title: Imidazo[4,5-b]pyridines as corticotropin releasing factor receptor ligands.
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.
authors.affiliation: Discovery Chemistry-Wilmington, Bristol-Myers Squibb Company, Experimental Station, DE 19880, USA. argyrios.arvanitis@bms.com
authors.forename: Argyrios G
authors.initials: AG
authors.lastname: Arvanitis
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Rescinito
authors.forename: Charles R
authors.initials: CR
authors.lastname: Arnold
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wilde
authors.forename: Gary A
authors.initials: GA
authors.lastname: Cain
authors.forename: Jung Hui
authors.initials: JH
authors.lastname: Sun
authors.forename: Jia-Sheng
authors.initials: JS
authors.lastname: Yan
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Teleha
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Fitzgerald
authors.forename: John
authors.initials: J
authors.lastname: McElroy
authors.forename: Robert
authors.initials: R
authors.lastname: Zaczek
authors.forename: Paul R
authors.initials: PR
authors.lastname: Hartig
authors.forename: Scott
authors.initials: S
authors.lastname: Grossman
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Arneric
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Gilligan
authors.forename: Richard E
authors.initials: RE
authors.lastname: Olson
authors.forename: David W
authors.initials: DW
authors.lastname: Robertson
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000188:drug therapy; D004285:Dogs; D006207:Half-Life; D008024:Ligands; D008657:Metabolic Clearance Rate; D011725:Pyridines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D014151:Anti-Anxiety Agents; D008024:Ligands; D011725:Pyridines; D018019:Receptors, Corticotropin-Releasing Hormone