Synthesis and structure-activity relationships of a novel oral carbapenem, CS-834

Article abstract of DOI:10.7164/antibiotics.50.429

We have studied an ester prodrug of a carbapenem to develop a potent orally active β-lactam antibiotic. A variety of 1β-methylcarbapenem derivatives have been synthesized. We have found that some derivatives having an amide group in the C-2 side chain show potent and well balanced antibacterial activities as well as high stability against dehydropeptidase-I. Oral absorption of derivatives has been optimized by modifying the C-3 ester promoiety. Pivaloyloxymethyl (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[(R)-5-oxopyrrolidin-3-ylthio]-1 -carbapen-2-em-3-carboxylate, CS-834, has been selected as the most promising compound for further evaluation.