JP-7856952-B2 - Compounds, preventive or therapeutic agents for neurological diseases

Inventors

• 村田 等
• 阪口 政清
• 安藤 隆幸
• 福田 達也
• 中村 仁

Assignees

• 国立大学法人 岡山大学
• 公益財団法人ふじのくに医療城下町推進機構

Dates

Publication Date

20260512

Application Date

20210823

Claims (2)

1. A preventive or therapeutic agent for neurological disorders, comprising a compound represented by CD388, CE9, or CE221 as an active ingredient.
2. The preventive or therapeutic agent for a neurological disease according to claim 1, wherein the neurological disease is selected from the group consisting of diabetic neuropathy, Parkinson's disease, amyotrophic lateral sclerosis (ALS), neuropathy, multiple sclerosis, spinocerebellar degeneration, Alzheimer's disease, Guillain-Barré syndrome, spinal cord injury, traumatic brain injury, chemotherapy-induced peripheral neuropathy (CIPN), Lewy body dementia, frontotemporal dementia, vascular dementia, Huntington's disease, Parkinson's syndrome, primary lateral sclerosis, Charcot-Marie-Tooth disease, collagen disease, familial amyloid polyneuropathy, progressive multifocal leukoencephalopathy, subacute combined degeneration of the spinal cord, prion disease, viral encephalitis, neuromyelitis optica, and glaucoma.

Description

There are few drugs that can suppress or treat the progression of neurological diseases. Patent Document 1 describes IA9 (Lansoprazole Sulfide) and NSC228155 as compounds effective against neurological disorders, but the efficacy of these compounds against neurological disorders was low. Special Publication No. 2019-535804 This demonstrates the efficacy of the present compound against an in vitro model of CIPN.The present invention demonstrates a protective effect on mitochondria.The present invention demonstrates the efficacy of the compound against Parkinson's disease (PD).This demonstrates the efficacy of the compound of the present invention against an in vivo model of CIPN.Purification and phosphorylation of SARM1-FLAG using the compound of the present inventionInhibition efficiency of NAD + degradation activity by the compound of the present inventionCompound evaluation using SARM1-overexpressing cells The compound of the present invention is represented by general formula (I). (In the formula, R1 represents a substituent; Y1 represents a single bond or a divalent linking group; Z1 represents an optionally substituted nitrogen-containing aromatic group; and n represents an integer from 1 to 5.) A more preferred compound of the present invention is represented by the following formula (I-1) or (I-2). (In the formula, R1 represents a substituent. Y1 represents a single bond or a divalent linking group. R2 represents a lower alkyl group, a cycloalkyl group, an optionally substituted aryl group, or an optionally substituted aralkyl group. R3 and R4 may be the same or different substituents, or R3 and R4 together with the carbon atoms to which they are bonded may form an optionally substituted aromatic ring or an optionally substituted heteroaromatic ring. X1 to X7 may be the same or different C- R5 or N, and R5 may be the same or different substituent. n is an integer from 1 to 5.) n represents an integer from 1 to 5, preferably 1, 2, or 3, more preferably 1 or 2. Examples of aromatic rings that can be formed by R3 and R4 and the carbon atoms to which they are bonded include phenyl and naphthyl, while examples of heteroaromatic rings include pyrrole, imidazole, thiazole, isothiazole, oxazole, isoxazole, triazole, quinoline, isoquinoline, pyridine, pyrimidine, pyridazine, quinoxaline, indole, benzimidazole, benzoisothiazole, benzoxazole, benzoisoxazole, and benzotriazole. Examples of divalent linking groups represented by Y1 include linear or branched alkylene groups of C1-6 , cycloalkylene groups, optionally substituted arylene groups, optionally substituted aralkylene groups, -O-, -NR6- (where R6 represents a hydrogen atom, a linear or branched alkyl group of C1-6 , an optionally substituted phenyl group, or an optionally substituted aralkyl group), -CH(OH)-, -S-, -CO-, -CONH-, -NHCO-, -CO-O-, -O-CO-, -NH-CO-O, -O-CO-NH-, -NH-CO-NH-, and others. One or more of these can be combined to form a divalent linking group. Examples of nitrogen-containing aromatic groups represented by Z1 include pyrrolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, quinolyl, isoquinolyl, pyridyl, pyrimidinyl, pyridadinyl, quinoxalinyl, indolyl, benzimidazolyl, benzoisothiazolyl, benzoxazolyl, benzoisoxazolyl, and benzotriazolyl. In this specification, substituents that may be present on groups or rings such as nitrogen-containing aromatic groups, aryl groups, aralkyl groups, heteroaryl groups, arylene groups, aralkylene groups, phenyl groups, aromatic rings, heteroaromatic rings, etc., or substituents represented by R 5 include halogen atoms, trifluoromethyl groups, hydroxyl groups, C1-6 alkyl groups, C2-6 alkenyl groups, C2-6 alkynyl groups, C1-6 alkoxy groups, C3-7 cycloalkyl groups, trifluoromethoxy groups, trifluoroethoxy groups, C1-6 alkylsulfonylamino groups, C1-2 alkylsulfonyl groups, cyano groups, nitro groups, amino groups, mono or disubstituted amino groups, C1-6 alkoxycarbonylamino groups, carbamoyl groups, mono or disubstituted carbamoyl groups, sulfamoyl groups, mono or disubstituted sulfamoyl groups, C1-6 alkylcarbonyloxy, arylcarbonyloxy, aryl-substituted C1-4 alkylcarbonyloxy, C Examples include 1-6 alkylaminocarbonyloxy, arylaminocarbonyloxy or aryl-substituted C1-4 alkylaminocarbonyloxy, aryl-substituted C1-4 alkyloxy, aryl group, heteroaryl group, C1-6 alkoxycarbonyl group, arylmethyloxycarbonyl group, carboxyl group, 5-tetrazolyl group, sulfo group ( -SO2OH ), or fluorosulfonyl group. The number of substituents that groups such as nitrogen-containing aromatic groups, aryl groups, aralkyl groups, heteroaryl groups, arylene groups, aralkylene groups, and phenyl groups may have is 1 to 5, preferably 1 to 3, and more preferably 1 or 2. Examples of cycloalkylene groups include cyclopentylene and cyclohexylene. Examples of halogen atoms include fluorine, chlorine, bromine, and iodine, with fluorine, chlorine, and bromine being preferred. The C1-6 linear or branched alkyl group may be linea