Patent GB-876608-A (GB)
Title: Manufacture of new sulphonyl-ureas
Filed: 1957-12-06
Abstract: The invention comprises sulphonyl ureas of the formula C6H5-(CH2)n-SO2-NH-CO-NHR1\t (wherein R1 is an aliphatic or cycloaliphatic, saturated or unsaturated hydrocarbon radical containing 2 to 8 carbon atoms, or a saturated or unsaturated, open chain or cyclic hydrocarbon radical interrupted by oxygen and containing 3 to 8 carbon atoms, or the radical -(CH2)n-C6H5 and n is an integer from 2 to 4) and their salts with bases yielding physiologically tolerable salts, pharmaceutical preparations containing these compounds (see Group VI), and the preparation of the sulphonyl ureas by the following processes: (a) reacting an aralkylsulphonyl isocyanate C6H5(CH2)n-SO2-NCO or a corresponding urethane or carbamyl halide with an amine R1NH2; (b) reacting an isocyanate R1NCO or a corresponding urethane or carbamyl halide with an aralkylsulphonic acid amide or preferably a salt thereof; (c) reacting a compound C6H5(CH2)n-SO2-NHCONHX (wherein X represents a hydrogen atom or an acyl group) with an amine R1NH2; (d) reacting a compound R1NHCONH2 or an N-acyl or N-nitro derivative thereof with an aralkylsulphonic acid amide or a salt thereof; (e) reacting an isourea ether with an aralkylsulphonic acid halide and hydrolysing the product; (f) desulphurizing an aralkylsulphonylthiourea by means of a heavy metal oxide in the presence of a solvent, or by oxidation, e.g. with sodium peroxide or nitrous acid; or (g) hydrolysing a corresponding aralkylsulphonylguanidine (obtainable by reacting an aralkylsulphonylcyanamide with a primary amine, or an aralkylsulphonic acid chloride with an alkylguanidine in the presence of alkali).  N-(2-Phenylethane-(1)-sulphonyl)- carbamic acid methyl ester is prepared by reacting 2-phenylethane-(1)-sulphonamide w with methyl chloroformate in the presence of potassium carbonate and acetone.  3-Phenylpropane-(1)- and 4-phenylbutane-(1)-sulphonamides are prepared by reacting benzene with propane sultone and butane sultone respectively, in the presence of anhydrous aluminium chloride, and converting the resulting sulphonic acids to their amides via the acid chlorides.  Specifications 808,071, 808,072, 808,073, 814,234, 815,885 and 822,090 are referred to.ALSO:Preparations suitable for oral administration for lowering the blood sugar level comprise a compound of the general formula <FORM:0876608/VI/1> (wherein n is an integer from 2 to 4 and R1 represents an aliphatic or cycloaliphatic, saturated or unsaturated hydrocarbon radical of 2-8 carbon atoms, or a saturated or unsaturated, open-chain or cyclic hydrocarbon radical interrupted by oxygen and containing 3-8 carbon atoms, or the radical -(CH2)n-C6H5) or a salt thereof with a base yielding physiologically tolerable salts, in admixture with a pharmaceutically suitable carrier.  If desired, the free sulphonamides may be administered in conjunction with substances forming physiologically tolerated salts therewith, e.g. ammonnia, alkali or alkaline-earth metal hydroxides, alkali metal carborates or bicarbonates, or organic bases.  Specifications 808,071, 808,072, 808,073, 814,234, 815,885 and 822,090 are referred to.