Synthesis and beta-lactamase inhibitory properties of 2 beta-[(1,2,3-triazol-1-yl)methyl]-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide and related triazolyl derivatives.
Benzhydryl 2 beta-[(1,2,3-triazol-1-yl)methyl]-2 alpha-methylpenam- 3 alpha-carboxylate 1,1-dioxide was prepared by heating benzhydryl 2 beta-(azidomethyl)-2 alpha-methylpenam-3 alpha-carboxylate 1,1-dioxide with (trimethylsilyl)acetylene. The ester group was removed by hydrogenolysis to give sodium 2 beta-[(1,2,3-triazol-1-yl)methyl]-2 alpha-methylpenam-3 alpha-carboxylate 1,1-dioxide (3i, YTR-830), which was found to be a potent inhibitor of various bacterial beta-lactamases. A series of related compounds was prepared in a similar way, and all of these compounds show excellent beta-lactamase inhibitory properties.
D000667:Ampicillin / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology; D055598:Chemical Phenomena; D002621:Chemistry; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D010397:Penicillanic Acid / Q000138:chemical synthesis / Q000494:pharmacology*; D013407:Sulbactam; D000078142:Tazobactam; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors
D002969:Clavulanic Acids; D014230:Triazoles; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; D000667:Ampicillin; D010397:Penicillanic Acid; D013407:Sulbactam; D000078142:Tazobactam