Patent GB-1185395-A (GB)
Title: Benzenesulphonyl-Ureas and process for preparing them
IPC: C07D209/08
Filed: 1967-05-11
Abstract: 1,185,395. Benzenesulphonyl-ureas. FARBWERKE HOECHST A.G. 11 May, 1967 [14 May, 1966], No. 21972/67. Heading C2C. Novel benzenesulphonyl-ureas I (including salts thereof) in which R represents an alkyl radical (C 1  to C 3 ) and may also represent a grouping derived from said radical which is bound at the oposition of the benzene nucleus to which the nitrogen atom is bound thus forming a heterocyclic ring, R<SP>1</SP> represents: (a) an alkyl or alkenyl radical (C 3 -C 6 ), (b) an endoalkylene-cyclohexyl, endoalkylene-cyclohexenyl, endoalkylene-cyclohexylmethyl or endoalkylenecyclohexenylmethyl radical containing 1 or 2 endoalkylene carbon atoms, (c) a C 1  to C 4  alkyl-cyclohexyl or dialkyl-oyclohexyl radical, (d) a cycloalkyl radical containing 5 to 8 carbons which may be substituted by alkyl or linked to the nitrogen atom by means of alkylene, (e) a cyclohexenyl or cyclohexenylmethyl radical, or (f) a nortricyolyl or adamantyl radical, X and X<SP>1</SP> may be the same or different and represent a hydrogen atom, alkyl or alkoxy radical or halogen atom or when X is hydrogen X<SP>1</SP> may also be a -CF 3  or -NO 2  group or X and X<SP>1</SP> may together represent a methylenedioxy group and Y represents a hydrocarbon straight or branched chain containing 2 or 3 carbons, are prepared: (a) by the interaction of an amine, R<SP>1</SP>NH 2 , or salt thereof and a benzenesulphonyl-isocyanate, -carbamic acid ester, -thiolcarbamic acid ester, -urea, -semicarbazide or -carbazone which is substituted at the 4-position by the Group II (b) by the interaction of a corresponding benzenesulphonamide (prepared by acylating the appropriate amino-alkylbenzene-sulphonamide) substituted at the 4-position by the Group II and an R<SP>1</SP>-substituted isocyanate, carbamic acid ester, thiolcarbamic acid ester, carbamic acid halide or urea, (c) by hydrolysis of compounds comprising the above group attached at -Y- to the 4-position of a benzenesulphonylisourea ether, -isothiourea ether, -haloformic acid amidine or -parabamic acid, (d) by replacement of the thiocarbonyl sulphur atom in the corresponding benzenesulphonylthioureas by an oxygen atom, (e) by hydrogenating the corresponding benzenesulphonylureas containing unsaturation, or (f) by acylating a benzene-sulphonyl-urea of the formula N- [4 - (# -Indolino - carbamoylethyl ) benzenesulphonyl]-urea and N-[4-(#-<N-phenyl-N-methylureido> -ethyl) benzenesulphonyl]-urea are prepared by the interaction of the corresponding benzenesulphonamide and potassiumisocyanate. N.[4.-(#-Indolino-carbamoylethyl) benzenesulphonyl] - N<SP>1</SP> - (2,5 - endomethylene - cyclohexylmethyl)-thiourea and N-[4-(#- <N-methyl-N- phenyl - ureido> ethyl) - benzenesulphonyl]-N<SP>1</SP>- cyclohexyl-thiourea are prepared by the interaction of the corresponding benzenesulphonamide and 2,5-endomethylene-cyclohexylmethyl isothiocyanate or cyclohexyl isothiocyanate respectively. N - [4 - (# - Indolinocarbamoylethyl) benzenesulphonyl] - N<SP>1</SP> - (2,5 - endomethylene-cyclohexylmethyl) - isoureamethylether is obtained by treating the above corresponding thiourea with HgO(MeOH. 4 - [# - (N - 4 - Chlorophenyl - - N - methyl - ureido) ethyl]-benzenesulphonyl-methyl-urethane is prepared from the corresponding benzenesulphonamide and methyl chloroformate. Pharmaceutical preparations having hypoglycaemic activity comprise compounds I in admixture or conjunction with a carrier, preferably in a form adapted to oral administration, e.g. tablets.