Novel nucleotide triphosphates as potent P2Y2 agonists with enhanced stability over UTP

The synthesis of a series of novel C-linked nucleotide triphosphates is reported. These exhibit excellent agonist potency and selectivity for the P2Y2 receptor with a number of examples having EC50 values below 10 nM. Representative compounds from the N-linked and C-linked series showed enhanced metabolic stability compared with that of the natural ligand UTP.

The synthesis and P2Y2 activities of some novel C-linked nucleotide triphosphates are reported. These exhibit excellent agonist potency and selectivity for the P2Y2 receptor. Stability studies were carried out on representative compounds from the N-linked and C-linked series; these showed enhanced metabolic stability compared with that of UTP.Figure optionsDownload as PowerPoint slide