Glycoprotein Ilb/IIIa antagonists

Shuaib A, Yang Y, Nakada MT, Li Q, Yang T. Glycoprotein Ilb/IIIa antagonist, murine 7e3 f(ab ) 2, and tissue plasminogen activator in focal ischemia evaluation of efficacy and risk of hemorrhage with combination therapy. J Cereb Blood Flow Metab 2002 22 215-222. 

Wang W, Borchardt RT, Wang B. Orally active peptidomimetic analogues that are glycoprotein Ilb/IIIa antagonists. Curr Med Chem 2000 7 437-53. 

Palmer, S., M. Sculpher, M. Robinson Philips, L. Ginnelly, and D. Gary. 2005. Management of Non-ST-Elevation Acute Coronary Syndromes How Cost-Effective Are Glycoprotein Ilb/IIIa Antagonists in the UK National Health Service International Journal of Cardiology 100(2) 229-240. 

Mousa SA. Antiplatelet therapies Recent advances in the development of platelet glycoprotein Ilb/IIIa antagonists. Curr Interv Cardiol Rep 1999 1 243-252. 

The pyrrolidinyl enamino keto-diester 77 reacted with 3-hydrazinylpropan-l-amine in the presence of 1 N HC1 to afford the pyrazolodiazepine 78, a key intermediate in the preparation of a glycoprotein Ilb/IIIa antagonist, in 40% yield (Scheme 35) <2003TL5867>. The requirement for the presence of 1 N HC1 to promote this process suggested that the diketo diester is the actual intermediate in the process, evaluated by examining the outcome with a mixed methyl/ethyl ester. The product was isolated as a 1 1 mixture of ester isomers, consistent with the intervention of a hydrolytic step that led to symmetrization of the electrophile. 

Curtin R. Intravenous glycoprotein Ilb/IIIa antagonists their benefits, problems and future developments. Curr Pharm Des. 2004 10 1577-1585. 

Khurana et al. (1997) introduced tissue factor-modified TEG to study platelet glycoprotein Hb/IIIa function and to establish a quantitative assay of platelet function. With this modification, Mousa et al. (2000) found two classes of glycoprotein Ilb/IIIa antagonists, one with high binding affinity for resting and activated platelets and slow platelet dissociation rates (class I) demonstrating potent inhibition of platelet function, in contrast to those with fast platelet dissociation rates (class II). Additionally, Mousa et al. (2005) utilized the... 

Mousa SA, Abulencia JP, McCarty OJ et al. (2002) Comparative efficacy between glycoprotein Ilb/IIIa antagonists roxifiban and orbofiban in inhibiting platelet responses in flow models of thrombosis. J Cardiovasc Pharmacol 39 552-560... 

Cook NS, Zerwes H-G, Tapparelli C et al. (1993) Platelet aggregation and fibrinogen binding in human, rhesus monkey, guinea-pig, hamster and rat blood activation by ADP and thrombin receptor peptide and inhibition by glycoprotein Ilb/IIIa antagonists. Thromb Haemostasis 70 531-539... 

Panzer-Knodle S, Taite BB, Mehrotra DV et al. (1993) Species variation in the effect of glycoprotein Ilb/IIIa antagonists on inhibition of platelet aggregation. J Pharm Tox Meth 30 47-53... 

Scarborough, R. M., and Gretler, D. D. (2000). Platelet glycoprotein Ilb-IIIa antagonists as prototypical integrin blockers Novel parenteral and potential oral antithrombotic agents. /. Med. Chem. 43, 3453-3473. 

S. Cannon CP, McCabe CH, Borzak S, et al. Randomized trial of an oral platdet glycoprotein Ilb/IIIa antagonist, sibrofiban, in patients after an acute coronary syndrome results of the TIMI 12 Trial. Circulation 1998 97 340-349. 

It must be emphasized that very few episodes of abcixi-mab-related bleeding are life-threatening and that in none of the trials with abciximab as well as with other glycoprotein Ilb/IIIa antagonists has there been an excess of intracranial hemorrhage (15). 

Cines DB. Glycoprotein Ilb/IIIa antagonists Potential induction and detection of drug-dependent antiplatelet antibodies. Am Heart J 1998 135 S152-S159. 

Stiegler H, Fischer Y, Steiner S, et al. Sudden onset of EDTA-dependent pseudothrombocytopenia after therapy with the glycoprotein Ilb/IIIa antagonists c7E3 Fab. Ann Hematol 2000 79 161-164. 

Dennis, M.S., Henzel, W.J., Pitti, R.M., Lipari, M.T., Napier, M.A, Deisher, T.A., and Bunting, S. (1990). Platelet glycoprotein Ilb-IIIa antagonists from snake venoms Evidence for a family of platelet-aggregation inhibitors. Proc. Natl. Acad. Sci. USA. 57 2471-2475. 

Mbikay, M., Tadros, H., Ishida, N., Lemer, C.P., De Lamirande, E., Chen, A., El-Alfy, M., Clermont, Y., Seidah, N.G., Chretien, M., Gagnon, C., and Simpson, E.M. (1997). Impaired fertility in mice deficient for the testicular germ-cell protease PC4. Proc. Natl. Acad. Sci. USA 94 6842-6846. McDowell, R.S., Dennis, M., Louie, A., Shuster, M., Mulkerrin, M.G., and Lazarus, R.A. (1992). Mambin, a potent glycoprotein Ilb-IIIa antagonist and platelet aggregation inhibitor. Biochemistry 37 4766-4772. 

Inhibitors of glycoprotein Ilb/IIIa antagonists abciximab, eptifibatide, tirofiban glycoprotein Ilb/IIIa lefradafiban. 

Heterocycles as platelet glycoprotein Ilb-IIIa antagonists 00JMC3453. 

The development of novel and powerful antiplatelet agents has improved outcomes after PCI. In the CADILLAC trial, the use of a glycoprotein Ilb-IIIa inhibitor improved outcome in those treated with either balloon angioplasty or an intracoronary stent (21). Similarly, treatment with clopidogrel, a thienopyridine, decreases the incidence of adverse events after PCI (22,23). Neither thienopyridines nor glycoprotein Ilb-IIIa antagonists were available at the time the early trials designed to test the potential clinical efficacy of a combined approach were performed. 

The risk of bleeding with glycoprotein Ilb/IIIa antagonists may be increased by heparin and thrombolytics, but low-dose thrombolytic therapy appears less likely to cause a problem. 

Glycoprotein Ilb/IIIa antagonists Abciximab Reopro IV Launched... 

Mandava P, Thiagarajan P, Kent TA. Glycoprotein Ilb/IIIa antagonists in acute ischaemic stroke current status and fiimre directions. Drugs. 2008 68 1019-1028. 

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