2-arylaminothiazoles as high-affinity corticotropin-releasing factor 1 receptor (CRF1R) antagonists: synthesis, binding studies and behavioral efficacy

Gene M Dubowchik; Jodi A Michne; Dmitry Zuev; Wendy Schwartz; Paul M Scola; Clint A James; Edward H Ruediger; Sokhom S Pin; Kevin D Burris; Lynn A Balanda; Qi Gao; Dedong Wu; Lawrence Fung; Tracey Fiedler; Kaitlin E Browman; Matthew T Taber; Jie Zhang

doi:10.1016/j.bmcl.2003.08.055

2-arylaminothiazoles as high-affinity corticotropin-releasing factor 1 receptor (CRF1R) antagonists: synthesis, binding studies and behavioral efficacy

Bioorg Med Chem Lett. 2003 Nov 17;13(22):3997-4000. doi: 10.1016/j.bmcl.2003.08.055.

Authors

Gene M Dubowchik¹, Jodi A Michne, Dmitry Zuev, Wendy Schwartz, Paul M Scola, Clint A James, Edward H Ruediger, Sokhom S Pin, Kevin D Burris, Lynn A Balanda, Qi Gao, Dedong Wu, Lawrence Fung, Tracey Fiedler, Kaitlin E Browman, Matthew T Taber, Jie Zhang

Affiliation

¹ Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5100, Wallingford, CT 06492-7660, USA. dubowchik@bms.com

PMID: 14592493
DOI: 10.1016/j.bmcl.2003.08.055

Abstract

2-arylamino-4-trifluoromethyl-5-aminomethylthiazoles represent a novel series of high-affinity corticotropin releasing factor-1 receptor (CRF(1)R) antagonists that are prepared in three steps in good overall yields. Herein, we report binding SAR as well as anxiolytic activity of an exemplary compound (7a, K(i)=8.6 nM) in a mouse canopy model.

MeSH terms

Animals
Binding Sites
Humans
Kinetics
Rats
Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
Receptors, Corticotropin-Releasing Hormone / chemistry
Receptors, Corticotropin-Releasing Hormone / metabolism
Structure-Activity Relationship
Thiazoles / chemical synthesis*
Thiazoles / pharmacology*

Substances

Receptors, Corticotropin-Releasing Hormone
Thiazoles
CRF receptor type 1