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

The synthesis and biological properties of the new penem antibiotic MEN 107 00 (6) and of its selected oral prodrug MEN 11505 (8f) are described. MEN 1 0700 showed a broad spectrum of activity, with high potency both on Gram-po sitive and Gram-negative strains. It also exhibited good antibacterial acti vity toward anaerobes and on strains selected for their resistance to other antibacterial agents (cefotaxime- or ceftazidime-resistant Gram-negative s trains, ciprofloxacin-resistant E. coli, extended spectrum beta -lactamase producing and cephalosporinase inducible enterobacteria). MEN 10700 showed a very high stability to enzymatic degradation by renal dehydropeptidase DH P-I. After oral administration in rats of the pivaloyloxymethyl ester prodr ug MEN 11505, the relative bioavailability of MEN 10700 was calculated as F =43%.