Patent EP-2338485-A1 (EP)
IPC: A61P29/00
Filed: 2009-12-14
Abstract: Substituted 1,3-dioxoisoindoline compounds (I) and their racemic mixtures, enantiomers, diastereomers, mixture of enantiomers, diastereoisomers or a single enantiomer or diastereoisomer and/or their salts are new. Substituted 1,3-dioxoisoindoline compounds of formula (I) and their racemic mixtures, enantiomers, diastereomers, mixture of enantiomers, diastereoisomers or a single enantiomer or diastereoisomer and/or their salts are new. X : -C(=O)-NH-, -NH(C=O)- or aryl group of formula (a1); R1 : OR6 or NR6R7; R6-R9 : H, 1-10C-alkyl (optionally saturated, optionally branched, optionally substituted by one or more substituents), 3-10C-cycloalkyl or heterocyclyl (both optionally bridged by 1-8C-alkyl, optionally saturated, optionally substituted by one or more substituents) or (hetero)aryl (optionally substituted by one or more substituents and optionally bridged by 1-8C-alkyl), where the alkyl chain is optionally branched, optionally saturated and optionally substituted by one or more substituents; either R2-R5 : H, F, Cl, Br, I, OR8, SR8, C(=O)OR8, CN, CF 3, NO 2, NR8R9, 1-10C-alkyl (optionally saturated, optionally branched, optionally substituted by one or more substituents), 3-10C-cycloalkyl or heterocyclyl (both optionally bridged by 1-8C-alkyl, optionally saturated, optionally substituted by one or more substituents) or (hetero)aryl (optionally substituted by one or more substituents and optionally bridged by 1-8C-alkyl), where the alkyl chain is optionally branched, optionally saturated and optionally substituted by one or more substituents; or R4CR5 : C(=O)-NR10-C(=O)-; and R10 : 1-10C-alkyl (optionally saturated, optionally branched, optionally substituted by one or more substituents), 3-10C-cycloalkyl or heterocyclyl (both optionally bridged by 1-8C-alkyl, optionally saturated, optionally substituted by one or more substituents) or (hetero)aryl (optionally substituted by one or more substituents and optionally bridged by 1-8C-alkyl), where the alkyl chain is optionally branched, optionally saturated and optionally substituted by one or more substituents, where the alkyl-, heterocyclyl- and cycloalkyl-substituents are F, Cl, Br, I, NO 2, CN, =O, CF 3, 1-8C-alkyl, (hetero)aryl, 3-10C-cycloalkyl, heterocyclyl, C(=O)OH, C(=O)O-1-8C-alkyl, C(=O)O-3-10C-cycloalkyl, C(=O)O-(hetero)aryl, C(=O)NH 2, C(=O)NH-1-8C-alkyl, C(=O)NH-3-10C-cycloalkyl, C(=O)NH-(hetero)aryl, C(=O)N(1-8C-alkyl) 2, C(=O)N(3-10C-cycloalkyl) 2, C(=O)N((hetero)aryl) 2, C(=O)N(1-8C-alkyl) (3-10C-cycloalkyl), C(=O)N(1-8C-alkyl)((hetero)aryl), C(=O)N(3-10C-cycloalkyl)((hetero)aryl), C(=O)N(aryl)(heteroaryl), OH, OCF 3, O-1-8C-alkyl, O-3-10C-cycloalkyl, O-(hetero)aryl, O-C(=O)-1-8C-alkyl, O-C(=O)-3-10C-cycloalkyl, O-C(=O)-(hetero)aryl, SH, SCF 3, S-1-8C-alkyl, S-3-10C-cycloalkyl, S-(hetero)aryl, NH 2, NH-1-8C-alkyl, NH-3-10C-cycloalkyl, NH-(hetero)aryl, N(1-8C-alkyl) 2, N(3-10C-cycloalkyl) 2, N((hetero)aryl) 2, N(1-8C-alkyl)(3-10C-cycloalkyl), N(1-8C-alkyl)((hetero)aryl), N(3-10C-cycloalkyl)((hetero)aryl), N(aryl)(heteroaryl), NH-C(=O)-1-8C-alkyl, NH-C(=O)-3-10C-cycloalkyl and NH-C(=O)-(hetero)aryl, and the (hetero)aryl substituents are F, Cl, Br, I, NO 2, CN, CF 3, 1-8C-alkyl, (hetero)aryl, 3-10C-cycloalkyl, heterocyclyl, C(=O)OH, C(=O)O-1-8C-alkyl, C(=O)O-3-10C-cycloalkyl, C(=O)O-(hetero)aryl, C(=O)NH 2, C(=O)NH-1-8C-alkyl, C(=O)NH-3-10C-cycloalkyl, C(=O)NH-(hetero) aryl, C(=O)N(1-8C-alkyl) 2, C(=O)N(3-10C-cycloalkyl) 2, C(=O)N((hetero)aryl) 2, C(=O)N(1-8C-alkyl)(3-10C-cycloalkyl), C(=O)N(1-8C-alkyl)((hetero)aryl), C(=O)N(3-10C-cycloalkyl)((hetero)aryl), C(=O)N(aryl)(heteroaryl), OH, OCF 3, O-1-8C-alkyl, O-3-10C-cycloalkyl, O-(hetero)aryl, O-C(=O)-1-8C-alkyl, O-C(=O)-3-10C-cycloalkyl, O-C(=O)-(hetero)aryl, SH, SCF 3, S-1-8C-alkyl, S-3-10C-cycloalkyl, S-(hetero)aryl, NH 2, NH-1-8C-alkyl, NH-3-10C-cycloalkyl, NH-(hetero)aryl, N(1-8C-alkyl) 2, N(3-10C-cycloalkyl) 2, N((hetero)aryl) 2, N(1-8C-alkyl)(3-10C-cycloalkyl), N(1-8C-alkyl)((hetero)aryl), N(3-10C-cycloalkyl)((hetero)aryl), N(aryl)(heteroaryl), NH-C(=O)-1-8C-alkyl, NH-C(=O)-3-10C-cycloalkyl or NH-C(=O)-(hetero)aryl. [Image] [Image] ACTIVITY : Analgesic; Antimigraine; Neuroprotective; Nootropic; Antiparkinsonian; Anticonvulsant; Eating-Disorders-Gen.; Anabolic; Anorectic; Ophthalmological; Neuroleptic; Antidiabetic; Antidepressant; Anesthetic; Antiemetic; Antiaddictive; Respiratory-Gen.; Laxative. MECHANISM OF ACTION : Vesicular glutamate transporter 1 modulator; Vesicular glutamate transporter 2 modulator. The ability of (I) to inhibit vesicular glutamate transporter 1 was tested in rats. The results showed that 2-(4-(5-(2-carboxy-4-hydroxyphenylcarbamoyl)-1,3-dioxoisoindolin-2-yl)benzamido)-5-hydroxybenzoic acid exhibited an inhibitory activity of 98%.