Studies on condensed-heterocyclic azolium cephalosporins: IV. Synthesis and antibacterial activity of 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(z)-alkoxyiminoacetamido]-3-(conden ed-heterocyclic azolium)methyl cephalosporins including sce-2787

Abstract

The synthesis and in vitro antibacterial activity of 7β-[2-(5-amino-l,2,4-thiadiazol-3-yl)-2(Z)-alkoxyiminoacetamido] cephalosporins bearing various condensed-heterocyclic azolium groups at the 3 position in the cephalosporin nucleus are described. The thiadiazolyl cephalosporins showed good antibacterial activity against both Gram-positive and Gram-negative bacteria and the MICs of the thiadiazolyl cephalosporins against Pseudomonas aeruginosa was more potent than that of the corresponding 7β-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl cephalosporins. Also, the thiadiazolyl cephalosporins bearing (imidazo[1,2-6]-pyridazinium-l-yl)methyl groups at the 3 position showed antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Among the cephalosporins tested, 7β-[2-(5-amino-l,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido]-3-(imidazo[l,2-6]pyridazinium-l-yl)methyl-3-cephem-4-carboxylate (4, SCE-2787) which exhibited the most potent antibacterial activity and the broadest antibacterial spectrum was selected as a parenteral cephalosporin candidate for further biological evaluation. © 1992, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.