Overcoming clopidogrel resistance: Discovery of vicagrel as a highly potent and orally bioavailable antiplatelet agent

Journal of Medicinal Chemistry

Volumn 55, Issue 7, 2012, Pages 3342-3352

  Shan, Jiaqi ^a   Zhang, Boyu ^a   Zhu, Yaoqiu ^b   Jiao, Bo ^c   Zheng, Weiyi ^d   Qi, Xiaowei ^e   Gong, Yanchun ^a   Yuan, Fang ^e   Lv, Fusheng ^e   Sun, Hongbin ^a  

^a CHINA PHARMACEUTICAL UNIVERSITY   (China)

^b MetabQuest Research Laboratory   (United States)

^c SHANDONG UNIVERSITY   (China)

^d Concord Pharmatech Co Ltd ^*  (China)

^e Jiangsu Vcare PharmaTech Co Ltd   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE DIPHOSPHATE; ANTICOAGULANT AGENT; ANTITHROMBOCYTIC AGENT; CLOPIDOGREL; CLOPIDOGREL THIOLACTONE; CYTOCHROME P450 2C19; PRASUGREL; THIENOPYRIDINE DERIVATIVE; UNCLASSIFIED DRUG; VICAGREL;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DESIGN; DRUG EFFICACY; DRUG INHIBITION; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENCY; DRUG SAFETY; DRUG SYNTHESIS; FEMALE; IN VITRO STUDY; IN VIVO STUDY; LOW DRUG DOSE; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; OPTICS; PHARMACOLOGICAL PARAMETERS; RAT; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; THROMBOCYTE AGGREGATION; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; DRUG RESISTANCE; FEMALE; MALE; MICE; MICROSOMES, LIVER; PHENYLACETATES; PLATELET AGGREGATION INHIBITORS; PRODRUGS; RATS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES; TICLOPIDINE;

EID: 84859788635     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm300038c     Document Type: Article

References (16)

1. Yusuf, S.; Zhao, F.; Mehta, S. R.; Chrolavicius, S.; Tognoni, G.; Fox, K. K. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation N. Engl. J. Med. 2001, 345, 494-502
2. Hagihara, K.; Kazui, M.; Ikenaga, H.; Nanba, T.; Fusegawa, K.; Takahashi, M.; Kurihara, A.; Okazaki, O.; Farid, N. A.; Ikeda, T. Comparison of formation of thiolactones and active metabolites of prasugrel and clopidogrel in rats and dogs Xenobiotica 2009, 39, 218-226
3. Dangas, G.; Mehran, R.; Guagliumi, G.; Caixeta, A.; Witzenbichler, B.; Aoki, J.; Peruga, J. Z.; Brodie, B. R.; Dudek, D.; Kornowski, R.; Rabbani, L. E.; Parise, H.; Stone, G. W.; HORIZONS-AMI Trial Investigators. Role of clopidogrel loading dose in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty: results from the HORIZONSAMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trial J. Am. Coll. Cardiol. 2009, 54, 1438-1446
4. Mega, J. L.; Close, S. L.; Wiviott, S. D.; Shen, L.; Hockett, R. D.; Brandt, J. T.; Walker, J. R.; Antman, E. M.; Macias, W.; Braunwald, E.; Sabatine, M. S. Cytochrome P-450 plymorphisms and response to clopidogrel N. Engl. J. Med. 2009, 360, 354-362
5. Mega, J. L.; Simon, T.; Collet, J. P.; Anderson, J. L.; Antman, E. M.; Bliden, K.; Cannon, C. P.; Danchin, N.; Giusti, B.; Gurbel, P.; Horne, B. D.; Hulot, J. S.; Kastrati, A.; Montalescot, G.; Neumann, F. J.; Shen, L.; Sibbing, D.; Steg, P. G.; Trenk, D.; Wiviott, S. D.; Sabatine, M. S. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI A meta-analysis JAMA, J. Am. Med. Assoc. 2010, 304, 1821-1830
6. Kim, J. Y. Strategy for the treatment of clopidogrel low responsiveness in diabetes mellitus and stent implantation Korean Circ. J. 2009, 39, 459-461
7. Serenbyany, V. L.; Malinin, A. I.; Makarov, L. M. Clopidogrel resistance: myth or reality Kardiologiia 2007, 47, 69-72
8. Born, G. V. Aggregation of blood platelets by adenosine diphosphate and its reversal Nature 1962, 194, 927-929
9. Dansette, P. M.; Libraire, J.; Bertho, G.; Mansuy, D. Metabolic oxidative cleavage of thioesters: evidence for the formation of sulfenic acid intermediates in the bioactivation of the antithrombotic prodrugs ticlopidine and clopidogrel Chem. Res. Toxicol. 2009, 22, 369-373
10. Kazui, M.; Nishiya, Y.; Ishizuka, T.; Hagihara, K.; Farid, N. A.; Okazaki, O.; Ikeda, T.; Kurihara, A. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite Drug Metab. Dispos. 2010, 38, 92-99
11. Dansette, P. M.; Thébault, S.; Bertho, G.; Mansuy, D. Formation and fate of a sulfenic acid intermediate in the metabolic activation of the antithrombotic prodrug prasugrel Chem. Res. Toxicol. 2010, 23, 1268-1274
12. Pereillo, J. M.; Maftouh, M.; Andrieu, A.; Uzabiaga, M. F.; Fedeli, O.; Savi, P.; Pascal, M.; Herbert, J. M.; Maffrand, J. P.; Picard, C. Structure and stereochemistry of the active metabolite of clopidogrel Drug Metab. Dispos. 2002, 30, 1288-1295
13. Paré, G.; Mehta, S. R.; Yusuf, S.; Anand, S. S.; Connolly, S. J.; Hirsh, J.; Simonsen, K.; Bhatt, D. L.; Fox, K. A. A.; Eikelboom, J. W. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment N. Engl. J. Med. 2010, 363, 1704-1714
14. Holmes, M. V.; Perel, P.; Shah, T.; Hingorani, A. D.; Casas, J. P. CYP2C19 genotype, clopidogrel metabolism, platelet function, and cardiovascular events: a systematic review and meta-analysis JAMA, J. Am. Med. Assoc. 2011, 306, 2704-2714
15. Fox, K. A. A. Progress from trials to practice Nat. Rev. Cardiol. 2011, 8, 68-70
16. Goldstein, J. A.; Ishizaki, T.; Chiba, K.; de Morais, S. M. F.; Bell, D.; Krahn, P. M.; Evans, D. A. P. Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations Pharmacogenetics 1997, 7, 59-64