Imidazo[4,5- b]pyridines as corticotropin releasing factor receptor ligands

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 1; pp. 125 - 128
• Main Authors: Arvanitis, Argyrios G., Rescinito, Joseph T., Arnold, Charles R., Wilde, Richard G., Cain, Gary A., Sun, Jung Hui, Yan, Jia-Sheng, Teleha, Christopher A., Fitzgerald, Lawrence W., McElroy, John, Zaczek, Robert, Hartig, Paul R., Grossman, Scott, Arneric, Stephen P., Gilligan, Paul J., Olson, Richard E., Robertson, David W.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 06.01.2003; Elsevier
• Subjects: Animals; Anti-Anxiety Agents - chemical synthesis; Anti-Anxiety Agents - metabolism; Anti-Anxiety Agents - pharmacology; Anxiety Disorders - drug therapy; Biological and medical sciences; Dogs; Half-Life; Ligands; Medical sciences; Metabolic Clearance Rate; Neuropharmacology; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Pyridines - chemical synthesis; Pyridines - metabolism; Pyridines - pharmacology; Rats; Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors; Receptors, Corticotropin-Releasing Hormone - metabolism; Structure-Activity Relationship; Rat; Nitrogen heterocycle; Ligand; Psychotropic; Corticotropin releasing factor; Peptide hormone; Non peptide compound; Structure activity relation; Chlorine Organic compounds; Area under the curve; Bicyclic compound; Peptidergic receptor; Hormone releasing factor; Chemical synthesis; Dog; Fissipedia; Carnivora; Ether; Rodentia; Oral administration; In vitro; Hypothalamic hormone; In vivo; Vertebrata; Biological fixation; Mammalia; Tranquillizer; Animal; Pharmacokinetics
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00833-8

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 1 mg/kg (po) and in the rat situational anxiety model to assess anxiolytic efficacy at 3 mg/kg (po). The structure–activity relationships for good receptor binding affinity are described herein. A series of high affinity CRF receptor ligands with an imidazo[4,5- b]pyridine core is described. Analogues were synthesized and tested in a rat CRF receptor binding assay. The best compounds were tested in the dog N-in-1 pharmacokinetic at 1 mg/kg (po) and in the rat situational anxiety model at 3 mg/kg (po).