Synthesis and biological evaluation of novel 1β-methylcarbapenems with isothiazoloethenyl side chains

The synthesis of novel 1beta-methylcarbapenems la,b bearing isothiazoloethenyl moieties at C-5 position of pyrrolidine ring and their biological evaluation are described. Both compounds showed potent and well-balanced antibacterial activity as well as high stability to DHP-I. Especially, 5-isothiazole derivative la exhibited excellent DHP-I stability and advanced pharmacokinetics profiles, compared to 5-isoxazole derivative 2, imipenem, and meropenem. (C) 2002 Elsevier Science Ltd. All rights reserved.