Substituted 1,2-Dihydroquinoline-N-Carboxylic Acids and -Thioncarboxylic Acids

摘要

1,158,264. Substituted 1,2-dihydroquinoline- N-carboxylic and -thioncarboxylic acids. BRISTOL-MYERS CO. 12 Oct., 1966 [13 Oct., 1965], No. 45586/66. Heading C2C. Novel substituted 1,2-dihydroquinoline-N- carboxylic and -thioncarboxylic acids of the general formula wherein RSP1/SP, RSP2/SP and RSP3/SP are each hydrogen, chloro, bromo, iodo, fluoro, trifluoromethyl, C 1-6 alkyl, C 1 _ 6 alkoxy, C 1-6 alkylthio, C 1 _ 6 alkylsulphonyl, hydroxy, C 1 _ 6 alkanoyloxy, amino, alkoxycarbonylamino or a group of the formula (C 1 _ 6 alkyl) 2 N(CH 2 ) n - in which n is 0 or an integer from 1 to 3 inclusive, X is oxygen or sulphur, and RSP4/SP is a monovalent non- aromatic radical containing only carbon and hydrogen and having less than eleven carbon atoms, halo-C 1-6 alkyl other than α-haloalkyl,or aralkyl, and non-toxic, pharmaceutically acceptable acid addition salts thereof are prepared by reaction of a compound of the general formula X = CZ-O-RSP4/SP, wherein Z is a chlorine, bromine or iodine atom, with (a) a 1,2-dihydroquinoline of the general formula or (b) a quinoline of the general formula followed by reduction with an alkali metal borohydride; followed by optional conversion of the product to a non-toxic, pharmaceutically acceptable acid addition salt thereof. 1,2-Dihydroquinolines of the second general formula above are prepared by reduction of quinolines of the third general formula above. 5-Aminoquinoline is prepared by the hydrazine- Raney nickel reduction of 5-nitroquinoline. 1 - Ethoxycarbonyl - 5 - isocyanato - 1,2 - dihydroquinoline is prepared by distillation under vacuum of 1 -ethoxycarbonyl - 5 -ethoxycarbonylamino- 1,2-dihydroquinoline. Pharmaceutical compositions having analgesic, tranquilizing, sedative, depressant, anorexic and hypotensive activity comprise, as active ingredient, a substituted 1,2-dihydroquinoline- N-carboxylic or -thioncarboxylie acid of the first general formula above or a non-toxic, pharmaceutically acceptable acid addition salt thereof, together with an inert diluent or carrier.