Abstract
Novel arylpyrazole derivatives were synthesized and evaluated as neuropeptide Y (NPY) Y5 receptor antagonists. Compound (-)-7, which features a novel chiral 2,3-dihydro-1H-cyclopenta[a]naphthalene moiety, showed good binding affinity and antagonistic activity for the Y5 receptor. After intracerebroventricular administration in SD rats, (-)-7 significantly inhibited food intake that was induced by the centrally administered Y5-preferring agonist, bovine pancreatic polypeptide, but had only a negligible effect on NPY-induced feeding.
MeSH terms
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Administration, Oral
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Animals
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Brain / metabolism*
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Cattle
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Eating / drug effects
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Humans
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Injections, Intraventricular
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Naphthalenes / chemical synthesis*
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Naphthalenes / pharmacokinetics
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Naphthalenes / pharmacology
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Pancreatic Polypeptide / pharmacology
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Permeability
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Pyrazoles / chemical synthesis*
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Pyrazoles / pharmacokinetics
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Pyrazoles / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Neuropeptide Y / antagonists & inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Naphthalenes
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Pyrazoles
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Receptors, Neuropeptide Y
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neuropeptide Y5 receptor
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Pancreatic Polypeptide