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Design, synthesis, and thrombin-inhibitory activity of pyridin-2-ones as P2/P3 core motifs
Stephen Hanessian1, Daniel Simard, Malken Bayrakdarian
1Department of Chemistry, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Que., Canada H3C 3J7. stephen.hanessian@umontreal.ca
Abstract:
Guided by available X-ray crystal structure data on the serine protease thrombin, a series of pyridin-2-one derivatives were designed and synthesized having diverse functionality at the P(1) and P(3) sites. Potent in vitro activity against thrombin, with excellent selectivity over trypsin was found for selected analogues.
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