Antithrombotic P2Y12 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.