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 P1 and P3 sites. Potent in vitro activity against thrombin, with excellent selectivity over trypsin was found for selected analogues.