163213-77-2Relevant academic research and scientific papers
Non-peptide fibrinogen receptor antagonists. 2. The synthesis of [3H]L- 738,167
Hamill, Terence G.,Askew, Ben C.,Hartman, George D.,Claremon, David A.,McIntyre, Charles J.,Burns, H. Donald
, p. 273 - 277 (2007/10/03)
The synthesis of [2H]L-738,167, an orally active fibrinogen receptor antagonist, is described. A precursor containing the 2-bromotolyl moiety was synthesized, and a reductive debromination reaction using tritium gas and Pearlman's catalyst gave
Non-peptide glycoprotein IIb/IIIa inhibitors. 17. Design and synthesis of orally active, long-acting non-peptide fibrinogen receptor antagonists
Askew, Benny C.,Bednar, Rodney A.,Bednar, Bohumil,Claremon, David A.,Cook, Jacquelynn J.,McIntyre, Charles J.,Hunt, Cecila A.,Gould, Robert J.,Lynch, Robert J.,Lynch Jr., Joseph J.,Gaul, Stanley L.,Stranieri, Maria T.,Sitko, Gary R.,Holahan, Marie A.,Glass, Joan D.,Hamill, Terrence,Gorham, Lynn M.,Prueksaritanont, Thomayant,Baldwin, John J.,Hartman, George D.
, p. 1779 - 1788 (2007/10/03)
The synthesis and pharmacological evaluation of 5 (L-738,167), a potent, selective non-peptide fibrinogen receptor antagonist is reported. Compound 5 inhibited the aggregation of human gel-filtered platelets with an IC50 value of 8 nM and was found to be >33000-fold less effective at inhibiting the attachment of human endothelial cells to fibrinogen, fibronectin, and vitronectin than it was at inhibiting platelet aggregation. Ex vivo platelet aggregation was inhibited by >85% 24 h after the oral administration of 5 to dogs at 100 μg/kg. The extended pharmacodynamic profile exhibited by 5 appears to be a consequence of its high-affinity binding to GPIIb/IIIa on circulating platelets and suggests that 5 is suitable for once-a-day dosing.
