Covalent Modifiers of AKT1 and Uses Thereof

Abstract

Provided herein are covalent modifiers of AKT1 of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), and pharmaceutical compositions thereof. In some embodiments, the present disclosure provides methods of modulating AKT1 using a compound of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B) or salts thereof, and pharmaceutical compositions thereof.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 486,884, filed February 24, 2023, U.S. Provisional Patent Application No. 63 / 506,224, filed June 5, 2023, and U.S. Provisional Patent Application No. 63 / 618,164, filed January 5, 2024, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] The AKT or protein kinase B (PKB) family of serine / threonine protein kinases consists of three highly homologous members: AKT1, AKT2, and AKT3. The AKT family of proteins participates in signaling pathways that regulate cellular processes, including apoptosis, proliferation, differentiation, and metabolism. The most frequently dysregulated signaling pathway in human cancer is the AKT1 pathway. Increased activation of all isoforms may contribute to tumor initiation and progression, as demonstrated in breast, ovarian, pancreatic, and prostate cancers, among others (Song et al., 2019). In cancer cells, AKT1 is involved in proliferation and growth, promoting tumorigenesis and suppressing apoptosis, while AKT2 regulates cytoskeletal dynamics, favoring local tissue invasion and metastasis. The role of AKT3 hyperactivation in cancer has been hypothesized to involve potential stimulation of cell proliferation (Hinz et al., Cell Commun Signal 2019, 17(1), 154; Pascual et al., Ann. Oncol. 2019, 30(7), 1051–1060). Expression of these AKT family members is altered in many human malignancies, including gastric, breast, prostate, ovarian, and pancreatic cancers. Mutations in AKT family members are rare, but the most common mutation is AKT1 E17K, which has been reported in 6–8% of human breast cancers, 2–6% of colorectal cancers, and 6% of meningiomas (Yu et al., PLoS One 2015, 10(10), No. e0140479). Therefore, there is a need to develop novel therapeutics to modulate AKT1 and its mutants. Summary of the Invention

[0003] In one aspect, the present disclosure provides a compound of formula (A):

[0004] [ka] or a pharmaceutically acceptable salt thereof, wherein R 1 teeth, Hydrogen, halogen, -OR 10 , -SR10 , -N(R 10 )2, -C(O)N(R 10 )2, -N(R 10 )C(O)R 10 , -C(O)OR 10 , -OC(O)R 10 , -N(R 10 )C(O)OR 10 , -OC(O)N(R 10 )2, -N(R 10 )C(O)N(R 10 )2, -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, -NO2, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -N(R 10 )C(O)R 10 , -C(O)OR 10 , -OC(O)R 10 , -N(R 10 )C(O)OR 10 , -OC(O)N(R 10 )2, -N(R 10 )C(O)N(R 10 )2, -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 ) optionally substituted with one or more substituents selected from -N, -NO, and -CN; and 3-6 membered heterocycles and C 3-6 Carbocyclic rings (any of which may independently be halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10)2, -N(R 10 )C(O)R 10 , -C(O)OR 10 , -OC(O)R 10 , -N(R 10 )C(O)OR 10 , -OC(O)N(R 10 )2, -N(R 10 )C(O)N(R 10 )2, -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, =O, -NO2, -CN, C 1-6 Alkyl, and C 1-6 haloalkyl) is selected from A 1 and A 2 are each independently Hydrogen, halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11)2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (one of which is independently halogen, -OR 11, -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN; q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2, and 3; R 2 are independently halogens in each example, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -NO2, and -CN; R 3 Independently, in each example Halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -NO2, and -CN, and Independently halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -NO2, =O, =S, =N(R 13 ), and —CN, optionally substituted with one or more substituents selected from 1-6 Alkyl is selected from p is selected from 0, 1, 2, 3, 4, and 5; R 4 Independently, in each example Halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl (one of which is independently halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, =O, =S, =N(R 14 ), and —CN), Selected from, or Two Rs bonded to the same atom 4 are united, =O, =S, and =N(R 14 ) or forming a group selected from Two Rs attached to the same atom or adjacent atoms 4 together with the carbon to which they are attached form a 3- to 8-membered heterocyclic ring and C 3-8 Carbocyclic rings (any of which may independently contain halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14) optionally substituted with one or more substituents selected from -NO2, -CN, L is a bond or -L 1 -L 2 -L 3 -L 4 wherein L 1 , L 2 , L 3 , and L 4 are each independently (a) and (b) (a) -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15 )N(R 15 )-, and (b)C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 3-8 Carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, -OR 15 , -SR 15 , ═O, ═S, and —CN) is selected from L 2 , L 3 , and L 4 are each optionally absent, L 1 , L 2 , L 3 , and L4 At most two of are selected from (a), but the two selected are not adjacent; R 5 is a 3- to 12-membered heterocycle and C 3-12 carbocycles, any of which is substituted by -C(O)H or -C(O)D; R 5 Furthermore, independently Halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -N(R 16 )S(O)2N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R16 , -N(R 16 )S(O)2N(R 16 )2, -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), optionally substituted with one or more substituents selected from -CN, and Independently halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -CN, C 1-6 Alkyl, and C 1-6 a 4- to 6-membered heterocycle optionally substituted with one or more substituents selected from haloalkyl and optionally substituted by one or more substituents selected from R 10 , R 11 , R 12 , R 13 , R 14 , and R 15are each independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 haloalkyl; R 16 independently, at each occurrence, hydrogen, C 1-4 Alkyl (C 1-4 Alkyl is independently Halogen, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20 )2, -NO2, and -CN, and C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -SR 20 , -N(R 20 )2, -B(OR 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20 ) optionally substituted with one or more substituents selected from -2, -NO2, and -CN), and C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)N(R 20 )2, -C(O)OR 20 , -OC(O)R 20 , -N(R 20 )C(O)R 20 , -N(R 20 )S(O)2R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -NO2, and -CN), is selected from R 20 independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 The present invention provides a compound, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from a carbocycle and a 3- to 8-membered heterocycle.

[0005] In one aspect, the disclosure provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula (A), (A-1), or (I), or a pharmaceutically acceptable salt thereof.

[0006] In one aspect, the present disclosure provides a method of modulating mutant AKT1 activity, comprising administering to a subject in need of modulation of mutant AKT1 activity a compound of Formula (A), (A-1), or (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the present disclosure comprising a pharmaceutically acceptable excipient and a compound of Formula (A), (A-1), or (I), or a pharmaceutically acceptable salt thereof. In some embodiments, the mutant AKT1 is AKT1 E17K.

[0007] In one aspect, the present disclosure provides a method for selectively modulating the activity of mutant AKT1 over wild-type AKT, comprising administering to a subject in need of modulation of mutant AKT1 activity a compound of Formula (A), (A-1), or (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the present disclosure comprising a pharmaceutically acceptable excipient and a compound of Formula (A), (A-1), or (I), or a pharmaceutically acceptable salt thereof, wherein the wild-type AKT is selected from wild-type AKT1 and wild-type AKT2. In some embodiments, the mutant AKT1 is AKT1 E17K.

[0008] In one aspect, the present disclosure provides a method of treating cancer in a subject in need thereof, comprising administering to the subject a compound of Formula (A), (A-1), or (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the present disclosure comprising a pharmaceutically acceptable excipient and a compound of Formula (A), (A-1), or (I), or a pharmaceutically acceptable salt thereof. In some embodiments, the cancer is selected from breast cancer, colorectal cancer, and meningioma. In some embodiments, the administration modulates the activity of mutant AKT1. In some embodiments, the mutant AKT1 is AKT1 E17K.

[0009] Incorporation by Reference All publications, patents, and patent applications mentioned herein are hereby incorporated by reference for the specific purposes identified herein. DETAILED DESCRIPTION OF THE INVENTION

[0010] The AKT or protein kinase B (PKB) family of serine / threonine protein kinases regulates numerous important cellular functions, including apoptosis, proliferation, differentiation, and metabolism. The AKT family is composed of three highly homologous members, AKT1, AKT2, and AKT3, each of which has a unique tissue distribution and can perform a unique set of biological functions. Abnormal expression and / or activation of all AKT isoforms has been implicated in the development of tumors, including breast, ovarian, pancreatic, and prostate cancers, among others.

[0011] Inhibitors of the AKT protein are being developed for the treatment of cancer, and two major classes of small molecule AKT inhibitors are undergoing clinical trials: allosteric inhibitors and ATP-competitive inhibitors. First, allosteric inhibitors (such as milansertib (ARQ092) and MK-2206) interfere with PH domain-mediated membrane recruitment (the first step in AKT activation) and inhibit AKT kinase activation and AKT phosphorylation. Second, ATP-competitive inhibitors of AKT (such as ipatasertib and capivasertib) bind to the active kinase, displacing the PH domain from the kinase domain to expose the ATP-binding pocket, thus inhibiting ATP binding.

[0012] However, none of these examples covalently bind to the AKT protein, creating a covalent complex (e.g., a reversible covalent complex with a slow dissociation rate). Covalent inhibitors (especially reversible covalent inhibitors) offer several advantages over non-covalent inhibitors, including, but not limited to, increased residence time on the target, increased selectivity for specific isoforms, increased selectivity for mutant targets, and improved pharmacokinetics.

[0013] Provided herein are compounds for modulating (e.g., inhibiting) AKT1 function, as well as methods and compositions for using the disclosed compounds in the treatment of cancer. The disclosure provides compounds having a reversible covalent electrophile that forms a covalent complex between an amine on the AKT1 protein and an electrophile on the compound. In some embodiments, the reversible covalent electrophile is an aldehyde (e.g., an aromatic aldehyde) that forms a reversible covalent bond between an amine on the AKT1 protein (e.g., an amine on a lysine side chain). In some embodiments, the compound selectively inhibits AKT1 protein over AKT2 and / or AKT3 protein (e.g., 2-fold, 5-fold, 10-fold, 50-fold, 100-fold, etc.). In some embodiments, the compound selectively inhibits mutant AKT1 (e.g., E17K AKT1) over wild-type AKT1 protein (e.g., 2-fold, 5-fold, 10-fold, 50-fold, 100-fold, etc.).

[0014] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications mentioned herein are incorporated by reference.

[0015] As used in this specification and claims, the singular forms "a," "an," and "the" include the plural forms unless the context clearly dictates otherwise.

[0016] "Alkyl" consists solely of carbon and hydrogen atoms, without unsaturation, and preferably has 1 to 12 carbon atoms (e.g., C 1-12 Alkyl) refers to a straight or branched hydrocarbon chain monovalent radical. An alkyl is attached to the rest of the molecule by a single bond. The alkyl chain can be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, an alkyl contains 1 to 12 carbon atoms (i.e., C 1-12 In certain embodiments, alkyl contains 1 to 8 carbon atoms (i.e., C 1-8In other embodiments, alkyl contains 1 to 5 carbon atoms (i.e., C 1-5 In other embodiments, alkyl contains 1 to 4 carbon atoms (i.e., C 1-4 In other embodiments, alkyl contains 1 to 3 carbon atoms (i.e., C 1-3 In other embodiments, alkyl contains 1 to 2 carbon atoms (i.e., C 1-2 In other embodiments, alkyl contains 1 carbon atom (i.e., C alkyl). In other embodiments, alkyl contains 5 to 15 carbon atoms (i.e., C 5-15 In other embodiments, the alkyl contains 5 to 8 carbon atoms (i.e., C 5-8 In other embodiments, alkyl contains 2 to 5 carbon atoms (i.e., C 2-5 In other embodiments, alkyl contains 3 to 5 carbon atoms (i.e., C 3-5 For example, an alkyl group may be attached to the remainder of the molecule by a single bond and includes methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl), and the like.

[0017] "Alkenyl" refers to an alkyl group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having 2 to 12 carbon atoms (i.e., C 2-12 Alkenyl) refers to a straight or branched hydrocarbon chain radical group. The alkenyl chain can be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, alkenyl contains 2 to 8 carbon atoms (i.e., C 2-8 In certain embodiments, alkenyl contains 2 to 6 carbon atoms (i.e., C 2-6 In other embodiments, the alkenyl contains 2 to 4 carbon atoms (i.e., C 2-4Alkenyl is attached to the rest of the molecule by a single bond, for example, ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like.

[0018] "Alkynyl" refers to an alkyl group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having 2 to 12 carbon atoms (i.e., C 2-12 Alkynyl refers to a straight or branched hydrocarbon chain radical group. The alkynyl chain can be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, the alkynyl contains 2 to 8 carbon atoms (i.e., C 2-8 In other embodiments, alkynyl contains 2 to 6 carbon atoms (i.e., C 2-6 In other embodiments, alkynyl contains 2 to 4 carbon atoms (i.e., C 2-4 Alkynyl is attached to the rest of the molecule by a single bond and is, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

[0019] "Alkylene" refers to a straight or branched divalent hydrocarbon chain that links the rest of the molecule to a radical group, consists solely of carbon and hydrogen, contains no unsaturation, and preferably has 1 to 12 carbon atoms, e.g., methylene, ethylene, propylene, (methyl)ethylene, butylene, etc. The alkylene chain is attached to the rest of the molecule by a single bond and to the radical group by a single bond. The alkylene chain can be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, the alkylene contains 1 to 10 carbon atoms (i.e., C 1-10 In certain embodiments, the alkylene contains 1 to 8 carbon atoms (i.e., C 1-8 In other embodiments, the alkylene contains 1 to 5 carbon atoms (i.e., C 1-5In other embodiments, the alkylene contains 1 to 4 carbon atoms (i.e., C 1-4 In other embodiments, the alkylene contains 1 to 3 carbon atoms (i.e., C 1-3 In other embodiments, the alkylene contains 1 to 2 carbon atoms (i.e., C 1-2 In other embodiments, the alkylene contains 1 carbon atom (i.e., a C alkylene). In other embodiments, the alkylene contains 5 to 8 carbon atoms (i.e., a C 5-8 In other embodiments, the alkylene contains 2 to 5 carbon atoms (i.e., C 2-5 In other embodiments, the alkylene contains 3 to 5 carbon atoms (i.e., C 3-5 alkylene).

[0020] "Alkenylene" refers to a straight or branched divalent hydrocarbon chain that links the rest of the molecule to a radical group, consists solely of carbon and hydrogen, contains at least one carbon-carbon double bond, and preferably has 2 to 12 carbon atoms. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The alkenylene chain can be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, the alkenylene contains 2 to 10 carbon atoms (i.e., C 2-10 In certain embodiments, the alkenylene contains 2 to 8 carbon atoms (i.e., C 2-8 In other embodiments, the alkenylene contains 2 to 5 carbon atoms (i.e., C 2-5 In other embodiments, the alkenylene contains 2 to 4 carbon atoms (i.e., C 2-4 In other embodiments, the alkenylene contains 2 to 3 carbon atoms (i.e., C 2-3 In other embodiments, the alkenylene contains 2 carbon atoms (i.e., C alkenylene). In other embodiments, the alkenylene contains 5 to 8 carbon atoms (i.e., C 5-8In other embodiments, the alkenylene contains 3 to 5 carbon atoms (i.e., C 3-5 alkenylene).

[0021] "Alkynylene" refers to a straight or branched divalent hydrocarbon chain that links the rest of the molecule to a radical group, consists solely of carbon and hydrogen, contains at least one carbon-carbon triple bond, and preferably has 2 to 12 carbon atoms. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The alkynylene chain can be optionally substituted with one or more substituents, such as those described herein. In certain embodiments, the alkynylene contains 2 to 10 carbon atoms (i.e., C 2-10 In certain embodiments, the alkynylene contains 2 to 8 carbon atoms (i.e., C 2-8 In other embodiments, the alkynylene contains 2 to 5 carbon atoms (i.e., C 2-5 In other embodiments, the alkynylene contains 2 to 4 carbon atoms (i.e., C 2-4 In other embodiments, the alkynylene contains 2 to 3 carbon atoms (i.e., C 2-3 In other embodiments, the alkynylene contains 2 carbon atoms (i.e., C2 alkynylene). In other embodiments, the alkynylene contains 5 to 8 carbon atoms (i.e., C 5-8 In other embodiments, the alkynylene contains 3 to 5 carbon atoms (i.e., C 3-5 alkynylene).

[0022] "C x-y The term "alkyl," when used with a chemical moiety such as alkyl, alkenyl, or alkynyl, is meant to include groups containing x to y carbons in the chain. For example, "C 1-6 The term "alkyl" refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain and branched-chain alkyl groups, containing 1 to 6 carbons. x-yThe term alkylene- refers to an alkylene chain having x to y carbons in the chain. For example, -C 1-6 Alkylene- may be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any one of which may be optionally substituted.

[0023] "C x-y alkenyl" and "C x-y The term "alkynyl" refers to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but which contain at least one double or triple bond respectively. x-y The term alkenylene- refers to an alkenylene chain having x to y carbons in the chain. For example, -C 2-6 Alkenylene- can be selected from ethenylene, propenylene, butenylene, pentenylene, and hexenylene, any one of which can be optionally substituted. The alkenylene chain can have one double bond or more than one double bond in the alkenylene chain. -C x-y The term alkynylene- refers to an alkynylene chain having x to y carbons in the chain. For example, -C 2-6 Alkynylene- can be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, any one of which can be optionally substituted. The alkynylene chain can have one triple bond or more than one triple bond along the alkynylene chain.

[0024] As used herein, the term "carbocycle" refers to a saturated, unsaturated, or aromatic ring in which each atom of the ring is carbon. Carbocycles include 3- to 10-membered monocyclic rings and polycyclic rings (e.g., 6- to 12-membered bicyclic rings). Each ring of a polycyclic carbocycle can be selected from saturated, unsaturated, and aromatic rings. Polycyclic carbocycles can be fused, bridged, or spiro ring systems. Each ring of a bicyclic carbocycle can be selected from saturated, unsaturated, and aromatic rings. Bicyclic carbocycles can be fused, bridged, or spiro ring systems. In some embodiments, a carbocycle is aryl. In some embodiments, a carbocycle is cycloalkyl. In some embodiments, a carbocycle is cycloalkenyl. In exemplary embodiments, an aromatic ring, such as phenyl, can be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. All combinations of saturated, unsaturated, and aromatic bicyclic rings are included in the definition of carbocycle, as long as valences permit. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. The carbocycle can be optionally substituted with one or more substituents, such as those described herein.

[0025] As used herein, the term "carbocyclene" refers to a divalent saturated, unsaturated, or aromatic ring in which each atom of the ring is carbon. The carbocyclene is attached to the rest of the molecule by a single bond and to the radical group by a single bond. The carbocyclene can be optionally substituted with one or more substituents, such as those described herein. Carbocyclenes include 3- to 10-membered monocyclic rings and divalent polycyclic rings (e.g., 6- to 12-membered bicyclic rings). Each ring of a polycyclic carbocyclene can be selected from saturated, unsaturated, and aromatic rings. Polycyclic carbocyclenes can be fused, bridged, or spiro ring systems. Polycyclic carbocyclenes can be fused, bridged, or spiro ring systems. The single bond connecting the carbocyclene to the rest of the molecule and the single bond connecting the carbocyclene to the radical group can be located in the same ring or different rings of the polycyclic carbocyclene. In some embodiments, the carbocycle is an arylene, such as phenylene. As used herein, "phenylene" refers to a divalent benzene group. The phenylene is bonded to the rest of the molecule by a single bond and to the radical group by a single bond. The phenylene can be optionally substituted with one or more substituents, such as those described herein.

[0026] "Cycloalkyl" refers to a group consisting solely of carbon and hydrogen atoms, including fused, bridged, or spiro ring systems, and preferably having from 3 to 12 carbon atoms (i.e., C 3-12 Cycloalkyl) refers to a stable, fully saturated, monocyclic or polycyclic hydrocarbon radical. In certain embodiments, cycloalkyl contains 3 to 10 carbon atoms (i.e., C 3-10 In other embodiments, the cycloalkyl contains 5 to 7 carbon atoms (i.e., C 5-7Cycloalkyl). A cycloalkyl can be attached to the remainder of the molecule by a single bond. Examples of monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. A cycloalkyl can be optionally substituted with one or more substituents, such as those described herein.

[0027] "Cycloalkenyl" refers to a group consisting solely of carbon and hydrogen atoms, including fused or bridged ring systems, preferably having from 3 to 12 carbon atoms and containing at least one double bond (i.e., "C3-C 12 "cycloalkyl" refers to a stable, unsaturated, non-aromatic, monocyclic or polycyclic hydrocarbon radical. In certain embodiments, cycloalkenyl contains 3 to 10 carbon atoms (i.e., C 3-10 In other embodiments, the cycloalkenyl contains 5 to 7 carbon atoms (i.e., C 5-7 Cycloalkenyl). The cycloalkenyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. The cycloalkenyl may be optionally substituted with one or more substituents, such as those described herein.

[0028] "Aryl" refers to a radical derived from an aromatic monocyclic or aromatic polycyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or aromatic polycyclic hydrocarbon ring system contains only hydrogen and carbon atoms of 5 to 18 carbon atoms, and at least one ring in the ring system is aromatic, i.e., contains a cyclic delocalized (4n+2) π-electron system according to Hückel's theory. Ring systems from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene. An aryl can be optionally substituted with one or more substituents, such as those described herein.

[0029] "C x-y "Carbocyclic" means a group containing x to y carbons in the ring. For example, "C 3-6 The term "carbocycle" may be a saturated, unsaturated, or aromatic ring system containing 3 to 6 carbon atoms, any one of which may be optionally substituted as provided herein.

[0030] As used herein, the term "heterocycle" refers to a saturated, unsaturated, non-aromatic, or aromatic ring containing one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3- to 10-membered monocyclic rings and polycyclic rings (e.g., 6- to 12-membered bicyclic rings). Polycyclic heterocycles can be fused, bridged, or spiro ring systems. Each ring in a polycyclic heterocycle can be selected from saturated, unsaturated, and aromatic rings. In some embodiments, a heterocycle contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, a heterocycle contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, a heterocycle contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, a heterocycle contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. In some embodiments, a heterocycle contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. A heterocycle may be attached to the remainder of the molecule through any atom of the heterocycle, such as a carbon atom or nitrogen atom of the heterocycle, if valence allows. In some embodiments, the heterocycle is heteroaryl. In some embodiments, the heterocycle is heterocycloalkyl. Exemplary heterocycles include pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiophenyl, oxazolyl, thiazolyl, morpholinyl, indazolyl, indolyl, and quinolinyl. A heterocycle may be optionally substituted with one or more substituents, such as those described herein. Bicyclic heterocycles may be fused, bridged, or spiro ring systems. In exemplary embodiments, a heterocycle, such as pyridyl, may be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. A heterocycle may be optionally substituted with one or more substituents, such as those described herein.

[0031] As used herein, the term "heterocyclene" refers to a divalent saturated, unsaturated, non-aromatic, or aromatic ring containing one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. A heterocyclene is attached to the remainder of the molecule and to the radical group by a single bond. The single bond connecting the heterocyclene group to the remainder of the molecule and the single bond connecting the heterocyclene group to the radical group may each independently be connected by a carbon atom in the heterocyclene ring or by any atom in the heterocyclene containing a heteroatom in the heterocyclene ring, as valence permits. A heterocyclene may be optionally substituted with one or more substituents, such as those described herein. Heterocyclenes include 3- to 10-membered monocyclic rings and polycyclic rings (e.g., 6- to 12-membered bicyclic rings). Each ring in a polycyclic heterocyclene may be selected from saturated, unsaturated, and aromatic rings. Polycyclic heterocyclenes can be fused, bridged, or spirocyclic ring systems. The single bond connecting the heterocyclene to the rest of the molecule and the single bond connecting the heterocyclene to the radical group may be located on the same ring or different rings of the polycyclic heterocyclene, and, if valence allows, may be attached to the rest of the molecule or the radical group through any atom of the heterocyclene, such as a carbon or nitrogen atom of the heterocyclene. In some embodiments, the heterocyclene contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocyclene contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocyclene contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heterocyclene contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocyclene is a heteroarylene. In some embodiments, the heterocyclene is a heterocycloalkylene.

[0032] "Heterocycloalkyl" refers to a stable 3- to 12-membered non-aromatic ring radical containing 2 to 12 carbon atoms and at least one heteroatom, where each heteroatom may be selected from N, O, Si, P, B, and S atoms. In some embodiments, a heterocycloalkyl contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, a heterocycloalkyl contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, a heterocycloalkyl contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, a heterocycloalkyl contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. Heterocycloalkyls may be selected from monocyclic or bicyclic ring systems, and fused, bridged, or spirocyclic ring systems. The heteroatoms in a heterocycloalkyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. A heterocycloalkyl radical is partially or fully saturated. The heterocycloalkyl is attached to the remainder of the molecule by any atom of the heterocycloalkyl, including any carbon or nitrogen atom of the heterocycloalkyl, if valence allows. Examples of heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxothiomorpholinyl, and 1,1-dioxothiomorpholinyl. Heterocycloalkyl can be optionally substituted with one or more substituents, such as those described herein.

[0033] The term "heteroaryl" refers to a radical derived from a 5- to 12-membered aromatic ring radical having a ring structure containing at least one heteroatom, preferably between 1 and 4 heteroatoms. In some embodiments, a heteroaryl contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, a heteroaryl contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, a heteroaryl contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, a heteroaryl contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. As used herein, heteroaryl rings may be selected from monocyclic or bicyclic, fused or bridged ring systems, in which at least one of the rings in the ring system is aromatic, i.e., contains a cyclic delocalized (4n+2) p-electron system according to Hückel theory. The heteroatoms in a heteroaryl radical can be optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. Heteroaryls can be attached to the remainder of the molecule through any atom of the heteroaryl, such as a carbon or nitrogen atom of the heteroaryl, if valence allows. Heteroaryls include aromatic monocyclic ring structures, preferably 5-6 membered rings, whose ring structures contain at least one heteroatom, preferably 1-4 heteroatoms, and more preferably 1 or 2 heteroatoms. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine. Heteroaryls can be optionally substituted with one or more substituents, such as those described herein. Heteroaryls also include polycyclic ring systems having two or more rings, in which two or more atoms are common to two adjacent rings, and at least one of the rings is heteroaromatic; for example, the other ring can be aromatic or non-aromatic, carbocyclic, or heterocyclic. Heteroaryls can be optionally substituted with one or more substituents, such as those described herein.

[0034] An "X-membered heterocycle" refers to the number of ring atoms in the ring, i.e., X. For example, a 5-membered heteroaryl ring or a 5-membered heteroaromatic ring has 5 ring atoms, such as triazole, oxazole, thiophene, etc.

[0035] "Alkoxy" refers to a radical attached through an oxygen atom of the formula --O-alkyl, where alkyl is an alkyl chain as defined above.

[0036] "Halo" or "halogen" refers to halogen substituents such as bromo, chloro, fluoro, and iodo substituents.

[0037] As used herein, the term "haloalkyl" or "haloalkane" refers to an alkyl radical, as defined above, that is substituted with one or more halogen radicals, such as trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc. In some embodiments, the alkyl portion of the fluoroalkyl radical is optionally further substituted. Examples of halogen-substituted alkanes ("haloalkanes") include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), ditrihalomethanes and trihalomethanes (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethanes, 2-haloethanes, 1,2-dihaloethanes, 1-halopropanes, 2-halopropanes, 3-halopropanes, 1,2-dihalopropanes, 1,3-dihalopropanes, 2,3-dihalopropanes, 1,2,3-trihalopropanes, and any other suitable combination of alkanes (or substituted alkanes) and halogens (e.g., Cl, Br, F, and I). When an alkyl group is substituted with more than one halogen radical, each halogen can be independently selected from, for example, 1-chloro, 2-fluoroethane.

[0038] The term "adjacent" refers to the connectivity of the moieties, which are defined as adjacent moieties covalently attached or bonded to another atom. For example, -L 1 -L 2 -L 3 -L 4 -, L 1 , and L 2 is adjacent, and L 2 and L 3 is adjacent, and L 3 and L 4 are adjacent, or

[0039] [ka] wherein C 1 and C 2 Adjacent substituents are, for example, R w1 and R w2 is the adjacent substituent CH2R w1 CH2R w2 refers to a substituent bonded to a different atom where the two atoms are covalently bonded.

[0040] The term "substituted" refers to moieties having substituents replacing hydrogen on one or more carbon or substitutable heteroatoms, such as the NH or NH of a compound. Unless otherwise specified (e.g., by use of the terms "substituted" or "optionally substituted" or by inclusion of "-R"), chemical groups described herein are not substituted. It is understood that "substituted" or "substituted with" includes the implicit proviso that such substitution is subject to the permissible valences of the substituted atom and substituent, and that the substitution results in a stable compound, i.e., a compound that does not spontaneously undergo transformation, such as rearrangement, cyclization, or excretion. In certain embodiments, substituted refers to moieties having substituents replacing two hydrogen atoms on the same carbon atom, such as replacing two hydrogen atoms on a single carbon with an oxo, imino, or thioxo group. As used herein, the term "substituted" is intended to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, and aromatic and aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds.

[0041] In some embodiments, a substituent may be any substituent described herein, for example, halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO), imino (=NH), oximo (=N-OH), hydrazino (=N-NH), -R b -OR a , -R b -OC(O)R a , -R b -OC(O)OR a , -R b -OC(O)N(R a )2, -R b -N(R a )2, -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b-OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 0, 1, or 2), -R b -S(O) t OR a (t is 1 or 2), -R b -S(O) t N(R a )2 (t is 1 or 2), and P(O)(R a )2, and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroaralkyl, any one of which may be alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oximo (=N-OH), hydrazine (=N-NH2), -R b -OR a , -R b -OC(O)R a , -R b -OC(O)OR a , -R b -OC(O)N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -ORc -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 0, 1, or 2), -R b -S(O) t OR a (t is 1 or 2), -R b -S(O) t N(R a )2 (t is 1 or 2), and -P(O)(R a )2, and R a are each independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl; R a are each, when valence allows, alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oximo (=N-OH), hydrazine (=N-NH2), -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a)2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (t is 1 or 2), -R b -S(O) t R a (t is 0, 1, or 2), -R b -S(O) t OR a (t is 1 or 2), -R b -S(O) t N(R a )2 (t is 1 or 2), and -P(O)(R a )2, and R b are each independently selected from a direct bond or a straight or branched alkylene, alkenylene, or alkynylene chain; R c are respectively straight or branched alkylene, alkenylene, or alkynylene chains. Those skilled in the art will recognize that the substituents themselves may be substituted, if appropriate.

[0042] The term "salt" or "pharmaceutically acceptable salt" refers to salts derived from a variety of organic and inorganic counterions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic and organic acids. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases.

[0043] The phrase "pharmaceutically acceptable" is used herein to refer to compounds, materials, compositions, and / or dosage forms that are, within the bounds of sound medical good sense, suitable for use in contact with the tissues of human beings and animals without undue toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit-risk ratio.

[0044] As used herein, the phrase "pharmaceutically acceptable excipient" or "pharmaceutically acceptable carrier" means a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient.

[0045] The terms "subject," "individual," and "patient" are used interchangeably and can refer to humans as well as non-human mammals (e.g., non-human primates, dogs, horses, cats, pigs, cows, ungulates, rabbits, etc.). In various embodiments, a subject can be a human (e.g., an adult male, adult female, adolescent male, adolescent female, boy, girl) receiving care from a physician or other health worker while hospitalized as an outpatient or in other clinical settings. In certain embodiments, a subject may not be receiving care from or prescribed by a physician or other health worker.

[0046] As used herein, "a subject in need thereof" refers to a subject, as described below, suffering from or at risk for a condition to be treated prophylactically or therapeutically with a compound or salt described herein.

[0047] The terms "administer," "administered," "administers," and "administering" are defined as providing a composition to a subject via a route known in the art, including, but not limited to, intravenous, intraarterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal routes of administration. In certain embodiments, the oral route of administering the composition can be used. The terms "administer," "administered," "administers," and "administering" should be understood to mean providing a compound of the invention or a prodrug of a compound or salt of the invention to an individual in need thereof.

[0048] As used herein, "treatment" or "treating" refers to an approach for obtaining a beneficial or desired result with respect to a disease, disorder, or condition, including, but not limited to, a therapeutic benefit and / or a preventative benefit. In certain embodiments, treating or treating includes administering a compound or composition disclosed herein to a subject. A "therapeutic benefit" can include eradication or amelioration of the underlying disorder being treated. A therapeutic benefit can also be achieved by eradicating or alleviating one or more physiological symptoms associated with the underlying disease, such as observing an improvement in a subject, even though the subject may still suffer from the underlying disease. In certain embodiments, for preventative benefit, a composition is administered to a subject who is at risk of developing a particular disease or who reports one or more physiological symptoms of the disease, even if the disease has not been diagnosed. Treating can include, for example, reducing, delaying, or alleviating one or more symptoms of a disease or condition, or can include reducing the frequency with which a patient experiences a disease, disorder, disorder, or adverse condition. Treating can be used herein to refer to a method of bringing about some level of treatment or amelioration of a disease or disorder, and can contemplate a range of end results, including, but not limited to, prevention of the disease altogether.

[0049] In certain embodiments, the terms "prevent" or "preventing" in relation to a disease or disorder may refer to a compound that, in a statistical sample, reduces the occurrence of the disorder or disease in a treated sample relative to an untreated control sample, or delays the onset of or reduces the severity of one or more symptoms of the disorder or disease relative to an untreated control sample.

[0050] A "therapeutic effect," as that term is used herein, encompasses the therapeutic and / or prophylactic benefits described above. A prophylactic effect includes delaying or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof.

[0051] compound In one aspect, the present disclosure provides a compound of formula (A):

[0052] [ka] or a pharmaceutically acceptable salt thereof, During the ceremony, R 1 teeth, Hydrogen, halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -N(R 10 )C(O)R 10 , -C(O)OR 10 , -OC(O)R 10 , -N(R 10 )C(O)OR 10 , -OC(O)N(R 10 )2, -N(R 10 )C(O)N(R 10 )2, -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, -NO2, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -N(R 10 )C(O)R 10, -C(O)OR 10 , -OC(O)R 10 , -N(R 10 )C(O)OR 10 , -OC(O)N(R 10 )2, -N(R 10 )C(O)N(R 10 )2, -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 ) optionally substituted with one or more substituents selected from -N, -NO, and -CN; and 3-6 membered heterocycles and C 3-6 Carbocyclic rings (any of which may independently be halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -N(R 10 )C(O)R 10 , -C(O)OR 10 , -OC(O)R 10 , -N(R 10 )C(O)OR 10 , -OC(O)N(R 10 )2, -N(R 10 )C(O)N(R 10 )2, -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, =O, -NO2, -CN, C 1-6 Alkyl, and C 1-6 haloalkyl) is selected from A 1 and A 2 are each independently Hydrogen, halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11)C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and —CN) is selected from q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2, and 3; R 2 are independently halogens in each example, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -NO2, and -CN; R 3 Independently, in each example Halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13, -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -NO2, and -CN, and Independently halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -NO2, =O, =S, =N(R 13 ), and —CN, optionally substituted with one or more substituents selected from 1-6 Alkyl is selected from p is selected from 0, 1, 2, 3, 4, and 5; R 4 Independently, in each example Halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl (one of which is independently halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, =O, =S, =N(R14 ), and —CN), Selected from, or Two Rs bonded to the same atom 4 are united, =O, =S, and =N(R 14 ) or forming a group selected from Two Rs attached to the same atom or adjacent atoms 4 together with the carbon to which they are attached form a 3- to 8-membered heterocyclic ring and C 3-8 Carbocyclic rings (any of which may independently contain halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 ) optionally substituted with one or more substituents selected from -NO2, -CN, L is a bond or -L 1 -L 2 -L 3 -L 4 wherein L 1 , L 2 , L 3 , and L 4 are each independently (a) and (b) (a) -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15)N(R 15 )-, and (b)C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 3-8 Carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, -OR 15 , -SR 15 , ═O, ═S, and —CN) is selected from L 2 , L 3 , and L 4 are each optionally absent, L 1 , L 2 , L 3 , and L 4 At most two of are selected from (a), but the two selected are not adjacent; R 5 is a 3- to 12-membered heterocycle and C 3-12 carbocycles, any of which is substituted by -C(O)H or -C(O)D; R 5 Furthermore, independently Halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -N(R 16 )S(O)2N(R 16)2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )S(O)2N(R 16 )2, -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), optionally substituted with one or more substituents selected from -CN, and Independently halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16)C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -CN, C 1-6 Alkyl, and C 1-6 a 4- to 6-membered heterocycle optionally substituted with one or more substituents selected from haloalkyl and optionally substituted by one or more substituents selected from R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 are each independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 haloalkyl; R 16 independently, at each occurrence, hydrogen, C 1-4 Alkyl (C 1-4 Alkyl is independently Halogen, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R20 )2, -NO2, and -CN, and C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -SR 20 , -N(R 20 )2, -B(OR 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20 ) optionally substituted with one or more substituents selected from -2, -NO2, and -CN), and C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)N(R 20 )2, -C(O)OR 20 , -OC(O)R 20 , -N(R 20 )C(O)R 20 , -N(R 20 )S(O)2R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -NO2, and -CN), is selected from R 20 independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 The present invention provides a compound, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from a carbocycle and a 3- to 8-membered heterocycle.

[0053] In some embodiments, with respect to the compound or salt of Formula (A), R 1 is hydrogen, halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -N(R 10 )C(O)R 10 , -C(O)OR 10 , -OC(O)R 10 , -N(R 10 )C(O)OR 10 , -OC(O)N(R 10 )2, -N(R 10 )C(O)N(R 10 )2, -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, —NO2, and —CN. In some embodiments, R 1 is hydrogen, halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -C(O)OR 10 , -OC(O)R 10 , -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10, -S(O)2N(R 10 )2, —NO2, and —CN. In some embodiments, R 1 is hydrogen, halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -C(O)OR 10 , -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, —NO2, and —CN. In some embodiments, R 1 is hydrogen, halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, —NO2, and —CN. In some embodiments, R 1 is hydrogen, halogen, -OR 10 , -N(R 10 )2, -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, and -CN. In some embodiments, R 1 is hydrogen, fluoro, chloro, -OR 10 , -N(R 10 )2, -N(R 10 )S(O)2R 10 , and -S(O)N(R 10 In some embodiments, R 1 is hydrogen, fluoro, chloro, -N(R 10 )2, -N(R 10 )S(O)2R 10 , and -S(O)N(R 10 In some embodiments, R1 is hydrogen, fluoro, chloro, -N(R 10 )2, and -N(R 10 )S(O)2R 10 In some embodiments, R 1 is hydrogen, -N(R 10 )2, and -N(R 10 )S(O)2R 10 In some embodiments, R 1 is -N(R 10 )S(O)2R 10 In some embodiments, R 1 teeth,

[0054] [ka] In some embodiments, R 1 teeth,

[0055] [ka] is.

[0056] In some embodiments, with respect to the compound or salt of Formula (A), R 1 is C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 alkynyl, any of which may be independently selected from halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -N(R 10 )C(O)R 10 , -C(O)OR 10 , -OC(O)R 10 , -N(R 10 )C(O)OR 10 , -OC(O)N(R 10 )2, -N(R 10 )C(O)N(R 10 )2, -S(O)R 10 , -S(O)2R 10 , -N(R 10)S(O)2R 10 , -S(O)2N(R 10 )2, —NO2, and —CN. In some embodiments, R 1 is C 1-6 Alkyl and C 2-6 alkynyl, any of which may be independently selected from halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -N(R 10 )C(O)R 10 , -C(O)OR 10 , -OC(O)R 10 , -N(R 10 )C(O)OR 10 , -OC(O)N(R 10 )2, -N(R 10 )C(O)N(R 10 )2, -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, —NO2, and —CN. In some embodiments, R 1 is C 1-6 Alkyl and C 2-6 alkynyl, any of which may be independently selected from halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -C(O)OR 10 , -OC(O)R 10 , -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, —NO2, and —CN. In some embodiments, R 1 is C 1-6 Alkyl and C2-6 alkynyl, any of which may be independently selected from halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -C(O)OR 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, —NO2, and —CN. In some embodiments, R 1 is C 1-6 Alkyl and C 2-6 alkynyl, any of which may be independently selected from halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -C(O)OR 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, —NO2, and —CN. In some embodiments, R 1 is C 1-4 Alkyl and C 2-4 alkynyl, any of which may be independently selected from halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -C(O)OR 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, —NO2, and —CN. In some embodiments, R 1 is C 1-6 Alkyl and C 2-6alkynyl, any of which may be independently selected from halogen, -OR 10 , -SR 10 , -N(R 10 )2, -N(R 10 )S(O)2R 10 , —NO, and —CN. In some embodiments, R 1 is C 1-6 Alkyl and C 2-6 alkynyl, each of which is independently selected from halogen, -OR 10 , -SR 10 , -N(R 10 )2, -NO2, and -CN. 1 is C 1-6 Alkyl and C 2-6 alkynyl, each of which is independently selected from halogen, -OR 10 , -SR 10 , and -N(R 10 ) optionally substituted with one or more substituents independently selected from any of the following: 1 is C 1-6 Alkyl and C 2-6 alkynyl, each of which is independently selected from fluoro, chloro, -OR 10 , and -N(R 10 ) optionally substituted with one or more substituents independently selected from any of the following: 1 is C 1-6 Alkyl and C 2-6 alkynyl, each of which is independently selected from fluoro, -OR 10 , and -N(R 10) optionally substituted with one or more substituents independently selected from any of the following: 1 is C 1-6 Alkyl and C 2-6 alkynyl, each of which is independently selected from -OR 10 and -N(R 10 ) optionally substituted with one or more substituents independently selected from any of the following: 1 is C 1-6 Alkyl and C 2-6 alkynyl, each of which is independently selected from -OR 10 In some embodiments, R is optionally substituted with one or more substituents independently selected from any of the following: 1 is C 1-4 Alkyl and C 2-4 alkynyl, each of which is independently selected from -OR 10 In some embodiments, R is optionally substituted with one or more substituents independently selected from any of the following: 1 is C 1-6 Alkyl and C 2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from any of -OCH, -OCHCH, -OCH(CH), -OCHCHCH, -OCHCHCH, -OCH(CH)CH, -OCHCH(CH)CH, -OC(CH), and -OPh. 1 is C 1-6 Alkyl and C 2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from any of -OCH, -OCHCH, -OCH(CH), and -OC(CH). In some embodiments, R 1 is C 1-6 Alkyl and C 2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from any of -OCH3. 1 teeth,

[0057] [ka] In some embodiments, R 1 teeth,

[0058] [ka] In some embodiments, R 1 is C 1-6 Alkyl and C 2-6 In some embodiments, R is selected from alkynyl. 1 is C 1-6 In some embodiments, R 1 is C 2-6 In some embodiments, R is selected from alkynyl. 1 teeth,

[0059] [ka] is.

[0060] In some embodiments, with respect to the compound or salt of Formula (A), R 1 is C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6In some embodiments, R is selected from alkynyl. 1 is C 1-6 Alkyl and C 2-6 In some embodiments, R is selected from alkynyl. 1 is C 1-6 Alkyl and C 2-6 In some embodiments, R is selected from alkynyl. 1 is C 1-6 Alkyl and C 2-6 In some embodiments, R is selected from alkynyl. 1 is C 1-6 In some embodiments, R 1 is C 2-6 alkynyl.

[0061] In some embodiments, with respect to the compound or salt of Formula (A), R 1 is a 3- to 6-membered heterocycle and C 3-6 carbocyclic rings, any of which may independently be halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -N(R 10 )C(O)R 10 , -C(O)OR 10 , -OC(O)R 10 , -N(R 10 )C(O)OR 10 , -OC(O)N(R 10 )2, -N(R 10 )C(O)N(R 10 )2, -S(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, =O, -NO2, -CN, C 1-6 Alkyl, and C 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 1 is a 3- to 6-membered heterocycle and C 3-6carbocyclic rings, any of which may independently be halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)N(R 10 )2, -C(O)OR 10 , -OC(O)R 10 , -S(O)2R 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, =O, -NO2, -CN, C 1-6 Alkyl, and C 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 1 is a 3- to 6-membered heterocycle and C 3-6 carbocyclic rings, any of which may independently be halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)OR 10 , -N(R 10 )S(O)2R 10 , -S(O)2N(R 10 )2, =O, -NO2, -CN, C 1-6 Alkyl, and C 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 1 is a 3- to 6-membered heterocycle and C 3-6 carbocyclic rings, any of which may independently be halogen, -OR 10 , -SR 10 , -N(R 10 )2, -C(O)OR 10 , =O, -NO2, -CN, C 1-6 Alkyl, and C 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 1 is a 3- to 6-membered heterocycle and C 3-6 carbocyclic rings, any of which may independently be halogen, -OR 10 , -SR 10 , -N(R 10)2, =O, -NO2, -CN, C 1-6 Alkyl, and C 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 1 is a 3- to 6-membered heterocycle and C 3-6 carbocyclic rings, any of which may independently be halogen, -OR 10 , -N(R 10 )2, =O, C 1-6 Alkyl, and C 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 1 is a 3- to 6-membered heterocycle and C 3-6 carbocyclic rings, any of which may independently be fluoro, chloro, -OR 10 , =O, C 1-6 Alkyl, and C 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 1 is a 3- to 6-membered heterocycle and C 3-6 carbocyclic rings, any of which is independently selected from fluoro, chloro, -OCH3, -OCH2CH3, -OCH(CH3)2, -OC(CH3)3, ═O, C 1-6 Optionally substituted with one or more substituents selected from alkyl, -CHF, -CHF, -CF, and -CFCF. In some embodiments, R 1 is a 4- to 6-membered heterocycle and C 3-5 carbocyclic rings, any of which may independently be halogen, -OR 10 , -SR 10 , -N(R 10 )2, =O, -NO2, -CN, C 1-6 Alkyl, and C 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 1 is selected from a 4- to 6-membered heterocycle, cyclopropyl, and cyclobutyl, any of which is independently selected from halogen, -OR 10 , -SR 10, -N(R 10 )2, =O, -NO2, -CN, C 1-6 Alkyl, and C 1-6 and optionally substituted with one or more substituents selected from haloalkyl.

[0062] In some embodiments, with respect to the compound or salt of Formula (A), R 1 is selected from azetidinyl, imidazolyl, triazolyl, morpholinyl, piperazinyl, and cyclopropyl, any of which is independently selected from halogen, -OR 10 , -SR 10 , -N(R 10 )2, =O, -NO2, -CN, C 1-6 Alkyl, and C 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 1 is selected from azetidinyl, imidazolyl, triazolyl, morpholinyl, piperazinyl, and cyclopropyl, any of which may independently be fluoro, chloro, -OR 10 , -N(R 10 )2, =O, C 1-6 Alkyl, and C 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 1 is selected from azetidinyl, imidazolyl, triazolyl, morpholinyl, piperazinyl, and cyclopropyl, any of which is independently fluoro, chloro, OCH3, -OCH2CH3, -OCH(CH3)2, -OC(CH3)3, =O, C 1-6 Alkyl, and C 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from haloalkyl. 1is selected from azetidinyl, imidazolyl, triazolyl, morpholinyl, piperazinyl, and cyclopropyl, any of which is optionally substituted with one or more substituents independently selected from fluoro, chloro, —OCH, —OCHCH, ═O, —CH, —CHCH, —CH(CH), —CHF, —CHF, —CF, and —CFCF. In some embodiments, R 1 is selected from azetidinyl, imidazolyl, triazolyl, morpholinyl, piperazinyl, and cyclopropyl, any of which is optionally substituted with one or more substituents independently selected from fluoro, ═O, —CH, —CHCH, —CH(CH), —CHF, —CHF, and —CF. In some embodiments, R 1 is selected from azetidinyl, imidazolyl, triazolyl, morpholinyl, piperazinyl, and cyclopropyl, any of which is optionally substituted with one or more substituents independently selected from =O and -CH3.

[0063] In some embodiments, with respect to the compound or salt of Formula (A), R 1 teeth,

[0064] [ka] In some embodiments, R 1 teeth,

[0065] [ka] In some embodiments, R 1 teeth,

[0066] [ka] In some embodiments, R 1 teeth,

[0067] [ka] In some embodiments, R 1 teeth,

[0068] [ka] In some embodiments, R 1 teeth,

[0069] [ka] In some embodiments, R 1 teeth,

[0070] [ka] is selected from.

[0071] In some embodiments, with respect to the compound or salt of Formula (A), R 5 is a 3- to 12-membered heterocycle substituted with —C(O)H or —C(O)D, and R 5 Furthermore, independently Halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -N(R 16 )S(O)2N(R16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )S(O)2N(R 16 )2, -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), optionally substituted with one or more substituents selected from -CN, and Independently halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -CN, C 1-6 Alkyl, and C 1-6 a 4- to 6-membered heterocycle optionally substituted with one or more substituents selected from haloalkyl and optionally substituted with one or more substituents selected from:

[0072] In some embodiments, with respect to the compound or salt of Formula (A), R 5 is a 3- to 12-membered heterocycle substituted with —C(O)H or —C(O)D, and R 5 Furthermore, independently Halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -N(R 16 )S(O)2N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, and C 1-6 Alkyl, C 2-6Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )S(O)2N(R 16 )2, -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), and —CN), and optionally substituted with one or more substituents selected from:

[0073] In some embodiments, with respect to the compound or salt of Formula (A), R 5 is selected from 3- to 8-membered monocyclic heterocycles and 6- to 12-membered bicyclic heterocycles, each of which is substituted with —C(O)H or —C(O)D; R 5 Furthermore, independently Halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -N(R 16 )S(O)2N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )S(O)2N(R 16 )2, -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), optionally substituted with one or more substituents selected from -CN, and Independently halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16)2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -CN, C 1-6 Alkyl, and C 1-6 a 4- to 6-membered heterocycle optionally substituted with one or more substituents selected from haloalkyl and optionally substituted with one or more substituents selected from:

[0074] In some embodiments, with respect to the compound or salt of Formula (A), R 5 is selected from 3- to 8-membered monocyclic heterocycles and 6- to 12-membered bicyclic heterocycles, each of which is substituted with —C(O)H or —C(O)D; R 5 Furthermore, independently Halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16)C(O)OR 16 , -OC(O)N(R 16 )2, -N(R 16 )S(O)2N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )S(O)2N(R 16 )2, -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), and —CN), and optionally substituted with one or more substituents selected from:

[0075] In some embodiments, with respect to the compound or salt of Formula (A), R 5 is selected from 3- to 8-membered monocyclic heterocycles and 6- to 12-membered bicyclic heterocycles, each of which is substituted with —C(O)H or —C(O)D; R 5is further optionally substituted with one or more substituents. In some embodiments, R 5 is selected from 3-8 membered monocyclic heterocycles substituted with -C(O)H or -C(O)D, and R 5 is further optionally substituted with one or more substituents. In some embodiments, R 5 is selected from 6-12 membered bicyclic heterocycles substituted with -C(O)H or -C(O)D, and R 5 is further optionally substituted with one or more substituents.

[0076] In some embodiments, with respect to the compound or salt of Formula (A), R 5 are 6- to 12-membered bicyclic heterocycles each substituted with -C(O)H or -C(O)D, and R 5 Furthermore, independently Halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -N(R 16 )S(O)2N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6Alkynyl (any of which may independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )S(O)2N(R 16 )2, -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), and —CN), and optionally substituted with one or more substituents selected from:

[0077] In some embodiments, with respect to the compound or salt of Formula (A), R 5 are 6- to 12-membered bicyclic heterocycles each substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16)2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -N(R 16 )S(O)2N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, and independently halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -NO2, =O, =S, =N(R 16 ), and —CN, optionally substituted with one or more substituents selected from 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from alkyl. 5 are each a 6- to 12-membered bicyclic heterocycle substituted with —C(O)H or —C(O)D, and R 5 may further independently be halogen, -OR 16 , -N(R 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -NO2, =O, =S, =N(R 16 ), -N3, and -CN, and independently halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -NO2, =O, =S, =N(R 16 ), and —CN, optionally substituted with one or more substituents selected from 1-6alkyl.

[0078] In some embodiments, with respect to the compound or salt of Formula (A), R 5 are 6- to 12-membered bicyclic heterocycles each substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, -OR 16 , -N(R 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -NO2, =O, =S, =N(R 16 ), -N3, and -CN, and independently halogen, -OR 16 , -N(R 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -NO2, =O, =S, =N(R 16 ), and —CN, optionally substituted with one or more substituents selected from 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from alkyl. 5 are 6- to 12-membered bicyclic heterocycles each substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, -OR 16 , -N(R 16 )2, =O, =S, =N(R 16 ), and -CN, and independently a halogen, -OR 16 , -N(R 16 )2, and —CN, optionally substituted with one or more substituents selected from 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from alkyl. 5 are 6- to 12-membered bicyclic heterocycles each substituted with -C(O)H or -C(O)D, and R5 may further independently be halogen, -OR 16 , -N(R 16 )2, and =O, and independently halogen and -OR 16 C optionally substituted with one or more substituents selected from 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from alkyl. 5 are 6- to 12-membered bicyclic heterocycles each substituted with -C(O)H or -C(O)D, and R 5 is further optionally substituted with one or more substituents independently selected from fluoro, chloro, and ═O, and fluoro. 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from alkyl. 5 are 6- to 12-membered bicyclic heterocycles each substituted with -C(O)H or -C(O)D, and R 5 may further independently be ═O and C 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from alkyl. 5 are 6- to 12-membered bicyclic heterocycles each substituted with -C(O)H or -C(O)D, and R 5 is further optionally substituted with one or more substituents independently selected from: ═O.

[0079] In some embodiments, with respect to the compound or salt of Formula (A), R 5 teeth,

[0080] [ka] is.

[0081] In some embodiments, with respect to the compound or salt of Formula (A), L is a bond and R 5 teeth,

[0082] [ka] In some embodiments, L is a bond and R 5 teeth,

[0083] [ka] In some embodiments, L is a bond and R 5 teeth,

[0084] [ka] In some embodiments, L is a bond and R 5 teeth,

[0085] [ka] In some embodiments, L is a bond and R 5 teeth,

[0086] [ka] is selected from.

[0087] In some embodiments, with respect to the compound or salt of Formula (A), R 5 is a 3- to 12-membered heterocycle and C 3-12 carbocycles, any of which is substituted by -C(O)H or -C(O)D; R 5 is further optionally substituted by one or more substituents. In some embodiments, R 5 is a 3- to 8-membered monocyclic heterocycle, a 6- to 12-membered bicyclic heterocycle, and C 3-6 carbocycles, any of which is substituted by -C(O)H or -C(O)D; R 5 is further optionally substituted by one or more substituents. In some embodiments, R 5is selected from 3- to 8-membered monocyclic heterocycles and 6- to 12-membered bicyclic heterocycles, either of which is substituted by —C(O)H or —C(O)D; R 5 is further optionally substituted by one or more substituents. In some embodiments, R 5 is selected from 3-8 membered monocyclic heterocycles substituted with -C(O)H or -C(O)D, and R 5 is further optionally substituted with one or more substituents. In some embodiments, R 5 is selected from 6-12 membered bicyclic heterocycles substituted with -C(O)H or -C(O)D, and R 5 is further optionally substituted with one or more substituents. In some embodiments, R 5 is C substituted with -C(O)H or -C(O)D 3-6 carbocyclic rings, R 5 is further optionally substituted with one or more substituents. In some embodiments, R 5 is selected from phenyl substituted with —C(O)H or —C(O)D, and R 5 is further optionally substituted with one or more substituents.

[0088] In some embodiments, with respect to the compound or salt of Formula (A), R 5 is C substituted with -C(O)H or -C(O)D 3-6 is a carbocyclic ring, and R 5 Furthermore, independently Halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16)C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -N(R 16 )S(O)2N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )S(O)2N(R 16 )2, -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), optionally substituted with one or more substituents selected from -CN, and Independently halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -CN, C 1-6 Alkyl, and C 1-6 a 4- to 6-membered heterocycle optionally substituted with one or more substituents selected from haloalkyl and optionally substituted with one or more substituents selected from:

[0089] In some embodiments, with respect to the compound or salt of Formula (A), R 5 is C substituted with -C(O)H or -C(O)D 3-6 is a carbocyclic ring, and R 5 Furthermore, independently Halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -N(R 16 )S(O)2N(R 16 )2, -S(O)R16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )S(O)2N(R 16 )2, -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), and —CN), and optionally substituted with one or more substituents selected from:

[0090] In some embodiments, with respect to the compound or salt of Formula (A), R 5 is C substituted with -C(O)H or -C(O)D 3-6 is a carbocyclic ring, and R 5 may further independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16)2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -N(R 16 )S(O)2N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, and independently halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )S(O)2N(R 16 )2, -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), and —CN, optionally substituted with one or more substituents selected from 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from alkyl. 5is phenyl substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -N(R 16 )S(O)2N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, and independently halogen, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )S(O)2N(R 16 )2, -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R16 , -NO2, =O, =S, =N(R 16 ), and —CN, optionally substituted with one or more substituents selected from 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from alkyl. 5 is phenyl substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, and -CN, and independently halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -S(O)2N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), and —CN, optionally substituted with one or more substituents selected from 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from alkyl. 5 is phenyl substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -N(R 16 )S(O)2N(R16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), -N3, -CN, and independently halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)R 16 , -NO2, =O, =S, =N(R 16 ), and —CNCl, optionally substituted with one or more substituents selected from 1-6 In some embodiments, R is optionally substituted with one or more substituents selected from alkyl. 5 teeth,

[0091] [ka] In some embodiments, R 5 teeth,

[0092] [ka] In some embodiments, R 5 teeth,

[0093] [ka] is selected from.

[0094] In another embodiment, formula (A) is formula (A-1):

[0095] [ka] or a pharmaceutically acceptable salt thereof, During the ceremony, R 1 is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 10 , -SR 10 , -N(R10 )2, -NO2, and -CN; A 1 and A 2 are each independently Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11), optionally substituted with one or more substituents selected from -CN, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11, -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and —CN) is selected from q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2, and 3; R 2 are independently halogens in each example, C 1-4 Alkyl, C1-4 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -NO2, and -CN; R 3 Independently, in each example Halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -NO2, and -CN, and Independently halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -NO2, =O, =S, =N(R 13 ), and —CN, optionally substituted with one or more substituents selected from 1-6 Alkyl is selected from p is selected from 0, 1, 2, 3, 4, and 5; R 4 Independently, in each example Halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6Alkynyl (one of which is independently halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, =O, =S, =N(R 14 ), and —CN), Selected from, or Two Rs bonded to the same atom 4 are united, =O, =S, and =N(R 14 ) or forming a group selected from Two Rs attached to the same atom or adjacent atoms 4 together with the carbon to which they are attached form a 3- to 8-membered heterocyclic ring and C 3-8 carbocyclic rings, any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 Optionally substituted with one or more substituents selected from —N—C, —NO, and —CN; L is -L 1 -L 2 -L 3 -L 4 wherein L 1 , L 2 , L 3 , and L 4 are each independently (a) and (b) (a) -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15)S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15 )N(R 15 )-, and (b)C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 3-8 Carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, -OR 15 , -SR 15 , ═O, ═S, and —CN) is selected from L 2 , L 3 , and L 4 are each optionally absent, L 1 , L 2 , L 3 , and L 4 At most two of are selected from (a), but the two selected are not adjacent; R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by -C(O)H or -C(O)D; R 5 Furthermore, independently Halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16, -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -NO2, and -CN, optionally substituted with one or more substituents selected from and optionally substituted by one or more substituents selected from R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 are each independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 haloalkyl; R 16 independently, at each occurrence, hydrogen, C 1-4 Alkyl (C 1-4 Alkyl is independently Halogen, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20)2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20 )2, -NO2, and -CN, C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -SR 20 , -N(R 20 )2, -B(OR 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20 ) optionally substituted with one or more substituents selected from -2, -NO2, and -CN), and C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -SR 20 , -N(R 20)2, -C(O)R 20 , -C(O)N(R 20 )2, -C(O)OR 20 , -OC(O)R 20 , -N(R 20 )C(O)R 20 , -N(R 20 )S(O)2R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -NO2, and -CN), is selected from R 20 independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 It is selected from carbocycles and 3- to 8-membered heterocycles.

[0096] In some embodiments, with respect to a compound or salt of Formula (A) or (A-1), R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocycles, any of which is substituted by -C(O)H or -C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), and -CN, and independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 In some embodiments, R is optionally substituted with one or more substituents selected from a 4-6 membered heterocycle optionally substituted with one or more substituents selected from —N—O, —N—O, and —CN. 5 is a 3- to 10-membered heterocycle and C 3-10 carbocycles, any of which is substituted by -C(O)H or -C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R16 ), and -CN, and independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -NO2, and -CN; R 16 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 It is selected from carbocycles and 3- to 8-membered heterocycles.

[0097] In some embodiments, with respect to a compound or salt of Formula (A) or (A-1), R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocycles, any of which is substituted by -C(O)H or -C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16), and —CN. In some embodiments, R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocycles, any of which is substituted by -C(O)H or -C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -NO2, =O, =S, =N(R 16 ), and —CN. In some embodiments, R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocycles (any of which is substituted with -C(O)H or -C(O)D), R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 and -CN.

[0098] In some embodiments, with respect to a compound or salt of Formula (A) or (A-1), R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocycles, any of which is substituted by -C(O)H or -C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16)2, -NO2, and -CN. 5 is a 3- to 10-membered heterocycle and C 3-10 carbocycles, any of which is substituted by -C(O)H or -C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -NO2, and -CN; R 16 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 It is selected from carbocycles and 3- to 8-membered heterocycles.

[0099] In some embodiments, with respect to a compound or salt of Formula (A) or (A-1), R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocycles (any of which is substituted with -C(O)H or -C(O)D), R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, and -OR 16 In some embodiments, R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocycles (any of which is substituted with -C(O)H or -C(O)D), R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, and -OR 16and R 16 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 It is selected from carbocycles and 3- to 8-membered heterocycles.

[0100] In some embodiments, with respect to a compound or salt of Formula (A) or (A-1), R 5 is C substituted with -C(O)H or -C(O)D 3-10 is a carbocyclic ring, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, and -OR 16 In some embodiments, R 5 is C substituted with -C(O)H or -C(O)D 3-10 is a carbocyclic ring, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, and -OR 16 , and -OR 16 and R 16 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 In some embodiments, R 5 is C substituted with -C(O)H or -C(O)D 3-6 is a carbocyclic ring, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, and -OR 16 , and -OR 16 and R 16 is hydrogen, C 1-4 Alkyl, C 1-4Haloalkyl, C 3-8 In some embodiments, R 5 is phenyl substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, and -OR 16 and optionally substituted with one or more substituents selected from:

[0101] In some embodiments, with respect to a compound or salt of Formula (A) or (A-1), R 5 is phenyl substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, and -OR 16 and R 16 is hydrogen, C 1-4 Alkyl, and C 1-4 In some embodiments, R is selected from haloalkyl. 5 is phenyl substituted with —C(O)H, and R 5 Furthermore, independently C 2-6 Alkynyl and -OR 16 and R 16 is hydrogen, C 1-4 Alkyl, and C 1-4 In some embodiments, R is selected from haloalkyl. 5 teeth,

[0102] [ka] In some embodiments, R 5 teeth,

[0103] [ka] In some embodiments, R 5 teeth,

[0104] [ka] In some embodiments, R 5 teeth,

[0105] [ka] In some embodiments, R 5 teeth,

[0106] [ka] is.

[0107] In another embodiment, Formula (A) or Formula (A-1) is Formula (I):

[0108] [ka] or a pharmaceutically acceptable salt thereof, wherein: R 1 is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 10 , -SR 10 , -N(R 10 )2, -NO2, and -CN; A 1 and A 2 are each independently Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11)C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and —CN) is selected from q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2, and 3; R 2 are independently halogens in each example, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -NO2, and -CN; R 3 Independently, in each example Halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13, -OC(O)R 13 , -NO2, and -CN, and Independently halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -NO2, =O, =S, =N(R 13 ), and —CN, optionally substituted with one or more substituents selected from 1-6 Alkyl is selected from p is selected from 0, 1, 2, 3, 4, and 5; R 4 Independently, in each example Halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl (one of which is independently halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, =O, =S, =N(R 14 ), and —CN), Selected from, or Two Rs bonded to the same atom 4 are united, =O, =S, and =N(R 14 ) or forming a group selected from Two Rs attached to the same atom or adjacent atoms 4 together with the carbon to which they are attached form a 3- to 8-membered heterocyclic ring and C 3-8 Carbocyclic rings (any of which may independently contain halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 ) optionally substituted with one or more substituents selected from -NO2, -CN, L is -L 1 -L 2 -L 3 -L 4 wherein L 1 , L 2 , L 3 , and L 4 are each independently (a) and (b) (a) -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15 )N(R 15 )-, and (b)C 1-6 Alkylene, C 2-6 Alkenylene, C2-6 Alkynylene, C 3-8 Carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, -OR 15 , -SR 15 , ═O, ═S, and —CN) is selected from L 2 , L 3 , and L 4 are each optionally absent, L 1 , L 2 , L 3 , and L 4 At most two of are selected from (a), but the two selected are not adjacent; R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by -C(O)H or -C(O)D; R 5 Furthermore, independently Halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -NO2, and -CN, optionally substituted with one or more substituents selected from and optionally substituted by one or more substituents selected from R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 are each independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 haloalkyl; R 16 independently, at each occurrence, hydrogen, C 1-4 Alkyl (C 1-4 Alkyl is independently Halogen, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20 )2, -NO2, and -CN, C 3-8Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -SR 20 , -N(R 20 )2, -B(OR 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20 ) optionally substituted with one or more substituents selected from -2, -NO2, and -CN), and C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)N(R 20 )2, -C(O)OR 20 , -OC(O)R 20 , -N(R 20 )C(O)R 20 , -N(R 20 )S(O)2R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20, -S(O)2R 20 , -NO2, and -CN), is selected from R 20 independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 It is selected from carbocycles and 3- to 8-membered heterocycles.

[0109] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), or (I), q is selected from 1, 2, and 3. In some embodiments, q is selected from 1 and 2. In some embodiments, q is selected from 1 and 3. In some embodiments, q is selected from 2 and 3. In some embodiments, q is selected from 1 and 2. In some embodiments, q is 1.

[0110] In some embodiments, the compound of formula (A), (A-1), or (I) has formula (IA):

[0111] [ka] or a pharmaceutically acceptable salt thereof, wherein: R 1 is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 10 , -SR 10 , -N(R 10 )2, -NO2, and -CN; A 1 and A 2 are each independently Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11, -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and —CN) is selected from m and n are each independently selected from 0, 1, 2, and 3; R 2 are independently halogens in each example, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -NO2, and -CN; R 3 Independently, in each example Halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13, -C(O)OR 13 , -OC(O)R 13 , -NO2, and -CN, and Independently halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -NO2, =O, =S, =N(R 13 ), and —CN, optionally substituted with one or more substituents selected from 1-6 Alkyl is selected from p is selected from 0, 1, 2, 3, 4, and 5; R 4 Independently, in each example Halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl (one of which is independently halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, =O, =S, =N(R 14 ), and —CN), Selected from, or Two Rs bonded to the same atom 4 are united, =O, =S, and =N(R 14 ) or forming a group selected from Two Rs attached to the same atom or adjacent atoms 4 together with the carbon to which they are attached form a 3- to 8-membered heterocyclic ring and C 3-8 Carbocyclic rings (any of which may independently contain halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 ) optionally substituted with one or more substituents selected from -NO2, -CN, L is -L 1 -L 2 -L 3 -L 4 wherein L 1 , L 2 , L 3 , and L 4 are each independently (a) and (b) (a) -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15 )N(R 15 )-, and (b)C 1-6 Alkylene, C 2-6Alkenylene, C 2-6 Alkynylene, C 3-8 Carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, -OR 15 , -SR 15 , ═O, ═S, and —CN) is selected from L 2 , L 3 , and L 4 are each optionally absent, L 1 , L 2 , L 3 , and L 4 At most two of are selected from (a), but the two selected are not adjacent; R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by -C(O)H or -C(O)D; R 5 Furthermore, independently Halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16), and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -NO2, and -CN, optionally substituted with one or more substituents selected from and optionally substituted by one or more substituents selected from R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 are each independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 haloalkyl; R 16 independently, at each occurrence, hydrogen, C 1-4 Alkyl (C 1-4 Alkyl is independently Halogen, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20 )2, -NO2, and -CN, C 3-8Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -SR 20 , -N(R 20 )2, -B(OR 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20 ) optionally substituted with one or more substituents selected from -2, -NO2, and -CN), and C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)N(R 20 )2, -C(O)OR 20 , -OC(O)R 20 , -N(R 20 )C(O)R 20 , -N(R 20 )S(O)2R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20, -S(O)2R 20 , -NO2, and -CN), is selected from R 20 independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 It is selected from carbocycles and 3- to 8-membered heterocycles.

[0112] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is a compound of Formula (II):

[0113] [ka] or a pharmaceutically acceptable salt thereof, wherein A 1 , A 2 , R 1 , R 2 , R 3 , R 4 , R 5 , m, n, p, and L are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0114] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) has the formula (II-A):

[0115] [ka] or a pharmaceutically acceptable salt thereof, wherein A 1 , A 2 , R 1 , R 2 , R 3 , R 4 , R 5 , m, n, p, and L are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0116] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is represented by Formula (II-B):

[0117] [ka] or a pharmaceutically acceptable salt thereof, wherein A 1 , A 2 , R 1 , R 2 , R 3 , R 4 , R 5 , m, n, p, and L are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0118] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), or (II-B), R 1 is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 10 , -SR 10 , -N(R 10 )2, -NO2, and -CN.

[0119] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), or (II-B), R 1 is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 10 In some embodiments, R is selected from -CN. 1 is selected from fluoro, chloro, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, —CHF, —CHF, —CF, —OCH, —OCHF, —OCHF, —OCF, and —CN. 1is selected from fluoro, chloro, methyl, ethyl, propyl, isopropyl, —CHF, —CF, —OCH, —OCHF, —OCF, and —CN. 1 is selected from fluoro, chloro, methyl, ethyl, propyl, isopropyl, —CHF 2 , —OCH 3 , —OCHF 2 , and —CN.

[0120] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), or (II-B), R 1 teeth, Hydrogen, halogens, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 10 , -SR 10 , -N(R 10 )2, -NO2, and -CN; R 10 represents hydrogen and C at each occurrence. 1-4 alkyl.

[0121] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), or (II-B), R 1 is hydrogen, halogen, C 1-4 Alkyl, and C 1-4 In some embodiments, R is selected from haloalkyl. 1 is hydrogen and C 1-4 In some embodiments, R 1 is hydrogen. In some embodiments, R 1 is C 1-4 In some embodiments, R 1 is selected from methyl, ethyl, propyl, and isopropyl.

[0122] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), or (II-B), R 2 are independently halogens in each example, C1-4 Alkyl, C 1-4 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -NO2, and -CN.

[0123] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), or (II-B), R 2 Independently, in each example Halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 12 , -SR 12 , -N(R 12 )2, -NO2, and -CN; R 12 represents hydrogen and C at each occurrence. 1-4 alkyl.

[0124] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), or (II-B), R 2 are independently halogens in each example, C 1-4 Alkyl, and C 1-4 haloalkyl.

[0125] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), or (II-B), R 2 are independently halogens in each example, C 1-4 Alkyl, and C 1-4 haloalkyl.

[0126] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), or (II-B), R 2 are independently halogens and C in each example. 1-4 In some embodiments, R2 is independently selected at each instance from fluoro, chloro, methyl, ethyl, propyl, and isopropyl. 2 is independently selected at each instance from fluoro, methyl, and ethyl. In some embodiments, R 2 is independently selected at each instance from fluoro and methyl.

[0127] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), or (II-B), m is selected from 0, 1, 2, and 3. In some embodiments, m is selected from 0 and 1. In some embodiments, m is selected from 0. In some embodiments, m is 1.

[0128] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is a compound of Formula (III):

[0129] [ka] or a pharmaceutically acceptable salt thereof, wherein A 1 , A 2 , R 3 , R 4 , R 5 , n, p, and L are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0130] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) has the formula (III-A):

[0131] [ka] or a pharmaceutically acceptable salt thereof, wherein A 1 , A 2 , R 3 , R 4 , R 5, n, p, and L are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0132] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is represented by Formula (III-B):

[0133] [ka] or a pharmaceutically acceptable salt thereof, wherein A 1 , A 2 , R 3 , R 4 , R 5 , n, p, and L are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0134] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 and A 2 are each independently Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, and -CN, C 1-6Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and —CN) is selected from.

[0135] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 and A 2 are each independently Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6Alkynyl (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and —CN) is selected from R 11 independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 haloalkyl.

[0136] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 and A 2 are each independently Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , ═O, and —CN), and 5-10 membered heterocycles and C 3-10Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , =O, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -NO2, =O, and -CN), and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , =O, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11, ═O, and —CN) is selected from.

[0137] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 and A 2 are each independently Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, and -CN, C 1-6 Alkyl and C 2-6 alkynyl, any of which is optionally substituted with one or more halogens, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may independently be halogen, -OR 11 , C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each have one or more C 1-6 and optionally substituted with one or more substituents selected from: is selected from.

[0138] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 and A 2 are each independently Hydrogen, halogen, -OR 11 , C 1-6 Alkyl, and C 2-6Alkynyl, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may independently contain halogen, C 1-6 Alkyl, C 1-6 haloalkyl, and 3- to 10-membered heterocycles (3- to 10-membered heterocycles may be one or more C 1-6 and optionally substituted with one or more substituents selected from: is selected from.

[0139] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 and A 2 are each independently Hydrogen, halogen, -OR 11 , C 1-6 Alkyl, and C 2-6 Alkynyl, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may independently contain halogen, C 1-6 Alkyl, C 1-6 haloalkyl, and 3- to 10-membered heterocycles (3- to 10-membered heterocycles may be one or more C 1-6 and optionally substituted with one or more substituents selected from: is selected from R 11 represents hydrogen and C at each occurrence. 1-4 alkyl.

[0140] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 and A 2 are each independently Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -SR11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), and —CN), is selected from.

[0141] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 and A 2 are each independently Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , ═O, and —CN) is selected from.

[0142] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 and A 2 are each independently hydrogen, halogen, or C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, -CN, C 1-6 Alkyl, and C 2-6 alkynyl, any of which is optionally substituted with one or more halogens.

[0143] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 and A2 are each independently hydrogen, halogen, or -OR 11 , C 1-6 Alkyl, and C 2-4 alkynyl, and R 11 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, and C 3-6 Carbocycles are selected from:

[0144] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 and A 2 are each independently hydrogen, halogen, or C 1-6 Alkyl, C 2-4 Alkynyl, -OH, -OC 1-4 Alkyl, and -OC 3-6 Carbocycles are selected from:

[0145] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 teeth, Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11)2, -NO2, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -S(O)2N(R11 )2, -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and —CN) is selected from.

[0146] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 teeth, Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, and -CN, C 1-6 Alkyl and C 2-6 alkynyl, any of which is optionally substituted with one or more halogens, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may independently be halogen, -OR 11 , C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each have one or more C 1-6 and optionally substituted with one or more substituents selected from: is selected from.

[0147] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 teeth, Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11, -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), -CN), is selected from.

[0148] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 teeth, Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , ═O, and —CN) is selected from.

[0149] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, and -CN. In some embodiments, A 1 is hydrogen, halogen, C 1-4 Alkyl, and C 1-4 In some embodiments, A is selected from haloalkyl.1 is selected from hydrogen, fluoro, and methyl. 1 is hydrogen.

[0150] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 1 is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, and -CN. In some embodiments, A 1 is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, and -OR 11 In some embodiments, A 1 is selected from hydrogen, fluoro, methyl, —OH, and —OCH. 1 is selected from fluoro, methyl, —OH, and —OCH. 1 is hydrogen.

[0151] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 teeth, Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -N(R 11 )2, -C(O)N(R 11)2, -N(R 11 )C(O)R 11 , ═O, and —CN), and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , =O, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -NO2, =O, and -CN), and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent a halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , =O, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -N(R 11 )2, -C(O)R11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , ═O, and —CN) is selected from.

[0152] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 teeth, Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, and -CN, C 1-6 Alkyl and C 2-6 alkynyl, any of which is optionally substituted with one or more halogens, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -CN, C 1-6 Alkyl, C 3-6 Alkynyl, C 1-6 Haloalkyl, C 3-10 optionally substituted with one or more substituents selected from carbocycles, and 3- to 10-membered heterocycles; 1-6 The alkyl groups are halogen, -OR 11 , or -N(R 11 )2 optionally substituted with one or more substituents selected from C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C 1-6 optionally substituted with alkyl is selected from.

[0153] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is hydrogen, fluoro, bromo, chloro, methyl, ethyl, ethynylene, trifluoromethyl,

[0154] [ka] , -OCH3, cyclopropyl,

[0155] [ka] is selected from.

[0156] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is a 5- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which may independently be Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , =O, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11)C(O)R 11 , -N(R 11 )S(O)2R 11 , -NO2, =O, and -CN), and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , =O, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , ═O, and —CN) and optionally substituted with one or more substituents selected from:

[0157] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is a 5- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -CN, C 1-6Alkyl, C 3-6 Alkynyl, C 1-6 Haloalkyl, C 3-10 optionally substituted with one or more substituents selected from carbocycles, and 3- to 10-membered heterocycles; 1-6 Alkyl and C 3-6 Each alkynyl is independently halogen, -OR 11 , and -N(R 11 )2 optionally substituted with one or more substituents selected from C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C 1-6 Optionally substituted with alkyl.

[0158] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is a 5- to 10-membered heterocycle and C 3-10 carbocycles, any of which is optionally substituted with one or more substituents independently selected from fluoro, chloro, methyl, -CHF2, -CF3, ethynylene, -OCH3, -SCH3, -NH2, -N(CH3)2, -C(O)H, -CN, -CHOCH3, -CH2OH, cyclopropyl, pyrazolyl, azetidinyl, and N-methylpiperazinyl, wherein azetidinyl is optionally substituted with methyl.

[0159] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, and thiazolyl, any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -CN, C1-6 Alkyl, C 3-6 Alkynyl, C 3-10 optionally substituted with one or more substituents selected from carbocycles, and 3- to 6-membered heterocycles; 1-6 Alkyl is independently selected from halogen and -OR 11 and optionally substituted with one or more substituents selected from C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C 1-6 Optionally substituted with alkyl.

[0160] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyrazolyl, furopyrazolyl, pyrazolopyridinyl, pyrazolooxazinyl, and thiazolyl, any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -CN, C 1-6 Alkyl, C 3-6 Alkynyl, C 3-10 optionally substituted with one or more substituents selected from carbocycles, and 3- to 6-membered heterocycles; 1-6 Alkyl is independently selected from halogen and -OR 11 and optionally substituted with one or more substituents selected from C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C 1-6 In some embodiments, A is optionally substituted with alkyl. 2is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyrazolyl, furopyrazolyl, pyrazolopyridinyl, pyrazolooxazinyl, and thiazolyl, any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -CN, C 1-6 Alkyl, C 3-6 Alkynyl, C 3-8 optionally substituted with one or more substituents selected from carbocycles, and 3- to 6-membered heterocycles; 1-6 Alkyl is independently selected from halogen and -OR 11 and optionally substituted with one or more substituents selected from C 3-8 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C 1-6 In some embodiments, A is optionally substituted with alkyl. 2 is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyrazolyl, furopyrazolyl, pyrazolopyridinyl, pyrazolooxazinyl, and thiazolyl, any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -CN, C 1-6 Alkyl, C 3-6 Alkynyl, C 3-6 optionally substituted with one or more substituents selected from carbocycles, and 3- to 6-membered heterocycles; 1-6 Alkyl is independently selected from halogen and -OR 11 and optionally substituted with one or more substituents selected from C 3-6 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C1-6 Optionally substituted with alkyl.

[0161] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyrazolyl, furopyrazolyl, pyrazolopyridinyl, pyrazolooxazinyl, and thiazolyl, any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -CN, C 1-6 Alkyl, C 3-6 Alkynyl, C 1-6 haloalkyl and one or more C 1-4 In some embodiments, A is optionally substituted with one or more substituents selected from a 3- to 10-membered heterocycle optionally substituted with alkyl. 2 is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyrazolyl, furopyrazolyl, pyrazolopyridinyl, pyrazolooxazinyl, and thiazolyl, any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -CN, C 1-6 Alkyl, C 3-6 Alkynyl, C 1-6 haloalkyl and one or more C 1-4 In some embodiments, A is optionally substituted with one or more substituents selected from a 3- to 6-membered heterocycle optionally substituted with alkyl. 2is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyrazolyl, furopyrazolyl, pyrazolopyridinyl, pyrazolooxazinyl, and thiazolyl, any of which may independently be halogen, -OR 11 , -N(R 11 )2, -CN, C 1-6 Alkyl, C 3-6 Alkynyl, C 1-6 haloalkyl and one or more C 1-4 In some embodiments, A is optionally substituted with one or more substituents selected from a 3- to 6-membered heterocycle optionally substituted with alkyl. 2 is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyrazolyl, furopyrazolyl, pyrazolopyridinyl, pyrazolooxazinyl, and thiazolyl, any of which may independently be fluoro, -OR 11 , -CN, C 1-6 Alkyl, C 3-6 Alkynyl, C 1-6 haloalkyl and one or more C 1-4 Optionally substituted with one or more substituents selected from 3-6 membered heterocycles optionally substituted with alkyl.

[0162] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, and thiazolyl, any of which may independently be halogen, -OR 11 , -SR 11, -N(R 11 )2, -C(O)R 11 , -CN, C 1-6 Alkyl, C 3-6 Alkynyl, C 1-6 haloalkyl and one or more C 1-4 Optionally substituted with one or more substituents selected from 3-6 membered heterocycles optionally substituted with alkyl.

[0163] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, and thiazolyl, any of which is optionally substituted with one or more substituents independently selected from fluoro, chloro, methyl, and N-methylpiperazinyl.

[0164] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyrazolyl, furopyrazolyl, pyrazolopyridinyl, pyrazolooxazinyl, and thiazolyl, any of which is optionally substituted with one or more substituents independently selected from fluoro, chloro, methyl, and N-methylpiperazinyl. 2is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyrazolyl, furopyrazolyl, pyrazolopyridinyl, pyrazolooxazinyl, and thiazolyl, any of which is optionally substituted with one or more substituents independently selected from fluoro, methyl, and N-methylpiperazinyl.

[0165] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is pyrazolyl optionally substituted with one or more oxteanyl, pyrazolyl, and azetidinyl, wherein oxteanyl, pyrazolyl, and azetidinyl are each C 1-6 In some embodiments, A is optionally substituted with alkyl. 2 is pyrazolyl optionally substituted with one or more of oxteanyl, pyrazolyl, and azetidinyl, wherein oxteanyl, pyrazolyl, and azetidinyl are optionally substituted with methyl, ethyl, propyl, isopropyl, and n-butyl, respectively. 2 is pyrazolyl optionally substituted with one or more of oxteanyl, pyrazolyl, and azetidinyl, wherein oxteanyl, pyrazolyl, and azetidinyl are each optionally substituted with methyl and ethyl. In some embodiments, A 2 is pyrazolyl optionally substituted with one or more of oxsteanyl, pyrazolyl, and azetidinyl, each of which is optionally substituted with methyl.

[0166] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 independently Halogen, -CN, -C(O)R 11 , -N(R 11 )2, -SR 11 , C 1-6 Alkyl, C 3-6 Alkynyl, C 1-6 Haloalkyl, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, and -OR 11 and C 1-6 C optionally substituted with alkyl 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings and pyrazolyl optionally substituted with one or more substituents selected from:

[0167] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is one or more C 3-10 In some embodiments, A is a pyrazolyl optionally substituted with a carbocyclic ring. 2 is pyrazolyl optionally substituted with one or more cyclopropyl.

[0168] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is one or more C 1-6 In some embodiments, A is a pyrazolyl optionally substituted with one or more 3- to 6-membered heterocyclic rings optionally substituted with alkyl. 2is pyrazolyl optionally substituted with one or more pyrazolyl and azetidinyl, wherein pyrazolyl and azetidinyl are each C 1-6 In some embodiments, A is optionally substituted with alkyl. 2 is pyrazolyl optionally substituted with one or more pyrazolyl and azetidinyl, each of which is optionally substituted with methyl.

[0169] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 -F, -Cl, -CH3, -CN, cyclopropyl, ethynylene, -CF3, phenyl,

[0170] [ka] is selected from.

[0171] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 is cyclopropyl, phenyl,

[0172] [ka] is selected from.

[0173] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), or (III-B), A 2 -F, -Cl, -CH3, -CN, cyclopropyl, ethynylene, -CF3, phenyl,

[0174] [ka]

[0175] [ka] is selected from.

[0176] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is represented by Formula (IV):

[0177] [ka] or a pharmaceutically acceptable salt thereof, wherein A 2 , R 3 , R 4 , R 5 , n, p, and L are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0178] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) has the formula (IV-A):

[0179] [ka] or a pharmaceutically acceptable salt thereof, wherein A 2 , R 3 , R 4 , R 5 , n, p, and L are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0180] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is represented by Formula (IV-B):

[0181] [ka] or a pharmaceutically acceptable salt thereof, wherein A 2 , R3 , R 4 , R 5 , n, p, and L are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0182] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 3 Independently, in each example Halogen, -OR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -NO2, and -CN, and Independently halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -NO2, =O, =S, =N(R 13 ), and —CN, optionally substituted with one or more substituents selected from 1-6 Alkyl is selected from.

[0183] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 3 Independently, in each example Halogen, -OR 13 , -N(R 13 )2, -C(O)R13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -NO2, and -CN, and Independently halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , -C(O)OR 13 , -OC(O)R 13 , -NO2, =O, =S, =N(R 13 ), and —CN, optionally substituted with one or more substituents selected from 1-6 Alkyl is selected from R 13 independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 haloalkyl.

[0184] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 3 Independently, in each example Halogen, -OR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13 )2, -N(R 13 )C(O)R 13 , and -CN, and Independently halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)N(R 13)2, -N(R 13 )C(O)R 13 C optionally substituted with one or more substituents selected from: ═O, and —CN 1-6 Alkyl is selected from.

[0185] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 3 are independently halogen, -OR in each example. 13 , -N(R 13 )2, -CN, C 1-6 Alkyl, and C 1-6 haloalkyl.

[0186] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 3 are independently halogen, -OR in each example. 13 , -N(R 13 )2, -CN, C 1-6 Alkyl, and C 1-6 haloalkyl; R 13 independently, at each occurrence, hydrogen and C 1-4 alkyl.

[0187] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 3 are independently halogens in each example, C 1-4 Alkyl, C 1-4 haloalkyl, and -CN.

[0188] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), n is selected from 0, 1, 2, and 3. In some embodiments, n is selected from 0 and 1. In some embodiments, n is 0.

[0189] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 4 Independently, in each example Halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl (one of which may be halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, =O, =S, =N(R 14 ), and —CN), Selected from, or Two Rs bonded to the same atom 4 are united, =O, =S, and =N(R 14 ) or forming a group selected from Two Rs attached to the same atom or adjacent atoms 4 together with the carbon to which they are attached form a 3- to 8-membered heterocyclic ring and C 3-8 Carbocyclic rings (any of which may independently contain halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 ) optionally substituted with one or more substituents selected from -2, -NO2, and -CN.

[0190] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 4 Independently, in each example Halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl (one of which may be halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , -C(O)OR 14 , -OC(O)R 14 , -NO2, =O, =S, =N(R 14), and —CN), Selected from, or Two Rs bonded to the same atom 4 are united, =O, =S, and =N(R 14 ) or forming a group selected from Two Rs attached to the same atom or adjacent atoms 4 together with the carbon to which they are attached form a 3- to 8-membered heterocyclic ring and C 3-8 Carbocyclic rings (any of which may independently contain halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -SR 14 , -N(R 14 ) optionally substituted with one or more substituents selected from -NO2, -CN, R 14 independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 haloalkyl.

[0191] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 4 Independently, in each example Halogen, -OR 14 , -N(R 14 )2, -C(O)R 14 , -C(O)N(R 14 )2, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl (one of which may be halogen, -OR 14 , -N(R 14 )2, -C(O)R 14, -C(O)N(R 14 )2, -N(R 14 )C(O)R 14 , ═O, and —CN) Selected from, or Two Rs bonded to the same atom 4 are united, =O, =S, and =N(R 14 ) or forming a group selected from Two Rs attached to the same atom or adjacent atoms 4 together with the carbon to which they are attached form a 3- to 8-membered heterocyclic ring and C 3-8 Carbocyclic rings (any of which may independently contain halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 14 , -N(R 14 ) optionally substituted with one or more substituents selected from —CN;

[0192] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 4 Independently, in each example Halogen, -OR 14 , -SR 14 , -N(R 14 )2, -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl is halogen, -OR 14 , -N(R 14 ) optionally substituted with one or more substituents selected from ═O, ═O, and —CN Selected from, or Two Rs bonded to the same atom4 come together to form =O, or Two Rs attached to the same atom or adjacent atoms 4 together with the carbon to which they are attached form a 3- to 8-membered heterocyclic ring and C 3-8 forming a group selected from carbocycles, R 14 is hydrogen and C 1-4 alkyl.

[0193] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 4 Independently, in each example Halogen, -OR 14 , C 1-6 Alkyl, and C 2-6 Alkynyl Selected from, or Two Rs bonded to the same atom 4 come together to form =O, or Two Rs attached to the same atom or adjacent atoms 4 together with the carbon to which they are attached form a 3- to 8-membered heterocyclic ring and C 3-8 forming a group selected from carbocycles, R 14 is hydrogen and C 1-4 alkyl.

[0194] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 4 Independently, in each example Halogen, -OH, C 1-6 Alkyl, and C 2-6 Alkynyl Selected from, or Two Rs bonded to the same atom 4come together to form =O, or Two Rs attached to the same atom or adjacent atoms 4 together with the carbon to which they are attached, C 3-8 Forms a carbocyclic ring.

[0195] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 4 are independently halogens, -OH, C in each example. 1-6 Alkyl, and C 2-6 alkynyl, or two R attached to the same atom or adjacent atoms; 4 together with the carbon to which they are attached, C 3-6 In some embodiments, R 4 are independently halogens, -OH, and C in each example. 1-6 alkyl, or two R attached to the same atom or adjacent atoms 4 are bonded to the carbon atoms to form C 3-6 In some embodiments, R 4 are independently halogens and C in each example. 1-6 alkyl, or two R attached to the same atom or adjacent atoms 4 are bonded to the carbon atoms to form C 3-6 In some embodiments, R 4 are independently selected at each instance from fluoro, chloro, methyl, ethyl, propyl, isopropyl, and n-butyl, or two R attached to the same atom or adjacent atoms; 4 are bonded to the carbon atoms to form C 3-6 In some embodiments, R 4 are independently selected from fluoro and methyl at each instance, or two R attached to the same atom or adjacent atoms; 4together with the carbon to which they are attached form a cyclopropyl.

[0196] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), p is selected from 0, 1, 2, 3, 4, and 5. In some embodiments, p is selected from 0, 1, and 2. In some embodiments, p is selected from 0 and 1. In some embodiments, p is 0.

[0197] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is a compound of Formula (V):

[0198] [ka] or a pharmaceutically acceptable salt thereof, wherein A 2 , R 5 , and L are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0199] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) has the formula (VA)

[0200] [ka] or a pharmaceutically acceptable salt thereof, wherein A 2 , R 5 , and L are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0201] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) has the formula (VB):

[0202] [ka] or a pharmaceutically acceptable salt thereof, wherein A 2 , R 5 , and L are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0203] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 1 , L 2 , L 3 , and L 4 are each independently (a) and (b) (a) -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15 )N(R 15 )-, and (b)C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 3-8 Carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, -OR 15 , -SR15 , ═O, ═S, and —CN) is selected from L 2 , L 3 , and L 4 are each optionally absent, L 1 , L 2 , L 3 , and L 4 At most two of are selected from (a), but the two selected are not adjacent.

[0204] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 1 , L 2 , L 3 , and L 4 are each independently (a) and (b) (a) -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15 )N(R 15 )-, and (b)C 1-6 Alkylene, C2-6 Alkenylene, C 2-6 Alkynylene, C 3-8 Carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, -OR 15 , -SR 15 , ═O, ═S, and —CN) is selected from R 15 independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 haloalkyl; L 2 , L 3 , and L 4 are each optionally absent, L 1 , L 2 , L 3 , and L 4 At most two of are selected from (a), but the two selected are not adjacent.

[0205] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 1 , L 2 , L 3 , and L 4 are each independently (a) and (b) (a) -O-, -N(R 15 )-, -S-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-N(R 15 )N(R 15 )-, and -(R 15)NC(O)N(R 15 )-, and (b)C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 3-6 Carbocyclene, and 3- to 6-membered heterocyclene (any of which may independently be halogen, -OR 15 , ═O, and —CN) is selected from L 2 , L 3 , and L 4 are each optionally absent, L 1 , L 2 , L 3 , and L 4 At most two of are selected from (a), but the two selected are not adjacent.

[0206] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 1 , L 2 , L 3 , and L 4 are each independently (a) and (b) (a)-N(R 15 )- and -N(R 15 )C(O)-, and (b)C 1-6 Alkylene, C 2-6 Alkynylene, and C 3-6 Carbocyclene is selected from L 2 , L 3 , and L 4 are each optionally absent, L 1 , L 2 , L 3 , and L 4 At most two of are selected from (a), but the two selected are not adjacent; R 15 is hydrogen and C 1-4 alkyl.

[0207] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 1 , L 2 , L 3 , and L 4 are each independently (a) and (b) (a)-N(R 15 )- and -N(R 15 )C(O)-, and (b)C 1-6 Alkylene and C 3-6 Carbocyclene is selected from L 2 , L 3 , and L 4 are each optionally absent, L 1 , L 2 , L 3 , and L 4 At most two of are selected from (a), but the two selected are not adjacent; R 15 is hydrogen and C 1-4 alkyl.

[0208] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 1 , L 2 , L 3 , and L 4 are each independently (a) and (b) (a) —NH— and —N(H)C(O)—, and (b) methylene,

[0209] [ka] is selected from L 2 , L 3 , and L 4 are each optionally absent, L 1 , L 2 , L 3 , and L 4 At most two of are selected from (a), but the two selected are not adjacent.

[0210] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 2 , L 3 , and L 4 does not exist, and L 1 teeth, (a) -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15 )N(R 15 )-, and (b)C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene is selected from.

[0211] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 2 , L 3 , and L 4 does not exist, and L 1 teeth, (a) -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15 )N(R 15 )-, and (b)C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene is selected from R 15 is hydrogen, C 1-4 Alkyl, and C 1-4 haloalkyl.

[0212] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 2 , L 3 , and L 4 does not exist, and L 1 is -N(R 15 )-, -N(R 15 )C(O)-, and C 1-6 alkylene.

[0213] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 2 , L 3 , and L 4 does not exist, and L 1 teeth, -N(R 15 )-, -N(R15 )C(O)-, and C 1-6 Alkylene is selected from R 15 is hydrogen and C 1-4 alkyl.

[0214] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 2 , L 3 , and L 4 does not exist, and L 1 teeth, -N(R 15 )-, -N(R 15 )C(O)-, and C 1-6 Alkylene is selected from R 15 is selected from hydrogen and methyl.

[0215] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 2 , L 3 , and L 4 does not exist, and L 1 -N(H)-, -N(H)C(O)-, and C 1-6 In some embodiments, L is selected from alkylene. 2 , L 3 , and L 4 does not exist, and L 1is selected from —N(H)— and —N(H)C(O)—.

[0216] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 3 and L 4 does not exist, L 1 is -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15 )N(R 15 )-selected from L 2 is C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 3-8 carbocyclene, and 3- to 8-membered heterocyclene, any of which may independently be halogen, -OR 15 , -SR 15 , ═O, ═S, and —CN.

[0217] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 3 and L 4 does not exist, L 1 is -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15 )N(R 15 )-selected from L 2 is C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 3-8 carbocyclene, and 3- to 8-membered heterocyclene, any of which may independently be halogen, -OR 15 , -SR 15 , ═O, ═S, and —CN; R 15 independently, at each occurrence, hydrogen, C 1-4 Alkyl, and C 1-4 haloalkyl.

[0218] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 3 and L 4 does not exist, L 1 is -N(R 15 )- and -N(R 15 )C(O)—; L 2 is C 1-6 Alkylene, C 2-6 Alkenylene, C 3-8 carbocyclenes.

[0219] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 3 and L 4 does not exist, L 1 is -N(R 15 )- and -N(R 15 )C(O)—; L 2 is C 1-6 Alkylene and C 3-6 carbocyclenes.

[0220] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 3 and L 4 does not exist, L 1 is -N(R 15 )- and -N(R 15 )C(O)—; L 2 is C 1-6 Alkylene and C 3-6 selected from carbocyclenes, R 15 is hydrogen and C 1-4 alkyl.

[0221] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is -L 1 -L 2 -L 3 -L 4 - represented by L 3 and L 4 does not exist, L 1 is selected from —N(H)— and —N(H)C(O)—; L 2 is methylene,

[0222] [ka] is selected from.

[0223] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is —N(H)—, —N(H)C(O)—,

[0224] [ka] is selected from.

[0225] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is selected from —N(H)— and —N(H)C(O)—.

[0226] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is

[0227] [ka] is selected from.

[0228] In some embodiments, with respect to a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is

[0229] [ka] is selected from.

[0230] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is represented by Formula (VI):

[0231] [ka] or a pharmaceutically acceptable salt thereof, a teeth, Direct bonding, and C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 3-8 Carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, -OR 15 , -SR 15 , ═O, ═S, and —CN) is selected from A 2 and R 5 are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0232] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) has the formula (VI-A):

[0233] [ka] or a pharmaceutically acceptable salt thereof, 2 and R 5 are defined as in formula (A), (A-1), (I), or (IA), respectively, and L a is defined as in formula (VI).

[0234] In some embodiments, the compound of formula (I) has formula (VI-B):

[0235] [ka] or a pharmaceutically acceptable salt thereof, 2 and R 5 are defined as in formula (A), (A-1), (I), or (IA), respectively, and L a is defined as in formula (VI).

[0236] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is represented by Formula (VII):

[0237] [ka] or a pharmaceutically acceptable salt thereof, wherein: R 21 teeth, Hydrogen, halogens, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, N(R 16 )C(O)N(R 16 )2, and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 and -CN. is selected from R 22 Independently, in each example Halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -NO2, and -CN, optionally substituted with one or more substituents selected from is selected from s is selected from 0, 1, 2, and 3; A 2 is defined as in formula (A), (A-1), (I), or (IA), and L a is defined as in formula (VI).

[0238] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) has the formula (VII-A):

[0239] [ka] or a pharmaceutically acceptable salt thereof, 2 is defined as in formula (A), (A-1), (I), or (IA), and L a is defined as in formula (VI), and R21 , R 22 , and s are each defined as in formula (VII).

[0240] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) has the formula (VII-B):

[0241] [ka] or a pharmaceutically acceptable salt thereof, 2 is defined as in formula (A), (A-1), (I), or (IA), and L a is defined as in formula (VI), and R 21 , R 22 , and s are each defined as in formula (VII).

[0242] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is represented by Formula (VIII):

[0243] [ka] or a pharmaceutically acceptable salt thereof, 2 is defined as in formula (A), (A-1), (I), or (IA), and L a is defined as in formula (VI), and R 22 and s are each defined as in formula (VII).

[0244] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) has the formula (VIII-A):

[0245] [ka] or a pharmaceutically acceptable salt thereof, 2is defined as in formula (A), (A-1), (I), or (IA), and L a is defined as in formula (VI), and R 22 and s are each defined as in formula (VII).

[0246] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is represented by Formula (VIII-B):

[0247] [ka] or a pharmaceutically acceptable salt thereof, 2 is defined as in formula (A), (A-1), (I), or (IA), and L a is defined as in formula (VI), and R 22 and s are each defined as in formula (VII).

[0248] In some embodiments, with respect to a compound or salt of formula (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), or (VIII-B), L a teeth, Direct bonding, and C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 3-8 Carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, -OR 15 , -SR 15 , ═O, ═S, and —CN) is selected from.

[0249] In some embodiments, with respect to a compound or salt of formula (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), or (VIII-B), L a teeth, Direct bonding, and C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 3-8 Carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, -OR 15 , -SR 15 , ═O, ═S, and —CN) is selected from R 15 independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 haloalkyl.

[0250] In some embodiments, with respect to a compound or salt of formula (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), or (VIII-B), L a teeth, Direct bonding, and C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 3-6 Carbocyclene, and 3- to 6-membered heterocyclene (any of which may independently be halogen, -OR 15 , ═O, and —CN) is selected from.

[0251] In some embodiments, with respect to a compound or salt of formula (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), or (VIII-B), L a teeth, Direct bonding, and C 1-6 Alkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C3-6 Carbocyclene, and 3- to 6-membered heterocyclene (any of which may independently be halogen, -OR 15 , ═O, and —CN) is selected from R 15 independently, at each occurrence, hydrogen, C 1-4 Alkyl, and C 1-4 haloalkyl.

[0252] In some embodiments, with respect to a compound or salt of formula (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), or (VIII-B), L a teeth, Direct bonding, and C 1-6 Alkylene, C 2-6 Alkynylene, and C 3-6 Carbocyclene is selected from.

[0253] In some embodiments, with respect to a compound or salt of formula (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), or (VIII-B), L a teeth, Direct bonding, and methylene,

[0254] [ka] is selected from.

[0255] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is represented by Formula (IX):

[0256] [ka] or a pharmaceutically acceptable salt thereof, wherein A2 and R 5 are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0257] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) has the formula (IX-A):

[0258] [ka] or a pharmaceutically acceptable salt thereof, wherein A 2 and R 5 are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0259] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is represented by Formula (IX-B):

[0260] [ka] or a pharmaceutically acceptable salt thereof, wherein A 2 and R 5 are defined as in formula (A), (A-1), (I), or (IA), respectively.

[0261] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by -C(O)H or -C(O)D; R 5 furthermore, Halogen, C 1-4 Alkyl, C 1-4Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -NO2, and -CN, optionally substituted with one or more substituents selected from and optionally substituted with one or more substituents selected from:

[0262] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by -C(O)H or -C(O)D; R 5 furthermore, Halogen, C 1-4Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, N(R 16 )C(O)N(R 16 )2, =O, and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 and -CN. and optionally substituted with one or more substituents selected from:

[0263] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by —C(O)H; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -C(O)R 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16)2, -N(R 16 )C(O)N(R 16 )2, —CN, and a 4- to 6-membered heterocycle. 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by —C(O)H; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -C(O)R 16 , -SR 16 , -N(R 16 )2, -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, —CN, and a 4- to 6-membered heterocycle. 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by —C(O)H; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, —CN, and a 4- to 6-membered heterocycle. 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by —C(O)H; R 5 can further independently be fluoro, chloro, C 1-4 Alkyl, C 1-4 Haloalkyl, -OH, -OCH3, -N(R 16 )2, -N(R 16 )S(O)2R 16 , -S(O)2N(R 16)2, —CN, and a 4- to 6-membered heterocycle. 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by —C(O)H; R 5 may further independently be fluoro, C 1-4 Alkyl, C 1-4 Optionally substituted with one or more substituents selected from haloalkyl, -OH, -OCH3, -CN, and 4- to 6-membered heterocycle.

[0264] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -CN, -B(OR 16 )2, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and the 3-8 membered heterocycle is selected from C1-4 In some embodiments, R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -CN, -C(O)R 16 , -S(O)2N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and the 3-8 membered heterocycle is selected from C 1-4 In some embodiments, R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 can further independently be fluoro, chloro, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -CN, -S(O)2N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and the 3-8 membered heterocycle is selected from C 1-4 In some embodiments, R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5can further independently be fluoro, chloro, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and the 3-8 membered heterocycle is selected from C 1-4 Optionally substituted with alkyl.

[0265] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from 3- to 10-membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D, and further independently selected from halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -CN, -B(OR 16 )2, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and the 3-8 membered heterocycle is selected from C 1-4In some embodiments, R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -CN, -C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, wherein the 3-8 membered heterocycle is optionally substituted with methyl. 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, wherein the 3-8 membered heterocycle is optionally substituted with methyl. 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, wherein the 3-8 membered heterocycle is optionally substituted with methyl. 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 can further independently be fluoro, chloro, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, wherein the 3-8 membered heterocycle is optionally substituted with methyl.

[0266] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -CN, -B(OR 16 )2, -C(O)R 16 , -N(R16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and C 1-6 The alkyl is optionally substituted with halogen. In some embodiments, R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -CN, -C(O)R 16 , -N(R 16 )C(O)R 16 , -S(O)2N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and C 1-6 The alkyl is optionally substituted with halogen. In some embodiments, R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16)2, —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and C 1-6 The alkyl is optionally substituted with halogen. In some embodiments, R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and C 1-6 The alkyl is optionally substituted with fluoro. In some embodiments, R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and C 1-6 The alkyl is optionally substituted with halogen. In some embodiments, R 5is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and C 1-6 The alkyl is optionally substituted with fluoro.

[0267] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -CN, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and C 1-6 The alkyl is optionally substituted with fluoro or chloro. In some embodiments, R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -CN, -N(R 16 )C(O)R 16 , -S(O)2N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and C 1-6 The alkyl is optionally substituted with fluoro or chloro. In some embodiments, R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and C 1-6 The alkyl is optionally substituted with fluoro or chloro. In some embodiments, R 5is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and C 1-6 The alkyl is optionally substituted with fluoro or chloro.

[0268] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted by —C(O)H; R 5 may further independently be halogen, C 1-4 Alkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -CN, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, and C 3-6In some embodiments, R is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H; 5 may further independently be halogen, C 1-4 Alkyl, -OR 16 , -N(R 16 )2, -CN, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 and a 4- to 6-membered heterocycle, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, and C 3-6 In some embodiments, R is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H; 5 may further independently be halogen, C 1-4 Alkyl, -OR 16 , -N(R 16 )2, —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-6 Alkyl, and C 3-6 In some embodiments, R is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H; 5 can further independently be fluoro, chloro, C 1-4 Alkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-6 Alkyl, and C 3-6 cycloalkyl.

[0269] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -CN, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )C(O)N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is selected from hydrogen, methyl, -CHF2, -morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 In some embodiments, R is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -CN, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 and a 4- to 6-membered heterocycle, optionally substituted with one or more substituents selected from R16 is selected from hydrogen, methyl, -CHF2, -morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 In some embodiments, R is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, —CN, and a 4- to 6-membered heterocycle; R 16 is selected from hydrogen, methyl, -CHF2, -morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 In some embodiments, R is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is selected from hydrogen, methyl, -CHF2, -morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 In some embodiments, R is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D, and R 5 can further independently be fluoro, chloro, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16is selected from hydrogen, methyl, -CHF2, -morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 In some embodiments, R is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D, and R 5 may further independently be fluoro, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is selected from hydrogen, methyl, -CHF2, -morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 Optionally substituted with alkyl.

[0270] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by -C(O)H or -C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, and -N(R 16 )C(O)N(R 16)2, and —CN. In some embodiments, R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by —C(O)H; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, and —CN.

[0271] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by —C(O)H; R 5 is furthermore a halogen, C 1-4 Alkyl, -OR 16 , and -N(R 16 )C(O)R 16In some embodiments, with respect to a compound or salt of Formula (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by —C(O)H; R 5 is further substituted with halogen, methyl, -OH, and -N(R 16 )C(O)R 16 and optionally substituted with one or more substituents selected from:

[0272] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is a 3- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which is substituted by —C(O)H; R 5 is further fluoro, chloro, -OH, methyl,

[0273] [ka] In some embodiments, R 5 is phenyl substituted by —C(O)H, and R 5 is further fluoro, chloro, -OH, methyl,

[0274] [ka] In some embodiments, R 5 is phenyl substituted by —C(O)H and —OH, and R 5 is further fluoro, chloro, -OH, methyl,

[0275] [ka] and optionally substituted with one or more substituents selected from:

[0276] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from a 3- to 10-membered heterocycle and phenyl, any of which is substituted by —C(O)H or —C(O)D, and R 5 furthermore, Halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16, -NO2, =O, =S, =N(R 16 ), and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -NO2, and -CN, optionally substituted with one or more substituents selected from and optionally substituted with one or more substituents selected from:

[0277] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from a 3- to 10-membered heterocycle and phenyl, any of which is substituted by —C(O)H or —C(O)D, and R 5 furthermore, Halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, N(R 16 )C(O)N(R 16 )2, =O, and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 and -CN. and optionally substituted with one or more substituents selected from:

[0278] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from a 3- to 10-membered heterocycle and phenyl, any of which is substituted by —C(O)H or —C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, N(R 16 )C(O)N(R 16 )2, and —CN. In some embodiments, R 5 is selected from a 3- to 10-membered heterocycle and phenyl, any of which is substituted by —C(O)H; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, N(R 16 )C(O)N(R 16)2, and —CN.

[0279] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from a 3- to 10-membered heterocycle and phenyl, any of which is substituted by —C(O)H; R 5 is furthermore a halogen, C 1-4 Alkyl, -OR 16 , and -N(R 16 )C(O)R 16 In some embodiments, R 5 is selected from a 3- to 10-membered heterocycle and phenyl, any of which is substituted by —C(O)H; R 5 is further substituted with halogen, methyl, -OH, and -N(R 16 )C(O)R 16 and optionally substituted with one or more substituents selected from:

[0280] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from a 3- to 10-membered heterocycle and phenyl, any of which is substituted by —C(O)H; R 5 is further fluoro, chloro, -OH, methyl,

[0281] [ka] and optionally substituted with one or more substituents selected from:

[0282] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted by —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -CN, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-4 Alkyl, and C 3-6 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -CN, C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-4 Alkyl, and C 3-6 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-4 Alkyl, and C 3-6 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-4 Alkyl, and C3-6 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-4 Alkyl, and C 3-6 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is selected from hydrogen, methyl, cyclopropyl, cyclobutyl, and cyclopentyl.

[0283] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from pyridine, isoquinoline, indazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted by —C(O)H; R5 may further independently be halogen, C 1-4 Alkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -CN, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-4 Alkyl, and C 3-6 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H; R 5 may further independently be halogen, C 1-4 Alkyl, -OR 16 , -N(R 16 )2, -CN, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 ) 2, and 4- to 6-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-4 Alkyl, and C 3-6 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H; R 5 may further independently be halogen, C 1-4 Alkyl, -OR 16 , -N(R 16)2, —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-4 Alkyl, and C 3-6 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H; R 5 may further independently be halogen, C 1-4 Alkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-4 Alkyl, and C 3-6 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H; R 5 can further independently be fluoro, chloro, C 1-4 Alkyl, -OR 16 , —CN, and a 4- to 6-membered heterocycle; R 16 is hydrogen, C 1-4 Alkyl, and C 3-6 cycloalkyl.

[0284] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted by —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -CN, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )C(O)N(R 16 ) 2-, and 5-membered heterocycles, optionally substituted with one or more substituents selected from R 16 is selected from hydrogen, methyl, -CHF2, morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted by —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -CN, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 and a 5-membered heterocycle, optionally substituted with one or more substituents selected from R 16is selected from hydrogen, methyl, -CHF2, morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted by —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, —CN, and a 5-membered heterocycle; R 16 is selected from hydrogen, methyl, -CHF2, morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted by —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, —CN, and a 5-membered heterocycle; R 16 is selected from hydrogen, methyl, -CHF2, morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 In some embodiments, R 5is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted by —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 5-membered heterocycle; R 16 is selected from hydrogen, methyl, -CHF2, morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted by —C(O)H or —C(O)D; R 5 may further independently be fluoro, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , —CN, and a 5-membered heterocycle; R 16 is selected from hydrogen, methyl, -CHF2, morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 Optionally substituted with alkyl.

[0285] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from pyridine, isoquinoline, indazole, and phenyl, any of which is substituted by —C(O)H or —C(O)D; R5 furthermore, Halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ), and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -NO2, and -CN, optionally substituted with one or more substituents selected from and optionally substituted with one or more substituents selected from:

[0286] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5is selected from pyridine, isoquinoline, indazole, and phenyl, any of which is substituted by —C(O)H or —C(O)D; R 5 furthermore, Halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, N(R 16 )C(O)N(R 16 )2, =O, and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 and -CN. and optionally substituted with one or more substituents selected from:

[0287] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from pyridine, isoquinoline, indazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, and —CN. In some embodiments, R 5 is selected from pyridine, isoquinoline, indazole, and phenyl, any of which is substituted with —C(O)H; R 5 may further independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, and —CN.

[0288] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from pyridine, isoquinoline, indazole, and phenyl, any of which is substituted with —C(O)H; R 5 is furthermore a halogen, C 1-4 Alkyl, -OR 16 , and -N(R 16 )C(O)R 16In some embodiments, R 5 is selected from a 3- to 10-membered heterocycle and phenyl, any of which is substituted by —C(O)H; R 5 is further substituted with halogen, methyl, -OH, and -N(R 16 )C(O)R 16 and optionally substituted with one or more substituents selected from:

[0289] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from pyridine, isoquinoline, indazole, and phenyl, any of which is substituted with —C(O)H; R 5 is further fluoro, chloro, -OH, methyl,

[0290] [ka] and optionally substituted with one or more substituents selected from:

[0291] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4Haloalkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, and -N(R 16 )C(O)N(R 16 )2, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and the 3-8 membered heterocycle is selected from C 1-4 Optionally substituted with alkyl.

[0292] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, and -N(R 16 )C(O)N(R 16)2, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, wherein the 3-8 membered heterocycle is optionally substituted with methyl.

[0293] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, and -N(R 16 )C(O)N(R 16 )2, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and C 1-6 The alkyl is optionally substituted with a halogen.

[0294] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R 5 may further independently be halogen, C 1-4 Alkyl, C 2-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, and -N(R 16 )C(O)N(R 16 )2, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, 3- to 8-membered heterocycle, and -N(R 20 )2, and C 1-6 The alkyl is optionally substituted with fluoro or chloro.

[0295] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with -C(O)H or -C(O)D, and R5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , and -N(R 16 )C(O)N(R 16 )2, optionally substituted with one or more substituents selected from R 16 is selected from hydrogen, methyl, -CHF2, -morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 Optionally substituted with alkyl.

[0296] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from pyridine, isoquinoline, indazole, thiazole, and phenyl, any of which is substituted by —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, and -N(R 16 )C(O)N(R16 )2, optionally substituted with one or more substituents selected from R 16 is hydrogen, C 1-4 Alkyl, and C 3-6 cycloalkyl.

[0297] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from pyridine, isoquinoline, indazole, thiazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R 5 may further independently be halogen, C 1-4 Alkyl, C 3-6 Alkynyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , and -N(R 16 )C(O)N(R 16 )2, optionally substituted with one or more substituents selected from R 16 is selected from hydrogen, methyl, -CHF2, -morpholinyl, imidazolyl, and cyclopropyl, and imidazolyl is C 1-4 Optionally substituted with alkyl.

[0298] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from pyridine, isoquinoline, indazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R 5 is further fluoro, chloro, methyl, -OH, -OCH3, -OCHF2, -CF3, -B(OH)2,

[0299] [ka] and optionally substituted with one or more substituents selected from:

[0300] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 is selected from pyridine, isoquinoline, indazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R 5 is further fluoro, chloro, methyl, -OH, -OCH3, -OCHF2, -CF3, -B(OH)2, -NH2, -CN,

[0301] [ka] In some embodiments, R 5is selected from pyridine, isoquinoline, indazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R 5 is further fluoro, chloro, methyl, -OH, -OCH3, -OCHF2, -CF3, -CN,

[0302] [ka] and optionally substituted with one or more substituents selected from:

[0303] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 teeth,

[0304] [ka]

[0305] [ka] is selected from.

[0306] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 teeth,

[0307] [ka]

[0308] [ka] is selected from.

[0309] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (IX), (IX-A), or (IX-B), R 5 teeth,

[0310] [ka] is selected from.

[0311] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is a compound of Formula (X):

[0312] [ka] or a pharmaceutically acceptable salt thereof, 2 is defined as in formula (A), (A-1), (I), or (IA), and R 21 , R 22 , and s are each defined as in formula (VII).

[0313] In some embodiments, the compound or salt of formula (A), (A-1), (I), or (IA) has the formula (XA):

[0314] [ka] or a pharmaceutically acceptable salt thereof, 2is defined as in formula (A), (A-1), (I), or (IA), and R 21 , R 22 , and s are each defined as in formula (VII).

[0315] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) has the formula (XB):

[0316] [ka] or a pharmaceutically acceptable salt thereof, 2 is defined as in formula (A), (A-1), (I), or (IA), and R 21 , R 22 , and s are each defined as in formula (VII).

[0317] In some embodiments, with respect to a compound or salt of formula (VII), (VII-A), (VII-B), (X), (XA), or (XB), R 21 teeth, Hydrogen, halogens, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, N(R 16 )C(O)N(R 16 )2, and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 and -CN. is selected from.

[0318] In some embodiments, with respect to a compound or salt of formula (VII), (VII-A), (VII-B), (X), (XA), or (XB), R 21 is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -N(R 16 )C(O)N(R 16 )2, and -CN, and R 16 independently represent hydrogen, C at each occurrence. 1-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0319] In some embodiments, with respect to a compound or salt of formula (VII), (VII-A), (VII-B), (X), (XA), or (XB), R 21 is hydrogen, halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, -B(OR 16 )2, and -CN, and R 16 independently represent hydrogen, C at each occurrence. 1-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0320] In some embodiments, with respect to a compound or salt of formula (VII), (VII-A), (VII-B), (X), (XA), or (XB), R 21 is hydrogen, C 1-4 Haloalkyl, -OR 16 , -N(R 16 )2, and -B(OR 16 )2 and R 16independently represent hydrogen, C at each occurrence. 1-6 It is selected from carbocycles and 3- to 6-membered heterocycles.

[0321] In some embodiments, with respect to a compound or salt of formula (VII), (VII-A), (VII-B), (X), (XA), or (XB), R 21 are hydrogen, -OH, -CHF2, -B(OH)2, and -N(R 16 In some embodiments, R 21 are hydrogen, -OH, -CHF2, -B(OH)2, -NH2,

[0322] [ka] In some embodiments, R 21 is selected from hydrogen and —OH. 21 is -OH.

[0323] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is represented by Formula (XI):

[0324] [ka] or a pharmaceutically acceptable salt thereof, 2 is defined as in formula (A), (A-1), (I), or (IA), and R 22 and s are each defined as in formula (VII).

[0325] In some embodiments, the compound or salt of formula (A), (A-1), (I), or (IA) has formula (XI-A):

[0326] [ka] or a pharmaceutically acceptable salt thereof, 2is defined as in formula (A), (A-1), (I), or (IA), and R 22 and s are each defined as in formula (VII).

[0327] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) has the formula (XI-B):

[0328] [ka] or a pharmaceutically acceptable salt thereof, 2 is defined as in formula (A), (A-1), (I), or (IA), and R 22 and s are each defined as in formula (VII).

[0329] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 teeth, Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11, -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11)C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and -CN, C1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and —CN) is selected from.

[0330] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 teeth, Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11, -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , ═O, and —CN), and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , =O, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -NO2, =O, and -CN), and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , =O, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6Alkynyl (one of which is independently halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , ═O, and —CN) is selected from.

[0331] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 teeth, Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, and -CN, C 1-6 Alkyl and C 2-6 alkynyl, any of which is optionally substituted with one or more halogens, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may independently be halogen, -OR 11 , C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each have one or more C 1-6and optionally substituted with one or more substituents selected from: is selected from.

[0332] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 teeth, Hydrogen, halogen, -OR 11 , C 1-6 Alkyl, and C 2-6 Alkynyl, and 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may independently contain halogen, C 1-6 Alkyl, C 1-6 haloalkyl, and 3- to 10-membered heterocycles (3- to 10-membered heterocycles may be one or more C 1-6 and optionally substituted with one or more substituents selected from: is selected from.

[0333] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 teeth, Hydrogen, halogens, C 1-4Haloalkyl, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), and —CN), is selected from.

[0334] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 teeth, Hydrogen, halogens, C 1-4 Haloalkyl, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 2-6 Alkynyl (any of which may independently be halogen, -OR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , ═O, and —CN) is selected from.

[0335] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 is hydrogen, halogen, C 1-4 Haloalkyl, -OR11 , -N(R 11 )2, and -CN, C 1-6 Alkyl, and C 2-6 alkynyl, any of which is optionally substituted with one or more halogens. 2 is hydrogen, halogen, -OR 11 , C 1-6 Alkyl, and C 2-6 alkynyl.

[0336] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 is hydrogen, halogen, -OR 11 , C 1-6 Alkyl, and C 2-6 alkynyl, and R 11 is hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, and C 3-6 Carbocycles are selected from:

[0337] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 is hydrogen, halogen, C 1-6Alkyl, C 2-4 Alkynyl, -OH, -OC 1-4 Alkyl, and -OC 3-6 In some embodiments, A is selected from carbocyclic rings. 2 is hydrogen, fluoro, bromo, methyl, ethyl, ethynylene, trifluoromethyl, -OCH3, and

[0338] [ka] In some embodiments, A 2 is hydrogen, bromo, methyl, ethyl, -OCH3, and

[0339] [ka] is selected from.

[0340] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 teeth, 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ), optionally substituted with one or more substituents selected from -CN, and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11, -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), and —CN) is selected from.

[0341] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 teeth, 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may be independently Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R11 , -N(R 11 )S(O)2R 11 , =O, and -CN, C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -NO2, =O, and -CN), and C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each independently represent Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , =O, and -CN, and C 1-6 Alkyl, C 2-6 Alkenyl, and C 3-6 Alkynyl (one of which is independently halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , ═O, and —CN) is selected from.

[0342] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 teeth, 5-10 membered heterocycles and C 3-10 Carbocyclic rings (any of which may independently be halogen, -OR 11 , C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Carbocyclic and 3- to 10-membered heterocyclic rings (C 3-10 The carbocyclic ring and the 3- to 10-membered heterocyclic ring each have one or more C 1-6 and optionally substituted with one or more substituents selected from: is selected from.

[0343] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 is a 5- to 10-membered heterocycle and C 3-10 carbocyclic rings, any of which may independently be halogen, C 1-6 Alkyl, C 1-6haloalkyl, and a 3- to 10-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more substituents selected from one or more C 1-6 Optionally substituted with alkyl.

[0344] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 is a 5- to 10-membered heterocycle and C 3-10 carbocycles, any of which is optionally substituted with one or more substituents independently selected from fluoro, methyl, and N-methylpiperazinyl.

[0345] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 is selected from phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, and pyrazinyl, any of which may independently be halogen, -OR 11 , C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 optionally substituted with one or more substituents selected from carbocycles, and 3- to 6-membered heterocycles; 3-10The carbocyclic ring and the 3- to 10-membered heterocyclic ring each have one or more C 1-6 Optionally substituted with alkyl.

[0346] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 is selected from phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, and pyrazinyl, any of which may independently be halogen, C 1-6 Alkyl, C 1-6 haloalkyl, and 3- to 6-membered heterocycle, wherein the 3- to 10-membered heterocycle is optionally substituted with one or more substituents selected from one or more C 1-6 Optionally substituted with alkyl.

[0347] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 is selected from phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, and pyrazinyl, any of which is optionally substituted with one or more substituents independently selected from fluoro, methyl, and N-methylpiperazinyl.

[0348] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), A 2 is cyclopropyl, phenyl,

[0349] [ka] is selected from.

[0350] In some embodiments, with respect to a compound or salt of formula (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R 22 Independently, in each example Halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R16 , -S(O)2R 16 , -NO2, and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -NO2, and -CN, optionally substituted with one or more substituents selected from is selected from.

[0351] In some embodiments, with respect to a compound or salt of formula (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R 22 Independently, in each example Halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, N(R 16 )C(O)N(R 16 )2, and -CN, and Independently halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 and -CN. is selected from.

[0352] In some embodiments, with respect to a compound or salt of formula (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R 22 are independently halogens in each example, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, N(R 16 )C(O)N(R 16 )2, and -CN. In some embodiments, R 22 are independently halogens in each example, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 16 , -SR 16 , -N(R 16 )2, -B(OR 16 )2, -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, N(R 16 )C(O)N(R 16 )2, and -CN.

[0353] In some embodiments, with respect to a compound or salt of formula (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R 22 are independently halogens in each example, C 1-4 Alkyl, -OR 16 , and -N(R 16 )C(O)R 16 In some embodiments, R22 are independently selected in each instance from halogen, methyl, -OH, and -N(R 16 )C(O)R 16 is selected from.

[0354] In some embodiments, with respect to a compound or salt of formula (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R 22 is independently fluoro, chloro, -OH, methyl,

[0355] [ka] is selected from.

[0356] In some embodiments, with respect to a compound or salt of Formula (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), s is selected from 0, 1, 2, and 3. In some embodiments, s is selected from 0, 1, and 2. In some embodiments, s is selected from 0 and 1. In some embodiments, s is 0.

[0357] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R 16 independently at each occurrence hydrogen, C 1-4 Alkyl (C 1-4Alkyl is independently Halogen, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20 )2, -NO2, and -CN, C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -SR 20 , -N(R 20 )2, -B(OR 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20) optionally substituted with one or more substituents selected from -2, -NO2, and -CN), and C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)N(R 20 )2, -C(O)OR 20 , -OC(O)R 20 , -N(R 20 )C(O)R 20 , -N(R 20 )S(O)2R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -NO2, and -CN), is selected from.

[0358] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R 16 independently at each occurrence hydrogen, C 1-4 Alkyl (C 1-4 Alkyl is independently Halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , and -CN, and C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -N(R 20 )2, -B(OR 20 )2, -C(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 and -CN), and C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, C 1-4 Haloalkyl, -OR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 and —CN), is selected from.

[0359] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R 16 independently at each occurrence One or more -B(OR 20 )2 optionally substituted with hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, and C 3-8 Carbocycles, and C 3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, and -OR 20 and optionally substituted with one or more substituents selected from is selected from.

[0360] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R 16 independently at each occurrence One or more -B(OR 20 )2 optionally substituted with hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, and C 3-8 Carbocycles, and C3-8 Carbocyclic rings and 3- to 8-membered heterocyclic rings (any of which may independently be halogen, C 1-4 Alkyl, and -OR 20 and optionally substituted with one or more substituents selected from is selected from R 20 are independently hydrogen and C 1-4 alkyl.

[0361] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R 16 independently represent hydrogen, C at each occurrence. 1-4 Alkyl, and C 3-8 In some embodiments, R 16 independently represent hydrogen, C at each occurrence. 1-4 Alkyl, and C 3-6 In some embodiments, R 16 is independently selected at each occurrence from hydrogen, methyl, and cyclopropyl. 16 is selected at each occurrence from hydrogen and methyl. In some embodiments, R 16 is hydrogen.

[0362] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R 20 independently represent hydrogen, C at each occurrence. 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 In some embodiments, R 20 independently represent hydrogen and C at each occurrence. 1-4 In some embodiments, R 20 is hydrogen.

[0363] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 are each independently hydrogen, C 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 In some embodiments, R is selected from haloalkyl. 10 , R 11 , R 12 , R 13 , R14 , and R 15 are each independently, at each occurrence, hydrogen, C 1-4 Alkyl, C 3-6 Carbocycles, 3- to 6-membered heterocycles, and C 1-4 In some embodiments, R is selected from haloalkyl. 10 , R 11 , R 12 , R 13 , R 14 , and R 15 are each independently, at each occurrence, hydrogen and C 1-4 In some embodiments, R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 are hydrogen atoms.

[0364] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), or (II-B), R 10 independently represent hydrogen, C at each occurrence. 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 In some embodiments, R is selected from haloalkyl. 10 independently represent hydrogen and C at each occurrence. 1-4 In some embodiments, R 10 is hydrogen.

[0365] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B), R11 independently represent hydrogen, C at each occurrence. 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 In some embodiments, R is selected from haloalkyl. 11 independently represent hydrogen, C at each occurrence. 1-4 Alkyl, and C 3-6 In some embodiments, R 11 independently represent hydrogen and C at each occurrence. 1-4 In some embodiments, R 11 is hydrogen.

[0366] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), or (II-B), R 12 independently represent hydrogen, C at each occurrence. 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 In some embodiments, R is selected from haloalkyl. 12 independently represent hydrogen and C at each occurrence. 1-4 In some embodiments, R 12 is hydrogen.

[0367] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 13 independently represent hydrogen, C at each occurrence. 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 In some embodiments, R is selected from haloalkyl. 13 independently represent hydrogen and C at each occurrence. 1-4 In some embodiments, R 13 is hydrogen.

[0368] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 14 independently represent hydrogen, C at each occurrence. 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 In some embodiments, R is selected from haloalkyl. 14 independently represent hydrogen and C at each occurrence. 1-4 In some embodiments, R 14 is hydrogen.

[0369] In some embodiments, with respect to a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), or (VIII-B), R 15 independently represent hydrogen, C at each occurrence. 1-4 Alkyl, C 3-8 Carbocycles, 3- to 8-membered heterocycles, and C 1-4 In some embodiments, R is selected from haloalkyl. 15 independently represent hydrogen and C at each occurrence. 1-4 In some embodiments, R 15 is independently selected at each occurrence from hydrogen and methyl. 15 is hydrogen.

[0370] In some embodiments, the compound or salt of Formula (A), (A-1), (I), or (IA) is a compound of Table 1. In some embodiments, the compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B) is a compound of Table 1.

[0371] [Table 1-1]

[0372] [Table 1-2]

[0373] [Table 1-3]

[0374] [Table 1-4]

[0375] [Table 1-5]

[0376] [Table 1-6]

[0377] [Table 1-7]

[0378] Table 1-8

[0379] Table 1-9

[0380] Table 1-10

[0381] Table 1-11

[0382] Table 1-12

[0383] Table 1-13

[0384] Table 1-14

[0385] Table 1-15

[0386] Table 1-16

[0387] Table 1-17

[0388] Table 1-18

[0389] Table 1-19

[0390] Table 1-20

[0391] Table 1-21

[0392] Table 1-22

[0393] Table 1-23

[0394] Table 1-24

[0395] Table 1-25

[0396] Table 1-26

[0397] Table 1-27

[0398] Table 1-28

[0399] [Table 1-29]

[0400] [Table 1-30]

[0401] [Table 1-31]

[0402] In certain embodiments, the compound of the present disclosure is selected from the compounds described in the Examples herein, or salts thereof.

[0403] In certain aspects, the present disclosure provides compounds or salts represented by the structure of formula (A), (A-1), or (I), wherein: R 1 is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Haloalkyl, C 2-6 Haloalkenyl, and C 2-6 haloalkynyl, for example, R 1 is selected from hydrogen, A 1 is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-10 membered heterocycle, and C 3-10 selected from carbocyclic rings, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-10 membered heterocycle, and C 3-10 Each carbocycle may independently be a halogen, -OR 11 , N(R 11 )2, -C(O)R11 , -NO2, -CN, C 1-6 Alkyl, and C 1-6 and optionally substituted with one or more substituents selected from haloalkyl, e.g., A 1 is hydrogen, A 2 is hydrogen, halogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-10 membered heterocycle, and C 3-10 selected from carbocyclic rings, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, 5-10 membered heterocycle, and C 3-10 Each carbocycle may independently be a halogen, -OR 11 , N(R 11 )2, -C(O)R 11 , -NO2, -CN, C 1-6 Alkyl, and C 1-6 and optionally substituted with one or more substituents selected from haloalkyl, e.g., A 2 is a halogen, C 1-6 Alkyl, and C 1-6 pyrazolyl optionally substituted with haloalkyl; q is selected from 1 and 2, for example, q is 1; m is selected from 0 and 1, for example, m is 0; n is selected from 0 and 1, for example, n is 0; R 2 are independently halogens in each example, C 1-4 Alkyl, and C 1-4 haloalkyl, for example, R 2 is a halogen, R 3 are independently halogens in each example, C 1-4 Alkyl, and C 1-4 haloalkyl, for example, R 3 is a halogen, p is selected from 0 and 1, for example, p is 0; R4 are independently halogens in each example, C 1-4 Alkyl, and C 1-4 haloalkyl, for example, R 4 is a halogen, L is -L 1 -L 2 wherein L 1 and L 2 are each independently (a) and (b) (a) -O-, -N(R 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15 )N(R 15 )-, and (b)C 1-6 Alkylene, C 3-8 Carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, -OR 15 and —CN), is selected from L 2 is optionally absent, and L 1 and L 2 are not both selected from (a), e.g., L is -L 1 - and L 1 is -N(R 15 )-, -N(R 15 )C(O)-, and -N(R 15 )C(O)O-; R 5 is C substituted with -C(O)H or -C(O)D 3-12 is a carbocyclic ring, and R 5 may further independently be halogen, -OR 16, -N(R 16 )2, -C(O)R 16 halogen, -OR optionally substituted with one or more substituents selected from -NO, and -CN; 16 , -N(R 16 )2, -C(O)R 16 , -NO2, -CN, and C 1-6 Optionally substituted with one or more substituents independently selected from alkyl, e.g., R 5 is halogen, OR 16 , C 1-6 Alkyl, and C 1-6 phenyl optionally substituted with haloalkyl; R 11 , R 15 , and R 16 are each independently, at each occurrence, hydrogen, C 1-4 Alkyl, and C 1-4 haloalkyl, e.g., R 11 , R 15 , and R 16 are hydrogen atoms.

[0404] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will occur to those skilled in the art without departing from the invention. It is understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention, and that methods and structures within the scope of these claims and their equivalents be covered thereby.

[0405] Chemical entities that have a carbon-carbon or carbon-nitrogen double bond can exist in either the Z or E form (i.e., cis or trans form). Additionally, some chemical entities can exist in various tautomeric forms. Unless otherwise specified, a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B) is intended to include all Z-forms, E-forms, and tautomeric forms as well.

[0406] "Isomers" are different compounds with the same molecular formula. "Stereoisomers" are isomers that differ only in the way their atoms are arranged in space. "Enantiomers" are a pair of stereoisomers that are non-superimposable mirror images of each other. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture. The term "(±)" is used to designate a racemic mixture where appropriate. "Diastereoisomers" or "diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other. Absolute stereochemistry is specified by the Cahn-Ingold-Prelog RS system. When a compound is a pure enantiomer, the stereochemistry of each chiral carbon can be specified as either R or S. Resolved compounds whose absolute configuration is unknown can be designated as (+) or (-) depending on the direction (dextrorotatory or levorotatory) they rotate plane-polarized light at the wavelength of the sodium D line. Certain compounds described herein contain one or more asymmetric centers and can therefore give rise to enantiomers, diastereomers, and other stereoisomeric forms, which can be defined in terms of absolute stereochemistry as (R)- or (S)-. The subject chemical entities, pharmaceutical compositions, and methods are intended to encompass all such possible stereoisomers, including racemic mixtures, optically pure forms, mixtures of diastereomers, and intermediate mixtures. Optically active (R)- and (S)-isomers can be prepared using chiral synthons or chiral reagents or resolved using conventional techniques. The optical activity of a compound can be analyzed by any suitable method, including, but not limited to, chiral chromatography and polarimetry, to determine the degree of predominance of one stereoisomer over another.

[0407] The compounds or salts of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B) may in some cases exist in diastereomeric, enantiomeric, or other stereoisomeric forms. The compounds presented herein include all diastereomeric, enantiomeric, and epimeric forms, as well as racemates, mixtures of diastereomers, and other mixtures thereof, to the extent that one skilled in the art can do so through routine experimentation. Separation of stereoisomers may be carried out by chromatography, or by forming diastereomers and separating them by recrystallization or chromatography, or any combination thereof ("Enantiomers, Racemates, and Resolutions," by Jean Jacques, Andre Collet, and Samuel H. Wilen, John Wiley and Sons, Inc., 1981, incorporated herein by reference in this disclosure). Stereoisomers may also be obtained by stereoselective synthesis. Furthermore, a mixture of two enantiomers enriched in one of the two can be purified to give a more optically enriched form of the major enantiomer by recrystallization and / or trituration.

[0408] In certain embodiments, formulas (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V ), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX- A compound or salt of (B), (X), (XA), (XB), (XI), (XI-A), or (XI-B) may contain two or more enantiomers or diastereomers of the compound, with one enantiomer or diastereomer comprising at least about 70%, at least about 80%, at least about 90%, at least about 98%, or at least about 99% by weight or more of the total weight of all stereoisomers. Methods for producing substantially pure enantiomers are well known to those skilled in the art. For example, a single stereoisomer, e.g., an enantiomer, substantially free of stereoisomers may be obtained by resolving a racemic mixture using methods such as the formation of diastereomers with an optically active resolving agent (E.L. Eliel, Stereochemistry of Carbon Compounds, (1962), McGraw Hill, Lochmuller (1975) J. Chromatogr., 113(3):283-302). Racemic mixtures of chiral compounds can be separated and isolated by any suitable method, including, but not limited to, (1) formation of ionic diastereomeric salts with chiral compounds and separation by fractional crystallization or other methods, (2) formation of diastereomeric compounds with chiral derivatizing agents, separation of the diastereomers, and conversion to pure stereoisomers, and (3) direct separation of substantially pure or enriched stereoisomers under chiral conditions. Another approach to enantiomer separation is the use of Diacel chiral columns and elution with organic mobile phases, such as that offered as a fee-based service by Chiral Technologies (www.chiraltech.com).

[0409] "Tautomer" refers to a molecule that can undergo proton transfer from one atom to another atom of the molecule. In certain embodiments, a compound or salt of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B) exists as a tautomer. In situations where tautomerization is possible, a chemical equilibrium of tautomers may exist. The exact ratio of tautomers depends on various factors, including physical conditions, temperature, solvent, and pH. Some non-limiting examples of tautomeric equilibria include:

[0410] [ka] Examples include:

[0411] In some embodiments, the compounds disclosed herein are used in various isotopically enriched forms, e.g., 2 H, 3 H, 11 C. 13 C, and / or 14 C content is abundant. In a particular embodiment, the compound is deuterated at at least one position. Such deuterated forms can be prepared by the procedures described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos. 5,846,514 and 6,334,997, deuteration can improve the metabolic stability and / or efficacy of drugs, thereby prolonging their duration of action.

[0412] In certain embodiments, the compounds disclosed herein are 2 exchanged with H atoms 1Some or all of the H atoms are present. Methods for synthesizing deuterium-containing compounds are known in the art, and non-limiting examples include the following synthetic methods:

[0413] Deuterium-substituted compounds are synthesized using a variety of methods, including those described in Dean, Dennis C., ed., Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000;6(10)] 2000, p. 110; George W., Varma, Rajender S., The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony., Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0414] Deuterated starting materials are readily available and amenable to the synthetic methods described herein to effect the synthesis of deuterated compounds. Many deuterated reagents and building blocks are commercially available from chemical suppliers such as Aldrich Chemical Co.

[0415] Unless otherwise specified, the compounds described herein are intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, the replacement of a hydrogen by deuterium or tritium, or 13 C or 14 Compounds having this structure, except for the replacement of a carbon with a C-rich carbon, are within the scope of this disclosure.

[0416] The compounds of the present disclosure may optionally contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may contain unnatural proportions of atomic isotopes, such as deuterium ( 2 H), tritium ( 3 H), iodine-125( 125 I), or carbon-14 ( 14 It can be labeled with an isotope such as C. 2 H, 11 C. 13 C. 14 C. 15 C. 12 N, 13 N, 15 N, 16 N, 16 O. 17 O. 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34 S, 35 S, 36 S, 35 Cl, 37 Cl, 79 Br, 81 Br, and 125 All isotopic substitutions at I are contemplated. All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention.

[0417] The present disclosure includes salts, particularly pharmaceutically acceptable salts, of compounds of formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B). The compounds of the present disclosure may have sufficient acidic, sufficient basic, or both functional groups to form salts with any of a number of inorganic bases, and inorganic and organic acids. Alternatively, inherently charged compounds, such as those with tetravalent nitrogen, can form salts with a suitable counterion, e.g., a halide such as bromide, chloride, or fluoride, especially bromide.

[0418] The methods and compositions of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B) encompass the use of amorphous forms as well as crystalline forms (also known as polymorphs). The compounds described herein may also be in the form of pharmaceutically acceptable salts. Similarly, in some embodiments, active metabolites of these compounds having the same type of activity are included within the scope of this disclosure. Additionally, the compounds described herein can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, etc. The solvated forms of the compounds provided herein are also considered to be disclosed herein.

[0419] Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), ( VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), ( Compounds of X), (XA), (XB), (XI), (XI-A), or (XI-B) also include crystalline and amorphous forms of these compounds, pharmaceutically acceptable salts of these compounds having the same type of activity, and active metabolites, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, nonsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms of the compounds, as well as mixtures thereof.

[0420] The present disclosure includes salts, particularly pharmaceutically acceptable salts, of compounds represented by Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B). Compounds of the present invention that have functional groups that are sufficiently acidic, sufficiently basic, or both, can react with any of a number of inorganic bases, and inorganic and organic acids, to form salts. Alternatively, inherently charged compounds, such as those with tetravalent nitrogen, can form salts with a suitable counterion, e.g., a halide such as bromide, chloride, or fluoride, especially bromide.

[0421] In certain embodiments, a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B) may be a prodrug, for example, where a "hydroxyl" in the parent compound is present as an ester or carbonate, or a carboxylic acid present in the parent compound is present as an ester. The term "prodrug" is intended to encompass compounds that are converted into pharmaceutical agents of the present disclosure under physiological conditions. One method of making a prodrug is to include one or more selected moieties that are hydrolyzed under physiological conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by the enzymatic activity of a host animal, such as a specific target cell in the host animal. For example, esters or carbonates (e.g., esters or carbonates of alcohols or carboxylic acids, and esters of phosphonic acids) are preferred prodrugs of the present disclosure.

[0422] Pharmaceutical preparations In some aspects, the present disclosure provides pharmaceutical compositions comprising a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B) and at least one pharmaceutically acceptable excipient.

[0423] Pharmaceutical compositions can be formulated using one or more physiologically acceptable carriers, including excipients and auxiliary agents.The formulation can be modified according to the selected route of administration.Pharmaceutical compositions containing compounds, salts, or conjugates can be prepared, for example, by lyophilizing the compounds, salts, or conjugates, and then mixing, dissolving, emulsifying, encapsulating, or trapping the conjugates.Pharmaceutical compositions can also contain compounds, salts, or conjugates in free base form or in the form of pharmaceutically acceptable salts.

[0424] The compounds or salts of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B) may be formulated in any suitable pharmaceutical formulation. Pharmaceutical compositions of the present disclosure typically contain an active ingredient (e.g., a compound of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VII), (VII-B), (VIII), (VIII-A), (VII), (VII-B), (VIII), (VIII-A), (VII), (VII-B), (VIII), (VIII-A), (VII), (VII-B), (VIII), (VIII-B), (VII), (VII-C), (VII-D), (VII), (VII-E), (VII-F), (VII-G), (VII), (VII-H), (VII-I ... (II-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B) or a salt thereof) and one or more pharmaceutically acceptable excipients or carriers, including, but not limited to, inert solid diluents and fillers, diluents, sterile aqueous solutions and various organic solvents, penetration enhancers, antioxidants, solubilizing agents, and adjuvants.

[0425] Pharmaceutical formulations may be provided in any suitable form, which may depend on the route of administration. In some embodiments, the pharmaceutical compositions disclosed herein can be formulated into a dosage form for administration to a subject. In some embodiments, the pharmaceutical compositions are formulated for oral, intravenous, intraarterial, aerosol, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, intranasal, pulmonary, transmucosal, inhalation, and / or intraperitoneal administration. In some embodiments, the dosage form is formulated for oral administration. For example, the pharmaceutical compositions can be formulated in the form of pills, tablets, capsules, inhalers, suspensions, emulsions, gels, or powders. In some embodiments, the pharmaceutical compositions can be formulated as unit dosages in the form of liquids, gels, semi-liquids, semi-solids, or solids. The preparation of such pharmaceutical compositions is well known in the art. See, for example, Anderson, Philip O., Knoben, James E., and Troutman, William G., eds., Handbook of Clinical Drug Data, Tenth Edition, McGraw-Hill, 2002; Pratt and Taylor, eds., Principles of Drug Action, Third Edition, Churchill Livingston, New York, 1990; Katzung, eds., Basic and Clinical Pharmacology, Ninth Edition, McGraw-Hill, 2003; Goodman and Gilman, eds., The Pharmacological Basis of Therapeutics, Tenth Edition, McGraw-Hill, 2001; Remington's Pharmaceutical Sciences, 20th Ed., Lippincott Williams & Wilkins, 2000; and Martindale, Thirty-Second Edition (The Pharmaceutical Press, London, 1999).

[0426] Treatment method The compounds described herein can be used in the preparation of a medicament for the prevention or treatment of a disease or disorder. Additionally, methods for treating any of the diseases or disorders described herein in a subject in need of such treatment include administering to the mammal a therapeutically effective amount of a pharmaceutical composition containing at least one compound described herein, or a pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof.

[0427] The compositions containing the compounds described herein can be administered for prophylactic and / or therapeutic treatments. In therapeutic applications, the compositions are administered to a patient already suffering from a disease or condition in an amount sufficient to cure or at least partially arrest the symptoms of the disease or condition. Amounts effective for this use will depend on the severity and course of the disease or condition, previous treatments, the patient's health status, weight, and response to the drugs, and the judgment of the treating physician.

[0428] In prophylactic applications, compositions containing the compounds described herein are administered to a patient susceptible to or at risk of a particular disease, disorder, or condition. Such an amount is defined to be a "prophylactically effective amount or dose." For this use, the precise amount may further depend on the patient's health, weight, and the like. When used in a patient, the amount effective for this use will depend on the severity and course of the disease, disorder, or condition, previous treatments, the patient's health status, response to the drugs, and the judgment of the treating physician.

[0429] In some aspects, the present disclosure provides methods of treatment comprising administering to a subject in need thereof an effective amount of a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B). In some aspects, the present disclosure provides a method for treating cancer in a patient in need thereof, comprising administering to the subject an effective amount of a compound or salt of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B). In some embodiments, the cancer is selected from breast cancer, colorectal cancer, and meningioma. In some embodiments, the cancer is breast cancer. In some embodiments, the cancer is colorectal cancer. In some embodiments, the cancer is meningioma.

[0430] In certain embodiments, the present disclosure may be used as a method of inhibiting AKT1 protein in a subject in need thereof, the method comprising administering to a subject a compound of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), ( XI), (XI-A), or (XI-B), or a pharmaceutical composition of Formula (A), (A-1), (I), (IA), (II), (II-A), (II-B), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), (VI-B), (VII), (VII-A), (VII-B), (VIII), (VIII-A), (VIII-B), (IX), (IX-A), (IX-B), (X), (XA), (XB), (XI), (XI-A), or (XI-B) to a subject. In some embodiments, the AKT protein is a mutant AKT1 protein. In some embodiments, the mutant AKT1 protein comprises an E17K mutation. In some embodiments, the administering step modulates the activity of mutant AKT1.

[0431] Terremoto Biosciences, Inc. and The Regents of the University of California are parties to a collaborative research agreement entered into on or before February 24, 2023. [Example]

[0432] Having now generally described the invention, it will be more readily understood by reference to the following examples, which are included merely for the purpose of illustrating certain aspects and embodiments of the invention and are not intended to limit the invention in any way.

[0433] chemical synthesis The following examples illustrate various methods for preparing the compounds described herein. The examples are illustrative but not comprehensive. It will be understood by those skilled in the art that the compounds described may be synthesized by similar methods.

[0434] Example 1: 4-(2-((5-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)amino)ethyl)-2-hydroxybenzaldehyde

[0435] [ka]

[0436] Step 1: Synthesis of 3-(3-{1-[(2-{3-[(tert-butyldimethylsilyl)oxy]-4-(1,3-dioxolan-2-yl)phenyl}ethyl)amino]-2,3-dihydro-1H-inden-5-yl}-5-phenylimidazo[4,5-b]pyridin-2-yl)pyridin-2-amine 3-[3-(1-amino-2,3-dihydro-1H-inden-5-yl)-5-phenylimidazo[4,5-b]pyridin-2-yl]pyridin-2-amine (Intermediate 1-4) (80 mg, 0.19 mmol, 1 equiv.) and 2-{3-[(tert-butyldimethylsilyl)oxy]-4-(1,3-dioxolan-2-yl)phenyl}acetaldehyde (Intermediate 1-5) (124 mg, 0.38 mmol, 2 equiv.) were dissolved in 1,2-dichloroethane (7 mL) and methanol (7 mL). The mixture was stirred at room temperature for 30 minutes, followed by the addition of sodium cyanoborohydride (36 mg, 0.58 mmol, 3 equiv.). The reaction mixture was stirred at room temperature for an additional hour. The reaction was quenched with water (20 mL). The resulting mixture was extracted with ethyl acetate (3 x 20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by reverse-phase flash chromatography on C18 silica gel using a 20-60% gradient of acetonitrile in water (+0.05% TFA) to give 3-(3-{1-[(2-{3-[(tert-butyldimethylsilyl)oxy]-4-(1,3-dioxolan-2-yl)phenyl}ethyl)amino]-2,3-dihydro-1H-inden-5-yl}-5-phenylimidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (45 mg, 32%) as a yellow oil. MS(ESI) calculated for C 43 H 48 N6O3Si:724.36,found 725.20[M+H] + .

[0437] Step 2: Synthesis of 4-(2-((5-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)amino)ethyl)-2-hydroxybenzaldehyde (Example 1) 3-(3-{1-[(2-{3-[(tert-butyldimethylsilyl)oxy]-4-(1,3-dioxolan-2-yl)phenyl}ethyl)amino]-2,3-dihydro-1H-inden-5-yl}-5-phenylimidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (70 mg, 0.097 mmol, 1 equiv.) was dissolved in tetrahydrofuran (1 mL). EtN 3HF (17 mg) was added, and the mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure and purified by preparative HPLC on a Sunfire Prep C18 OBD column (19x250 mm, 10 μm) using a 15-33% gradient of acetonitrile in water (+0.05% TFA) to give 4-(2-((5-(2-(2-aminopyridin-3-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)amino)ethyl)-2-hydroxybenzaldehyde (Example 1) (4 mg, 3%) as a pale yellow solid. MS (ESI) calculated for C 35 H 30 N6O2:566.24m / z,found 567.25[M+H] + . 1 H NMR(400MHz,DMSO-d6)δ(ppm):10.16-10.20(m,1H),8.26-8.29(m,1H),7.98-8.02(m,4H),7.66-7.73(m,2H),7.30-7.55(m,6H),6.91-6.95( m,2H),6.44-6.46(m,1H),4.89-4.90(m,1H),3.26-3.28(m,2H),3.12- 3.13(m,1H),2.95-2.97(m,3H),2.54-2.57(m,1H),2.25-2.26(m,1H).

[0438] Intermediate 1-1: N-{5-[2-(2-aminopyridin-3-yl)-5-phenylimidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl}acetamide

[0439] [ka]

[0440] Intermediate 1-2: (R)-3-(3-(1-amino-2,3-dihydro-1H-inden-5-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

[0441] [ka]

[0442] Intermediate 1-3: (S)-3-(3-(1-amino-2,3-dihydro-1H-inden-5-yl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine

[0443] [ka]

[0444] Step 1: Synthesis of N-(5-bromo-2,3-dihydro-1H-inden-1-yl)acetamide 5-Bromo-2,3-dihydro-1H-inden-1-amine (10 g, 47 mmol, 1 equiv.) was dissolved in dichloromethane (500 mL), followed by the addition of acetic anhydride (7.2 g, 71 mmol, 1.5 equiv.) and triethylamine (14 g, 141 mmol, 3 equiv.). The reaction mixture was stirred overnight at room temperature. The reaction was quenched by pouring into water (500 mL), and the mixture was extracted with dichloromethane (2 x 500 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The product was purified by silica gel chromatography using a gradient of 50-80% ethyl acetate in petroleum ether to give N-(5-bromo-2,3-dihydro-1H-inden-1-yl)acetamide (10 g, 83%) as a white solid. MS (ESI) calculated for C 11 H 12 BrNO:253.01m / z,found 254.15 / 256.15[M+H] + .

[0445] Step 2: Synthesis of benzyl N-(1-acetamido-2,3-dihydro-1H-inden-5-yl)carbamate A microwave tube was charged with Pd2(dba)3 (0.54 g, 0.59 mmol, 0.1 equiv.), N-(5-bromo-2,3-dihydro-1H-inden-1-yl)acetamide (1.5 g, 5.9 mmol, 1 equiv.), O-benzylcarbamate (1.1 g, 7.1 mmol, 1.2 equiv.), cesium carbonate (4.8 g, 15 mmol, 2.5 equiv.), and 1,4-dioxane (10 mL). The microwave tube was then flushed with nitrogen and degassed three times. The reaction was stirred at 100 °C for 3 h. Six batches were run in parallel. The reaction was quenched with water at room temperature. The resulting mixture was extracted with dichloromethane (3 x 50 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography using a gradient of 50-80% ethyl acetate in petroleum ether to give benzyl N-(1-acetamido-2,3-dihydro-1H-inden-5-yl)carbamate (5.6 g, 78%) as a red / brown oil. MS(ESI) calculated for C 19 H 20 N2O3:324.15m / z,found 325.10[M+H] + .

[0446] Step 3: Synthesis of N-(5-amino-2,3-dihydro-1H-inden-1-yl)acetamide A round-bottom flask was charged with benzyl N-(1-acetamido-2,3-dihydro-1H-inden-5-yl)carbamate (5.6 g, 17 mmol, 1 equiv.), 10% Pd / C (2.8 g, 26 mmol, 1.5 equiv.), methanol (50 mL), and ethyl acetate (200 mL). The reaction mixture was stirred overnight at room temperature under H2. The reaction mixture was filtered and concentrated. The product was purified by silica gel chromatography using a 50-80% gradient of ethyl acetate in petroleum ether to give N-(5-amino-2,3-dihydro-1H-inden-1-yl)acetamide (2.9 g, 88%) as a brown oil. MS (ESI) calculated for C 11 H 14 N2O:190.11m / z,found 191.15[M+H] + .

[0447] Step 4: Synthesis of N-{5-[(3-nitro-6-phenylpyridin-2-yl)amino]-2,3-dihydro-1H-inden-1-yl}acetamide A microwave tube was charged with Pd2(dba)3 (0.48 g, 0.53 mmol, 0.1 equiv.), N-(5-amino-2,3-dihydro-1H-inden-1-yl)acetamide (1 g, 5.3 mmol, 1 equiv.), 2-chloro-3-nitro-6-phenylpyridine (1.5 g, 6.3 mmol, 1.2 equiv.), RuPhos (0.25 g, 0.53 mmol, 0.1 equiv.), sodium carbonate (1.1 g, 11 mmol, 2 equiv.), and 1,4-dioxane (15 mL). The mixture was stirred under N2 at 90 °C for 3 h. Three batches were run in parallel. The reaction was quenched with water at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography using a gradient of 60-80% ethyl acetate in petroleum ether to give N-{5-[(3-nitro-6-phenylpyridin-2-yl)amino]-2,3-dihydro-1H-inden-1-yl}acetamide (4.5 g, 83%) as a brown oil. MS (ESI) calculated for C 22 H 20 N4O3:388.15m / z,found 389.15[M+H] + .

[0448] Step 5: Synthesis of N-{5-[2-(2-aminopyridin-3-yl)-5-phenylimidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl}acetamide (Intermediate 1-1) A round-bottom flask was charged with N-{5-[(3-nitro-6-phenylpyridin-2-yl)amino]-2,3-dihydro-1H-inden-1-yl}acetamide (4.5 g, 12 mmol, 1 equiv.), 2-aminopyridine-3-carbaldehyde (1.7 g, 14 mmol, 1.2 equiv.), sodium dithionite (6.1 g, 35 mmol, 3 equiv.), DMSO (180 mL), and methanol (30 mL). The reaction mixture was refluxed at 100 °C overnight. The reaction was quenched by pouring into water (500 mL), and the mixture was extracted with ethyl acetate (3 x 100 mL). The combined organic fractions were dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by reverse-phase flash chromatography on C18 silica gel using a 10-50% gradient of acetonitrile in water (+0.05% ammonium bicarbonate) to give N-{5-[2-(2-aminopyridin-3-yl)-5-phenylimidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl}acetamide (Intermediate 1-1) (2.9 g, 89%) as a yellow solid. MS(ESI) calculated for C 28 H 24 N6O:460.20m / z,found 461.20[M+H] + .

[0449] Step 6: Chiral separation of N-{5-[2-(2-aminopyridin-3-yl)-5-phenylimidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl}acetamide The two enantiomers of N-{5-[2-(2-aminopyridin-3-yl)-5-phenylimidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl}acetamide (Intermediate 1-1) were separated by chiral preparative HPLC using a (R,R)-WHELK-O1-Kromasi column (5x25cm, 5µm) in 40% ethanol in hexane (in methanol + 0.5% 2N ammonia). N-[(1R)-5-[2-(2-aminopyridin-3-yl)-5-phenylimidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl]acetamide was obtained as the first eluting peak, and N-[(1S)-5-[2-(2-aminopyridin-3-yl)-5-phenylimidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl]acetamide was obtained as the second eluting peak.

[0450] Step 7: Synthesis of 3-{3-[(1R)-1-amino-2,3-dihydro-1H-inden-5-yl]-5-phenylimidazo[4,5-b]pyridin-2-yl}pyridin-2-amine (Intermediate 1-2) To a stirred solution of N-[(1R)-5-[2-(2-aminopyridin-3-yl)-5-phenylimidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl]acetamide (280 mg, 0.65 mmol, 1 equiv.) in methanol (4 mL) was added HCl (0.5 mL, concentrated). The resulting mixture was stirred at 90 °C overnight. The mixture was concentrated under reduced pressure to give 3-{3-[(1R)-1-amino-2,3-dihydro-1H-inden-5-yl]-5-phenylimidazo[4,5-b]pyridin-2-yl}pyridin-2-amine (Intermediate 1-2) (200 mg, 73%) as a red / brown oil, which was used in subsequent transformations without further purification. MS (ESI) calculated for C 26 H 22 N6:418.19m / z,found 419.20[M+H] + .

[0451] Step 8: Synthesis of 3-{3-[(1S)-1-amino-2,3-dihydro-1H-inden-5-yl]-5-phenylimidazo[4,5...

Claims

1. Formula (A) 【Chemistry 1】 or a pharmaceutically acceptable salt thereof, During the ceremony, R １ teeth, Hydrogen, halogen, -OR １０ , -SR １０ , -N(R １０ ) ２ , -C(O)N(R １０ ) ２ , -N(R １０ ) C(O)R １０ , -C(O)OR １０ , -OC(O)R １０ , -N(R １０ )C(O)OR １０ , -OC(O)N(R １０ ) ２ , -N(R １０ )C(O)N(R １０ ) ２ , -S(O)R １０ , -S(O) ２ R １０ , -N(R １０ ) S (O) ２ R １０ , -S(O) ２ N (R １０ ) ２ , -NO ２ , and -CN, C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any of which independently represents halogen, -OR １０ , -SR １０ , -N(R １０ ) ２ , -C(O)N(R １０ ) ２ , -N(R １０ ) C(O)R １０ , -C(O)OR １０ , -OC(O)R １０ , -N(R １０ )C(O)OR １０ , -OC(O)N(R １０ ) ２ , -N(R １０ )C(O)N(R １０ ) ２ , -S(O)R １０ , -S(O) ２ R １０ , -N(R １０ ) S (O) ２ R １０ , -S(O) ２ N (R １０ ) ２ , -NO ２ and —CN), and 3- to 6-membered heterocycle and C ３－６ Carbocyclic rings (any of which may independently be halogen, -OR １０ , -SR １０ , -N(R １０ ) ２ , -C(O)N(R １０ ) ２ , -N(R １０ ) C(O)R １０ , -C(O)OR １０ , -OC(O)R １０ , -N(R １０ )C(O)OR １０ , -OC(O)N(R １０ ) ２ , -N(R １０ )C(O)N(R １０ ) ２ , -S(O)R １０ , -S(O) ２ R １０ , -N(R １０ ) S (O) ２ R １０ , -S(O) ２ N (R １０ ) ２ , =O, -NO ２ , -CN,C １－６ Alkyl, and C １－６ haloalkyl) is selected from A １ and A ２ are each independently Hydrogen, halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -N(R １１ )C(O)OR １１ , -OC(O)N(R １１ ) ２ , -N(R １１ )C(O)N(R １１ ) ２ , -S(O)R １１ , -S(O) ２ R １１ , -N(R １１ ) S (O) ２ R １１ , -S(O) ２ N (R １１ ) ２ , -NO ２ , and -CN, C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any of which independently represents halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -N(R １１ )C(O)OR １１ , -OC(O)N(R １１ ) ２ , -N(R １１ )C(O)N(R １１ ) ２ , -S(O)R １１ , -S(O) ２ R １１ , -N(R １１ ) S (O) ２ R １１ , -S(O) ２ N (R １１ ) ２ , -NO ２ , =O, =S, =N(R １１ ), and —CN), and 5- to 10-membered heterocycle and C ３－１０ Carbocyclic rings (any of which may be independently ハロゲン、-OR １１ 、-SR １１ 、-N(R １１ ) ２ 、-C(O)R １１ 、-C(O)N(R １１ ) ２ 、-N(R １１ )C(O)R １１ 、-N(R １１ )S(O) ２ R １１ 、-C(O)OR １１ 、-OC(O)R １１ 、-N(R １１ )C(O)OR １１ 、-OC(O)N(R １１ ) ２ 、-N(R １１ )C(O)N(R １１ ) ２ 、-S(O)R １１ 、-S(O) ２ R １１ 、-S(O) ２ N(R １１ ) ２ 、-NO ２ 、=O、=S、=N(R １１ )、および-CN、 C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any one of which is independently halogen, —OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -N(R １１ )C(O)OR １１ , -OC(O)N(R １１ ) ２ , -N(R １１ )C(O)N(R １１ ) ２ , -S(O)R １１ , -S(O) ２ R １１ , -N(R １１ ) S (O) ２ R １１ , -S(O) ２ N (R １１ ) ２ , -NO ２ , =O, =S, =N(R １１ ), and —CN), and C ３－１０ Carbocyclic rings and 3- to 10-membered heterocyclic rings (see above C ３－１０ The carbocycle and the 3- to 10-membered heterocycle each independently Halogen, -OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , =O, =S, =N(R １１ ), and -CN, C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any one of which is independently halogen, —OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , =O, =S, =N(R １１ ), optionally substituted with one or more substituents selected from -CN; is selected from q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2, and 3; R ２ are independently halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １２ , -SR １２ , -N(R １２ ) ２ , -NO ２ -CN; R ３ Independently, in each example Halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -C(O)OR １３ , -OC(O)R １３ , -NO ２ , and -CN, and independently a halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -C(O)OR １３ , -OC(O)R １３ , -NO ２ , =O, =S, =N(R １３ ), and —CN, optionally substituted with one or more substituents selected from １－６ Alkyl is selected from p is selected from 0, 1, 2, 3, 4, and 5; R ４ Independently, in each example Halogen, -OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -C(O)OR １４ , -OC(O)R １４ , -NO ２ , and -CN, and C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl (any one of which is independently halogen, —OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -C(O)OR １４ , -OC(O)R １４ , -NO ２ , =O, =S, =N(R １４ ), and —CN, optionally substituted with one or more substituents selected from Selected from, or Two Rs bonded to the same atom ４ are united, =O, =S, and =N(R １４ ) or forming a group selected from Two Rs attached to the same atom or adjacent atoms ４ together with the carbon to which they are attached form a 3- to 8-membered heterocycle and C ３－８ Carbocyclic rings (any of which may independently be halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １４ , -SR １４ , -N(R １４ ) ２ , -NO ２ and —CN, L is a bond or -L １ -L ２ -L ３ -L ４ -, wherein L １ , L ２ , L ３ , and L ４ are each independently (a) and (b) (a)-O-、-N(R １５ )-、-S-、-S(O)-、-S(O) ２ -、-S(O)(NR １５ )-、-N(R １５ )C(O)-、-N(R １５ )C(O)O-、-N(R １５ )S(O) ２ -、-N(R １５ )S(O) ２ N (R) １５ )-、-S(O)(NR １５ ) N ( R １５ )-、-N(R １５ ) N ( R １５ )-、-(R １５ )NC(O)N(R) １５ )-、および-(R １５ )NC(O)N(R) １５ ) N ( R １５ )-、ならびに (b) C １－６ Alkylene, C ２－６ Alkenylene, C ２－６ Alkynylene, C ３－８ carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, —OR １５ , -SR １５ , ═O, ═S, and —CN), is selected from L ２ , L ３ , and L ４ are each optionally absent, L １ , L ２ , L ３ , and L ４ are selected from (a), and the two selected are not adjacent; R ５ is a 3- to 12-membered heterocycle and C ３－１２ carbocycles, any of which is substituted by —C(O)H or —C(O)D; R ５ Furthermore, independently ハロゲン、-OR １６ 、-SR １６ 、-N(R １６ ) ２ 、-B(OR １６ ) ２ 、-C(O)R １６ 、-C(O)N(R １６ ) ２ 、-C(O)OR １６ 、-OC(O)R １６ 、-N(R １６ )C(O)R １６ 、-N(R １６ )S(O) ２ R １６ 、-S(O) ２ N(R １６ ) ２ 、-N(R １６ )C(O)N(R １６ ) ２ 、-N(R １６ )C(O)OR １６ 、-OC(O)N(R １６ ) ２ 、-N(R １６ )S(O) ２ N(R １６ ) ２ 、-S(O)R １６ 、-S(O) ２ R １６ 、-NO ２ 、=O、=S、=N(R １６ )、-N ３ 、および-CN、 C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any of which independently represents halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -C(O)OR １６ , -OC(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -N(R １６ ) S (O) ２ N (R １６ ) ２ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ , -N(R １６ )C(O)OR １６ , -OC(O)N(R １６ ) ２ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), and —CN), and independently a halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -C(O)OR １６ , -OC(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ , -N(R １６ )C(O)OR １６ , -OC(O)N(R １６ ) ２ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), -CN, C １－６ Alkyl, and C １－６ a 4- to 6-membered heterocycle optionally substituted with one or more substituents selected from haloalkyl and optionally substituted by one or more substituents selected from R １０ , R １１ , R １２ , R １３ , R １４ , and R １５ are each independently, at each occurrence, hydrogen, C １－４ Alkyl, C ３－８ Carbocycles, 3- to 8-membered heterocycles, and C １－４ haloalkyl; R １６ independently, at each occurrence, hydrogen, C １－４ Alkyl (the above C １－４ Alkyl is independently Halogen, -OR ２０ , -SR ２０ , -N(R ２０ ) ２ , -C(O)R ２０ , -C(O)OR ２０ , -OC(O)R ２０ , -C(O)N(R ２０ ) ２ , -N(R ２０ ) C(O)R ２０ , -N(R ２０ )C(O)N(R ２０ ) ２ , -N(R ２０ )C(O)OR ２０ , -OC(O)N(R ２０ ) ２ , -S(O)R ２０ , -S(O) ２ R ２０ , -N(R ２０ ) S (O) ２ R ２０ , -S(O) ２ N (R ２０ ) ２ , -NO ２ , and -CN, and C ３－８ Carbocycles and 3- to 8-membered heterocycles (any of which may independently be halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR ２０ , -SR ２０ , -N(R ２０ ) ２ , -B(OR ２０ ) ２ , -C(O)R ２０ , -C(O)OR ２０ , -OC(O)R ２０ , -C(O)N(R ２０ ) ２ , -N(R ２０ ) C(O)R ２０ , -N(R ２０ )C(O)N(R ２０ ) ２ , -N(R ２０ )C(O)OR ２０ , -OC(O)N(R ２０ ) ２ , -S(O)R ２０ , -S(O) ２ R ２０ , -N(R ２０ ) S (O) ２ R ２０ , -S(O) ２ N (R ２０ ) ２ , -NO ２ and —CN, optionally substituted with one or more substituents selected from optionally substituted with one or more substituents selected from C ３－８ Carbocycles and 3- to 8-membered heterocycles (any of which may independently be halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR ２０ , -SR ２０ , -N(R ２０ ) ２ , -C(O)R ２０ , -C(O)N(R ２０ ) ２ , -C(O)OR ２０ , -OC(O)R ２０ , -N(R ２０ ) C(O)R ２０ , -N(R ２０ ) S (O) ２ R ２０ , -N(R ２０ )C(O)N(R ２０ ) ２ , -N(R ２０ )C(O)OR ２０ , -OC(O)N(R ２０ ) ２ , -S(O)R ２０ , -S(O) ２ R ２０ , -NO ２ and —CN, optionally substituted with one or more substituents selected from is selected from R ２０ independently, at each occurrence, represent hydrogen, C １－４ Alkyl, C １－４ Haloalkyl, C ３－８ A compound, or a pharmaceutically acceptable salt thereof, selected from a carbocycle and a 3- to 8-membered heterocycle.

2. R １ is hydrogen, halogen, -OR １０ , -SR １０ , -N(R １０ ) ２ , -C(O)N(R １０ ) ２ , -N(R １０ ) C(O)R １０ , -C(O)OR １０ , -OC(O)R １０ , -N(R １０ )C(O)OR １０ , -OC(O)N(R １０ ) ２ , -N(R １０ )C(O)N(R １０ ) ２ , -S(O)R １０ , -S(O) ２ R １０ , -N(R １０ ) S (O) ２ R １０ , -S(O) ２ N (R １０ ) ２ , -NO ２ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

3. R １ is hydrogen, halogen, -OR １０ , -SR １０ , -N(R １０ ) ２ , -C(O)N(R １０ ) ２ , -S(O)R １０ , -S(O) ２ R １０ , -N(R １０ ) S (O) ２ R １０ , -S(O) ２ N (R １０ ) ２ , -NO ２ 3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

4. R １ but, 【Chemistry 2】 4. The compound of claim 3, wherein:

5. R １ But C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any of which independently represents halogen, -OR １０ , -SR １０ , -N(R １０ ) ２ , -C(O)N(R １０ ) ２ , -N(R １０ ) C(O)R １０ , -C(O)OR １０ , -OC(O)R １０ , -N(R １０ )C(O)OR １０ , -OC(O)N(R １０ ) ２ , -N(R １０ )C(O)N(R １０ ) ２ , -S(O)R １０ , -S(O) ２ R １０ , -N(R １０ ) S (O) ２ R １０ , -S(O) ２ N (R １０ ) ２ , -NO ２ 10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the group is selected from the group consisting of -CH, ...

6. R １ But C １－６ Alkyl and C ２－６ Alkynyl (each of which independently represents a halogen, -OR １０ , -SR １０ , -N(R １０ ) ２ , -NO ２ 6. The compound of claim 5, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from: optionally substituted with one or more substituents independently selected from: -CH, ...

7. R １ but, 【Transformation 3】 7. The compound of claim 6, selected from:

8. R １ is a 3- to 6-membered heterocycle and C ３－６ Carbocyclic rings (any of which may independently be halogen, -OR １０ , -SR １０ , -N(R １０ ) ２ , -C(O)N(R １０ ) ２ , -N(R １０ ) C(O)R １０ , -C(O)OR １０ , -OC(O)R １０ , -N(R １０ )C(O)OR １０ , -OC(O)N(R １０ ) ２ , -N(R １０ )C(O)N(R １０ ) ２ , -S(O)R １０ , -S(O) ２ R １０ , -N(R １０ ) S (O) ２ R １０ , -S(O) ２ N (R １０ ) ２ , =O, -NO ２ , -CN,C １－６ Alkyl, and C １－６ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of: haloalkyl, optionally substituted with one or more substituents selected from:

9. R １ is a 3- to 6-membered heterocycle and C ３－６ Carbocyclic rings (any of which may independently be halogen, -OR １０ , -SR １０ , -N(R １０ ) ２ , =O, -NO ２ , -CN,C １－６ Alkyl, and C １－６ 9. The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of: haloalkyl, optionally substituted with one or more substituents selected from:

10. R １ azetidinyl, imidazolyl, triazolyl, morpholinyl, piperazinyl, and cyclopropyl (any of which independently represents a halogen, -OR １０ , -SR １０ , -N(R １０ ) ２ , =O, -NO ２ , -CN,C １－６ Alkyl, and C １－６ 10. The compound of claim 9, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of: haloalkyl, optionally substituted with one or more substituents selected from:

11. R １ but, 【Chemistry 4】 11. The compound of claim 10, selected from:

12. R ５ is a 3- to 12-membered heterocycle substituted with —C(O)H or —C(O)D, and R ５ Furthermore, independently ハロゲン、-OR １６ 、-SR １６ 、-N(R １６ ) ２ 、-B(OR １６ ) ２ 、-C(O)R １６ 、-C(O)N(R １６ ) ２ 、-C(O)OR １６ 、-OC(O)R １６ 、-N(R １６ )C(O)R １６ 、-N(R １６ )S(O) ２ R １６ 、-S(O) ２ N(R １６ ) ２ 、-N(R １６ )C(O)N(R １６ ) ２ 、-N(R １６ )C(O)OR １６ 、-OC(O)N(R １６ ) ２ 、-N(R １６ )S(O) ２ N(R １６ ) ２ 、-S(O)R １６ 、-S(O) ２ R １６ 、-NO ２ 、=O、=S、=N(R １６ )、-N ３ 、および-CN、 C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any of which independently represents halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -C(O)OR １６ , -OC(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -N(R １６ ) S (O) ２ N (R １６ ) ２ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ , -N(R １６ )C(O)OR １６ , -OC(O)N(R １６ ) ２ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), and —CN), and independently a halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -C(O)OR １６ , -OC(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ , -N(R １６ )C(O)OR １６ , -OC(O)N(R １６ ) ２ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), -CN, C １－６ Alkyl, and C １－６ a 4- to 6-membered heterocycle optionally substituted with one or more substituents selected from haloalkyl 12. The compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from:

13. R ５ is selected from a 3- to 8-membered monocyclic heterocycle and a 6- to 12-membered bicyclic heterocycle, each of which is substituted with —C(O)H or —C(O)D; R ５ 13. The compound of claim 12, or a pharmaceutically acceptable salt thereof, wherein: is further optionally substituted with one or more substituents.

14. R ５ is a 6-12 membered bicyclic heterocycle, each of which is substituted with —C(O)H or —C(O)D, and R ５ Furthermore, independently ハロゲン、-OR １６ 、-SR １６ 、-N(R １６ ) ２ 、-B(OR １６ ) ２ 、-C(O)R １６ 、-C(O)N(R １６ ) ２ 、-C(O)OR １６ 、-OC(O)R １６ 、-N(R １６ )C(O)R １６ 、-N(R １６ )S(O) ２ R １６ 、-S(O) ２ N(R １６ ) ２ 、-N(R １６ )C(O)N(R １６ ) ２ 、-N(R １６ )C(O)OR １６ 、-OC(O)N(R １６ ) ２ 、-N(R １６ )S(O) ２ N(R １６ ) ２ 、-S(O)R １６ 、-S(O) ２ R １６ 、-NO ２ 、=O、=S、=N(R １６ )、-N ３ 、および-CN、ならびに C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any of which independently represents halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -C(O)OR １６ , -OC(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -N(R １６ ) S (O) ２ N (R １６ ) ２ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ , -N(R １６ )C(O)OR １６ , -OC(O)N(R １６ ) ２ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), and —CN, optionally substituted with one or more substituents selected from 14. The compound of claim 13, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from:

15. R ５ is a 6-12 membered bicyclic heterocycle, each of which is substituted with —C(O)H or —C(O)D, and R ５ further independently represent halogen, -OR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -C(O)OR １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -NO ２ , =O, =S, =N(R １６ ), -N ３ , and —CN, and independently halogen, —OR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -C(O)OR １６ , -NO ２ , =O, =S, =N(R １６ ), -N ３ C optionally substituted with one or more substituents selected from -CN, １－６ 15. The compound of claim 14, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from alkyl.

16. R ５ but, 【Transformation 5】 16. The compound of claim 15, wherein:

17. L is a bond and R ５ but 【Transformation 6】 16. The compound of claim 15, selected from:

18. R ５ is substituted with —C(O)H or —C(O)D ３－６ is a carbocyclic ring, and R ５ Furthermore, independently ハロゲン、-OR １６ 、-SR １６ 、-N(R １６ ) ２ 、-B(OR １６ ) ２ 、-C(O)R １６ 、-C(O)N(R １６ ) ２ 、-C(O)OR １６ 、-OC(O)R １６ 、-N(R １６ )C(O)R １６ 、-N(R １６ )S(O) ２ R １６ 、-S(O) ２ N(R １６ ) ２ 、-N(R １６ )C(O)N(R １６ ) ２ 、-N(R １６ )C(O)OR １６ 、-OC(O)N(R １６ ) ２ 、-N(R １６ )S(O) ２ N(R １６ ) ２ 、-S(O)R １６ 、-S(O) ２ R １６ 、-NO ２ 、=O、=S、=N(R １６ )、-N ３ 、および-CN、 C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any of which independently represents halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -C(O)OR １６ , -OC(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -N(R １６ ) S (O) ２ N (R １６ ) ２ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ , -N(R １６ )C(O)OR １６ , -OC(O)N(R １６ ) ２ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), and —CN), and independently a halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -C(O)OR １６ , -OC(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ , -N(R １６ )C(O)OR １６ , -OC(O)N(R １６ ) ２ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), -CN, C １－６ Alkyl, and C １－６ a 4- to 6-membered heterocycle optionally substituted with one or more substituents selected from haloalkyl 12. The compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from:

19. R ５ is phenyl substituted with —C(O)H or —C(O)D, and R ５ further independently represent halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) S (O) ２ N (R １６ ) ２ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), -N ３ , —CN, and independently a halogen, —OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -NO ２ , =O, =S, =N(R １６ ), and —CN, optionally substituted with one or more substituents selected from １－６ 20. The compound of claim 18, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from alkyl.

20. R ５ but, 【Transformation 7】 20. The compound of claim 19, selected from:

21. Formula (A) is Formula (A-1) 【Transformation 8】 or a pharmaceutically acceptable salt thereof, During the ceremony, R １ is hydrogen, halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １０ , -SR １０ , -N(R １０ ) ２ , -NO ２ -CN; A １ and A ２ are each independently Hydrogen, halogens, C １－４ Haloalkyl, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -N(R １１ )C(O)OR １１ , -OC(O)N(R １１ ) ２ , -N(R １１ )C(O)N(R １１ ) ２ , -S(O)R １１ , -S(O) ２ R １１ , -N(R １１ ) S (O) ２ R １１ , -S(O) ２ N (R １１ ) ２ , -NO ２ , and -CN, C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any of which independently represents halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -N(R １１ )C(O)OR １１ , -OC(O)N(R １１ ) ２ , -N(R １１ )C(O)N(R １１ ) ２ , -S(O)R １１ , -S(O) ２ R １１ , -N(R １１ ) S (O) ２ R １１ , -S(O) ２ N (R １１ ) ２ , -NO ２ , =O, =S, =N(R １１ ), and —CN), and 5- to 10-membered heterocycle and C ３－１０ Carbocyclic rings (any of which may be independently ハロゲン、-OR １１ 、-SR １１ 、-N(R １１ ) ２ 、-C(O)R １１ 、-C(O)N(R １１ ) ２ 、-N(R １１ )C(O)R １１ 、-N(R １１ )S(O) ２ R １１ 、-C(O)OR １１ 、-OC(O)R １１ 、-N(R １１ )C(O)OR １１ 、-OC(O)N(R １１ ) ２ 、-N(R １１ )C(O)N(R １１ ) ２ 、-S(O)R １１ 、-S(O) ２ R １１ 、-S(O) ２ N(R １１ ) ２ 、-NO ２ 、=O、=S、=N(R １１ )、および-CN、 C １－６ Alkyl, C ２－６ alkenyl, and C ３－６ Alkynyl (any one of which is independently halogen, —OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -N(R １１ )C(O)OR １１ , -OC(O)N(R １１ ) ２ , -N(R １１ )C(O)N(R １１ ) ２ , -S(O)R １１ , -S(O) ２ R １１ , -N(R １１ ) S (O) ２ R １１ , -S(O) ２ N (R １１ ) ２ , -NO ２ , =O, =S, =N(R １１ ), and —CN), and C ３－１０ Carbocyclic rings and 3- to 10-membered heterocyclic rings (see above C ３－１０ The carbocycle and the 3- to 10-membered heterocycle each independently Halogen, -OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , =O, =S, =N(R １１ ), and -CN, C １－６ Alkyl, C ２－６ alkenyl, and C ３－６ Alkynyl (any one of which is independently halogen, —OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , =O, =S, =N(R １１ ), and —CN) is selected from q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2, and 3; R ２ are independently halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １２ , -SR １２ , -N(R １２ ) ２ , -NO ２ -CN; R ３ Independently, in each example Halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -C(O)OR １３ , -OC(O)R １３ , -NO ２ , and -CN, and independently a halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -C(O)OR １３ , -OC(O)R １３ , -NO ２ , =O, =S, =N(R １３ ), and —CN, optionally substituted with one or more substituents selected from １－６ Alkyl is selected from p is selected from 0, 1, 2, 3, 4, and 5; R ４ Independently, in each example Halogen, -OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -C(O)OR １４ , -OC(O)R １４ , -NO ２ , and -CN, and C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl (any one of which is independently halogen, —OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -C(O)OR １４ , -OC(O)R １４ , -NO ２ , =O, =S, =N(R １４ ), and —CN, optionally substituted with one or more substituents selected from Selected from, or Two Rs bonded to the same atom ４ are united, =O, =S, and =N(R １４ ) or forming a group selected from Two Rs attached to the same atom or adjacent atoms ４ together with the carbon to which they are attached form a 3- to 8-membered heterocycle and C ３－８ Carbocyclic rings (any of which may independently be halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １４ , -SR １４ , -N(R １４ ) ２ , -NO ２ and —CN, L is -L １ -L ２ -L ３ -L ４ -, wherein L １ , L ２ , L ３ , and L ４ are each independently (a) and (b) (a)-O-、-N(R １５ )-、-S-、-S(O)-、-S(O) ２ -、-S(O)(NR １５ )-、-N(R １５ )C(O)-、-N(R １５ )C(O)O-、-N(R １５ )S(O) ２ -、-N(R １５ )S(O) ２ N (R) １５ )-、-S(O)(NR １５ ) N ( R １５ )-、-N(R １５ ) N ( R １５ )-、-(R １５ )NC(O)N(R) １５ )-、および-(R １５ )NC(O)N(R) １５ ) N ( R １５ )-、ならびに (b) C １－６ Alkylene, C ２－６ Alkenylene, C ２－６ Alkynylene, C ３－８ carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, —OR １５ , -SR １５ , ═O, ═S, and —CN), is selected from L ２ , L ３ , and L ４ are each optionally absent, L １ , L ２ , L ３ , and L ４ are selected from (a), and the two selected are not adjacent; R ５ is a 3- to 10-membered heterocycle and C ３－１０ carbocyclic rings, any of which is substituted by —C(O)H or —C(O)D; R ５ Furthermore, independently Halogen, C １－４ Alkyl, C ２－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -SR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -C(O)OR １６ , -OC(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ , -N(R １６ )C(O)OR １６ , -OC(O)N(R １６ ) ２ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), and -CN, and Independently halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １６ , -SR １６ , -N(R １６ ) ２ , -NO ２ and -CN; and optionally substituted by one or more substituents selected from R １０ , R １１ , R １２ , R １３ , R １４ , and R １５ are each independently, at each occurrence, hydrogen, C １－４ Alkyl, C ３－８ Carbocycles, 3- to 8-membered heterocycles, and C １－４ haloalkyl; R １６ independently, at each occurrence, hydrogen, C １－４ Alkyl (the above C １－４ Alkyl is independently ハロゲン、-OR ２０ 、-SR ２０ 、-N(R ２０ ) ２ 、-C(O)R ２０ 、-C(O)OR ２０ 、-OC(O)R ２０ 、-C(O)N(R ２０ ) ２ 、-N(R ２０ )C(O)R ２０ 、-N(R ２０ )C(O)N(R ２０ ) ２ 、-N(R ２０ )C(O)OR ２０ 、-OC(O)N(R ２０ ) ２ 、-S(O)R ２０ 、-S(O) ２ R ２０ 、-N(R ２０ )S(O) ２ R ２０ 、-S(O) ２ N(R ２０ ) ２ 、-NO ２ 、および-CN、 C ３－８ Carbocycles and 3- to 8-membered heterocycles (any of which may independently be halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR ２０ , -SR ２０ , -N(R ２０ ) ２ , -B(OR ２０ ) ２ , -C(O)R ２０ , -C(O)OR ２０ , -OC(O)R ２０ , -C(O)N(R ２０ ) ２ , -N(R ２０ ) C(O)R ２０ , -N(R ２０ )C(O)N(R ２０ ) ２ , -N(R ２０ )C(O)OR ２０ , -OC(O)N(R ２０ ) ２ , -S(O)R ２０ , -S(O) ２ R ２０ , -N(R ２０ ) S (O) ２ R ２０ , -S(O) ２ N (R ２０ ) ２ , -NO ２ and —CN), and C ３－８ Carbocycles and 3- to 8-membered heterocycles (any of which may be independently Halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR ２０ , -SR ２０ , -N(R ２０ ) ２ , -C(O)R ２０ , -C(O)N(R ２０ ) ２ , -C(O)OR ２０ , -OC(O)R ２０ , -N(R ２０ ) C(O)R ２０ , -N(R ２０ ) S (O) ２ R ２０ , -N(R ２０ )C(O)N(R ２０ ) ２ , -N(R ２０ )C(O)OR ２０ , -OC(O)N(R ２０ ) ２ , -S(O)R ２０ , -S(O) ２ R ２０ , -NO ２ and —CN, optionally substituted with one or more substituents selected from is selected from R ２０ independently, at each occurrence, represent hydrogen, C １－４ Alkyl, C １－４ Haloalkyl, C ３－８ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from a carbocycle and a 3- to 8-membered heterocycle.

22. R ５ is a 3- to 10-membered heterocycle and C ３－１０ carbocycles, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ２－６ Alkynyl, C １－４ haloalkyl, and —OR １６ 22. The compound of claim 21, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from:

23. R ５ is substituted with —C(O)H or —C(O)D ３－１０ is a carbocyclic ring, and R ５ further independently represent halogen, C １－４ Alkyl, C ２－６ Alkynyl, C １－４ haloalkyl, and —OR １６ 23. The compound of claim 22, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from:

24. R ５ is phenyl substituted with —C(O)H or —C(O)D, and R ５ further independently represent halogen, C １－４ Alkyl, C ２－６ Alkynyl, C １－４ haloalkyl, and —OR １６ and R １６ But hydrogen, C １－４ Alkyl, and C １－４ 24. The compound of claim 23, or a pharmaceutically acceptable salt thereof, selected from haloalkyl.

25. R ５ is phenyl substituted with —C(O)H, and R ５ Furthermore, independently C ２－６ Alkynyl and -OR １６ and R １６ But hydrogen, C １－４ Alkyl, and C １－４ 25. The compound of claim 24, or a pharmaceutically acceptable salt thereof, selected from haloalkyl.

26. R ５ but, 【Chemistry 9】 26. The compound of claim 25, selected from: or a pharmaceutically acceptable salt thereof.

27. Formula (A) is Formula (I) 【Chemistry 10】 or a pharmaceutically acceptable salt thereof, During the ceremony, R １ is hydrogen, halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １０ , -SR １０ , -N(R １０ ) ２ , -NO ２ -CN; A １ and A ２ are each independently Hydrogen, halogens, C １－４ Haloalkyl, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -N(R １１ )C(O)OR １１ , -OC(O)N(R １１ ) ２ , -N(R １１ )C(O)N(R １１ ) ２ , -S(O)R １１ , -S(O) ２ R １１ , -N(R １１ ) S (O) ２ R １１ , -S(O) ２ N (R １１ ) ２ , -NO ２ , and -CN, C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any of which independently represents halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -N(R １１ )C(O)OR １１ , -OC(O)N(R １１ ) ２ , -N(R １１ )C(O)N(R １１ ) ２ , -S(O)R １１ , -S(O) ２ R １１ , -N(R １１ ) S (O) ２ R １１ , -S(O) ２ N (R １１ ) ２ , -NO ２ , =O, =S, =N(R １１ ), and —CN), and 5- to 10-membered heterocycle and C ３－１０ Carbocyclic rings (any of which may be independently ハロゲン、-OR １１ 、-SR １１ 、-N(R １１ ) ２ 、-C(O)R １１ 、-C(O)N(R １１ ) ２ 、-N(R １１ )C(O)R １１ 、-N(R １１ )S(O) ２ R １１ 、-C(O)OR １１ 、-OC(O)R １１ 、-N(R １１ )C(O)OR １１ 、-OC(O)N(R １１ ) ２ 、-N(R １１ )C(O)N(R １１ ) ２ 、-S(O)R １１ 、-S(O) ２ R １１ 、-S(O) ２ N(R １１ ) ２ 、-NO ２ 、=O、=S、=N(R １１ )、および-CN、 C １－６ Alkyl, C ２－６ alkenyl, and C ３－６ Alkynyl (any one of which is independently halogen, —OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -N(R １１ )C(O)OR １１ , -OC(O)N(R １１ ) ２ , -N(R １１ )C(O)N(R １１ ) ２ , -S(O)R １１ , -S(O) ２ R １１ , -N(R １１ ) S (O) ２ R １１ , -S(O) ２ N (R １１ ) ２ , -NO ２ , =O, =S, =N(R １１ ), and —CN), and C ３－１０ Carbocyclic rings and 3- to 10-membered heterocyclic rings (see above C ３－１０ The carbocycle and the 3- to 10-membered heterocycle each independently Halogen, -OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , =O, =S, =N(R １１ ), and -CN, C １－６ Alkyl, C ２－６ alkenyl, and C ３－６ Alkynyl (any one of which is independently halogen, —OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , =O, =S, =N(R １１ ), and —CN) is selected from q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2, and 3; R ２ are independently halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １２ , -SR １２ , -N(R １２ ) ２ , -NO ２ -CN; R ３ Independently, in each example Halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -C(O)OR １３ , -OC(O)R １３ , -NO ２ , and -CN, and independently a halogen, -OR １３ , -SR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)N(R １３ ) ２ , -N(R １３ ) C(O)R １３ , -C(O)OR １３ , -OC(O)R １３ , -NO ２ , =O, =S, =N(R １３ ), and —CN, optionally substituted with one or more substituents selected from １－６ Alkyl is selected from p is selected from 0, 1, 2, 3, 4, and 5; R ４ Independently, in each example Halogen, -OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -C(O)OR １４ , -OC(O)R １４ , -NO ２ , and -CN, and C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl (any one of which is independently halogen, —OR １４ , -SR １４ , -N(R １４ ) ２ , -C(O)R １４ , -C(O)N(R １４ ) ２ , -N(R １４ ) C(O)R １４ , -C(O)OR １４ , -OC(O)R １４ , -NO ２ , =O, =S, =N(R １４ ), and —CN, optionally substituted with one or more substituents selected from Selected from, or Two Rs bonded to the same atom ４ are united, =O, =S, and =N(R １４ ) or forming a group selected from Two Rs attached to the same atom or adjacent atoms ４ together with the carbon to which they are attached form a 3- to 8-membered heterocycle and C ３－８ Carbocyclic rings (any of which may independently be halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １４ , -SR １４ , -N(R １４ ) ２ , -NO ２ and —CN, L is -L １ -L ２ -L ３ -L ４ -, wherein L １ , L ２ , L ３ , and L ４ are each independently (a) and (b) (a)-O-、-N(R １５ )-、-S-、-S(O)-、-S(O) ２ -、-S(O)(NR １５ )-、-N(R １５ )C(O)-、-N(R １５ )C(O)O-、-N(R １５ )S(O) ２ -、-N(R １５ )S(O) ２ N (R) １５ )-、-S(O)(NR １５ ) N ( R １５ )-、-N(R １５ ) N ( R １５ )-、-(R １５ )NC(O)N(R) １５ )-、および-(R １５ )NC(O)N(R) １５ ) N ( R １５ )-、ならびに (b) C １－６ Alkylene, C ２－６ Alkenylene, C ２－６ Alkynylene, C ３－８ carbocyclene, and 3- to 8-membered heterocyclene (any of which may independently be halogen, —OR １５ , -SR １５ , ═O, ═S, and —CN), is selected from L ２ , L ３ , and L ４ are each optionally absent, L １ , L ２ , L ３ , and L ４ are selected from (a), and the two selected are not adjacent; R ５ is a 3- to 10-membered heterocycle and C ３－１０ carbocyclic rings, any of which is substituted by —C(O)H or —C(O)D; R ５ Furthermore, independently Halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １６ , -SR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -C(O)OR １６ , -OC(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ , -N(R １６ )C(O)OR １６ , -OC(O)N(R １６ ) ２ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), and -CN, and Independently halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １６ , -SR １６ , -N(R １６ ) ２ , -NO ２ and -CN; and optionally substituted by one or more substituents selected from R １０ , R １１ , R １２ , R １３ , R １４ , and R １５ are each independently, at each occurrence, hydrogen, C １－４ Alkyl, C ３－８ Carbocycles, 3- to 8-membered heterocycles, and C １－４ haloalkyl; R １６ independently, at each occurrence, hydrogen, C １－４ Alkyl (the above C １－４ Alkyl is independently ハロゲン、-OR ２０ 、-SR ２０ 、-N(R ２０ ) ２ 、-C(O)R ２０ 、-C(O)OR ２０ 、-OC(O)R ２０ 、-C(O)N(R ２０ ) ２ 、-N(R ２０ )C(O)R ２０ 、-N(R ２０ )C(O)N(R ２０ ) ２ 、-N(R ２０ )C(O)OR ２０ 、-OC(O)N(R ２０ ) ２ 、-S(O)R ２０ 、-S(O) ２ R ２０ 、-N(R ２０ )S(O) ２ R ２０ 、-S(O) ２ N(R ２０ ) ２ 、-NO ２ 、および-CN、 C ３－８ Carbocycles and 3- to 8-membered heterocycles (any of which may independently be halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR ２０ , -SR ２０ , -N(R ２０ ) ２ , -B(OR ２０ ) ２ , -C(O)R ２０ , -C(O)OR ２０ , -OC(O)R ２０ , -C(O)N(R ２０ ) ２ , -N(R ２０ ) C(O)R ２０ , -N(R ２０ )C(O)N(R ２０ ) ２ , -N(R ２０ )C(O)OR ２０ , -OC(O)N(R ２０ ) ２ , -S(O)R ２０ , -S(O) ２ R ２０ , -N(R ２０ ) S (O) ２ R ２０ , -S(O) ２ N (R ２０ ) ２ , -NO ２ and —CN), and C ３－８ Carbocycles and 3- to 8-membered heterocycles (any of which may be independently Halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR ２０ , -SR ２０ , -N(R ２０ ) ２ , -C(O)R ２０ , -C(O)N(R ２０ ) ２ , -C(O)OR ２０ , -OC(O)R ２０ , -N(R ２０ ) C(O)R ２０ , -N(R ２０ ) S (O) ２ R ２０ , -N(R ２０ )C(O)N(R ２０ ) ２ , -N(R ２０ )C(O)OR ２０ , -OC(O)N(R ２０ ) ２ , -S(O)R ２０ , -S(O) ２ R ２０ , -NO ２ and —CN, optionally substituted with one or more substituents selected from is selected from R ２０ independently, at each occurrence, represent hydrogen, C １－４ Alkyl, C １－４ Haloalkyl, C ３－８ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from a carbocycle and a 3- to 8-membered heterocycle.

28. Formula (II) 【Chemistry 11】 28. The compound of claim 27, represented by the structure: or a pharmaceutically acceptable salt thereof.

29. Formula (II-A) 【Chemistry 12】 29. The compound of claim 27 or 28, represented by the structure: or a pharmaceutically acceptable salt thereof.

30. R １ But hydrogen, halogen, C １－４ Alkyl, and C １－４ 30. The compound of any one of claims 27 to 29, or a pharmaceutically acceptable salt thereof, selected from haloalkyl.

31. R １ The compound of any one of claims 27 to 30, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

32. R １ is hydrogen and C １－４ 31. The compound of any one of claims 27 to 30, or a pharmaceutically acceptable salt thereof, wherein:

33. R １ 31. The compound of any one of claims 27 to 30, or a pharmaceutically acceptable salt thereof, wherein is selected from methyl, ethyl, propyl, and isopropyl.

34. R １ But hydrogen, halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １０ 30. The compound of any one of claims 27 to 29, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

35. R １ is hydrogen, fluoro, chloro, methyl, ethyl, propyl, isopropyl, -CHF ２ , -OCH ３ , -OCHF ２ 35. The compound of claim 34, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

36. R ２ But halogen, C １－４ Alkyl, and C １－４ 36. The compound of any one of claims 27 to 35, or a pharmaceutically acceptable salt thereof, selected from haloalkyl.

37. R ２ but halogen and C １－４ 37. The compound of claim 36, or a pharmaceutically acceptable salt thereof, wherein:

38. R ２ 38. The compound of claim 37, or a pharmaceutically acceptable salt thereof, wherein is selected from fluoro and methyl.

39. 39. The compound of any one of claims 27 to 38, or a pharmaceutically acceptable salt thereof, wherein m is 0.

40. 39. The compound of any one of claims 27 to 38, or a pharmaceutically acceptable salt thereof, wherein m is 1.

41. Formula (III) 【Chemistry 13】 28. The compound of claim 27, represented by the structure: or a pharmaceutically acceptable salt thereof.

42. Formula (IV-A) 【Chemistry 14】 42. The compound of claim 27 or 41, represented by the structure: or a pharmaceutically acceptable salt thereof.

43. A １ But hydrogen, halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １１ , -N(R １１ ) ２ 43. The compound of any one of claims 27 to 42, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

44. A １ But hydrogen, halogen, C １－４ Alkyl, and C １－４ 44. The compound of any one of claims 27 to 43, or a pharmaceutically acceptable salt thereof, selected from haloalkyl.

45. A １ 45. The compound of any one of claims 7 to 44, or a pharmaceutically acceptable salt thereof, wherein is selected from hydrogen, fluoro, and methyl.

46. A １ 46. ​​The compound of any one of claims 27 to 45, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

47. A １ But hydrogen, halogen, C １－４ Alkyl, C １－４ haloalkyl, and —OR １１ 44. The compound of any one of claims 27 to 43, or a pharmaceutically acceptable salt thereof, selected from:

48. A １ is hydrogen, fluoro, methyl, —OH, and —OCH ３ 48. The compound of claim 47, selected from: or a pharmaceutically acceptable salt thereof.

49. A ２ but, Hydrogen, halogens, C １－４ Haloalkyl, -OR １１ , -N(R １１ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , and -CN, C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any of which independently represents halogen, -OR １１ , -N(R １１ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , ═O, and —CN), and 5- to 10-membered heterocycle and C ３－１０ Carbocyclic rings (any of which may be independently Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , ═O, and —CN, C １－６ Alkyl, C ２－６ alkenyl, and C ３－６ Alkynyl (any one of which is independently halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , -NO ２ , ═O, and —CN), and C ３－１０ Carbocyclic rings and 3- to 10-membered heterocyclic rings (see above C ３－１０ The carbocycle and the 3- to 10-membered heterocycle each independently Halogen, -OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , ═O, and —CN, and C １－６ Alkyl, C ２－６ alkenyl, and C ３－６ Alkynyl (any one of which is independently halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , ═O, and —CN) 49. The compound of any one of claims 27 to 48, or a pharmaceutically acceptable salt thereof, selected from:

50. A ２ but, Hydrogen, halogens, C １－４ Haloalkyl, -OR １１ , -N(R １１ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , and -CN, C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any of which independently represents halogen, -OR １１ , -N(R １１ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , ═O, and —CN), and 5- to 10-membered heterocycle and C ３－１０ Carbocyclic rings (any of which may be independently Halogen, -OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , ═O, and —CN, C １－６ Alkyl, C ２－６ alkenyl, and C ３－６ Alkynyl (any one of which is independently halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , -NO ２ , ═O, and —CN), and C ３－１０ Carbocyclic rings and 3- to 10-membered heterocyclic rings (see above C ３－１０ The carbocycle and the 3- to 10-membered heterocycle each independently Halogen, -OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , ═O, and —CN, and C １－６ Alkyl, C ２－６ alkenyl, and C ３－６ Alkynyl (any one of which is independently halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , ═O, and —CN) 49. The compound of any one of claims 27 to 48, or a pharmaceutically acceptable salt thereof, selected from:

51. A ２ but, Hydrogen, halogens, C １－４ Haloalkyl, -OR １１ , -N(R １１ ) ２ , and -CN, C １－６ Alkyl and C ２－６ alkynyl, any of which is optionally substituted with one or more halogens; and 5- to 10-membered heterocycle and C ３－１０ Carbocyclic rings (any of which may independently be halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -CN,C １－６ Alkyl, C ３－６ Alkynyl, C １－６ Haloalkyl, C ３－１０ optionally substituted with one or more substituents selected from a carbocycle, and a 3- to 10-membered heterocycle; １－６ Each alkyl is a halogen, —OR １１ , or -N(R １１ ) ２ and wherein said C is optionally substituted with one or more substituents selected from ３－１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C １－６ optionally substituted with alkyl 50. The compound of claim 49, selected from:

52. A ２ but, Hydrogen, halogens, C １－４ Haloalkyl, -OR １１ , -N(R １１ ) ２ , and -CN, C １－６ Alkyl and C ２－６ alkynyl, any of which is optionally substituted with one or more halogens; and 5- to 10-membered heterocycle and C ３－１０ Carbocyclic rings (any of which may independently be halogen, -OR １１ , C １－６ Alkyl, C １－６ Haloalkyl, C ３－１０ optionally substituted with one or more substituents selected from a carbocycle, and a 3- to 10-membered heterocycle; ３－１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C １－６ optionally substituted with alkyl 51. The compound of claim 50, selected from:

53. A ２ but, Hydrogen, halogens, C １－４ Haloalkyl, -OR １１ , -N(R １１ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , and -CN, and C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (any of which independently represents halogen, -OR １１ , -N(R １１ ) ２ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , ═O, and —CN), 51. The compound of any one of claims 27 to 50, or a pharmaceutically acceptable salt thereof, selected from:

54. A ２ But hydrogen, halogen, C １－４ Haloalkyl, -OR １１ , -N(R １１ ) ２ , -CN,C １－６ Alkyl, and C ２－６ alkynyl, wherein C １－６ Alkyl and the C ２－６ 54. The compound of claim 53, or a pharmaceutically acceptable salt thereof, wherein each alkynyl is optionally substituted with one or more halogens.

55. A ２ But hydrogen, halogen, C １－４ Haloalkyl, -OR １１ , -N(R １１ ) ２ , -CN,C １－６ Alkyl, and C ２－４ alkynyl, and R １１ But hydrogen, C １－４ Alkyl, and C ３－６ 54. The compound of claim 53, or a pharmaceutically acceptable salt thereof, selected from carbocycles.

56. A ２ is hydrogen, halogen, -OR １１ , C １－６ Alkyl, and C ２－４ alkynyl, and R １１ But hydrogen, C １－４ Alkyl, and C ３－６ 56. The compound of claim 55, or a pharmaceutically acceptable salt thereof, selected from carbocycles.

57. A ２ is hydrogen, fluoro, bromo, chloro, methyl, ethyl, ethynylene, trifluoromethyl, 【Chemistry 15】 , -OCH ３ , cyclopropyl, 【Chemistry 16】 53. The compound of claim 52, selected from:

58. A ２ is hydrogen, fluoro, bromo, methyl, ethyl, ethynylene, trifluoromethyl, —OCH ３ , and 【Chemistry 17】 58. The compound of claim 57, selected from:

59. A ２ is a 5- to 10-membered heterocycle and C ３－１０ carbocyclic rings, any of which may independently be Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , ═O, and —CN, C １－６ Alkyl, C ２－６ alkenyl, and C ３－６ Alkynyl (any one of which is independently halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , -NO ２ , ═O, and —CN), and C ３－１０ Carbocyclic rings and 3- to 10-membered heterocyclic rings (see above C ３－１０ The carbocycle and the 3- to 10-membered heterocycle each independently Halogen, -OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , ═O, and —CN, and C １－６ Alkyl, C ２－６ alkenyl, and C ３－６ Alkynyl (any one of which is independently halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , ═O, and —CN) 50. The compound of any one of claims 27 to 49, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from:

60. A ２ is a 5- to 10-membered heterocycle and C ３－１０ carbocyclic rings, any of which may independently be Halogen, -OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , ═O, and —CN, C １－６ Alkyl, C ２－６ alkenyl, and C ３－６ Alkynyl (any one of which is independently halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , -NO ２ , ═O, and —CN), and C ３－１０ Carbocyclic rings and 3- to 10-membered heterocyclic rings (see above C ３－１０ The carbocycle and the 3- to 10-membered heterocycle each independently Halogen, -OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , ═O, and —CN, and C １－６ Alkyl, C ２－６ alkenyl, and C ３－６ Alkynyl (any one of which is independently halogen, —OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ ) S (O) ２ R １１ , ═O, and —CN) 51. The compound of any one of claims 27 to 50, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from:

61. A ２ is a 5- to 10-membered heterocycle and C ３－１０ Carbocyclic rings (any of which may independently be halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -CN,C １－６ Alkyl, C ３－６ Alkynyl, C １－６ Haloalkyl, C ３－１０ optionally substituted with one or more substituents selected from carbocycle, and 3- to 10-membered heterocycle; １－６ Alkyl and C ３－６ Each alkynyl is independently a halogen, —OR １１ , and -N(R １１ ) ２ and wherein said C is optionally substituted with one or more substituents selected from ３－１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C １－６ 61. The compound of claim 60, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

62. A ２ is a 5- to 10-membered heterocycle and C ３－１０ Carbocyclic rings (any of which may independently be halogen, -OR １１ , C １－６ Alkyl, C １－６ Haloalkyl, C ３－１０ optionally substituted with one or more substituents selected from a carbocycle, and a 3- to 10-membered heterocycle; ３－１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C １－６ 61. The compound of claim 60, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

63. A ２ is a 5- to 10-membered heterocycle and C ３－１０ Carbocyclic rings (any of which may independently be fluoro, chloro, methyl, -CHF ２ , -CF ３ , ethynylene, -OCH ３ , -SCH ３ , -NH ２ , -N(CH ３ ) ２ , -C(O)H, -CN, -CH ２ OCH ３ , -CH ２ OH, cyclopropyl, pyrazolyl, azetidinyl, and N-methylpiperazinyl, wherein azetidinyl is optionally substituted with methyl, or a pharmaceutically acceptable salt thereof.

64. A ２ is a 5- to 10-membered heterocycle and C ３－１０ 61. The compound of claim 60, or a pharmaceutically acceptable salt thereof, wherein the ring is selected from carbocycles, any of which is optionally substituted with one or more substituents independently selected from fluoro, methyl, and N-methylpiperazinyl.

65. A ２ is cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, and thiazolyl (any of which may independently be halogen, —OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -CN,C １－６ Alkyl, C ３－６ Alkynyl, C ３－１０ optionally substituted with one or more substituents selected from carbocycles, and 3- to 6-membered heterocycles, １－６ Alkyl is independently selected from halogen and -OR １１ and wherein said C is optionally substituted with one or more substituents selected from ３－１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C １－６ 62. The compound of claim 61, or a pharmaceutically acceptable salt thereof, wherein:

66. A ２ is cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyrazolyl, furopyrazolyl, pyrazolopyridinyl, pyrazolooxazinyl, and thiazolyl, any of which may independently be halogen, —OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -CN,C １－６ Alkyl, C ３－６ Alkynyl, C ３－１０ optionally substituted with one or more substituents selected from carbocycles, and 3- to 6-membered heterocycles, １－６ Alkyl is independently selected from halogen and -OR １１ and wherein said C is optionally substituted with one or more substituents selected from ３－１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C １－６ 62. The compound of claim 61, or a pharmaceutically acceptable salt thereof, wherein:

67. A ２ is phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, and pyrazinyl (any of which independently represents a halogen, -OR １１ , C １－６ Alkyl, C １－６ Haloalkyl, C ３－１０ optionally substituted with one or more substituents selected from carbocycles, and 3- to 6-membered heterocycles, ３－１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C １－６ 63. The compound of claim 62, or a pharmaceutically acceptable salt thereof, wherein:

68. A ２ is cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, and thiazolyl (any of which may independently be halogen, —OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -CN,C １－６ Alkyl, C ３－６ Alkynyl, C １－６ haloalkyl and one or more C １－４ 62. The compound of claim 61, or a pharmaceutically acceptable salt thereof, wherein the heterocyclic ring is selected from the group consisting of a 3- to 6-membered heterocycle optionally substituted with alkyl, and wherein the heterocyclic ring is optionally substituted with alkyl.

69. A ２ is cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyrazolyl, furopyrazolyl, pyrazolopyridinyl, pyrazolooxazinyl, and thiazolyl, any of which may independently be halogen, —OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -CN,C １－６ Alkyl, C ３－６ Alkynyl, C １－６ haloalkyl and one or more C １－４ 62. The compound of claim 61, or a pharmaceutically acceptable salt thereof, wherein the heterocyclic ring is selected from the group consisting of a 3- to 6-membered heterocycle optionally substituted with alkyl, and wherein the heterocyclic ring is optionally substituted with alkyl.

70. A ２ phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, and pyrazinyl (any of which may independently be halogen, C １－６ Alkyl, C １－６ haloalkyl and one or more C １－４ 63. The compound of claim 62, or a pharmaceutically acceptable salt thereof, wherein the heterocyclic ring is selected from the group consisting of a 3- to 6-membered heterocycle optionally substituted with alkyl, optionally substituted with one or more substituents selected from:

71. A ２ is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, and thiazolyl, any of which is optionally substituted with one or more substituents independently selected from fluoro, chloro, methyl, and N-methylpiperazinyl, or a pharmaceutically acceptable salt thereof.

72. A ２ is selected from cyclopropyl, phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazolyl, oxazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyrrolopyrazolyl, furopyrazolyl, pyrazolopyridinyl, pyrazolooxazinyl, and thiazolyl, any of which is optionally substituted with one or more substituents independently selected from fluoro, chloro, methyl, and N-methylpiperazinyl, or a pharmaceutically acceptable salt thereof.

73. A ２ is selected from phenyl, morpholinyl, piperazinyl, pyrazolyl, pyridinyl, pyridazinyl, and pyrazinyl, any of which is optionally substituted with one or more substituents independently selected from fluoro, methyl, and N-methylpiperazinyl, or a pharmaceutically acceptable salt thereof.

74. A ２ are independently halogen, -OR １１ , C １－６ Alkyl, C １－６ Haloalkyl, -CN, C ３－１０ pyrazolyl optionally substituted with one or more substituents selected from a carbocycle and a 3- to 6-membered heterocycle, ３－１０ The carbocyclic ring and the 3- to 10-membered heterocyclic ring each contain one or more C １－６ 61. The compound of claim 60, or a pharmaceutically acceptable salt thereof, optionally substituted with alkyl.

75. A ２ But independently Halogen, —CN, —C(O)R １１ , -N(R １１ ) ２ , -SR １１ , C １－６ Alkyl, C ３－６ Alkynyl, C １－６ Haloalkyl, —OC １－６ Alkyl, —OC １－６ haloalkyl, and -OR １１ and C １－６ C optionally substituted with alkyl ３－１０ Carbocycles and 3- to 10-membered heterocycles 52. The compound of claim 49 or 51, or a pharmaceutically acceptable salt thereof, which is pyrazolyl optionally substituted with one or more substituents selected from:

76. A ２ However, one or more C ３－１０ 76. The compound of claim 75, which is pyrazolyl optionally substituted on a carbocyclic ring, or a pharmaceutically acceptable salt thereof.

77. A ２ 77. The compound of claim 76, or a pharmaceutically acceptable salt thereof, wherein is pyrazolyl optionally substituted with one or more cyclopropyl.

78. A ２ However, one or more C １－６ 76. The compound of claim 75, or a pharmaceutically acceptable salt thereof, which is pyrazolyl optionally substituted with one or more 3- to 6-membered heterocycles optionally substituted with alkyl.

79. A ２ is pyrazolyl optionally substituted with one or more pyrazolyl and azetidinyl, wherein said pyrazolyl and said azetidinyl are each C １－６ 79. The compound of claim 78, or a pharmaceutically acceptable salt thereof, optionally substituted with alkyl.

80. A ２ 80. The compound of claim 79, or a pharmaceutically acceptable salt thereof, wherein is pyrazolyl optionally substituted with one or more pyrazolyl and azetidinyl, wherein said pyrazolyl and said azetidinyl are each optionally substituted with methyl.

81. A ２ is pyrazolyl optionally substituted with one or more oxetanyl, pyrazolyl, and azetidinyl, wherein said oxetanyl, said pyrazolyl, and said azetidinyl are each C １－６ 76. The compound of claim 75, or a pharmaceutically acceptable salt thereof, optionally substituted with alkyl.

82. A ２ 82. The compound of claim 81, or a pharmaceutically acceptable salt thereof, wherein is pyrazolyl optionally substituted with one or more of oxetanyl, pyrazolyl, and azetidinyl, wherein said oxetanyl, said pyrazolyl, and said azetidinyl are each optionally substituted with methyl.

83. A ２ are independently halogen, C １－６ Alkyl, C １－６ Haloalkyl, —OC １－６ Alkyl, —OC １－６ 75. The compound of claim 74, or a pharmaceutically acceptable salt thereof, which is pyrazolyl optionally substituted with one or more substituents selected from haloalkyl, and -CN.

84. A ２ is -F, -Cl, -CH ３ , -CN, cyclopropyl, ethynylene, -CF ３ , phenyl, [Chemistry 18] 60. The compound of any one of claims 49 to 59, or a pharmaceutically acceptable salt thereof, selected from:

85. A ２ However, cyclopropyl, phenyl, 【Chemistry 19】 34. The compound of any one of claims 49 to 33, or a pharmaceutically acceptable salt thereof, selected from:

86. A ２ is -F, -Cl, -CH ３ , -CN, cyclopropyl, ethynylene, -CF ３ , phenyl, 【Chemistry 20】 【Chemistry 21】 61. The compound of any one of claims 49 to 60, or a pharmaceutically acceptable salt thereof, selected from:

87. R ３ Independently, in each instance, halogen, C １－４ Alkyl, C １－４ 87. The compound of any one of claims 27 to 86, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from haloalkyl, and -CN.

88. 87. The compound of any one of claims 27 to 86, or a pharmaceutically acceptable salt thereof, wherein n is 0.

89. R ４ But independently, in each example Halogen, -OR １４ , -SR １４ , -N(R １４ ) ２ , -CN,C １－６ Alkyl, C ２－６ alkenyl, and C ２－６ Alkynyl (as defined above) １－６ alkyl, the C ２－６ alkenyl, and the C ２－６ Each alkynyl is independently a halogen, —OR １４ , -N(R １４ ) ２ , ═O, and —CN), Selected from, or Two Rs bonded to the same atom ４ come together to form =O, or Two Rs attached to the same atom or adjacent atoms ４ However, together with the carbon to which they are bonded, C ３－８ forming a carbocyclic ring, R １４ is hydrogen and C １－４ 89. The compound of any one of claims 27 to 88, or a pharmaceutically acceptable salt thereof, wherein:

90. R ４ But independently, in each example Halogen, -OH, C １－６ Alkyl, and C ２－６ Alkynyl Selected from, or Two Rs bonded to the same atom ４ come together to form =O, or Two Rs attached to the same atom or adjacent atoms ４ However, together with the carbon to which they are bonded, C ３－８ 90. The compound of any one of claims 27 to 89, or a pharmaceutically acceptable salt thereof, which forms a carbocyclic ring.

91. R ４ But independently, in each example Halogen, -OH, C １－６ Alkyl, and C ２－６ Alkynyl Selected from, or Two Rs attached to the same atom or adjacent atoms ４ However, together with the carbon to which they are bonded, C ３－６ 81. The compound of any one of claims 27 to 80, or a pharmaceutically acceptable salt thereof, which forms a carbocyclic ring.

92. R ４ independently, in each instance, halogen and C １－６ alkyl, or two R bonded to the same atom or adjacent atoms; ４ However, together with the carbon to which they are bonded, C ３－６ 92. The compound of claim 91, or a pharmaceutically acceptable salt thereof, which forms a carbocyclic ring.

93. R ４ are independently selected at each instance from fluoro and methyl, or two R attached to the same atom or adjacent atoms ４ 93. The compound of claim 92, or a pharmaceutically acceptable salt thereof, wherein: together with the carbon to which they are attached form a cyclopropyl.

94. L １ , L ２ , L ３ , and L ４ are each independently (a) and (b) (a) -O-, -N(R １５ )-, -S-, -N(R １５ )C(O)-,-N(R １５ )C(O)O-,-N(R １５ ) S (O) ２ -N(R １５ ) N (R １５ )- and -(R １５ )NC(O)N(R １５ ) -, and (b) C １－６ Alkylene, C ２－６ Alkenylene, C ２－６ Alkynylene, C ３－６ carbocyclene, and 3- to 6-membered heterocyclene (any of which may independently be halogen, —OR １５ , ═O, and —CN), is selected from L ２ , L ３ , and L ４ are each optionally absent, L １ , L ２ , L ３ , and L ４ or a pharmaceutically acceptable salt thereof, wherein no more than two of are selected from (a), but the two selected are not adjacent.

95. L １ , L ２ , L ３ , and L ４ are each independently (a) and (b) (a) -N(R １５ )- and -N(R １５ )C(O)—, and (b) C １－６ Alkylene, C ２－６ Alkynylene, and C ３－６ Carbocyclene is selected from L ２ , L ３ , and L ４ are each optionally absent, L １ , L ２ , L ３ , and L ４ are selected from (a), but the two selected are not adjacent; R １５ is hydrogen and C １－４ 95. The compound of any one of claims 72 to 94, or a pharmaceutically acceptable salt thereof, wherein:

96. L ２ , L ３ , and L ４ and each are absent, or a pharmaceutically acceptable salt thereof.

97. 86. The compound of claim 85, or a pharmaceutically acceptable salt thereof, wherein L is selected from -N(H)- and -N(H)C(O)-.

98. L ３ and L ４ and each are absent, or a pharmaceutically acceptable salt thereof.

99. L １ But -N(R １５ )- and -N(R １５ )C(O)—, and L ２ But C １－６ Alkylene and C ３－６ carbocyclene; R １５ is hydrogen and C １－４ 99. The compound of claim 98, or a pharmaceutically acceptable salt thereof, wherein:

100. L, 【Chemistry 22】 100. The compound of any one of claims 94 to 99, or a pharmaceutically acceptable salt thereof, selected from:

101. L, 【Chemistry 23】 100. The compound of any one of claims 94 to 99, or a pharmaceutically acceptable salt thereof, selected from:

102. R ５ is a 3- to 10-membered heterocycle and C ３－１０ carbocycles, any of which is substituted with —C(O)H; R ５ further independently represent halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １６ , -C(O)R １６ , -SR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , N(R １６ )C(O)N(R １６ ) ２ 102. The compound of any one of claims 27 to 101, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from:

103. R ５ is a 3- to 10-membered heterocycle and C ３－１０ carbocycles, any of which is substituted with —C(O)H; R ５ may further independently represent halogen, C １－４ Alkyl, C １－４ Haloalkyl, -OR １６ , -C(O)R １６ , -SR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , N(R １６ )C(O)N(R １６ ) ２ 102. The compound of any one of claims 27 to 101, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from -, -CN, and a 4- to 6-membered heterocycle.

104. R １６ But independently, at each occurrence hydrogen, independently a halogen, and -B(OR ２０ ) ２ C optionally substituted with ３－８ C optionally substituted with one or more substituents selected from carbocycles １－４ Alkyl, and C ３－８ Carbocycles and 3- to 8-membered heterocycles (any of which may independently be halogen, C １－４ alkyl, and —OR ２０ and optionally substituted with one or more substituents selected from is selected from R ２０ independently represents hydrogen and C at each occurrence. １－４ 104. The compound of any one of claims 27 to 103, or a pharmaceutically acceptable salt thereof, wherein:

105. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ２－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , and -N(R １６ )C(O)N(R １６ ) ２ and R １６ But hydrogen, C １－６ Alkyl, C ３－６ Cycloalkyl, 3- to 8-membered heterocycle, and —N(R ２０ ) ２ wherein the 3-8 membered heterocycle is selected from １－４ 105. The compound of any one of claims 27 to 104, or a pharmaceutically acceptable salt thereof, optionally substituted with alkyl.

106. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ２－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -CN, -B(OR １６ ) ２ , -C(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ and a 4- to 6-membered heterocycle, optionally substituted with one or more substituents selected from R １６ But hydrogen, C １－６ Alkyl, C ３－６ Cycloalkyl, 3- to 8-membered heterocycle, and —N(R ２０ ) ２ wherein the 3-8 membered heterocycle is selected from １－４ 105. The compound of any one of claims 27 to 104, or a pharmaceutically acceptable salt thereof, optionally substituted with alkyl.

107. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ２－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , and -N(R １６ )C(O)N(R １６ ) ２ and R １６ But hydrogen, C １－６ Alkyl, C ３－６ Cycloalkyl, 3- to 8-membered heterocycle, and —N(R ２０ ) ２ or a pharmaceutically acceptable salt thereof, wherein said 3-8 membered heterocycle is optionally substituted with methyl.

108. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ２－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -CN, -B(OR １６ ) ２ , -C(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ and a 4- to 6-membered heterocycle, optionally substituted with one or more substituents selected from R １６ But hydrogen, C １－６ Alkyl, C ３－６ Cycloalkyl, 3- to 8-membered heterocycle, and —N(R ２０ ) ２ or a pharmaceutically acceptable salt thereof, wherein said 3-8 membered heterocycle is optionally substituted with methyl.

109. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ２－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , and -N(R １６ )C(O)N(R １６ ) ２ and R １６ But hydrogen, C １－６ Alkyl, C ３－６ Cycloalkyl, 3- to 8-membered heterocycle, and —N(R ２０ ) ２ and C is selected from １－６ 93. The compound of any one of claims 27 to 92, or a pharmaceutically acceptable salt thereof, wherein alkyl is optionally substituted with halogen.

110. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ２－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -CN, -B(OR １６ ) ２ , -C(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ and a 4- to 6-membered heterocycle, optionally substituted with one or more substituents selected from R １６ But hydrogen, C １－６ Alkyl, C ３－６ Cycloalkyl, 3- to 8-membered heterocycle, and —N(R ２０ ) ２ and C is selected from １－６ 93. The compound of any one of claims 27 to 92, or a pharmaceutically acceptable salt thereof, wherein alkyl is optionally substituted with halogen.

111. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ２－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , and -N(R １６ )C(O)N(R １６ ) ２ and R １６ But hydrogen, C １－６ Alkyl, C ３－６ Cycloalkyl, 3- to 8-membered heterocycle, and —N(R ２０ ) ２ and C is selected from １－６ 96. The compound of claim 95, or a pharmaceutically acceptable salt thereof, wherein alkyl is optionally substituted with fluoro or chloro.

112. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ２－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -CN, -C(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ and a 4- to 6-membered heterocycle, optionally substituted with one or more substituents selected from R １６ But hydrogen, C １－６ Alkyl, C ３－６ Cycloalkyl, 3- to 8-membered heterocycle, and —N(R ２０ ) ２ and C is selected from １－６ 96. The compound of claim 95, or a pharmaceutically acceptable salt thereof, wherein alkyl is optionally substituted with fluoro or chloro.

113. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H; R ５ further independently represent halogen, C １－４ Alkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , and -N(R １６ )C(O)N(R １６ ) ２ and R １６ But hydrogen, C １－６ Alkyl, and C ３－６ 105. The compound of any one of claims 27 to 104, or a pharmaceutically acceptable salt thereof, selected from cycloalkyl.

114. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H; R ５ further independently represent halogen, C １－４ Alkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -CN, -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ and a 4- to 6-membered heterocycle, optionally substituted with one or more substituents selected from R １６ But hydrogen, C １－６ Alkyl, and C ３－６ 105. The compound of any one of claims 27 to 104, or a pharmaceutically acceptable salt thereof, selected from cycloalkyl.

115. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ３－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -C(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , and -N(R １６ )C(O)N(R １６ ) ２ and R １６ is hydrogen, methyl, -CHF ２ , -morpholinyl, imidazolyl, and cyclopropyl, wherein said imidazolyl is C １－４ 106. The compound of claim 105, or a pharmaceutically acceptable salt thereof, optionally substituted with alkyl.

116. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ３－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -CN, -C(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -N(R １６ )C(O)N(R １６ ) ２ and a 4- to 6-membered heterocycle, optionally substituted with one or more substituents selected from R １６ is hydrogen, methyl, -CHF ２ , -morpholinyl, imidazolyl, and cyclopropyl, wherein said imidazolyl is C １－４ 106. The compound of claim 105, or a pharmaceutically acceptable salt thereof, optionally substituted with alkyl.

117. R ５ is selected from 3-10 membered heteroaryl and phenyl, any of which is substituted with —C(O)H; R ５ further independently represent halogen, C １－４ Alkyl, -OR １６ , and -N(R １６ ) C(O)R １６ and R １６ 112. The compound of claim 111, or a pharmaceutically acceptable salt thereof, wherein is selected from hydrogen, methyl, and cyclopropyl.

118. R ５ is selected from pyridine, isoquinoline, indazole, thiazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ３－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , C(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , and -N(R １６ )C(O)N(R １６ ) ２ and R １６ But hydrogen, C １－４ Alkyl, and C ３－６ 105. The compound of any one of claims 27 to 104, or a pharmaceutically acceptable salt thereof, selected from cycloalkyl.

119. R ５ is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ３－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -CN,C(O)R １６ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ and a 4- to 6-membered heterocycle, optionally substituted with one or more substituents selected from R １６ But hydrogen, C １－４ Alkyl, and C ３－６ 105. The compound of any one of claims 27 to 104, or a pharmaceutically acceptable salt thereof, selected from cycloalkyl.

120. R ５ is selected from pyridine, isoquinoline, indazole, and phenyl, any of which is substituted with —C(O)H; R ５ further independently represent halogen, C １－４ Alkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , and -N(R １６ )C(O)N(R １６ ) ２ and R １６ But hydrogen, C １－４ Alkyl, and C ３－６ 119. The compound of any one of claims 27 to 118, or a pharmaceutically acceptable salt thereof, selected from cycloalkyl.

121. R ５ is selected from pyridine, isoquinoline, indazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H; R ５ further independently represent halogen, C １－４ Alkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -CN, -N(R １６ ) C(O)R １６ , -N(R １６ ) S (O) ２ R １６ , -S(O) ２ N (R １６ ) ２ , -N(R １６ )C(O)N(R １６ ) ２ and a 4- to 6-membered heterocycle, optionally substituted with one or more substituents selected from R １６ But hydrogen, C １－４ Alkyl, and C ３－６ 119. The compound of any one of claims 27 to 118, or a pharmaceutically acceptable salt thereof, selected from cycloalkyl.

122. R ５ is selected from pyridine, isoquinoline, indazole, thiazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ３－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , C(O)R １６ , -N(R １６ ) C(O)R １６ , N(R １６ ) S (O) ２ R １６ , and -N(R １６ )C(O)N(R １６ ) ２ and R １６ is hydrogen, methyl, -CHF ２ , morpholinyl, imidazolyl, and cyclopropyl, wherein said imidazolyl is C １－４ 106. The compound of claim 105, or a pharmaceutically acceptable salt thereof, optionally substituted with alkyl.

123. R ５ is selected from pyridine, isoquinoline, indazole, thiazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently represent halogen, C １－４ Alkyl, C ３－６ Alkynyl, C １－４ Haloalkyl, -OR １６ , -N(R １６ ) ２ , -B(OR １６ ) ２ , -CN,C(O)R １６ , -N(R １６ ) C(O)R １６ , N(R １６ ) S (O) ２ R １６ , -N(R １６ )C(O)N(R １６ ) ２ and a 5-membered heterocycle, R １６ is hydrogen, methyl, -CHF ２ , morpholinyl, imidazolyl, and cyclopropyl, wherein said imidazolyl is C １－４ 106. The compound of claim 105, or a pharmaceutically acceptable salt thereof, optionally substituted with alkyl.

124. R ５ is selected from pyridine, isoquinoline, indazole, and phenyl, any of which is substituted with —C(O)H; R ５ further independently represent halogen, C １－４ Alkyl, -OR １６ , and -N(R １６ ) C(O)R １６ and R １６ 121. The compound of claim 120, or a pharmaceutically acceptable salt thereof, wherein is selected from hydrogen, methyl, and cyclopropyl.

125. R ５ is selected from pyridine, isoquinoline, indazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently selected from fluoro, chloro, methyl, —OH, —OCH ３ , -OCHF ２ , -CF ３ , -B(OH) ２ , 【Chemistry 24】 106. The compound of claim 105, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from:

126. R ５ is selected from pyridine, isoquinoline, indazole, benzothiazole, benzoxazole, pyrazolopyridine, benzimidazole, and phenyl, any of which is substituted with —C(O)H or —C(O)D; R ５ further independently selected from fluoro, chloro, methyl, —OH, —OCH ３ , -OCHF ２ , -CF ３ , -B(OH) ２ , -NH ２ , -CN, 【Chemistry 25】 106. The compound of claim 105, or a pharmaceutically acceptable salt thereof, optionally substituted with one or more substituents selected from:

127. R ５ but, 【Chemistry 26】 【Chemistry 27】 126. The compound of any one of claims 105 to 125, or a pharmaceutically acceptable salt thereof, selected from:

128. R ５ but, 【Chemistry 28】 【Chemistry 29】 127. The compound of any one of claims 105 to 126, or a pharmaceutically acceptable salt thereof, selected from:

129. R ５ but, 【Transformation 30】 126. The compound of any one of claims 105 to 125, or a pharmaceutically acceptable salt thereof, selected from: 【Request Item 130】 【Chemistry 31】 【Chemistry 32】 【Transformation 33】 【Transformation 34】 【Chemistry 35】 【Transformation 36】 【Chemistry 37】 【Transformation 38】 【Chemistry 39】 【Chemistry 40】 【Chemistry 41】 【Chemistry 42】 【Chemistry 43】 【Chemistry 44】 【Chemistry 45】 【Chemistry 46】 【Chemistry 47】 【Chemistry 48】 【Chemistry 49】 130. The compound of any one of claims 1 to 129, or a pharmaceutically acceptable salt thereof, selected from: 【Request Item 131】 【Chemistry 50】 【Chemistry 51】 【Chemistry 52】 【Chemistry 53】 【Chemistry 54】 【Transformation 55】 【Transformation 56】 【Chemistry 57】 【Transformation 58】 【Chemistry 59】 【Transformation 60】 【Chemistry 61】 【Transformation 62】 130. The compound of any one of claims 1 to 129, or a pharmaceutically acceptable salt thereof, selected from:

132. 132. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound according to any one of claims 1 to 131, or a pharmaceutically acceptable salt thereof.

133. 132. A method of modulating mutant AKT1 activity, comprising administering to a subject in need of modulation of mutant AKT1 activity a compound of any one of claims 1 to 131, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 132.

134. 132。 A method for selectively modulating the activity of mutant AKT1 over wild-type AKT, comprising administering to a subject in need of modulation of mutant AKT1 activity a compound of any one of claims 1 to 131, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 132, wherein the wild-type AKT is selected from wild-type AKT1 and wild-type AKT2.

135. 132. A method of treating cancer in a subject in need thereof, comprising administering to the subject a compound of any one of claims 1 to 131 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 132.

136. 136. The method of claim 135, wherein the cancer is selected from breast cancer, colorectal cancer, and meningioma.

137. 136. The method of claim 135, wherein said administering modulates the activity of mutant AKT1.

138. 138. The method of claim 133, 134, or 137, wherein the mutant AKT1 is AKT1 E17K.

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