Benzolsulfonylharnstoffe und Verfahren zu ihrer Herstellung

摘要

1,125,591. Sulphonyl ureas. FARBWERKE HOECHST A.G. 19 Nov., 1965 [21 Nov., 1964], No. 49279/65. Heading C2C. Novel benzenesulphonyl ureas of the formula and salts thereof, wherein R is hydrogen, C 1-4 alkyl or phenyl-C 1-4 alkyl; R1 represents (a) C 2-8 alkyl, alkenyl or mercaptoalkyl, (b) C 4-8 alkoxyalkyl, alkylmercaptoalkyl or alkylsulphinylalkyl, (c) lower phenylalkyl or phenylpropyl, (d) lower cyclohexylalkyl, cycloheptylmethyl, cycloheptylethyl or cyclooctylmethyl, (e) an endoalkylene-cyclohexyl, -cyclohexenyl, -cyclohexylmethyl or -cyclohexenylmethyl radical having 1 or 2 carbon atoms in the endoalkylene part, (f) lower alkyl- or lower alkoxycyclohexyl, (g) C 5-8 cycloalkyl, (h) cyclohexenyl or cyclohexenylmethyl, (i) a heterocyclic ring having 4 or 5 carbon atoms and 1 oxygen or sulphur atom which may have up to 2 ethylenic double bonds or (k) a heterocyclic ring linked to the adjacent N-atom through a CH 2 group and containing 1 oxygen or sulphur and optionally up to 2 ethylenic double bonds; X represents (a) C 1-8 alkyl, alkenyl or haloalkyl, (b) C 3-8 alkoxyalkyl or alkylmercaptoalkyl, (c) a phenylalkyl radical having 1-6 alkyl carbon atoms optionally having 1 or more double bonds in the alkylene chain and/or substituents on the phenyl group, (d) a C 3-8 cycloalkyl group or corresponding cycloalkyl-alkyl group, (e) an endoalkylene - cyclohexyl, -cyclohexenyl, -cyclohexylmethyl or -cyclohexenylmethyl radical containing 1 or 2 endoalkylene carbon atoms, (f) a lower alkyl- or alkoxy-cyclohexyl radical, (g) a cycloalkoxyalkyl or phenoxyalkyl radical of 2-4 alkyl carbon atoms, (h) a cyclohexenyl or cyclohexenylmethyl radical, (i) a heterocyclic ring linked to the oxygen atom through a CH 2 group and containing 4 or 5 carbon atoms and 1 oxygen or sulphur atom and which may contain up to 2 ethylenic double bonds, and Y is a C 1-4 hydrocarbon chain, are made by known methods for the synthesis of benzenesulphonyl ureas, e.g. reaction between a benzenesulphonyl isocyanate or its equivalent and an R1 substituted amine; reaction between a benzenesulphonamide and an isocyanate R1NCO, conversion of corresponding benzenesulphonyl isourea ethers, parabanic acids, isothiourea ethers or thioureas and oxidation of corresponding benzenesulphenyl or benzenesulphuryl ureas, and also by introducing the radical X-O-CO into the appropriate aminosubstituted benzenesulphonyl urea. N - [4 - (Carbomethoxyamido - ethyl) - benzenesulphonyl]> N1 - isobutyl and N1 - phenylethylthioureas are made by reaction of 4-(#-carbomethoxyamidoetbyl) benzenesulphonamide with isobutyl mustard oil and phenylethyl mustard oil respectively. Pharmaceutical preparations for the treatment of diabetes mellitus comprise the above compounds of the invention in admixture or conjunction with a carrier, preferably in a form adapted to oral administration.