Patent GB-1171070-A (GB)
Title: Anti-Diabetically Effective Sulphonamides
IPC: C07D239/69
Filed: 1968-10-22
Abstract: 1,171,070. Sulphonamides. BOEHRINGER MANNHEIM G.m.b.H. 22 Oct., 1968 [24 Oct., 1967], No. 50135/68. Heading C2C. Novel anti-diabetically effective sulphonamides (including salts thereof) of the general formula wherein A is an unsubstituted or substituted alkyl, alkenyl, aryl, aralkyl, aryloxyalkyl, arylmercaptoalkyl, cycloalkyl, cycloalkenyl, thienyl, furyl, alkoxy, alkenyloxy, aralkoxy, cycloalkoxy, cycloalkylalkoxy, cycloalkenylalkoxy radical or a radical of the general formula V.W.N- where V and W, which may be the same or different, are hydrogen atoms, unsubstituted or substituted alkyl, cycloalkyl, aryl or aralkyl radicals or, together with the adjacent N-atom, can also signify an unsubstituted or substituted heterocyclic ring, R 1  is a hydrogen atom or an alkyl or aralkyl radical, R 2  is an alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, alkoxy, cycloalkoxy, alkoxyalkyl, alkoxyalkoxy or alkylmercapto radical, which may be substituted by halogen atoms, hydroxy groups or alkyl radicals, and R 3  is a hydrogen atom or an alkyl radical and R 2  and R 3  can also together signify 3 to 5 methylene groups thereby comprising a ring on the pyrimidine nucleus, are obtained: (a) by interacting the appropriate 2-amino-pyrimidine and a hydrindene compound of the general formula A.CO.NR 1 - (hydrindene)- S(O) n Cl (n is 0, 1 or 2), followed, if necessary, by oxidation, (b) by reacting a sulphonyl-guanidine of the general formula A.CONR 1 -(hydrindene)- SO. 2 .NH.C(: NH).NH 2  with a compound of the general formula Z.CO.CHR 2 .CO.Z<SP>1</SP> or Z.CO CHR 2 .COR 3 , wherein Z and Z<SP>1</SP> which may be the same or different, are hydrogen atoms or alkoxy radicals, or with functional derivatives thereof, whereafter, when the pyrimidines obtained are hydroxylated in the 4- and/or 6-position, they are converted into the corresponding halo-compounds and subsequently reductively dehalogenated, (c) by acylation utilizing reactive derivatives of acids of the general formula A.COOH, and (d) by reacting a sulphonamide, A.CONR 1 -(hydrindene)-SO 2 NH 2 , with the appropriate pyrimidine substituted at the 2-position by a reactive ester group (e.g. a halo-group) or a trialkylammonium salt group. 2 - (5 - Chloro - 2 - methoxy - benzamido)- hydrindene - 5 - sulphochloride is obtained by the sulphochlorination of 2-(5-chloro-2-methoxy - benzamido) - hydrindene; 2 - (5 - chloro- 2 - ethoxy - benzamido) - hydrindene - 5 - sulphochloride, 2 - (5 - bromo - 2 - methoxy - benzamido)- hydrindene - 5 - sulphochloride, 2 - (N - methyl- 5 - chloro - 2 - methoxy - benzamido) - hydrindene- 5 - sulphochloride and 2 - (ethoxy - carbonylamino) - hydrindene - 5 - sulphochloride are similarly obtained. 2 - N - Methylamino - hydrindene, obtained by the reduction of 2-formylamino-hydrindene, is acylated to afford 2-(N-methyl-5-chloro-2- methoxy-benzamido)-hydrindene. 2 - Amino - N - [5 - isobutyl - pyrimidinyl- (2)] - hydrindene - 5 - sulphonamide and 2- amino - N - [5 - ethoxy - pyrimidinyl - (2)]- hydrindene-5-sulphonamide are prepared by the alkaline hydrolysis of the corresponding 2- ethoxy-carbonylamino-compounds.