441764-63-2Relevant academic research and scientific papers
Novel morpholinone-based D-Phe-Pro-Arg mimics as potential thrombin inhibitors: design, synthesis, and X-ray crystal structure of an enzyme inhibitor complex.
Dahlgren, Anders,Johansson, Per Ola,Kvarnstroem, Ingemar,Musil, Djordje,Nilsson, Ingemar,Samuelsson, Bertil
, p. 1829 - 1839 (2007/10/03)
A morpholinone structural motif derived from D(+)- and L(-)-malic acid has been used as a mimic of D-Phe-Pro in the thrombin inhibiting tripeptide D-Phe-Pro-Arg. In place of Arg the more rigid P1 truncated p-amidinobenzylamine (Pab) or 2-amino-5-aminomethyl-3-methyl-pyridine have been utilized. The synthetic strategy developed readily delivers these novel thrombin inhibitors used to probe the alpha-thrombin inhibitor binding site. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC(50) of 720 nM. The X-ray crystal structure of this candidate co-crystallized with alpha-thrombin is discussed.
