Design, synthesis, and thrombin-inhibitory activity of pyridin-2-ones as P2/P3 core motifs.

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.