Download MendeleyNovel non-covalent thrombin inhibitors incorporating P(1) 4,5,6,7-tetrahydrobenzothiazole arginine side chain mimetics
Marinko, P., Krbavcic, A., Mlinsek, G., Solmajer, T., Trampus-Bakija, A., Stegnar, M., Stojan, J., Kikelj, D.(2004) Eur J Med Chem 39: 257-265
- PubMed: 15051174
- DOI: https://doi.org/10.1016/j.ejmech.2003.12.006
- Primary Citation of Related Structures:
1SB1 - PubMed Abstract:
The design, synthesis and biological activity of a series of novel non-covalent D-Phe-Pro-Arg motif-based thrombin inhibitors incorporating 4,5,6,7-tetrahydrobenzothiazol-2-amine as a novel arginine surrogate are described. Compound 9, the most potent in the series of thrombin inhibitors, exhibited an in vitro K(i) of 128 nM and 342-fold selectivity against trypsin. The binding mode of this novel class of thrombin inhibitors in the enzyme active site, based on the X-ray crystal structure of compound 9 co-crystallized with human alpha-thrombin, is discussed.
Organizational Affiliation:
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
