| 14505681 |
Sun Q, Tafesse L, Islam K, Zhou X, Victory SF, Zhang C, Hachicha M, Schmid LA, Patel A, Rotshteyn Y, Valenzano KJ, Kyle DJ: 4-(2-pyridyl) piperazine-1-carboxamides: potent vanilloid receptor 1 antagonists. Bioorg Med Chem Lett. 2003 Oct 20;13(20):3611-6.
A series of 4-(2-pyridyl) piperazine-1-carboxamide analogues based on the lead compound 1 was synthesized and evaluated for VR1 antagonist activity in capsaicin-induced (CAP) and pH (5.5)-induced (pH) FLIPR assays in a rat VR1-expressing HEK293 cell line. Potent VR1 antagonists were identified through SAR studies. From these studies, 18 was found to be very potent in the in vitro assay [IC (50)=4.8 nM (pH) and 35 nM (CAP)] and orally available in rat (F%=15.1). |
82(1,1,1,2) |