Patent AU-4301097-A (AU)
Title: Nitric ester derivatives and their use in urinary incontinence and other diseases
Inventor: SOLDATO PIERO DEL
IPC: A61P7/02
Filed: 1997-09-02
Abstract: The use of compounds of formula (I), or their salts, for the preparation of medicaments for the treatment of urinary incontinence, is new. A-X1-NO2 (I). A = R(COX)t; t = 0 or 1; X = O, NH or NR1c; R1c = 1-10C alkyl; when t = 1, R = (IAa), 2-((2-methyl-3-(trifluoromethyl)phenyl)amino)-3-pyrid-3-yl (i.e flunixin residue) (IAb), a group C(R1a)(R2a)(R3a) (IIA), (IIIA), a group (4) - i.e. indomethacin residue, 2-((2-phenylethyl)amino)-phenyl- (VAa1), 2-[(3-trifluoromethyl)-phenyl]-amino-phenyl- (VAa2), 2-[(2,6-dichloro-3-methylphenyl)amino]-phenyl (VAa3), 2-[(2,3-dimethylphenyl)amino]-phenyl- (VAa4), 2-[(3-chloro-2-methylphenyl)-amino]-phenyl- (VAa5), 2-[[3-(trifluoromethyl)phenyl]amino]-pyrid-3-yl (VAb1), 3-(aminosulphonyl)-5-(butylamino)-4-phenoxy-phenyl- (VAd1), [2,3-dichloro-4-(2-thienylcarbonyl)-phenoxy]-methyl- (VAd2), (2,3-dichloro-4-(2-methylene-1-oxobutyl)phenoxy)-methyl- (VAd3), 3-(aminosulphonyl)-4-phenoxy-5-(1-pyrrolidinyl)-phenyl (i.e. piretanide residue) (V Ad4); when t = 0, R = a group of formula (VAc1); 3-formylamino-6-phenoxy-4H-1-benzopyran-4-one-7-(N-methylsulphonamido)- (VAc2); a group of formula (VAc3), 4-(5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl) benzenesulphonamido (VAc4); 6-(2-(3-ethyl-2,3-dihydro-thiazolyl)thio-3H-isobenzofuran-1-one-5-(N-methyl-sulphonamido)- (VAc5); (3aalpha ,4alpha ,7alpha ,7aalpha )-4-chloro-N-(octahydro-4,7-methano-2H-isoindol-2-yl)benzamide-3-sulphonamido (VAe1); N-(((1-methylethyl)amino)carbonyl)4-((3-methylphenyl)amino)-3-pyrinesulphonamido (VAe2); 2-chloro-5-(1H-tetrazol-5-yl)-4-((2-thienylmethyl)amino)benzenesulphonamido, (VAe3); 3,4-dihydro-3-(phenyl-methyl)-6-(trifluoromethyl)-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulphonamido- (VAe4); 6-chloro-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulphonamido- (VAe5); 6-chloro-3,4-dihydro-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulphonamido (VAe6); (6-chloro-3-(chloromethyl)-3,4-dihydro-2-methyl-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulphonamido- (VAe7); 2-chloro-5-(2,3-dihydro-1-hydroxy-3-oxo-1H-isoindol-1-yl)-benzenesulphonamido- (VAe8); 2-chloro-5-(2,3-dihydro-2-methyl-1H-indol-1-yl-aminocarbonyl)-benzenesulphonamido- (VAe9); 7-chloro-1,2,3,4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-quinazoline-6-sulphonamido- (VAe10); 7-chloro-2-ethyl-1,2,3,4-tetrahydro-4-oxo-quinazoline-6-sulphonamido- (VAe11), 2-chloro-4-(furan-2-yl-methylamino)-5-carboxy-benzenesulphonamido- (VAe12); Rii5 = H or 1-3C alkyl; Rii6 = H or 1-3C alkyl or when Rii5 = H, Rii6 may be benzyl; Rii1, Rii2 and Rii3 = H, 1-6C alkyl, 1-6 alkoxy, Cl, F or Br; Rii4 = Rii1 or bromine; R2a and R3a = H, 1-12C alkyl or allyl with the proviso that when one of R2a and R3a = allyl, the other = H; R1a = e.g. 4-(thien-2-ylcarbonyl)-phenyl, 3-phenoxy-phenyl, N-methyl-5-(4-methylphenylcarbonyl)-pyrrol-2-yl- or 4-phenyl-phenylcarbonyl-methyl-; at least one of Rivd and Rivd1 is H and the other 1-6C alkyl or 1-6C difluoroalkyl; or Rivd+Rivd1 = methylene; Riv = (xii)-(xiv); Riv-ii = 1-6C alkyl, 3-7C cycloalkyl, 1-7 C alkoxymethyl, 1-3C trifluoroalkyl, vinyl, ethynyl, halogen, 1-6C alkoxy, 1-7C difluoroalkoxy, 1-7C alkoxymethyloxy, 1-7C alkylthiomethoxy, 1-7C alkyl-methylthio, cyano, difluoromethylthio, substituted phenyl- or phenyl 1-8C alkyl; Riv-iii = 2-5C alkyl, 2-3C alkyloxy, allyloxy, phenoxy, phenylthio or 5-7C cycloalkyl, optionally substituted at position 1 by 1-2C alkyl; Rvac1 = phenyl or cyclohexane; X4 = sulphur or oxygen; X1 = e.g. -YO; Y = 1-20C alkylene or optionally substituted 5-7C cycloalkylene.