Abstract
Ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and biological activity. In this study, we explored the replacement of the alpha-aminoisobutyryl moiety by aromatic or heteroaromatic groups. Compounds 5 and 34 acted as potent in vivo antagonists of hexarelin-stimulated food intake. These two compounds did not stimulate growth hormone secretion in rodents and did not antagonize growth hormone secretion induced by hexarelin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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 / drug effects
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Growth Hormone / metabolism
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Humans
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LLC-PK1 Cells
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Oligopeptides / pharmacology
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Picolines / chemical synthesis*
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Picolines / chemistry
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Picolines / pharmacology
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Pyrazines / chemical synthesis*
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Pyrazines / chemistry
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Pyrazines / pharmacology
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Radioligand Assay
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Rats
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Receptors, Ghrelin / antagonists & inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
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Swine
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Triazoles / chemical synthesis*
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Triazoles / chemistry
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Triazoles / pharmacology
Substances
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Anti-Obesity Agents
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N-(1-(4-(2,4-dimethoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)picolinamide
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N-(1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)pyrazine-2-carboxamide
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Oligopeptides
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Picolines
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Pyrazines
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Receptors, Ghrelin
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Triazoles
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hexarelin
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Growth Hormone