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

  • Bioorg Med Chem Lett. 2009 Mar 15;19(6):1632-5. doi: 10.1016/j.bmcl.2009.01.097.
Alam Jahangir  1 ,  Muzaffar Alam ,  David S Carter ,  Michael P Dillon ,  Daisy Joe Du Bois ,  Anthony P D W Ford ,  Joel R Gever ,  Clara Lin ,  Paul J Wagner ,  Yansheng Zhai ,  Jeff Zira
Affiliations
  • 1. Department of Medicinal Chemistry, Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA.
PMID: 19231178 DOI: 10.1016/j.bmcl.2009.01.097
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.

Products