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ID: ALA1153300

Journal: Bioorg Med Chem Lett

Title: Identification and SAR of novel diaminopyrimidines. Part 2: The discovery of RO-51, a potent and selective, dual P2X(3)/P2X(2/3) antagonist for the treatment of pain.

Authors: Jahangir A, Alam M, Carter DS, Dillon MP, Bois DJ, Ford AP, Gever JR, Lin C, Wagner PJ, Zhai Y, Zira J.

Abstract: The purinoceptor subtypes P2X(3) and P2X(2/3) have been shown to play a pivotal role in models of various pain conditions. Identification of a potent and selective dual P2X(3)/P2X(2/3) diaminopyrimidine antagonist RO-4 prompted subsequent optimization of the template. This paper describes the SAR and optimization of the diaminopyrimidine ring and particularly the substitution of the 2-amino group. The discovery of the highly potent and drug-like dual P2X(3)/P2X(2/3) antagonist RO-51 is presented.

CiteXplore: 19231178

DOI: 10.1016/j.bmcl.2009.01.097