Synthesis and biological activity of the penem antibiotic MEN 10700 and its orally absorbed ester MEN 11505

Article abstract of DOI:10.7164/antibiotics.53.1086

The synthesis and biological properties of the new penem antibiotic MEN 10700 (6) and of its selected oral prodrug MEN 11505 (8f) are described. MEN 10700 showed a broad spectrum of activity, with high potency both on Gram-positive and Gram-negative strains. It also exhibited good antibacterial activity toward anaerobes and on strains selected for their resistance to other antibacterial agents (cefotaxime- or ceftazidime-resistant Gram-negative strains, ciprofloxacin-resistant E. coli, extended spectrum β-lactamase producing and cephalosporinase inducible enterobacteria). MEN 10700 showed a very high stability to enzymatic degradation by renal dehydropeptidase DHP-I. After oral administration in rats of the pivaloyloxymethyl ester prodrug MEN 11505, the relative bioavailability of MEN 10700 was calculated as F=43%.