GB1392156A - 7-3-substituted ureido and thioureido cephalosporins - Google Patents

Abstract

1392156 7 - (3 - Substituted ureido and thioureido)cephalosporins RECHERCHE ET INDUSTRIE THERAPEUTIQUES 22 June 1973 [22 June 1972] 29699/73 Heading C2C A novel compound has the formula wherein R<SP>1</SP> is a saturated or unsaturated ali phatic group of up to 6 carbon atoms having a straight or branched chain, unsubstituted or substituted with from one to two groups selected from halogen, hydroxy, methoxy, azido, amino, carboxy, cyano, nitro or diloweralkylamino, aryl, saturated or unsaturated alicyclic of up to 6 carbon atoms and 5 or 6 membered heterocyclic ring having up to 4 atoms which are N, O or S, said aryl, alicyclic and heterocyclic rings being unsubstituted or substituted with one or two groups selected from halogen, hydroxy, cyano, nitro, acetamido, sulphamoyl, mercapto, methylthio, lower alkyl, lower alkoxy and diloweralkylamino; an aryl group of a saturated or unsaturated alicyclic group of up to 6 carbon atoms or a heterocyclic ring containing up to 4 atoms which are N, O or S said aryl, alicyclic or heterocyclic rings being unsubstituted or substituted with one or two groups selected from hydroxy, cyano, nitro, acetamido, sulphamoyl, mercapto, methylthio, lower alkyl, lower alkoxyl and diloweralkylamino; Z is O or S ; R<SP>2</SP> is hydrogen, pyridinium, N-piperidino- or N-piperazino-dithiocarboxylate or 8-Het wherein Het is a 5- or 6-membered heterocyclic ring containing one or more atoms which are N, O, or S, with or without ring substituents such as halogen, lower alkyl, lower alkoxy, amino, lower alkylamino or dialkylamine; and M is hydrogen, alkali metal cation, alkaline earth cation or an ammonium cation. The compound may be prepared by forming a ureido or thioureido bond by reacting in a non-reactive organic solvent the isocyanate or isothiocyanate derived from one of 7-aminocephalosporanic acid and the amine of formula R<SP>1</SP>NH 2 with the other of said reactants and then either catalytically hydrogenating the 3-acetoxy group to yield the 3-methyl group or displacing the 3-acetoxy group with the desired mercaptoheterocyclic compound, the displacement reaction being carried out at neutral pH in a non-reactive polar solvent at 40‹ to 80‹ C., and, when R<SP>1</SP> is substituted by hydroxy, mercapto, amino or carboxy, protecting the corresponding reactant according to any known method from the art for affording such protection, the compounds wherein M is not hydrogen being prepared from the free acid by reacting said free acid with the appropriate base.