STUDIES ON 3'-QUATERNARY AMMONIUM CEPHALOSPORINS .4. SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 3'-(2-ALKYL-3-AMINOPYRAZOLIUM)CEPHALOSPORINS RELATED TO FK037

The synthesis and in vitro antibacterial activity of 7 )-2-(2-aminothi azol-4-yl)-2-methoxyiminoacetamido] cephalosporins bearing various 2-a lkyl-3-aminopyrazolium groups at the 3-position are described. Antibac terial activity against MRSA was affected by the nature of the substit uent at the 2-position on the 3'-aminopyrazolium groups. Among the cep halosporins prepared in this study, 7 roxyethyl)-pyrazolio]methyl-3-ce phem-4-carboxylate sulfate (23e, FK037) showed extremely potent broad- spectrum activity against both Gram-positive bacteria including MRSA, and Gram-negative bacteria including Pseudomonas aeruginosa. In partic ular, the in vivo activity against MRSA of FK037 was the highest of al l the beta-lactam antibiotics tested. (C) 1997 Elsevier Science Ltd.