Uses
AZD 1283 is a non-nucleotide reversible antagonist of P2Y12R, which regulates platelet activation and thrombus formation.
Biological Activity
the central role of the p2y12 receptor in platelet function makes it an attractive target for the development of novel antiplatelet therapies. azd1283 is found to be a potent, selective and reversible antagonist of the p2y12 receptor.
in vitro
it was observed that the benzylic azd1283 and its analogue 13 were both potent in the higher order residual platelet count assay in which the two tested 5-chlorothienyls showed low (ic50 >22 μm) potency [1].
in vivo
in a modified folts model in dog, both azd1283 and its analogue 13 could dose-dependently induce increases in blood flow and inhibition of adp-induced platelet aggregation with antithrombotic ed50 values of 3.0 and 10.0 μg/kg/min, respectively. the dose that induced a larger than 3-fold increase in bleeding time were 33 and 100 μg/kg/min for azd1283 and 13, respectively [2].
IC 50
0.011, 0.025 and 3.2 μm for binding, gtpγs and residual platelet count (rpc), respectively
References
[1] bach p, antonsson t, bylund r, björkman ja, österlund k, giordanetto f, van giezen jj, andersen sm, zachrisson h, zetterberg f. lead optimization of ethyl 6-aminonicotinate acyl sulfonamides as antagonists of the p2y12 receptor. separation of the antithrombotic effect and bleeding for candidate drug azd1283. j med chem. 2013;56(17):7015-24.
