Novel P2Y12 adenosine diphosphate receptor antagonists for inhibition of platelet aggregation (I): In vitro effects on platelets

Thrombosis Research

Volumn 122, Issue 4, 2008, Pages 523-532

  Bryant, Judi ^a   Post, Joseph M ^a   Alexander, Serene ^a   Wang, Yi Xin ^a   Kent, Lorraine ^a   Schirm, Sabine ^a   Tseng, Jih Lie ^a   Subramanyam, Babu ^a   Buckman, Brad ^a   Islam, Imadul ^a   Yuan, Shendong ^a   Sullivan, Mark E ^a   Snider, Mike ^a   Morser, John ^a  

^a BAYER AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

4 [[4 [1 (ETHOXYCARBONYL) 1 METHYLETHOXY] 7 METHYL 2 QUINOLYL]CARBAMOYL] 5 [4 (ETHOXYCARBONYL) PIPERAZIN 1 YL] 5 OXOPENTANOIC ACID; 4 [[[4 (1 CARBOXY 1 METHYLETHOXY)7 METHYLQUINOLIN 2 YL]CARBONYL]AMINO] 5 [4 (ETHOXYCARBONYL) PIPERAZIN 1 YL] 5 OXOPENTANOIC ACID; ADENOSINE DIPHOSPHATE; ANTITHROMBOCYTIC AGENT; BX 048; BX 667; CYCLIC AMP; PURINERGIC P2Y1 RECEPTOR; PURINERGIC P2Y6 RECEPTOR; 4 (((4 (1 CARBOXY 1 METHYLETHOXY) 7 METHYLQUINOLIN 2 YL)CARBONYL)AMINO) 5 (4 (ETHOXYCARBONYL)PIPERAZIN 1 YL) 5 OXOPENTANOIC ACID; 4 ((4 (1 (ETHOXYCARBONYL) 1 METHYLETHOXY) 7 METHYL 2 QUINOLYL)CARBAMOYL) 5 (4 (ETHOXYCARBONYL)PIPERAZIN 1 YL) 5 OXOPENTANOIC ACID; 4-(((4-(1-CARBOXY-1-METHYLETHOXY)-7-METHYLQUINOLIN-2-YL)CARBONYL)AMINO)-5-(4-(ETHOXYCARBONYL)PIPERAZIN-1-YL)-5-OXOPENTANOIC ACID; 4-((4-(1-(ETHOXYCARBONYL)-1-METHYLETHOXY)-7-METHYL-2-QUINOLYL)CARBAMOYL)-5-(4-(ETHOXYCARBONYL)PIPERAZIN-1-YL)-5-OXOPENTANOIC ACID; CALCIUM; LIGAND; OXOACID; PURINERGIC P2 RECEPTOR; PURINERGIC P2Y12 RECEPTOR; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL LINE; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; DRUG POTENCY; DRUG SPECIFICITY; HUMAN; HUMAN CELL; IN VITRO STUDY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; THROMBOCYTE AGGREGATION INHIBITION; ANIMAL; BIOLOGICAL MODEL; CHEMISTRY; DOG; DRUG ANTAGONISM; DRUG SCREENING; METABOLISM; PROTEIN BINDING; SPECIES DIFFERENCE; THROMBOCYTE; THROMBOCYTE AGGREGATION;

ADENOSINE DIPHOSPHATE; ANIMALS; BLOOD PLATELETS; CALCIUM; DOGS; DRUG EVALUATION, PRECLINICAL; HUMANS; KETO ACIDS; LIGANDS; MODELS, BIOLOGICAL; PLATELET AGGREGATION; PLATELET AGGREGATION INHIBITORS; PROTEIN BINDING; QUINOLINES; RATS; RECEPTORS, PURINERGIC P2; SPECIES SPECIFICITY;

EID: 48049098530     PISSN: 00493848     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.thromres.2008.03.026     Document Type: Article

References (33)

1. Born G.V., and Cross M.J. The aggregation of blood platelets. J Physiol 168 (Aug 1963) 178-195
2. Born G.V., and Cross M.J. Effect of adenosine diphosphate on the concentration of platelets in circulating blood. Nature 197 (Mar 9 1963) 974-976
3. Gaarder A., Jonsen J., Laland S., Hellem A., and Owren P.A. Adenosine diphosphate in red cells as a factor in the adhesiveness of human blood platelets. Nature 192 (Nov 11 1961) 531-532
4. Cattaneo M. Platelet P2 receptors: old and new targets for antithrombotic drugs. Expert Rev Cardiovasc Ther 5 1 (Jan 2007) 45-55
5. Daniel J.L., Dangelmaier C., Jin J., Ashby B., Smith J.B., and Kunapuli S.P. Molecular basis for ADP-induced platelet activation. I. Evidence for three distinct ADP receptors on human platelets. J Biol Chem 273 4 (Jan 23 1998) 2024-2029
6. Hechler B., Cattaneo M., and Gachet C. The P2 receptors in platelet function. Semin Thromb Hemost 31 2 (Apr 2005) 150-161
7. Hechler B., Magnenat S., Zighetti M.L., Kassack M.U., Ullmann H., Cazenave J.P., et al. Inhibition of platelet functions and thrombosis through selective or nonselective inhibition of the platelet P2 receptors with increasing doses of NF449 [4,4′,4″,4″-(carbonylbis(imino-5,1,3-benzenetriylbis-(carbonylimino)))t etrakis-benzene-1,3-disulfonic acid octasodium salt]. J Pharmacol Exp Ther 314 1 (Jul 2005) 232-243
8. Jantzen H.M., Milstone D.S., Gousset L., Conley P.B., and Mortensen R.M. Impaired activation of murine platelets lacking G alpha(i2). J Clin Invest 108 3 (Aug 2001) 477-483
9. Jin J., Daniel J.L., and Kunapuli S.P. Molecular basis for ADP-induced platelet activation. II. The P2Y1 receptor mediates ADP-induced intracellular calcium mobilization and shape change in platelets. J Biol Chem 273 4 (Jan 23 1998) 2030-2034
10. Storey R.F. Biology and pharmacology of the platelet P2Y12 receptor. Curr Pharm Des 12 10 (2006) 1255-1259
11. Foster C.J., Prosser D.M., Agans J.M., Zhai Y., Smith M.D., Lachowicz J.E., et al. Molecular identification and characterization of the platelet ADP receptor targeted by thienopyridine antithrombotic drugs. J Clin Invest 107 12 (Jun 2001) 1591-1598
12. Quinn M.J., and Fitzgerald D.J. Ticlopidine and clopidogrel. Circulation 100 15 (Oct 12 1999) 1667-1672
13. Savi P., Labouret C., Delesque N., Guette F., Lupker J., and Herbert J.M. P2y(12), a new platelet ADP receptor, target of clopidogrel. Biochem Biophys Res Commun 283 2 (May 4 2001) 379-383
14. van Giezen J.J., and Humphries R.G. Preclinical and clinical studies with selective reversible direct P2Y12 antagonists. Semin Thromb Hemost 31 2 (Apr 2005) 195-204
15. Pereillo J.M., Maftouh M., Andrieu A., Uzabiaga M.F., Fedeli O., Savi P., et al. Structure and stereochemistry of the active metabolite of clopidogrel. Drug Metab Dispos 30 11 (Nov 2002) 1288-1295
16. Savi P., Herbert J.M., Pflieger A.M., Dol F., Delebassee D., Combalbert J., et al. Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel. Biochem Pharmacol 44 3 (Aug 4 1992) 527-532
17. Savi P., Pereillo J.M., Uzabiaga M.F., Combalbert J., Picard C., Maffrand J.P., et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 84 5 (Nov 2000) 891-896
18. Thebault J.J., Kieffer G., Lowe G.D., Nimmo W.S., and Cariou R. Repeated-dose pharmacodynamics of clopidogrel in healthy subjects. Semin Thromb Hemost 25 Suppl 2 (1999) 9-14
19. Wang T.H., Bhatt D.L., and Topol E.J. Aspirin and clopidogrel resistance: an emerging clinical entity. Eur Heart J 27 6 (Mar 2006) 647-654 Electronic publication 2005 Dec 19
20. Wiviott S.D., Braunwald E., McCabe C.H., Montalescot G., Ruzyllo W., Gottlieb S., et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357 20 (Nov 15 2007) 2001-2015
21. Cannon C.P., Husted S., Harrington R.A., Scirica B.M., Emanuelsson H., Peters G., et al. Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the DISPERSE-2 trial. J Am Coll Cardiol 50 19 (Nov 6 2007) 1844-1851
22. Fugate S.E., and Cudd L.A. Cangrelor for treatment of coronary thrombosis. Ann Pharmacother 40 5 (May 2006) 925-930
23. Storey R.F., Husted S., Harrington R.A., Heptinstall S., Wilcox R.G., Peters G., et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol 50 19 (Nov 6 2007) 1852-1856
24. Camaioni E., Boyer J.L., Mohanram A., Harden T.K., and Jacobson K.A. Deoxyadenosine bisphosphate derivatives as potent antagonists at P2Y1 receptors. J Med Chem 41 2 (Jan 15 1998) 183-190
25. Humphries R.G., Tomlinson W., Clegg J.A., Ingall A.H., Kindon N.D., and Leff P. Pharmacological profile of the novel P2T-purinoceptor antagonist, FPL 67085 in vitro and in the anaesthetized rat in vivo. Br J Pharmacol 115 6 (Jul 1995) 1110-1116
26. Schoenfeld H., Muhm M., Doepfmer U., Exadaktylos A., and Radtke H. Platelet activity in washed platelet concentrates. Anesth Analg 99 1 (Jul 2004) 17-20
27. Walkowiak B., Kralisz U., Michalec L., Majewska E., Koziolkiewicz W., Ligocka A., et al. Comparison of platelet aggregability and P-selectin surface expression on platelets isolated by different methods. Thromb Res 99 5 (Sep 1 2000) 495-502
28. Copeland R.A., Pompliano D.L., and Meek T.D. Drug-target residence time and its implications for lead optimization. Nat Rev Drug Discov 5 9 (Sep 2006) 730-739
29. Kahner B.N., Shankar H., Murugappan S., Prasad G.L., and Kunapuli S.P. Nucleotide receptor signaling in platelets. J Thromb Haemost 4 11 (Nov 2006) 2317-2326
30. Shankar H., Garcia A., Prabhakar J., Kim S., and Kunapuli S.P. P2Y12 receptor-mediated potentiation of thrombin-induced thromboxane A2 generation in platelets occurs through regulation of Erk1/2 activation. J Thromb Haemost 4 3 (Mar 2006) 638-647
31. Mangin P., Ohlmann P., Eckly A., Cazenave J.P., Lanza F., and Gachet C. The P2Y1 receptor plays an essential role in the platelet shape change induced by collagen when TxA2 formation is prevented. J Thromb Haemost 2 6 (Jun 2004) 969-977
32. Daniel J.L., Dangelmaier C., Jin J., Kim Y.B., and Kunapuli S.P. Role of intracellular signaling events in ADP-induced platelet aggregation. Thromb Haemost 82 4 (Oct 1999) 1322-1326
33. Quinton T.M., Murugappan S., Kim S., Jin J., and Kunapuli S.P. Different G protein-coupled signaling pathways are involved in alpha granule release from human platelets. J Thromb Haemost 2 6 (Jun 2004) 978-984