New benzenesulphonyl ureas, processes for their manufacture and pharmaceutical preparations containing them

摘要

The invention comprises sulphonyl ureas of the formula and salts thereof with physiologically tolerable bases, wherein R is a C1- 6 alkyl group, X is a C2- 3 alkylene group and R1 is (a) a saturated or unsaturated aliphatic hydrocarbon radical of 2-8 carbon atoms which, when it contains 3-8 carbon atoms may be interrupted by an oxygen and/or sulphur atom, (b) an alicyclic hydrocarbon radical of 3-8 carbon atoms which may be interrupted by oxygen and/or sulphur, (c) a benzyl radical or (d) a b -phenethyl radical. The compounds are prepared by (a) reacting an appropriately substituted benzenesulphonyl isocyanate or a compound which during the reaction forms or behaves as an isocyanate, e.g. a benzenesulphonyl carbamic ester, thiocarbamic ester or carbamic halide or a benzenesulphonyl urea, N1-acyl urea or bis-benzenesulphonyl urea, with an amine R1NH2, (b) reacting an isocyanate of the formula R1NCO or a compound which forms or behaves as an isocyanate, e.g. a carbamic ester, thiocarbamic ester or carbamic halide, with a benzenesulphonamide; (c) reacting a guanidine, isourea ether, or a tertiary amine salt of a mono R1 substituted parabanic acid, with a benzenesulphonyl halide and converting the sulphonyl-isourea ether or sulphonyl-parabanic acid formed into a benzenesulphonyl urea, by hydrolysis; (d) treating a benzene sulphonyl-thiourea to replace the sulphur by an oxygen atom, e.g. by reaction with oxides of heavy metals or oxidizing agents; or (e) oxidizing the corresponding sulphenyl or sulphinyl ureas. 4 - (b - Methoxyethoxy) - benzenesulphonamide and 4 - (b - ethoxyethoxy) - benzenesulphonamide are made by reacting the appropriate b -alkoxyethoxybenzene with amidosulphonic acid, converting the resulting benzenesulphonic acid to the sulphonyl chloride by reaction with phosphorus pentachloride and reacting with ammonia. Pharmaceutical preparations for the oral treatment of diabetes comprise the above sulphonyl ureas or their salts with bases, e.g. alkali or alkaline earth metals in admixture or conjunction with a carrier, preferably in the form of tablets.