From ATP to AZD6140: the discovery of an orally active reversible P2Y 12 receptor antagonist for the prevention of thrombosis

…, D Chapman, J Dixon, SD Guile, RG Humphries…

Index: Springthorpe, Brian; Bailey, Andrew; Barton, Patrick; Birkinshaw, Timothy N.; Bonnert, Roger V.; Brown, Roger C.; Chapman, David; Dixon, John; Guile, Simon D.; Humphries, Robert G.; Hunt, Simon F.; Ince, Francis; Ingall, Anthony H.; Kirk, Ian P.; Leeson, Paul D.; Leff, Paul; Lewis, Richard J.; Martin, Barrie P.; McGinnity, Dermot F.; Mortimore, Michael P.; Paine, Stuart W.; Pairaudeau, Garry; Patel, Anil; Rigby, Aaron J.; Riley, Robert J.; Teobald, Barry J.; Tomlinson, Wendy; Webborn, Peter J.H.; Willis, Paul A. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 21 p. 6013 - 6018

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Citation Number: 161

Abstract

Starting from adenosine triphosphate (ATP), the identification of a novel series of P2Y12 receptor antagonists and exploitation of their SAR is described. Modifications of the acidic side chain and the purine core and investigation of hydrophobic substituents led to a series of neutral molecules. The leading compound, 17 (AZD6140), is currently in a large phase III clinical trial for the treatment of acute coronary syndromes and prevention of ...