Patent EP-0765871-B1 (EP)
Inventor: WEIDMANN KLAUS DR
IPC: C07D215/48
Filed: 1996-09-20
Granted: 2004-03-31
Abstract: 3-Hydroxyquinoline-2-carboxamide derivs. (I) and their salts are new. A =1-4C alkylene (opt. mono- or disubstd. by V, 1-6C hydroxyalkyl, Ph, benzyl, OPh, benzyloxy, anilino, N-methylanilino, SPh, SOPh or SO2Ph; or opt. monosubstd. by 6-12C aryl, 6-12C aryloxy, 7-11C aralkyl or 7-11C aralkoxy (all opt. mono- to penta- substd. by V, OCF2Cl or O-CF2-CHFCl); or 1 or more Rx); V = halo, CN, NO2, CF3, 1-6C alkyl, 1-6C alkoxy, -O-(CH2)x-CfH(2f+1-g)Halg, 1-6C alkylthio, 1-6C alkylsulphinyl, 1-6C alkylsulphonyl, 1-6C alkylcarbonyl, 1-6C alkoxycarbonyl, CONH2 (opt. mono- or disubstd. by 1-4C alkyl), 1-6C alkylcarbonyloxy, 3-8C cycloalkyl or SO2NH2 (opt. mono- or disubstd. by 1-4C alkyl); B = COOH, CONHCOR''', CONHSOR''', CONHSO2R''', NHSO2CF3, tetrazolyl, imidazolyl or 3-hydroxyisoxazolyl; R''' = aryl, heteroaryl, 3-7C cycloalkyl or 1-4C alkyl, opt. monosubstd. by 6-12C aryl, heteroaryl, OH, SH, 1-4C alkyl, 1-4C alkoxy, 1-4C alkylthio, alkylsulphinyl or alkylsulphonyl, CF3, Cl, Br, F, I, NO2, COOH, 2-5C alkoxycarbonyl, mono- or di- (1-4C alkyl)amino or 1-4C perfluoroalkyl; R1-R5 =H, OH, halo, CN, CF3, NO2, COOH, V', OV', 1-12C alkyl or alkoxy (both substd. by 3-8C cycloalkyl, 3-8C cycloalkoxy or 1-20C alkoxy), 3-8C cycloalkyl-1-8C alkyl-1-6C alkoxy, 7-16C aralkenyl; 7-16C aralkynyl, retinyloxy, 1-12C alkoxy-1-12C alkyl, 1-12C alkoxy-1-8C alkoxy-1-8C alkyl, OV', 1-6C alkoxy (substd. by 6-12C aryloxy or 7-16C aralkoxy), 1-16C hydroxyalkyl, 1-8C alkyl (substd. by 6-16C aryloxy or 7-16C aralkoxy), 1-6C alkyl (substd. by OCyc-substd. 1-8C alkoxy, 1-12C alkyl-thio, -sulphinyl, -sulphonyl, 6-12C arylthio, etc., -O-(CH2)x-CfH(2f+1-g)Halg, 1-6C chlorofluoroalkoxy, COV', COCyc, cinnamoyl, COOV', COOCyc, OCOV", OCOCyc, cinnamoyloxy, OCOOV', OCOOCyc, CONH2 (opt. mono- or disubstd., by 1-12C alkyl or by 3-8C cycloalkyl), CONE, COÄNRq-CHRx-COÜs-T, carbamoyloxy (opt. mono- or disubstd. by 1-12C alkyl), OCONHCyc, NRyRz, 1-8C alkyl (substd. by 1-12C alkanoylamino, etc.), 1-20C alkyl-thio, -sulphinyl, -sulphonyl, 6-12C arylthio, etc.; or 2 adjacent gps. of R1-R5 form 3-5C n-alkylene or n-alkenylene (opt. with 1 or 2 CH2 replaced by O, S, SO, SO2 or NR'); V' = 1-20 C alkyl, 2-20C alkenyl or 2-20C alkynyl; V" = 1-12C alkyl, 2-12C alkenyl or 2-12C alkynyl; Cyc = 3-8C cycloalkyl, 6-12C aryl or 7-16C aralkyl; E = 3-7C n-alkylene (opt. with one CH2 replaced by O, S, 1-8C alkylimino, N(Cyc), 3-8C cycloalkyl-1-12C alkylimino or 1-12C alkoxy-1-6C alkylimino); Rx = L- or D- alpha -amino acid substit.; T = OH, OR, or NRqRq; Rq = independently H, 6-12C aryl, 7-11C aralkyl, 1-8C alkyl, 3-8C cycloalkyl, (+)-dehydroabietyl, 1-8C alkyl (substd. by 1-8C alkoxy, 7-12C aralkoxy or 6-12C aryloxy), 1-10C alkanoyl, opt. substd. 7-16C aralkanoyl or opt. substd. 6-12C aroyl; or Rq+Rq = 3-7C n-alkylene (opt. with one CH2 replaced by O, S, SO, SO2, N-acylimino, etc.); R' = H, 6-12C aryl, 1-8C alkyl (opt. substd. by 1-8C alkoxy, 7-12C aralkoxy or 6-12C aryloxy), 1-10C alkanoyl, opt. substd. 7-16C aralkanoyl or opt. substd. 6-12C aroyl; Ry, Rz = V", 1-12C alkoxy, 3-8C cycloalkyl, 6-12C aryl, 7-11C aralkyl, 7-12C aralkoxy, 1-12C alkanoyl, 3-8C cycloalkanoyl, 6-12C aroyl or 7-16C aralkanoyl; or Ry+Rz = 3-6C n-alkylene, opt. with 1 CH2 replaced by O, S, N-(1-4C alkyl)carbonylimino or N-(1-4C alkoxy)carbonylimino; f = 1-8; g = 0 - (2f+1); m = 0 or 1; s = 1-5; x = 0-3; aryl gps. are all opt. substd., (where two of the substits. may be fused to form a CH2 chain (opt. with a CH2 replaced by O, S, SO, SO2 or NR') or CH=CH-CH=CH).