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ID: ALA1136919

Journal: Bioorg Med Chem Lett

Title: Synthesis and P2Y receptor activity of nucleoside 5'-phosphonate derivatives.

Authors: Cosyn L, Van Calenbergh S, Joshi BV, Ko H, Carter RL, Kendall Harden T, Jacobson KA.

Abstract: Ribose-based nucleoside 5'-diphosphates and triphosphates and related nucleotides were compared in their potency at the P2Y receptors with the corresponding nucleoside 5'-phosphonate derivatives. Phosphonate derivatives of UTP and ATP activated the P2Y(2) receptor but were inactive or weakly active at P2Y(4) receptor. Uridine 5'-(diphospho)phosphonate was approximately as potent at the P2Y(2) receptor as at the UDP-activated P2Y(6) receptor. These results suggest that removal of the 5'-oxygen atom from nucleotide agonist derivatives reduces but does not prevent interaction with the P2Y(2) receptor. Uridine 5'-(phospho)phosphonate as well as the 5'-methylenephosphonate equivalent of UMP were inactive at the P2Y(4) receptor and exhibited maximal effects at the P2Y(2) receptor that were 50% of that of UTP suggesting novel action of these analogues.

CiteXplore: 19419868

DOI: 10.1016/j.bmcl.2009.04.027