A NEW PARENTERAL CEPHALOSPORIN. SK&F 59962: 7-TRIFLUOROMETHYLTHIOACETAMIDO-3-(1-METHYL-1H-TETRAZOL-5-YLTHIOMETHYL)-3-CEPHEM-4-CARBOXYLIC ACID. CHEMISTRY AND STRUCTURE ACTIVITY RELATIONSHIPS

Abstract

The synthesis, microbiological profile and in vivo effectiveness in laboratory animals of a series of cephalosporins having 7-acyl substituents derived from methylthioacetic acid are described. Structure-activity relationships examined include the effect of oxidation of the side-chain sulfur atom, replacement of the (side-chain) methyl hydrogens by fluorine and replacement of the 3-acetoxy substituent by thioheterocycles. One derivative, 7-trifluoromethylthioacetamido-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (SK&F 59962), was found to have outstanding antibacterial activity in vitro and in vivo.