Author/Authors :
Qun Sun، نويسنده , , Laykea Tafesse، نويسنده , , Khondaker Islam، نويسنده , , Xiaoming Zhou، نويسنده , , Sam F. Victory، نويسنده , , Chongwu Zhang، نويسنده , , Mohamed Hachicha، نويسنده , , Lori A. Schmid، نويسنده , , Aniket Patel، نويسنده , , Yakov Rotshteyn، نويسنده , , Kenneth J. Valenzano، نويسنده , , Donald J. Kyle، نويسنده ,
Abstract :
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 [IC50=4.8 nM (pH) and 35 nM (CAP)] and orally available in rat (F%=15.1).
