxycinnoline, or (ii) RAis methyl and Ring B is isoquinoline, or 3-fluoroisoquinoline, then Ring A is not tetrahydropyran. In some embodiments, if if RAis fluoro and Ring B is indazole, Ring A is not selected from N-cyanopyrrolidine. In some embodiments, if RAis methyl and Ring A is 6,7-dihydroindolizin-8(5H)-one, then Ring B is not methylenedioxyphenyl substituted with two fluoro. Non-Limiting Exemplary Compounds In some embodiments, the compound is selected from the group consisting of Compounds 1-419), 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.

[0013] Pharmaceutical Compositions Some embodiments provide a pharmaceutical composition comprising a compound of the present disclosure, e.g., a compound of Formula (I), (II), (III), or (IV), or any subformulae thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. Methods of Treatment Provided herein are methods for inhibiting dual specificity tyrosine-phosphorylation- regulated kinase 1A, encoded by the DYRK1A gene. For example, provided herein are inhibitors of DYRK1A useful for treating disorders associated with dysregulation of a DYRK1A 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 DYRK1A-associated neurological disorder. A “DYRK1A inhibitor” as used herein includes any compound exhibiting DYRK1A inactivation activity (e.g., inhibiting or decreasing). Indications Compounds of the present disclosure, including compounds of Formula (I), (II), (III), and (IV), and subformulae thereof, or pharmaceutically acceptable salts thereof, are useful for treating disorders which can be treated with a DYRK1A inhibitor, such as DYRK1A-associated disorders, e.g., neurological disorders such as those described herein. 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 disclsure, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. 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 CNS and PNS), including both structural and / or functional disorders (e.g., neurological syndrome). 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 peripheral 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; DandyWalker 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; hemifacial spasm; hereditary spastic paraplegia: heredopathia atactic a polyneuritiformis; herpes zoster oticus; herpes zoster; Hirayama syndrome; HIVassociated dementia and neuropathy (also neurological manifestations of AIDS); holoprosencephaly; Huntington's disease and other polyglutamine repeat diseases; hydranencephaly: hydrocephalus; hypercortisolism; hypoxia; immune-mediated encephalomyelitis; inclusion body myositis; incontinentia pigmenti; infantile phytanic acid storage disease; infantile spasms; inflammatory myopathy; intracranial cyst; intracranial hypertension; Joubert syndrome; Kearns-Sayre syndrome; Kennedy disease Kinsboume syndrome; Klippel Feil syndrome; Krabbe disease; Kugelberg-Welander disease; kuru; Lafora disease; Lambert-Eaton myasthenic syndrome; Landau-Kleffner syndrome; lateral medullary (Wallenberg) syndrome; learning disabilities; Leigh's disease; Lennox-Gustaut syndrome; Lesch-Nyhan syndrome; leukodystrophy; Lewy body dementia; Lissencephaly; locked-in syndrome; Lou Gehrig's disease (i.e., motor neuron disease or amyotrophic lateral sclerosis); lumbar disc disease; Lyme disease-neurological sequelae; Machado-Joseph disease; macrencephaly; megalencephaly; Melkersson-Rosenthal syndrome; Menieres disease; meningitis; Menkes disease; metachromatic leukodystrophy; microcephaly; migraine; Miller Fisher syndrome; mini-strokes; mitochondrial myopathies; Mobius syndrome; monomelic amyotrophy; motor neuron disease; Moyamoya disease; mucopolysaccharidoses; milti-infarct dementia; multifocal motor neuropathy; multiple sclerosis and other demyelinating disorders; multiple system atrophy with postural hypotension; p muscular dystrophy; myasthenia gravis; myelmociastic diffuse sclerosis; myoclonic encephalopathy of infants; myoclonus; myopathy; myotonia congenital; narcolepsy: neurofibromatosis; neuroleptic malignant syndrome; neurological manifestations of AIDS; neurological sequelae oflupus; neuromyotonia; neuronal ceroid lipofuscinosis; neuronal migration disorders; Niemann-Pick disease; O'Sullivan-McLeod syndrome; occipital neuralgia; occult spinal dysraphism sequence; Ohtahara syndrome; olivopontocerebellar atrophy; opsoclonus myoclonus; optic neuritis; orthostatic hypotension; overuse syndrome; paresthesia; Neurodegenerative disease or disorder (Parkinson's disease, Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), dementia, multiple sclerosis and other diseases and disorders associated with neuronal cell death); paramyotonia congenital; paraneoplastic diseases; paroxysmal attacks; Parry Romberg syndrome; Pelizaeus-Merzbacher disease; periodic paralyses; peripheral neuropathy; painful neuropathy and neuropathic pain; persistent vegetative state; pervasive developmental disorders; photic sneeze reflex; phytanic acid storage disease; Pick's disease; pinched nerve; porencephaly; post-polio syndrome; postherpetic neuralgia; postinfectious encephalomyelitis; postural hypotension; Prader- Willi syndrome; primary lateral sclerosis; prion diseases; progressive hemifacial atrophy; progressive multifocalleukoencephalopathy; progressive sclerosing poliodystrophy; progressive supranuclear palsy; Ramsay-Hunt syndrome (types I and I1); Rasmussen's encephalitis: reflex sympathetic dystrophy syndrome; Refsum disease; repetitive motion disorders, repetitive stress injuries; restless legs syndrome; retrovirus-associated myelopathy; Rett syndrome; Reye's syndrome; Saint Vitus dance; Sandhoff disease; Schilder’s disease; schizencephaly; septo-optic dysplasia: shaken baby syndrome: shingles: Shy-Drager syndrome; Sjogren’s syndrome; Soto's syndrome; spasticity; spina bifida; spinal cord injury; spinal muscular atrophy; Stiff-Person syndrome; stroke; Sturge-Weber syndrome; subacute sclerosing panencephalitis; subcortical arteriosclerotic encephalopathy; Sydenham chorea; syncope; syringomyelia; tardive dyskinesia; Tay-Sachs disease; temporal arteritis; tethered spinal cord syndrome; Thomsen disease; thoracic outlet syndrome; Tic Douloureux; Todd's paralysis; Tourette syndrome; transient ischemic attack; transmissible spongiform encephalopathies; transverse myelitis; traumatic brain injury; tremor, trigeminal neuralgia; tropical spastic paraparesis: tuberous sclerosis; vascular dementia (multi- infarct dementia); vasculitis including temporal arteritis; Von Hippel-Lindau disease; Wallenberg's syndrome; Werdnig-Hoffman disease; West syndrome; Williams syndrome; Wildoris disease; and Zellweger syndrome. In some embodiments, the neurological disease is a tauopathy. In some embodiments, the neurological disease is a synucleinopathy. In some embodiments, the neurological disease or neurological disorder is Alzheimer’s disease, Down syndrome, Alzheimer’s disease associated with Down syndrome, Parkinson’s disease, ALS, dementia, Huntington’s disease, multiple sclerosis, proximal lateral sclerosis, stroke, stroke, or mild cognitive impairment. In some embodiments, the dementia may be Alzheimer’s dementia, cerebrovascular dementia, dementia due to head injury, multi-infarct dementia, mixed or alcoholic dementia of Alzheimer’s disease and multi-infarct dementia. Provided herein is 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 the present disclosure, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. In some embodiments, the metabolic disorder is diabetes (e.g., Type 1 diabetes or Type 2 diabetes). In some embodiments, the metabolic disorder is Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Provided herein is a method for treating a cancer 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. In some embodiments, the cancer is a hemotological cancer (e.g., a leukemia, a lymophoma, or myeloma) or a solid tumor (e.g., carcinoma or sarcoma). In some embodiments, the cancer is selected from Acute Lymphocytic Leukemia (ALL, Acute Lymphoblastic Leukemia, Colorectal Cancer; Non-Small Cell Lung Cancer, Glioblastoma Multiforme (GBM), Prostate Cancer, and Pancreatic Cancer. Provided herein is a method for treating an immunological disorder or disease (e.g., an autoimmune 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. In some embodiments, the immunological disorder is an autoimmune disorder. In some embodiments, the immunological disorder is selected from Psoriasis; Rheumatoid Arthritis; Systemic Lupus Erythematosus, osteoarthritis, degenerative disc disease, and inflammatory bowel disease. Provided herein is a method for treating an dermatological disorder or disease 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. In some embodiments, the immunological disorder is atopic dermatitis (atopic eczema). Provided herein is 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 the present disclosure, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. In some embodiments, the cardiovascular disease or disorder comprises heart failure. In some embodiments, the cardiovascular disease or disorder is myocardial infarct restoration. In some embodiments, the treatment of the cardiovascular disease or disorder comprises stimulating cardiomyocyte proliferation. Use of compounds of the present disclosure for treatment, as described herein, include the use of any compounds of Formula (I), (II), (III), or (IV), or a subformulae thereof, and all compounds described herein. The ability of test compounds to act as inhibitors of DYRK1A may be demonstrated by assays known in the art. The activity of the compounds and compositions provided herein as DYRK1A inhibitors can be assayed in vitro, in vivo, or in a cell line. In vitro assays include assays that determine inhibition of the kinase. Alternate in vitro assays quantitate the ability of the inhibitor to bind to the protein kinase and can be measured either by radio labeling the compound prior to binding, isolating the compound / kinase complex and determining the amount of radiolabel bound, or by running a competition experiment where new compounds are incubated with the kinase bound to known radio ligands. Potency of a DYRK1A inhibitor as provided herein can be determined by EC50or IC50values. A compound with a lower EC50or IC50value, as determined under substantially similar conditions, is a more potent inhibitor relative to a compound with a higher EC50or IC50value. In some embodiments, the substantially similar conditions comprise determining a DYRK1A- dependent phosphorylation level, in vitro or in vivo (e.g., in neural cells, such as neurons, astrocytes, oligodendrocytes, microglia, ependymal cells, Schwann cells, and satellite cells, expressing a wild type DYRK1A, a mutant DYRK1A, or a fragment of any thereof). Potency of a DYRK1A inhibitor as provided herein can also be determined by IC50value. A compound with a lower IC50value, as determined under substantially similar conditions, is a more potent inhibitor relative to a compound with a higher IC50value. In some embodiments, the substantially similar conditions comprise determining a DYRK1A-dependent phosphorylation level, in vitro or in vivo (e.g., in neural cells, such as neurons, astrocytes, oligodendrocytes, microglia, ependymal cells, Schwann cells, and satellite cells, expressing a wild type DYRK1A, a mutant DYRK1A, or a fragment of any thereof). The selectivity between DYRK1A and other kinases (e.g., glycogen synthase kinase-3β, GSK3β) can also be measured using in vitro assays such as surface plasmon resonance and fluorence-based binding assays, and cellular assays. In some embodiments, the compounds of Formula (I), (II), (III), and (IV), and subformulae thereof, or a pharmaceutically acceptable salt thereof, can selectively target DYRK1A. For example, a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, can selectively target DYRK1A over another kinase or non-kinase target, for example, GSK3β. In some embodiments, a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, can exhibit greater inhibition of DYRK1A relative to inhibition of GSK3β. In some embodiments, a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof can exhibit at least 2- fold, 3-fold, 5-fold, 10-fold, 25-fold, 50-fold or 100-fold greater inhibition of DYRK1A relative to inhibition of GSK3β. In some embodiments, a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, can exhibit up to 1000-fold greater inhibition of DYRK1A relative to inhibition of GSK3β. In some embodiments, a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, can exhibit up to 10000-fold greater inhibition of DYRK1A relative to inhibition of GSK3 β. In some embodiments, the compounds described herein (e.g., compounds of Formula (I), (II), (III), or (IV), or a subformulae thereof) readily cross the blood-brain barrier. In some embodiments, the compounds described herein (e.g., compounds of Formula (I), (II), (III), or (IV), or a subformulae thereof) cross the blood-brain barrier in an amount sufficient to inhibit DYRK1A activity in brain tissue. Also provided herein is a method for treating a neurological disorder in a subject in need thereof, the method comprising (a) determining or having determined that the subject has a neurological disorder; and (b) administering to the subject a therapeutically effective amount of a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. In some embodiments, the subject is at risk of developing a neurological disorder, e.g., a DYRK1A- associated neurological disorder. In some embodiments, the subject is suspected of having a neurological disorder, e.g., a DYRK1A-associated neurological disorder. In some embodiments, the subject has been previously determined to have a neurological disorder associated with a dysregulation of a DYRK1A gene, a DYRK1A protein, or expression or activity, or level of any of the same (a DYRK1A-associated neurological disorder) (e.g., as determined using a regulatory agency-approved, e.g., FDA-approved, assay or kit). In some embodiments, the subject is suspected of having a DYRK1A-associated neurological disorder. In some embodiments, the subject has a clinical record indicating that the subject has a dysregulation of a DYRK1A gene, a neurological disorder protein, or expression or activity, or level of any of the same (and optionally the clinical record indicates that the subject should be treated with any of the compositions provided herein). In some embodiments, the subject is at risk of developing a DYRK1A-associated neurological disorder. The term “DYRK1A-associated disorder” as used herein refers to disorders associated with or having a dysregulation of a DYRK1A gene, a DYRK1A protein, or the expression or activity or level of any (e.g., one or more) of the same (e.g., any of the types of dysregulation of a DYRK1A gene, or a DYRK1A protein, or the expression or activity or level of any of the same described herein). The term “DYRK1A-associated neurological disorder” as used herein refers to neurological disorders associated with or having a dysregulation of a DYRK1A gene, a DYRK1A protein, or the expression or activity or level of any (e.g., one or more) of the same (e.g., any of the types of dysregulation of a DYRK1A gene, or a DYRK1A protein, or the expression or activity or level of any of the same described herein). Non-limiting examples of a DYRK1A-associated neurological disorders are described herein. The phrase “dysregulation of a DYRK1A gene, a DYRK1A protein, or the expression or activity or level of any of the same” refers to a genetic mutation (e.g., a mutation in a DYRK1A gene that results in the expression of a DYRK1A that includes a deletion of at least one amino acid as compared to a wild type DYRK1A, a mutation in a DYRK1A gene that results in the expression of DYRK1A with one or more point mutations as compared to a wild type DYRK1A, a mutation in a DYRK1A gene that results in the expression of DYRK1A with at least one inserted amino acid as compared to a wild type DYRK1A, a gene duplication that results in an increased level of DYRK1A in a cell, or a mutation in a regulatory sequence (e.g., a promoter and / or enhancer) that results in an increased level of DYRK1A in a cell), an alternative spliced version of DYRK1A mRNA that results in DYRK1A having a deletion of at least one amino acid in the DYRK1A as compared to the wild type DYRK1A), or increased expression (e.g., increased levels) of a wild type DYRK1A in a mammalian cell due to aberrant cell signaling (e.g., as compared to a control cell). As another example, a dysregulation of a DYRK1A gene, a DYRK1A protein, or expression or activity, or level of any of the same, can be a mutation in a DYRK1A gene that encodes a DYRK1A that is constitutively active or has increased activity as compared to a protein encoded by a DYRK1A gene that does not include the mutation. In some embodiments, the dysregulation of a DYRK1A gene, a DYRK1A protein, or expression or activity or level of any of the same, includes at least one point mutation in a DYRK1A gene that results in the production of a DYRK1A protein that has one or more amino acid substitutions or insertions or deletions in a DYRK1A gene that results in the production of a DYRK1A protein that has one or more amino acids inserted or removed, as compared to the wild type DYRK1A protein. In some cases, the resulting mutant DYRK1A protein has increased activity, as compared to a wild type DYRK1A protein or a DYRK1A protein not including the same mutation. Exemplary Sequence of Human Dual specificity tyrosine-phosphorylation-regulated kinase 1A (UniProtKB entry Q13627) (SEQ ID NO: 1) In some embodiments, compounds of Formula (I), (II), (III), or (IV), or a subformulae thereof, or pharmaceutically acceptable thereof, are useful for treating a neurological disorder that has been identified as having one or more DYRK1A mutations. Accordingly, provided herein are methods for treating a subject diagnosed with (or identified as having) a neurological disorder that include administering to the subject a therapeutically effective amount of a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof. Some embodiments provide a method for treating a neurological disorder in a subject in need thereof, the method comprising (a) determining or having determined that the neurological disorder is associated with a dysregulation of a 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), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. Also provided herein is a method for treating a neurological disorder in a subject in need thereof, the method comprising (a) determining or having determined 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), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. Provided herein is a method of treating a DYRK1A-associated disorder in a subject, the method comprising administering to a subject previously determined to have a DYRK1A- associated disorder a therapeutically effective amount of a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. In some embodiments, the subject that has been previously determined to have a DYRK1A-associated neurological disorder through the use of a regulatory agency-approved, e.g., FDA-approved test or assay for identifying dysregulation of a DYRK1A gene, a DYRK1A protein, or expression or activity or level of any of the same, in a subject or a sample from the subject. In some embodiments, the test or assay is provided as a kit. The term “regulatory agency” refers to a country's agency for the approval of the medical use of pharmaceutical agents with the country. For example, a non-limiting example of a regulatory agency is the U.S. Food and Drug Administration (FDA). 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), or (IV), or a 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 DYRK1A gene, a DYRK1A protein, or expression or activity or level of any of the same. Also provided is a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, for use in the treatment of a neurological disorder in a subject in need thereof, or a subject previously determined to have a DYRK1A-associated neurological disorder. Also provided is the use of a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for treating a neurological disorder in a subject previously determined to have a DYRK1A-associated neurological disorder. Compounds of the present disclosure (including compounds of Formula (I), (II), (III), (IV), (V), or (VI), or any subformulae thereof) or a pharmaceutically acceptable salt thereof, can be used for the treatment of additional DYRK1A-mediated diseases an disorders, including the following: musculoskeletal disorders, genetic disorders (e.g., Fragile X syndrome), CNS disorders (e.g., pain, tauopathies, Attention Deficit Hyperactivity Disorder (ADHD); Depression; Post-Traumatic Stress Disorder (PTSD), traumatic brain injury, epilepsy), gastrointestinal disorders (e.g., irritiable bowel syndrome), metabolic disorders, cancer, immunological disorders and dermatological disorders. When employed as pharmaceuticals, the compounds of Formula (I), (II), (III), or (IV), or a subformulae thereof, including pharmaceutically acceptable salts thereof, can be administered in the form of pharmaceutical compositions as described herein. Methods of Inhibiting DYRK1A Activity Some embodiments provide 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 Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof. Also provided herein is a method for inhibiting DYRK1A activity in a mammalian cell, the method comprising contacting the mammalian cell with a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof. In some embodiments, the mammalian cell comprises DYRK1A. In some embodiments, the mammalian cell is a mammalian neural cell. Also provided herein is a method for inhibiting DYRK1A activity, the method comprising contacting a DYRK1A protein with a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof. In some embodiments, the mammalian cell comprises DYRK1A. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. In some embodiments, the contacting is in vivo, wherein the method comprises administering an effective amount of a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, to a subject having a cell having aberrant DYRK1A activity. In some embodiments, the cell is a neural cell. As used herein, the term “contacting” refers to the bringing together of indicated moieties in an in vitro system or an in vivo system. For example, “contacting” a DYRK1A protein with a compound provided herein includes the administration of a compound provided herein to a subject, such as a human, having a DYRK1A protein, as well as, for example, introducing a compound provided herein into a sample containing a cellular or purified preparation containing the DYRK1A protein. In some embodiments, the contacting occurs after a compound described herein (e.g., a compound of Formula (I), (II), (III), or (IV), or a subformulae thereof) has crossed the blood-brain barrier. In some embodiments, the compound of Formula (I), (II), (III), or (IV), or a subformulae thereof, or a pharmaceutically acceptable salt thereof, contacting a mammalian cell and / or DYRK1A protein is present in an amount effective to inhibit the activity of a DYRK1A protein. In some embodiments, the amount is a therapeutically effective amount. EXAMPLES Compound Preparation The compounds disclosed herein can be prepared in a variety of ways using commercially available starting materials, compounds known in the literature, or from readily prepared intermediates, by employing standard synthetic methods and procedures either known to those skilled in the art, or in light of the teachings herein. The synthesis of the compounds disclosed herein can be achieved by generally following the schemes provided herein, with modification for specific desired substituents. Standard synthetic methods and procedures for the preparation of organic molecules and functional group transformations and manipulations can be obtained from the relevant scientific literature or from standard textbooks in the field. Although not limited to any one or several sources, classic texts such as R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis, John Wiley and Sons (1994); Smith, M. B., March, J., March' s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th edition, John Wiley & Sons: New York, 2001; and Greene, T.W., Wuts, P.G. M., Protective Groups in Organic Synthesis, 3rd edition, John Wiley & Sons: New York, 1999, are useful and recognized reference textbooks of organic synthesis known to those in the art. The following descriptions of synthetic methods are designed to illustrate, but not to limit, general procedures for the preparation of compounds of the present disclosure. The synthetic processes disclosed herein can tolerate a wide variety of functional groups; therefore, various substituted starting materials can be used. The processes generally provide the desired final compound at or near the end of the overall process, although it may be desirable in certain instances to further convert the compound to a pharmaceutically acceptable salt thereof. Synthetic Procedures General Scheme 1: Synthesis of 2-Aminothiazole Intermediates Preparation of 2-aminothiazoles of type P4. A heterocyclic ring containing a halogen similar to P1 is combined with a boronic acid or ester like P2, and a series of reagents to perform a carbon-carbon bond forming reaction similar to a palladium mediated Suzuki coupling, such as a palladium (II) salt coordinated to one or more ligands, an inorganic or organic base, and a mixture of organic and aqueous solvents. The reaction is heated and stirred for a period of time and monitored for the formation of P3. P3 is purified using one or more of any standard methods, including but not limited to reverse phase high pressure liquid chromatography (RP- HPLC, HPLC, or semi-prep HPLC) using standard eluents and additives, silica gel chromatography using automated instruments and pre-packed silica gel cartridges of various sizes and common normal phase organic solvents. The desired fractions are combined, concentrated to dryness to provide the intermediate P3. It is then combined with an electrophilic bromine source, such as N- bromosuccinimide, and thiourea in a mixture of organic and aqueous solvents. The mixture is heated while stirring for a period and then cooled and the mixture concentrated to dryness to provide an intermediate like P4 that is used without further purification. General Scheme 2: Synthesis of 2-Aminothiazole Carboxamides Preparation of 2-aminothiazoles of type P6. An intermediate P4 is combined with an acid or acid chloride or activated ester of type P5 that is arrived at either via commercially available reagent or single in situ formation according to usual procedures. When using an acid such as P5, the regent is stirred with an amide bond forming reagent similar to 1-(3-dimethylpropyl)-3- ethylcarbodiimide hydrochloride (EDC), a mild base, and a solvent. The mixture is stirred at ambient temperature or with heating to progress the formation of the product of similar type P6. P6 is purified using one or more of any standard methods as previously described to purify P3 (Scheme 1). The desired fractions are combined, concentrated to dryness to provide the title compound P6.

[0014] General Scheme 3: Synthesis of Cinnoline / Isoquinoline Thiazole Intermediates Preparation of 5-cinnolinyl-2-aminothiazoles of type P9. A cinnoline ring containing a halogen P7 is combined with a boronic acid or ester like P2, and a series of reagents to perform a carbon-carbon bond forming reaction similar to a palladium mediated Suzuki coupling, such as a palladium (II) salt coordinated to one or more ligands, an inorganic or organic base, and a mixture of organic and aqueous solvents. The reaction is heated and stirred for a period and monitored for the formation of P8. P8 is purified using one or more of any standard methods, including but not limited to reverse phase high pressure liquid chromatography (RP- HPLC, HPLC, or semi-prep HPLC) using standard eluents and additives, silica gel chromatography using automated instruments and pre-packed silica gel cartridges of various sizes and common normal phase organic solvents. The desired fractions are combined and concentrated to dryness to provide the intermediate P8. It is then combined with an electrophilic bromine source, such as N- bromosuccinimide, and thiourea in a mixture of aqueous and organic solvents. The mixture is heated while stirring for a period and then cooled and the mixture concentrated to dryness to provide an intermediate like P9 that is used without further purification or purified in a similar manner to P8.

[0015] General Scheme 4: Synthesis of Cinnoline / Isoquinoline Thiazole Carboxamides Preparation of cinnoline / isoquinoline thiazole carboxamides of type P10 or P11. An intermediate P9 is combined with an acid or acid chloride or activated ester of either type P5 or P12 that is arrived at either via commercially available reagent or single in situ formation according to usual procedures. When using an acid such as P5 or P12 the regent is stirred with an amide bond forming reagent similar to 1-(3-dimethylpropyl)-3-ethylcarbodiimide hydrochloride (EDC), a mild base, and a solvent. The mixture is stirred at ambient temperature or with heating to progress the formation of the product of similar type to either P10 or P11. Purification of a compound of either type P10 or P11 using one or more of any standard methods as previously described to purify P3 (Scheme 1). The desired fractions are combined, concentrated to dryness to provide the title compound of type either P10 or P11. Example 1: Synthesis of Intermediates Synthesis of Interemdiate 1 Preparation of 5-(3-methylcinnolin-6-yl)thiazol-2-amine (Intermediate 1) Step 1. Preparation of 1-(2-amino-5-bromophenyl)propan-1-one Ethyl magnesium bromide (3M in Et2O, 17.8 mL, 53.3 mmol) was added dropwise to a 0 ºC solution of 2-amino-5-bromobenzonitrile (3.5 g, 17.8 mmol) in THF (100 mL). The solution was allowed to warm to ambient temperature and stirred for one hour. The solution was cooled to 0 ºC and additional ethyl magnesium bromide (3M in Et2O, 8.9 mL, 26.7 mmol) was added dropwise. The solution was allowed to warm to ambient temperature and stirred for an additional hour. The solution was cooled to 0 ºC and 1M aqueous HCl (15 mL) was added dropwise. The solution was warmed to ambient temperature and stirred overnight. The reaction mixture was diluted with water (100 mL), extracted with EtOAc (3x100 mL) and the combined organic layers washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash column chromatography on silica gel (0-20% EtOAc / hexanes) afforded 1-(2-amino-5- bromophenyl)propan-1-one (2.86 g, 71% yield) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ 7.86 (d, J = 2.4 Hz, 1H), 7.35 (dd, J = 8.9, 2.4 Hz, 1H), 7.30 (s, 2H), 6.74 (d, J = 8.9 Hz, 1H), 2.96 (d, J = 7.2 Hz, 2H), 1.04 (t, J = 7.2 Hz, 3H). LCMS: RT = 0.65 min; ES-MS [M+H]+: 227.9 / 229.9. Step 2. Preparation of 6-bromo-3-methylcinnolin-4(1H)-one HCl (37% aq, 20 mL, 250.8 mmol) was added to a 0 ºC solution of 1-(2-amino-5- bromophenyl)propan-1-one (2.86 g, 12.5 mmol) in water (50 mL). A solution of sodium nitrite (1.05 g, 15.0 mmol) in water (10 mL) was added dropwise. After stirring one hour at 0 ºC, the solution was heated to 65 ºC for six hours. The reaction was placed in a ~5 ºC refrigerator for 48 hours and the resulting precipitate filtered, washing with ice-cold water. The product was dried overnight to give 6-bromo-3-methylcinnolin-4(1H)-one (2.48 g, 83% yield) as a yellow solid, which was used without further purification. LCMS: RT = 0.43 min; ES-MS [M+H]+: 239.1 / 241.0. Step 3. Preparation of 6-bromo-4-chloro-3-methylcinnoline Phosphorus(V) oxychloride (4.8 mL, 51.9 mmol) was added to a solution of 6-bromo-3- methylcinnolin-4(1H)-one (2.48 g, 10.4 mmol) in DMF (10 mL). After stirring for 16 hours, additional phosphorus(V) oxychloride (4.8 mL, 51.9 mmol) was added, and the reaction stirred an additional 24 hours. The reaction was then stirred at 60 ºC for two hours. After cooling to ambient temperature, the reaction was concentrated in vacuo. The resulting residue was dissolved in DCM (50 mL) and washed sequentially with saturated aqueous NaHCO3(50 mL), water (50 mL), brine (50 mL), passed through a phase separator and concentrated in vacuo. Purification by flash column chromatography on silica gel (0-20% EtOAc / hexanes) afforded 2.13 g (80% yield) of 6-bromo-4- chloro-3-methylcinnoline (along with ~15% 4,6-dichloro-3-methylcinnoline) as a red-brown solid.1H NMR (400 MHz, DMSO) δ 8.45 (d, J = 9.0 Hz, 1H), 8.35 (d, J = 2.0 Hz, 1H), 8.11 (dd, J = 9.0, 2.0 Hz, 1H), 2.97 (s, 3H). LCMS: RT = 0.43 min; ES-MS [M+H]+: 239.1 / 241.0 Step 4. Preparation of 6-bromo-3-methylcinnoline 4-Methylbenzenesulfonohydrazide (3038 mg, 16.3 mmol) was added to a solution of 6- bromo-4-chloro-3-methylcinnoline (2100 mg, 8.2 mmol) in CHCl3(45 mL). The reaction was stirred at 60 ºC for 16 hours. The reaction mixture was concentrated in vacuo and the resulting residue dissolved in water (50 mL) and 1,4-dioxane (10 mL). Sodium carbonate (8808 mg, 81.6 mmol) was added and the reaction stirred at 95 ºC for 2 hours. Reaction was extracted with DCM (3x 100 mL) and the combined organic layers passed through a phase separator and concentrated in vacuo. Purification by flash column chromatography on silica gel (0-100% EtOAc / hexanes) afforded 1.46 g (80% yield) of 6-bromo-3-methylcinnoline (along with 6-chloro-3- methylcinnoline ) as a red solid.1H NMR (400 MHz, DMSO) δ 8.37 (dt, J = 9.1, 0.7 Hz, 1H), 8.31 (d, J = 2.1 Hz, 1H), 8.02 – 7.96 (m, 2H), 2.87 (d, J = 0.8 Hz, 3H). LCMS: RT = 0.43 min; ES-MS [M+H]+: 223.0 / 225.0 Step 5. Preparation of (E / Z)-6-(2-ethoxyvinyl)-3-methylcinnoline 6-bromo-3-methylcinnoline (1.45 g, 6.5 mmol), (E)-1-ethoxyethen-2-boronic acid pinacol ester (1.55 g, 7.8 mmol), dichloro[1,1’-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (532 mg, 0.65 mmol) and sodium carbonate (2.1 g, 19.5 mmol) in 1,4- dioxane (50 mL) and water (5 mL) was stirred at 120 ºC for 8 hr. The mixture was diluted with water (100 mL) and extracted sequentially with EtOAc (3x100 mL) and 3:1 CHCl3:IPA (3x100 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (30-100% EtOAc / hexanes) to give (E / Z)-6-(2-ethoxyvinyl)-3-methylcinnoline (1.08 g, 77% yield) as a red-brown solid.1H NMR (400 MHz, DMSO) δ 8.22 (dd, J = 9.0, 0.9 Hz, 1H), 7.94 (dd, J = 9.0, 1.9 Hz, 1H), 7.79 (d, J = 0.9 Hz, 1H), 7.60 (dd, J = 7.4, 5.5 Hz, 2H), 6.06 (d, J = 12.9 Hz, 1H), 4.00 (q, J = 7.0 Hz, 2H), 2.79 (d, J = 0.7 Hz, 3H), 1.29 (t, J = 7.0 Hz, 3H) (major isomer). LCMS: RT = 0.53 min; ES-MS [M+H]+: 215.2. Step 6. Preparation of 5-(3-methylcinnolin-6-yl)thiazol-2-amine N-Bromosuccinimide (973 mg, 5.5 mmol) was added to (E / Z)-6-(2-ethoxyvinyl)-3- methylcinnoline (1.07 g, 5.0 mmol) in 1,4-dioxane (15 mL) and water (15 mL) at 0 ºC and the reaction stirred for 30 minutes. Thiourea (416 mg, 5.5 mmol) was added, and the solution stirred at 90 ºC for 90 minutes. The solution was concentrated to afford 1.2 g (quantitative yield) of the title compound as a brown solid, which was used without further purification. LCMS: RT = 0.37 min; ES-MS [M+H]+: 243.1. Synthesis of Intermediate 2 Preparation of 5-(cinnolin-6-yl)thiazol-2-amine (Intermediate 2) Step 1. Preparation of (E)-6-(2-ethoxyvinyl)cinnoline 6-Bromocinnoline (504 mg, 2.41 mmol) was combined with (E)-2-(2-ethoxyvinyl)- 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (716 mg, 3.62 mmol), Na2CO3(0.78 g, 7.23 mmol, 3.0 eq), Pd(dppf)Cl2(177 mg, 0.24 mmol) followed by 1,4-dioxane (10 mL) and water (3 mL). The mixture was purged with nitrogen 3 times. The reaction was then heated to 90 ºC. After 16 h, the reaction was cooled to room temperature, diluted with EtOAc, and filtered through a pad of Celite. The filtrate was concentrated under reduced pressure to give the crude. The crude was purified by flash silica gel chromatography (0-100% EtOAc / hexanes) to give (E)-6-(2-ethoxyvinyl)cinnoline (478 mg, 99% yield). LCMS: RT = 0.60 min, ES-MS [M+H]+= 201.1. Step 2. Preparation of 5-(cinnolin-6-yl)thiazol-2-amine To a solution of (E)-6-(2-ethoxyvinyl)cinnoline (478 mg, 2.39 mmol) in a mixture of 1,4- dioxane (10 mL) and water (10 mL) was added N-bromosuccinimide (467 mg, 2.63 mmol) at 0 ºC. After stirring 30 min at 0 ºC, thiourea (200 mg, 2.63 mmol) was added. The reaction was then heated to 100 ºC. After 1 h, the reaction was cooled to RT and concentrated. The residue was diluted with sat. aq. NaHCO3, and extracted with CHCl3 / IPA (3:1) 5 times. The combined extracts were dried (Na2SO4), filtered and concentrated to give the crude 5-(cinnolin-6-yl)thiazol-2-amine (495 mg, 91% yield). The crude was used in the next step directly..1H NMR (400 MHz, DMSO- d6) δ 9.38 (d, J = 4.9 Hz, 1H), 9.17-8.92 (bs, 2H), 8.46 (d, J = 9.0 Hz, 1H), 8.34 (dd, J =9.0 Hz, 2.0 Hz, 1H), 8.30 (d, J = 5.9 Hz, 1H), 8.13 (s, 1H), 8.06 (d, J = 2.0 Hz, 1H); LCMS: RT = 0.42 min, ES-MS [M+H]+= 229.2. Synthesis of Intermediate 3 Preparation of 5-(3-(difluoromethyl)cinnolin-6-yl)thiazol-2-amine (Intermediate 3) Step 1. Preparation of 6-bromo-3-(difluoromethyl)cinnoline To a solution of 6-bromocinnoline-3-carbaldehyde (120 mg, 0.51 mmol) in DCM (3.4 mL) at -20 ºC was added (diethylamino)sulfur trifluoride (0.27 mL, 2.02 mmol). The reaction was warmed to ambient temperature and stirred for 1 hour. Water (10 mL) was added, the layers separated, and the aqueous layer was further extracted with DCM (3x10 mL). Combined organics were passed through a phase separator and concentrated in vacuo. Purification by column chromatography on silica gel (0-30% EtOAc / hexanes) afforded 6-bromo-3- (difluoromethyl)cinnoline (81.5 mg, 63% yield) as a white solid.1H NMR (400 MHz, CDCl3) δ 8.50 (dt, J = 9.0, 0.7 Hz, 1H), 8.14 (dd, J = 7.8, 1.6 Hz, 2H), 8.03 (dd, J = 9.1, 2.0 Hz, 1H), 7.24 (t, J = 54.8 Hz, 1H). LCMS: RT = 0.578 min, ES-MS [M+H]+: 259.0 / 261.0. Step 2. Preparation of (E)-3-(difluoromethyl)-6-(2-ethoxyvinyl)cinnoline 6-Bromo-3-(difluoromethyl)cinnoline (80 mg, 0.31 mmol), (E)-2-(2-ethoxyvinyl)-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (67.3 mg, 0.34 mmol), Pd(dppf)Cl2•DCM (25.3 mg, 0.031 mmol), and sodium carbonate (100.1 mg, 0.93 mmol,) in 1,4-dioxane (2.0 mL) and water (0.2 mL) was microwave irradiated to 120 ºC for 20 min. Reaction was filtered through Celite, washing with EtOAc. Purification by column chromatography on silica gel (0-40% EtOAc / hexanes) afforded (E)-3-(difluoromethyl)-6-(2-ethoxyvinyl)cinnoline (30.5 mg, 39% yield)as a white solid. LCMS: RT = 0.655 min, ES-MS [M+H]+: 251.0. Step 3. Preparation of 5-(3-(difluoromethyl)cinnolin-6-yl)thiazol-2-amine N-Bromosuccinimide (24 mg, 0.13 mmol) was added to (E)-3-(difluoromethyl)-6-(2- ethoxyvinyl)cinnoline (30 mg, 0.12 mmol) in 1,4-dioxane (0.5 mL) and water (0.5 mL) at 0ºC and the reaction stirred for 30 minutes. Thiourea (10 mg, 0.13 mmol) was added, and the solution stirred at 100 ºC for 1 hour. The solution was concentrated to afford 5-(3- (difluoromethyl)cinnolin-6-yl)thiazol-2-amine (33 mg, 99% yield)as a yellow solid, which was used without further purification. LCMS: RT = 0.37 min; ES-MS [M+H]+: 278.9. Synthesis of Intermediate 4 Preparation of 5-(3-(morpholinomethyl)cinnolin-6-yl)thiazol-2-amine (Intermediate 4) Step 1. Preparation of 4-((6-bromocinnolin-3-yl)methyl)morpholine To a solution of 6-bromocinnoline-3-carbaldehyde (50 mg, 0.21 mmol) in DCE (2 mL) was added morpholine (20 μL, 0.23 mmol) and acetic acid (24, μL, 0.42 mmol). After stirring 30 minutes, sodium triacetoxyborohydride (67 mg, 0.32 mmol) was added and the reaction stirred 16 hours. The reaction was diluted with DCM (5 mL) and saturated aqueous sodium carbonate was added. The layers were separated, and the aqueous layer was further extracted with DCM (2x10 mL). The combined organic layers were passed through a phase separator and concentrated to afford 4-((6-bromocinnolin-3-yl)methyl)morpholine (65 mg, 100% yield) as a brown oil which was used without further purification. LCMS: RT = 0.56 min; ES-MS [M+H]+: 308.0 / 310.0. Step 2. Preparation of (E)-4-((6-(2-ethoxyvinyl)cinnolin-3-yl)methyl)morpholine 4-((6-Bromocinnolin-3-yl)methyl)morpholine (65 mg, 0.21 mmol) (E)-1-ethoxyethen-2- boronic acid pinacol ester (46 mg, 0.23 mmol), dichloro[1,1’-bis(diphenylphosphino)- ferrocene]palladium(II) dichloromethane adduct (17 mg, 0.02 mmol) and sodium carbonate (68 mg, 0.63 mmol) in 1,4-dioxane (1 mL) and water (0.1 mL) was stirred at 100 ºC for 2 hours. The reaction was filtered through Celite, washing with EtOAc and the filtrate concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel (0-5% MeOH / DCM (with 1% NH4OH)) to afford (E)-4-((6-(2-ethoxyvinyl)cinnolin-3- yl)methyl)morpholine (51 mg, 81% yield) as an off-white solid.1H NMR (400 MHz, CD3OD) δ 8.22 (dd, J = 9.0, 0.9 Hz, 1H), 8.03 (s, 1H), 7.94 (dd, J = 9.1, 1.9 Hz, 1H), 7.62 (d, J = 1.9 Hz, 1H), 7.49 (d, J = 12.9 Hz, 1H), 6.07 (d, J = 12.9 Hz, 1H), 4.06 – 3.97 (m, 4H), 3.74 – 3.68 (m, 4H), 2.61 – 2.54 (m, 4H), 1.35 (t, J = 7.0 Hz, 3H). LCMS: RT = 0.60 min; ES-MS [M+H]+: 300.2. Step 3. Preparation of 5-(3-(morpholinomethyl)cinnolin-6-yl)thiazol-2-amine N-Bromosuccinimide (30 mg, 0.17 mmol) was added to (E)-4-((6-(2-ethoxyvinyl)- cinnolin-3-yl)methyl)morpholine (51 mg, 0.17 mmol) in 1,4-dioxane (1 mL) and water (1 mL) at 0ºC and the reaction stirred for 30 minutes. Thiourea (14 mg, 0.19 mmol) was added, and the solution stirred at 100 ºC for 1 hour. The solution was concentrated to afford 5-(3- (morpholinomethyl)cinnolin-6-yl)thiazol-2-amine (55 mg, 99% yield) as a brown oil, which was used without further purification. LCMS: RT = 0.43 min; ES-MS [M+H]+: 328.2. Synthesis of Intermediate 5 Preparation of 5-(3,4-dimethylcinnolin-6-yl)thiazol-2-amine (Intermediate 5) Step 1. Preparation of (E)-6-(2-ethoxyvinyl)-3,4-dimethylcinnoline 6-Bromo-3,4-dimethylcinnoline (200.0 mg, 0.844 mmol) was combined with (E)-2-(2- ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (200.5 mg, 1.01 mmol), Na2CO3(273.3 mg, 2.53 mmol, 3.0 eq), Pd(dppf)Cl2(69.1 mg, 0.084 mmol) followed by 1,4-dioxane (5 mL) and water (1 mL). The mixture was purged with nitrogen 3 times. The reaction was then heated to 90 ºC. Upon completion, the reaction was cooled to room temperature, diluted with EtOAc, and filtered through a pad of Celite. The filtrate was concentrated under reduced pressure to give the crude. The crude was purified by flash chromatography on silica gel (0-40% EtOAc / hexanes) to give (E)-6-(2-ethoxyvinyl)-3,4-dimethylcinnoline (192.1 mg, 99% yield). LCMS: RT = 0.662 min, ES- MS [M+H]+= 229.3. Step 2. Preparation of 5-(3,4-dimethylcinnolin-6-yl)thiazol-2-amine To a solution of (E)-6-(2-ethoxyvinyl)-3,4-dimethylcinnoline (192.0 mg, 0.84 mmol) in a mixture of 1,4-dioxane (5 mL) and water (5 mL) was added N-bromosuccinimide (164.7 mg, 0.93 mmol, 1.1 eq) at 0 ºC. After stirring 30 min at 0 ºC, thiourea (80.4 mg, 1.06 mmol, 1.25 eq) was added. The reaction was then heated to 100 ºC. After 1 h, the reaction was cooled to rt, concentrated in vacuo and dried to give 5-(3,4-dimethylcinnolin-6-yl)thiazol-2-amine (420.0 mg,97% yield). The crude was used in the next step directly.1H NMR (400 MHz, DMSO-d6) δ 8.28 – 8.21 (m, 1H), 8.03 (dd, J = 9.0, 1.9 Hz, 1H), 7.83 (s, 1H), 7.80 (d, J = 1.9 Hz, 1H), 7.51 (s, 2H), 2.81 (s, 3H), 2.62 – 2.57 (m, 3H). LCMS: RT = 0.47 min, ES-MS [M+H]+= 257.1. Synthesis of Intermediate 6 Preparation of 5-(3-chlorocinnolin-6-yl)thiazol-2-amine (Intermediate 6) Step 1. Preparation of 6-bromo-3-chlorocinnoline To a solution of 6-bromo-3,4-dichlorocinnoline (1.08 g, 3.89 mmol) in anhydrous ethanol (40 mL) was added hydrazine (1.22 mL, 38.9 mmol) at rt under N2. After 16 h, the reaction was quenched with water and extracted with DCM / MeOH (3:1) 3 times. The combined organic was washed with water, dried (Na2SO4) and concentrated to give the crude 6-bromo-3-chloro-4- hydrazineylcinnoline. The crude was used in the next step immediately. LCMS: RT = 0.54 min, ES-MS [M+H]+= 275.0. The crude 6-bromo-3-chloro-4-hydrazineylcinnoline from the previous step was dissolved in MeOH (50 mL) and 1 M aqueous CuSO4solution (3.9 mL, 3.89 mmol) was added at ambient temperature. Upon completion, the reaction was concentrated and extracted with DCM (3 x). The organic was washed with 3% aqueous NH4OH and water. The combined organic was dried (Na2SO4), filtered and concentrated to give the crude. The crude was purified by flash chromatography on silica gel (0-50% EtOAc / hexanes) to give 6-bromo-3-chlorocinnoline (673.3 mg71% yield over 2 steps).1H NMR (400 MHz, CDCl3) δ 8.41 (dt, J = 9.1, 0.8 Hz, 1H), 7.98 (d, J = 2.0 Hz, 1H), 7.91 (dd, J = 9.1, 2.0 Hz, 1H), 7.84 (d, J = 1.0 Hz, 1H). LCMS, R.T. = 0.71 min, ES-MS [M+H]+= 245.0. Step 2. Preparation of (E)-3-chloro-6-(2-ethoxyvinyl)cinnoline 6-Bromo-3-chlorocinnoline (401.0 mg, 1.65 mmol) was combined with (E)-2-(2- ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (342.5 mg, 1.73 mmol), Na2CO3(533.6 mg, 4.94 mmol), Pd(dppf)Cl2(120.8 mg, 0.165 mmol) followed by 1,4-dioxane (8 mL) and water (2 mL). The mixture was purged with nitrogen 3 times. The reaction was then heated to 90 ºC. After 3 h, the reaction was cooled to ambient temperature, diluted with EtOAc, and filtered through a pad of Celite. The filtrate was concentrated under reduced pressure to give the crude. The crude was purified by flash chromatography on silica gel (0-50% EtOAc / hexanes) to give (E)-3-chloro- 6-(2-ethoxyvinyl)cinnoline (385.2 mg, 99% yield).1H NMR (400 MHz, DMSO-d6) δ 8.33 – 8.27 (m, 1H), 8.27 (d, J = 1.0 Hz, 1H), 8.08 (dd, J = 9.1, 1.9 Hz, 1H), 7.72 – 7.65 (m, 2H), 6.10 (d, J = 12.9 Hz, 1H), 4.03 (q, J = 7.0 Hz, 2H), 1.30 (t, J = 7.0 Hz, 3H). LCMS: RT = 0.81 min, ES-MS [M+H]+= 235.1. Step 3. Preparation of 5-(3-chlorocinnolin-6-yl)thiazol-2-amine To a solution of (E)-3-chloro-6-(2-ethoxyvinyl)cinnoline (385.0 mg, 1.64 mmol) in a mixture of 1,4-dioxane (8 mL) and water (8 mL) was added N-Bromosuccinimide (321.2 mg, 1.80 mmol) at 0 ºC. After stirring 30 min at 0 ºC, thiourea (137.4 mg, 1.80 mmol) was added. The reaction was then heated to 100 ºC. After 1 h, the reaction was cooled to ambient temperature, concentrated in vacuo and dried to give 5-(3-chlorocinnolin-6-yl)thiazol-2-amine. (860 mg, 99% yield) The crude was used in the next step directly. LCMS: RT = 0.49 min, ES-MS [M+H]+= 263.1. Synthesis of Intermediate 7 Preparation of 4-(2-aminothiazol-5-yl)-2-isopropoxybenzonitrile (Intermediate 7) Step 1. Preparation of (E)-4-(2-ethoxyvinyl)-2-isopropoxybenzonitrile 4-bromo-2-isopropoxy-benzonitrile (2.0 g, 8.33 mmol), (E)-1-ethoxyethen-2-boronic acid pinacol ester (2.47 g, 12.4 mmol), dichloro[1,1’-bis(diphenylphosphino)ferrocene]palladium(II) (340mg, 0.42 mmol) and sodium carbonate (0.89 mL, 20.8 mmol) in 1,4-dioxane (25 mL) and water (5 mL) was stirred at 90ºC for 2 hr. The mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4then concentrated. The residue was purified by flash chromatography on silica gel (120 g, eluting with 0-20% EtOAc in hexanes over 30 min) to give (E)-4-(2-ethoxyvinyl)-2-isopropoxybenzonitrile (1.61 g, 83% yield) as a clear viscous oil. LCMS: RT = 0.84 min; ES-MS [M+H]+: 232.0. Step 2. Preparation of 4-(2-aminothiazol-5-yl)-2-isopropoxybenzonitrile N-bromosuccinimide (1.35 g, 7.61 mmol) was added to (E)-4-(2-ethoxyvinyl)-2- isopropoxybenzonitrile (1.6 g, 6.92 mmol) in 1,4-dioxane (20 mL) and Water (5 mL) at 0ºC then stirred at 0ºC for 20 min. Thiourea (579 mg, 7.61 mmol) was added, and the solution stirred at 80ºC for 1 hr. The solution was then diluted with EtOAc, washed with H2O and brine, dried over Na2SO4then concentrated to give 4-(2-aminothiazol-5-yl)-2-isopropoxybenzonitrile (1.55g, 86% yield) as a tan solid. LCMS: RT = 0.54 min, ES-MS [M+H]+: 260.1;1H NMR (400 MHz, DMSO- d6) δ 9.26 – 8.98 (bs, 1H), 8.04 (s, 1H), 7.72 (d, J = 8.1 Hz, 1 H), 7.41 (s, 1H), 7.14 (d, J = 8.1 Hz, 1H), 4.97 (sept, J = 5.8 Hz, 1 H), 1.33 (d, J = 5.6 Hz, 6H). Synthesis of Intermediate 8 Preparation of 2'-amino-[2,5'-bithiazole]-5-carbonitrile (Intermediate 8) Step 1. Preparation of (E)-2-(2-ethoxyvinyl)thiazole-5-carbonitrile 2-bromo-5-cyanothiazole (191 mg, 1.01 mmol), (E)-1-ethoxyethen-2-boronic acid pinacol ester (200 mg, 1.01 mmol), dichloro[1,1’-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (55 mg, 0.07 mmol) and sodium carbonate (202 mg, 1.68 mmol) in 1,4- dioxane (4 mL) and water (1 mL) was stirred at 80ºC for 2 hr. The solution was dried over Na2SO4then the solution was purified by semi-prep HPLC (0-50% MeCN in 0.05% NH4OH (aq) over 10 min) to give (E)-2-(2-ethoxyvinyl)thiazole-5-carbonitrile (122 mg, 67% yield) as a clear glass. LCMS: RT = 0.51 min; ES-MS [M+H]+: 180.9. Step 2. Preparation of 2'-amino-[2,5'-bithiazole]-5-carbonitrile N-bromosuccinimide (38 mg, 0.21 mmol) was added to (E)-2-(2-ethoxyvinyl)thiazole-5- carbonitrile (35 mg, 0.19 mmol) in 1,4-dioxane (1 mL) and water (0.25 mL) at 0ºC then was stirred for 15 min. Thiourea (16 mg, 0.21 mmol) was added and the solution stirred at 90ºC for 90 min. The solution was concentrated to give 2'-amino-[2,5'-bithiazole]-5-carbonitrile (62 mg) as a tan solid which was used without purification. LCMS: RT = 0.32 min; ES-MS [M+H]+: 209.1. Synthesis of Intermediate 9 Preparation of 4-(2-aminothiazol-5-yl)-1-methyl-1H-indole-7-carbonitrile (Intermediate 9) Step 1. Preparation of (E)-4-(2-ethoxyvinyl)-1-methyl-1H-indole-7-carbonitrile 4-Bromo-1-methyl-indole-7-carbonitrile (106 mg, 0.45 mmol) [(E)-2- ethoxyvinyl]thiazole-5-carbonitrile (108 mg, 0.55 mmol), dichloro[1,1’- bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (24 mg, 0.03 mmol) and sodium carbonate (74 mg, 0.68 mmol) in 1,4-dioxane (2 mL) and water (0.5 mL) was stirred at 80ºC for 2 hr. The solution was dried over Na2SO4then the solution was purified by flash chromatography on silica gel (24g, eluting with 0-40% EtOAc in hexanes over 20 min) to give (E)-4-(2-ethoxyvinyl)-1-methyl-1H-indole-7-carbonitrile (68 mg, 66% yield) as a viscous clear oil. LCMS: RT = 0.94 min; ES-MS [M+H]+: 227.1. Step 2. Preparation of 4-(2-aminothiazol-5-yl)-1-methyl-1H-indole-7-carbonitrile N-Bromosuccinimide (58 mg, 0.33 mmol) was added to (E)-4-(2-ethoxyvinyl)-1-methyl- indole-7-carbonitrile in 1,4-dioxane (1.5 mL) and water (0.25 mL) at 0ºC then stirred at 15 min. Thiourea (25 mg, 0.33 mmol) was added and the solution stirred at 90ºC for 2 hr. The solution was purified by semi-prep HPLC (0-50% MeCN in 0.05% NH4OH (aq) over 10 min) to give 4-(2-aminothiazol-5-yl)-1-methyl-1H-indole-7-carbonitrile (39 mg, 51% yield) as a tan solid. LCMS: RT = 0.44 min; ES-MS [M+H]+: 255.1. Synthesis of Intermediate 10 Preparation of 7-(2-aminothiazol-5-yl)-2-methylquinazolin-4(3H)-one (Intermediate 10) Step 1. Preparation of (E)-7-(2-ethoxyvinyl)-2-methylquinazolin-4(3H)-one 7-Bromo-2-methylquinazoline-4(3H)-one (1.0 g, 4.18 mmol), (E)-1-ethoxythene-2- boronic acid pinacol ester (1.24g, 6.27 mmol), dichloro[1,1’-bis(diphenylphosphino)- ferrocene]palladium dichloromethane adduct (171 mg, 0.21 mmol) and sodium carbonate (1.13 g, 10.4 mmol) in 1,4-dioxane (12 mL) and water (3 mL) was stirred at 90ºC for 2 hr. The mixture was diluted with EtOAc, washed with H2O and brine, dried over Na2SO4then concentrated. The residue was purified by flash chromatography on silica gel (120 g, eluting with 0-20% EtOAc in hexanes over 30 min) to give (E)-7-(2-ethoxyvinyl)-2-methylquinazolin-4(3H)-one (940 mg, 97% yield) as a clear viscous oil. LCMS: RT = 0.45 min; ES-MS [M+H]+: 231.1. Step 2. Preparation of 7-(2-aminothiazol-5-yl)-2-methylquinazolin-4(3H)-one N-Bromosuccinimide (799 mg, 4.49 mmol) was added to (E)-7-(2-ethoxyethenyl)-2- methyl-3H-quinazolin-4-one (940 mg, 4.08 mmol) in 1,4-dioxane (15 mL) and water (3 mL) at 0ºC then stirred at 0ºC for 20 min. Thiourea (341 mg, 4.49 mmol) was added and the solution stirred at 80ºC for 2 hr. The solution was allowed to stand at RT for 16 hr. The resulting solids were collected by suction filtration, washed with H2O and dioxane then dried to give 7-(2- aminothiazol-5-yl)-2-methylquinazolin-4(3H)-one (920 mg, 87% yield) as a tan solid. LCMS: RT = 0.39 min; ES-MS [M+H]+: 259.1. Synthesis of Intermediate 11 Preparation of 5-(2-methyl-2H-indazol-5-yl)thiazol-2-amine (Intermediate 11) Step 1. Preparation of (E)-5-(2-ethoxyvinyl)-2-methyl-2H-indazole 5-Bromo-2-methyl-2H-indazole (0.70 g, 3.32 mmol) was combined with (E)-2-(2- ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (854 mg, 4.31 mmol), Na2CO3(1.07 g, 9.95 mmol), Pd(dppf)Cl2(243 mg, 0.33 mmol) followed by 1,4-dioxane (10 mL) and water (3 mL). The mixture was purged with nitrogen 3 times. The reaction was heated to 90 ºC. After 16 h, the reaction was cooled to room temperature, diluted with EtOAc, and filtered through a pad of Celite. The filtrate was concentrated under reduced pressure to give the crude. Crude was purified by flash chromatography on silica gel (0-100% EtOAc / hexanes) to give (E)-5-(2-ethoxyvinyl)-2-methyl- 2H-indazole (533 mg, 80%). LCMS, RT = 0.56 min, ES-MS [M+H]+= 203.1. Step 2. Preparation of 5-(2-methyl-2H-indazol-5-yl)thiazol-2-amine To a solution of (E)-5-(2-ethoxyvinyl)-2-methyl-2H-indazole (539 mg, 2.66 mmol) in a mixture of 1,4-dioxane (10 mL) and water (10 mL) was added N-bromosuccinimide (521 mg, 2.93 mmol) at 0 ºC. After stirring 30 min at 0 ºC, thiourea (223 mg, 2.93 mmol) was added. The reaction was then heated to 100 ºC. After 1 h, the reaction was cooled to RT and concentrated. The residue was diluted with sat. aq. NaHCO3, and extracted with CH3Cl / IPA (3:1) 5 times. The combined extracts were dried (Na2SO4), filtered and concentrated to give the crude. Crude was purified by flash chromatography on silica gel (0-10% MeOH / DCM) to give 5-(2-methyl-2H- indazol-5-yl)thiazol-2-amine (570.6 mg, 93%). LCMS, RT = 0.50 min, ES-MS [M+H]+= 231.1. Synthesis of Intermediate 12 Preparation of 5-(2-methylquinazolin-7-yl)thiazol-2-amine (Intermediate 12) Step 1. Preparation of (E)-7-(2-ethoxyvinyl)-2-methylquinazoline 7-Bromo-2-methylquinazoline (0.60 g, 2.69 mmol), (E)-2-(2-ethoxyvinyl)-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (0.59 g, 2.96 mmol), Na2CO3(0.87 g, 8.07 mmol), Pd(dppf)Cl2(197 mg, 0.27 mmol) followed by 1,4-dioxane (10 mL) and water (3 mL). The mixture was purged with nitrogen 3 times. The reaction was then heated to 90 ºC. After 16 h, the reaction was cooled to RT, diluted with EtOAc, and filtered through a pad of Celite. The filtrate was concentrated under reduced pressure to give the crude. The crude was purified by flash chromatography on silica gel (0-100% EtOAc / hexanes) to give (E)-7-(2-ethoxyvinyl)-2-methylquinazoline (417.3 mg, 72%). LCMS: RT = 0.38 min, ES-MS [M+H]+= 215.2. Step 2. Preparation of 5-(2-methylquinazolin-7-yl)thiazol-2-amine To a solution of (E)-7-(2-ethoxyvinyl)-2-methylquinazoline (417 mg, 1.95 mmol) in a mixture of 1,4-dioxane (10 mL) and water (10 mL) was added N-bromosuccinimide (381 mg, 2.14 mmol) at 0 ºC. After stirring 45 min at 0 ºC, thiourea (163 mg, 2.14 mmol) was added. The reaction was then heated to 100 ºC. After 1 h, the reaction was cooled to RT and concentrated. The residue was diluted with sat. aq. NaHCO3, and extracted with CHCl3 / IPA (3:1) 3 times. The combined extracts were dried (Na2SO4), filtered and concentrated to give the 5-(2- methylquinazolin-7-yl)thiazol-2-amine (376.1 mg, 80%). The crude was used in the next step directly. LCMS: RT = 0.46 min, ES-MS [M+H]+= 243.3. Synthesis of Intermediate 13 Preparation of 5-([1,2,4]triazolo[4,3-a]pyridin-6-yl)thiazol-2-amine (Intermediate 13) Step 1. Preparation of (E)-6-(2-ethoxyvinyl)-[1,2,4]triazolo[4,3-a]pyridine 6-Bromo-[1,2,4]triazolo[4,3-a]pyridine (600 mg, 3.03 mmol) was combined with (E)-2- (2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (720 mg, 3.64 mmol), Na2CO3(981 mg, 9.09 mmol) Pd(dppf)Cl2(222 mg, 0.30 mmol) followed by 1,4-dioxane (8 mL) and water (2 mL). The mixture was purged with nitrogen 3 times. The reaction was then heated to 90 ºC. After 6 h, the reaction was cooled to RT, diluted with EtOAc, and filtered through a pad of Celite. The filtrate was concentrated under reduced pressure to give the crude. The crude was purified by flash silica gel chromatography (0-100% EtOAc / hexanes) to give (E)-6-(2-ethoxyvinyl)- [1,2,4]triazolo[4,3-a]pyridine (557 mg, 97%). LCMS: RT = 0.47 min, ES-MS [M+H]+= 190.2. Step 2. Preparation of 5-([1,2,4]triazolo[4,3-a]pyridin-6-yl)thiazol-2-amine To a solution of (E)-6-(2-ethoxyvinyl)-[1,2,4]triazolo[4,3-a]pyridine (557 mg, 2.94 mmol) in a mixture of 1,4-dioxane (7 mL) and water (7 mL) was added N-bromosuccinimide (576 mg, 3.24 mmol) at 0 ºC. After stirring 30 min at 0 ºC, thiourea (246 mg, 3.24 mmol) was added. The reaction was then heated to 100 ºC. After 1 h, the reaction was cooled to RT and concentrated and dried to give the crude 5-([1,2,4]triazolo[4,3-a]pyridin-6-yl)thiazol-2-amine (1.23 g, 96%). The crude was used in the next step directly. LCMS: RT = 0.34 min, ES-MS [M+H]+= 218.1. Synthesis of Intermediate 14 Preparation of 7-(2-aminothiazol-5-yl)-2,3-dimethylquinazolin-4(3H)-one (Intermediate 14) Step 1. Preparation of 7-bromo-2,3-dimethylquinazolin-4(3H)-one To a solution of 7-bromo-2-methylquinazolin-4(3H)-one (350 mg, 1.46 mmol) in DMF (3 mL) was added Cs2CO3(720 mg, 2.2 mmol) and followed by MeI (182 μL, 2.93 mmol) at RT. After 2 h, the reaction was quenched with water and extracted with CHCl3 / IPA (3:1) 3 times. The organic was combined, dried (Na2SO4), filtered and concentrated to give the crude 7- bromo-2,3-dimethylquinazolin-4(3H)-one (370.2 mg, 99%). The crude was used in the next step directly.1H NMR (400 MHz, DMSO) δ 8.01 (d, J = 8.5 Hz, 1H), 7.79 (d, J = 1.9 Hz, 1H), 7.63 (dd, J = 8.5, 2.0 Hz, 1H), 3.52 (s, 3H), 2.57 (s, 3H); LCMS: RT = 0.58 min, ES-MS [M+H]+= 253.1 / 255.1. Step 2. Prepara...

Claims

WHAT IS CLAIMED IS:

1. A compound represented by the structure of Formula (I):or a pharmaceutically acceptable salt thereof, wherein: D is selected from -N(R1)C(O)-L-, -X-, and -X-C1-6alkylene; X is selected from -O-, -S-, and -N(R6)-, L is absent or L is selected from -O-, -S-, -N(R6)-, C1-6alkylene, -N(R6)-C1-6alkylene, -O-C1-6alkylene, and -S- C1-6alkylene, wherein each C1-6alkylene of D or L is optionally substituted with one or more substituents independently selected from halogen, -OR7, and -CN; Ring A is selected from C3-C12 carbocycle and 3- to 12-membered 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, =O, and -CN; and 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, and -CN; and C3-C6carbocycle 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, -C(O)R11, -C(O)OR11, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R1is selected from hydrogen, C1-4alkyl, and C1-4haloalkyl; R2is selected from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; R3and R4are each independently selected from: hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN;C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, -OR13, -SR13, -N(R13)2, and -CN; or R3and R4come together to form a 3- to 7-membered heterocycle optionally substituted with one or more substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R5is selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)OR15, -OC(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl; R6and R7are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; R11and R15are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; R13is independently selected at each occurrence from hydrogen, C1-4alkyl, C1-4haloalkyl, C3-6carbocycle, and 3-to-6 membered heterocycle optionally substituted with one or more substituent selected from halogen, C1-4alkyl, and C1-4haloalkyl; and n is selected from 0, 1, and 2; provided that: (A) if D is -N(R1)C(O)-L-, L is absent and R3and R4are both hydrogen, Ring A is selected from (i), (ii), (iii), (iv), (v), (vi), or (vii): (i) bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2- oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane; (ii) phenyl and monocyclic heteroaryl, provided that Ring A is not 2- methylpyridine or 1-methyl-2-pyridone; (iii) monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur; (iv) monocyclic heterocycloalkyl substituted with two or more halogen; (v) monocyclic heterocycloalkyl substituted with one or more substituents selected from C1-6haloalkyl, -OR11, C3-C6carbocycle, and 3- to 6-membered heterocycle;(vi) monocyclic C3-C4carbocycle substituted with at least one –OH or 1-2 fluorine; and (vii) cyclohexyl substituted with -OH, 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, =O, and -CN; 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, and -CN; and C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, =O, -CN, C1-6alkyl, and C1-6haloalkyl;(B) if D is -N(R1)C(O)-L-, L is methylene and Ring A is tetrahydropyran, then at least one of R3and R4is not hydrogen; (B) if D is -N(R1)C(O)-L-, L is absent and R3and R4are each methyl, then Ring A is not 2,2,5,5-tetramethyltetrahydrofuranyl, 2,2-dimethyltetrahydropyranyl, or 2,2,6,6- tetramethyltetrahydropyranyl; (C) if D is -N(R1)C(O)-L-, L is absent, R3is 3-methylmorpholinyl, and R4is hydrogen, then Ring A is not 2,2,5,5-tetramethyltetrahydrofuranyl; and (D) if D is -N(R1)C(O)-L-, L is absent, R3is OH, and R4is hydrogen, then Ring A is not 4-fluorotetrahydropyranyl.

2. The compound or salt of claim 1, wherein R1is hydrogen.

3. The compound or salt of claim 1 or claim 2, wherein R2is hydrogen.

4. The compound or salt of any one of claims 1 to 3, wherein n is 0.

5. The compound or salt of any one of claims 1 to 4, wherein L is absent or L is selected from -O-, C1-2alkylene, and -N(R6)-C1-2alkylene, wherein the C1-2alkylene is optionally substituted with one or more -F.

6. The compound or salt of any one of claims 1 to 5, wherein L is absent, or L is selected from -O-, -CH2-, -CFH-, -CF2-, and -N(H)CH2-.

7. The compound or salt of any one of claims 1 to 6, wherein L is selected from -O-, -CH2-, -CFH-, and -N(H)CH2-.

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

9. The compound or salt of any one of claims 1 to 8, wherein R3and R4are each independently selected from: hydrogen, halogen, -OR13, -N(R13)2, and -C(O)N(R13)2; C1-6alkyl optionally substituted with one or more substituents independently selected from -F and morpholinyl; and 3- to 6-membered heterocycle optionally substituted with one or more C1-6alkyl; or R3and R4come together to form a 5- to 7-membered heterocycle optionally substituted with one or more C1-4alkyl; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and 3-to-6 membered heterocycle.

10. The compound or salt of any one of claims 1 to 8, wherein R3and R4are each independently selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, -OR13, -SR13, -N(R13)2, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and 3-to-6 membered heterocycle.

11. The compound or salt of any one of claims 1 to 9, wherein R3and R4are each independently selected from hydrogen, halogen, -OR13, -N(R13)2, and -C(O)N(R13)2; C1-6alkyl optionally substituted with one or more substituents independently selected from -F and morpholinyl; and3- to 6-membered heterocycle optionally substituted with one or more C1-6alkyl; and R13is independently selected at each occurrence from hydrogen, C1-4alkyl, and 3-to-6 membered heterocycle 12. The compound or salt of any one of claims 1 to 8 and 10, wherein R3and R4are each independently selected from C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle.

13. The compound or salt of any one of claims 1 to 12, wherein R3and R4are each independently selected from C1-4alkyl.

14. The compound or salt of any one of claims 1 to 8, wherein R3is selected from15. The compound or salt of any one of claims 1 to 11 and 14, wherein R4is selected from hydrogen, -F, -Cl, -CH3, -CHF2, and .

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

17. The compound or salt of any one of claims 1 to 16, wherein R4is hydrogen.

18. The compound or salt of any one of claims 1 to 9, wherein R3and R4come together to form a 3- to 7-membered heterocycle optionally substituted with one or more substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl.

19. The compound or salt of any one of claims 1 to 9 and 18, wherein R3and R4come together to form a 5- to 7-membered heterocycle optionally substituted with one or more C1-4alkyl.

20. The compound or salt of any one of claims 1 to 9, 18, and 19, wherein R3and R4come together to form a 5- to 7-membered heterocycle selected from: , , , , and .

21. The compound or salt of any one of claims 1 to 20, wherein Ring A is selected from C3-C12carbocycle and 3- to 12-membered 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, -C(O)N(R11)2, -N(R11)C(O)R11, S(O)2R11, =O, and -CN; 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, -C(O)N(R11)2, -N(R11)C(O)R11, S(O)2R11, and -CN; and phenyl and 6-membered heterocycle, each of which is optionally substituted with one or more substituent independently selected from halogen, -OR11, C1-4alkyl, and C1-4haloalkyl; and R11is independently selected at each occurrence from hydrogen and C1-4alkyl.

22. The compound or salt of any one of claims 1 to 21, wherein Ring A is selected from C3-C12carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -C(O)R11, S(O)2R11, -CN, =O; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen and -OR11; phenyl; and 6-membered heteroaryl; and wherein R11is selected at each occurrence from hydrogen and C1-4alkyl.

23. The compound or salt of any one of claims 1 to 22, wherein Ring A is selected from cyclopropyl, cyclobutyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, oxazolidinyl, tetrahydropyranyl, 1,4,-dioxanyl, pyrrolidinyl, piperidinyl, morpholinyl, quinuclidinyl, spiro[2.2]pentanyl, 2-oxa-5- azabicyclo[2.2.1]heptane, 3-bicyclo[1.1.1]pentyl, 3-oxabicyclo[3.1.0]hexanyl, 2- oxabicyclo[3.1.0]hexanyl, hexahydro-2,5-dioxaindenyl, 2-oxabicyclo[2.1.1]hexanyl, 7- oxabicyclo[2.2.1]heptanyl, 2-oxabicyclo[2.2.1]heptanyl, 2-oxabicyclo[2.2.2]octanyl, 8-oxabicyclo[3.2.1]octanyl, 2-oxaspiro[3.3]heptanyl, 5-oxaspiro[2.4]heptanyl, 4- oxaspiro[2.5]octanyl, 6-oxaspiro[2.5]octanyl, 6-oxaspiro[4.5]decanyl, 5-oxaspiro[3.5]nonanyl, 2- oxaspiro[3.5]nonanyl, 1-oxaspiro[5.5]undecanyl, 1,9-dioxaspiro[5.5]undecanyl, 4,5,6,7- tetrahydroindazolyl, 2-oxaindazolyl, chromanyl, isochromanyl, phenyl, pyrimidinyl, pyrrolyl, pyridinyl, 2-pyridonyl, and pyrazolyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -C(O)R11, S(O)2R11, -CN, =O; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen and -OR11; phenyl; and 6-membered heterocycle optionally substituted with one or more C1-4alkyl; and wherein R11is independently selected at each occurrence from hydrogen and C1-4alkyl.

24. The compound or salt of any one of claims 1 to 23, wherein Ring A is selected from: cyclopropyl, cyclobutyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, oxazolidinyl, tetrahydropyranyl, 1,4,-dioxanyl, pyrrolidinyl, piperidinyl, morpholinyl, quinuclidinyl, spiro[2.2]pentanyl, 2-oxa-5-azabicyclo[2.2.1]heptane, 3-bicyclo[1.1.1]pentyl, 3- oxabicyclo[3.1.0]hexanyl, 2-oxabicyclo[3.1.0]hexanyl, hexahydro-2,5-dioxaindenyl, 2- oxabicyclo[2.1.1]hexanyl, 7-oxabicyclo[2.2.1]heptanyl, 2-oxabicyclo[2.2.1]heptanyl, 2- oxabicyclo[2.2.2]octanyl, 8-oxabicyclo[3.2.1]octanyl, 2-oxaspiro[3.3]heptanyl, 5- oxaspiro[2.4]heptanyl, 4-oxaspiro[2.5]octanyl, 6-oxaspiro[2.5]octanyl, 6-oxaspiro[4.5]decanyl, 5- oxaspiro[3.5]nonanyl, 2-oxaspiro[3.5]nonanyl, 1-oxaspiro[5.5]undecanyl, 1,9- dioxaspiro[5.5]undecanyl, 4,5,6,7-tetrahydroindazolyl, 2-oxaindazolyl, chromanyl, isochromanyl, phenyl, pyrimidinyl, pyrrolyl, pyridinyl, 2-pyridonyl, and pyrazolyl, each of which is optionally substituted with one or more substituents independently selected from: -F, -CH3, ethyl, isopropyl, isobutyl, tert-butyl, -C(CH3)2OH, -CF3, -CHF2, -OH, -OCH3, -SCH3, -S(O)2CH3, =O, -CN, - C(O)CH3, -C(O)-tert-butyl, phenyl, N-methylpiperidinyl, and pyridinyl.

25. The compound or salt of any one of claims 1 to 23, wherein Ring A is selected from:

26. The compound or salt of any one of claims 1 to 17, wherein D is -N(R1)C(O)-L-; L is absent; R3and R4are both hydrogen, and Ring A is selected from (i), (ii), (iii), (iv), (iv), (v), (vi), or (vii): (i) bicyclic heterocycle, provided that Ring A is not 3-oxabicyclo[3.1.0]hexane, 2- oxabicyclo[2.1.1]hexane, 1-methyl-2-oxabicyclo[2.1.1]hexane, or chromane; (ii) phenyl and monocyclic heteroaryl, provided that Ring A is not 2-methylpyridine or 1-methyl-2-pyridone; (iii) monocyclic heterocycloalkyl comprising two or more heteroatoms selected from nitrogen, oxygen, and sulfur; (iv) monocyclic heterocycloalkyl substituted with two or more halogen;(v) monocyclic heterocycloalkyl substituted with one or more substituents selected from C1-6haloalkyl, -OR11, C3-C6carbocycle, and 3- to 6-membered heterocycle; (vi) monocyclic C3-C4 carbocycle substituted with at least one –OH or 1-2 fluorine; and (vii) cyclohexyl substituted with -OH, 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, =O, and -CN; and 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, and -CN; and C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)OR11, =O, -CN, C1-6alkyl, and C1-6haloalkyl.

27. The compound or salt of claim 26, wherein Ring A is optionally substituted with one or more substituents independently selected from: halogen, -CN, -OR11, C(O)R11, C(O)OR11, C1-6alkyl, C1-4haloalkyl, and 6-membered heterocycle optionally substituted with C1-4alkyl; and wherein R11is selected from hydrogen and C1-4alkyl.

28. The compound or salt of claim 26 or 27, wherein Ring A is selected from:

29. The compound or salt of any one of claims 1 to 28, wherein at least one of R3and R4is not hydrogen.

30. The compound or salt of any one of claims 1 to 29, wherein D is selected from - N(R1)C(O)-L-, -X-, and -X-C1-6alkylene; X is selected from -S-, and -N(R6)-, L is absent or L is selected from -O-, -N(R6)-, C1-6alkylene, -N(R6)-C1-6alkylene, - O-C1-6alkylene, wherein each C1-6alkylene of D or L is optionally substituted with one or more - OR7; R6is selected from hydrogen and methyl; and R7 is independently selected at each occurrence from hydrogen and methyl.

31. The compound or salt of claim 30, wherein D is selected from ,32. The compound or salt of any one of claims 1 to 30, wherein D is selected from - N(R1)C(O)-L-, 33. The compound or salt of claim 30 or 32, wherein L is absent.

34. The compound or salt of claim 32, wherein D is selected from ,35. The compound or salt of any one of claims 1 to 30, wherein D is selected from -X- and -X-C1-6alkylene.

36. The compound or salt of claim 35, wherein X is selected from -S-, and -N(R6)-.

37. The compound or salt of claim 35, wherein D is selected from , , and , 38. The compound or salt of any one of claims 1 to 37, wherein R3is hydrogen, and R4is selected from halogen, C1-4alkyl, and C1-4haloalkyl.

39. The compound or salt of of claim 38, wherein R4is methyl.

40. The compound or salt of of claim 38, wherein R4is chloro.

41. A compound represented by the structure of Formula III: (III), or a pharmaceutically acceptable salt thereof, wherein: RAis selected from: halogen, -OR10, -SR10, -N(R10)2, -CN, C1-6alkyl, C1-6alkoxy, and C1-6haloalkyl; andC3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more halogen; Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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, =O, and -CN; 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, C3-C6carbocycle, and 3- to 6-membered heterocycle; and C3-C6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, C1-4haloalkyl, -OR11, -SR11, -N(R11)2, -C(O)R11, =O, and -CN; Ring B is selected from a polycyclic C7-C12 carbocycle, a polycyclic 7- to 14-membered heterocycle and a monocyclic heterocycle selected from thiazole and thiophene, any 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 3- to 6-membered heterocycle; 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, C1-4alkyl, and C1-4haloalkyl; R2is independently selected at each occurrence from hydrogen, halogen, C1-4alkyl, and C1-4haloalkyl; and R10, R11, and R12are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; provided that if RAis methyl or ethyl and Ring B is cinnoline, 3-chloroisoquinoline, or 2- methylquinazolinyl, then Ring A is not tetrahydrofuran, tetrahydropyran, 2- methyltetrahydrofuran, or 2,6-dimethyltetrahydropyran; provided that if (i) RAis fluoro and Ring B is 4-hydroxycinnoline, or (ii) RAis methyl and Ring B is isoquinoline or 3-fluoroisoquinoline, then Ring A is not tetrahydropyran; provided that if RAis fluoro and Ring B is indazole, Ring A is not selected from N- cyanopyrrolidine; and provided that if RAis methyl and Ring A is 6,7-dihydroindolizin-8(5H)-one, then Ring B is not methylenedioxyphenyl substituted with two fluoro.

42. The compound or salt of claim 41, wherein R1is hydrogen, -CH3, or -CF3.

43. The compound or salt of claim 41 or claim 42, wherein R1is hydrogen.

44. The compound or salt of any one of claims 41 to 43, wherein R2is hydrogen.

45. The compound or salt of any one of claims 41 to 44, wherein the compound or salt is a compound of Formula (IV): or a pharmaceutically acceptable salt thereof; wherein X is N or CR6; R3and R4are each independently selected fromhydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; 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, -OR13, -SR13, -N(R13)2, and -CN; or R3and R4come together to form a 3- to 6-membered heterocycle optionally substituted with one or more substituents selected from: halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, - C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl; R5is selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)OR15, -OC(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl; R6is selected from hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)OR16, -OC(O)R16, -C(O)N(R16)2, -N(R16)C(O)R16, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl; R13, R15, R16are each independently selected at each occurrence from hydrogen, C1-4alkyl, and C1-4haloalkyl; and n is selected from 0, 1, and 2.

46. The compound or salt claim 45, wherein n is 0.

47. The compound or salt of claim 45 or claim 46, wherein X is N.

48. The compound or salt of claim 45 or claim 46, wherein X is CR6; and R6is selected from hydrogen, halogen, -C1-6alkyl, and C1-6haloalkyl.

49. The compound or salt of any one of claims 45, 46, and 48, wherein X is CH.

50. The compound or salt of any one of claims 45 to 49, wherein R3and R4are each independently selected from hydrogen, halogen, -OR13, -SR13, -N(R13)2, -C(O)R13, -C(O)OR13, -OC(O)R13, -C(O)N(R13)2, -N(R13)C(O)R13, -NO2, and -CN; C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR13, -SR13, -N(R13)2, -CN, and 3- to 6-membered heterocycle; andC3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C1-6alkyl, C1-6haloalkyl, -OR13, -SR13, -N(R13)2, and -CN.

51. The compound or salt of any one of claims 45 to 50, wherein R3and R4are each independently selected from: hydrogen, halogen, -OR13, C1-6alkyl optionally substituted with one or more substituents independently selected from halogen and morpholinyl, and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more C1-6alkyl.

52. The compound or salt of any one of claims 45 to 51, wherein R3is hydrogen.

53. The compound or salt of any one of claims 45 to 52, wherein R4is hydrogen, -Cl, or - CH3.

54. The compound or salt of any one of claims 45 to 49, wherein R3and R4come together to form a 3- to 6-membered heterocycle optionally substituted with one or more C1-6alkyl.

55. The compound or salt of any one of claims 41 to 54, wherein Ring A is selected from a C3-C10saturated cycloalkyl, a C3-C10partially 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, -C(O)N(R11)2, -N(R11)C(O)R11, -S(O)2R11, -S(O)2N(R11)2, and -CN; and 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, -C(O)N(R11)2, -N(R11)C(O)R11, -CN, and C3-C6carbocycle; and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, =O, and -CN.

56. The compound or salt of any one of claims 1 to 15, wherein Ring A is selected from a C3- C10saturated cycloalkyl, a C3-C10partially 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, -S(O)2R11, and -CN;C1-6alkyl optionally substituted with C3-C6carbocycle; and 3- to 6-membered heterocycle.

57. The compound or salt of any one of claims 41 to 56, wherein Ring A is selected from a C3- C10saturated cycloalkyl, a C3-C10partially saturated carbocycle, a 3- to 10-membered saturated heterocycloalkyl, and 3- to 10-membered partially saturated heterocycle, each of which is optionally substituted with one or more C1-6alkyl.

58. The compound or salt of any one of claims 41 to 57, wherein Ring A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, dihydrobenzopyranyl, and tetrahydronaphthyl, 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, -S(O)2R11, and -CN; C1-6alkyl optionally substituted with cyclopropyl; and oxetanyl.

59. The compound or salt of any one of claims 41 to 58, wherein R11is selected from hydrogen and C1-4alkyl.

60. The compound or salt of any one of claim 41 to 59, wherein Ring A is selected from: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydronaphthyl, and dihydrobenzopyranyl, each of which is optionally substituted with one or more -CH3.

61. The compound or salt of any one of claims 41 to 60, wherein RAis selected from halogen, -OR10, -CN, C1-6alkyl, and C1-6haloalkyl; C3-C6carbocycle; and phenyl substituted with halogen.

62. The compound or salt of any one of claims 41 to 61, wherein RAis selected from -F, -CN, -CH3, -CH2CH3, -CH2F, -CHF2, -CF3, -CH2CH2F, -OCH3, and .

63. The compound or salt of any one of claims 41 to 62, wherein is selected from:

64. The compound or salt of any one of claims 41 to 44 and 56 to 63, wherein Ring B is selected from a polycyclic 7- to 12-membered heterocycle and a monocyclic heterocycle selected from thiazole and thiophene, any 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, -C(O)N(R12)2, -N(R12)C(O)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, -C(O)N(R12)2, -N(R12)C(O)R12, -CN, and 6-membered heterocycloalkyl;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, -C(O)N(R12)2, -N(R12)C(O)R12, =O, and -CN; and provided that if RAis fluoro and Ring B is indazole, Ring A is not selected from N- cyanopyrrolidine.

65. The compound or salt of any one of claims 41 to 54 and 56 to 64, wherein Ring B is a polycyclic 7- to 12-membered heterocycle or a monocyclic heterocycle selected from thiazole and thiophene, any of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, =O, -CN, C1-6alkyl optionally substituted with one or more halogen or morpholinyl, and 3- to 6-membered heterocycle optionally substituted with one or more C1-6alkyl; provided that when RAis fluoro, Ring B is not indazole.

66. The compound or salt of any one of claims 41 to 44 and 56 to 65, wherein Ring B is selected from 3,4-dihydrothieno[3,2-d]pyrimidinyl, thiophenyl, thiazolyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, isoquinolinyl, quinazolinyl, phthalazinyl, cinnolinyl, 2,3- dihydropyrrolo[2,1-b]quinazolin-9(1H)-one, tetrahydropyrrolo[2,1-b]quinazolinyl, pyrido[3,2-d]pyrimidinyl, pyrido[1,2-a]pyrimidinyl, 2H-pyrazolo[3,4-c]isoquinolinyl, 1,2-dihydroquinazolinyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR12, =O, -CN, C1-6alkyl optionally substituted with one or more halogen or morpholinyl, and 3- to 6-membered heterocycle optionally substituted with one or more C1-6alkyl.

67. The compound or salt of any one of claims 41 to 66, wherein R12is selected from hydrogen and C1-4alkyl.

68. The compound or salt of any one of claims 41 to 67, wherein R12is selected from hydrogen and -CH3.

69. The compound or salt of any one of claims 41 to 44 and 56 to 68, wherein Ring B is selected from 3,4-dihydrothieno[3,2-d]pyrimidinyl, thiophenyl, thiazolyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, isoquinolinyl, quinazolinyl, phthalazinyl, cinnolinyl, 2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one, tetrahydropyrrolo[2,1-b]quinazolinyl, pyrido[3,2-d]pyrimidinyl, pyrido[1,2-a]pyrimidinyl, 2H-pyrazolo[3,4-c]isoquinolinyl, 1,2-dihydroquinazolinyl, each of which is optionally substituted with one or more substituents independently selected from: -F, -Cl, -CN, -OH, =O, -CH3, -CF3, -CHF2,70. The compound or salt of any one of claims 41 to 44 and 56 to 69, wherein Ring B is selected from:

71. A compound selected from the compounds of Table 1, or a pharmaceutically acceptable salt thereof.

72. A pharmaceutical composition comprising a compound of any one of Claims 1 to 71, or a pharmaceutically acceptable salt thereof, and pharmaceutically acceptable diluent or carrier.

73. 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 any one of Claims 1 to 71, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to Claim 72.

74. The method of Claim 73, wherein the neurological disorder is selected from the group consisting of Down Syndrome, Alzheimer’s disease, and Alzheimer’s disease associated with Down Syndrome.

75. The method of Claim 73 or 74, wherein the neurological disorder is selected Alzheimer’s disease associated with Down syndrome.

76. A method for treating a metabolic disorder in a subject in need thereof, the methodcomprising administering to the subject a therapeutically effective amount of a compound of any one of Claims 1 to 71, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to Claim 72.

77. The method of claim 76, wherein the metabolic disorder is diabetes.

78. A method for treating a cardiovascular 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 71, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to Claim 72.

79. 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 71, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to Claim 72.

80. 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 1-71, or a pharmaceutically acceptable salt thereof.

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