Discovery of 6-chloro-2-trifluoromethyl-7-aryl-7H-imidazo[1,2-a]imidazol-3-ylmethylamines, a novel class of corticotropin-releasing factor receptor type 1 (CRF1R) antagonists

Dmitry Zuev; Vivekananda M Vrudhula; Jodi A Michne; Bireshwar Dasgupta; Sokhom S Pin; Xiaohua Stella Huang; Dedong Wu; Qi Gao; Jie Zhang; Matthew T Taber; John E Macor; Gene M Dubowchik

doi:10.1016/j.bmcl.2010.04.094

Discovery of 6-chloro-2-trifluoromethyl-7-aryl-7H-imidazo[1,2-a]imidazol-3-ylmethylamines, a novel class of corticotropin-releasing factor receptor type 1 (CRF1R) antagonists

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3669-74. doi: 10.1016/j.bmcl.2010.04.094. Epub 2010 Apr 24.

Authors

Dmitry Zuev¹, Vivekananda M Vrudhula, Jodi A Michne, Bireshwar Dasgupta, Sokhom S Pin, Xiaohua Stella Huang, Dedong Wu, Qi Gao, Jie Zhang, Matthew T Taber, John E Macor, Gene M Dubowchik

Affiliation

¹ Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA. [email protected]

PMID: 20471832
DOI: 10.1016/j.bmcl.2010.04.094

Abstract

A novel series of [6-chloro-2-trifluoromethyl-7-aryl-7H-imidazo[1,2-a]imidazol-3-ylmethyl]-dialkylamines was discovered as potent CRF(1)R antagonists. The optimization of binding affinity in the series by the parallel reaction approach is discussed herein.

MeSH terms

CRF Receptor, Type 1
Humans
Imidazoles / chemistry*
Imidazoles / pharmacology
Methylamines / chemistry*
Methylamines / pharmacology
Protein Binding
Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Imidazoles
Methylamines
Receptors, Corticotropin-Releasing Hormone
CRF Receptor, Type 1