Benzenesulphonyl-Ureas and process for preparing them

摘要

1,163,171. Benzenesulphonyl-ureas. FARBWERKE HOECHST A.G. 9 Sept., 1966 [10 Sept., 1965], No. 40409/66. Heading C2C. Novel benzenesulphonyl-ureas of Formula I X-CO-N(R)-Y-phenylene-SO 2 -NHCO-NH-R1, in which R is hydrogen, C 1-4 alkyl or phenyl- C 1-4 alkyl, R1 is a nortricyclyl or adamantyl radical and X is (a) a phenyl radical carrying in any desired position Z and Z1, which may be the same or different, wherein Z is hydrogen, halogen, C 1-4 alkyl, alkenyl, alkoxy, alkenyloxy, halogen-alkoxy, alkoxyalkoxy, phenalkoxy, phenalkyl, cycloalkoxy, phenyl, phenoxy, C 1-4 acyl, benzoyl, trifluoromethyl, hydroxy or C 1-4 alkoxy, and Z1 is hydrogen, halogen, C 1-4 alkyl, alkoxy, alkoxyalkoxy, halogen-alkoxy, acyloxy or hydroxy; (b) a naphthyl radical which may contain one or two substituents selected from halogen atoms and C 1-4 alkyl, C 1-4 alkoxy, hydroxy and acetoxy groups; (c) a tetrahydronaphthyl or indanyl radical; (d) a thienyl radical which may contain one or two substituents selected from C 1-4 alkyl, phenalkyl, alkoxy, alkoxyalkoxy, alkenyloxy, phenylalkoxy, halogen-alkoxy and aryl radicals and halogen atoms; or (e) a tetramethylene- or trimethylene - thienyl radical; and Y is a C 1-4 hydrocarbyl chain, and their salts, are prepared by (a) reacting a benzenesulphonyl-isocyanate, benzene - sulphonyl - carbamic acid ester, benzenesulphonylthiocarbamic acid ester, benzenesulphonylcarbamic acid halide or benzenesulphonylurea substituted by the group X-CO-N(R)-Y- with an R1-substituted amine or salt thereof, or (b) reacting a benzenesulphonamide of formula X-CON(R)-Y-phenylene-SO 2 -NH 2 or a salt thereof, with an R1-substituted isocyanate carbamic acid ester, thiocarbamic acid ester, carbamic acid halide or urea, or (c) hydrolysing a correspondingly substituted benzenesulphonyl-isourea ether, benzenesulphonyl - isothioether or benzenesulphonyl - parabanic acid, or (d) replacing in a correspondingly substituted benzenesulphonyl - thiourea the sulphur atom by an oxygen atom, or (e) introducing into a benzenesulphonyl-urea of formula HN(R)-Y-phenylene-SO 2 -NH-CONH-R1 the radical X-CO- by acylation and, if required, treating the reaction product with an alkaline agent, in order to effect salt formation. N [4 - (# - Benzamido - ethyl) - benzenesulphonyl] - N1 - nortricyclyl - urea is prepared by reacting 4 - (# - benzamidoethyl) - benzenesulphonamide with carbon disulphide and potassium hydroxide to form the potassium salt of N - [4 - # - benzamidoethyl) - benzenesulphonyl]- amino-dithiocarbonic acid and reacting a solution of this compound in methanol with nortricyclylamine followed by mercury oxide. Pharmaceutical compositions having hypoglycaemic activity, for oral administration, comprise a compound of Formula I, or a salt thereof, together with a carrier.