Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 52, Issue 9, Pages 3084-3092Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm900025h
Keywords
-
Categories
Ask authors/readers for more resources
This report describes the syntheses and structure-activity relationships of 8-(substituted pyridyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF1) receptor antagonists. These CRF1 receptor antagonists may be potential anxiolytic or antidepressant drugs. This research resulted in the discovery of compound 13-15, which is a potent, selective CRF1 antagonist (hCRF(1) IC50 = 6.1 +/- 0.6 nM) with weak affinity for the CRF-binding protein and biogenic amine receptors. This compound also has a good pharmacokinetic profile in dogs. Analogue 13-15 is orally effective in two rat models of anxiety: the defensive withdrawal (situational anxiety) model and the elevated plus maze test. Analogue 13-15 has been advanced to clinical trials.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available