Patent GB-808073-A (GB)
Title: Manufacture of new sulphonyl-ureas
IPC: C07C311/54
Filed: 1956-05-08
Abstract: The invention comprises sulphonyl-urea derivatives of the general formula <FORM:0808073/IV (b)/1> in which R1 is an aliphatic or cycloaliphatic hydrocarbon radical of 2 to 8, preferably 3 to 5, carbon atoms, R2 is a chlorine or bromine atom and R3 is hydrogen, chlorine or bromine or an alkyl or alkoxy radical of 1 to 6 carbon atoms, and physiologically tolerable salts of these compounds. Preferred compounds are the p-chloro-or p-bromo-benzenesulphonyl ureas in which R1 is an aliphatic or cycloaliphatic hydrocarbon radical of 3-5 carbon atoms.  The products are made by known methods for the production of sulphonyl ureas, for example, (1) a halogen substituted benzene-sulphonyl isocyanate is reacted with an aliphatic or cycloaliphatic amine or a halogen-substituted benzene sulphonamide is reacted with an aliphatic or cycloaliphatic isocyanate; in place of the isocyanate a compound convertible to an isocyanate in the course of the reaction such as an azide may be used, or a urethane or carbamic acid halide; (2) a halogeno-phenyl-sulphonyl urea is treated with an alkylamine, alkenylamine, cycloalkylamine or cycloalkyl-alkyl-amine, or alternatively an alkyl-urea may be reacted with a halogenated benzenesulphonamide; in place of the alkyl urea, a corresponding iso-urea ether may be used which is reacted with a halogenated benzene-sulphonyl chloride; (3) a corresponding thiourea compound is first formed and sulphur is eliminated therefrom by known methods, e.g. by treatment with a heavy metal oxide or salt; and (4) an N-halogeno-benzene sulphonyl-N1-alkyl-guanidine is prepared, for example by reacting a halogeno - benzenesulphonyl - cyanamide with a primary amine, and is then hydrolysed.  The products are used in the treatment of diabetes.  Examples describe the preparation of N - 4 - chlorobenzenesulphonyl -, N - 4 - bromobenzenesulphonyl - and N - (4 - methyl - 3-chlorobenzenesulphonyl-derivatives of N1-n-butyl - urea; N - 4 - chlorobenzenesulphonyl-N1 - cyclohexyl - urea and N - (4 - methyl - 3-chlorobenzenesulphonyl) - N1 - isobutyl - urea.  4 - Methyl - 3 - chlorobenzenesulphonyl - carbamic acid ethyl ester is made by the action of ethyl chlorocarbonate on 4-methyl-3-chlorobenzene sulphonamide.ALSO:Anti-diabetic preparations for oral administration comprise compounds of the formula <FORM:0808073/VI/1> in which R1 is an aliphatic or cycloaliphatic hydrocarbon radical of 2-8 carbon atoms such as an ethyl, propyl, allyl, butyl, butenyl, pentyl, hexyl, cyclohexyl or hexahydrobenzyl group, R2 is a chlorine or bromine atom and R3 is hydrogen, chlorine or bromine or an alkyl or alkoxy group of 1-6 carbon atoms or physiologically tolerable salts of these compounds, in admixture with a pharmaceutically suitable carrier. The preparations suitably take the form of tablets, pills, capsules, cachets, mixtures, solutions or powders, containing, for example, 0.5 grams of sulphonyl urea compound per dosage unit. Many suitable active compounds are specified (see Group IV (b)). In an example, N - (4 - chlorobenzenesulphonyl) - N1-n-butyl-urea is made into tablets with wheat or maize starch, talc and magnesium stearate; in place of the above sulphonyl urea, the corresponding N-(3-chlorobenzenesulphonyl) N1-n-butyl urea or N-(3-chloro-4-methylbenzenesulphonyl)-N1-isobutyl urea may be used.