McComsey D F, Hecker L R, Andrade-Gordon P, Addo M F, Maryanoff B E
R. W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477, USA.
Bioorg Med Chem Lett. 1999 Jan 18;9(2):255-60. doi: 10.1016/s0960-894x(98)00731-8.
The thrombin receptor (PAR-1) is activated by alpha-thrombin to stimulate various cell types, including platelets, through the tethered-ligand sequence SFLLRN. Macrocyclic peptide analogues of SFLLRN were synthesized and evaluated in vitro. In general, the compounds were much less potent in inducing platelet aggregation relative to SFLLRN-NH2 and did not act as antagonists of alpha-thrombin. Derivative 3c was the most potent macrocycle in activating PAR-1, with an EC50 of 24 microM.
