Aryl Sulphonyl Ureas

摘要

1,176,288. Sulphonyl-ureas. FARBENFABRIKEN BAYER A.G. 28 Oct., 1968 [2 Nov., 1967; 2 Jan., 1968; 2 Sept., 1968], No. 51080/68. Heading C2C. Novel compounds (including salts thereof) of the general Formula (I) wherein R is hydrogen or alkyl, R1 and R11 each signify hydrogen, halogen, alkyl, aryl, aralkyl or cycloalkyl which may be substituted by at least one halogen atom or alkyl, alkoxy or -CF 3 group, or R1 and R11 may be joined together to constitute an alkylene chain, R111 and R1111 each signify hydrogen, alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, tetrahydrofurfuryl, phenoxyalkyl, unsubstituted or alkyl substituted cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, bicycloalkyl, bicycloalkylalkyl, tricycloalkyl, tricycloalkylalkyl, tetracycloalkyl, tetracycloalkyl-alkyl, aryl or aralkyl which may be substituted by at least one halogen atom, or alkyl, alkoxy or -CF 3 group, or, together with the adjacent nitrogen atom comprise a monocyclic or polycyclic group containing one or more hetero atoms and which may be alkyl substituted, X is O, S or a nitrogen atom linked to a hydrogen atom or to an alkyl, aryl or aralkyl group which itself may be substituted by at least one halogen atom or alkyl, alkoxy or -CF 3 group, Y is a direct bond or a straight chain or branched C 1-8 alkylene group and n is 0, 1, 2, 3 or 4, are obtained: (a) by reacting an amine, HNR111R1111, or salt thereof, either (i) with a compound of the general formula Het.(CH 2 ) n .CO.NR.Y.phenylene.SO 2 NHCO.A wherein A is a radical which is eliminated as HA in the course of the reaction and Het is a heterocyclic group as illustrated on the lefthand side of Formula (I), or (ii) with an isocyanate Het.(CH 2 ) n -CO.NR.Y.phenylene.SO 2 .N : C : O; (b) by reacting an arylsulphonamide, Het.(CH 2 ) n .CO.NR.Y.phenylene.SO 2 NH 2 , (obtained by acylation of H.NR.Y.phenylene.SO 2 NH 2 or an acid salt thereof) or an alkali metal salt thereof, either (i) a compound of the general formula B.CO.N.R111R1111 wherein B is a radical which is eliminated as HB or MB (M is an alkali metal atom), or (ii) with an isocyanate, O : C : N.R1111 to give products in which R111 is hydrogen; (c) by reacting an arylsulphonyl halide, Het.(CH 2 ) n .CO.NR.Y.phenylene.SO 2 .Hal, with a urea, H 2 N.CO.NR111R1111 (Hal is a halogen atom); (d) by subjecting a compound of the general formula (i) when Z is a mercapto group, to oxidative hydrolysis, (ii) when Z is amino, alkoxy, alkylmercapto or chloro to acid or alkaline hydrolysis; (e) by acylating a compound of the general formula HNR.Y.phenylene.SO 2 NH.CO.NR111R1111; (f) by oxidizing a corresponding sulphenyl-urea or sulphinyl urea; (g) by reacting a compound of the general formula with a formamide OHC.NR111R1111; (h) by hydrolysing a corresponding parabanic acid of compound (I); or (i) by treating a compound of the general formula (the products of methods (h) and (i) have hydrogen as the substituent R1111); the radicals A and B are preferably halogen, azido, alkoxy, aryloxy, alkylmercapto, arylmercapto or a substituted or unsubstituted amino, cyclic amino or acylamino group. N - {4 - (# - [3 - and 5 - Methyl - isoxazolyl - 5 - carboxamido] - ethyl) - benzenesulphonyl} - methyl-urethanes are obtained by the interaction of 4 - {# - (3 - or 5 - methyl - isoxazolyl - (5) - carboxamido) - ethyl} - benzenesulphonamide and methyl chloroformate. 1 - Phenylpyrazole - 4 - carboxylic acid chloride hydrochloride is prepared from the free acid utilizing thionyl chloride; 1,5-dimethylpyrazole-(3)-carboxylic acid chloride is obtained in a similar manner. Pharmaceutical preparations suitable for the treatment of diabetes mellitus contain as active ingredient the above novel compounds, administration may be parenterally or orally.