Analogifremgangsmåde til fremstilling af benzensulfonylurinstoffer eller salte deraf.

摘要

The invention comprises sulphonyl ureas of the formula and their physiologically tolerable salts, wherein R1 is a C1- 8 alkyl, C5- 8 cycloalkyl or ((C5- 8 cycloalkyl)-alkyl group having 1-3 carbon atoms in the alkyl portion, X is a hydrocarbon group of 1 or 2 carbon atoms, e.g. methylene, ethylene, ethenylene or ethylidene and R2 is (a) a C2- 8 alkyl group, (b) a phenyl-C1- 3 alkyl or cyclohexyl-C1- 3 alkyl group, (c) an endoalkylenecyclohexyl, -cyclohexenyl, -cyclohexylmethyl or -cyclohexenylmethyl group containing 1 or 2 endoalkylene carbon atoms, (d) a C1- 4-alkylcyclohexyl group, or (e) a C5- 8 cycloalkyl group. The compounds are prepared by (a) reaction of an R1OOC.X- substituted benzenesulphonamide (suitably in the form of a salt) with an isocyanate R2CNO or a corresponding carbamic acid ester or halide, thiocarbamic ester, urea or N2-substituted urea, (b) reaction of an amine R2NH2 or a salt thereof with a benzenesulphonyl urea isocyanate, R1OOC.X.C6H4.SO2-NCO or a corresponding carbamic ester or halide, thiocarbamic ester, urea or N2-substituted urea, (c) reaction of a benzenesulphonyl chloride R1OOC.X.C6H4.SO2Cl with an R2 substituted urea, isourea ether, isothiourea ether or parabanic and hydrolysis of a benzenesulphonyl isourea ether, isothiourea ether or parabanic acid obtained in this way or by another method, (d) exchange of the sulphur atom in a corresponding benzenesulphonylthiourea for an oxygen atom by oxidation or reaction with a heavy metal salt, and (e) oxidation of a corresponding benzenesulphenyl or benzenesulphinyl urea. If desired, carboxylic acids HOOC.X.C6H4.SO2.NH.CO.NHR2 formed by the above reactions or in another way may be esterified to introduce the group R1. Alternatively a compound wherein X is -CH = CH- may be hydrogenated to form a product wherein X is -CH2-CH2-. 4 - Sulphamoyl - phenylacetic acid is made by chlorosulphonating phenylacetic acid and reacting the resulting acid chloride with ammonia. N - (4 - Carbo - n - butoxy - methyl - benzenesulphonyl)-urea is made by the action of potassium cyanate on the corresponding benzenesulphonamide. 4 - b - Carbethoxyvinyl - benzenesulphonamide is made by esterifying the free acid. N - 4 - Carbethoxymethyl - benzenesulphonyl - N1-cyclohexyl-urea is made by the action of chloroformic methyl ester on the corresponding sulphonamide. Pharmaceutical preparations for the treatment of diabetes comprise the above compounds of the invention in admixture or conjunction with a carrier, preferably in a form suitable for oral administration such as tablets.