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

…, JR Gever, C Lin, PJ Wagner, Y Zhai, J Zira

Index: Jahangir, Alam; Alam, Muzaffar; Carter, David S.; Dillon, Michael P.; Bois, Daisy Joe Du; Ford, Anthony P.D.W.; Gever, Joel R.; Lin, Clara; Wagner, Paul J.; Zhai, Yansheng; Zira, Jeff Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 6 p. 1632 - 1635

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Citation Number: 35

Abstract

The purinoceptor subtypes P2X3 and P2X2/3 have been shown to play a pivotal role in models of various pain conditions. Identification of a potent and selective dual P2X3/P2X2/3 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 ...