Antithrombotic P2Y12 Receptor Antagonists: Recent Developments in Drug Discovery

Published: 2019
Drug Discovery Today, Volume 24, Issue 1, January 2019, Pages 325-333
ISBN: 1359-6446

  • Antiplatelet agents play a key role in the therapy of acute coronary syndromes (ACS).
  • P2Y12 antagonists inhibit processes important for both thrombosis and haemostasis.
  • New scaffolds being developed to overcome the drawbacks of current antiplatelet drugs.
  • Antiplatelet agents are currently in preclinical and clinical trials.
  • Synergistic inhibition of P2 receptors serve as novel antiplatelet strategy.


The P2Y12 receptor is one of eight known P2Y receptor subtypes, and belongs to the G-protein-coupled receptor (GPCR) family. The P2Y12 receptor is highly expressed on blood platelets and in the brain. Potent, selective, peripherally acting antagonists for the P2Y12 receptor are used clinically as antithrombotic drugs. Several different scaffolds have been identified as P2Y12 receptor antagonists, including irreversibly acting thienotetrahydropyridines (prodrugs), and reversible competitive antagonists, including adenine nucleotide analogs, piperazinyl-glutamate-quinolines, -pyridines, and -pyrimidines, and anthraquinone derivatives. Here, we provide an overview of the different scaffolds that have been developed as P2Y12 receptor antagonists, some of which have become important therapeutics.