Abstract
A series of 2-aminobenzimidazole-based MCH1R antagonists was identified by core replacement of the aminoquinoline lead 1. Subsequent modification of the 2- and 5-positions led to improvement in potency and intrinsic clearance. Compound 25 exhibited good plasma and brain exposure, and attenuated MCH induced food intake at 30mg/kg PO in rats.
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 / pharmacokinetics
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Benzimidazoles / chemical synthesis
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Benzimidazoles / chemistry*
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Benzimidazoles / pharmacokinetics
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Eating / drug effects
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Rats
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Rats, Sprague-Dawley
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Receptors, Somatostatin / antagonists & inhibitors*
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Receptors, Somatostatin / metabolism
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Structure-Activity Relationship
Substances
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Anti-Obesity Agents
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Benzimidazoles
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MCHR1 protein, rat
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Receptors, Somatostatin
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2-aminobenzimidazole