Author/Authors :
William J. Hoekstra، نويسنده , , Becky L. Hulshizer، نويسنده , , David F. McComsey، نويسنده , , Patricia Andrade-Gordon، نويسنده , , Jack A. Kauffman، نويسنده , , Michael F. Addo، نويسنده , , Donna Oksenberg، نويسنده , , Robert M. Scarborough، نويسنده , , Bruce E. Maryanoff، نويسنده ,
Abstract :
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.
