title: 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.
abstract: 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.
authors.affiliation: Cardiovascular and Metabolic Diseases, PGRD, Pfizer Inc., Groton, Connecticut 06340, and Neurogen Corporation, Branford, Connecticut 06405, USA. richard_l_elliot@groton.pfizer.com
authors.forename: Richard L
authors.initials: RL
authors.lastname: Elliott
authors.forename: Robert M
authors.initials: RM
authors.lastname: Oliver
authors.forename: Marlys
authors.initials: M
authors.lastname: Hammond
authors.forename: Terrell A
authors.initials: TA
authors.lastname: Patterson
authors.forename: Li
authors.initials: L
authors.lastname: She
authors.forename: Diane M
authors.initials: DM
authors.lastname: Hargrove
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Martin
authors.forename: Tristan S
authors.initials: TS
authors.lastname: Maurer
authors.forename: J Cory
authors.initials: JC
authors.lastname: Kalvass
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Morgan
authors.forename: Paul A
authors.initials: PA
authors.lastname: DaSilva-Jardine
authors.forename: Ralph W
authors.initials: RW
authors.lastname: Stevenson
authors.forename: Christine M
authors.initials: CM
authors.lastname: Mack
authors.forename: James V
authors.initials: JV
authors.lastname: Cassella
mesh_terms: 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
chemical_list: 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