Non-Peptide Glycoprotein IIb/IIIa Inhibitors. 17. Design and Synthesis of Orally Active, Long-Acting Non-Peptide Fibrinogen Receptor Antagonists

التفاصيل البيبلوغرافية
العنوان:	Non-Peptide Glycoprotein IIb/IIIa Inhibitors. 17. Design and Synthesis of Orally Active, Long-Acting Non-Peptide Fibrinogen Receptor Antagonists
المؤلفون:	Askew, B. C., Bednar, R. A., Bednar, B., Claremon, D. A., Cook, J. J., McIntyre, C. J., Hunt, C. A., Gould, R. J., Lynch, R. J., Lynch, J. J., Jr., Gaul, S. L., Stranieri, M. T., Sitko, G. R., Holahan, M. A., Glass, J. D., Hamill, T., Gorham, L. M., Prueksaritanont, T., Baldwin, J. J., Hartman, G. D.
المصدر:	Journal of Medicinal Chemistry; June 6, 1997, Vol. 40 Issue: 12 p1779-1788, 10p
مستخلص:	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.
قاعدة البيانات:	Supplemental Index

الوصف
تدمد:	00222623 15204804