GB953097A - New benzenesulphonyl ureas and process for their manufacture - Google Patents

Abstract

The invention comprises compounds of the formula: <FORM:0953097/C2/1> in which X is oxygen or sulphur and R1 is a saturated or unsaturated aliphatic or alicyclic hydrocarbon radical of 2 to 8 carbon atoms, with the exception of n-propyl and n-butyl, or is an alkyl or cycloalkyl radical of 4-8 carbon atoms, interrupted by an oxygen and/or sulphur atom or is a benyyl or b -phenethyl radical, and salts of these compounds with physiologically tolerable bases. The compound are made by standard methods for the preparation of sulphonyl ureas e.g. by reacting a benzenesulphonyl isocyanate, carbamic ester, carbamic halide or mono-thiocarbamic ester or a benzenusulphonyl urea, N1-acyl urea or bis benzenesulphonyl urea with an amine R1-NH2 or conversely by reaction of a benzenesulphonamide with an isocyanate R1NCO, a carbamic ester R1-NH-COOR2, wherein R2 is alkyl or phenyl, or a carbamic halide. The sulphonyl ureas may also be made by forming a benzenesulphonyl isourea ether, benzenesulphonyl guanidine, benzenesulphonyl parabamic acid or benzenesulphony thiourea and converting these by known means such as hydrolysis or oxidation into the desired sulphonyl urea. Products are specified in which R1 is a cycloheptyl, isobutyl, cyclooctyl or cyclohexyl group. N-(4-Trifluoromethoxy - benzenesulphony)-N1-cyclohepty thiourea is made by reaction of 4-trifluoromethoxy - benzenesulphonamide with cycloheptyl mustard oil. 4-Tribluoromethylthio - benzenesulphonamide is made by diazotising trifluoromethyl 4-aminophenyl sulphide and reacting the product with sulphur dioxide and cuprous chloride in glacial acetic acid to give trifluoromethylthio - benzenesulphonyl chloride which is then treated with ammonia. Methyltrifluoroemthoxy-benzenesulphony -urethane is prepared by reaction of 4-trifluoromethoxy-benzensulphonamide and chloroformic ester. N-Trifluoromethoxy - benzenesulphony - N1-acetyl urea is made by the action of acetic anhydride on trifluoromethoxy-benzenesulphonyl urea. N,N-diphenyl-N1-cycloheptyl urea is prepared from dephenyl carbamoyl chloride and cycloheptylamine. Pharmaceutical preparations for oral treatment of diabetes mellitus comprise the above compounds of the invention in admixture or conjunction with a carrier, preferably in the form of a tablet.