title: Synthesis and biological activity of the penem antibiotic MEN 10700 and its orally absorbed ester MEN 11505.
abstract: 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 beta-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%.
authors.affiliation: CNR-ICOCEA, Bologna, Italy.
authors.forename: F M
authors.initials: FM
authors.lastname: Arcamone
authors.forename: M
authors.initials: M
authors.lastname: Altamura
authors.forename: E
authors.initials: E
authors.lastname: Perrotta
authors.forename: A
authors.initials: A
authors.lastname: Crea
authors.forename: S
authors.initials: S
authors.lastname: Manzini
authors.forename: D
authors.initials: D
authors.lastname: Poma
authors.forename: A
authors.initials: A
authors.lastname: Salimbeni
authors.forename: A
authors.initials: A
authors.lastname: Triolo
authors.forename: C A
authors.initials: CA
authors.lastname: Maggi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001682:Biological Availability; D015780:Carbapenems / Q000493:pharmacokinetics / Q000494:pharmacology; D004150:Dipeptidases / Q000378:metabolism; D007769:Lactams; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D010406:Penicillins / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D007769:Lactams; C418196:MEN 11505; C106870:Men 10700; D010406:Penicillins; D011355:Prodrugs; C040033:ritipenem; D004150:Dipeptidases; C038937:dipeptidase