Novel morpholinone-based D-Phe-Pro-Arg mimics as potential thrombin inhibitors: design, synthesis, and X-ray crystal structure of an enzyme inhibitor complex
2002 (English)In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 10, no 6, 1829-1839 p.Article in journal (Refereed) Published
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 α-thrombin inhibitor binding site. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 720 nM. The X-ray crystal structure of this candidate co-crystallized with α-thrombin is discussed.
Place, publisher, year, edition, pages
2002. Vol. 10, no 6, 1829-1839 p.
Engineering and Technology
IdentifiersURN: urn:nbn:se:liu:diva-47039DOI: 10.1016/S0968-0896(02)00023-8OAI: oai:DiVA.org:liu-47039DiVA: diva2:267935