4-(2-Pyridyl)piperazine-1-carboxamides: Potent vanilloid receptor 1 antagonists

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 throug...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2003-10, Vol.13 (20), p.3611-3616
Hauptverfasser: QUN SUN, TAFESSE, Laykea, VALENZANO, Kenneth J, KYLE, Donald J, ISLAM, Khondaker, XIAOMING ZHOU, VICTORY, Sam F, CHONGWU ZHANG, HACHICHA, Mohamed, SCHMID, Lori A, PATEL, Aniket, ROTSHTEYN, Yakov
Format: Artikel
Sprache:eng
Schlagworte:
Analgesics
Animals
Biological and medical sciences
Cell Line
Humans
Medical sciences
Neuropharmacology
Pharmacology. Drug treatments
Piperazines - chemistry
Piperazines - pharmacology
Rats
Receptors, Drug - antagonists & inhibitors
Structure-Activity Relationship
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Zusammenfassung: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).
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(03)00759-5