Studies on the synthesis and structure-activity relationships of 2-(2-functionalized pyrrolidin-4-ylthio)-1 beta-methylcarbapenems.

A series of new carbapenem derivatives, which have a pyrrolidin-4-ylthio group substituted with a hydroxyalkyl or carbamoyl group at the 2' position as the C-2 side chain, have been prepared. The antibacterial activity and the stability to renal dehydropeptidase-I of these compounds were investigated, and the structure-activity relationships were studied. Among these new carbapenems, (1R,5S,6S)-2-[(2S,4S)-2-¿(2-hydroxy)ethylmercaptomethyl¿pyrroli din-4 -ylthio]-6-[(1R)-I-hydroxyethyl]-1-methyl-1-carbapen-2-em-3- carboxylic acid (1a) showed the most potent and well balanced activity and was selected as a candidate for further evaluation.