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.
MeSH terms
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Animals
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Brain / metabolism
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Calcium / metabolism
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Cattle
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Cerebrospinal Fluid / metabolism
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Eating / drug effects
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Humans
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Imidazoles / chemical synthesis*
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Imidazoles / pharmacokinetics
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Imidazoles / pharmacology
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In Vitro Techniques
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Male
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Nitriles / chemical synthesis*
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Nitriles / pharmacokinetics
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Nitriles / pharmacology
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Pancreatic Polypeptide / pharmacology
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Rats
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Rats, Sprague-Dawley
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Rats, Wistar
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Receptors, Neuropeptide Y / antagonists & inhibitors*
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Receptors, Neuropeptide Y / metabolism
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Tissue Distribution
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Tumor Cells, Cultured
Substances
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3-(2-(6-(2-tert-butoxyethoxy)pyridin-3-yl)-1H-imidazol-4-yl)benzonitrile
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Imidazoles
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Nitriles
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Receptors, Neuropeptide Y
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neuropeptide Y5 receptor
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Pancreatic Polypeptide
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Calcium