Abstract
A series of high affinity CRF receptor ligands with an imidazo[4,5-b]pyridine core is described. Individual analogues were synthesized and tested in a rat CRF receptor binding assay. The best compounds were further tested in the dog N-in-1 pharmacokinetic model to assess plasma levels at 1mg/kg (po) and in the rat situational anxiety model to assess anxiolytic efficacy at 3mg/kg (po). The structure-activity relationships for good receptor binding affinity are described herein.
MeSH terms
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Animals
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Anti-Anxiety Agents / chemical synthesis
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Anti-Anxiety Agents / metabolism
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Anti-Anxiety Agents / pharmacology*
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Anxiety Disorders / drug therapy
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Dogs
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Half-Life
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Ligands
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Metabolic Clearance Rate
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Pyridines / chemical synthesis
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Pyridines / metabolism
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Pyridines / pharmacology*
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Rats
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Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
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Receptors, Corticotropin-Releasing Hormone / metabolism*
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Structure-Activity Relationship
Substances
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Anti-Anxiety Agents
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Ligands
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Pyridines
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Receptors, Corticotropin-Releasing Hormone