SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF NOVEL 4-PYRROLIDINYLTHIO CARBAPENEMS .1. 2-ALKOXYMETHYL DERIVATIVES

The synthesis and in vitro antibacterial activity of a novel series of 2-alkoxymethyl-4-pyrrolidinylthio-1 beta-methyl carbapenems are descr ibed. As a result of these studies, we discovered that FR27743 (19j) c ontaining a novel,2-fluoroethoxymethyl substituent possesses a broad s pectrum of antibacterial activity against both Gram-positive and Gram- negative organisms, including Pseudomonas aeruginosa. Furthermore, FR2 7743 exhibited excellent stability against renal dehydropeptidase-I (D HP-I), good urinary recovery, and superior in vivo activity compared t o that for Meropenem against several systemic infections. (C) 1997 Els evier Science Ltd.