Patent GB-1116355-A (GB)
Title: Benzenesulphonyl-ureas and process for preparing them
IPC: C07D333/38
Filed: 1965-08-02
Abstract: Novel benzenesulphonyl ureas of the formula X - CO - NR - Y - phenylene - SO2-NH-CO-NHR1 in which R is hydrogen, lower alkyl or lower phenylalkyl, R1 represents (a) C2- 8 alkyl, alkenyl or mercapto alkyl; (b) C4- 8 alkoxyalkyl, alkylmercaptoalkyl or alkysulphinylalkyl having at least 2 carbon atoms in the alkylene part of the radical; (c) phenyl-lower alkyl or phenylcyclopropyl; (d) cyclohexyl - lower alkyl, cycloheptylmethyl, cycloheptylethyl or cyclooctylmethy; (e) endoalkylene - cyclohexyl, endoalkylene-cyclohexenyl, endoalkylene - cyclohexylmethyl or endoalkylene - cyclohexenylmethyl, having 1 or 2 endoalkylene carbon atoms; (f) lower alkyl- or lower alkoxycyclohexyl; (g) C5- 8 cycloalkyl; (h) cyclohexenyl or cyclohexenylmethyl; (i) a heterocyclic ring with 4 or 5 carbon atoms and one O or S atom, optionally containing one or two ethylenic double bonds; or (k) a heterocyclic ring as in (i) linked to the nitrogen atom through a -CH2- linkage, X represents (a) thiophenyl or thiophenoxy optionally containing 1 or 2 halogen, lower alkyl, lower alkoxy, lower alkenyloxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy or aryl substituents or a -(CH2)3- or -(CH2)4-chain linked at both ends to the thiophene nucleus; (b) furyl optionally bearing halogen or methyl substituents; or (c) pyridyl optionally bearing 1 or 2 halogen or lower alkyl substituents, the radicals specified under (a), (b) and (c) being linked to the rest of the molecule directly or through a hydrocarbon chain of 1 or 2 carbon atoms, and Y is a hydrocarbon chain of 1-4 carbon atoms (the word "lower" throughout indicating a group having up to 4 carbon atoms), are made by the following processes:  (a) reacting a benzenesulphonyl-isocyanate, -carbamic ester, -carbamic halide, -thiocarbamic ester or -urea, substituted by the group X.CO.NR.Y- with an amine R1NH2; (b) reacting a benzenesulphonamide, X.CO.NR.Y.-phenylene. SO2NH2, with an R1-substituted isocyanate, carbamic acid ester, thiocarbamic acid ester, carbamic halide or urea; (d) hydrolysing a correspondingly substituted benzenesulphonyl-isourea ether, -isothiourea ether or parabanic acid; (e) replacing the sulphur atom in a correspondingly substituted benzenesulphonyl-thiourea by an oxygen atom; (f) oxidizing a corresponding benzenesulphinyl or benzenesulphenyl urea; or (g) introducing the radical X-CO- by acylation into a benzenesulphonyl urea of the formula R.NH.Y.-phenylene.SO2.NH.CO.NHR1., and if desired treating the reaction products with an alkaline agent to form the salts.  The preparation of 4 - (b  - thiophene - 2 - carbonamido - ethyl) - benzenesulphonamide, 4-(b  - 5 - chlorothiophene - 2 - carbonamidoethyl)-benzenesulphonamide, N - [4 - (b  - thiophene - 2-carbonamidoethyl) - benzenesulphonyl] - N1-cyclohexyl thiourea, N - [4 - (b  - thiophene - 2-carbonamidoethyl) - benzenesulphonyl] - N1-cyclohexylisourea methyl ether, 4 - (b  - furoylaminoethyl) - benzenesulphonamide, 4 - (b -furyl - 2 - propionamidoethyl) - benzenesulphonamide, N - [4 - (b  - furoylaminoethyl) - benzenesulphonyl] - carbamic acid methyl ester, N-[4-(b  - furoylaminoethyl) - benzenesulphonyl] - urea, N - [4 - (b  - furoylaminoethyl) - benzenesulphonyl]-N1 - isobutyl urea, N - [4 - (b - furoylaminoethyl) - benzenesulphonyl] - N1 - isobtuyl - isourea methyl ether and 4-(pyridine-3-carboxamidomethyl) -benzenesulphonamide, used as starting materials, is described. 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 adapted to oral administration.