CEPHALOSPORINS HAVING A HETEROCYCLIC CATECHOL IN THE C3 SIDE-CHAIN .2. IMPROVEMENT OF PHARMACOKINETIC PROFILE

7-[(Z)-2-(2-Aminothiazol-4-yl)-2-methoxy-(or xy)-iminoacetamido]-3-[pr open-1-yl]-cephalosporins having a variety of heterocyclic catechol in 3-position of the propenyl group were synthesized. Among them, 6,7-di hydroxyisoquinoline derivatives, 2a and 2b, showed very high and prolo nged blood levels after intramuscular administration to mice and highe r in vivo anti activity than expected from their in vitro activity. Th e former cephalosporin (2a) gave well-balanced in vitro and in vivo an tibacterial spectra including anti-methicillin-resistant Staphylococcu s aureus (MRSA) activity. The latter cephalosporin (2b) also showed go od in vitro and in vivo activities against Gram-positive bacteria, esp ecially against S. aureus A15036, a strain of MRSA, the in vivo activi ty being comparable to vancomycin but was lacking in anti-pseudomonal activity.