Discovery of a novel non-steroidal GR antagonist with in vivo efficacy in the olanzapine-induced weight gain model in the rat

Hazel J Hunt; Nicholas C Ray; George Hynd; Jon Sutton; Mohammed Sajad; Elizabeth O'Connor; Shahadat Ahmed; Peter Lockey; Steve Daly; Gerry Buckley; Robin D Clark; Robert Roe; Christine Blasey; Joe Belanoff

doi:10.1016/j.bmcl.2012.10.074

Discovery of a novel non-steroidal GR antagonist with in vivo efficacy in the olanzapine-induced weight gain model in the rat

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7376-80. doi: 10.1016/j.bmcl.2012.10.074. Epub 2012 Oct 23.

Authors

Hazel J Hunt¹, Nicholas C Ray, George Hynd, Jon Sutton, Mohammed Sajad, Elizabeth O'Connor, Shahadat Ahmed, Peter Lockey, Steve Daly, Gerry Buckley, Robin D Clark, Robert Roe, Christine Blasey, Joe Belanoff

Affiliation

¹ Corcept Therapeutics, 149 Commonwealth Drive, Menlo Park, CA 94025, USA. [email protected]

PMID: 23131342
DOI: 10.1016/j.bmcl.2012.10.074

Abstract

We report the optimization of a series of non-steroidal GR antagonists that led to the identification of compound 7. This compound is efficacious when dosed orally in an olanzapine-induced weight gain model in rats.

MeSH terms

Administration, Oral
Animals
Benzodiazepines / administration & dosage
Benzodiazepines / chemistry
Benzodiazepines / pharmacology*
Dose-Response Relationship, Drug
Drug Discovery*
Models, Animal
Molecular Structure
Olanzapine
Rats
Rats, Sprague-Dawley
Receptors, Glucocorticoid / antagonists & inhibitors*
Structure-Activity Relationship
Thymine / administration & dosage
Thymine / analogs & derivatives*
Thymine / chemistry
Thymine / pharmacology
Weight Gain / drug effects*

Substances

CORT118335
Receptors, Glucocorticoid
Benzodiazepines
Olanzapine
Thymine