SYNTHESIS AND BIOLOGICAL EVALUATION OF A SERIES OF NEW PARENTERAL OPTICALLY-ACTIVE ALKYLPYRIDINIUM-4'-YL)THIO]METHYL]-2-OXAISOCEPHEMS

The preparation and biological evaluation of a series of azol-4-yl)-2- (Z)-[(cyclopentyloxy)imino]acetamido] optically active 2-oxaisocephems , substituted at the 3-position with [(N-alkylpyridinium-4'-yl)thio]me thyl groups, are described. The resulting family of parenteral compoun ds displays a broad spectrum of in vitro antibacterial activity. These compounds exhibit increased activity against Gram-positive organisms including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis which are resistant to most cephalosporins with a similar le vel of Gram-negative activity to that of the third-generation antibiot ics. In vivo efficacy of new antibacterial agents in this investigatio n is excellent against both Gram-positive and Gram-negative bacteria a s compared with reference compounds. The in vitro and in vivo antimicr obial activity and the structure-activity relationships are presented.