In vitro and in vivo characterization of 3-[2-[6-(2-tert-butoxyethoxy)pyridin-3-yl]-1H-imidazol-4-yl]benzonitrile hydrochloride salt, a potent and selective NPY5 receptor antagonist.
To investigate the anorectic potential of NPY5 receptor antagonists, we have profiled the in vitro and in vivo properties of 3-[2-[6-(2-tert-butoxyethoxy)pyridin-3-yl]-1H-imidazol-4-yl]benzonitrile hydrochloride salt (1). This compound was found to have excellent NPY5 receptor affinity and selectivity, potent functional antagonism, and good peripheral and central nervous system exposure in rats. This compound attenuated bovine pancreatic polypeptide induced food intake in rats but failed to demonstrate anorectic activity in rodent natural feeding models.
Elliott
Richard L
RL
Cardiovascular and Metabolic Diseases, PGRD, Pfizer Inc., Groton, Connecticut 06340, and Neurogen Corporation, Branford, Connecticut 06405, USA. richard_l_elliot@groton.pfizer.com
Oliver
Robert M
RM
Hammond
Marlys
M
Patterson
Terrell A
TA
She
Li
L
Hargrove
Diane M
DM
Martin
Kelly A
KA
Maurer
Tristan S
TS
Kalvass
J Cory
JC
Morgan
Bradley P
BP
DaSilva-Jardine
Paul A
PA
Stevenson
Ralph W
RW
Mack
Christine M
CM
Cassella
James V
JV
D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002555:Cerebrospinal Fluid / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009570:Nitriles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D010191:Pancreatic Polypeptide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
C472565:3-(2-(6-(2-tert-butoxyethoxy)pyridin-3-yl)-1H-imidazol-4-yl)benzonitrile; D007093:Imidazoles; D009570:Nitriles; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor; D010191:Pancreatic Polypeptide; D002118:Calcium