| Title : Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists - Nelson_2006_J.Med.Chem_49_3659 |
| Author(s) : Nelson DW , Gregg RJ , Kort ME , Perez-Medrano A , Voight EA , Wang Y , Grayson G , Namovic MT , Donnelly-Roberts D , Niforatos W , Honore P , Jarvis MF , Faltynek CR , Carroll WA |
| Ref : Journal of Medicinal Chemistry , 49 :3659 , 2006 |
| Abstract : 1-Benzyl-5-aryltetrazoles were discovered to be novel antagonists for the P2X(7) receptor. Structure-activity relationship (SAR) studies were conducted around both the benzyl and phenyl moieties. In addition, the importance of the regiochemical substitution on the tetrazole was examined. Compounds were evaluated for activity to inhibit calcium flux in both human and rat recombinant P2X(7) cell lines using fluorometric imaging plate reader technology. Analogues were also assayed for their ability to inhibit IL-1beta release and to inhibit P2X(7)-mediated pore formation in human THP-1 cells. Compound 15d was advanced to efficacy studies in a model of neuropathic pain where significant reversal of mechanical allodynia was observed at doses that did not affect motor coordination. |
| ESTHER : Nelson_2006_J.Med.Chem_49_3659 |
| PubMedSearch : Nelson_2006_J.Med.Chem_49_3659 |
| PubMedID: 16759108 |
Nelson DW, Gregg RJ, Kort ME, Perez-Medrano A, Voight EA, Wang Y, Grayson G, Namovic MT, Donnelly-Roberts D, Niforatos W, Honore P, Jarvis MF, Faltynek CR, Carroll WA (2006)
Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists
Journal of Medicinal Chemistry
49 :3659
Nelson DW, Gregg RJ, Kort ME, Perez-Medrano A, Voight EA, Wang Y, Grayson G, Namovic MT, Donnelly-Roberts D, Niforatos W, Honore P, Jarvis MF, Faltynek CR, Carroll WA (2006)
Journal of Medicinal Chemistry
49 :3659