212756-40-6Relevant articles and documents
Thrombin receptor (PAR-1) antagonists. Heterocycle-based peptidomimetics of the SFLLR agonist motif
Hoekstra, William J.,Hulshizer, Becky L.,McComsey, David F.,Andrade-Gordon, Patricia,Kauffman, Jack A.,Addo, Michael F.,Oksenberg, Donna,Scarborough, Robert M.,Maryanoff, Bruce E.
, p. 1649 - 1654 (2007/10/03)
The thrombin receptor (PAR-1) is activated by α-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 α-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 μM, and gave IC50 values of 25 μM and 6.6 μM against α-thrombin- and SFLLRN-NH2-induced platelet aggregation, respectively.