142374-06-9Relevant academic research and scientific papers
Non-Peptide Fibrinogen Receptor Antagonists. 2. Optimization of a Tyrosine Template as a Mimic for Arg-Gly-Asp
Egbertson, Melissa S.,Chang, Charles T.-C.,Duggan, Mark E.,Gould, Robert J.,Halczenko, Wasyl,et al.
, p. 2537 - 2551 (2007/10/02)
Inhibitors of platelet-fibrinogen binding offer an opportunity to interrupt the final, common pathway for platelet aggregation.Small molecule inhibitors of the platelet fibrinogen receptor GPIIb/IIIa were prepared and evaluated for their ability to prevent platelet aggregation.Compound 23m (L-700, 462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9 nM and demonstrated a selectivity of >24000-fold between platelet and human umbilical vein endothelial cell fibrinogen receptors.Dose-dependent inhibition of ex vivo platelet aggregation induced by ADP was achieved with iv infusions 0.1-10 μg/kg/min of 23m in anesthetized dogs, with 10 μg/kg/min completely inhibiting platelet aggregation during the entire 6 h infusion protocol.Platelet aggregatability returned rapidly after the termination of the 23m infusions.These features suggest that 23m may be useful in the treatment of arterial occlusive disorders.
