Abstract
Continuing medicinal chemistry studies to identify spiropiperidine-derived NPY Y5 receptor antagonists are described. Aryl urea derivatives of a variety of spiropiperidines were tested for their NPY Y5 receptor binding affinities. Of the spiropiperidines so far examined, spiro[3-oxoisobenzofurane-1(3H),4'-piperidine] was a useful scaffold for producing orally active NPY Y5 receptor antagonists. Oral administration of 5c significantly inhibited the Y5 agonist-induced food intake in rats with a minimum effective dose of 3mg/kg. In addition, this compound was efficacious in decreasing body weight in diet-induced obese mice.
MeSH terms
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Administration, Oral
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Animals
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Anti-Obesity Agents / chemical synthesis
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Anti-Obesity Agents / chemistry*
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Anti-Obesity Agents / pharmacology
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Eating
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Humans
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Mice
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Piperidines / chemical synthesis
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Piperidines / chemistry*
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Piperidines / pharmacology
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Rats
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Receptors, Neuropeptide Y / antagonists & inhibitors*
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Receptors, Neuropeptide Y / metabolism
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Spiro Compounds / chemical synthesis
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Spiro Compounds / chemistry*
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Spiro Compounds / pharmacology
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Urea / analogs & derivatives*
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Urea / chemical synthesis
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Urea / pharmacology
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Weight Loss
Substances
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Anti-Obesity Agents
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Piperidines
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Receptors, Neuropeptide Y
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Spiro Compounds
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neuropeptide Y5 receptor
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spiro(3-oxoisobenzofurane-1(3H),4'-piperidine)
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Urea