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

Highlights

• 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.

Abstract

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.