Patent GB-1176288-A (GB)
Title: Aryl Sulphonyl Ureas
Inventor: PLUMPE HANS
IPC: C07D275/03
Filed: 1968-10-28
Abstract: 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, R<SP>1</SP> and R<SP>11</SP> 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 R<SP>1</SP> and R<SP>11</SP> may be joined together to constitute an alkylene chain, R<SP>111</SP> and R<SP>1111</SP> 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, HNR<SP>111</SP>R<SP>1111</SP>, 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.R<SP>111</SP>R<SP>1111</SP> 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.R<SP>1111</SP> to give products in which R<SP>111</SP> 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.NR<SP>111</SP>R<SP>1111</SP> (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.NR<SP>111</SP>R<SP>1111</SP>; (f) by oxidizing a corresponding sulphenyl-urea or sulphinyl urea; (g) by reacting a compound of the general formula with a formamide OHC.NR<SP>111</SP>R<SP>1111</SP>; (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 R<SP>1111</SP>); 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.