Imidazo[4,5-b]pyridines as corticotropin releasing factor receptor ligands.
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.
Arvanitis
Argyrios G
AG
Discovery Chemistry-Wilmington, Bristol-Myers Squibb Company, Experimental Station, DE 19880, USA. argyrios.arvanitis@bms.com
Rescinito
Joseph T
JT
Arnold
Charles R
CR
Wilde
Richard G
RG
Cain
Gary A
GA
Sun
Jung Hui
JH
Yan
Jia-Sheng
JS
Teleha
Christopher A
CA
Fitzgerald
Lawrence W
LW
McElroy
John
J
Zaczek
Robert
R
Hartig
Paul R
PR
Grossman
Scott
S
Arneric
Stephen P
SP
Gilligan
Paul J
PJ
Olson
Richard E
RE
Robertson
David W
DW
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
D014151:Anti-Anxiety Agents; D008024:Ligands; D011725:Pyridines; D018019:Receptors, Corticotropin-Releasing Hormone