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

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 21; pp. 6013 - 6018
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 2007
• Subjects: ATP; AZD6140; P2Y 12 receptor antagonist; Thrombosis; AZD6140; P2Y 12 receptor antagonist; ATP; Thrombosis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2007.07.057

Starting with ATP, the identification of novel P2Y 12 receptor antagonists are described. The leading compound, 17 (AZD6140), is currently in a phase III clinical trial for the treatment of acute coronary syndromes. Starting from adenosine triphosphate (ATP), the identification of a novel series of P2Y 12 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 thromboembolic clinical sequelae.