Abstract
New cholecystokinin-1 receptor (CCK1R) agonist 'triggers' were identified using iterative library synthesis. Structural activity relationship studies led to the discovery of compound 10e, a potent CCK1R agonist that demonstrated robust weight loss in a diet-induced obese rat model with very low systemic exposure. Pharmacokinetic data suggest that efficacy is primarily driven through activation of CCK1R's located within the intestinal wall.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacology
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Animals
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Cells, Cultured
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Disease Models, Animal
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Drug Discovery*
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Humans
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Inhibitory Concentration 50
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Male
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Mice
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Mice, Obese
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Piperidines / chemical synthesis*
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Piperidines / chemistry
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Piperidines / pharmacology
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Protein Binding / drug effects
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Rats
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Rats, Sprague-Dawley
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Receptor, Cholecystokinin A / agonists*
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Structure-Activity Relationship
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Weight Loss / drug effects
Substances
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Amides
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Piperidines
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Receptor, Cholecystokinin A
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piperidine