Substitution 6-imidazopyridazine IL-17A modulator and its use

Abstract

This disclosure provides substituted 6-imidazopyridazine compounds for the modulation of IL-17A and pharmaceutical compositions thereof. These compounds are useful in the treatment of inflammatory conditions such as psoriasis, psoriatic arthritis, or ankylosing spondylitis.

Description

[Background technology]

[0001] The IL-17 family consists of six cytokines (IL-17A to IL-17F). Interleukin-17A (IL-17A) is an established pro-inflammatory cytokine involved in the induction of IL-6, IL-8, G-CSF, TNF-α, IL-1β, PGE2, and IFN-γ, as well as numerous chemokines and other effectors. IL-17A can form homodimers or heterodimers with its family member IL-17F and can bind to both IL-17 receptors, IL-17RA and IL-17RC, to mediate signaling. IL-17A is a major pathological cytokine expressed by Th17 cells, as well as CD8+ T cells, γδ cells, NK cells, NKT cells, macrophages, and dendritic cells, which are involved in inflammatory and autoimmune pathologies. In addition, IL-17A and Th17 are necessary for defense against various microorganisms, despite their involvement in inflammation and autoimmune disorders. Furthermore, IL-17A can act in cooperation with other inflammatory cytokines such as TNF-α, IFN-γ, and IL-1β to mediate pro-inflammatory effects.

[0002] To date, several biologics (secukinumab and ixekizumab) have been approved to modulate IL-17A for the treatment of inflammatory diseases such as psoriasis, ankylosing spondylitis, and psoriatic arthritis. These treatments require injection into the patient because they are not readily absorbed by the intestines when taken orally. Furthermore, these approved biologics have a high cost to the patient, limiting their availability to the patient population that needs them.

[0003] Several small molecule IL-17A modulators are approved for oral administration. However, while these offer the convenience of oral administration and lower patient cost, they lack the efficacy of approved biologics. Therefore, there is a need for the development of potent small molecule IL-17A modulators for the treatment of inflammatory diseases and other related disorders.

Summary of the Invention

Means for Solving the Problems

[0004] In certain embodiments, the present invention provides a compound of the structure represented by formula (A):

[0005]

Chem.

[0006] In certain embodiments, formula (A) or formula (I) is formula (Ia):

[0007] [ka] This is represented by the structure of [this structure].

[0008] In certain embodiments, formula (A) or formula (I) is formula (Ib):

[0009] [ka] This is represented by the structure of [this structure].

[0010] In certain embodiments, the Disclosure provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound or salt of formula (A), (I), (Ia), or (Ib).

[0011] In certain embodiments, the Disclosure provides a method for modulating IL-17A in a subject requiring modification of IL-17A, comprising administering to the subject a compound or salt of formula (A), (I), (Ia), or (Ib), or a pharmaceutical composition thereof.

[0012] In certain embodiments, the Disclosure provides a method for treating an inflammatory disease or condition, comprising administering a compound or salt of formula (A), (I), (Ia), or (Ib), or a pharmaceutical composition thereof, to a subject. In some embodiments, the inflammatory disease or condition is selected from psoriasis vulgaris, guttate psoriasis, psoriasis reversal, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis, and noninfectious uveitis.

[0013] Built-in by reference All publications, patents, and patent applications referenced in this specification are incorporated herein by reference to the same extent that each individual publication, patent, or patent application is specifically and individually indicated as being incorporated by reference. [Modes for carrying out the invention]

[0014] Preferred embodiments of the present invention have been shown and described herein, but it will be apparent to those skilled in the art that such embodiments are provided only as examples. Those skilled in the art will be able to conceive of numerous variations, modifications, and substitutions without departing from the present invention. It should be understood that various alternatives to the embodiments of the present invention described herein may be used in carrying out the present invention. The following claims define the scope of the present invention, and methods and structures within these claims, as well as their equivalents, are intended to be encompassed thereby.

[0015] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art in which this invention pertains. All patents and publications cited herein are incorporated by reference.

[0016] As used herein and in the appended claims, the singular forms “a,” “an,” and “the” refer to multiple subjects unless the context clearly indicates otherwise.

[0017] "Alkyl" refers to a monovalent radical of a linear or branched hydrocarbon chain consisting only of carbon and hydrogen atoms, without unsaturation, and preferably having 1 to 12 carbon atoms (i.e., C1-C 12 Alkyl). The alkyl is bonded to the rest of the molecule via a single bond. In certain embodiments, the alkyl contains 1 to 12 carbon atoms (i.e., C1-C12). 12Alkyl). In certain embodiments, the alkyl group contains 1 to 8 carbon atoms (i.e., C1-C8 alkyl). In other embodiments, the alkyl group contains 1 to 5 carbon atoms (i.e., C1-C5 alkyl). In other embodiments, the alkyl group contains 1 to 4 carbon atoms (i.e., C1-C4 alkyl). In other embodiments, the alkyl group contains 1 to 3 carbon atoms (i.e., C1-C3 alkyl). In other embodiments, the alkyl group contains 1 to 2 carbon atoms (i.e., C1-C2 alkyl). In other embodiments, the alkyl group contains 1 carbon atom (i.e., C1 alkyl). In other embodiments, the alkyl group contains 5 to 15 carbon atoms (i.e., C5-C 15 Alkyl). In other embodiments, the alkyl group contains 5 to 8 carbon atoms (i.e., C5-C8 alkyl). In other embodiments, the alkyl group contains 2 to 5 carbon atoms (i.e., C2-C5 alkyl). In other embodiments, the alkyl group contains 3 to 5 carbon atoms (i.e., C3-C5 alkyl). For example, the alkyl group may be bonded to the rest of the molecule by a single bond, such as 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), etc.

[0018] "Alkenyl" refers to a linear or branched hydrocarbon chain radical group consisting only of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having 2 to 12 carbon atoms (i.e., C2-C 12Alkenyls. In certain embodiments, alkenyls contain 2 to 8 carbon atoms (i.e., C2-C8 alkenyls). In certain embodiments, alkenyls contain 2 to 6 carbon atoms (i.e., C2-C6 alkenyls). In other embodiments, alkenyls contain 2 to 4 carbon atoms (i.e., C2-C4 alkenyls). Alkenyls are bonded to the rest of the molecule by single bonds, such as ethenyl (i.e., vinyl), propa-1-enyl (i.e., allyl), buta-1-enyl, penta-1-enyl, penta-1,4-dienyl, etc.

[0019] "Alkynyl" refers to a linear or branched hydrocarbon chain radical group consisting only of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having 2 to 12 carbon atoms (i.e., C2-C 12 Alkynnyls. In certain embodiments, the alkynyl contains 2 to 8 carbon atoms (i.e., C2-C8 alkynyls). In other embodiments, the alkynyl contains 2 to 6 carbon atoms (i.e., C2-C6 alkynyls). In other embodiments, the alkynyl contains 2 to 4 carbon atoms (i.e., C2-C4 alkynyls). The alkynyl is bonded to the rest of the molecule by a single bond, such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, etc.

[0020] "Alkylene" refers to a straight-chain divalent hydrocarbon chain consisting only of carbon and hydrogen, without unsaturation, with the remaining portion bonded to a radical group, preferably having 1 to 12 carbon atoms, where the rest of the molecule is linked to the radical group, such as methylene, ethylene, propylene, and butylene. The alkylene chain is bonded to the rest of the molecule via single bonds and to the radical group via single bonds. The bonding sites of the alkylene chain to the rest of the molecule and the radical group are each via terminal carbons. The alkylene chain may be optionally substituted with one or more substituents, such as the substituents described herein. In certain embodiments, the alkylene contains 1 to 10 carbon atoms (i.e., C1-C1). 10Alkylene). In certain embodiments, the alkylene contains 1 to 8 carbon atoms (i.e., C1-C8 alkylene). In other embodiments, the alkylene contains 1 to 5 carbon atoms (i.e., C1-C5 alkylene). In other embodiments, the alkylene contains 1 to 4 carbon atoms (i.e., C1-C4 alkylene). In other embodiments, the alkylene contains 1 to 3 carbon atoms (i.e., C1-C3 alkylene). In other embodiments, the alkylene contains 1 to 2 carbon atoms (i.e., C1-C2 alkylene). In other embodiments, the alkylene contains 1 carbon atom (i.e., C1 alkylene). In other embodiments, the alkylene contains 5 to 8 carbon atoms (i.e., C5-C8 alkylene). In other embodiments, the alkylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkylene). In other embodiments, the alkylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkylene).

[0021] "Alkenylene" refers to a linear divalent hydrocarbon chain consisting only of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having 2 to 12 carbon atoms, linking the rest of the molecule to a radical group. The alkenylene chain is bonded to the rest of the molecule via single bonds and to the radical group via single bonds. The bonding sites of the alkenylene chain to the rest of the molecule and the radical group are each via terminal carbons. The alkenylene chain may be optionally substituted with one or more substituents, such as substituents described herein. In certain embodiments, the alkenylene contains 2 to 10 carbon atoms (i.e., C2-C2). 10Alkenylenes). In certain embodiments, alkenylenes contain 2 to 8 carbon atoms (i.e., C2-C8 alkenylenes). In other embodiments, alkenylenes contain 2 to 5 carbon atoms (i.e., C2-C5 alkenylenes). In other embodiments, alkenylenes contain 2 to 4 carbon atoms (i.e., C2-C4 alkenylenes). In other embodiments, alkenylenes contain 2 to 3 carbon atoms (i.e., C2-C3 alkenylenes). In other embodiments, alkenylenes contain 2 carbon atoms (i.e., C2 alkenylenes). In other embodiments, alkenylenes contain 5 to 8 carbon atoms (i.e., C5-C8 alkenylenes). In other embodiments, alkenylenes contain 3 to 5 carbon atoms (i.e., C3-C5 alkenylenes).

[0022] "Alkenylene" refers to a linear divalent hydrocarbon chain consisting only of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having 2 to 12 carbon atoms, linking the rest of the molecule to a radical group. The alkylylene chain is bonded to the rest of the molecule via single bonds and to the radical group via single bonds. The bonding sites of the alkylylene chain to the rest of the molecule and the radical group are each via terminal carbons. The alkylylene chain may be optionally substituted with one or more substituents, such as substituents described herein. In certain embodiments, the alkylylene contains 2 to 10 carbon atoms (i.e., C2-C2). 10Alkynylene). In certain embodiments, the alkynylene contains 2 to 8 carbon atoms (i.e., C2-C8 alkynylene). In other embodiments, the alkynylene contains 2 to 5 carbon atoms (i.e., C2-C5 alkynylene). In other embodiments, the alkynylene contains 2 to 4 carbon atoms (i.e., C2-C4 alkynylene). In other embodiments, the alkynylene contains 2 to 3 carbon atoms (i.e., C2-C3 alkynylene). 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., C5-C8 alkynylene). In other embodiments, the alkynylene contains 3 to 5 carbon atoms (i.e., C3-C5 alkynylene).

[0023] "C x-y The term "C" means, when used in conjunction with chemical parts such as alkyl, alkenyl, or alkynyl, a group containing x to y carbon atoms in the chain. For example, "C 1-6 The term "alkyl" refers to substituted or unsubstituted saturated hydrocarbon groups, including linear alkyl and branched alkyl groups containing 1 to 6 carbon atoms. -C x-y The term "alkylene-" refers to a substituted or unsubstituted alkylene chain having x to y carbon atoms in the alkylene chain. For example, -C 1-6 The alkylene- can be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, and one of them is optionally substituted.

[0024] "C x-y "Alkenil" and "C x-y The term "alkynyl" refers to an unsaturated aliphatic group that is similar in length and possible substitutions to the alkyl group described above, but each contains at least one double or triple bond. x-y The term alkenylene refers to a substituted or unsubstituted alkenylene chain having x to y carbon atoms in the alkenylene chain. For example, -C 2-6The alkenylene- may be selected from etenylene, propenylene, butenylene, pentenylene, and hexenylene, one of which may be optionally substituted. The alkenylene chain may have one or more double bonds in the alkenylene chain. -C x-y The term -alkynylene refers to a substituted or unsubstituted alkynylene chain having x to y carbon atoms in the alkynylene chain. For example, -C 2-6 The alkynylene- may be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, one of which may be optionally substituted. The alkynylene chain may have one triple bond or two or more triple bonds within the alkynylene chain.

[0025] As used herein, the term “carbocyclic” refers to a saturated, unsaturated, or aromatic ring in which each atom of the ring is carbon. Carbocyclics include 3- to 12-membered monocyclic rings and 6- to 12-membered bicyclic rings. Each ring in a bicyclic carbocyclic may be selected from saturated, unsaturated, and aromatic rings. Bicyclic carbocyclics may be condensed, bridged, or spirocyclic systems. In some embodiments, bicyclic carbocyclics are selected from condensed carbocyclics, bridged carbocyclics, and spirocyclic carbocyclics. In some embodiments, the carbocyclic is aryl. In some embodiments, the carbocyclic is cycloalkyl. In some embodiments, the carbocyclic is cycloalkenyl. In exemplary embodiments, an aromatic ring, e.g., phenyl, may be condensed to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings is included in the definition of a carbocyclic system, as long as the valence allows. Examples of carbocyclic compounds include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. The carbocyclic compounds may be optionally substituted with one or more substituents, such as those described herein.

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

[0027] "Cycloalkenyl" refers to a stable unsaturated non-aromatic monocyclic or polycyclic hydrocarbon radical consisting only of carbon and hydrogen atoms, preferably having 3 to 12 carbon atoms and including at least one double bond, and including a condensed or bridging ring system (i.e., C 3-12 Cycloalkenyl). In certain embodiments, the cycloalkenyl contains 3 to 10 carbon atoms (i.e., C 3-10 (Cycloalkenyl). In other embodiments, the cycloalkenyl contains 5 to 7 carbon atoms (i.e., C 5-7 Cycloalkenyls. Cycloalkenyls 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. Cycloalkenyls may be optionally substituted with one or more substituents, such as those described herein.

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

[0029] "C x-y A "carbocyclic ring" means a group containing x to y carbon atoms within the ring. For example, "C 3-6 The term "carbocyclic ring" can refer to a saturated, unsaturated, or aromatic cyclic system containing 3 to 6 carbon atoms, any of which are 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 6- to 12-membered bicyclic rings. Each ring in a bicyclic heterocycle may be selected from saturated, unsaturated, and aromatic rings. In some embodiments, the heterocycle contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocycle contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocycle contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heterocycle contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. The heterocycle may be bonded to the rest of the molecule via any valence-acceptable atom of the heterocycle, such as a carbon or nitrogen atom of the heterocycle. In some embodiments, the heterocycle is a heteroaryl. In some embodiments, the heterocycle is a heterocycloalkyl. Exemplary heterocycles include pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, pyrimidinyl, pyridadinyl, pyrazinyl, thiophenyl, oxazolyl, thiazolyl, morpholinyl, indazolyl, indolyl, and quinolinyl. The heterocycle may be optionally substituted with one or more substituents, such as those described herein. The bicyclic heterocycle may be a condensed heterocycle, a bridging heterocycle, or a spirocyclic heterocycle. In exemplary embodiments, the heterocycle, e.g., pyridyl, may be condensed to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. In some embodiments, the bicyclic heterocycle is a bridging heterocycle (e.g., 6-oxa-3-azabicyclo[3.1.1]heptanyl). In some embodiments, the bicyclic heterocycle is a spirocyclic heterocycle (e.g., from 2-oxa-6-azaspiro[3.3]heptanyl or 4-oxa-7-azaspiro[2.5]octanyl).The heterocycle may be optionally substituted with one or more substituents, such as those described herein.

[0031] A "heterocycloalkyl" refers to a stable 3-12 membered non-aromatic ring radical containing 2-12 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, the heterocycloalkyl contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocycloalkyl contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocycloalkyl contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heterocycloalkyl contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. Heterocycloalkyls can be monocyclic or bicyclic, and condensed or bridging ring systems. Heteroatoms in the heteroaryl group are optionally oxidized. If present, one or more nitrogen atoms are optionally quaternized. Heterocycloalkyl groups are partially or completely saturated. The heterocycloalkyl group is bonded to the rest of the molecule via any valence-acceptable atom of the heterocycloalkyl group, such as any carbon or nitrogen atom of the heterocycloalkyl group. Examples of heterocycloalkyl radicals include, but are not limited to, dioxolanil, thienyl[1,3]dithianil, decahydroisoquinolyl, imidazolinil, imidazolidinil, isothiazolidinil, isoxazolidinil, morpholinil, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinil, 2-oxopiperidinil, 2-oxopyrrolidinil, oxazolidinil, piperidinil, piperazinil, 4-piperidonyl, pyrrolidinil, pyrazolidinil, quinuclidinil, thiazolidinil, tetrahydrofuryl, trithianil, tetrahydropyranil, thiomorpholinil, thiamorpholinil, 1-oxo-thiomorpholinil, and 1,1-dioxo-thiomorpholinil. Heterocycloalkyls may be optionally substituted with one or more substituents, such as those described herein.

[0032] The term "heteroaryl" refers to a group derived from a 5-12 membered aromatic ring group, comprising at least one heteroatom, preferably 1-4 heteroatoms. In some embodiments, the heteroaryl comprises at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heteroaryl comprises at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heteroaryl comprises at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heteroaryl comprises at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. As used herein, the heteroaryl ring may be selected from monocyclic or bicyclic and fused or bridging ring systems, where at least one of the rings in the ring system is aromatic, i.e., contains a cyclic delocalized (4n+2)π-electron system according to Hückel's theory. Heteroatoms in the heteroaryl group may optionally be oxidized. If present, one or more nitrogen atoms are optionally quaternized. Heteroaryls can be bonded to the rest of the molecule via any valence-acceptable atom of the heteroaryl, such as a carbon or nitrogen atom of the heteroaryl. Heteroaryls include aromatic monocyclic structures, preferably 5-6 membered rings, the ring structure containing at least one heteroatom, preferably 1-4 heteroatoms, more preferably 1 or 2 heteroatoms. Examples of heteroaryl groups include 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, at least one of which is heteroaromatic, and the other rings may be aromatic or nonaromatic carbocyclic or heterocyclic, for example. Heteroaryls can be optionally substituted with one or more substituents, such as those described herein.

[0033] "X-membered heterocycle" refers to the number of ring atoms within the ring, i.e., X. For example, a 5-membered heteroaryl ring or a 5-membered aromatic heterocycle has 5 ring atoms, such as triazole, oxazole, or thiophene.

[0034] "Alkoxy" refers to a group bonded via an oxygen atom in the formula -O-alkyl, and alkyl is the alkyl chain defined above.

[0035] "Halo" or "halogen" refers to halogen substituents such as bromo, chloro, fluoro, and iodo substituents.

[0036] As used herein, the terms “haloalkyl” or “haloalkane” refer to the alkyl groups defined above, which are substituted with one or more halogen groups, such as trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc. In some embodiments, the alkyl portion of the fluoroalkyl group is optionally further substituted. Examples of halogen-substituted alkanes ("haloalkanes") include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), di- and trihalomethanes (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2-haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combination of alkanes (or substituted alkanes) and halogens (e.g., Cl, Br, F, and I). When an alkyl group is substituted with two or more halogen groups, each halogen can be independently selected from, for example, 1-chloro and 2-fluoroethanes.

[0037] The term “substituted” refers to a moiety having substituents that replace hydrogen atoms on one or more carbon atoms or substituteable heteroatoms, for example, NH or NH2 atoms in a compound. “Substituted” or “substituted with” will be understood to imply the implicit condition that such substitution results in a stable compound, i.e., a compound that does not spontaneously undergo transformation by rearrangement, cyclization, elimination, etc., depending on the acceptable valences of the substituted atoms and substituents. In certain embodiments, “substituted” refers to a moiety having substituents that replace two hydrogen atoms on the same carbon atom, such as substituting two hydrogen atoms on a single carbon atom with an oxo, imino, or thioxo group. As used herein, the term “substituted” is intended to include all acceptable substituents in an organic compound. In a broad view, acceptable substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents in an organic compound. There may be one or more acceptable substituents, and they may be the same or different for a given organic compound. Preferably, "optionally substituted with one or more substituents" means that it is substituted once or twice. Preferably, "optionally substituted with one or more substituents" means that it is substituted once.

[0038] In some embodiments, the substituent is any substituent described herein, for example, halogen, hydroxyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxymo (=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(Ra )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 1 or 2), -R b -S(O) t Ure a (t is 1 or 2), and -R b -S(O) t N(R a )2 (t is 1 or 2), alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralquinyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl, any of which is alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro-NO2), imino (=NH), oxymo (=N-OH), hydrazine (=NNH2), -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 1 or 2), -R b -S(O) t Ure a (t is 1 or 2), and -R b -S(O) t N(R a )2 (where t is 1 or 2) may contain substituents that can be optionally substituted, and each R a R is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, where each R a This includes alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxymo (=N-OH), hydrazine (=NNH2), and -R, as long as their valence allows. 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, -Rb -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 1 or 2), -R b -S(O) t Ure a (t is 1 or 2), and -R b -S(O) t N(R a )2 (where t is 1 or 2) can be optionally replaced, and each R b The R is independently selected from directly bonded or linear or branched linear alkylene chains, alkenylene chains, or alkynylene chains, and each R c These are linear or branched alkylene, alkenylene, or alkynylene chains. It will be understood by those skilled in the art that the substituents themselves can be substituted as appropriate.

[0039] The terms “salt” or “pharmaceutically acceptable salt” refer to salts derived from various organic and inorganic counterions known in the art. pharmaceutically acceptable acid addition salts can be formed from inorganic and organic acids. pharmaceutically acceptable base addition salts can be formed using inorganic and / or organic bases.

[0040] The term "pharmaceutically acceptable" is used herein to mean a compound, material, composition, and / or dosage form that is suitable for use in contact with human and animal tissues, within the bounds of sound medical judgment, without excessive toxicity, irritation, allergic reactions, or other problems or complications, or in proportion to a reasonable benefit / risk ratio.

[0041] The terms “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier,” as used herein, mean 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 that it is compatible with the other components of the formulation and does not cause harm to the patient.

[0042] The terms “subject,” “individual,” and “patient” may be used interchangeably and refer to humans and non-human mammals (e.g., non-human primates, dogs, horses, cats, pigs, cattle, ungulates, rabbits, etc.). In various embodiments, the subject may be a human being (e.g., adult male, adult female, adolescent male, adolescent female, boy, girl) under the care of a physician or other patient in a hospital, either as an outpatient or in other clinical setting. In certain embodiments, the subject may not be receiving care or prescriptions from a physician or other healthcare professional.

[0043] As used herein, the phrase "subjects requiring treatment" refers to subjects described herein who are suffering from or at risk of suffering from a condition that should be treated prophylactically or therapeutically with the compounds or salts described herein.

[0044] The terms “administer,” “administered,” “administering,” and “administering” are defined as providing a composition to a subject via a route known in the art, including but not limited to intravenous, intra-arterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal administration routes. In certain embodiments, an oral route for administering the composition may be used. The terms “administer,” “administered,” “administers,” and “administering” should be understood as meaning providing the compound of the present invention or a prodrug of the compound of the present invention to an individual in need.

[0045] As used herein, “treatment” or “treating” refers to an approach to obtain beneficial or desired outcomes with respect to a disease, disorder, or medical condition, including but not limited to therapeutic and / or preventive benefits. In certain embodiments, treatment or treating involves administering a compound or composition disclosed herein to a subject. Therapeutic benefits may include the eradication or improvement of the underlying disease being treated. Therapeutic benefits may also be achieved by the eradication or improvement of one or more physiological symptoms associated with the underlying disease, such as observing improvement in the subject, even though the subject may still have the underlying disease. In certain embodiments, for a preventive benefit, a composition is administered to a subject at risk of developing a particular disease, or to a subject reporting one or more physiological symptoms of the disease, even if the disease has not been diagnosed. Treating may include, for example, reducing, delaying, or mitigating the severity of one or more symptoms of a disease or condition, or reducing the frequency with which symptoms such as a disease, defect, disorder, or adverse condition are experienced by a patient. The term "treating" can be used herein to refer to a method that brings about a certain level of treatment or improvement of a disease or condition, and may aim for a range of results directed toward its purpose, including but not limited to the complete prevention of the condition.

[0046] In certain embodiments, the terms “prevent” or “prevent” in relation to a disease or disorder may refer to a compound that reduces the incidence of the disorder or condition in a treated sample compared to an untreated control sample, or delays the onset or reduces the severity of one or more symptoms of the disorder or condition compared to an untreated control sample.

[0047] "Therapeutic effect," as used herein, encompasses the therapeutic and / or preventive benefits described above. Preventive effects include delaying or eliminating the onset 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.

[0048] compound In some embodiments, this disclosure relates to formula (A):

[0049] [ka] A compound with a structure represented by the following: Or a pharmaceutically acceptable salt thereof is provided, in the formula, X is N or CR 2 Selected from, A is (a) and (b) below: (a) Halogen, -OR 11A , -SR 11A , -N(R 11A )2, -C(O)R 11A ,-C(O)N(R 11A )2, -N(R 11A )C(O)R 11A 、 -C(O)OR 11A ,-OC(O)R 11A ,-S(O)R 11A -S(O)2R 11A -NO2, =O, =S, =N(R 11A ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 Alkyl, (b)-(CR'R'') m (3- to 10-membered complex ring), -(CR'R'') m (C 3-10 carbocycle), -O-(CR'R'') m (3- to 10-membered heterogeneous rings), and -O-(CR'R'') m (C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 Each of the carbocyclic rings is as follows: 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(R11 )S(O)2R 11 , -C(O)OR 11 ,-OC(O)R 11 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN, 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 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, =N(R 11 ), -CN and halogen, -OR 11A , -SR 11A , -N(R 11A )2, -C(O)R 11A ,-C(O)N(R 11A )2, -N(R 11A )C(O)R 11A , -C(O)OR 11A ,-OC(O)R 11A ,-S(O)R 11A -S(O)2R 11A -NO2, =O, =S, =N(R 11A ) and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 C is optionally substituted with one or more substituents selected from alkyl groups. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles.1-10 Alkyl, C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 (a) and (b) are selected, and are optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. Each R' represents hydrogen, halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 ,-C(O)N(R 18 )2, -NO2, -CN and halogens, -OR 18 , -N(R 18 )2, -C(O)R 18 ,-C(O)N(R 18 )C is optionally replaced with one or more from -NO2 and -CN. 1-6 Selected from alkyl groups, Each R'' represents hydrogen, halogen, -OR 19 , -N(R19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -NO2, -CN and halogens, -OR 19 , -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )C is optionally replaced with one or more from -NO2 and -CN. 1-6 Selected from alkyl groups, B is -C(R 5 )3 and C 3-10 Selected from the carbon ring, C 3-10 The carbocyclic ring is as follows: Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )S(O)2R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-S(O)R 12 -S(O)2R 12 -NO2, =O, =S, =N(R 12 ), -CN, C 1-10 Alkyl and C 3-10 A carbon ring, in which any of them is a halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-S(O)R 12 -S(O)2R 12 -NO2, =O, =S, =N(R 12 ), -CN, halogen, -OR respectively 12 , -N(R 12 )2, -C(O)R 12 ,-C(O)N(R12 )2, -N(R 12 )C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 -NO2, =O, =N(R 12 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. 1-10 Alkyl and C 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring. Each R 5 Each instance of this is (i), (ii), and (iii): (i) Hydrogen, 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, -CN, (ii) 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), C is optionally substituted with one or more substituents independently selected from -CN. 1-10 alkyl, and (iii) C 3-10 A carbon ring, 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), -CN, and 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 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 Selected independently from the carbon ring, Each R 1 Each time it appears, 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 , -N(R 14 )S(O)2R 14 , -C(O)OR 14 ,-OC(O)R 14,-S(O)R 14 -S(O)2R 14 -NO2, =O, =S, =N(R 14 ), -CN, C 1-10 Alkyl and C 3-10 A carbon ring, each of which is a 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 ,-S(O)R 14 -S(O)2R 14 -NO2, =O, =S, =N(R 14 ), -CN, halogen, -OR respectively 14A , -SR 14A , -N(R 14A )2, -C(O)R 14A ,-C(O)N(R 14A )2, -N(R 14A )C(O)R 14A , -C(O)OR 14A ,-OC(O)R 14A ,-S(O)R 14A -S(O)2R 14A -NO2, =O, =S, =N(R 14A ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. 1-10 Alkyl and C 3-10 Selected from the carbon ring, or two R 1 The substituents together are C 3-6 A carbon ring or a 3-6 membered carbon ring may be formed, C 3-6 Carbon rings and 3- to 6-membered carbon rings are halogens, -OR, respectively. 20 , -N(R 20 )2, -C(O)R 20 ,-C(O)N(R 20 )2, -NO2, =O, =S, =N(R20 ), -CN, C 1-10 Alkyl and C 3-10 Optionally substituted with one or more substituents independently selected from the carbon ring, C 1-10 Alkyl and C 3-10 The carbon rings are, respectively, halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 ,-C(O)N(R 20 )2, -NO2, =O, =S, =N(R 20 ), and are optionally substituted with one or more substituents independently selected from -CN, R 2 teeth, Hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 )2, -C(O)R 15 ,-C(O)N(R 15 )2, -N(R 15 )C(O)R 15 , -N(R 15 )S(O)2R 15 , -C(O)OR 15 ,-OC(O)R 15 ,-S(O)R 15 -S(O)2R 15 -NO2, -CN, Halogen, -OR 15 , -SR 15 , -N(R 15 )2, -C(O)R 15 ,-C(O)N(R 15 )2, -N(R 15 )C(O)R 15 , -C(O)OR 15 ,-OC(O)R 15 ,-S(O)R 15 -S(O)2R 15 -NO2, =O, =S, =N(R 15 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 Selected from alkyl groups, or R 2 and one R 1may together form a 3- to 6-membered carbon ring, and the 3- to 6-membered carbon ring is halogen, -OR 21 , -N(R 21 )2, -C(O)R 21 , -C(O)N(R 21 )2, -NO2, =O, =S, =N(R 21 ), -CN, C 1-10 alkyl and C 3-10 carbocyclic ring, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR 20 , -N(R 10 )2, -C(O)R 21 , -C(O)N(R 21 )2, -NO2, =O, =S, =N(R 21 ), and -CN, and is optionally substituted with one or more substituents independently selected from C 1-10 alkyl and C 3-10 carbocyclic ring, each R 3 is, each time it appears, hydrogen, halogen, -OR 16 , -SR 16 , -N(R 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 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O)2R 16 , -NO2, -CN, and halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)R 16 , -C(O)N(R 16 )2, -N(R 16 )C(O)R 16 , -C(O)OR 16 , -OC(O)R 16 , -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R16 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 Selected independently of alkyl, L is halogen, -OC 1-6 Alkyl, -OC 1-6 C is optionally substituted with one or more substituents independently selected from haloalkyl, -NH2, -NO2, =O, and -CN. 1-6 Alkylene, -O-, selected from bond, Ring D is C 3-10 A carbocyclic ring and a 3- to 10-membered heterocyclic ring, each of which is: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 ,-OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN, Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 ,-OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN, C 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 alkyl, and halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)N(R 17 )2, -N(R 17 )、-C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O)2R 17 , -NO2, =O, =S, =N(R 17 ), -CN and halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 , -C(O)N(R 17 )2, -N(R 17 ), -C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 , -OC(O)R 17 , -S(O)R 17 , -S(O)2R 17 , -NO2, =O, =S, =N(R 17 ), and -CN, and is optionally substituted with one or more substituents independently selected from 1-6 a 3- to 10-member heterocyclic ring optionally substituted with one or more substituents independently selected from and C 3-10 a carbocyclic ring optionally substituted with one or more substituents independently selected from, R 11 , R 11A , R 12 , R 13 , R 14 , R 14A , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , and R 21 each, upon each occurrence: hydrogen, halogen, -O-C1-6 Alkyl, -OC 1-6 Haloalkyl, -NH 2、 -NO2, =O, -CN, C 3-10 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. 1-6 Alkyl, each C 3-10 Carbon rings and 3- to 10-membered heterocycles are halogens, -OH, and -OC. 1-6 Alkyl, -OC 1-6 Haloalkyl, -NH 2、 -NO2, =O, and -CN are optionally substituted with one or more substituents independently selected from C 1-6 alkyl, and Halogen, -OH, -OC 1-6 Alkyl, -OC 1-6 C is optionally substituted with one or more substituents independently selected from haloalkyl, -NH2, -NO2, =O, and -CN. 3-10 Independently selected from carbon rings and 3- to 10-membered heterocycles, m is selected from 0, 1, and 2. z is selected from 1 and 2. n is selected from 1, 2, and 3. p is selected from 0, 1, 2, 3, 4, 5, and 6.

[0050] In some embodiments, for a compound or salt of formula (A), L is a halogen, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -NH 2、 C is optionally substituted with one or more substituents independently selected from -NO2, =O, or -CN. 1-6 Selected from alkylenes and bonds. In some embodiments, L is a halogen, -OC 1-6 Alkyl, -OC 1-6 C is optionally substituted with one or more substituents independently selected from haloalkyl, -NH2, -NO2, =O, or -CN. 1-6 It is an alkylene. In some embodiments, L is a halogen, -OC 1-6Alkyl and -OC 1-6 C is optionally substituted with one or more substituents independently selected from the haloalkyl group. 1-3 It is an alkylene. In some embodiments, L is a halogen, -OC, etc. 1-6 Alkyl and -OC 1-6 Selected from methylene, ethylene, and propylene, which are optionally substituted with one or more substituents independently selected from the haloalkyl. L is a halogen, -OC, respectively. 1-6 Alkyl and -OC 1-6 Selected from methylene and ethylene, which are optionally substituted with one or more substituents independently selected from the haloalkyl. In some embodiments, L is methylene. In some embodiments, L is a bond.

[0051] In some embodiments, for a compound or salt of formula (A), ring D is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 ,-OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN and halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 ,-OC(O)R 17 ,-S(O)R 17 -S(O)2R 17-NO2, =O, =S, =N(R 17 ), -CN, C 3-10 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. 1-10 It is a 3- to 10-membered heterocycle that is optionally substituted with one or more substituents independently selected from the alkyl group. In some embodiments, ring D is a halogen, C 1-6 Alkyl and C 1-6 It is a 4- to 7-membered saturated heterocycle that is optionally substituted with one or more substituents independently selected from the haloalkyl group.

[0052] In some embodiments, for a compound or salt of formula (A),

[0053] [ka] but,

[0054] [ka] Selected from: In some embodiments,

[0055] [ka] teeth,

[0056] [ka] Selected from: In some embodiments,

[0057] [ka] teeth,

[0058] [ka] Selected from.

[0059] In some embodiments, z is 1 for the compound or salt of formula (A).

[0060] In some embodiments, z is 2 for the compound or salt of formula (A).

[0061] In some embodiments, X is N.

[0062] In some embodiments, X is CR 2 That is the case.

[0063] In some embodiments, for a compound or salt of formula (A), n is selected from 3. In some embodiments, n is selected from 2. In some embodiments, n is selected from 1.

[0064] In some embodiments, for a compound or salt of formula (A), A is a halogen, -OR 11A , -SR 11A , -N(R 11A )2, -C(O)R 11A ,-C(O)N(R 11A )2, -N(R 11A )C(O)R 11A , -C(O)OR 11A ,-OC(O)R 11A ,-S(O)R 11A -S(O)2R 11A -NO2, =O, =S, =N(R 11A ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 It is alkyl. In some embodiments, A is halogen, -OR 11A , -SR 11A , -N(R 11A )2, -C(O)R 11A ,-C(O)N(R 11A )2, -N(R 11A )C(O)R 11A , -C(O)OR 11A,-OC(O)R 11A ,-S(O)R 11A -S(O)2R 11A -NO2, =O, =S, =N(R 11A ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 It is alkyl. In some embodiments, C 1-6 Alkyl is a halogen, -OR 12 , -N(R 12 )2, -C(O)R 12 -NO2, =O, =S, =N(R 12 ), and -CN are optionally substituted with one or more substituents independently selected from -CN. In some embodiments, A is C 1-6 Alkyl, or C 1-6 It is a haloalkyl group.

[0065] In some embodiments, for a compound or salt of formula (A), A is -(CR'R'') m (3- to 10-membered complex ring), -(CR'R'') m (C 3-10 carbocycle), -O-(CR'R'') m (3- to 10-membered heterogeneous rings), and -O-(CR'R'') m (C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 The carbon rings are, respectively, 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, C 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10Optionally substituted with one or more substituents independently selected from the alkyl group, C 3-10 Carbon rings and 3- to 10-membered heterocycles are halogens, -OR rings, and so on. 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, =N(R 11 ), -CN and halogen, -OR 11A , -SR 11A , -N(R 11A )2, -C(O)R 11A ,-C(O)N(R 11A )2, -N(R 11A )C(O)R 11A , -C(O)OR 11A ,-OC(O)R 11A ,-S(O)R 11A -S(O)2R 11A -NO2, =O, =S, =N(R 11A ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 It is optionally substituted with one or more substituents independently selected from the alkyl group. In some embodiments, A is -(CR'R'') m (3- to 10-membered complex ring), -(CR'R'') m (C 3-10 carbocycle), -O-(CR'R'') m (3- to 10-membered heterogeneous rings), and -O-(CR'R'') m (C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 Each carbon ring is C 3-10 It is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 3-10 Carbon rings and 3- to 10-membered heterocycles are halogens, -OR 11A , -SR 11A , -N(R 11A )2, -C(O)R 11A ,-C(O)N(R11A )2, -N(R 11A , -C(O)R 11A , -C(O)OR 11A ,-OC(O)R 11A ,-S(O)R 11A -S(O)2R 11A -NO2=O, =S, =N(R) 11A ), one or more C atoms optionally substituted with one or more substituents independently selected from -CN. 1-10 Each alkyl group is optionally substituted.

[0066] In some embodiments, for a compound or salt of formula (A), B is -C(R 5 )3, and each R 5 Each instance of this is (i), (ii), and (iii): (i) Hydrogen, 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, -CN, (ii) 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13), C is optionally substituted with one or more substituents independently selected from -CN. 1-10 alkyl, and (iii) C 3-10 A carbon ring, 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), -CN, and 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 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is selected independently of the carbon ring.

[0067] In some embodiments, for a compound or salt of formula (A), B is -C(R 5 )3 and each R 5 Each occurrence of (i) and (ii): (i) Hydrogen, 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, -CN, and (ii) 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), C is optionally substituted with one or more substituents independently selected from -CN. 1-10 It is selected independently of alkyl.

[0068] In some embodiments, for a compound or salt of formula (A), B is -C(R 5 )3, and each R 5 Each occurrence is 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 Alkyl and hydrogen are independently selected. In some embodiments, B is -C(R 5 )3, and each R 5 Each occurrence is 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 It is independently selected from alkyl and hydrogen.

[0069] In some embodiments, for a compound or salt of formula (A), each R 1 Each time it appears, C 1-10 Alkyl and C 3-10 Selected independently from the carbon ring, each of them is a 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 ,-S(O)R 14 -S(O)2R 14 -NO2, =O, =S, =N(R 14 ), -CN, C 3-10 It is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle, C 3-10 The carbon ring and the 3- to 10-membered heterocycle are, respectively, halogens, -OR14A , -SR 14A , -N(R 14A )2, -C(O)R 14A ,-C(O)N(R 14A )2, -N(R 14A )C(O)R 14A , -C(O)OR 14A ,-OC(O)R 14A ,-S(O)R 14A -S(O)2R 14A -NO2, =O, =S, =N(R 14A ), and -CN are optionally substituted with one or more substituents selected from the above. In some embodiments, each R 1 Independently, each time it appears, C 1-10 Alkyl and C 3-10 Selected from the carbon ring, each of these is C 3-10 It is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle, C 3-10 Carbon rings and 3- to 10-membered heterocycles are halogens, -OR rings, and so on. 14A , -SR 14A , -N(R 14A )2, -C(O)R 14A ,-C(O)N(R 14A )2, -N(R 14A )C(O)R 14A , -C(O)OR 14A ,-OC(O)R 14A ,-S(O)R 14A -S(O)2R 14A -NO2, =O, =S, =N(R 14A ), and -CN are optionally substituted with one or more substituents selected from these.

[0070] In some embodiments, for a compound or salt of formula (A), two R 1 The substituents together are C 3-6 A carbon ring or a 3-6 membered carbon ring may be formed, C 3-6 Carbon rings and 3- to 6-membered carbon rings are halogens, -OR, respectively. 20 , -N(R 20 )2, -C(O)R 20 ,-C(O)N(R 20)2, -NO2, =O, =S, =N(R 20 ), -CN, C 1-10 Alkyl and C 3-10 Optionally substituted with one or more substituents independently selected from the carbon ring, C 1-10 Alkyl and C 3-10 The carbon rings are, respectively, halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 ,-C(O)N(R 20 )2, -NO2, =O, =S, =N(R 20 ), and are optionally substituted with one or more substituents independently selected from -CN. In some embodiments, two R 1 The substituents together are C 3-6 A carbon ring may be formed, C 3-6 The carbon ring is a halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 ,-C(O)N(R 20 )2, -NO2, =O, =S, =N(R 20 ), -CN, C 1-10 Alkyl and C 3-10 Optionally substituted with one or more substituents independently selected from the carbon ring, C 1-10 Alkyl and C 3-10 The carbon rings are, respectively, halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 ,-C(O)N(R 20 )2, -NO2, =O, =S, =N(R 20 ), and are optionally substituted with one or more substituents independently selected from -CN. In some embodiments, two R 1 The substituents together are C 3-6 A carbon ring may be formed, C 3-6 The carbon ring is a halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 ,-C(O)N(R 20 )2, -NO2, =O, =S, =N(R 20 ), -CN, C 1-3 Alkyl and C3-6 Optionally substituted with one or more substituents independently selected from the carbon ring, C 1-3 Alkyl and C 3-6 The carbon rings are, respectively, halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 ,-C(O)N(R 20 )2, -NO2, =O, =S, =N(R 20 ), and -CN are optionally substituted with one or more substituents independently selected from each other.

[0071] In some embodiments, equation (A) is equation (I):

[0072] [ka] Structure or represented by its pharmaceutically acceptable salt, in the formula, A is -(CR'R'') m (3- to 10-membered complex ring), -(CR'R'') m (C 3-10 carbocycle), -O-(CR'R'') m (3- to 10-membered heterogeneous rings), and -O-(CR'R'') m (C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 The carbocyclic rings are as follows: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN, 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 alkyl, and C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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)R11 -NO2, =O, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from carbon rings and 3- to 10-membered heterocycles. Each R' represents hydrogen, halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 ,-C(O)N(R 18 )2, -NO2, -CN and halogens, -OR 18 , -N(R 18 )2, -C(O)R 18 ,-C(O)N(R 18 )C is optionally replaced with one or more from -NO2 and -CN. 1-6 Selected from alkyl groups, Each R'' represents hydrogen, halogen, -OR 19 , -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -NO2, -CN and halogens, -OR 19 , -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )C is optionally replaced with one or more from -NO2 and -CN. 1-6 Selected from alkyl groups, B is -C(H)(R 5 )2 and C 3-10 Selected from the carbon ring, C 3-10 The carbocyclic ring is as follows: Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )S(O)2R 12 , -C(O)OR 12,-OC(O)R 12 ,-S(O)R 12 -S(O)2R 12 -NO2, =O, =S, =N(R 12 ), -CN, C 1-10 Alkyl and C 3-10 A carbon ring, in which any of them is a halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 ,-S(O)R 12 -S(O)2R 12 -NO2, =O, =S, =N(R 12 ), -CN, halogen, -OR respectively 12 , -N(R 12 )2, -C(O)R 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 -NO2, =O, =N(R 12 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. 1-10 Alkyl and C 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring. Each R 5 Each instance of this is (i), (ii), and (iii): (i) 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 , -N(R13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, -CN, (ii)C 1-10 Alkyl, 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), C is optionally substituted with one or more substituents independently selected from -CN. 1-10 alkyl, and (iii) C 3-10 A carbon ring, 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 ,-OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), -CN, and 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 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 Selected independently from the carbon ring, Each R 1 Each time it appears, 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 , -N(R 14 )S(O)2R 14 , -C(O)OR 14 ,-OC(O)R 14 ,-S(O)R 14 -S(O)2R 14 -NO2, =O, =S, =N(R 14 ), -CN, C 1-10 Alkyl and C 3-10 A carbon ring, each of which is a 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 ,-S(O)R 14 -S(O)2R 14 -NO2, =O, =S, =N(R 14 ), C is optionally substituted with one or more substituents independently selected from -CN. 1-10 Alkyl and C 3-10 Selected independently from the carbon ring, or Two R's 1 The substituents may together form a 3- to 6-membered carbon ring, and the 3- to 6-membered carbon rings are as follows: Halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 ,-C(O)N(R 20 )2, -NO2, =O, =S, =N(R 20 ), -CN, C 1-10 Alkyl and C 3-10 A carbon ring, each of which is a halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 ,-C(O)N(R 20 )2, -NO2, =O, =S, =N(R 20 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 Alkyl and C 3-10 Selected independently from the carbon ring, R 2 is hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 )2, -C(O)R 15 ,-C(O)N(R 15 )2, -N(R 15 )C(O)R 15 , -N(R 15 )S(O)2R 15 , -C(O)OR 15 ,-OC(O)R 15 ,-S(O)R 15 -S(O)2R 15 -NO2, -CN, and halogens, -OR 15 , -SR 15 , -N(R 15 )2, -C(O)R 15 ,-C(O)N(R 15 )2, -N(R 15 )C(O)R 15 , -C(O)OR 15 ,-OC(O)R 15 ,-S(O)R 15 -S(O)2R 15-NO2, =O, =S, =N(R 15 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 Selected from alkyl groups, or R 2 and one R 1 However, they may also form a 3-6 membered carbon ring, and the 3-6 membered carbon ring is Halogen, -OR 21 , -N(R 21 )2, -C(O)R 21 ,-C(O)N(R 21 )2, -NO2, =O, =S, =N(R 21 ), -CN, C 1-10 Alkyl and C 3-10 A carbon ring, each of which is a halogen, -OR 20 , -N(R 10 )2, -C(O)R 21 ,-C(O)N(R 21 )2, -NO2, =O, =S, =N(R 21 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 Alkyl and C 3-10 Optionally substituted with one or more substituents independently selected from the carbon ring, Each R 3 Each instance of this occurs, it is hydrogen, halogen, -OR 16 , -SR 16 , -N(R 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 , -C(O)OR 16 ,-OC(O)R 16 ,-S(O)R 16 -S(O)2R 16 -NO2, -CN, and halogens, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)R 16 ,-C(O)N(R 16)2, -N(R 16 )C(O)R 16 , -C(O)OR 16 ,-OC(O)R 16 ,-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R 16 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 Selected independently of alkyl, Ring D is C 3-10 A carbocyclic ring and a 3- to 10-membered heterocyclic ring, each of which is: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 ,-OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN, Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 ,-OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN, C 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 alkyl, and Halogen, -OR17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 ,-OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN and halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 ,-OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 A 3- to 10-membered heterocycle and C are optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring. R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , and R 21 Each of these, upon appearance: hydrogen, Halogen, -OC 1-6 Alkyl, -OC 1-6Haloalkyl, -NH2, -NO2, =O, -CN, C 3-10 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. 1-6 Alkyl, each C 3-10 Carbon rings and 3- to 10-membered heterocycles are halogens, -OH, and -OC. 1-6 Alkyl, -OC 1-6 C is optionally substituted with one or more substituents independently selected from haloalkyl, -NH2, -NO2, =O, and -CN. 1-6 alkyl, and Halogen, -OH, -OC 1-6 Alkyl, -OC 1-6 C is optionally substituted with one or more substituents independently selected from haloalkyl, -NH2, -NO2, =O, and -CN. 3-10 Independently selected from carbon rings and 3- to 10-membered heterocycles, m is selected from 0, 1, and 2. n is selected from 1 and 2. p is selected from 0, 1, 2, 3, 4, 5, and 6.

[0073] In some embodiments, n is 1 for a compound or salt of formula (A) or formula (I).

[0074] In some embodiments, formula (A) or formula (I) is formula (Ia):

[0075] [ka] It is represented by the structure of or a pharmaceutically acceptable salt thereof.

[0076] In some embodiments, for a compound or salt of formula (Ia), R 1 , R 2 , R 3 The rings D, A, B, and p are defined as shown in equation (A) or equation (I), respectively.

[0077] In some embodiments, n is 2 for a compound or salt of formula (A) or formula (I).

[0078] In some embodiments, formula (A) or formula (I) is formula (Ib):

[0079] [ka] It is represented by the structure of or a pharmaceutically acceptable salt thereof.

[0080] In some embodiments, for a compound or salt of formula (Ib), R 1 , R 2 , R 3 The rings D, A, B, and p are defined in the same way as in equation (A) or equation (I), respectively.

[0081] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), p is selected from 0, 1, 2, 3, 4, 5, and 6. In some embodiments, p is selected from 1, 2, 3, 4, 5, and 6. In some embodiments, p is selected from 0, 1, 2, 3, 4, and 5. In some embodiments, p is selected from 0, 1, 2, 3, and 4. In some embodiments, p is selected from 0, 1, 2, and 3. 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 selected from 1, 2, 3, 4, and 5. In some embodiments, p is selected from 2, 3, 4, and 5. In some embodiments, p is selected from 3, 4, and 5. In some embodiments, p is selected from 4 and 5. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4. In some embodiments, p is 5. In some embodiments, p is 6.

[0082] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), m is 1. In some embodiments, m is 1, and A is -(CR'R'')-(3-10 membered heterocycle), -(CR'R'')-(C 3-10 (Carbon ring), -O-(CR'R'')-(3-10 member heterocycle), and -O-(CR'R'')-(C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 The carbocyclic rings are as follows: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN, 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 12 , -N(R 12 )2, -C(O)R 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -C(O)OR 12 ,-OC(O)R 12 -NO2, =O, =N(R 12), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. 1-10 Alkyl, C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from carbon rings and 3- to 10-membered heterocycles.

[0083] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), m is 1, and R' and R'' are each independently halogens, -OR 18 , -N(R 18 )2, -CN, C 1-3 Alkyl and C 1-3Selected from haloalkyls. In some embodiments, m is 1, and R' and R'' are independently hydrogen, halogen, and C. 1-3 Alkyl and C 1-3 Selected from haloalkyls. In some embodiments, m is 1, and each of R' and R'' is independently selected from hydrogen and halogens. In some embodiments, m is 1, and each of R' and R'' is independently selected from hydrogen and fluorocarbons.

[0084] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), R' and R'' are, independently, hydrogen, halogen, -OR 18 , -N(R 18 )2, -CN, C 1-3 Alkyl and C 1-3 Selected from haloalkyls. In some embodiments, R' and R'' are independently hydrogen, halogen, and C 1-3 Alkyl and C 1-3 Selected from haloalkyls. In some embodiments, R' and R'' are each independently selected from hydrogen and halogens. In some embodiments, R' and R'' are each independently selected from hydrogen and fluorocarbons.

[0085] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), m is 0. In some embodiments, m is 0 and -(CR'R") is absent. In some embodiments, m is 0 and A is a 3- to 10-membered heterocycle, C 3-10 Carbon rings, -O-(3-10 membered heterocycles), and -O-(C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 The carbon rings are optionally substituted as shown in formula (A) or (I). In some embodiments, m is 0, and A is a 3- to 10-membered heterocycle, C 3-10 Carbon rings, -O-(3-10 membered heterocycles), and -O-(C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 The carbocyclic rings are as follows: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN, 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 alkyl, and C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 , -C(O)OR 11 ,-OC(O)R 11 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring and the 3- to 10-membered heterocycle.

[0086] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), each R 1 is 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 , -N(R 14 )S(O)2R 14 , -C(O)OR 14 ,-OC(O)R 14 ,-S(O)R 14 -S(O)2R 14 -NO2, =O, =S, =N(R 14 ), -CN, C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a 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 ,-S(O)R 14 -S(O)2R 14 -NO2, =O, =S, =N(R 14 ), C is optionally substituted with one or more substituents independently selected from -CN. 1-6 Alkyl and C 3-6 Selected from the carbon rings. In some embodiments, each R 1 is halogen, -OR 14 , -N(R 14 )2, -C(O)R 14 -NO2, =O, =S, =N(R 14 ), -CN and C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 14 , -N(R 14 )2, -C(O)R 14 -NO2, =O, =S, =N(R 14 ), C is optionally substituted with one or more substituents independently selected from -CN. 1-6 Alkyl and C 3-6 Selected from the carbon ring. In some embodiments, each R 1 is halogen, -OR 14 , -N(R 14 )2, -C(O)R 14 -NO2, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from cycloalkyl groups.

[0087] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), each R 1 is 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 , -N(R 14 )S(O)2R 14 , -C(O)OR 14 ,-OC(O)R 14 ,-S(O)R 14 -S(O)2R 14 -NO2, =O, =S, =N(R 14 ), -CN and 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 ,-S(O)R 14 -S(O)2R 14 -NO2, =O, =S, =N(R 14 ), and C, which is optionally substituted with one or more substituents selected from -CN. 1-6 Selected from alkyl groups. In some embodiments, each R 1 is 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 , -N(R 14 )S(O)2R 14 , -C(O)OR 14 ,-OC(O)R 14 ,-S(O)R 14 -S(O)2R 14 -NO2, =O, =S, =N(R 14 ), and -CN are selected. In some embodiments, each R 1 is halogen, -OR 14 , -SR 14 , -N(R 14 )2, -C(O)R 14 ,-C(O)N(R 14 )2, -N(R14 )C(O)R 14 , -C(O)OR 14 ,-OC(O)R 14 ,-S(O)R 14 -S(O)2R 14 -NO2, =O, =S, =N(R 14 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 Selected from alkyl groups. In some embodiments, each R 1 is halogen, -OR 14 , -N(R 14 )2, -NO2, -CN, C 1-6 Alkyl and C 1-6 Selected from haloalkyls. In some embodiments, each R 1 The halogen is selected from halogen and -CF3. In some embodiments, each 1 It is -CF3.

[0088] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), two R 1 The substituents may together form a 3- to 6-membered carbon ring, which may be a halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 ,-C(O)N(R 20 )2, -NO2, =O, =S, =N(R 20 ), -CN, C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 ,-C(O)N(R 20 )2, -NO2, =O, =S, =N(R 20 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 Alkyl and C 3-6 It is optionally substituted with one or more substituents independently selected from the carbon ring. In some embodiments, two R 1The substituents may together form a 3- to 6-membered cycloalkyl group, which may be halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 , -NO2, CN, C 1-3 Alkyl and C 3-6 Cycloalkyl, where each of them is a halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-3 Alkyl and C 3-6 It is optionally substituted with one or more substituents independently selected from the cycloalkyl group. In some embodiments, two R 1 Substituents, together, include halogens, -OR 20 , -N(R 20 )2, -C(O)R 20 -NO2, -CN, C 1-3 Alkyl and C 3-6 Cycloalkyl, where each of them is a halogen, -OR 20 , -N(R 20 )2, -C(O)R 20 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-3 Alkyl and C 3-6 Three-membered cycloalkyls can be formed by optionally substituting one or more substituents independently selected from the cycloalkyl. In some embodiments, two R atoms on adjacent carbon atoms 1 The substituents together can form an optionally substituted three-membered cycloalkyl group. In some embodiments, two R atoms on adjacent carbon atoms 1 The substituents together are two R 1 It is possible to form an optionally substituted three-membered cycloalkyl group containing two carbon atoms to which the substituents are attached. For example,

[0089] [ka] It is not limited to,

[0090] [ka] It may also be represented by and may be optionally replaced as described herein. In some embodiments, two R 1 Substituents, together, include halogens, -OR 20 , -N(R 20 )2, -C(O)R 20 , -NO2, and -CN, C 1-3 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 20 , N(R 20 )2, -C(O)R 20 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-3 Alkyl and C 3-6 A four-membered cycloalkyl group can be formed, which is optionally substituted with one or more substituents independently selected from the carbon ring. In some embodiments, two R atoms on different carbon atoms 1 The substituents together can form a optionally substituted four-membered cycloalkyl group. In some embodiments, two R groups on different carbon atoms 1 The substituents together are two R 1 It is possible to form an optionally substituted four-membered cycloalkyl group containing two carbon atoms to which the substituents are attached. For example,

[0091] [ka] It is not limited to,

[0092] [ka] It may also be represented by and may be optionally replaced as described herein. In some embodiments,

[0093] [ka] teeth,

[0094] [ka] In some embodiments,

[0095] [ka] teeth,

[0096] [ka] In some embodiments,

[0097] [ka] teeth,

[0098] [ka] That is the case.

[0099] In some embodiments, for compounds or salts of formulas (A), (I), (Ia), and (Ib), R 2 is hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 )2, -C(O)R 15 ,-C(O)N(R 15 )2, -N(R 15 )C(O)R 15 , -N(R 15)S(O)2R 15 , -C(O)OR 15 ,-OC(O)R 15 ,-S(O)R 15 -S(O)2R 15 -NO2, -CN, and halogens, -OR 15 , -SR 15 , -N(R 15 )2, -C(O)R 15 ,-C(O)N(R 15 )2, -N(R 15 )C(O)R 15 , -C(O)OR 15 ,-OC(O)R 15 ,-S(O)R 15 -S(O)2R 15 -NO2, =O, =S, =N(R 15 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 Selected from alkyl groups. In some embodiments, R 2 is hydrogen, halogen, -OR 15 , -SR 15 , -N(R 15 )2, -C(O)R 15 ,-C(O)N(R 15 )2, -N(R 15 )C(O)R 15 , -N(R 15 )S(O)2R 15 , -C(O)OR 15 ,-OC(O)R 15 ,-S(O)R 15 -S(O)2R 15 Selected from -NO2 and -CN. In some embodiments, R 2 is halogen, -OR 15 , -SR 15 , -N(R 15 )2, -C(O)R 15 ,-C(O)N(R 15 )2, -N(R 15 )C(O)R 15 , -C(O)OR 15 ,-OC(O)R 15 ,-S(O)R 15 -S(O)2R 15-NO2, =O, =S, =N(R 15 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 Selected from alkyl groups. In some embodiments, R 2 is hydrogen, halogen, -OR 15 , -N(R 15 )2, -C(O)R 15 -NO2, -CN, C 1-3 Alkyl and C 1-3 Selected from haloalkyls. In some embodiments, R 2 These are hydrogen, halogens, and C 1-3 Selected from alkyl groups. In some embodiments, R 2 R is selected from hydrogen, halogen, methyl, and ethyl. In some embodiments, R 2 It is hydrogen.

[0100] In some embodiments, for compounds of formula (A), (I), (Ia), or (Ib), R 2 and one R 1 These may together form a 3-6 membered carbon ring, and the 3-6 membered carbon ring may be a halogen, -OR 21 , -N(R 21 )2, -C(O)R 21 ,-C(O)N(R 21 )2, -NO2, =O, =S, =N(R 21 ), -CN, C 1-6 Alkyl and C 3-6 Carbon rings (each of which is a halogen, -OR 20 , -N(R 10 )2, -C(O)R 21 ,-C(O)N(R 21 )2, -NO2, =O, =S, =N(R 21 ), and (optionally substituted with one or more substituents independently selected from -CN). In some embodiments, R 2 and one R 1 However, a 3-6 membered carbon ring may also be formed, and the 3-6 membered carbon ring may be a halogen, -OR 21, -N(R 21 )2, -C(O)R 21 -NO2, -CN, C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 21 , N(R 21 )2, -C(O)R 21 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-6 Alkyl and C 3-6 It is optionally substituted with one or more substituents independently selected from the carbon ring. In some embodiments, R 2 and one R 1 These may together form a 3-6 member cycloalkyl group, and the 3-6 member cycloalkyl group may be halogen, -OR 21 , -N(R 21 )2, -C(O)R 21 -NO2, -CN, C 1-6 Alkyl and C 3-6 Cycloalkyl, where each of them is a halogen, -OR 21 , N(R 21 )2, -C(O)R 21 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-6 Alkyl and C 3-6 It is optionally substituted with one or more substituents independently selected from the cycloalkyl group.

[0101] In some embodiments, for compounds or salts of formulas (A), (I), (Ia), and (Ib), each R 3 Each instance of this occurs, it is hydrogen, halogen, -OR 16 , -SR 16 , -N(R 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 , -C(O)OR 16 ,-OC(O)R 16 ,-S(O)R16 -S(O)2R 16 -NO2, -CN, and halogens, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)R 16 , and -C(O)N(R 16 )2, -N(R 16 )C(O)R 16 , -C(O)OR 16 ,-OC(O)R 16 ,-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R 16 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 Selected independently of alkyl. In some embodiments, each R 3 Each instance of this occurs, it is hydrogen, halogen, -OR 16 , -SR 16 , -N(R 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 , -C(O)OR 16 ,-OC(O)R 16 ,-S(O)R 16 -S(O)2R 16 Selected independently from -NO2 and -CN. In some embodiments, each R 3 Each occurrence is halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)R 16 , and -C(O)N(R 16 )2, -N(R 16 )C(O)R 16 , -C(O)OR 16 ,-OC(O)R 16 ,-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R 16), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 Selected from alkyl groups. In some embodiments, each R 3 Each occurrence is halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)R 16 , and -C(O)N(R 16 )2, -N(R 16 )C(O)R 16 , -C(O)OR 16 ,-OC(O)R 16 ,-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R 16 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 Selected independently from alkyl and hydrogen. In some embodiments, each R 3 Each instance of this occurs, it is hydrogen, halogen, -OR 16 , -N(R 16 )2, -NO2, -CN, C 1-3 Alkyl and C 1-3 Selected independently from haloalkyls. In some embodiments, each R 3 Each R is independently selected from hydrogen and methyl. In some embodiments, each R 3 It is hydrogen.

[0102] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is -O-(CR'R'') m -(C 3-10 It is a carbon ring. In some embodiments, A is -O-(CR'R) m -(C 3-10 It is a carbon ring, C 3-10 The carbon ring is a saturated carbon ring that has been optionally substituted. 3-10 It is a carbon ring. In some embodiments, A is -O-(CR'R) m -(C 3-10 It is a carbon ring, C 3-10The carbon ring is an unsaturated carbon that has been optionally substituted. 3-10 It is a carbon ring. In some embodiments, A is -O-(CR'R'') m -(C 3-10 It is a carbon ring, C 3-10 The carbon ring is a C that is optionally substituted. 3-4 Carbon ring, optionally substituted C 3-5 Carbon ring, optionally substituted C 3-6 Carbon ring, optionally substituted C 3-7 Carbon ring, optionally substituted C 3-8 Carbon rings and optionally substituted C 3-9 Selected from a carbon ring. In some embodiments, A is -O-(CR'R'') m -(C 3-10 It is a carbon ring, C 3-10 The carbon rings are optionally substituted C3, C4, C5, C6, C7, C8, C9, and C 10 Selected from the carbocyclic ring.

[0103] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is -(CR'R'') m -(C 3-10 It is a carbon ring. In some embodiments, A is (CR'R'') m -(C 3-10 It is a carbon ring, C 3-10 The carbon ring is a saturated carbon ring that has been optionally substituted. 3-10 It is a carbon ring. In some embodiments, A is -(CR'R'') m -(C 3-10 It is a carbon ring, C 3-10 The carbon ring is an unsaturated carbon that has been optionally substituted. 3-10 It is a carbon ring. In some embodiments, A is -(CR'R'') m -(C 3-10 It is a carbon ring, C 3-10The carbon ring is a C that is optionally substituted. 3-4 Carbon ring, optionally substituted C 3-5 Carbon ring, optionally substituted C 3-6 Carbon ring, optionally substituted C 3-7 Carbon ring, optionally substituted C 3-8 Carbon rings and optionally substituted C 3-9 Selected from a carbon ring. In some embodiments, A is -(CR'R'') m -(C 3-10 It is a carbon ring, C 3-10 The carbon rings are optionally substituted C3, C4, C5, C6, C7, C8, C9, and C 10 Selected from the carbocyclic ring.

[0104] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is optionally substituted with C. 3-10 It is a carbon ring. In some embodiments, A is a saturated C which is optionally substituted. 3-10 It is a carbon ring. In some embodiments, A is an optionally substituted unsaturated C 3-10 It is a carbon ring. In some embodiments, A is optionally substituted with C 3-4 Carbon ring, optionally substituted C 3-5 Carbon ring, optionally substituted C 3-6 Carbon ring, optionally substituted C 3-7 Carbon ring, optionally substituted C 3-8 Carbon rings and optionally substituted C 3-9Selected from a carbon ring. In some embodiments, A is an optionally substituted C3 carbon ring, an optionally substituted C4 carbon ring, an optionally substituted C5 carbon ring, an optionally substituted C6 carbon ring, an optionally substituted C7 carbon ring, an optionally substituted C8 carbon ring, an optionally substituted C9 carbon ring, and an optionally substituted C 10 Selected from the carbocyclic ring.

[0105] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is optionally substituted with C. 3-6 It is a carbon ring. In some embodiments, A is a saturated C which is optionally substituted. 3-6 It is a carbon ring. In some embodiments, A is an optionally substituted unsaturated C 3-6 It is a carbon ring. In some embodiments, A is optionally substituted with C 3-5 Carbon ring, optionally substituted C 3-4 Carbon ring, optionally substituted C 4-6 Carbon rings and optionally substituted C 5-6 A is selected from a carbon ring. In some embodiments, A is selected from an optionally substituted C3 carbon ring, an optionally substituted C4 carbon ring, an optionally substituted C5 carbon ring, and an optionally substituted C6 carbon ring.

[0106] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is -O-(CR'R'') m -(3-10 member complex ring). In some embodiments, A is -O-(CR'R'') m -(3-10 membered hetero ring), where the 3-10 membered hetero ring is a saturated 3-10 membered hetero ring that has been optionally substituted. In some embodiments, A is -O-(CR'R'') m -(3-10 membered hetero ring), where the 3-10 membered hetero ring is an unsaturated 3-10 membered hetero ring that has been optionally substituted. In some embodiments, A is -O-(CR'R'') m-(3-10 member complex ring), where the 3-10 member complex ring is selected from the optionally substituted 3-4 member complex rings, the optionally substituted 3-5 member complex rings, the optionally substituted 3-6 member complex rings, the optionally substituted 3-7 member complex rings, the optionally substituted 3-8 member complex rings, and the optionally substituted 3-9 member complex rings. In some embodiments, A is -O-(CR'R'') m -(3- to 10-membered complex rings), and the 3- to 10-membered complex rings are selected from the arbitrarily substituted 3-membered complex rings, arbitrarily substituted 4-membered complex rings, arbitrarily substituted 5-membered complex rings, arbitrarily substituted 6-membered complex rings, arbitrarily substituted 7-membered complex rings, arbitrarily substituted 8-membered complex rings, arbitrarily substituted 9-membered complex rings, and arbitrarily substituted 10-membered complex rings.

[0107] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is -(CR'R'') m -(3- to 10-membered complex ring). In some embodiments, A is -(CR'R'') m -(3-10 membered complex ring), where the 3-10 membered complex ring is a saturated 3-10 membered complex ring that has been optionally substituted. In some embodiments, A is -(CR'R'') m -(3-10 membered hetero ring), where the 3-10 membered hetero ring is an unsaturated 3-10 membered hetero ring that has been optionally substituted. In some embodiments, A is -(CR'R'') m -(3-10 member complex ring), where the 3-10 member complex ring is selected from the optionally substituted 3-4 member complex rings, the optionally substituted 3-5 member complex rings, the optionally substituted 3-6 member complex rings, the optionally substituted 3-7 member complex rings, the optionally substituted 3-8 member complex rings, and the optionally substituted 3-9 member complex rings. In some embodiments, A is -(CR'R'') m-(3- to 10-membered complex rings), and the 3- to 10-membered complex rings are selected from the arbitrarily substituted 3-membered complex rings, arbitrarily substituted 4-membered complex rings, arbitrarily substituted 5-membered complex rings, arbitrarily substituted 6-membered complex rings, arbitrarily substituted 7-membered complex rings, arbitrarily substituted 8-membered complex rings, arbitrarily substituted 9-membered complex rings, and arbitrarily substituted 10-membered complex rings.

[0108] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is a 3- to 10-membered heterocycle. In some embodiments, A is a 3- to 10-membered heterocycle, and the 3- to 10-membered heterocycle is an optionally substituted saturated 3- to 10-membered heterocycle. In some embodiments, A is a 3- to 10-membered heterocycle, and the 3- to 10-membered heterocycle is an optionally substituted unsaturated 3- to 10-membered heterocycle. In some embodiments, A is a -3- to 10-membered heterocycle, and the 3- to 10-membered heterocycle is selected from optionally substituted 3- to 4-membered heterocycles, optionally substituted 3- to 5-membered heterocycles, optionally substituted 3- to 6-membered heterocycles, optionally substituted 3- to 7-membered heterocycles, optionally substituted 3- to 8-membered heterocycles, and optionally substituted 3- to 9-membered heterocycles. In some embodiments, A is a 3- to 10-membered complex ring, which is selected from an arbitrarily substituted 3-membered complex ring, an arbitrarily substituted 4-membered complex ring, an arbitrarily substituted 5-membered complex ring, an arbitrarily substituted 6-membered complex ring, an arbitrarily substituted 7-membered complex ring, an arbitrarily substituted 8-membered complex ring, an arbitrarily substituted 9-membered complex ring, and an arbitrarily substituted 10-membered complex ring.

[0109] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is an optionally substituted 5-6 member heteroaryl compound. In some embodiments, A is an optionally substituted 5-6 member heteroaryl compound containing at least one heteroatom selected from nitrogen, oxygen, and sulfur. In some embodiments, A is an optionally substituted 5-6 member heteroaryl compound containing at least one nitrogen or oxygen heteroatom. In some embodiments, A is an optionally substituted 5-6 member heteroaryl compound containing at least one nitrogen or sulfur heteroatom. In some embodiments, A is an optionally substituted 5-6 member heteroaryl compound containing at least one sulfur or oxygen heteroatom. In some embodiments, A is an optionally substituted 5-6 member heteroaryl compound containing at least one sulfur heteroatom. In some embodiments, A is an optionally substituted 5-6 member heteroaryl compound containing at least one oxygen heteroatom. In some embodiments, A is an optionally substituted 5- to 6-membered heteroaryl containing at least one nitrogen heteroatom.

[0110] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is -O-(CR'R'') m (3- to 10-membered heterogeneous rings) and -O-(CR'R'') m -(C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 The carbocyclic rings are as follows: 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 ,-S(O)R 11 -S(O)2R11 -NO2, -CN, 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 alkyl, and C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring and the 3- to 10-membered heterocycle.

[0111] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), m is 0, and A is -O-(3-10 membered heterocycle) and -O-(C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 The carbocyclic rings are as follows: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN, 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively11 , -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, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 alkyl, and C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring and the 3- to 10-membered heterocycle.

[0112] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), A is -O-(CR'R'')-(3-10 membered heterocycle) and -O-(CR'R'')-(C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 The carbocyclic rings are as follows: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN, 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10alkyl, and C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring and the 3- to 10-membered heterocycle.

[0113] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is -O-(CR'R'') m (3- to 10-membered heterogeneous rings) and -O-(CR'R'') m (C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 The carbocyclic rings are as follows: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN, 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 alkyl, and C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 ,-S(O)R 11 -S(O)2R11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring and the 3- to 10-membered heterocycle.

[0114] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), m is 0, and A is a 3-10 membered heterocycle and C 3-10 Selected from carbon rings, 3- to 10-membered heterocycles and C 3-10 The carbocyclic rings are as follows: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN, 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)OR11 -OC(O)R 11 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 alkyl, and C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring and the 3- to 10-membered heterocycle.

[0115] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), A is -(CR'R'')-(3-10 member heterocycle) and -(CR'R'')-(C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 The carbocyclic rings are as follows: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN, 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, C 3-10 Carbon rings and 3- to 10-membered heterocycles are halogens, -OR rings, and so on. 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR11 -OC(O)R 11 -NO2, =O, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 alkyl, and C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring and the 3- to 10-membered heterocycle.

[0116] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is saturated C 3-6 Selected from carbocyclic and 5-6 membered heteroaryls, any of which are: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN and 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 12 , -N(R 12 )2, -C(O)R 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 、 -C(O)OR 12 -OC(O)R 12 -NO2, =O, =N(R 12 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 It is optionally substituted with one or more substituents independently selected from the alkyl group.

[0117] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is saturated C 3-6Selected from carbocyclic and 5-6 membered heteroaryls, any of which are: 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 ,-S(O)R 11 -S(O)2R 11 , -NO2, -CN, and 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), C selected independently of -CN 3-10 Carbon rings and halogens, -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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 It is optionally substituted with one or more substituents independently selected from the alkyl group.

[0118] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is saturated C3-6 Selected from carbocyclic and 5-6 membered heteroaryls, any of which are: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 alkyl, and 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), C selected independently of -CN 3-10 Carbon rings and halogens, -OR 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 -OC(O)R 11 -NO2, =O, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 It is optionally substituted with one or more substituents independently selected from the alkyl group.

[0119] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is saturated C 3-6 Selected from carbocyclic and 5-6 membered heteroaryls, any of which are: Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 -NO2, -CN, Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 -NO2, -CN, C 3-10 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. 1-6 alkyl, and Halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 -NO2, -CN, C 1-6 Alkyl and C 1-6 Saturated C, optionally substituted with one or more substituents selected from haloalkyl groups. 3-6 It is optionally substituted with one or more substituents independently selected from the carbon ring.

[0120] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is C 3-10 Selected from carbocyclic and 3- to 10-membered heteroaryls, each is as follows: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN, 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 alkyl, and C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring and the 3- to 10-membered heterocycle.

[0121] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is a 5-6 member heteroaryl compound, and any of them is: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN, Halogen, -OR 11 , -SR 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN. 3-10 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. 1-10 alkyl, and C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring and the 3- to 10-membered heterocycle.

[0122] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is a 5-6 member heteroaryl compound, and any of them is: 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 ,-S(O)R 11 -S(O)2R 11 , -NO2, -CN, and 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN.3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-6 alkyl, and C 3-6 A saturated carbon ring, containing halogens, -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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-6 It is optionally substituted with one or more substituents independently selected from the saturated carbon ring.

[0123] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), A is a halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R 11 )2, -C(O)OR 11 -OC(O)R 11A is a 5- to 6-membered heteroaryl that is optionally substituted with one or more substituents independently selected from -NO2 and -CN. In some embodiments, A is a halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R 11 )2, -C(O)OR 11 -OC(O)R 11 -NO2, -CN, C 3-6 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 6-membered heterocycle. 1-6 A 5-6 member heteroaryl that is optionally substituted with one or more substituents independently selected from the alkyl, C 3-6 Carbon rings and 3- to 6-membered heterocycles are each -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R 11 )2, -C(O)OR 11 -OC(O)R 11 It is optionally substituted with one or more substituents selected from -NO2 and -CN. In some embodiments, A is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-6 It is a 5-6 member heteroaryl molecule that is optionally substituted with one or more substituents independently selected from the carbon ring.

[0124] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is as follows: Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R 11 )2, -C(O)OR 11 -OC(O)R 11 -NO2, -CN and Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R 11 )2, -C(O)OR 11 -OC(O)R 11 -NO2, -CN, respectively, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R 11 )2, -C(O)OR 11 -OC(O)R 11 C is substituted with one or more substituents selected from -NO2 and -CN. 3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-6 Alkyl, and, C 3-6 A saturated carbon ring, containing halogens, -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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-6 It is a five-membered heteroaryl molecule that is optionally substituted with one or more substituents independently selected from a saturated carbon ring.

[0125] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), A is a halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R 11 )2, -C(O)OR 11 -OC(O)R 11 It is a five-membered heteroaryl that is optionally substituted with one or more substituents independently selected from -NO2 and -CN. In some embodiments, A is a halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -C(O)OR 11 -OC(O)R 11C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-6 Alkyl, C 3-6 It is a 5-membered heteroaryl compound that is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 6-membered heterocycle. 3-6 Carbon rings and 3- to 6-membered heterocycles are each -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -C(O)OR 11 -OC(O)R 11 It is optionally substituted with one or more substituents selected from -NO2 and -CN. In some embodiments, A is a 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 11A ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-6 It is a five-membered heteroaryl molecule that is optionally substituted with one or more substituents independently selected from the carbon ring.

[0126] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, and tetrazolyl, any one of which is a halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R 11 )2, -C(O)OR 11 -OC(O)R 11 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-6 It is optionally substituted with an alkyl group. In some embodiments, A is selected from pyrazolyl and oxadiazolyl, each of which is C 1-6 Alkyl, halogen, -OR 11 , -N(R 11 )2, -C(O)O 11 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-6 It is optionally substituted with an alkyl group. In some embodiments, A is selected from pyrazolyls optionally substituted with methyl, ethyl, isopropyl, or propyl. In some embodiments, A is

[0127] [ka] Selected from. In some embodiments, A is

[0128] [ka] In some embodiments, A is

[0129] [ka] That is the case.

[0130] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), A is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is a five-membered heteroaryl with optional substitutions at the carbon ring.

[0131] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and oxadiazolyl, any of which is a halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 -NO2, -CN, C 1-6 Alkyl and C 1-6 C is optionally substituted with one or more substituents independently selected from the haloalkyl group. 3-6 The saturated carbocyclic rings are optionally substituted.

[0132] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), A is selected from pyrazolyl and oxadiazolyl, each of which is optionally substituted with cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, where cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl is a halogen, C 1-6 Alkyl and C 1-6 It is optionally substituted with a haloalkyl. In some embodiments, A is

[0133] [ka] Selected from. In some embodiments, A is

[0134] [ka] In some embodiments, A is

[0135] [ka] In some embodiments, A is

[0136] [ka] That is the case.

[0137] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), B is -C(H)(R 5 )2. In some embodiments, each R 5 Each occurrence is 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 -OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), and -CN are selected independently. In some embodiments, each R 5 Each occurrence is 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 -OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 Selected independently of alkyl. In some embodiments, each R 5 Each occurrence is 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 -OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 3-6Selected independently from the carbon ring. In some embodiments, each R 5 Each instance is independent and C 3-6 Selected from a carbon ring, this carbon ring is C 1-6 Alkyl, 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 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), and one or more substituents that are optionally substituted with one or more substituents independently selected from -CN, 1-6 Alkyl is optionally substituted.

[0138] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), -C(H)(R 5 )2 each R 5 teeth, Halogen, -OR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)OR 13 -NO2, -CN, Halogen, -OR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)OR 13 -NO2, =O, =S, =N(R 13 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 alkyl; paste Halogen, -OR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)OR 13 -NO2, =O, =S, =N(R 13 ), -CN, C 1-6Alkyl and C 1-6 C is optionally substituted with one or more substituents independently selected from the haloalkyl group. 3-10 It is selected independently of the carbon ring.

[0139] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), R 5 C is replaced by an optional substitution. 3-10 It is a carbon ring. In some embodiments, R 5 C is replaced by an optional substitution. 3-4 Carbon ring, optionally substituted C 3-5 Carbon ring, optionally substituted C 3-6 Carbon ring, optionally substituted C 3-7 Carbon ring, optionally substituted C 3-8 Carbon rings and optionally substituted C 3-9 Selected from a carbon ring. In some embodiments, R 5 C is replaced by an optional substitution. 4-10 Carbon ring, optionally substituted C 5-10 Carbon ring, optionally substituted C 6-10 Carbon ring, optionally substituted C 7-10 Carbon ring, optionally substituted C 8-10 Carbon rings and optionally substituted C 9-10 Selected from a carbon ring. In some embodiments, R 5 C is replaced by an optional substitution. 3-10 It is a saturated carbon ring. In some embodiments, R 5 C is replaced by an optional substitution. 3-10 It is an unsaturated carbon ring. In some embodiments, R 5 C is replaced by an optional substitution. 3-6 Carbon rings and optionally substituted C 6-10 Selected from a carbon ring. In some embodiments, R 5 C is replaced by an optional substitution. 3-8 Monocyclic carbocyclic structures and optionally substituted C 6-10 It is selected from bicyclic carbon rings.

[0140] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), -C(H)(R 5 )2 each R 5 is halogen, -OR 13 , -N(R 13 )2, -C(O)R 13 , -C(O)OR 13 -NO2, =O, =S, =N(R 13 ), -CN, C 1-6 Alkyl and C 1-6 C is optionally substituted with one or more substituents independently selected from the haloalkyl group. 3-6 It is selected independently of the carbon ring.

[0141] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), B is optionally substituted with C. 3-10 It is a carbon ring. In some embodiments, B is optionally substituted with C 3-4 Carbon ring, optionally substituted C 3-5 Carbon ring, optionally substituted C 3-6 Carbon ring, optionally substituted C 3-7 Carbon ring, optionally substituted C 3-8 Carbon rings and optionally substituted C 3-9 Selected from a carbon ring. In some embodiments, B is optionally substituted with C 4-10 Carbon ring, optionally substituted C 5-10 Carbon ring, optionally substituted C 6-10 Carbon ring, optionally substituted C 7-10 Carbon ring, optionally substituted C 8-10 Carbon rings and optionally substituted C 9-10 Selected from a carbon ring. In some embodiments, B is optionally substituted with C 3-10 It is a saturated carbon ring. In some embodiments, B is optionally substituted with C 3-10 It is an unsaturated carbon ring. In some embodiments, B is optionally substituted with C 3-6Carbon rings and optionally substituted C 6-10 Selected from a carbon ring. In some embodiments, B is optionally substituted with C 3-8 Monocyclic carbocyclic structures and optionally substituted C 6-10 Selected from a bicyclic carbon ring. In some embodiments, B is optionally substituted with C 3-7 Monocyclic carbocyclic structures and optionally substituted C 5-10 It is selected from bicyclic carbon rings.

[0142] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), B is a halogen, -OR 12 , N(R 12 )2, -C(O)R 12 -NO2, =O, =S, =N(R 12 ), -CN; and halogen, -OR 12 , N(R 12 )2, -C(O)R 12 -NO2, =O, =S, =N(R 12 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 6-10 It is a carbon ring. In some embodiments, B is a halogen, -OR 12 , N(R 12 )2, -C(O)R 12 -NO2, =O, =S, =N(R 12 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 6-10 It is a carbon ring. In some embodiments, B is a halogen, -OR 12 , N(R 12 )2, -C(O)R 12 -NO2, =O, =S, =N(R 12 ), and one or more C atoms optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with alkyl. 6-10 It is a carbon ring.

[0143] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), B is selected from cyclohexyl and cycloheptyl, each of which is a halogen, -OR 12 , N(R 12 )2, -NO2, -CN and halogens, -OR 12 , N(R 12 )2, -C(O)R 12 -NO2, =O, =S, =N(R 12 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 It is optionally substituted with one or more substituents independently selected from alkyl. In some embodiments, B is selected from cyclohexyl and cycloheptyl, each of which is a halogen, C 1-6 Alkyl and C 1-6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group. In some embodiments, B is cyclohexyl, and C is halogen. 1-6 Alkyl and C 1-6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group. In some embodiments, B is

[0144] [ka] Selected from. In some embodiments, B is

[0145] [ka] In some embodiments, B is

[0146] [ka] In some embodiments, B is

[0147] [ka] That is the case.

[0148] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), B is optionally substituted with C. 3-10 It is a carbon ring. In some embodiments, ring D is optionally substituted with C 3-10 A carbon ring, where any optional substituent of ring D is defined as shown in formula (A) or formula (I). In some embodiments, B is optionally substituted with C 3-10 It is a saturated carbon ring. In some embodiments, B is optionally substituted with C 3-10 It is an unsaturated carbon ring. In some embodiments, the R ring is optionally substituted with C 3-4 Carbon ring, optionally substituted C 3-5 Carbon ring, optionally substituted C 3-6 Carbon ring, optionally substituted C 3-7 Carbon ring, optionally substituted C 3-8 Carbon ring, optionally substituted C 3-9 Carbon rings and optionally substituted C 3-10 Selected from a carbon ring. In some embodiments, the R ring is an optionally substituted C3 carbon ring, an optionally substituted C4 carbon ring, an optionally substituted C5 carbon ring, an optionally substituted C6 carbon ring, an optionally substituted C7 carbon ring, an optionally substituted C8 carbon ring, an optionally substituted C9 carbon ring, and an optionally substituted C 10 Selected from a carbon ring. In some embodiments, ring D is optionally substituted with C 3-8 Monocyclic carbon ring, optionally substituted C 5-10 Bridged carbon rings and optionally substituted C 5-10 Selected from a spirocyclic carbon ring. In some embodiments, ring D is optionally substituted with C 3-8 Monocyclic carbon ring, optionally substituted C 5-10 Bridged carbon rings and optionally substituted C5-10 Selected from a spirocyclic carbon ring, optional substituents of ring D are defined in formula (A) or formula (I).

[0149] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is a 3-10 membered heterocycle containing at least one heteroatom selected from nitrogen, oxygen, and sulfur. In some embodiments, ring D is an optionally substituted 3- to 10 membered heterocycle containing a nitrogen heteroatom, an oxygen heteroatom, or a sulfur heteroatom, or a combination thereof. In some embodiments, ring D is an optionally substituted 3- to 10 membered saturated heterocycle. In some embodiments, ring D is an optionally substituted 3- to 10 membered unsaturated heterocycle. In some embodiments, ring D is an optionally substituted 3- to 10 membered heterocycloalkyl. In some embodiments, ring D is an optionally substituted 5- to 6 membered heteroaryl. In some embodiments, ring D is selected from optionally substituted 3- to 4-membered complex rings, optionally substituted 3- to 5-membered complex rings, optionally substituted 3- to 6-membered complex rings, optionally substituted 3- to 7-membered complex rings, optionally substituted 3- to 8-membered complex rings, optionally substituted 3- to 9-membered complex rings, and optionally substituted 3- to 10-membered complex rings. In some embodiments, ring D is selected from optionally substituted 3-membered complex rings, optionally substituted 4-membered complex rings, optionally substituted 5-membered complex rings, optionally substituted 6-membered complex rings, optionally substituted 7-membered complex rings, optionally substituted 8-membered complex rings, optionally substituted 9-membered complex rings, and optionally substituted 10-membered complex rings. In some embodiments, ring D is a 3- to 10-membered heterocycle that is optionally substituted, and the optional substituents of ring D are as defined in formula (A) or formula (I).

[0150] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is optionally substituted with a 3- to 10-membered heterocycloalkyl group. In some embodiments, ring D is selected from optionally substituted with a 3- to 4-membered heterocycloalkyl group, an optionally substituted with a 3- to 5-membered heterocycloalkyl group, an optionally substituted with a 3- to 6-membered heterocycloalkyl group, an optionally substituted with a 3- to 7-membered heterocycloalkyl group, an optionally substituted with a 3- to 8-membered heterocycloalkyl group, an optionally substituted with a 3- to 9-membered heterocycloalkyl group, and an optionally substituted with a 3- to 10-membered heterocycloalkyl group. In some embodiments, ring D is selected from optionally substituted 3-membered heterocycloalkyl, optionally substituted 4-membered heterocycloalkyl, optionally substituted 5-membered heterocycloalkyl, optionally substituted 6-membered heterocycloalkyl, optionally substituted 7-membered heterocycloalkyl, optionally substituted 8-membered heterocycloalkyl, optionally substituted 9-membered heterocycloalkyl, and optionally substituted 10-membered heterocycloalkyl. In some embodiments, ring D is optionally substituted 3- to 10-membered heterocycloalkyl, and the optionally substituted substituents of ring D are as defined in formula (A) or formula (I).

[0151] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), the R ring D is an optionally substituted 5- to 10-membered bicyclic heterocycle. In some embodiments, ring D is selected from an optionally substituted 5- to 6-membered bicyclic heterocycle, an optionally substituted 5- to 7-membered bicyclic heterocycle, an optionally substituted 5- to 8-membered bicyclic heterocycle, an optionally substituted 5- to 9-membered bicyclic heterocycle, and an optionally substituted 5- to 10-membered bicyclic heterocycle. In some embodiments, ring D is selected from an optionally substituted 5-membered bicyclic heterocycle, an optionally substituted 6-membered bicyclic heterocycle, an optionally substituted 7-membered bicyclic heterocycle, an optionally substituted 8-membered bicyclic heterocycle, an optionally substituted 9-membered bicyclic heterocycle, and an optionally substituted 10-membered bicyclic heterocycle. In some embodiments, ring D is a 5- to 10-membered bicyclic heterocycle that is optionally substituted, and the optional substituents of ring D are as defined in formula (A) or formula (I).

[0152] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is an optionally substituted 5- to 10-membered bicyclic heterocycle, and the optionally substituted 5- to 10-membered bicyclic heterocycle is selected from optionally substituted 5- to 10-membered bridged heterocycles and optionally substituted 5- to 10-membered spirocyclic heterocycles, and any substituents of ring D are as defined in formula (A) or formula (I).

[0153] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), R2 is an optionally substituted 5- to 10-membered bridging heterocycle. In some embodiments, ring D is selected from an optionally substituted 5- to 6-membered bridging heterocycle, an optionally substituted 5- to 7-membered bridging heterocycle, an optionally substituted 5- to 8-membered bridging heterocycle, an optionally substituted 5- to 9-membered bridging heterocycle, and an optionally substituted 5- to 10-membered bridging heterocycle. In some embodiments, ring D is selected from an optionally substituted 5-membered bridging heterocycle, an optionally substituted 6-membered bridging heterocycle, an optionally substituted 7-membered bridging heterocycle, an optionally substituted 8-membered bridging heterocycle, an optionally substituted 9-membered bridging heterocycle, and an optionally substituted 10-membered bridging heterocycle. In some embodiments, ring D is an optionally substituted 5- to 10-membered bridged heterocycle, where the optionally substituted substituents of ring D are as defined in formula (A) or formula (I).

[0154] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is an optionally substituted 5- to 10-membered spirocyclic heterocycle. In some embodiments, ring D is selected from an optionally substituted 5- to 6-membered spirocyclic heterocycle, an optionally substituted 5- to 7-membered spirocyclic heterocycle, an optionally substituted 5- to 8-membered spirocyclic heterocycle, an optionally substituted 5- to 9-membered spirocyclic heterocycle, and an optionally substituted 5- to 10-membered spirocyclic heterocycle. In some embodiments, ring D is selected from an optionally substituted 5-membered spirocyclic heterocycle, an optionally substituted 6-membered spirocyclic heterocycle, an optionally substituted 7-membered spirocyclic heterocycle, an optionally substituted 8-membered spirocyclic heterocycle, an optionally substituted 9-membered spirocyclic heterocycle, and an optionally substituted 10-membered spirocyclic heterocycle. In some embodiments, ring D is an optionally substituted 5- to 10-membered spirocyclic heterocycle, where the optionally substituted substituents of ring D are defined in formula (A) or formula (I).

[0155] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), ring D is as follows: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN, Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C which is optionally substituted with one or more substituents independently selected from CN. 1-10 alkyl, and Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R17 -NO2, =O, =S, =N(R 17 ), -CN and halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 A 3- to 10-membered heterocycle and C are optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 C is optionally substituted with one or more substituents independently selected from the carbon ring. 3-10 It is a carbon ring.

[0156] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 3-10 It is a carbon ring. In some embodiments, ring D is a halogen, -OR 17 , -SR 17, -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), C is optionally substituted with three or more substituents independently selected from -CN. 3-10 It is a carbon ring, R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0157] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is a carbon ring. In some embodiments, ring D is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is a carbon ring. 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0158] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), a 3- to 10-membered heterocycle and C, optionally substituted with one or more substituents independently selected from -CN. 3-10 Carbon rings, as well as halogens, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is a carbon ring. In some embodiments, ring D is a halogen, -OR 17 -SR 17 -N(R 17 )2-C(O)R 17 -C(O)N(R 17 )2-N(R 17 C(O)R 17 -N(R 17 S(O)2R 17 -C(O)OR 17 -OC(O)R 17 -S(O)R 17 -S(O)2R 17 -NO2=O, =S, =N(R) 17 ), -CN and halogen, -OR 17 -SR 17 -N(R 17 )2-C(O)R 17 -C(O)N(R 17 )2-N(R 17 C(O)R 17 -N(R 17 S(O)2R 17 -C(O)OR 17 -OC(O)R 17 -S(O)R 17 -S(O)2R 17 -NO2=O, =S, =N(R) 17 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 A 3- to 10-membered heterocycle and C are optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 C is optionally substituted with one or more substituents independently selected from the carbon ring. 3-10 It is a carbon ring, R17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0159] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), ring D is Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN, and C 1-10 Alkyl and C 3-10 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-10 Alkyl and C 3-10 C is optionally substituted with one or more substituents independently selected from the carbon ring. 3-10 It is a carbon ring.

[0160] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), ring D is Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN, and C 1-10 Alkyl and C 3-10 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-10 Alkyl and C 3-10 C is optionally substituted with one or more substituents independently selected from the carbon ring. 3-10 It is a carbon ring, R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0161] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is a halogen, -OR 17, -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 C(O)R 17 , -N(R 17 S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2-CN and C 1-10 Alkyl and C 3-10 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2-C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 C(O)R 17 , -N(R 17 S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-10 Alkyl and C 3-10 C is optionally substituted with one or more substituents independently selected from the carbon ring. 3-10 It is a saturated carbon ring, R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 It is a carbon ring. In some embodiments, ring D is a halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 -NO2, -CN, C 1-6 Alkyl and C 1-6 C is optionally substituted with one or more substituents independently selected from the haloalkyl group. 3-6 It is a saturated carbon ring. In some embodiments, ring D is a halogen, -OR 17 -N(R17 )2-C(O)R 17 -NO2-CN, C 1-6 Alkyl and C 1-6 C is optionally substituted with one or more substituents independently selected from the haloalkyl group. 3-6 It is a saturated carbon ring, R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 It is a carbon ring.

[0162] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, each of which is a halogen, -OR 17 , -NR 17 2, -C(O)R 17 -NO2, -CN, C 1-6 Alkyl and C 1-6 R is optionally substituted with one or more substituents independently selected from the haloalkyl group. 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from a carbocyclic ring. In some embodiments, ring D is selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, any of which is a halogen, C 1-6 Alkyl and C 1ー6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group. In some embodiments, ring D is

[0163] [ka] Selected from. In some embodiments, ring D is

[0164] [ka] In some embodiments, ring D is

[0165] [ka] In some embodiments, ring D is

[0166] [ka] That is the case.

[0167] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), ring D is as follows: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN, Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C which is optionally substituted with one or more substituents independently selected from CN.1-10 alkyl, and Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN and halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 A 3- to 10-membered heterocycle and C are optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is a 3- to 10-membered heterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring.

[0168] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), ring D is as follows: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17)C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN, Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C which is optionally substituted with one or more substituents independently selected from CN. 1-10 Alkyl, Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN and halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17)S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 A 3- to 10-membered heterocycle and C are optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 A 3- to 10-membered heterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring, R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0169] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), ring D is as follows: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN, and C 1-10 Alkyl and C 3-10 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-10 Alkyl and C 3-10 It is a 3- to 10-membered heterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring.

[0170] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), ring D is as follows: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN, and C 1-10 Alkyl and C 3-10 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-10 Alkyl and C 3-10A 3- to 10-membered heterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring, R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0171] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is selected from 3-7 monocyclic heterocycles and 5-10 membered bicyclic heterocycles, any of which are as follows: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN, Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C which is optionally substituted with one or more substituents independently selected from CN. 1-10 alkyl, and Halogen, -OR 17 , -SR 17, -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN and halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 A 3- to 10-membered heterocycle and C are optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring.

[0172] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is selected from 3- to 7-membered monocyclic carbocyclic rings and 5- to 10-membered bicyclic heterocyclic rings, any of which are as follows: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17)S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =N(R 17 ), -CN, Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C which is optionally substituted with one or more substituents independently selected from CN. 1-10 alkyl, and Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), -CN and halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17-OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, =O, =S, =N(R 17 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 A 3- to 10-membered heterocycle and C are optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from the carbon ring. R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0173] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is selected from 3- to 7-membered monocyclic carbocyclic rings and 5- to 10-membered bicyclic heterocyclic rings, any of which are as follows: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN, and C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17, -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN are optionally substituted with one or more substituents independently selected from C 1-6 Alkyl and C 3-6 It is optionally substituted with one or more substituents independently selected from the carbon ring.

[0174] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is selected from 3- to 7-membered monocyclic carbocyclic rings and 5- to 10-membered bicyclic heterocyclic rings, any of which are as follows: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN, and C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN are optionally substituted with one or more substituents independently selected from C 1-6 Alkyl and C3-6 It is optionally substituted with one or more substituents independently selected from the carbon ring. R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0175] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), ring D is as follows: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN, and C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN are optionally substituted with one or more substituents independently selected from C 1-6 Alkyl and C 3-6 A 5-6 membered heterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring, R 17is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0176] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, -CN, C 1-6 Alkyl and C 1-6 It is a 5- to 6-membered heteroaryl that is optionally substituted with one or more substituents independently selected from the haloalkyl. In some embodiments, ring D is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 -NO2, -CN, C 1-6 Alkyl and C 1-6 A 5-6 member heteroaryl that is optionally substituted with one or more substituents independently selected from the heteroalkyl, R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Heteroalkyl and C 3-6Selected from a carbon ring. In some embodiments, ring D is selected from pyridinyl and pyrimidinyl, each of which is a halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 -NO2, -CN, C 1-6 Alkyl and C 1-6 It is optionally substituted with one or more substituents independently selected from the haloalkyl group. In some embodiments, ring D is

[0177] [ka] Selected from. In some embodiments, ring D is

[0178] [ka] In some embodiments, ring D is

[0179] [ka] That is the case.

[0180] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is selected from 3- to 6-membered saturated heterocycles and C3- to 6-unsaturated heterocycles, any of which are: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN, and C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN are optionally substituted with one or more substituents independently selected from C 1-6 Alkyl and C 3-6 It is optionally substituted with one or more substituents independently selected from the carbon ring. R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0181] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), ring D is as follows: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN, and C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 17, -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN are optionally substituted with one or more substituents independently selected from C 1-6 Alkyl and C 3-6 A 3- to 6-membered unsaturated heterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring, R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0182] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), ring D is as follows: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN, and C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN are optionally substituted with one or more substituents independently selected from C 1-6 Alkyl and C 3-6 It is a 3- to 6-membered heterocycloalkyl group that is optionally substituted with one or more substituents independently selected from the carbocyclic ring. R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0183] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is selected from 3- to 6-membered saturated heterocycles and 3- to 6-membered unsaturated heterocycles, and one of them is a halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 -NO2, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 The ring D is optionally substituted with one or more substituents independently selected from the carbon ring. In some embodiments, ring D is selected from 3- to 6-membered saturated heterocycles and 3- to 6-membered unsaturated heterocycles, any of which are halogens, -OR 17 , -NR 17 )2, -C(O)R 17 -NO2, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Optionally substituted with one or more substituents independently selected from the carbon ring, R 17 is hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and C 3-6 Selected from the carbocyclic ring.

[0184] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is a halogen, C 1-6 Haloalkyl and C 3-6 It is a 3- to 6-membered unsaturated heterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring. In some embodiments, ring D is selected from 2,5-dihydrofuranyl and 3,6-dihydro-2H-pyranyl. In some embodiments, ring D is

[0185] [ka] Selected from. In some embodiments, ring D is

[0186] [ka] In some embodiments, ring D is

[0187] [ka] That is the case.

[0188] In some embodiments, for compounds or salts of formula (I), (II), (II-a), or (II-b), ring D is a halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 -NO2, -CN, C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 These are 3- to 6-membered heterocycloalkyls optionally substituted with one or more substituents independently selected from the carbocyclic ring. In some embodiments, these are selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, and morpholinyl, each of which is a halogen, -OR 17, -N(R 17 )2, -C(O)R 17 -NO2, -CN, C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Optionally substituted with one or more substituents independently selected from the carbon ring, R 17 However, hydrogen, C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 Selected from a carbocyclic ring. In some embodiments, ring D is

[0189] [ka] Selected from. In some embodiments, ring D is

[0190] [ka] Selected from. In some embodiments, ring D is

[0191] [ka] Selected from. In some embodiments, ring D is

[0192] [ka] Selected from.

[0193] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is a 5-10 membered bicyclic carbon ring selected from 5-10 membered bridged carbon rings and 5-10 membered spirocyclic heterocycles, any of which is: Halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2, -CN, and C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 )C(O)R 17 , -N(R 17 )S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-6 Alkyl and C 3-6 It is optionally substituted with one or more substituents independently selected from the carbon ring.

[0194] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is a 5-10 membered bicyclic heterocycle selected from 5-10 membered condensed heterocycles, 5-10 membered bridging heterocycles, and 5-10 membered spirocyclic heterocycles, any of which is a halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 -NO2, -CN, C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is optionally substituted with one or more substituents independently selected from the carbon ring.

[0195] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is a halogen, -OR 17 , N(R 17 )2, -C(O)R 17 -NO2, -CN, C 1-3 Alkyl, C 1-3 Haloalkyl, C 3-6 It is a 5- to 10-membered condensed heterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring. In some embodiments, ring D is

[0196] [ka] That is the case.

[0197] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), ring D is a 5-10 membered bicyclic heterocycle selected from 5-10 membered bridged heterocycles and 5-10 membered spirocyclic heterocycles, and any of them is a halogen, -OR 17 , -NR 17 2, -C(O)R 17 -NO2, -CN, C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is optionally substituted with one or more substituents independently selected from the carbocyclic ring.

[0198] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), the 5-10 membered bicyclic heterocycle of ring D is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 C(O)R 17 , -N(R 17 S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R17 , -NO2-CN and C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2-C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 C(O)R 17 , -N(R 17 S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-6 Alkyl and C 3-6 It is a 5- to 10-membered bridged heterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring. In some embodiments, ring D is a 5- to 10-membered bridged heterocycle, and is halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 -NO2, -CN, C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 The ring D is optionally substituted with one or more substituents independently selected from the carbon ring. In some embodiments, ring D is a halogen, -OR 17 , C 1-3 Alkyl and C 1-3 The ring D is a 5- to 10-membered crosslinked heterocycle that is optionally substituted with one or more substituents independently selected from the haloalkyl group. In some embodiments, ring D is selected from 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, and 8-oxa-3-azabicyclo[3.2.1]octanyl, each of which is halogen, -OR 17 , C 1-3 Alkyl and C 1-3 It is optionally substituted with one or more substituents independently selected from the haloalkyl group. In some embodiments, ring A is

[0199] [ka] Selected from. In some embodiments, ring D is

[0200] [ka] In some embodiments, ring D is

[0201] [ka] In some embodiments, ring D is

[0202] [ka] That is the case.

[0203] In some embodiments, for compounds or salts of formula (A), (I), (Ia), or (Ib), the 5-10 membered bicyclic heterocycle of ring D is a halogen, -OR 17 , -SR 17 , -N(R 17 )2, -C(O)R 17 ,-C(O)N(R 17 )2, -N(R 17 C(O)R 17 , -N(R 17 S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 , -NO2-CN and C 1-6 Alkyl and C 3-6 A carbon ring, each of which is a halogen, -OR 17 , -SR 17 , -N(R 17 )2-C(O)R 17 ,-C(O)N(R17 )2, -N(R 17 C(O)R 17 , -N(R 17 S(O)2R 17 , -C(O)OR 17 -OC(O)R 17 ,-S(O)R 17 -S(O)2R 17 C is optionally substituted with one or more substituents independently selected from -NO2 and -CN. 1-6 Alkyl and C 3-6 It is a 5- to 10-membered spiroheterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring. In some embodiments, ring D is a halogen, -OR 17 , -N(R 17 )2, -C(O)R 17 , -NO2, -CN and C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It is a 5- to 10-membered spirocyclic heterocycle, optionally substituted with one or more substituents independently selected from the carbon ring. In some embodiments, ring D is a halogen, -OR 17 , C 1-3 Alkyl and C 1-3 The ring D is a 5- to 10-membered spirocyclic heterocycle that is optionally substituted with one or more substituents independently selected from the haloalkyl group. In some embodiments, ring D is selected from 2-oxa-6-azaspiro[3.3]heptanyl, 6-oxa-2-azaspiro[3.5]nonanyl, 7-oxa-2-azaspiro[3.5]nonanyl, 2-oxa-6-azaspiro[3.4]octanyl, 4-oxa-7-azaspiro[2.5]octanyl, and 4-methyl-4,7-diazaspiro[2.5]octanyl, each of which is a halogen, -OR 17 , C 1-3 Alkyl and C 1-3 It is optionally substituted with one or more substituents independently selected from the haloalkyl group. In some embodiments, ring D is

[0204] [ka] Selected from. In some embodiments, ring D is

[0205] [ka] In some embodiments, ring D is

[0206] [ka] In some embodiments, ring D is

[0207] [ka] In some embodiments, ring D is

[0208] [ka] In some embodiments, ring D is

[0209] [ka] That is the case.

[0210] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), ring D is

[0211] [ka] Selected from.

[0212] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), ring D is

[0213] [ka] Selected from.

[0214] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , and R 21 Each of these is selected from hydrogen each time it appears.

[0215] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , and R 21 Each of them, upon appearance, Hydrogen, and C 1-6 Alkyl, halogen, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -NH 2、 -NO2, =O, -CN, C 3-10 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. 1-6 Selected independently of alkyl, each C 3-10 Carbon rings and 3- to 10-membered heterocycles are halogens, -OH, and -OC. 1-6 Alkyl, -OC 1-6 Haloalkyl, -NH 2、 It is optionally substituted with one or more substituents independently selected from -NO2, =O, and -CN.

[0216] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , and R 21 Each of them, upon appearance, Hydrogen, and Halogen, -OH, -OC 1-6 Alkyl, -OC 1-6 C is optionally substituted with one or more substituents independently selected from haloalkyl, -NH2, -NO2, =O, and -CN. 3-10 They are independently selected from carbon rings and 3- to 10-membered heterocycles.

[0217] In some embodiments, for a compound or salt of formula (A), (I), (Ia), or (Ib), R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , and R 21 Each instance of appearance, independently, hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Selected from carbon rings and 3- to 6-membered heterocycles.

[0218] In another aspect, this disclosure is:

[0219] [ka] The present invention provides compounds or salts having a structure selected from the group consisting of the following.

[0220] Preferred embodiments of the present invention have been shown and described herein, but it will be apparent to those skilled in the art that such embodiments are provided only as examples. Those skilled in the art will be able to conceive of numerous variations, modifications, and substitutions without departing from the present invention. It should be understood that various alternatives to the embodiments of the present invention described herein may be used in carrying out the present invention. The following claims define the scope of the present invention, and methods and structures within these claims, as well as their equivalents, are intended to be encompassed thereby.

[0221] Chemicals containing carbon-carbon double bonds or carbon-nitrogen double bonds may exist in Z- or E- forms (or cis- or trans- forms). Furthermore, some chemicals may exist in various tautomerized forms. Unless otherwise specified, compounds or salts of formula (A), (I), (Ia), or (Ib) are intended to equally encompass all Z-, E-, and tautomerized forms.

[0222] "Isomers" are different compounds that have the same molecular formula. "Stereoisomers" are isomers that differ only in the arrangement of atoms in space. "Enantiomers" are a pair of stereoisomers that are mirror images of each other and cannot be superimposed. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture. The term "(±)" is used to specify a racemic mixture where appropriate. "Diastereoisomers" are stereoisomers that have at least two chiral atoms but are not mirror images of each other. Absolute stereochemistry is specified according to the Kahn-Ingold-Prelogue RS system. If a compound is a pure enantiomer, the stereochemistry at each chiral carbon can be specified by either R or S. Split compounds whose absolute configuration is unknown can be designated (+) or (-) depending on the direction in which they rotate plane-polarized light at the wavelength of the sodium D line (dextrorotatory or levorotatory). Certain compounds described herein contain one or more chiral centers and can therefore give rise to enantiomers, diastereomers, and other stereoisomeric forms, the chiral centers of which can be defined as (R)- or (S)- with respect to absolute stereochemistry. The chemicals, pharmaceutical compositions, and methods of the present invention mean that they include 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 they can be divided using conventional techniques. The optical activity of a compound can be analyzed by any suitable method, including but not limited to chiral chromatography and optical rotation analysis, to determine the dominance of one stereoisomer over other isomers.

[0223] Compounds or salts of formula (A), (I), (Ia), or (Ib) may, in some cases, exist as diastereomers, enantiomers, 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 they can be prepared by those skilled in the art through routine experiments. Separation of stereoisomers may be carried out by chromatography, or by forming diastereomers and separating them by recrystallization, chromatography, or any combination thereof. (Jean Jacques, Andre Collet, Samuel H. Wilen, "Enantiomers, Racemates and Resolutions," John Wiley and Sons, Inc., 1981, incorporated herein by reference for the purposes of this disclosure). Stereoiomers may be obtained by stereoselective synthesis. Furthermore, a mixture of the two enantiomers, in which one of the two enantiomers is concentrated, can be purified, and a more optically concentrated form of the major enantiomer can be obtained by recrystallization and / or grinding.

[0224] In certain embodiments, a compound or salt of formula (A), (I), (Ia), or (Ib) may comprise two or more enantiomers or diastereomers of the compound, wherein a single enantiomer or diastereomer accounts for at least about 70% by weight, at least about 80% by weight, at least about 90% by weight, at least about 98% by weight, 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 substantially free of its stereoisomers, e.g., an enantiomer, may be obtained by the resolution of a racemic mixture using methods such as the formation of diastereomers using optically active resolving agents (Stereochemistry of Carbon Compounds, (1962) by ELEliel, McGraw Hill, Lochmuller (1975) J. Chromatogr., 113(3):283-302). Racemic mixtures of chiral compounds can be separated and isolated by any suitable method, but are not limited to: (1) formation of ionic diastereomer salts with the chiral compound and separation by fractional crystallization or other means; (2) formation of diastereomer compounds with chiral derivatization reagents, separation of diastereomers, and conversion to pure stereoisomers; and (3) direct separation of substantially pure or concentrated stereoisomers under chiral conditions. Another approach for the separation of enantiomers is to use a Diacel chiral column and elute with an organic mobile phase, as performed by Chiral Technologies (www.chiraltech.com) at a service charge.

[0225] A "tautomer" refers to a molecule in which proton transfer is possible from one atom of the molecule to another atom of the same molecule. In certain embodiments, compounds or salts of formula (A), (I), (Ia), or (Ib) exist as tautomers. In situations where tautomerization is possible, a chemical equilibrium of tautomers may exist. The exact ratio of tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some non-limiting examples of tautomer equilibrium include:

[0226] [ka]

[0227] Compounds of formula (A), (I), (Ia), or (Ib) are available in different enriched isotopic forms, for example, 2 H, 3 H, 11 C, 13 C, and / or 14 The compound can be used in a form with a concentrated C content. In a particular embodiment, the compound is deuterated at at least one position. Such a deuterated form can be prepared by the procedure described in U.S. Patents 5,846,514 and 6,334,997. As described in U.S. Patents 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or efficacy, and thus extend the duration of action of the drug.

[0228] In certain embodiments, the compound of formula (A), (I), (Ia), or (Ib) is 1 Some or all of the H atoms 2 It is substituted with a hydrogen atom. Methods for synthesizing deuterium-containing compounds are known in the art, and the following synthesis method is given only as a non-limiting example.

[0229] Deuterium-substituted compounds are synthesized using various methods, as described in Dean, Dennis C., Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; 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.

[0230] Deuterated starting materials are readily available and, when used in the synthesis methods described herein, provide for the synthesis of deuterium-containing compounds. Numerous deuterium-containing reagents and components are commercially available from chemical suppliers such as Aldrich Chemical Co.

[0231] Unless otherwise stated, compounds of formula (A), (I), (Ia), or (Ib) are intended to include compounds that differ only in the presence of one or more isotopically enriched atoms, for example, hydrogen substitution with deuterium or tritium, or 13 C- or 14 Apart from the substitution of carbon atoms by carbon atoms, compounds having this structure are within the scope of this disclosure.

[0232] Compounds of formula (A), (I), (Ia), or (Ib) optionally contain one or more atomic isotopes in unnatural proportions in the atoms constituting such compounds. For example, the compound contains isotopes, such as deuterium ( 2 H), tritium ( 3 H), Iodine-125( 125I), or carbon-14 ( 14 It can be labeled with C), etc. 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 in I are intended. All isotopic variants of the compounds of this disclosure, whether radioactive or not, are intended to be included within the scope of this disclosure.

[0233] This disclosure includes salts, in particular pharmaceutically acceptable, of compounds of formula (A), (I), (Ia), or (Ib). The compounds of this disclosure may have a sufficiently acidic functional group, a sufficiently basic functional group, or both, and may react with several inorganic bases as well as either inorganic or organic acids to form salts. Alternatively, compounds that are inherently charged (e.g., compounds having quaternary nitrogen) may form salts with suitable counterions (e.g., halides (e.g., bromides, chlorides, or fluorides)).

[0234] In certain embodiments, a compound or salt of formula (A), (I), (Ia), or (Ib) may be a prodrug. The term “prodrug” is intended to encompass compounds that are converted to the pharmaceuticals of this disclosure under physiological conditions. One method for producing a prodrug is to include one or more selected moieties that are hydrolyzed under physiological conditions to exhibit a desired molecule. In other embodiments, the prodrug is converted by the enzymatic activity of a host animal, such as specific target cells in the host animal.

[0235] In some embodiments, the design of the prodrug increases the lipophilicity of the pharmaceutical. In some embodiments, the design of the prodrug increases its effective water solubility. For example, Fedorak et al., Am.J.Physiol., 269:G210-218 (1995), McLoed et al., Gastroenterol, 106:405-413 (1994), Hochhaus et al., Biomed.Chrom., 6:283-286 (1992), J.Larsen and H.Bundgaard, Int.J.Pharmaceutics, 37,87 (1987), J.Larsen et al., Int.J.Pharmaceutics, 47,103 (1988), Sinkula et al., J.Pharm.Sci. 64:181-210 (1975), T.Higuchi and V.Stella, Pro-drugs as Novel Delivery Systems, Vol.14 of the ACSSymposium, all of which are incorporated herein for such disclosures. See Series and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987. According to another embodiment, the present disclosure provides a method for producing the compounds defined above. The compounds can be synthesized using prior art. Advantageously, these compounds can be easily synthesized from readily available starting materials.

[0236] Useful synthetic chemical transformations and methodologies for synthesizing the compounds described herein are known in the art, for example, as described in R. Larock, Comprehensive Organic Transformations (1989); TW. Greene and PGMWuts, Protective Groups in Organic Synthesis, 2nd ed. (1991); Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis, 1994; and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, (1995).

[0237] Pharmaceutical preparations In some embodiments, the present disclosure provides a pharmaceutical composition comprising a compound or salt of formula (A), (I), (Ia), or (Ib) and at least one pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition comprises a compound or salt of formula (A), (I), (Ia), or (Ib) and a pharmaceutically acceptable excipient.

[0238] In some embodiments, this disclosure

[0239] [ka] The present invention provides a pharmaceutical composition comprising a compound selected from the group consisting of, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0240] Pharmaceutical compositions can be formulated using one or more physiologically acceptable carriers, including excipients and adjuvants. Formulations can be modified depending on the selected route of administration. Pharmaceutical compositions comprising compounds, salts, or conjugates can be prepared, for example, by lyophilizing the compounds, salts, or conjugates, or by mixing, dissolving, emulsifying, encapsulating, or encapsulating the conjugates. Pharmaceutical compositions may also contain compounds, salts, or conjugates in free base form or pharmaceutically acceptable salt form.

[0241] Pharmaceutical compositions may often further contain two or more active compounds (e.g., compounds, salts or conjugates and other agents) as needed for the specific indication being treated. The active compounds may have complementary activities that do not adversely affect each other. Such molecules may be present in combination in amounts effective for the intended purpose.

[0242] Any one compound or salt of formula (A), (I), (Ia), or (Ib) can be formulated into any suitable pharmaceutical formulation. Pharmaceutical formulations of the present disclosure typically contain an active ingredient (e.g., any one compound or salt of formula (A) or (I)) 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, permeation enhancers, antioxidants, solubilizers, and adjuvants.

[0243] In certain embodiments, the compound or salt of formula (A), (I), (Ia), or (Ib) is formulated with a chelating agent or other material that can bind to metal ions, such as ethylene diamine tetraacetic acid (EDTA), and the salt can enhance the stability of the compound or salt of formula (A), (I), (Ia), or (Ib).

[0244] Pharmaceutical preparations may be provided in any preferred form depending on the route of administration.

[0245] In some embodiments, the disclosure provides an orally administered pharmaceutical composition comprising at least one compound or salt of any one of formulas (A), (I), (Ia), or (Ib), and a pharmaceutical excipient suitable for oral administration. The composition may be in the form of a solid, liquid, gel, semi-liquid, or semi-solid. In some embodiments, the composition further comprises a second drug.

[0246] Pharmaceutical compositions of the present disclosure suitable for oral administration may be presented in individual dosage forms, such as hard or soft capsules, cachets, lozenges, tablets, or as powders or granules, each containing a predetermined amount of the active ingredient in a liquid or aerosol spray, solution, or suspension in an aqueous or non-aqueous liquid, an oil-in-water emulsion or water-in-oil emulsion, or as dispersible powders or granules, or as a syrup or elixir. Such dosage forms can typically be prepared by any pharmaceutical method that includes a step of associating the active ingredient with a carrier. Generally, compositions are prepared by homogeneously and closely mixing the active ingredient with a liquid carrier or a micronized solid carrier or both, and then, if necessary, shaping the product into a desired presentation. For example, tablets may be prepared by compression or shaping with one or more optional minor components. Compressed tablets can be prepared by compressing a free-flowing active ingredient, such as a powder or granules, which is optionally mixed with excipients such as binders, lubricants, inert diluents, and / or surfactants or dispersants, in a suitable machine. Molded tablets can be prepared by molding a mixture of any one of the powder compounds or salts of formula (A), (I), (Ia), or (Ib), moistened with an inert liquid diluent, in a suitable machine.

[0247] The pharmaceutical composition may further be prepared from one compound or salt of formula (A), (I), (Ia), or (Ib) and one or more pharmaceutically acceptable excipients. The preparation of such pharmaceutical compositions is well known in the art. For example, Anderson, Philip O.; Knoben, James E.; 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, ed., Basic and Clinical Pharmacology, Ninth Edition, McGraw. See Hill, 2003, Goodman and Gilman, eds., The Pharmacological Basis of Therapeutics, Tenth Edition, McGraw Hill, 2001, Remingtons Pharmaceutical Sciences, 20th Ed., Lippincott Williams & Wilkins., 2000, Martindale, The Extra Pharmacopoeia, Thirty-Second Edition (The Pharmaceutical Press, London, 1999).

[0248] Treatment method In some embodiments, the present disclosure provides a method for modulating IL-17A in a subject requiring modification of IL-17A, comprising administering to the subject a compound or salt of formula (A), (I), (Ia), or (Ib), or a pharmaceutical composition thereof.

[0249] Elevated IL-17A levels have been associated with several conditions, including airway inflammation, rheumatoid arthritis (RA), osteoarthritis, bone erosion, intra-abdominal abscesses and adhesions, inflammatory bowel disorder (IBD), allograft rejection, psoriasis, psoriatic arthritis, ankylosing spondylitis, certain types of cancer, angiogenesis, atherosclerosis, and multiple sclerosis (MS). Both IL-17A and IL-17R are upregulated in the synovial tissue of RA patients. IL-17A plays a role in the pathogenesis of RA via IL-1-β and TNF-α-dependent and independent pathways. IL-17A stimulates the secretion of other cytokines and chemokines, such as TNF-α, IL-1β, IL-6, IL-8, and Gro-α. IL-17A directly contributes to disease progression in RA. Injection of IL-17A into the mouse knee promotes joint destruction independently of IL-Iβ activity (Ann Rheum Dis 2000, 59:529-32). Anti-IL-1β antibodies are ineffective against IL-17A-induced inflammation and joint damage (J.Immunol 2001, 167:1004-1013). In a streptococcal cell wall (SCW)-induced mouse arthritis model, IL-17A induced inflammatory cell infiltration and proteoglycan depletion in wild-type, IL-1β knockout, and TNF-α knockout mice. IL-17A knockout mice were phenotypic normal in the absence of antigen challenge, but showed a significant reduction in arthritis after type II collagen immunization (J.Immunol 2003, 171:6173-6177). Increased levels of IL-17A-secreting cells have also been observed in the facet joints of patients with ankylosing spondylitis (H Appel et al., Arthritis Res Therap. 2011, 13:R95).

[0250] Multiple sclerosis (MS) is an autoimmune disease characterized by central nervous system (CNS) inflammation accompanied by damage to the myelin sheath surrounding axons. A prominent feature of MS is the infiltration of T cells into the CNS. Compared to remission, a greater number of mononuclear cells (MNCs) expressing IL-17A mRNA are detected during MS clinical exacerbations (Multiple Sclerosis, 5:101-104, 1999). Furthermore, experimental autoimmune encephalomyelitis (EAE), a preclinical animal model of MS, is significantly suppressed in IL-17A knockout mice.

[0251] In certain embodiments, the Disclosure provides a method for modulating IL-17A in subjects requiring modification of IL-17A, comprising administering a compound or salt of formula (A), (I), (Ia), or (Ib) to the subject. In certain embodiments, the compound or salt of formula (A), (I), (Ia), or (Ib) inhibits the activity of IL-17A in subjects requiring inhibition of IL-17A activity.

[0252] In certain embodiments, compounds or salts of formula (A), (I), (Ia), or (Ib) can be used to treat or prevent diseases or conditions directly or indirectly mediated by IL-17A. Such diseases include inflammatory diseases and conditions, proliferative diseases (e.g., cancer), autoimmune diseases, and other diseases described herein. The method generally involves administering a therapeutically effective amount of the compounds disclosed herein or their pharmaceutical compositions to a target. In some embodiments, the inflammatory diseases or conditions are selected from psoriasis vulgaris, guttate psoriasis, psoriasis reversal, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis, and non-infectious uveitis.

[0253] In some embodiments, the Disclosure provides a method for treating or preventing an inflammatory disease or condition in a subject that requires treatment or prevention of an inflammatory disease or condition, comprising administering a compound or salt of formula (A), (I), (Ia), or (Ib), or a pharmaceutical composition thereof, to the subject. In certain embodiments, a compound or salt of formula (A), (I), (Ia), or (Ib) is administered to a subject that requires treatment for an inflammatory disease or condition, such as psoriasis.

[0254] In certain embodiments, compounds or salts of formula (A), (I), (Ia), or (Ib) are used to treat or prevent inflammatory diseases or conditions selected from psoriasis vulgaris, guttate psoriasis, psoriasis reversal, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis, and non-infectious uveitis. In certain embodiments, compounds or salts of formula (A), (I), (Ia), or (Ib) are used to treat or prevent psoriasis. In certain embodiments, compounds or salts of formula (A), (I), (Ia), or (Ib) are used to treat or prevent conditions including, but not limited to, airway inflammation, ankylosing spondylitis, asthma, RA (including juvenile RA), and other inflammatory disorders, conditions, or diseases.

[0255] In certain embodiments, the present disclosure provides a method for adjusting IL-17A in an object requiring adjustment of IL-17A,

[0256] [ka] A method is provided comprising administering to a subject a compound selected from the group consisting of, or a pharmaceutically acceptable salt thereof. In a particular embodiment,

[0257] [ka] Compounds selected from the group comprising, or any one of the pharmaceutically acceptable salts thereof, inhibit the activity of IL-17A in subjects requiring it.

[0258] In a particular embodiment,

[0259] [ka] A compound selected from the group consisting of, or any one thereof, a pharmaceutically acceptable salt thereof, can be used to treat or prevent diseases or conditions directly or indirectly mediated by IL-17A. Such diseases include inflammatory diseases and conditions, proliferative diseases (e.g., cancer), autoimmune diseases, and other diseases described herein. The method generally involves administering a therapeutically effective amount of the compound disclosed herein or a pharmaceutical composition thereof to a target. In some embodiments, the inflammatory disease or condition is selected from psoriasis vulgaris, guttate psoriasis, psoriasis reversal, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis, and non-infectious uveitis.

[0260] In some aspects, the Disclosure relates to methods for treating or preventing inflammatory diseases or conditions, in which the treatment is necessary for the treatment of such conditions.

[0261] [ka] A method is provided which comprises administering a compound selected from the group consisting of, or any one thereof, in a pharmaceutical composition. In some embodiments,

[0262] [ka] A compound or salt selected from the group comprising the above is administered to a subject in need to treat an inflammatory disease or condition, such as psoriasis.

[0263] In a particular embodiment,

[0264] [ka] Compounds or salts selected from the group consisting of are used to treat or prevent inflammatory diseases or conditions selected from psoriasis vulgaris, guttate psoriasis, psoriasis reversal, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis, and non-infectious uveitis. In some embodiments,

[0265] [ka] Compounds or salts selected from the group consisting of are used to treat or prevent psoriasis. In certain embodiments,

[0266] [ka] Compounds or salts selected from the group consisting of the above are used for the treatment or prevention of conditions including, but not limited to, airway inflammation, ankylosing spondylitis, asthma, rheumatoid arthritis (including juvenile rheumatoid arthritis), and other inflammatory disorders, conditions, or diseases.

[0267] In certain embodiments, the Disclosure provides a method for treating psoriasis using a compound or salt disclosed herein. In some embodiments, a method for treating psoriasis includes administering a compound or salt disclosed herein to a subject in need. In certain embodiments, the Disclosure provides a method for treating psoriasis including administering a compound or salt of formula (A), (I), (Ia), or (Ib) to a subject in need. In some embodiments, a method for treating psoriasis includes administering a pharmaceutical composition comprising a compound or salt of formula (A), (I), (Ia), or (Ib) and a pharmaceutically acceptable excipient to a subject in need. In some embodiments, a method for treating psoriasis includes administering to a subject in need,

[0268] [ka] In some embodiments, a method for treating psoriasis involves administering a compound or salt selected from the group consisting of the following:

[0269] [ka] The method includes administering a pharmaceutical composition comprising a compound or salt selected from the group consisting of and a pharmaceutically acceptable excipient.

[0270] In certain embodiments, the Disclosure provides a method for treating psoriatic arthritis using a compound or salt disclosed herein. In some embodiments, a method for treating psoriatic arthritis includes administering a compound or salt disclosed herein to a subject in need. In certain embodiments, the Disclosure provides a method for treating psoriatic arthritis including administering a compound or salt of formula (A), (I), (Ia), or (Ib) to a subject in need. In some embodiments, a method for treating psoriatic arthritis includes administering a pharmaceutical composition to a subject in need comprising a compound or salt of formula (A), (I), (Ia), or (Ib) and a pharmaceutically acceptable excipient. In some embodiments, a method for treating psoriatic arthritis includes administering to a subject in need,

[0271] [ka] The method comprises administering a compound selected from the group consisting of the following. In some embodiments, a method for treating psoriatic arthritis involves administering it to a subject in need.

[0272] [ka] The method includes administering a pharmaceutical composition comprising a compound or salt selected from the group consisting of and a pharmaceutically acceptable excipient.

[0273] In certain embodiments, the Disclosure provides a method for treating ankylosing spondylitis using a compound or salt disclosed herein. In some embodiments, a method for treating ankylosing spondylitis includes administering a compound or salt disclosed herein to a subject in need. In certain embodiments, the Disclosure provides a method for treating ankylosing spondylitis including administering a compound or salt of formula (A), (I), (Ia), or (Ib) to a subject in need. In some embodiments, a method for treating ankylosing spondylitis includes administering a pharmaceutical composition to a subject in need, comprising a compound or salt of formula (A), (I), (Ia), or (Ib) and a pharmaceutically acceptable excipient. In some embodiments, a method for treating ankylosing spondylitis includes administering to a subject in need,

[0274] [ka] The method comprises administering a compound or salt selected from the group consisting of the following. In some embodiments, the method for treating ankylosing spondylitis involves administering it to a subject in need.

[0275] [ka] The method includes administering a pharmaceutical composition comprising a compound or salt selected from the group consisting of and a pharmaceutically acceptable excipient. [Examples]

[0276] Although the present invention is described in general terms, these examples, which can be more readily understood by referring to the following embodiments, are included solely for illustrative purposes of specific aspects and embodiments of the invention and are not intended to limit the invention.

[0277] The following synthesis schemes are provided for illustrative purposes only, not limitation. The following examples illustrate various methods for preparing the compounds described herein. Those skilled in the art will understand that these compounds can be prepared by similar methods or by combining them with other methods known to those skilled in the art. Those skilled in the art will also understand that they can be prepared in a manner similar to those described below, using appropriate starting materials and modifying the synthesis route as necessary. Generally, starting materials and reagents can be obtained from commercial suppliers, synthesized according to sources known to those skilled in the art, or prepared as described herein.

[0278] Examples 1-25 illustrate exemplary procedures for the preparation of the claimed IL-17A modulator. Example 26 shows the IL-17 A / A bioassay IC 50 Provide inhibitory data.

[0279] Example 1: General Synthesis Procedure 1-6 General Procedure 1

[0280] [ka]

[0281] To a tetrahydrofuran solution of aminopyridazine 1 (1.00 equivalent) and bromoketone 2 (1.00-1.20 equivalents), N,N-diisopropylethylamine (5.00-10.0 equivalents) and trimethyl borate (5.00-10.0 equivalents) were added. The reaction mixture was stirred at 70°C for 1-3 hours. The reaction mixture was then diluted with water and extracted with ethyl acetate. The combined organic layers were washed with water, then brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a residue, which was then purified by prep-TLC, column chromatography, prep-HPLC, and / or prep-SFC to obtain imidazo[1,2-b]pyridazine 3.

[0282] General Procedure 2

[0283] [ka]

[0284] To a dichloromethane solution of Cbz-protected primary amine 4 (1.00 equivalent), iodotrimethylsilane (1.50-8.55 equivalents) was added at 0°C. The mixture was stirred at 0°C for 2 hours. The reaction mixture was diluted with 1.0 M aqueous hydrochloric acid and washed with ethyl acetate. The aqueous phase was adjusted to pH 8-9 with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain free primary amine 5.

[0285] General Procedure 3

[0286] [ka]

[0287] To a solution of Cbz-protected primary amine 4 (1.00 equivalent) (optionally containing the additive NH3·H2O) in tetrahydrofuran, dichloromethane, and / or methanol, Pd / C (10.0% purity) was added under an N2 atmosphere. The suspension was degassed and purged three times with H2. The mixture was stirred at 25°C for 1 to 20 hours under H2 (15 psi). The reaction mixture was filtered and then concentrated under reduced pressure to obtain free primary amine 5.

[0288] General Procedure 4

[0289] [ka]

[0290] A pyridine solution of primary amine 5 (1.00 equivalent), carboxylic acid 6 (1.20-3.00 equivalents), and EDCI (2.00-3.00 equivalents) was stirred at room temperature for 1-18 hours. The reaction mixture was then diluted with water and extracted with ethyl acetate. The combined organic layer was optionally washed with water and then brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by prep-TLC, column chromatography, prep-HPLC, and / or prep-SFC to obtain amide 7.

[0291] General Procedure 5

[0292] [ka]

[0293] A solution of potassium (bromomethyl) trifluoroborate (1.00 equivalent) in THF (100 mL) was mixed with amine 8 (8.15 equivalents). The reaction mixture was stirred at 80°C for 0.5 hours. The reaction mixture was concentrated under reduced pressure to obtain a residue, to which potassium carbonate (1.04 equivalents) was added. The reaction mixture was stirred further at 25°C for 0.5 hours. The reaction mixture was filtered through ethyl acetate, and the filtrate was concentrated under reduced pressure to obtain a residue. This residue was then ground with acetone and petroleum ether (1 / 10) at 25°C for 5 minutes to obtain potassium trifluoro(aminomethyl)borate 9.

[0294] General Procedure 6

[0295] [ka]

[0296] To a solution of aldehyde 10 (1.00 equivalent) and amine 11 (10.0 equivalent) in methanol, NaBH3CN (3.00 equivalent) and AcOH (1.00 equivalent) or NaOAc (6.00 equivalent) were added. The reaction mixture was stirred at 25°C for 1 hour. The reaction mixture was filtered over MeOH, and the filtrate was concentrated under reduced pressure to obtain a residue. This residue was purified by prep-TLC, column chromatography, prep-HPLC, and / or prep-SFC to obtain amine 12.

[0297] Example 2. General scheme - Synthesis of intermediate A

[0298] [ka]

[0299] As described in Example 2,

[0300] [ka] In (A-COOH), A is an optionally substituted 5- to 6-membered heteroaryl defined by formula (A) or formula (I). In some embodiments,

[0301] [ka] (A-COOH) is,

[0302] [ka] It is represented as follows:

[0303] [ka] A is represented by formula (A) or formula (I). In some embodiments,

[0304] [ka] A is -(CR'R'') m (3- to 10-membered complex ring), -(CR'R'') m (C 3-10 carbocycle), -O-(CR'R'') m (3- to 10-membered heterogeneous rings), and -O-(CR'R'') m (C 3-10 Selected from carbon rings, 3-10 membered heterocycles and C 3-10 The carbocyclic rings are as follows: 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 ,-S(O)R 11 -S(O)2R 11 -NO2, -CN, 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN, halogen, -OR respectively 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, =N(R 11 ), C is optionally substituted with one or more substituents independently selected from -CN.3-10 C is optionally substituted with one or more substituents independently selected from carbocyclic and 3- to 10-membered heterocycles. 1-10 alkyl, and C 3-10 A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 ,-S(O)R 11 -S(O)2R 11 -NO2, =O, =S, =N(R 11 ), -CN and 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, =N(R 11 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-6 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 It is optionally substituted with one or more substituents independently selected from carbon rings and 3- to 10-membered heterocycles. Each R' is halogen, -OR 18 , -N(R 18 )2, -C(O)R 18 ,-C(O)N(R 18 )2, -NO2, -CN and halogens, -OR 18 , -N(R 18 )2, -C(O)R 18 ,-C(O)N(R 18 )C is optionally replaced with one or more from -NO2 and -CN. 1-6 Selected from alkyl groups, Each R'' is halogen, -OR 19 , -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )2, -NO2, -CN and halogens, -OR 19 , -N(R 19 )2, -C(O)R 19 ,-C(O)N(R 19 )C is optionally replaced with one or more from -NO2 and -CN. 1-6 Selected from alkyl groups, R 11 , R 18 , R 19 However, each time it appears, the following: hydrogen, Halogen, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -NH 2、 -NO2, =O, -CN, C 3-10 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. 1-6 Alkyl, each C 3-10 Carbon rings and 3- to 10-membered heterocycles are halogens, -OH, and -OC. 1-6 Alkyl, -OC 1-6 C is optionally substituted with one or more substituents independently selected from haloalkyl, -NH2, -NO2, =O, and -CN. 1-6 alkyl, and Halogen, -OH, -OC 1-6 Alkyl, -OC 1-6 C is optionally substituted with one or more substituents independently selected from haloalkyl, -NH2, -NO2, =O, and -CN. 3-10 Independently selected from carbon rings and 3-10 membered heterocycles, m is selected from 0 and 1.

[0305] As described in Example 2, B is replaced by C of any choice as defined in formula (A) or formula (I). 3-10 It is a carbon ring. In some embodiments, B is

[0306] [ka] It is represented by. In some embodiments, B is represented by B of formula (A) or formula (I). In some embodiments, B is -C(H)(R 5 )2 and C 3-10 Selected from the carbon ring, each C 3-10 The carbocyclic ring is as follows: Halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -N(R 12 )S(O)2R 12 , -C(O)OR 12 -OC(O)R 12 ,-S(O)R 12 -S(O)2R 12 -NO2, =O, =S, =N(R 12 ), -CN, C 1-10 Alkyl and C 3-10 A carbon ring, in which any of them is a halogen, -OR 12 , -SR 12 , -N(R 12 )2, -C(O)R 12 ,-C(O)N(R 12 )2, -N(R 12 )C(O)R 12 , -C(O)OR 12 -OC(O)R 12 ,-S(O)R 12 -S(O)2R 12 -NO2, =O, =S, =N(R 12 ), -CN, C 3-10 It is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle, C 3-10 Carbon rings and 3- to 10-membered heterocycles are halogens, -OR rings, and so on. 12 , -N(R 12 )2, C(O)R 12 ,-C(O)N(R 12)2, -N(R 12 )C(O)R 12 、 -C(O)OR 12 -OC(O)R 12 -NO2, =O, =N(R 12 ), and are optionally substituted with one or more substituents selected from -CN, Each R 5 Each instance of this is (i), (ii), and (iii): (i) 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 -OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, -CN, (ii) 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 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 -OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), C is optionally substituted with one or more substituents independently selected from -CN. 1-10 alkyl, and (iii) C 3-10 A carbon ring, Halogen, -OR 13 , -SR 13 , -N(R 13 )2, -C(O)R 13 ,-C(O)N(R13 )2, -N(R 13 )C(O)R 13 , -N(R 13 )S(O)2R 13 , -C(O)OR 13 -OC(O)R 13 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), -CN, and 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 ,-S(O)R 13 -S(O)2R 13 -NO2, =O, =S, =N(R 13 ), and C, which is optionally substituted with one or more substituents independently selected from -CN. 1-10 C is optionally substituted with one or more substituents independently selected from the alkyl group. 3-10 Selected independently from the carbon ring, Each R 12 and R 13 Each time it appears, the following occurs: hydrogen, Halogen, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -NH 2、 -NO2, =O, -CN, C 3-10 C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. 1-6 Alkyl, each C 3-10 Carbon rings and 3- to 10-membered heterocycles are halogens, -OH, and -OC. 1-6 Alkyl, -OC 1-6 C is optionally substituted with one or more substituents independently selected from haloalkyl, -NH2, -NO2, =O, and -CN. 1-6 alkyl, and Halogen, -OH, -OC 1-6 Alkyl, -OC 1-6 C is optionally substituted with one or more substituents independently selected from haloalkyl, -NH2, -NO2, =O, and -CN. 3-10 They are independently selected from carbon rings and 3- to 10-membered heterocycles.

[0307] Example 3: Synthesis of Intermediates 1 and 2

[0308] [ka]

[0309] [ka]

[0310] To a solution of methyl 4,6-dichloropyridazine-3-carboxylate (60.0 g, 290 mmol, 1.00 equivalent) in dioxane (1000 mL), diphenylmethaneimine (52.5 g, 290 mmol, 48.6 mL, 1.00 equivalent), Cs2CO3 (189 g, 580 mmol, 2.00 equivalent), Pd2(dba)3 (13.3 g, 14.5 mmol, 0.0500 equivalent), and xanthophos (16.8 g, 29.0 mmol, 0.100 equivalent) were added at room temperature. The reaction mixture was stirred at 90°C for 16 hours. The reaction mixture was diluted with DCM (1000 mL), then filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by column chromatography (SiO2, PE:SiO=5:1) to obtain methyl 4-chloro-6-((diphenylmethylene)amino)pyridazine-3-carboxylate (53.4 g, 152 mmol, 52.4% yield) as a yellow oil. LCMS[M+H] + = 352.1 m / z.

[0311] [ka]

[0312] To a solution of methyl 4-chloro-6-((diphenylmethylene)amino)pyridazine-3-carboxylate (53.4 g, 152 mmol, 1.00 equivalent) in HCl / dioxane (4 M, 534 mL, 14.1 equivalents), H2O (125 mL) was added at 0°C. The reaction mixture was stirred at 25°C for 12 hours. The reaction mixture was treated with saturated aqueous solution NaHCO3 until the pH was approximately 8, then diluted with Depositphotos (200 mL) and filtered. The filtrate was extracted with Depositphotos (500 mL x 3). The filtered cake was stirred with 150 mL of Depositphotos:MeOH (10:1) as a slurry and filtered. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by column chromatography (SiO2, PE:SiO2 1:1) to obtain methyl 6-amino-4-chloropyridazine-3-carboxylate (13.3 g, 70.9 mmol, 46.7% yield) as a white solid. LCMS[M+H] + = 188.0 m / z.

[0313] [ka]

[0314] To a solution of methyl 6-amino-4-chloropyridazine-3-carboxylate (1.20 g, 6.40 mmol, 1.00 equivalent) in THF (10.0 mL), benzyl(S)-(3-bromo-1-(4,4-difluorocyclohexyl)-2-oxopropyl)carbamate (2.07 g, 5.12 mmol, 0.800 equivalent), B(OMe)3 (3.32 g, 32.0 mmol, 3.61 mL, 5.00 equivalent), and DIEA (4.13 g, 32.0 mmol, 5.57 mL, 5.00 equivalent) were added at room temperature. The reaction mixture was stirred at 70°C for 2 hours. The reaction mixture was diluted with Depositphotos (50.0 mL), filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by column chromatography (SiO2, PE:SiO, 3:1) to obtain methyl(S)-2-((((benzyloxy)carbonyl)amino)(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazine-6-carboxylate (1.40 g, 2.84 mmol, 44.4% yield) as a yellow oil. LCMS[M+H] + = 493.2 m / z.

[0315] [ka]

[0316] To a solution of methyl(S)-2-((((benzyloxy)carbonyl)amino)(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazine-6-carboxylate (1.40 g, 2.84 mmol, 1.00 equivalent) in MeOH (20.0 mL), CaCl2 (946 mg, 8.52 mmol, 3.00 equivalent) and NaBH4 (537 mg, 14.2 mmol, 5.00 equivalent) were added at 0°C. The mixture was stirred at room temperature for 50 minutes. The reaction mixture was quenched with saturated aqueous solution NH4Cl (30.0 mL), and then concentrated under reduced pressure to remove MeOH. The aqueous layer was extracted with 90.0 mL (30.0 mL x 3) of ELISA. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to obtain crude benzyl(S)-((7-chloro-6-(hydroxymethyl)imidazo[1,2-b]p-pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl]carbamate (1.18 g, 2.54 mmol, 89.4% yield) as a yellow foam, which was used directly in the next step. LCMS[M+H] + = 465.2 m / z.

[0317] [ka]

[0318] To a solution of benzyl(S)-((7-chloro-6-(hydroxymethyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl]carbamate (1.18 g, 2.54 mmol, 1.00 equivalent) in DCM (10.0 mL), SOCl2 (906 mg, 7.61 mmol, 553 μL, 3.00 equivalent) was added at room temperature. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain crude benzyl(S)-((7-chloro-6-(hydroxymethyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl]carbamate (1.13 g, 2.34 mmol, 92.1% yield) as a yellow foam, which was used directly in the next step. LCMS[M+H] + = 483.1 m / z.

[0319] [ka]

[0320] To a solution of 1-(tert-butyl)3-methyl(5R)-2-oxo-5-(trifluoromethyl)piperidine-1,3-dicarboxylate (626 mg, 1.92 mmol, 1.00 equivalent) in THF (20.0 mL), Cs2CO3 (2.51 g, 7.70 mmol, 4.00 equivalent) was added at room temperature. The reaction mixture was stirred at room temperature for 1 hour. Benzyl(S)-((7-chloro-6-(hydroxymethyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl]carbamate (930 mg, 1.92 mmol, 1.00 equivalent) was added to the reaction mixture. The reaction mixture was stirred at 70°C for 11 hours. The reaction mixture was diluted with ELISA (100 mL), filtered, and concentrated under reduced pressure to obtain a residue. The residue was purified by column chromatography to obtain (SiO2 PE:SiO, 1:1), 1-(tert-butyl)3-methyl(5R)-3-((2-((S)-(((benzyloxy)carbonyl)amino)(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-1,3-dicarboxylate (507 mg, 657 μmol, 34.1% yield) was obtained as a colorless gum. LCMS[M+H] + = 772.4 m / z.

[0321] [ka]

[0322] 1-(tert-butyl)3-methyl(5R)-3-((2-((S)-(((benzyloxy)carbonyl)amino)(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-1,3-dicarboxylate (500 mg, 648 μmol, 1.00 equivalent) was dissolved in HCl (12 M, 5.00 mL, 92.7 equivalents) and AcOH (524 mg, 8.73 mmol, 0.500 mL, 13.5 equivalents) at room temperature. The reaction mixture was stirred at 60°C for 1 hour. The reaction mixture was treated with saturated aqueous solution NaHCO3 until the pH was approximately 8, and then extracted with ELISA (50.0 mL × 3). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to obtain crude methyl(5R)-3-((2-((S)-amino(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazin-6-yl)methyl]-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (200 mg, 372 μmol, 57.4% yield) as a yellow gum, which was used directly in the next step: LCMS[M+H] + = 538.2 m / z.

[0323] [ka]

[0324] Methyl(5R)-3-((2-((S)-amino(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (200 mg, 372 μmol, 1.00 equivalent) was dissolved in pyridine (2.00 mL), to which 1-ethyl-1H-pyrazole-5-carboxylic acid (52.1 mg, 372 μmol, 1.00 equivalent) and EDCI (143 mg, 744 μmol, 2.00 equivalent) were added at room temperature. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was treated with 1 M HCl until the pH was approximately 7, and then extracted with ELISA (10.0 mL × 3). The combined organic layers were dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by prep-TLC (SiO2, PE:SiO, 1:1) to obtain methyl(5R)-3-((7-chloro-2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazole-5-carboxamide)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (150 mg, 227 μmol, 61.1% yield) as a white foam. LCMS[M+H] + = 660.1 m / z.

[0325] [ka]

[0326] To a solution of methyl(5R)-3-((7-chloro-2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazole-5-carboxamide)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)piperidine-3-carboxylate (150 mg, 227 μmol, 1.00 equivalent) in THF (2.00 mL) and H2O (2.00 mL), LiOH·H2O (19.1 mg, 454 μmol, 2.00 equivalent) was added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was treated with 1 M HCl until the pH was approximately 4, and then extracted with ELISA (5.00 mL × 3). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to obtain crude (5R)-3-((7-chloro-2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazole-5-carboxamide)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylic acid (130 mg, 201 μmol, 88.6% yield) as a white solid, which was used directly in the next step. LCMS[M+H] + = 646.1 m / z.

[0327] [ka]

[0328] To a solution of (5R)-3-((7-chloro-2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazole-5-carboxamide)methyl)imidazo[1,2-b]pyridazin-6-yl)methyl)-2-oxo-5-(trifluoromethyl)pyrrolidine-3-carboxylic acid (130 mg, 201 μmol, 1.00 equivalent) in DMSO (1.00 mL), NaCl (11.8 mg, 201 μmol, 1.00 equivalent) was added at 20°C. The reaction mixture was stirred at 110°C for 30 minutes. The reaction mixture was diluted with H2O (10.0 mL) and extracted with ELISA (10.0 mL x 3). The combined organic layers were washed with brine (10.0 mL x 2) and H2O (10.0 mL x 2), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by prep-HPLC (FA conditions, column: Phenomenex luna C18 150 × 25 mm × 10 μm, mobile phase: [water (formic acid)-ACN], B%: 42~72%) to obtain N-((1S)-(7-chloro-6-(((5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (68.0 mg, 113 μmol, 56.1% yield) as a white solid (dr64-36). The residue was purified by prep-SFC (column: REGIS (R,R)WHELK-O1 (250mm x 25mm, 10 μm), mobile phase: [0.1% NH3H2O ​​EtOH], B%: 50%), and intermediate 1 (LCMS[M+H]) was prepared. + =602.1m / z) as the first eluting single stereoisomer, and intermediate 2 (LCMS[M+H] + (=602.2 m / z) was obtained as the second eluting single stereoisomer.

[0329] Example 4: Preparation of intermediates 3 and 4 Preparation of Intermediate 3

[0330] [ka]

[0331] N-((1S)-(7-chloro-6-(((5R)-5-methyl-2-oxopiperidinin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)((4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide is prepared according to General Procedure 1 using (5R)-3-((6-amino-4-dichloropyridazinin-3-yl)methyl)-5-methylpiperidine-2-one and benzyl(S)-(3-bromo-1-(4,4-difluorocyclohexyl)-2-oxopropyl)carbamate, according to General Procedure It was synthesized according to procedure 2 using benzyl((1S)-(7-chloro-6-(((5R)-5-methyl-2-oxopiperidinin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)((4,4-difluorocyclohexyl)methyl)carbamate, and according to general procedure 4 using ((5R)-3-((2-((S)-amino(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazin-6-yl)methyl)-5-methylpiperidine-2-one and 1-ethyl-1H-pyrazole-5-carboxylic acid.

[0332] Preparation of intermediate 4

[0333] [ka]

[0334] N-((1S)-(7-chloro-6-(((5S)-5-methyl-2-oxopiperidinin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)((4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide is prepared according to General Procedure 1 using (5S)-3-((6-amino-4-dichloropyridazinin-3-yl)methyl)-5-methylpiperidine-2-one and benzyl(S)-(3-bromo-1-(4,4-difluorocyclohexyl)-2-oxopropyl)carbamate, according to General Procedure It was synthesized according to procedure 2 using benzyl((1S)-(7-chloro-6-(((5S)-5-methyl-2-oxopiperidinin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)((4,4-difluorocyclohexyl)methyl)carbamate, and according to general procedure 4 using ((5S)-3-((2-((S)-amino(4,4-difluorocyclohexyl)methyl)-7-chloroimidazo[1,2-b]pyridazin-6-yl)methyl)-5-methylpiperidine-2-one and 1-ethyl-1H-pyrazole-5-carboxylic acid.

[0335] Example 5: Synthesis of Compound 21

[0336] [ka]

[0337] Intermediate 1 (80.0 mg, 133 μmol, 1.00 equivalent), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (558 mg, 2.66 mmol, 20 equivalents), K3PO4 (84.6 mg, 399 μmol, 3.00 equivalents), and Pd(dtbpf)Cl2 (8.66 mg, 13.29 μmol, 0.1 equivalent) were mixed in dioxane (2.00 mL) and H2O (0.5 mL). The mixture was degassed, purged three times with N2, and then stirred at 90°C for 1 hour under an N2 atmosphere. The reaction mixture was diluted with H2O (50.0 mL), extracted with ethyl (50.0 mL x 3), dried over Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. This residue was purified by prep-TLC (SiO2, DCM:MeOH = 10:1) to obtain N-((S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro-2H-pyran-4-yl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (60.0 mg, 92.4 μmol, 69.5% yield) as a yellow solid. LCMS[M+H] + = 650.4 m / z.

[0338] [ka]

[0339] To a solution of N-((S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro-2H-pyran-4-yl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (30.0 mg, 46.2 μmol, 1.00 equivalent) in THF (5.00 mL), Pd / C (20.0 mg, 18.8 μmol, 10% purity) was added with N2. The suspension was degassed under vacuum and purged several times with H2. The reaction mixture was stirred under H2 (15 Psi) at 15°C for 24 hours. The reaction mixture was filtered. The filtrate was diluted with MeOH (50.0 mL) and filtered again. The filtrate was concentrated under reduced pressure to obtain a residue, which was purified by prep-TLC (SiO2, DCM:MeOH = 10:1) to obtain N-((S)-(4,4-difluorocyclohexyl)(6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (7.68 mg, 11.04 μmol, 23.91% yield, 93.7% purity) as a white solid. LCMS[M+H] + = 652.5 m / z.

[0340] Example 6: Synthesis of Compound 33

[0341] [ka]

[0342] To a solution of N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (50.0 mg, 83.0 μmol, 1.00 equivalent) and (R)-2-methylmorpholine (84.0 mg, 830 μmol, 10.0 equivalent), Cs2CO3 (81.1 mg, 249 μmol, 3.00 equivalent) and PEPPSI-Pd-iHept (8.08 mg, 8.31 μmol, 0.100 equivalent) were added under N2 conditions. The reaction mixture was stirred under N2 at 90°C for 12 hours. The reaction mixture was diluted with H2O (10.0 mL) and extracted with toluene (10.0 mL x 3). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by prep-HPLC (column: Waters Xbridge 150×25mm×5um, mobile phase: [water (ammonia hydroxide v / v)-ACN], gradient: 34%~64%B) to obtain N-((S)-(4,4-difluorocyclohexyl)(7-((R)-2-methylmorpholine)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (15.2 mg, 22.3 μmol, 26.9% yield, 98.1% purity) as a white solid. LCMS[M+H] + = 667.4 m / z.

[0343] Example 7: Preparation of Compound 111

[0344] [ka]

[0345] Water (0.40 mL) was added to a solution of N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (100 mg, 166 μmol, 1.00 equivalent), potassium ((dimethylamino)methyl)trifluoroborate (prepared according to general procedure 5, 137 mg, 831 μmol, 5.00 equivalent), Pd(t-Bu3P)2 (25.5 mg, 49.8 μmol, 0.30 equivalent), and DIEA (64.4 mg, 498 μmol, 86.8 μL, 3.00 equivalent) in dioxane (2.00 mL). The reaction mixture was heated in a sealed tube under microwave irradiation at 90°C for 2 hours. The reaction mixture was filtered with MeOH (10.0 mL). The filtrate was concentrated under reduced pressure to obtain the residue, which was further purified by prep-HPLC (column: Phenomenex luna C18 150 mm × 25 mm, 10 μm, mobile phase: [water (FA)-ACN], gradient: 18%~38% B over 10 minutes), and then Prep-SFC (column: DAIEL CHIRALPAK) Further purification by AS (250 mm × 30 mm, 10 μm), mobile phase: [CO2-EtOH (0.1% NH3H2O)], B%: 25%, fixed composition elution mode) yielded N-((S)-(4,4-difluorocyclohexyl)(7-((dimethylamino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-methyl-1H-pyrazole-5-carboxamide (42.36 mg, 67.8 μmol, 40.8% yield, 99.9% purity) as a white solid. LCMS[M+H]+=625.3 m / z.

[0346] Example 8: Preparation of Compound 108

[0347] [ka]

[0348] N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (80.0 mg, 133 μmol, 1.00 equivalent), potassium ((mo Water (0.40 mL) was added to a solution of (2.00 mL) of (20.4 mg, 39.9 μmol, 0.300 equivalents) Pd(t-Bu3P)2 and (51.5 mg, 399 μmol, 69.4 μL, 3.00 equivalents) methyl trifluoroborate (prepared according to general procedure 5), Pd(t-Bu3P)2, and DIEA. The reaction mixture was heated in a sealed tube under microwave irradiation at 90°C for 2 hours. The reaction mixture was filtered with MeOH (10.0 mL). The filtrate was concentrated under reduced pressure to obtain a residue, which was purified by prep-HPLC (column: Phenomenex luna C18 150mm × 25mm, 10um, mobile phase: [water (FA)-ACN], gradient: 20%~40% B over 10 minutes) to obtain N-((S)-(4,4-difluorocyclohexyl)(7-morpholinomethyl-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-methyl-1H-pyrazole-5-carboxamide (42.58 mg, 63.2 μmol, 47.5% yield, 98.9% purity) as a white solid. LCMS[M+H]+=667.3 m / z.

[0349] Example 9: Preparation of Compound 107

[0350] [ka]

[0351] N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (60.0 mg, 99.6 μmol, 1.00 equivalent), potassium (piperidine) Water (0.40 mL) was added to a solution of dioxane (2.00 mL) containing din-1-ylmethyl trifluoroborate (prepared according to general procedure 5, 102 mg, 498 μmol, 5.00 equivalents), Pd(t-Bu3P)2 (15.2 mg, 29.90 μmol, 0.300 equivalents), and DIEA (38.6 mg, 299 μmol, 52.0 μL, 3.00 equivalents). The reaction mixture was heated in a sealed tube under microwave irradiation at 90°C for 2 hours. The reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a residue, which was purified by Prep-HPLC (column: Phenomenex luna C18 150mm × 25mm, 10um, mobile phase: [water (FA)-ACN], gradient: 15%~45% B over 10 minutes) to obtain N-((S)-(4,4-difluorocyclohexyl)(6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)-7-(piperidine-1-ylmethyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (25.8 mg, 38.77 μmol, 38.90% yield, 99.89% purity) as a yellow solid. LCMS[M+H]+=665.4m / z.

[0352] Example 10: Preparation of Compound 106

[0353] [ka]

[0354] N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (100 mg, 166 μmol, 1.00 equivalent), potassium (pyrrolidine) 159 mg, 831 μmol, 5.00 equivalents of 1-1-ylmethyl)trifluoroborate (prepared according to general procedure 5), Pd(t-Bu3P)2 (25.5 mg, 49.8 μmol, 0.300 equivalents), and DIEA (64.4 mg, 498 μmol, 86.8 μL, 3.00 equivalents) were dissolved in dioxane (2.00 mL), to which water (0.40 mL) was added. The reaction mixture was heated in a sealed tube under microwave irradiation at 90°C for 2 hours. The reaction mixture was filtered with MeOH (10.0 mL). The filtrate was concentrated under reduced pressure to obtain the residue, which was then subjected to prep-HPLC (column: Phenomenex luna C18). Further purification was performed by 150mm×25mm, 10um, mobile phase: [water(FA)-ACN], gradient: 23%~41% B over 9 minutes, and then further purification was performed by Prep-SFC (column: REGIS(S,S)WHELK-O1 (250mm×25mm, 10um), mobile phase: [CO2-ACN / MeOH (0.1%NH3H2O)], B%: 40%, fixed composition elution mode), and N-((S)-(4, 4-Difluorocyclohexyl)(6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)-7-(pyrrolidine-1-ylmethyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (46.21 mg, 70.7 μmol, 42.6% yield, 99.6% purity) was obtained as a white solid. LCMS[M+H]+=651.2 m / z.

[0355] Example 11: Preparation of Compound 115

[0356] [ka]

[0357] N-((S)-(4,4-difluorocyclohexyl)(6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)-7-(((2,2,2-trifluoroethyl)amino)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide according to general procedure 6, N-((S)-(4,4-difluorocyclohexyl)(7-formyl- Synthesized using 6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (100 mg, 168 μmol, 1.00 equivalent) and 2,2,2-trifluoroethane-1-amine (166 mg, 1.68 mmol, 132 μL, 10.0 equivalent), and Prep-HPLC (column: Waters The solution was purified by Xbridge 150mm×25mm, 5um, mobile phase: [water (ammonia hydroxide v / v)-ACN], gradient: 39%~69% (B) over 9 minutes to obtain N-((S)-(4,4-difluorocyclohexyl)(6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)-7-(((2,2,2-trifluoroethane)amino)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (28.39 mg, 40.7 μmol, 24.3% yield, 97.4% purity) as a yellow solid. LCMS[M+H]+=679.3 m / z.

[0358] Example 12: Preparation of Compound 109

[0359] [ka]

[0360] N-((S)-(7-((3,3-difluoroazetidine-1-yl)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide according to general procedure 6, N-((1S)-(4,4-difluorocyclohexyl)(7 Synthesized using -formyl-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (70.0 mg, 118 μmol, 1.00 equivalent) and 3,3-difluoroazetidine (152 mg, 1.18 mmol, 10.0 equivalent), and prep-HPLC (column: Waters The sample was purified by Xbridge 150×25mm, 5μm, mobile phase: [water (ammonia hydroxide v / v)-ACN], gradient: 38%~68% over 9 minutes to obtain N-((S)-(7-((3,3-difluoroazetidine-1-yl)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (39.3 mg, 57.7 μmol, 49.1% yield, 98.8% purity) as a yellow solid. LCMS[M+H]+=673.3 m / z.

[0361] Example 13: Preparation of Compound 105

[0362] [ka]

[0363] N-((S)-(4,4-difluorocyclohexyl)(7-((3,3-difluoroazetidine-1-yl)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide according to general procedure 6. It was synthesized using formyl-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (70.0 mg, 118 μmol, 1.00 equivalent) and 3,3-difluoropyrrolidine (126 mg, 1.18 mmol, 10.0 equivalent), and Prep-HPLC (column: Waters The mixture was purified by Xbridge 150mm×25mm, 5um, mobile phase: [water (ammonia hydroxide v / v)-ACN], gradient: 32%~62% (B) over 9 minutes to obtain N-((S)-(4,4-difluorocyclohexyl)(7-(3,3-difluoropyrrolidine-1-yl)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (44.8 mg, 65.2 μmol, 55.5% yield, 99.9% purity) as a yellow solid. LCMS[M+H]+=687.4 m / z.

[0364] Example 14: Preparation of Compound 112

[0365] [ka]

[0366] N-((S)-(4,4-difluorocyclohexyl)(7-((methylamino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide according to general procedure 6, N-((S)-(4,4-difluorocyclohexyl)(7-formyl- Synthesized using 6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (70.0 mg, 118 μmol, 1.00 equivalent) and methanamine (79.4 mg, 1.18 mmol, 10.0 equivalent, HCl salt), and analyzed by Prep-HPLC (column: Waters Further purification was performed using an Xbridge 150mm×25mm, 5um, mobile phase: [water (ammonia hydroxide v / v)-ACN], gradient: 42%~72% over 9 minutes to obtain N-((S)-(4,4-difluorocyclohexyl)(7-((methylamino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (37.17 mg, 56.4 μmol, 48.0% yield, 92.6% purity) as a white solid. LCMS[M+H]+=611.3 m / z.

[0367] Example 15: Preparation of Compound 116

[0368] [ka]

[0369] N-((S)-(4,4-difluorocyclohexyl)(7-((methyl(2,2,2-trifluoromethyl)amino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-methyl-1H-pyrazole-5-carboxamide according to general procedure 6, N-((S)-(4,4-difluorocyclohexyl)(7-formyl Synthesized using -6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-methyl-1H-pyrazole-5-carboxamide (70.0 mg, 118 μmol, 1.00 equivalent) and 2,2,2-trifluoro-N-methylethane-1-amine (176 mg, 1.18 mmol, 10.0 equivalent), and Prep-HPLC (column: Waters Further purification was performed using an Xbridge 150mm×25mm, 5um, mobile phase: [water (ammonia hydroxide v / v)-ACN], gradient: 43%~73% over 9 minutes to obtain N-((S)-(4,4-difluorocyclohexyl)(7-((methyl(2,2,2-trifluoromethyl)amino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (42.15 mg, 59.7 μmol, 50.8% yield, 98.1% purity) as a white solid. LCMS[M+H]+=693.3 m / z.

[0370] Example 16: Preparation of Compound 113

[0371] [ka]

[0372] N-((S)-(7-((3,3-difluoroazetidine-1-yl)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide according to general procedure 6, N-((S)-(4,4-difluorocyclohexyl)(7-form Synthesized using ru-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (80.0 mg, 134 μmol, 1.00 equivalent) and N-methylcyclopropylamine (145 mg, 1.34 mmol, 10.0 equivalent, HCl salt), and Prep-HPLC (column: Waters The mixture was purified by Xbridge 150mm×25mm, 5um, mobile phase: [water (ammonia hydroxide v / v)-ACN], gradient: 9 min over 42%~72% (B) to obtain N-((S)-(7-((cyclopropyl(methyl)amino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (45.53 mg, 68.6 μmol, 51.1% yield, 98.0% purity) as a yellow solid. LCMS[M+H]+=651.3 m / z.

[0373] Example 17: Preparation of Compound 114

[0374] [ka]

[0375] N-((S)-(4,4-difluorocyclohexyl)(7-((methyl(oxetan-3-yl)amino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-methyl-1H-pyrazole-5-carboxamide according to general procedure 6, N-((S)-(4,4-difluorocyclohexyl)(7-H Synthesized using lumyl-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-methyl-1H-pyrazole-5-carboxamide (80.0 mg, 134 μmol, 1.00 equivalent) and N-methyloxetane-3-amine (117 mg, 1.34 mmol, 10.0 equivalent), and prepared using Prep-HPLC (column: Waters The solution was purified by Xbridge 150mm×25mm, 5um, mobile phase: [water (ammonia hydroxide v / v)-ACN], gradient: 33%~63% (B) over 9 minutes to obtain N-((S)-(4,4-difluorocyclohexyl)(7-((methyl(oxetan-3-yl)amino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (41.97 mg, 62.0 μmol, 46.1% yield, 98.4% purity) as a white solid. LCMS[M+H]+=667.3 m / z.

[0376] Example 18: Preparation of Compound 117

[0377] [ka]

[0378] N-((S)-(7-((cyclopropylamine)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (100mg) according to general procedure 6. Synthesized using (168 μmol, 1.00 equivalent) and cyclopropylamine (95.9 mg, 1.68 mmol, 116 μL, 10.0 equivalent), and purified by Prep-TLC (SiO2, petroleum ether:ethyl acetate = 0:1, Rf = 0.30) to obtain N-((S)-(7-cyclopropylamino)methyl)(-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (28.0 mg, 44.0 μmol, 26.2% yield) as a white solid. LCMS[M+H]+ = 637.3 m / z.

[0379] [ka]

[0380] DIEA (34.1 mg, 264 μmol, 46.0 μL, 6.00 equivalents) was added to a solution of N-((S)-(7-cyclopropylamino)methyl)(-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (28.0 mg, 44.0 μmol, 1.00 equivalent) and 2,2,2-trifluoroethyltrifluoromethanesulfonate (102 mg, 440 μmol, 10.0 equivalent) in DMF (0.500 mL). The reaction mixture was stirred at 100 °C for 12 hours. The reaction mixture was cooled to room temperature, filtered with MeOH (10.0 mL), and the filtrate was concentrated under reduced pressure to obtain the residue. This residue was purified by Prep-HPLC (column: Waters Xbridge 150 mm × 25 mm, 10 μm, mobile phase: [water (ammonia hydroxide v / v)-ACN], gradient: 47%~77% B over 9 minutes) to obtain N-((S)-(7-((cyclopropyl(2,2,2-trifluoromethyl)amino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (10.74 mg, 14.2 μmol, 32.4% yield, 95.3% purity) as a white solid. LCMS[M+H]+=719.3m / z.

[0381] Example 19: Preparation of Compound 110

[0382] [ka]

[0383] To a solution of N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (0.28 g, 465 μmol, 1.00 equivalent) in dioxane (1.00 mL), tributyl(1-ethoxyvinyl) stannan (335 mg, 930 μmol, 314 μL, 2.00 equivalent) was added, followed by the addition of Pd(PPh3)2Cl2 (32.6 mg, 46.5 μmol, 0.100 equivalent). The reaction mixture was heated under microwave irradiation at 110°C for 6 hours. The reaction mixture was quenched by adding a saturated aqueous solution of KF (10.0 mL) at 20°C. The reaction mixture was diluted with 2M HCl (20.0 mL) and stirred further at 20°C for 2 hours. The reaction mixture was then adjusted to pH=7 with a saturated aqueous solution of NaHCO3, filtered, and extracted with ethyl acetate (3 × 30.0 mL). The combined organic layers were washed with a saturated aqueous solution of NaHCO3 (3 × 30.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. This residue was purified by Prep-TLC (SiO2, dichloromethane:methanol = 10:1) to obtain N-((S)-(7-acetyl-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (170 mg, 278 μmol, 59.9% yield) as a yellow solid.

[0384] [ka]

[0385] To a solution of N-((S)-(7-acetyl-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (160 mg, 262 μmol, 1.00 equivalent) in MeOH (2.00 mL), sodium borohydride (19.8 mg, 524 μmol, 2.00 equivalent) was added at N2, 0°C. The reaction mixture was stirred at 25°C for 1 hour. The reaction mixture was quenched at 0°C by adding a saturated aqueous solution of NH4Cl (10 mL), and then diluted with water (30.0 mL). Extraction was performed with ethyl acetate (3 × 30.0 mL), the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain N-((1S)-(4,4-difluorocyclohexyl)(7-(1-hydroxyethyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (160 mg, 261 μmol, 99.6% yield) as a white solid. LCMS[M+H]+=612.4 m / z.

[0386] [ka]

[0387] To a solution of N-((1S)-(4,4-difluorocyclohexyl)(7-(1-hydroxyethyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (80.0 mg, 130 μmol, 1.00 equivalent) in DCM (1.00 mL), thionyl chloride (46.6 mg, 392 μmol, 28.5 μL, 3.00 equivalent) was added at 0°C. The reaction mixture was stirred at 25°C for 0.5 hours. The reaction mixture was concentrated under reduced pressure to obtain a residue, and Prep-TLC (SiO2, dichloromethane:methanol = 10:1), N-((1S)-(7-(1-chloroethyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl))methyl)-1-ethyl-1H-pyrazole-5-carboxamide (70.0 mg, 111 μmol, 84.9% yield) was obtained as a white solid. LCMS[M+H]+=630.2 m / z.

[0388] [ka]

[0389] DIEA (43.0 mg, 333 μmol, 58.0 μL, 3.00 equivalents) was added to a solution of N-((1S)-(7-(1-chloroethyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-methyl)-1-ethyl-1H-pyrazole-5-carboxamide (70.0 mg, 111 μmol, 1.00 equivalent) and 2,2,2-trifluoroethane-1-amine (220 mg, 2.22 mmol, 174 μL, 20.0 equivalents) in DMF (1.00 mL). The reaction mixture was stirred at 70°C for 10 hours. The reaction mixture was diluted with water (30.0 mL) and extracted with ethyl acetate (3 × 30.0 mL). The combined organic layer was washed with brine (2 × 30.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue, which was purified by Prep-TLC (SiO2, petroleum ether:ethyl acetate = 0:1) to obtain N-((1S)-(4,4-difluorocyclohexyl)(6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)-7-(1-((2,2,2-trifluoroethyl)amino)ethyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (45.0 mg, 64.9 μmol, 58.4% yield) as a white solid. LCMS[M+H]+=693.2m / z.

[0390] [ka]

[0391] N-((1S)-(4,4-difluorocyclohexyl)(6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)-7-(1-((2,2,2-trifluoroethyl)amino)ethyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide( NaBH3CN (12.2 mg, 194 μmol, 3.00 equivalent) was added to a solution of 45.0 mg, 64.9 μmol, 1.00 equivalent of (NaBH3CN), 527 mg, 6.50 mmol, 483 μL, 37.0% purity, 100 equivalents of (NaBH3CN), and 3.90 mg, 64.9 μmol, 3.72 μL, 1.00 equivalent of (NaBH3CN), 12.2 mg, 194 μmol, 3.00 equivalent, in MeOH (1.00 mL). The reaction mixture was stirred at 25°C for 1 hour. The reaction mixture was filtered to obtain the residue, which was purified by Prep-HPLC (FA conditions, column: Phenomenex luna C18 150mm × 25mm, 10um, mobile phase: [water (FA)-ACN], gradient: 53%~73%B over 10 minutes) to obtain N-((1S)-(4,4-difluorocyclohexyl)(7-(1-(methyl(2,2,2-trifluoromethyl)amino)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (40.0 mg, 56.6 μmol, yield 87.1%) as a white solid. LCMS[M+H]+=707.3 m / z.

[0392] Compound 110 was isolated as a second eluted single stereoisomer by chiral SFC purification (column: Daicel Chiralpak AD (250 mm × 30 mm, 10 μm), mobile phase: [CO2-EtOH (0.1% NH3H2O)], B%: 20%, fixed composition elution mode) (10.21 mg, 14.3 μmol, 25.4% yield, 99.5% purity), obtained as a white solid. LCMS[M+H] + = 707.3 m / z.

[0393] Example 20: Preparation of Compound 104

[0394] [ka]

[0395] N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (100 mg, 166 μmol, 1.00 equivalent) and S-octahydropyrazino[2,1-c][1,4]oxadi To a 2.00 mL solution of dioxane (472 mg, 3.32 mmol, 20.0 equivalents) containing 1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-2H-imidazole-1-ium-2-oid, 3-chloropyridine, dichloropalladium (1.62 mg, 1.66 μmol, 0.01 equivalents), and Cs2CO3 (162 mg, 498 μmol, 3.00 equivalents) were added. The reaction mixture was stirred under N2 at 100°C for 6 hours. The reaction mixture was diluted with water (15.0 mL), extracted with ethyl acetate (3 × 15.0 mL), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure to obtain the residue, further purified by Prep-HPLC (column: Phenomenex luna C18 150 mm × 25 mm, 10 μm, mobile phase: [water (FA)-ACN], gradient: 25%~45% B over 10 minutes), and then purified by Prep-SFC (column: REGIS Further purification by (S,S)WHELK-O1 (250mm x 25mm, 10um), mobile phase: [CO2-i-PrOH / ACN], B%: 50%, fixed composition elution mode) yielded N-((S)-(4,4-difluorocyclohexyl)(7-((S)-hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-yl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-methyl-1H-pyrazole-5-carboxamide (20.49 mg, 28.7 μmol, 17.2% yield, 99.2% purity) as a white solid. LCMS[M+H] + = 708.3 m / z.

[0396] Example 21: Preparation of Compound 99

[0397] [ka]

[0398] N-((S)-(7-chloro-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (250 mg, 415 μmol, 1.00 equivalent) and tert-butylpiperazine-1-carboxylate (1. To a 3.00 mL solution of 55 g (8.31 mmol, 20.0 equivalents) of dioxane, 1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-2H-imidazole-1-ium-2-oid, 3-chloropyridine, dichloropalladium (4.04 mg, 4.15 μmol, 0.0100 equivalents) and Cs2CO3 (405 mg, 1.25 mmol, 3.00 equivalents) were added. The reaction mixture was stirred under N2 at 100°C for 10 hours. The reaction mixture was diluted with water (15.0 mL), extracted with ethyl acetate (3 × 15.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a residue. This residue was purified by Prep-HPLC (column: Waters Xbridge C18 150 mm × 50 mm, 10 μm, mobile phase: [water (NH4HCO3)-ACN], gradient: 38%~68% B over 10 minutes) to obtain tert-butyl 4-(2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazole-5-carboxamide)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-7-yl)piperidine-1-carboxylate (60 mg, 79.8 μmol, 19.2% yield) as a white solid. LCMS[M+H] + = 752.4 m / z.

[0399] [ka]

[0400] To a solution of tert-butyl 4-(2-((S)-(4,4-difluorocyclohexyl)(1-ethyl-1H-pyrazole-5-carboxamide)methyl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-7-yl)piperazine-1-carboxylate (55.0 mg, 73.1 μmol, 1.00 equivalent) in DCM (0.500 mL), ZnBr2 (82.3 mg, 365 μmol, 18.3 μL, 5.00 equivalent) was added. The reaction mixture was stirred at 25°C for 6 hours. The reaction mixture was diluted with water (10.0 mL), the pH was adjusted to 8 with saturated NaHCO3 aqueous solution, and extracted with DCM (15.0 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain N-((S)-(4,4-difluorocyclohexyl)(6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)-7-(piperazin-1-yl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (45.0 mg, 69.0 μmol, 94.3% yield) as a yellow solid. LCMS[M+H] + = 652.3 m / z.

[0401] [ka]

[0402] N-((1S)-(4,4-difluorocyclohexyl)(6-(((3R,5R)-2-oxo-5-(trifluoromethyl)-7-(piperidine-3-yl)methyl)-3-(piperidine-3-yl)imidazo[1,2-b]pyridazin-2-yl-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (45.0 mg, 69.0 μmol, 1.00 equivalent) and 1-bromo-2-methoxyethane (38.3 mg, 276 μmol, 25.9 μL, 4.00 To a solution of DMF (1.00 mL) (equivalent), DIEA (44.6 mg, 345 μmol, 60.1 μL, 5.00 equivalents) was added. The mixture was stirred at 25°C for 12 hours. The reaction mixture was diluted with water (15.0 mL), extracted with ethyl acetate (3 x 15.0 mL), dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure to obtain the residue, further purified by prep-TLC (SiO2, ethyl acetate:methanol = 9:1), and Prep-HPLC (column:Phenomenex). Further purification was performed on a luna C18 150mm×25mm, 10um, mobile phase: [water(FA)-ACN], gradient: 23%~43% over 10 minutes to obtain N-((1S)-(4,4-difluorocyclohexyl)(7-(4-(2-methoxyethyl)piperazin-1-yl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (6.58 mg, 9.24 μmol, 13.3% yield, 99.7% purity) as a white solid. LCMS[M+H] + = 710.3 m / z.

[0403] Example 22: Preparation of compounds 100 and 101

[0404] [ka]

[0405] N-((1S)-(7-chloro-6-(((5R)-5-methyl-2-oxopiperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (220 mg, 401 μmol, 1.0) in dioxane (3.00 mL) and water (0.60 mL) To a solution of 0 equivalents of (0 equivalents) and 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (169 mg, 803 μmol, 2.00 equivalents), Xphos-Pd-G3 (102 mg, 120 μmol, 0.300 equivalents) and Cs2CO3 (262 mg, 803 μmol, 2.00 equivalents) were added under an N2 atmosphere. The reaction mixture was stirred at 100°C for 2 hours. The reaction mixture was diluted with water (50.0 mL) and extracted with a mixture of dichloromethane and methanol (dichloromethane:methanol = 10:1). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a residue. Prep-TLC (SiO2, dichloromethane:methanol = 10:1), N-((1S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro-2H-pyran-4-yl)-6-(((5R)-5-methyl-2-oxopiperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (130 mg, 218 μmol, 54.4% yield) was obtained as a yellow oil. LCMS[M+H] + = 596.4 m / z.

[0406] [ka]

[0407] To a solution of N-((1S)-(4,4-difluorocyclohexyl)(7-(3.6-dihydro-2H-pyran-4-yl)-6-(((5R)-5-methyl-2-oxopiperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (130 mg, 218 μmol, 1.00 equivalent) in THF (3.00 mL), Pd / C (230 mg, 216 μmol, 10.0% purity, 0.99 equivalent) was added under an N2 atmosphere. The resulting suspension was degassed and purged three times with H2. The reaction mixture was stirred under H2 (15 Psi) at 25°C for 2 hours. The reaction mixture was filtered with THF (10.0 mL), and the filtrate was concentrated under reduced pressure to obtain N-((1S)-(4,4-difluorocyclohexyl)(6-((5R)-5-methyl-2-oxopiperidine-3-yl)methyl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (120 mg, 201 μmol, 92.0% yield) as a white solid. LCMS[M+H] + = 598.3 m / z.

[0408] Compound 100 was isolated as a second eluted single stereoisomer by chiral SFC purification (column: Daicel Chiralpak AD (250 mm × 30 mm, 10 μm), mobile phase: [CO2-i-PrOH (0.1% NH3·H2O)], B%: 25%, fixed composition elution mode) (30.31 mg, 50.4 μmol, 25.1% yield, 99.4% purity), obtained as a white solid. LCMS[M+H] + = 598.2 m / z.

[0409] Compound 101 was isolated as a second eluted single stereoisomer by chiral SFC purification (column: Daicel Chiralpak AD (250 mm × 30 mm, 10 μm), mobile phase: [CO2-i-PrOH (0.1% NH3·H2O)], B%: 25%, fixed composition elution mode) (60.0 mg, 99.5 μmol, 49.5% yield, 99.1% purity), obtained as a white solid. LCMS[M+H] + = 598.2 m / z.

[0410] Example 23: Preparation of compounds 102 and 103

[0411] [ka]

[0412] N-((1S)-(7-chloro-6-(((5S)-5-methyl-2-oxopiperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)(4,4-difluorocyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (166 mg, 302 μmol, 1.00) in dioxane (1.60 mL) and water (0.40 mL). To a solution of (190 mg, 908 μmol, 3.00 equivalents) and 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (190 mg, 908 μmol, 3.00 equivalents), Xphos-Pd-G3 (76.9 mg, 90.8 μmol, 0.300 equivalents) and Cs2CO3 (197 mg, 605 μmol, 2.00 equivalents) were added under an N2 atmosphere. The reaction mixture was stirred at 100°C for 2 hours. The reaction mixture was diluted with water (40.0 mL) and extracted with ethyl acetate (3 x 40.0 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a residue. Prep-TLC (SiO2, dichloromethane:methanol = 10:1), N-((1S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro-2H-pyran-4-yl)-6-(((5S)-5-methyl-2-oxopiperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (120 mg, 201.4 μmol, 66.5% yield) was obtained as a yellow oil. LCMS[M+H] + = 596.4 m / z.

[0413] [ka]

[0414] To a solution of N-((1S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro-2H-pyran-4-yl)-6-(((5S)-5-methyl-2-oxopiperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (120 mg, 201 μmol, 1.00 equivalent) in THF (2.00 mL), Pd / C (214 mg, 201 μmol, 10% purity, 1.00 equivalent) was added under an N2 atmosphere. The resulting suspension was degassed and purged three times with H2. The reaction mixture was stirred under H2 (15 Psi) at 25°C for 3 hours. The reaction mixture was diluted with MeOH, filtered, and the filtrate was concentrated under reduced pressure to obtain N-((1S)-(4,4-difluorocyclohexyl)(6-(((5S)-5-methyl-2-oxopiperidine-3-yl)methyl)-7-(tetrahydro-2H-pyran-4-yl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (100 mg, 167 μmol, 83.0% yield) as a white solid. LCMS[M+H] + = 598.4 m / z.

[0415] Compound 102 was isolated as a second eluted single stereoisomer by chiral SFC purification (column: Daicel Chiralpak AS (250 mm × 30 mm, 10 μm), mobile phase: [CO2-ACN / i-PrOH (0.1% NH3H2O)], B%: 30%, fixed composition elution mode) (56.84 mg, 92.9 μmol, 55.5% yield, 97.7% purity), obtained as a white solid. LCMS[M+H] + = 598.3 m / z.

[0416] Compound 103 was isolated as a second eluted single stereoisomer by chiral SFC purification (column: Daicel Chiralpak AS (250 mm × 30 mm, 10 μm), mobile phase: [CO2-ACN / i-PrOH (0.1% NH3H2O)], B%: 30%, fixed composition elution mode) (34.61 mg, 56.9 μmol, 34.0% yield, 98.4% purity), obtained as a white solid. LCMS[M+H] + = 598.3 m / z.

[0417] Example 24. Preparation of Compound 118

[0418] [ka]

[0419] Intermediate 1 (100.0 mg, 166 μmol, 1.00 equivalent), 2-(3,6-dihydro-2H-thiopyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (751 mg, 3.32 mmol, 20 equivalents), K3PO4 (68.8 mg, 498 μmol, 3.00 equivalents), and RuPhos Pd G3 (13.88 mg, 16.6 μmol, 0.1 equivalent) were mixed in dioxane (2.00 mL) and H2O (0.5 mL), degassed, purged three times with N2, and then stirred under microwave irradiation at 100°C for 2 hours. The reaction mixture was diluted with H2O (50.0 mL), extracted with ethyl (50.0 mL x 3), dried over Na2SO4, filtered, and concentrated under reduced pressure to obtain the residue. This residue was purified by prep-TLC (SiO2, DCM:MeOH = 10:1) to obtain N-((S)-(4,4-difluorocyclohexyl)(7-(3,6-dihydro-2H-thiopyran-4-yl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (90.0 mg, 135.2 μmol, 81.4% yield).

[0420] [ka]

[0421] N-((S-(4,4-difluorocyclohexyl)(7-(1,1-dioxidetetrahydro-2H-thiopyran-4-yl)-6-(((3R5R1-(2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide, N-((S-(4,4-difluorocyclohexyl)(7-(3,6-dihydro -2H-thiopyran-4-yl)-6-((3R5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (70.0 mg, 105.2 μmol, 1.00 equivalent) and m-chloroperoxybenzoic acid (39.9 mg, 231.4 μmol, 2.20 equivalents), followed by N-((S-(4,4-diflu The compound was synthesized by oxidation of orocyclohexyl)(7-(1,1-dioxide-3,6-dihydro-2H-thiopyran-4-yl)-6-(((3R5R)-(2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide with Pd / C under H2 conditions. The resulting residue was purified by Prep-HPLC. N-((S)-(4,4-difluorocyclohexyl)(7-(1,1-dioxidetetrahydro-2H-thiopyran-4-yl)-6-(((3R,5R)-2-oxo-5-(trifluoromethyl)piperidine-3-yl)methyl)imidazo[1,2-b]pyridazin-2-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (48.8 mg, 95.2% purity) was obtained as a white solid. LCMS[M+H] + = 700.3 m / z.

[0422] Example 25: Synthesis of selected IL-17 modulators The compounds in Table 1 were synthesized similarly according to Examples 1 to 24.

[0423] In some embodiments, the disclosure provides compounds of formula (A) or formula (I) selected from Table 1, or pharmaceutically acceptable salts thereof. Each compound in Table 1 represents a single isomer with a known stereocenter marked. The absolute stereochemistry is unknown for the single isomers in Table 1 that contain unmarked stereocenters.

[0424] [Table 1-1]

[0425] [Table 1-2]

[0426] [Table 1-3]

[0427] [Table 1-4]

[0428] [Table 1-5]

[0429] [Table 1-6]

[0430] [Table 1-7]

[0431] [Table 1-8]

[0432] [Table 1-9]

[0433] [Table 1-10]

[0434] [Table 1-11]

[0435] [Table 1-12]

[0436] [Table 1-13]

[0437] [Table 1-14]

[0438] [Table 1-15]

[0439] Example 26. IL-17A / A HEK-Blue cell assay The HEK-Blue IL-17A reporter cell line (Fisher no. NC1408637) was used in a cell-based IL-17A / A inhibition assay. Cells were grown and prepared for the assay according to the manufacturer's instructions. This cell line consists of HEK 293 cells designed to express IL-17RA, IL-17RC, and Act1 adapter molecules, which, when stimulated by IL-17A / A or IL17A / F, activate the NFκB promoter and drive the expression of the recombinant secreted alkaline phosphatase (SEAP) gene. The culture medium from the cells was then added to the chromogenic reagent (Quanti-Blue Substrate, Fisher no. NC9711613) and A 630 Read it that way.

[0440] The compound was partitioned into DMSO in an empty, clear 384-well tissue culture plate by titration in the range of 10 μM to 27 pM, and DMSO was added to each well until the final concentration was 0.1%. Cells were then added to the plate (45 μL / well at a concentration of 280,000 cells / mL). IL-17A / A (Genscript number Z03228) or IL-17A / F (R&D Systems) was added to the plate until the final well volume was 50 μL at a final concentration of 5 ng / mL. The cells, compound, and IL-17A / A or IL-17A / F were then incubated for 20 hours, after which the medium was removed for SEAP analysis. The resulting inhibition curves were then analyzed using Dotmatics' integrated 4-parameter fit screening protocol, and IC50 was obtained. 50 A value was generated.

[0441] Table 2 shows the IC for IL-17A / A inhibition of the selected compounds. 50 The compound includes ICs with values ​​A < 100 nM, B 100 ~ 1000 nM, and C > 1000 nM. 50 It has.

[0442] [Table 2-1]

[0443] Table 2-2

Claims

1. Formula (A): 【Chemistry 1】 or represented by its pharmaceutically acceptable salt, in the formula, X is N or CR ２ Selected from, A is (a) and (b) below: (a) halogen, -OR １１Ａ , -SR １１Ａ , -N(R １１Ａ ), ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ), ２ , -N(R １１Ａ )C(O)R １１Ａ 、 -C(O)OR １１Ａ , -OC(O)R １１Ａ , -S(O)R １１Ａ , -S(O) ２ R １１Ａ , -NO ２ , =O, =S, =N(R １１Ａ ), and -CN, optionally substituted with one or more substituents independently selected from １－１０ C alkyl (b)-(CR'R'') ｍ (3- to 10-membered heterogeneous ring), -(CR'R'') ｍ (C ３－１０ carbocycle), -O-(CR'R'') ｍ (3- to 10-membered heterocycles), and -O-(CR'R'') ｍ (C ３－１０ Selected from carbon rings, the aforementioned 3- to 10-membered heterocycles and C ３－１０ Each of the carbon rings is as follows: 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 、-S(O)R １１ 、-S(O) ２ R １１ 、-NO ２ 、-CN、 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 , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , =O, =S, =N(R １１ ), -CN, each, 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, =N(R １１ ), -CN and halogen, -OR １１Ａ , -SR １１Ａ , -N(R １１Ａ ), ２ , -C(O)R １１Ａ , -C(O)N(R １１Ａ ), ２ , -N(R １１Ａ ), C(O)R １１Ａ , -C(O)OR １１Ａ , -OC(O)R １１Ａ , -S(O)R １１Ａ , -S(O) ２ R １１Ａ , -NO ２ , =O, =S, =N(R １１Ａ ), and -CN, optionally substituted with one or more substituents independently selected from １－１０ C alkyl optionally substituted with one or more substituents independently selected from ３－１０ a carbocyclic ring, and a 3- to 10-membered heterocyclic ring, optionally substituted with one or more substituents independently selected from １－１０ alkyl, and C ３－１０ A carbon ring and a 3- to 10-member heterocyclic ring, each of which is halogen, -OR １１ , -SR １１ , -N(R １１ ), -C(O)R ２ , -C(O)N(R １１ ), -N(R １１ ), -N(R ２ ), -N(R １１ ), -C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , =O, =S, =N(R １１ ), -CN and; halogen, -OR １１ , -N(R １１ ), -C(O)R ２ , -C(O)N(R １１ ), -N(R １１ ), -N(R ２ ), -N(R １１ ), -C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , =O, =N(R １１ ), and -CN, and optionally substituted with one or more substituents independently selected from C １－１０ alkyl optionally substituted with one or more substituents independently selected from C ３－１０ a carbon ring and a 3- to 10-member heterocyclic ring, each optionally substituted with one or more substituents independently selected from, (a) and (b), Each R' is hydrogen, halogen, -OR １８ , -N(R １８ ) ２ , -C(O)R １８ , -C(O)N(R １８ ) ２ , -NO ２ -CN and halogen, -OR １８ , -N(R １８ ) ２ , -C(O)R １８ , -C(O)N(R １８ ) ２ , -NO ２ , and C which is optionally replaced by one or more from -CN. １－６ Selected from alkyl groups, Each R'' is hydrogen, halogen, -OR １９ , -N(R １９ ) ２ , -C(O)R １９ , -C(O)N(R １９ ) ２ , -NO ２ -CN and halogen, -OR １９ , -N(R １９ ) ２ , -C(O)R １９ , -C(O)N(R １９ ) ２ , -NO ２ , and C which is optionally replaced by one or more from -CN. １－６ Selected from alkyl groups, B is -C(R ５ ) ３ and C ３－１０ Selected from the carbon ring, the C ３－１０ The carbocyclic ring is as follows: ハロゲン、-OR １２ 、-SR １２ 、-N(R １２ ) ２ 、-C(O)R １２ 、-C(O)N(R １２ ) ２ 、-N(R １２ )C(O)R １２ 、-N(R １２ )S(O) ２ R １２ 、-C(O)OR １２ 、-OC(O)R １２ 、-S(O)R １２ 、-S(O) ２ R １２ 、-NO ２ 、=O、=S、=N(R １２ )、-CN、 C １－１０ Alkyl and C ３－１０ A carbon ring, in which any of them is a halogen, -OR １２ , -SR １２ , -N(R １２ ) ２ , -C(O)R １２ , -C(O)N(R １２ ) ２ , -N(R １２ ) C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -S(O)R １２ , -S(O) ２ R １２ , -NO ２ , =O, =S, =N(R １２ ), -CN, C ３－１０ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. １－１０ Alkyl and C ３－１０ The carbon ring is optionally substituted with one or more substituents independently selected from the carbon ring, and the C ３－１０ The carbon ring and the 3- to 10-membered heterocycle are, respectively, halogens and -OR １２ , -N(R １２ ) ２ , -C(O)R １２ , -C(O)N(R １２ ) ２ , -N(R １２ ) C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -NO ２ , = O, = N (R １２ ), and are optionally substituted with one or more substituents selected from -CN, Each R ５ However, each occurrence corresponds to (i), (ii), and (iii): (i) hydrogen, 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 , -N(R １３ ), S(O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , -CN, (ii) 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 , -N(R １３ ) S(O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), C which is optionally substituted with one or more substituents independently selected from -CN １－１０ alkyl, and (iii) C ３－１０ A carbon ring, 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 , -N(R １３ ) S(O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), -CN, and 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 , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－１０ C is optionally substituted with one or more substituents independently selected from alkyl. ３－１０ Selected independently from the carbon ring, Each R １ However, each time it appears, ハロゲン、-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 、-N(R １４ )S(O) ２ R １４ 、-C(O)OR １４ 、-OC(O)R １４ 、-S(O)R １４ 、-S(O) ２ R １４ 、-NO ２ 、=O、=S、=N(R １４ )、-CN、 C １－１０ Alkyl and C ３－１０ A carbon ring, each of which is a 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 , -S(O)R １４ , -S(O) ２ R １４ , -NO ２ , =O, =S, =N(R １４ ), -CN, C ３－１０ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. １－１０ Alkyl and C ３－１０ Selected independently from the carbon ring, the C ３－１０ The carbon ring and the 3- to 10-membered heterocycle are, respectively, halogens and -OR １４Ａ , -SR １４Ａ , -N(R １４Ａ ) ２ , -C(O)R １４Ａ , -C(O)N(R １４Ａ ) ２ , -N(R １４Ａ ) C(O)R １４Ａ , -C(O)OR １４Ａ , -OC(O)R １４Ａ , -S(O)R １４Ａ , -S(O) ２ R １４Ａ , -NO ２ , =O, =S, =N(R １４Ａ ), and optionally substituted with one or more substituents selected from -CN, or two R １ The substituents together are C ３－６ A carbon ring or a 3- to 6-membered carbon ring may be formed, and the C ３－６ The carbon rings and 3- to 6-membered carbon rings are halogens, -OR, respectively. ２０ , -N(R ２０ ) ２ , -C(O)R ２０ , -C(O)N(R ２０ ) ２ , -NO ２ , =O, =S, =N(R ２０ ), -CN, C １－１０ Alkyl and C ３－１０ The carbon ring is optionally substituted with one or more substituents independently selected from the carbon ring, and the C １－１０ Alkyl and C ３－１０ The carbon rings are halogen, -OR, respectively. ２０ , -N(R ２０ ) ２ , -C(O)R ２０ , -C(O)N(R ２０ ) ２ , -NO ２ , =O, =S, =N(R ２０ ), and optionally substituted with one or more substituents independently selected from -CN, R ２ but, Hydrogen, halogen, -OR １５ , -SR １５ , -N(R １５ ), ２ , -C(O)R １５ , -C(O)N(R １５ ), ２ , -N(R １５ )C(O)R １５ , -N(R １５ ),S(O) ２ R １５ , -C(O)OR １５ , -OC(O)R １５ , -S(O)R １５ , -S(O) ２ R １５ , -NO ２ , -CN, Halogen, -OR １５ , -SR １５ , -N(R １５ ) ２ , -C(O)R １５ , -C(O)N(R １５ ) ２ , -N(R １５ ) C(O)R １５ , -C(O)OR １５ , -OC(O)R １５ , -S(O)R １５ , -S(O) ２ R １５ , -NO ２ , =O, =S, =N(R １５ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－１０ Selected from alkyl groups, or R ２ and one R １ However, a 3- to 6-membered carbon ring may also be formed, and the 3- to 6-membered carbon ring is Halogen, -OR ２１ , -N(R ２１ ) ２ , -C(O)R ２１ , -C(O)N(R ２１ ) ２ , -NO ２ , =O, =S, =N(R ２１ ), -CN, C １－１０ Alkyl and C ３－１０ A carbon ring, each of which is a halogen, -OR ２０ , -N(R １０ ) ２ , -C(O)R ２１ , -C(O)N(R ２１ ) ２ , -NO ２ , =O, =S, =N(R ２１ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－１０ Alkyl and C ３－１０ Optionally substituted with one or more substituents independently selected from the carbon ring, Each R ３ However, each time it appears, hydrogen, halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S(O) ２ R １６ , -C(O)OR １６ , -OC(O)R １６ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ -CN and halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) C(O)R １６ , -C(O)OR １６ , -OC(O)R １６ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－６ Selected independently of alkyl, L is halogen, -O-C １－６ Alkyl, -O-C １－６ Haloalkyl, -NH ２ , -NO ２ C is optionally substituted with one or more substituents independently selected from ,=O and -CN. １－６ Alkylene, -O-, selected from bond, Ring D is C ３－１０ A carbocyclic ring and a 3- to 10-membered heterocyclic ring, each of which is: ハロゲン、-OR １７ 、-SR １７ 、-N(R １７ ) ２ 、-C(O)R １７ 、-C(O)N(R １７ ) ２ 、-N(R １７ )C(O)R １７ 、-N(R １７ )S(O) ２ R １７ 、-C(O)OR １７ 、-OC(O)R １７ 、-S(O)R １７ 、-S(O) ２ R １７ 、-NO ２ 、=O、=S、=N(R １７ )、-CN、 Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , =O, =S, =N(R １７ ), -CN, C ３－１０ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. １－１０ alkyl, and Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , =O, =S, =N(R １７ ), -CN and halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , =O, =S, =N(R １７ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－６ A 3- to 10-membered heterocycle and C are optionally substituted with one or more substituents independently selected from the alkyl group. ３－１０ A 3- to 10-membered heterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring, R １１ , R １１Ａ , R １２ , R １３ , R １４ , R １４Ａ , R １５ , R １６ , R １７ , R １８ , R １９ , R ２０ , and R ２１ However, each time it appears: hydrogen, Halogen, -O-C １－６ Alkyl, -O-C １－６ Haloalkyl, -NH ２、 - NO ２ , = O, -CN, C ３－１０ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. １－６ Alkyl, each C ３－１０ Carbon rings and 3- to 10-membered heterocycles are halogens, -OH, -O-C １－６ Alkyl, -O-C １－６ Haloalkyl, -NH ２、 - NO ２ C is optionally substituted with one or more substituents independently selected from ,=O and -CN. １－６ alkyl, and Halogen, -OH, -O-C １－６ Alkyl, -O-C １－６ Haloalkyl, -NH ２ , -NO ２ C is optionally substituted with one or more substituents independently selected from ,=O and -CN. ３－１０ Independently selected from carbon rings and 3- to 10-membered heterocycles, m is selected from 0, 1, and 2. z is selected from 1 and 2. n is selected from 1, 2, and 3. p is a compound selected from 0, 1, 2, 3, 4, 5, and 6.

2. L is halogen, -O-C １－６ Alkyl, -O-C １－６ Haloalkyl, -NH ２ - NO ２ C is optionally substituted with one or more substituents independently selected from ,=O, or -CN. １－６ A compound or salt according to claim 1, selected from alkylene and bonding.

3. L is halogen, -O-C １－６ Alkyl, -O-C １－６ Haloalkyl, -NH ２ - NO ２ C is optionally substituted with one or more substituents independently selected from ,=O, or -CN. １－６ The compound or salt according to claim 2, which is alkylene.

4. L is halogen, -O-C １－６ Alkyl and -O-C １－６ C is optionally substituted with one or more substituents independently selected from the haloalkyl group. １－３ The compound or salt according to claim 3, which is alkyl.

5. L represents halogen and -O-C respectively. １－６ Alkyl and -O-C １－６ The compound or salt according to claim 4, selected from methylene and ethylene, which are optionally substituted with one or more substituents independently selected from the haloalkyl.

6. The compound or salt according to claim 5, wherein L is methylene.

7. Ring D is a 3- to 10-membered heterocyclic ring, and the 3- to 10-membered heterocyclic ring is Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , =O, =S, =N(R １７ ), -CN, and Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , =O, =S, =N(R １７ ), -CN, C ３－１０ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. １－１０ The compound or salt according to any one of claims 1 to 6, which is optionally substituted with one or more substituents independently selected from the alkyl group.

8. Ring D is halogen, C １－６ Alkyl and C １－６ The compound or salt according to claim 7, which is a 4- to 7-membered saturated heterocycle optionally substituted with one or more substituents independently selected from the haloalkyl group. 【Request Item 9】 【Chemistry 2】 but, 【Transformation 3】 A compound or salt according to any one of claims 1 to 9, selected from the above.

10. L is a bond, the compound or salt according to claim 1.

11. Equation (A) is Equation (I) 【Chemistry 4】 Structure or represented by its pharmaceutically acceptable salt, in the formula, A is -(CR'R'') ｍ (3- to 10-membered heterogeneous ring), -(CR'R'') ｍ (C ３－１０ carbocycle), -O-(CR'R'') ｍ (3- to 10-membered heterocycles), and -O-(CR'R'') ｍ (C ３－１０ Selected from carbon rings, the aforementioned 3- to 10-membered heterocycles and C ３－１０ Each of the carbon rings is as follows: 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 、-S(O)R １１ 、-S(O) ２ R １１ 、-NO ２ 、-CN、 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 , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , =O, =S, =N(R １１ ), -CN, halogen, -OR respectively 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, = N (R １１ ), and C, which is optionally substituted with one or more substituents selected from -CN. ３－１０ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. １－１０ alkyl, and C ３－１０ A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , =O, =S, =N(R １１ ), -CN and 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, = N (R １１ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－６ C is optionally substituted with one or more substituents independently selected from the alkyl group. ３－１０ It is optionally substituted with one or more substituents independently selected from the carbon ring and the 3- to 10-membered heterocycle. Each R' is hydrogen, halogen, -OR １８ , -N(R １８ ) ２ , -C(O)R １８ , -C(O)N(R １８ ) ２ , -NO ２ -CN and halogen, -OR １８ , -N(R １８ ) ２ , -C(O)R １８ , -C(O)N(R １８ ) ２ , -NO ２ , and C which is optionally replaced by one or more from -CN. １－６ Selected from alkyl groups, Each R'' is hydrogen, halogen, -OR １９ , -N(R １９ ) ２ , -C(O)R １９ , -C(O)N(R １９ ) ２ , -NO ２ -CN and halogen, -OR １９ , -N(R １９ ) ２ , -C(O)R １９ , -C(O)N(R １９ ) ２ , -NO ２ , and C which is optionally replaced by one or more from -CN. １－６ Selected from alkyl groups, B is -C(H)(R ５ ) ２ and C ３－１０ Selected from the carbon ring, the C ３－１０ The carbocyclic ring is as follows: ハロゲン、-OR １２ 、-SR １２ 、-N(R １２ ) ２ 、-C(O)R １２ 、-C(O)N(R １２ ) ２ 、-N(R １２ )C(O)R １２ 、-N(R １２ )S(O) ２ R １２ 、-C(O)OR １２ 、-OC(O)R １２ 、-S(O)R １２ 、-S(O) ２ R １２ 、-NO ２ 、=O、=S、=N(R １２ )、-CN、 C １－１０ Alkyl and C ３－１０ A carbon ring, in which any of them is a halogen, -OR １２ , -SR １２ , -N(R １２ ) ２ , -C(O)R １２ , -C(O)N(R １２ ) ２ , -N(R １２ ) C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -S(O)R １２ , -S(O) ２ R １２ , -NO ２ , =O, =S, =N(R １２ ), -CN, C ３－１０ The C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. ３－１０ The carbon ring and the 3- to 10-membered heterocycle are, respectively, halogens and -OR １２ , -N(R １２ ) ２ , -C(O)R １２ , -C(O)N(R １２ ) ２ , -N(R １２ ) C(O)R １２ , -C(O)OR １２ , -OC(O)R １２ , -NO ２ , = O, = N (R １２ ), and are optionally substituted with one or more substituents selected from -CN, Each R ５ However, each occurrence corresponds to (i), (ii), and (iii): (i)ハロゲン、-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 、-N(R １３ )S(O) ２ R １３ 、-C(O)OR １３ 、-OC(O)R １３ 、-S(O)R １３ 、-S(O) ２ R １３ 、-NO ２ 、-CN、 (ii) 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 , -N(R １３ ) S(O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), which is optionally substituted with one or more substituents independently selected from -CN, C １－１０ alkyl, and (iii) C ３－１０ A carbon ring, 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 , -N(R １３ ) S(O) ２ R １３ , -C(O)OR １３ , -OC(O)R １３ , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), -CN, and 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 , -S(O)R １３ , -S(O) ２ R １３ , -NO ２ , =O, =S, =N(R １３ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－１０ C is optionally substituted with one or more substituents independently selected from alkyl. ３－１０ Selected independently from the carbon ring, Each R １ However, each time it appears, ハロゲン、-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 、-N(R １４ )S(O) ２ R １４ 、-C(O)OR １４ 、-OC(O)R １４ 、-S(O)R １４ 、-S(O) ２ R １４ 、-NO ２ 、=O、=S、=N(R １４ )、-CN、 C １－１０ alkyl and C ３－１０ carbocyclic ring, each of which is independently selected from halogen, -OR １４ , -SR １４ , -N(R １４ ), -C(O)R ２ , -C(O)N(R １４ ), -N(R １４ ), -N(R ２ ), -C(O)R １４ ), -C(O)OR １４ , -OC(O)R １４ , -S(O)R １４ , -S(O １４ R ２ R １４ , -NO ２ , =O, =S, =N(R １４ ), -CN, and is optionally substituted with one or more substituents independently selected from １－１０ alkyl and C ３－１０ carbocyclic ring, or Two R's １ The substituents may together form a 3- to 6-membered carbon ring, and the 3- to 6-membered carbon ring may Halogen, -OR ２０ , -N(R ２０ ) ２ , -C(O)R ２０ , -C(O)N(R ２０ ) ２ , -NO ２ , =O, =S, =N(R ２０ ), -CN, C １－１０ Alkyl and C ３－１０ A carbon ring, each of which is a halogen, -OR ２０ , -N(R ２０ ) ２ , -C(O)R ２０ , -C(O)N(R ２０ ) ２ , -NO ２ , =O, =S, =N(R ２０ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－１０ Alkyl and C ３－１０ Optionally substituted with one or more substituents independently selected from the carbon ring, R ２ is independently selected from hydrogen, halogen, -OR １５ , -SR １５ , -N(R １５ ), -C(O)R ２ , -C(O)N(R １５ ), -N(R １５ ), -N(R ２ ), -N(R １５ ), -N(R １５ ), -N(R １５ ), -N(R ２ ), -C(O)OR １５ , -OC(O)R １５ , -S(O)R １５ , -S(O １５ ), -S(O ２ ), -NO １５ , -CN and halogen, -OR ２ , -SR １５ , -N(R １５ ), -C(O)R １５ , -C(O)N(R ２ ), -N(R １５ ), -N(R １５ ), -N(R ２ ), -C(O)OR １５ ), -OC(O)R １５ , -S(O)R １５ , -S(O １５ ), -S(O １５ ), -NO ２ ), =O, =S, =N(R １５ ), and -CN and is optionally substituted with one or more substituents independently selected from ２ C alkyl １５ ), or １－６ is selected from R ２ and one R １ However, a 3- to 6-membered carbon ring may also be formed, and the 3- to 6-membered carbon ring is Halogen, -OR ２１ , -N(R ２１ ) ２ , -C(O)R ２１ , -C(O)N(R ２１ ) ２ , -NO ２ , =O, =S, =N(R ２１ ), -CN, C １－１０ Alkyl and C ３－１０ A carbon ring, each of which is a halogen, -OR ２０ , -N(R １０ ) ２ , -C(O)R ２１ , -C(O)N(R ２１ ) ２ , -NO ２ , =O, =S, =N(R ２１ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－１０ Alkyl and C ３－１０ Optionally substituted with one or more substituents independently selected from the carbon ring, Each R ３ However, each time it appears, hydrogen, halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) C(O)R １６ , -N(R １６ ) S(O) ２ R １６ , -C(O)OR １６ , -OC(O)R １６ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ -CN and halogen, -OR １６ , -SR １６ , -N(R １６ ) ２ , -C(O)R １６ , -C(O)N(R １６ ) ２ , -N(R １６ ) C(O)R １６ , -C(O)OR １６ , -OC(O)R １６ , -S(O)R １６ , -S(O) ２ R １６ , -NO ２ , =O, =S, =N(R １６ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－６ Selected independently of alkyl, Ring D is C ３－１０ A carbocyclic ring and a 3- to 10-membered heterocyclic ring, each of which is: ハロゲン、-OR １７ 、-SR １７ 、-N(R １７ ) ２ 、-C(O)R １７ 、-C(O)N(R １７ ) ２ 、-N(R １７ )C(O)R １７ 、-N(R １７ )S(O) ２ R １７ 、-C(O)OR １７ 、-OC(O)R １７ 、-S(O)R １７ 、-S(O) ２ R １７ 、-NO ２ 、=O、=S、=N(R １７ )、-CN、 Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , =O, =S, =N(R １７ ), -CN, C ３－１０ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. １－１０ alkyl, and Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , =O, =S, =N(R １７ ), -CN and halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , =O, =S, =N(R １７ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－６ A 3- to 10-membered heterocycle and C are optionally substituted with one or more substituents independently selected from the alkyl group. ３－１０ A 3- to 10-membered heterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring, R １１ , R １２ , R １３ , R １４ , R １５ , R １６ , R １７ , R １８ , R １９ , R ２０ , and R ２１ However, each time they appear, hydrogen, Halogen, -O-C １－６ Alkyl, -O-C １－６ Haloalkyl, -NH ２、 - NO ２ , = O, -CN, C ３－１０ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. １－６ Alkyl, each C ３－１０ Carbon rings and 3- to 10-membered heterocycles are halogens, -OH, -O-C １－６ Alkyl, -O-C １－６ Haloalkyl, -NH ２、 - NO ２ C is optionally substituted with one or more substituents independently selected from ,=O and -CN. １－６ alkyl, and Halogen, -OH, -O-C １－６ Alkyl, -O-C １－６ Haloalkyl, -NH ２ , -NO ２ C is optionally substituted with one or more substituents independently selected from ,=O and -CN. ３－１０ Independently selected from carbon rings and 3- to 10-membered heterocycles, m is selected from 0, 1, and 2. n is selected from 1 and 2. The compound or salt according to claim 1, wherein p is selected from 0, 1, 2, 3, 4, 5, and 6.

12. The compound or salt according to claim 11, wherein n is 1.

13. Equation (I) is given by equation (I-a): 【Transformation 5】 The compound or salt according to either claim 11 or claim 12, represented by its structure.

14. The compound or salt according to claim 11, wherein n is 2.

15. Equation (I) is given by equation (I-b): 【Transformation 6】 The compound or salt according to claim 11 or claim 4, represented by its structure.

16. A compound or salt according to any one of claims 11 to 15, wherein m is 1.

17. R' and R'' are, independently, hydrogen, halogen, and -OR. １８ , -N(R １８ ) ２ ,-CN,C １－３ Alkyl and C １－３ A compound or salt according to any one of claims 11 to 16, selected from haloalkyls.

18. R' and R'' are, independently, hydrogen, halogen, and C. １－３ Alkyl and C １－３ A compound or salt according to claim 17, selected from haloalkyls.

19. The compound or salt according to claim 18, wherein R' and R'' are each independently selected from hydrogen and halogen.

20. A compound or salt according to any one of claims 11 to 15, wherein m is 0.

21. A is a 5-6 member heteroaryl compound, and the 5-6 member heteroaryl compound is: 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 、-S(O)R １１ 、-S(O) ２ R １１ 、-NO ２ 、-CN、 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 , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , =O, =S, =N(R １１ ), -CN, halogen, -OR respectively 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, = N (R １１ ), and C, which is optionally substituted with one or more substituents selected from -CN. ３－１０ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. １－１０ alkyl, and C ３－１０ A carbon ring and a 3- to 10-membered heterocycle, each of which is a 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 , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , =O, =S, =N(R １１ ), -CN and 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, = N (R １１ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－６ C is optionally substituted with one or more substituents independently selected from the alkyl group. ３－１０ The compound or salt according to any one of claims 11 to 20, which is optionally substituted with one or more substituents independently selected from a carbocyclic ring and a 3- to 10-membered heterocyclic ring.

22. A is a five-membered heteroaryl, and the five-membered heteroaryl is: Halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , -CN, and C １－６ Alkyl, halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ ,-CN,C ３－１０ C is optionally substituted with one or more substituents independently selected from a carbon ring and a 3- to 10-membered heterocycle. １－６ Optionally substituted with one or more substituents independently selected from alkyl, C ３－１０ The carbon ring and the 3- to 10-membered heterocycle are, respectively, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ The compound or salt according to any one of claims 1 to 21, which is optionally substituted with one or more substituents selected from -CN.

23. A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, and tetrazolyl, and one of them is halogen, -OR １１ , -SR １１ , -N(R １１ ) ２ , -C(O)R １１ , -C(O)N(R １１ ) ２ , -C(O)OR １１ , -OC(O)R １１ , -NO ２ , and one or more C atoms optionally substituted with one or more substituents independently selected from -CN. １－６ The compound or salt according to claim 22, which is optionally substituted with an alkyl group.

24. A is selected from pyrazolyl and oxadiazolyl, each of which is a halogen, -OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -NO ２ , and C which is optionally substituted with one or more substituents independently selected from -CN. １－６ The compound or salt according to claim 23, which is optionally substituted with an alkyl group.

25. The compound or salt according to claim 24, wherein A is selected from pyrazolyls optionally substituted with methyl, ethyl, isopropyl, or propyl.

26. A, 【Transformation 7】 A compound or salt according to claim 25, selected from the above.

27. A is C ３－１０ A five-membered heteroaryl in which a carbon ring is optionally substituted, and the C ３－１０ The carbon ring is a 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 , -S(O)R １１ , -S(O) ２ R １１ , -NO ２ , =O, =S, =N(R １１ ), -CN and 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, = N (R １１ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－６ The compound or salt according to any one of claims 11 to 21, which is optionally substituted with one or more substituents independently selected from the alkyl group.

28. A is selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, and tetrazolyl, and any of them is halogen, -OR １１ , -N(R １１ ) ２ , -C(O)R １１ , -NO ２ ,-CN,C １－６ Alkyl and C １－６ C is optionally substituted with one or more substituents independently selected from the haloalkyl group. ３－６ The compound or salt according to claim 27, which is optionally substituted with a saturated carbon ring.

29. A is selected from pyrazolyl and oxadiazolyl, each of which is optionally substituted with cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, where cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl is a halogen, C １－６ Alkyl and C １－６ The compound or salt according to claim 28, which is optionally substituted with a haloalkyl group.

30. A, 【Transformation 8】 A compound or salt according to claim 29, selected from the above.

31. B is -C(H)(R ５ ) ２ The compound or salt according to any one of claims 1 to 30.

32. -C(H)(R ５ ) ２ Each R ５ but, Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ ,-CN, Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－６ alkyl, and Halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), -CN, C １－６ Alkyl and C １－６ C is optionally substituted with one or more substituents independently selected from the haloalkyl group. ３－１０ A compound or salt according to claim 31, independently selected from the carbocyclic ring.

33. -C(H)(R ５ ) ２ Each R ５ However, halogen, -OR １３ , -N(R １３ ) ２ , -C(O)R １３ , -C(O)OR １３ , -NO ２ , =O, =S, =N(R １３ ), -CN, C １－６ Alkyl and C １－６ C is optionally substituted with one or more substituents independently selected from the haloalkyl group. ３－６ A compound or salt according to claim 32, independently selected from the carbocyclic ring.

34. B is halogen, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ ), -CN; and halogens, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－６ C is optionally substituted with one or more substituents independently selected from alkyl. ６－１０ A compound or salt according to any one of claims 11 to 30, which is a carbon ring.

35. B is selected from cyclohexyl and cycloheptyl, and one of them is a halogen, -OR １２ , N(R １２ ) ２ , -NO ２ -CN and halogen, -OR １２ , N(R １２ ) ２ , -C(O)R １２ , -NO ２ , =O, =S, =N(R １２ ), and C which is optionally substituted with one or more substituents independently selected from -CN. １－６ The compound or salt according to claim 34, which is optionally substituted with one or more substituents independently selected from the alkyl group.

36. B, 【Chemistry 9】 A compound or salt according to claim 35, selected from the above.

37. Ring D is C ３－１０ It is a carbon ring, and the C ３－１０ The carbon ring is: Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , -CN, and C １－１０ Alkyl and C ３－１０ A carbon ring, each of which is a halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ C is optionally substituted with one or more substituents independently selected from ,=O,=S, and -CN. １－１０ Alkyl and C ３－１０ The compound or salt according to any one of claims 11 to 36, wherein it is optionally substituted with one or more substituents independently selected from the carbocyclic ring.

38. Ring D is halogen, -OR １７ , -N(R １７ ) ２ , -C(O)R １７ , -NO ２ ,-CN,C １－６ Alkyl and C １－６ C is optionally substituted with one or more substituents independently selected from the haloalkyl group. ３－６ The compound or salt according to claim 37, which is a saturated carbon ring.

39. Ring D is selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, each of which is C １－６ Alkyl and C １－６ The compound or salt according to claim 38, which is optionally substituted with a haloalkyl group.

40. Ring D is 【Chemistry 10】 A compound or salt according to claim 39, selected from the above.

41. Ring D is a 3- to 10-membered heterocyclic ring, and the 3- to 10-membered heterocyclic ring is Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , -CN, and C １－１０ Alkyl and C ３－１０ A carbon ring, each of which is a halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ C is optionally substituted with one or more substituents independently selected from ,=O,=S, and -CN. １－１０ Alkyl and C ３－１０ The compound or salt according to any one of claims 11 to 36, wherein it is optionally substituted with one or more substituents independently selected from the carbocyclic ring.

42. Ring D is selected from 3- to 7-membered monocyclic heterorings and 5- to 10-membered bicyclic heterorings, and any of them is Halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , -CN, and C １－６ Alkyl and C ３－６ A carbon ring, each of which is a halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ , and C which is optionally substituted with one or more substituents independently selected from -CN. １－６ Alkyl and C ３－６ The compound or salt according to claim 41, which is optionally substituted with one or more substituents independently selected from the carbocyclic ring.

43. Ring D is a 5-6 member heteroaryl, and the 5-6 member heteroaryl is a halogen, -OR １７ , -SR １７ , -N(R １７ ) ２ , -C(O)R １７ , -C(O)N(R １７ ) ２ , -N(R １７ ) C(O)R １７ , -N(R １７ ) S(O) ２ R １７ , -C(O)OR １７ , -OC(O)R １７ , -S(O)R １７ , -S(O) ２ R １７ , -NO ２ ,-CN,C １－６ Alkyl and C １－６ The compound or salt according to claim 42, which is optionally substituted with one or more substituents independently selected from the haloalkyl group.

44. Ring D is selected from pyridinyl and pyrimidinyl, each of which is a halogen, -OR １７ , N(R １７ ) ２ , -C(O)R １７ , -NO ２ ,-CN,C １－６ Alkyl and C １－６ The compound or salt according to claim 43, which is optionally substituted with one or more substituents independently selected from the haloalkyl group.

45. Ring D is 【Chemistry 11】 A compound or salt according to claim 44, selected from the above.

46. Ring D is selected from 3- to 6-membered saturated heterocycles and 3- to 6-membered unsaturated heterocycles, and one of them is a halogen, -OR １７ , -N(R １７ ) ２ , -C(O)R １７ , -NO ２ ,-CN,C １－６ Alkyl, C １－６ Haloalkyl and C ３－６ The compound or salt according to claim 42, which is optionally substituted with one or more substituents independently selected from the carbocyclic ring.

47. Ring D is halogen, C １－６ Haloalkyl and C ３－６ The compound or salt according to claim 46, which is a 3- to 6-membered unsaturated heterocycle that is optionally substituted with one or more substituents independently selected from the carbon ring.

48. The compound or salt according to claim 47, wherein ring D is selected from 2,5-dihydrofuranyl and 3,6-dihydro-2H-pyranyl.

49. Ring D is 【Chemistry 12】 A compound or salt according to claim 47, selected from the above.

50. Ring D is halogen, -OR １７ , -N(R １７ ) ２ , -C(O)R １７ , -NO ２ ,-CN,C １－３ Alkyl, C １－３ Haloalkyl and C ３－６ The compound or salt according to claim 46, which is a 3- to 6-membered heterocycloalkyl group that is optionally substituted with one or more substituents independently selected from the carbocyclic ring.

51. Ring D is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, and morpholinyl, and each of these is a halogen, -OR １７ , -N(R １７ ) ２ , -C(O)R １７ , -NO ２ ,-CN,C １－３ Alkyl, C １－３ Haloalkyl and C ３－６ Optionally substituted with one or more substituents independently selected from the carbon ring, R １７ However, hydrogen, C １－３ Alkyl, C １－３ Haloalkyl and C ３－６ A compound or salt according to claim 50, selected from a carbocyclic ring.

52. Ring D is 【Chemistry 13】 A compound or salt according to claim 51, selected from the above.

53. Ring D is 【Chemistry 14】 A compound or salt according to claim 50, selected from the above.

54. Ring D is 【Chemistry 15】 A compound or salt according to claim 51, selected from the above.

55. Ring D is a 5-10 member bicyclic heterocycle selected from 5-10 member condensed heterocycles, 5-10 member bridging heterocycles, and 5-10 member spirocyclic heterocycles, and any of these is a halogen, -OR １７ , -N(R １７ ) ２ , -C(O)R １７ , -NO ２ ,-CN,C １－３ Alkyl, C １－３ Haloalkyl and C ３－６ The compound or salt according to claim 42, which is optionally substituted with one or more substituents independently selected from the carbocyclic ring.

56. Ring D is a 5-10 membered bicyclic heterocycle selected from 5-10 membered bridging heterocycles and 5-10 membered spirocyclic heterocycles, and any of them is a halogen, -OR １７ , -N(R １７ ) ２ , -C(O)R １７ , -NO ２ ,-CN,C １－３ Alkyl, C １－３ Haloalkyl and C ３－６ The compound or salt according to claim 42, which is optionally substituted with one or more substituents independently selected from the carbocyclic ring.

57. Ring D is halogen, -OR １７ , C １－３ Alkyl and C １－３ The compound or salt according to claim 55, which is a 5- to 10-membered crosslinked heterocycle optionally substituted with one or more substituents independently selected from the haloalkyl group.

58. Ring D is selected from tetrahydropyranyl, morpholinyl 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, and 8-oxa-3-azabicyclo[3.2.1]octanyl, and any of these is a halogen, -OR １７ , C １－３ Alkyl and C １－３ The compound or salt according to claim 57, which is optionally substituted with one or more substituents independently selected from the haloalkyl group.

59. Ring D is, 【Chemistry 16】 A compound or salt according to claim 58, selected from the above.

60. Ring D is halogen, -OR １７ , C １－３ Alkyl and C １－３ The compound or salt according to claim 55, which is a 5- to 10-membered spirocyclic heterocycle optionally substituted with one or more substituents independently selected from the haloalkyl group.

61. Ring D is selected from 2-oxa-6-azaspiro[3.3]heptanyl, 6-oxa-2-azaspiro[3.5]nonanyl, 7-oxa-2-azaspiro[3.5]nonanyl, 2-oxa-6-azaspiro[3.4]octanyl, 4-oxa-7-azaspiro[2.5]octanyl, and 4-methyl-4,7-diazaspiro[2.5]octanyl, each of which is a halogen, -OR １７ , C １－３ Alkyl and C １－３ The compound or salt according to claim 60, which is optionally substituted with one or more substituents independently selected from the haloalkyl group.

62. Ring D is 【Chemistry 17】 A compound or salt according to claim 61, selected from the above.

63. Ring D is halogen, -OR １７ , C １－３ Alkyl and C １－３ The compound or salt according to claim 55, which is a 5- to 10-membered condensed heterocycle optionally substituted with one or more substituents independently selected from the haloalkyl group.

64. Ring D is [Chemistry 18] The compound or salt according to claim 63.

65. Ring D is 【Chemistry 19】 A compound or salt according to any one of claims 11 to 36, selected from the above.

66. Ring D is 【Chemistry 20】 A compound or salt according to any one of claims 11 to 36, selected from the above.

67. Each R ３ However, each time it appears, hydrogen, halogen, -OR １６ , -N(R １６ ) ２ , -NO ２ ,-CN,C １－３ Alkyl and C １－３ A compound or salt according to any one of claims 11 to 63, independently selected from haloalkyls.

68. Each R ３ The compound or salt according to claim 67, wherein the compound is hydrogen.

69. R ２ The compound or salt according to any one of claims 11 to 68, wherein the compound is hydrogen.

70. A compound or salt according to any one of claims 11 to 69, wherein p is selected from 0, 1, 2, 3, and 4.

71. Each R １ However, each time it appears, hydrogen, halogen, -OR １４ , -N(R １４ ) ２ , -NO ２ ,-CN,C １－６ Alkyl and C １－６ A compound or salt according to any one of claims 11 to 70, independently selected from haloalkyls.

72. Each R １ However, each time it appears, halogen and -CF ３ A compound or salt according to claim 71, independently selected from the above.

73. The compound or salt according to claim 11, wherein formula (I) is selected from the compounds in Table 1 or pharmaceutically acceptable salts thereof. 【Request Item 74】 【Chemistry 21】 A compound selected from the group consisting of pharmaceutically acceptable salts thereof.

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

76. A method for modulating IL-17A in a subject requiring modification of IL-17A, comprising administering to the subject a compound or salt according to any one of claims 1 to 74, or a pharmaceutical composition according to claim 75.

77. A method for treating an inflammatory disease or condition, comprising administering to a subject in need thereof a compound or salt according to any one of claims 1 to 74, or a pharmaceutical composition according to claim 75.

78. The method according to claim 77, wherein the inflammatory disease or condition is selected from psoriasis vulgaris, guttate psoriasis, psoriasis reversal, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, ankylosing spondylitis, hidradenitis suppurativa, rheumatoid arthritis, palmoplantar psoriasis, spondyloarthritis, and non-infectious uveitis.

79. A method for treating psoriasis, comprising administering to a subject in need of such treatment a compound or salt according to any one of claims 1 to 74, or a pharmaceutical composition according to claim 75.

80. A method for treating psoriatic arthritis, comprising administering to a subject in need of such treatment a compound or salt according to any one of claims 1 to 74, or a pharmaceutical composition according to claim 75.

81. A method for treating ankylosing spondylitis, comprising administering to a subject in need of such treatment a compound or salt according to any one of claims 1 to 74, or a pharmaceutical composition according to claim 75.

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