title: The synthesis, antibacterial, and beta-lactamase inhibitory activity of a novel asparenomycin analog.
abstract: An analog, 6-(2'-hydroxyethylidene)-4 beta-methyl-1-azabicyclo[3.2.0]hept-2-ene-2- carboxylate (11), of the carbapenem beta-lactamase inhibitor, asparenomycin A, was synthesized. It possessed a spectrum of antibacterial activity that was comparable to that of asparenomycin A but was less effective as a beta-lactamase inhibitor. With ampicillin, it only exhibited a moderate level of synergy against a variety of beta-lactamase-producing organisms. Although the presence of a 4 beta-methyl group in the analog brought about a significant increase in chemical stability relative to that of asparenomycin A, it did not result in an increase in stability to kidney dehydropeptidase enzyme.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492-7660.
authors.forename: G
authors.initials: G
authors.lastname: Bouthillier
authors.forename: H
authors.initials: H
authors.lastname: Mastalerz
authors.forename: M
authors.initials: M
authors.lastname: Menard
authors.forename: J
authors.initials: J
authors.lastname: Fung-Tomc
authors.forename: E
authors.initials: E
authors.lastname: Gradelski
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D002969:Clavulanic Acids / Q000494:pharmacology; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D013845:Thienamycins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D002969:Clavulanic Acids; D013845:Thienamycins; C073941:6-(2'-hydroxyethylidene)-4-methyl-3-(2-(methylthio)pyridinyl)-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylate; C031989:asparenomycin; D000667:Ampicillin