Antithrombotic P2Y ₁₂ receptor antagonists: recent developments in drug discovery

The P2Y ₁₂ receptor is one of eight known P2Y receptor subtypes, and belongs to the G-protein-coupled receptor (GPCR) family. The P2Y ₁₂ receptor is highly expressed on blood platelets and in the brain. Potent, selective, peripherally acting antagonists for the P2Y ₁₂ receptor are used clinically as antithrombotic drugs. Several different scaffolds have been identified as P2Y ₁₂ 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 P2Y ₁₂ receptor antagonists, some of which have become important therapeutics.