Abstract |
Selective CB2 receptor agonists are promising potential therapeutic agents for the treatment of inflammatory and neuropathic pain. A focused screen identified a pyrimidine ester as a partial agonist at the CB2 receptor with micromolar potency. Subsequent lead optimization identified 35, GW842166X, as the optimal compound in the series. 35 has an oral ED50 of 0.1 mg/kg in the rat FCA model of inflammatory pain and was selected as a clinical candidate for this indication.
|
Authors | Gerard M P Giblin, Celestine T O'Shaughnessy, Alan Naylor, William L Mitchell, Andrew J Eatherton, Brian P Slingsby, D Anthony Rawlings, Paul Goldsmith, Andrew J Brown, Carl P Haslam, Nick M Clayton, Alex W Wilson, Iain P Chessell, Andrew R Wittington, Richard Green |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 50
Issue 11
Pg. 2597-600
(May 31 2007)
ISSN: 0022-2623 [Print] United States |
PMID | 17477516
(Publication Type: Journal Article)
|
Chemical References |
- 2-((2,4-dichlorphenyl)amino)-N-((tetrahydro-2H-pyran-4-yl)methyl)-4-(trifluoromethyl)-5-pyrimidinecarboxamide
- Analgesics
- Pyrans
- Pyrimidines
- Receptor, Cannabinoid, CB2
|
Topics |
- Analgesics
(chemical synthesis, pharmacokinetics, pharmacology)
- Animals
- Biological Availability
- Half-Life
- Humans
- Inflammation
(drug therapy, metabolism)
- Pain
(drug therapy, metabolism)
- Pyrans
(chemical synthesis, pharmacokinetics, pharmacology)
- Pyrimidines
(chemical synthesis, pharmacokinetics, pharmacology)
- Rats
- Receptor, Cannabinoid, CB2
(agonists)
- Structure-Activity Relationship
|