From ATP to AZD6140: The discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 21, 2007, Pages 6013-6018

  Springthorpe, Brian ^a   Bailey, Andrew ^a   Barton, Patrick ^a   Birkinshaw, Timothy N ^a   Bonnert, Roger V ^a   Brown, Roger C ^a   Chapman, David ^a   Dixon, John ^a   Guile, Simon D ^a   Humphries, Robert G ^a   Hunt, Simon F ^a   Ince, Francis ^a   Ingall, Anthony H ^a   Kirk, Ian P ^a   Leeson, Paul D ^a   Leff, Paul ^a   Lewis, Richard J ^a   Martin, Barrie P ^a   McGinnity, Dermot F ^a   Mortimore, Michael P ^a   Paine, Stuart W ^a   Pairaudeau, Garry ^a   Patel, Anil ^a   Rigby, Aaron J ^a   Riley, Robert J ^a   Teobald, Barry J ^a   Tomlinson, Wendy ^a   Webborn, Peter J H ^a   Willis, Paul A ^a   more..

^a ASTRAZENECA   (United Kingdom)

Author keywords

ATP; AZD6140; P2Y12 receptor antagonist; Thrombosis

Indexed keywords

3 [7 [2 (3,4 DIFLUOROPHENYL)CYCLOPROPYLAMINO] 5 PROPYLTHIO 1,2,3 TRIAZOLO[4,5 D]PYRIMIDIN 3 YL] 5 HYDROXYMETHOXY 1,2 CYCLOPENTANEDIOL; ADENOSINE TRIPHOSPHATE; CANGRELOR; CLOPIDOGREL; PURINE P2Y12 RECEPTOR; PURINE P2Y12 RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG;

ACUTE CORONARY SYNDROME; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CHEMICAL MODIFICATION; CLINICAL TRIAL; CONTROLLED STUDY; DOG; DRUG RECEPTOR BINDING; HUMAN; HUMAN CELL; HYDROPHOBICITY; MOLECULAR MODEL; NONHUMAN; PHASE 3 CLINICAL TRIAL; RAT; STRUCTURE ACTIVITY RELATION; THROMBOEMBOLISM; THROMBOSIS PREVENTION;

ADENOSINE; ADENOSINE TRIPHOSPHATE; ADMINISTRATION, ORAL; ANIMALS; HUMANS; MEMBRANE PROTEINS; RECEPTORS, PURINERGIC P2; THROMBOSIS;

EID: 34548841427     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.07.057     Document Type: Article

References (21)

1. Frishman W.H., Burns B., Atac B., Alturak N., Altajar B., and Lerrick K. Am. Heart J. 130 (1995) 877
2. Leff P., Robertson M.J., and Humphries R.G. In: Jacobson K.A., and Jarvis M.J. (Eds). Purinergic Approaches in Experimental Therapeutics (1997), Wiley-Liss, New York 203-216
3. CAPRIE Steering Committee (CAPRIE). Lancet 1996, 348, 1329.
4. The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators (CURE). N. Engl. J. Med. 2001, 345, 494.
5. Ingall A.H., Dixon J., Bailey A., Coombs M.E., Cox D., McInally J.I., Hunt S.F., Kindon N.D., Teobald B.J., Willis P.A., Humphries R.G., Leff P., Clegg J.A., Smith J.A., and Tomlinson W. J. Med. Chem. 42 (1999) 213
6. Humphries R.G. Haematologica 85 (2000) 66
7. Albert A. In: Katritzky A.R. (Ed). Advances in Heterocyclic Chemistry 39 (1986), Academic Press 117-180
8. Marquez V.E., and Lim M.L. Med. Res. Rev. 6 (1986) 1
9. 50. Full assay details are given in:. Humphries R.G., Tomlinson W., Ingall A.H., Cage P.A., and Leff P. Br. J. Pharmacol. 113 (1994) 1057
10. i. Full assay details are given in: Kirk, I. PCT Int. Appl. WO200033080, 2000; Chem. Abstr. 2000, 133, 14307.
11. Bonnert, R. V.; Ingall, A. H.; Springthorpe, B.; Willis, P. A. PCT Int. Appl. W0199828300, 1998; Chem, Abstr. 1998, 129, 95506.
12. Guile, S. D.; Ingall, A. H.; Springthorpe, B.; Willis, P. A. PCT Int. Appl. WO199905143, 1999; Chem, Abstr. 1999, 130, 168386.
13. Mitscher L.A., Sharma P.N., Chu D.T.W., Shen L.L., and Pernet A.G. J. Med. Chem. 29 (1986) 2044
14. Martin, I. J.; Lewis, R. J.; Bernstein, M. A.; Beattie, I. G.; Martin, C. A.; Riley, R. J.; Springthorpe, B. Drug Metab. Dispos. 2006, 34, 1502.
15. Bouska, J. J.; Bell, R. L.; Goodfellow, C. L.; Stewart, A. O.; Brooks, C. D.; Carter, G. W. Drug Metab. Dispos. 1997, 25, 1032.
16. For review, see. Oppolzer W. Pure Appl. Chem. 62 (1990) 1241
17. Vallgarda J., and Hacksell U. Tetrahedron Lett. 32 (1991) 5625
18. Shiori T. In: Trost M.T., Fleming I., and Winterfeldt E. (Eds). Comprehensive Organic Synthesis, Selectivity, Strategy and Efficiency in Modern Organic Chemistry. 1st ed. (1991), Pergamon Press, London 795-827
19. Jumnah R., Williams J.M.J., and Williams A.C. Tetrahedron Lett. 34 (1993) 6619
20. See. Trost B.M., Kuo G.-H., and Benneche T. J. Am. Chem. Soc. 110 (1988) 621 and references cited therein
21. Husted S., Emanuelsson H., Heptinstall S., Sandset P.M., Wickens M., and Peters G. Eur. Heart J. 27 (2006) 1038