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ID: ALA1153301

Journal: Bioorg Med Chem Lett

Title: Identification and SAR of novel diaminopyrimidines. Part 1: The discovery of RO-4, a dual P2X(3)/P2X(2/3) antagonist for the treatment of pain.

Authors: Carter DS, Alam M, Cai H, Dillon MP, Ford AP, Gever JR, Jahangir A, Lin C, Moore AG, Wagner PJ, Zhai Y.

Abstract: P2X purinoceptors are ligand-gated ion channels whose endogenous ligand is ATP. Both the P2X(3) and P2X(2/3) receptor subtypes have been shown to play an important role in the regulation of sensory function and dual P2X(3)/P2X(2/3) antagonists offer significant potential for the treatment of pain. A high-throughput screen of the Roche compound collection resulted in the identification of a novel series of diaminopyrimidines; subsequent optimization resulted in the discovery of RO-4, a potent, selective and drug-like dual P2X(3)/P2X(2/3) antagonist.

CiteXplore: 19231180

DOI: 10.1016/j.bmcl.2009.02.003