609846-45-9Relevant academic research and scientific papers
Synthesis and SAR of thrombin inhibitors incorporating a novel 4-amino-morpholinone scaffold: Analysis of X-ray crystal structure of enzyme inhibitor complex
Nilsson, Jonas W.,Kvarnstr?m, Ingemar,Musil, Djordje,Nilsson, Ingemar,Samulesson, Bertil
, p. 3985 - 4001 (2007/10/03)
A 4-amino-2-carboxymethyl-3-morpholinone structural motif derived from malic acid has been used to mimic D-Phe-Pro in the thrombin inhibiting tripeptide D-Phe-Pro-Arg. The arginine in D-Phe-Pro-Arg was replaced by the more rigid P1 truncated p-amidinobenzylamine (Pab). These new thrombin inhibitors were used to probe the inhibitor binding site of α-thrombin. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 0.130 μM. Interestingly, the stereochemistry of the 4-amino-2-carboxymethyl-3-morpholinone motif is reversed for the most active compounds compared to that of a previously reported 2-carboxymethyl-3-morpholinone series. The X-ray crystal structure of the lead inhibitor cocrystallized with α-thrombin is discussed.
