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Bioorg Med Chem Lett
; 26(19): 4781-4784, 2016 10 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-27595421
RESUMO
The synthesis, SAR and preclinical characterization of a series of 6-chloro-N-(2-(4,4-difluoropiperidin-1-yl)-2-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)quinoline-5-carboxamide based P2X7 antagonists is described herein. The lead compounds are potent inhibitors in Ca(2+) flux and whole blood IL-1ß P2X7 release assays at both human and mouse isoforms. Compound 1e showed a robust reduction of IL-1ß release in a mouse ex vivo model with a 50mg/kg oral dose. Evaluation of compound 1e in the mouse SNI tactile allodynia, carrageenan-induced paw edema or CIA models resulted in no analgesic or anti-inflammatory effects.