10.1021/jm000020b.s001 Fernand-Pierre Gendron Fernand-Pierre Gendron Efrat Halbfinger Efrat Halbfinger Bilha Fischer Bilha Fischer Martine Duval Martine Duval Pédro D'Orléans-Juste Pédro D'Orléans-Juste Adrien R. Beaudoin Adrien R. Beaudoin Novel Inhibitors of Nucleoside Triphosphate Diphosphohydrolases:  Chemical Synthesis and Biochemical and Pharmacological Characterizations American Chemical Society 2000 10 μ M P 2X effect Pharmacological Characterizations nucleoside triphosphate diphosphohydrolase purinergic receptors NTPDase inhibitors NTPDase inhibitor Novel Inhibitors P 2Y 1 EC ATP analogues nonhydrolyzable analogue K i turkey erythrocytes enzyme source guinea pig purine ring blood pressure variations precontracted vessel 2000-05-11 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Novel_Inhibitors_of_Nucleoside_Triphosphate_Diphosphohydrolases_Chemical_Synthesis_and_Biochemical_and_Pharmacological_Characterizations/3679458 To elucidate the physiological role played by nucleoside triphosphate diphosphohydrolase (NTPDase; EC 3.6.1.5), adenine nucleotide analogues, modified on the purine ring, have been synthesized and tested as potential inhibitors. Resistance of ATP analogues to hydrolysis and their potency as NTPDase inhibitors were evaluated. For this purpose, a particulate fraction isolated from bovine spleen was used as the enzyme source. Among the synthesized analogues, 8-thiobutyladenosine 5‘-triphosphate (8-BuS-ATP) was found to be the most effective nonhydrolyzable competitive inhibitor, with an estimated <i>K</i><sub>i</sub> of 10 μM. This nonhydrolyzable analogue did not exert any P2X-receptor-mediated effect on endothelium-denuded blood vessels, from the guinea pig mesenteric bed. In agreement with this observation, infusion of the analogue did not cause any significant blood pressure variations of the precontracted vessel. Because in previous studies on isolated turkey erythrocytes and rat astrocytes 8-BuS-ATP was not able to trigger any P2Y<sub>1</sub>-receptor-mediated effect, it therefore appears that this NTPDase inhibitor does not interfere with purinergic receptors.