GB1348986A - Cephalosporin derivatives - Google Patents

Abstract

1348986 Cephem compounds MERCK & CO Inc 30 April 1971 [9 July 1970 10 Dec 1970] 16654/73 Divided out of 1348984 Heading C2A Cephem compounds having the general Formula (III) wherein R 1 is hydrogen or a substituted or unsubstituted hydroxy or mercapto group or a univalent hydrocarbon group, R and R‹ are the same or different and each is an acyl group and A is hydrogen, halogen, hydroxy, azido, cyano, mercapto, alkoxy, aryloxy, aralkoxy, heterocycleoxy, arylthio, heterocyclethio, sulphamoyloxy, alkylthio, aralkylthio, acyloxy, acylthio, carbamoyloxy, thiocarbamoyloxy, N- alkylcarbamoyloxy, N,N-dialkylcarbamoyloxy, alkoxycarbonyloxy, carbamoylthio, thiocarbamoylthio, N-alkylcarbamoylthio, N,N-dialkylcarbamoylthio, alkoxycarbonylthio, isothiouronium, alkylsulphonyloxy, heterocyclic tert. amino or quaternary ammonium, which compounds are novel when R 1 is other than hydrogen, are prepared by reacting a cephem compound of Formula II wherein R, R 1 and A are as defined above or a derivative thereof in which the 4-COOH group, A and/or R 1 are protected by blocking groups, with an acylating agent that provides an acyl group R‹, in the presence of a trihydrocarbylsilyl derivative of a sulphonamide, phthalimide, cyanoacetamide, trifluoroacetamide, benzamide, p - nitrobenzamide, or trichloroacetamide, and if necessary subsequently removing any blocking groups. If desired the compounds (III) may be reacted with an alkanol or an alkylthiol, or hydrolysed with dilute aqueous acid or base or merely heated in the reaction mixture of the inventive process, to replace the original acyl group R by hydrogen, giving a cephem compound of Formula (IV) in which R‹, R 1 and A have the aforesaid meanings. The cephem compounds (III) have antibacterial activity and may be formulated with a carrier or diluent into pharmaceutical compositions, either as the free acid or as a physiologically acceptable salt or ester thereof.