CEPHALOSPORINS HAVING A HETEROCYCLIC CATECHOL IN THE C3 SIDE-CHAIN .1. ENHANCEMENT OF EFFICACY AGAINST GRAM-NEGATIVE BACTERIA

Two groups of cephalosporins substituted with a variety of heterocycli c catechols in the C3 side chain were synthesized. One is a group of 3 -(heterocyclic catechol-substituted methyl)cephalosporins and another is 3-[(E)-3-heterocyclic catechol-substituted 1-propen-1-yl]cephalospo rins. Cephalosporins in the latter group showed higher in vivo efficac ies than those in the former group having the same heterocyclic catech ol, especially against Pseudomonas aeruginosa A9843A, although there w as no significant difference between their in vitro activity. Among th e latter group, the 5,6-dihydroxybenzimidazole derivative (6e) and the 2,6-dihydro-7-hydroxy-6-oxo-isoquinoline derivative (6b) showed much higher activity than ceftazidime (CAZ) and imipenem (IPM) against P. a eruginosa A9843A both in in vitro and in vivo studies.