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

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 thromboembolic clinical sequelae.

Graphical abstractStarting with ATP, the identification of novel P2Y12 receptor antagonists are described. The leading compound, 17 (AZD6140), is currently in a phase III clinical trial for the treatment of acute coronary syndromes.Figure optionsDownload full-size imageDownload as PowerPoint slide