Patent EP-2145873-A1 (EP)
Inventor: LOPEZ ROMAN
IPC: A61K31/404
Filed: 2008-06-17
Abstract: Use of aminoadamantane compound (I) and benzodiazepine compound (II) and their salts for the preparation of a composition for the prevention and/or treatment of poisoning at least one toxin intracellular mode of action or at least a virus using the route of internalization to infect eukaryotic cells of mammals, is claimed. Use of aminoadamantane compound of formula (Cy-(-CH 2-) p-NR 2>-X-R 1>) (I) and benzodiazepine compound of formula (II) and their salts for the preparation of a composition for the prevention and/or treatment of poisoning at least one toxin intracellular mode of action or at least a virus using the route of internalization to infect eukaryotic cells of mammals, is claimed. Cy : benzen-1-yl (optionally substituted by W 1>) or adamantane group of formula (a); W 1>H or halo; Y 1>H or OH; Z : C or bond (when Cy is a noradamantyl core); either X : bond, or 1-6C alkyl (optionally saturated and substituted by phenyl, acid and/or 1-3C alkyl ester), where the chain being optionally interrupted by an oxygen atom, -CO-, -O-CO-, -CO-NH- or -S(=O)(=O)-; and R 1>1-21C cyclic or branched radical, optionally saturated, where one or more carbon atoms can be replaced by an atom of nitrogen, oxygen and/or sulfur (where the radical being optionally mono or bi-substituted with a halo, a function-COOH, -OH,-NO 2, 1-3C alkyl, 1-3C alkoxy or 1-3C acyloxy); and R 2>H, 1-3C alkyl (optionally saturated), 2-4C acyl radical, or 1-bromo-3-methyl-benzene moiety; or NXR 1>R 2>a ring, preferably imidazole, oxazole, triazole, benzimidazole, optionally partially saturated, dihydroimidazole, optionally substituted by a phenyl or pyridine radical; p : 0 or 1; A, B 1>C or N, provided that if A is N, then B 1>is C and if A is C, then B is N; R 3>halo, 1-6C alkyl, 1-6C alkoxy, or 1-6C acyloxy (all optionally substituted by 1-6C alkoxy), H, aryloxy or heteroaryloxy; R 4>bond, H, 1-3C acyloxy radical, 1-3C acyloxy radical, or phenyl; and R 5>H, 1-3C alkyl, 1-3C alkoxy, 1-3C acyloxy or phenyl radical (optionally substituted by OH and/or halo, 1-3C alkyl, 1-3C alkoxy, 1-3C acyloxy, NO 2, -CF 3, or group of formula (CH 3-CH=CH-O)). Provided that: when R 2>is a bond, the nitrogen atom bearing R 2>and X or the adjacent carbon atom (when p is 1) are linked by a double bond; when the Cy is adamantyl core, then the chain (-(-CH 2-) p-NR 2>-X-R 1>) is attached to the position 1 or 2; R 4>and R 5>can not simultaneously be a bond and when R 4>or R 5>is a bond, then A and B 1>are linked by a double bound; and when B 1>is a carbon atom, then R 5>may also form with the adjacent hydrogen atom a cycle containing 5-6 atoms (optionally substituted by a phenyl radical, and optionally interrupted by a nitrogen, oxygen or sulfur atom). Independent claims are included for: (1) the compound (I) (where (I) excludes: N-benzyladamantylamine, N-(3-hydroxybenzyl)adamantylamine, N-(3-methoxybenzyl)adamantylamine, N-(4-nitrobenzyl)adamantylamine, N-((pyridin-4-yl)methyl)adamantylamine, N-phenethyladamantylamine, N-(3-phenylpropyl)adamantylamine, N-benzyl-2-adamantylamine, N-(3-bromobenzyl)-2-methylpropan-2-amine, N-(3-bromobenzyl)cyclohexanamine, N-benzyl(3-bromophenyl)methanamine, N-(3-fluorobenzyl)(3-bromophenyl)methanamine, (E)-N-(3-bromobenzylidene)adamantylamine, (E)-N-(3-fluorobenzylidene)adamantylamine, (E)-N-benzylideneadamantylamine, N-1-adamantylbenzamide, N-2-adamantylbenzamide, N-adamantyl benzenesulfonamide, N-2-adamantyl benzenesulfonamide, 1-(adamantyl)-2,5-dihydrooxazole, adamantylamino-4-phenyl-1H-1,2,3-triazole, or (E)-2-(2-(5-methylthiophen-2-yl)vinyl)-N-phenylbenzamide); and (2) the compound (II) (where (II) excludes: 5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one, 7-bromo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one, 7-bromo-5-phenyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-2-one, 4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one, 4-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-one, 4,5-dihydro-7-methoxy-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one, 5-phenyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-2-one, 7-chloro-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one, 7-chloro-5-phenyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-2-one or 7-bromo-5-phenyl-4-propionyl-4,5-dihydro-1H-benzo[e][1,4]diazepin-2(3H)-one). [Image] [Image] ACTIVITY : Antidote. MECHANISM OF ACTION : None given.