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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Thrombin receptor ( PAR-1) antagonists. Heterocycle-based peptidomimetics of the SFLLR agonist motif.

The thrombin receptor ( PAR-1) is activated by alpha-thrombin to stimulate various cell types, including platelets, through the tethered-ligand sequence SFLLRN. A series of azole-based carboxamides, designed after SFLLR, were synthesized and evaluated in vitro. The compounds inhibited platelet aggregation induced by SFLLRN-NH2 or alpha-thrombin, and blocked the binding of [3H]-S-(p-F-Phe)-Har-L-Har-KY-NH2 to a CHRF membrane preparation of PAR-1. Oxazole 30 bound to PAR-1 with an IC50 of 1.6 microM, and gave IC50 values of 25 microM and 6.6 microM against alpha-thrombin- and SFLLRN-NH2-induced platelet aggregation, respectively.[1]

References

  1. Thrombin receptor (PAR-1) antagonists. Heterocycle-based peptidomimetics of the SFLLR agonist motif. Hoekstra, W.J., Hulshizer, B.L., McComsey, D.F., Andrade-Gordon, P., Kauffman, J.A., Addo, M.F., Oksenberg, D., Scarborough, R.M., Maryanoff, B.E. Bioorg. Med. Chem. Lett. (1998) [Pubmed]
 
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