SCH 530348: A novel oral thrombin receptor antagonist

Future Cardiology

Volumn 5, Issue 5, 2009, Pages 435-442

  Bonaca, Marc P ^a   Morrow, David A ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Antagonists; PAR 1; Protease activated receptor 1; SCH 530348; Thrombin

Indexed keywords

ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; CLOPIDOGREL; CYTOCHROME P450; FIBRINOGEN RECEPTOR ANTAGONIST; HEPARIN; HIMBACINE; HIRULOG; LOW MOLECULAR WEIGHT HEPARIN; PLACEBO; SCH 530348; THROMBIN RECEPTOR ACTIVATING PEPTIDE; UNCLASSIFIED DRUG; 3-PHENYLPYRIDINE; LACTONE; PROTEINASE ACTIVATED RECEPTOR 1; PYRIDINE DERIVATIVE; THROMBIN RECEPTOR; VORAPAXAR;

ACUTE CORONARY SYNDROME; ARTICLE; BLEEDING; BLEEDING TIME; BLOOD TRANSFUSION; CLINICAL TRIAL; DRUG BIOAVAILABILITY; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG ELIMINATION; DRUG FATALITY; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG SCREENING; DRUG STRUCTURE; DRUG TOLERABILITY; HEART DISEASE; HEART INFARCTION; HUMAN; LOADING DRUG DOSE; MAINTENANCE THERAPY; NONHUMAN; PARTIAL THROMBOPLASTIN TIME; PERCUTANEOUS CORONARY INTERVENTION; PHARMACODYNAMICS; PRIORITY JOURNAL; PROTHROMBIN TIME; SECONDARY PREVENTION; STROKE; THROMBOCYTE AGGREGATION INHIBITION; THROMBOSIS; ANTAGONISTS AND INHIBITORS; CHEMISTRY; CORONARY THROMBOSIS; DRUG EFFECTS; THROMBOCYTE AGGREGATION; THROMBOEMBOLISM;

ACUTE CORONARY SYNDROME; CORONARY THROMBOSIS; HUMANS; LACTONES; PLATELET AGGREGATION; PYRIDINES; RECEPTOR, PAR-1; RECEPTORS, THROMBIN; THROMBOEMBOLISM;

EID: 70349212530     PISSN: 14796678     EISSN: 17448298     Source Type: Journal    
DOI: 10.2217/fca.09.27     Document Type: Article

References (33)

1. WHO: Atlas of Heart Disease and Stroke. World Health Organization, Geneva, Switzerland (2004).
2. WHO: Global Burden of Disease Study. World Health Organization, Geneva, Switzerland 2004.
3. Lloyd-Jones D, Adams R, Carnethon M et al.: Heart disease and stroke statistics - 2009 update: a report from the American Heart Association statistics committee and stroke statistics subcommittee. Circulation. 119(3), 480-486 (2009).
4. Anderson JL, Adams CD, Antman EM et al.: ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/ American Heart Association task force on practice guidelines (writing committee to revise the 2002 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J. Am. Coll. Cardiol. 50(7), E1-E157 (2007).
5. Antman EM, Hand M, Armstrong PW et al.: 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/ American Heart Association task force on practice guidelines: developed in collaboration with the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 writing group to review new evidence and update the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction, writing on behalf of the 2004 writing committee. Circulation 117(2), 296-329 (2008).
6. Van de Werf F, Bax J, Betriu A et al.: Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the task force on the management of ST-segment elevation acute myocardial infarction of the european society of cardiology. Eur Heart J. 29(23), 2909-2945 (2008).
7. Patrono C, Bachmann F, Baigent C et al.: Expert consensus document on the use of antiplatelet agents. the task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the european society of cardiology. Eur. Heart J. 25(2), 166-181 (2004).
8. Anderson JL, Adams CD, Antman EM et al.: ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/ American Heart Association task force on practice guidelines (writing committee to revise the 2002 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J. Am. Coll. Cardiol. 50(7), E1-E157 (2007).
9. Yusuf S, Zhao F, Mehra SR et al.: Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N. Engl. J. Med. 345(7), 494-502 (2007).
10. Wiviott SD, Braunwald E, McCabe CH et al.: Prasugrel versus clopidogrel in patients with acute coronary syndromes. N. Engl. J. Med. 357(20), 2001-2015 (2007).
11. Davi G, Patrono C: Platelet activation and atherothrombosis. N. Engl. J. Med. 357(24), 2482-2494 (2007).
12. Kulkarni S, Dopheide SM, Yap CL et al.: A revised model of platelet aggregation. J. Clin. Invest. 105(6), 783-791 (2000).
13. Schwertz H, Tolley ND, Foulks JM et al.: Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenicity of human platelets. J. Exp. Med. 203(11), 2433-2440 (2006).
14. Offermanns S: Activation of platelet function through G protein-coupled receptors. Circ. Res. 99(12), 1293-1304 (2006)
15. Coughlin SR: Protease-activated receptors in hemostasis, thrombosis and vascular biology. J. Thromb. Haemost. 3(8), 1800-1814 (2005).
16. Nakanishi-Matsui M, Zheng YW, Sulciner DJ et al.: PAR3 is a cofactor for PAR4 activation by thrombin. Nature 404(6778), 609-613 (2000).
17. Coughlin SR: Thrombin signalling and protease-activated receptors. Nature 407(6801), 258-264 (2000).
18. Patterson C, Stouffer GA, Madamanchi N, Runge MS: New tricks for old dogs: nonthrombotic effects of thrombin in vessel wall biology. Circ. Res. 88(10), 987-997 (2001).
19. Coughlin SR: Protea se-activated receptors and platelet function. Thromb. Haemost. 82(2), 353-356 (1999).
20. Jennings LK: Role of platelets in atherothrombosis. Am. J. Cardiol. 103(Suppl. 3), 4A-10A (2009).
21. Ahn HS, Foster C, Boykow G, Stamford A, Manna M, Graziano M: Inhibition of cellular action of thrombin by N3-cyclopropyl-7- 4-(1-methylethyl)phenyl]methyl]-7H-pyrrolo[3, 2-f]quinazoline-1,3-diamine (SCH 79797), a nonpeptide thrombin receptor antagonist. Biochem Pharmacol. 60(10), 1425-1434 (2000).
22. Feng DM, Veber DF, Connolly TM et al.: Development of a potent thrombin receptor ligand. J. Med. Chem. 38(20), 4125-4130 (1995).
23. Chackalamannil S, Davies RJ, Wang Y et al.: Total synthesis of (+)-himbacine and (+)-himbeline. J. Org. Chem. 64(6), 1932-1940 (1999).
24. Chackalamannil S, Xia Y, Greenlee WJ et al.: Discovery of potent orally active thrombin receptor (protease activated receptor 1) antagonists as novel antithrombotic agents. J. Med. Chem. 48(19), 5884-5887 (2005).
25. Chelliah MV, Chackalamannil S, Xia Y et al.: Heterotricyclic himbacine analogs as potent, orally active thrombin receptor (protease activated receptor-1) antagonists. J. Med. Chem. 50(21), 5147-5160 (2007).
26. Chackalamannil S, Wang Y, Greenlee WJ et al.: Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (SCH 530348) with potent antiplatelet activity. J. Med. Chem. 51(11), 3061-3064 (2008).
27. Chintala M, Shimizu K, Ogawa M et al.: Basic and translational research on proteinase-activated receptors: antagonism of the proteinase-activated receptor 1 for thrombin, a novel approach to antiplatelet therapy for atherothrombotic disease. J. Pharmacol. Sci. 108(4), 433-438 (2008).
28. Chintala M, Vemulapalli S, Kurowski S et al.: SCH 530348, a novel oral antiplatelet agent, demonstrated no bleeding risk alone or in combination with aspirin and clopidogrel in cynomolgus monkeys. Arterioscler. Thromb. Vasc. Biol. 28, E138-EI39 (2008).
29. Kosoglou T, Reyderman L, Fales RR et al.: Pharmacodynamics and pharmacokinetics of a novel protease-activated receptor (PAR-1) antagonist SCH 530348. Circulation. 112(Suppl. II), 32 (2005).
30. Kosoglou T, Reyderman L, Kasserra C et al.: Optimizing dose of Teh novel thrombin receptor antagonist SCH 530348 based on pharmacodynamics and pharmacokinetics in healthy subjects. Clin, Pharmacol. Ther. 83, S55 (2008).
31. Becker RC, Moliterno DJ, Jennings LK et al.: Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled Phase II study. Lancet 373(9667), 919-928 (2009).
32. Goto S, Yamaguchi T, Ikeda Y et al.: Phase II trial of Teh Novel antiplatelet agent, SCH 530348, in Japapese patients with non-ST Segment elevationg acute coronary syndromes (NSTE ACS). Eur. Heart J. 29(Suppl.), 829 (abstract P4767) (2008).
33. Shinohata Y, Goto S, Shimizu K, Jensen P: A Phase II safety study of novel antiplatelet agent, SCH 530348, in Japanese patients with prior ischemic stroke. Int. J. Stroke 3(Suppl. 1), 139 (Abstract PO01-193) (2008).