The synthesis, antibacterial, and beta-lactamase inhibitory activity of a novel asparenomycin analog.
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.
Bouthillier
G
G
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492-7660.
Mastalerz
H
H
Menard
M
M
Fung-Tomc
J
J
Gradelski
E
E
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
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