Synthesis and anti-MRSA activity of novel cephalosporin derivatives

Cephalosporin derivatives containing a unique combination of lipophilic C-7 sidechains and polar C-3 thiopyridinium groups were synthesized and found to exhibit potent anti-MRSA activity in vitro and in vivo. The optimum C-7 sidechains utilized were 2,5-dichlorophenylthioacetamido and 2,6-dichloropy rid-4-ylthioacetamido. The C-3 thiopyridinium rings were substituted at nit rogen wi th amino acid and pyruvic acid groups that were designed to confer aqueous solubility as required for TV formulation. This paper describes th e characteristics of these novel cephalosporins and highlights synthetic me thods developed to allow their practical, large-scale syntheses. (C) 2000 E lsevier Science Ltd. All rights reserved.