4-(2-pyridyl)piperazine-1-carboxamides: potent vanilloid receptor 1 antagonists.
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).
D000818:Animals; D002460:Cell Line; D006801:Humans; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D010879:Piperazines; D011955:Receptors, Drug