title: 6-(substituted methylene)penems, potent broad spectrum inhibitors of bacterial beta-lactamase. IV. Kidney stability, serum binding and additional biological evaluation of racemic derivatives.
abstract: Sodium (5RS)-Z-6-(substituted methylene)penem-3-carboxylates (3) are extremely potent inhibitors of bacterial beta-lactamases, but some members of this group of compounds are highly bound to human serum, while others are readily degraded by renal dehydropeptidase I enzyme. Consequently, the stability of a variety of 6-(substituted methylene)penems (3) to human kidney homogenate, their binding to human serum and their activity in a mouse infection model was investigated at an early stage, and were instrumental in the selection of the 1,2,3-triazolylmethylene derivatives (e.g. 3k) as a class of compounds worthy of further evaluation.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Chemotherapeutic Research Centre, Surrey, UK.
authors.forename: I S
authors.initials: IS
authors.lastname: Bennett
authors.forename: N J
authors.initials: NJ
authors.lastname: Broom
authors.forename: K
authors.initials: K
authors.lastname: Coleman
authors.forename: S
authors.initials: S
authors.lastname: Coulton
authors.forename: P D
authors.initials: PD
authors.lastname: Edwards
authors.forename: I
authors.initials: I
authors.lastname: Francois
authors.forename: D R
authors.initials: DR
authors.lastname: Griffin
authors.forename: N F
authors.initials: NF
authors.lastname: Osborne
authors.forename: P M
authors.initials: PM
authors.lastname: Woodall
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D001798:Blood Proteins / Q000378:metabolism*; D004355:Drug Stability; D004927:Escherichia coli Infections / Q000188:drug therapy; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008968:Molecular Conformation; D011485:Protein Binding; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams