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
; 19(6): 1632-5, 2009 Mar 15.
Article
in En
| MEDLINE
| ID: mdl-19231178
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pain
/
Pyrimidines
/
Chemistry, Pharmaceutical
/
Purinergic P2 Receptor Antagonists
/
Analgesics
Type of study:
Diagnostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2009
Document type:
Article
Affiliation country:
United States