371143-27-0Relevant articles and documents
Design, synthesis, and evaluation of α-ketoheterocycles as class C β-lactamase inhibitors
Kumar, Sanjai,Pearson, Andre L.,Pratt
, p. 2035 - 2044 (2007/10/03)
A series of specific α-ketoheterocycles (benzoxazole, thiazole, imidazole, tetrazole, and thiazole-4-carboxylate) has been synthesized in order to assess their potential as β-lactamase inhibitors. The syntheses were achieved either by construction of the heterocycle (benzoxazole) from an appropriate α-hydroxyimidate, followed by oxidation of the alcohol, or by direct reaction of methyl phenaceturate with a lithiated heterocycle. The properties of these compounds in aqueous solution are described and their inhibitory activity against β-lactamases assessed. They did inhibit the class C β-lactamase of Enterobacter cloacae P99 but not the TEM β-lactamase. The most effective inhibitor of the former enzyme (Ki = 0.11 mM) was 5-(phenylacetylglycyl) tetrazole, probably because it is an anion at neutral pH. Interpretation of the results was aided by computational models of the tetrahedral adducts. Most of the compounds also inhibited α-chymotrypsin but not porcine pancreatic elastase.