SYNTHESIS AND BIOLOGICAL PROPERTIES OF A NEW SERIES OF ANTI-MRSA BETA-LACTAMS - 2-(THIAZOL-2-YLTHIO)CARBAPENEMS

A series of 1 beta-methylcarbapenems containing variously C-2 substitu ted thiazol-2-ylthio groups were synthesized, and their in vitro anti- MRSA activity was examined. Among them, 1 beta-methyl-2-(4-arylthiazol -2-ylthio) carbapenems exhibited superior anti-MRSA activity. Introduc tion of a cationic moiety in the C-2 side chain not only reduced the b inding to HSA but also increased the stability against DHP-I, without affecting the anti-MRSA, activity. It was also found that the distance between the cationic moiety and the carbapenem skeleton was related t o the strength of HSA binding and the stability against DHP-I. (C) 199 7 Elsevier Science Ltd.