Synthesis, structure-activity relationships, and anxiolytic activity of 7-aryl-6,7-dihydroimidazoimidazole corticotropin-releasing factor 1 receptor antagonists

Xiaojun Han; Jodi A Michne; Sokhom S Pin; Kevin D Burris; Lynn A Balanda; Lawrence K Fung; Tracey Fiedler; Kaitlin E Browman; Matthew T Taber; Jie Zhang; Gene M Dubowchik

doi:10.1016/j.bmcl.2005.05.117

Synthesis, structure-activity relationships, and anxiolytic activity of 7-aryl-6,7-dihydroimidazoimidazole corticotropin-releasing factor 1 receptor antagonists

Bioorg Med Chem Lett. 2005 Sep 1;15(17):3870-3. doi: 10.1016/j.bmcl.2005.05.117.

Authors

Xiaojun Han¹, Jodi A Michne, Sokhom S Pin, Kevin D Burris, Lynn A Balanda, Lawrence K Fung, Tracey Fiedler, Kaitlin E Browman, Matthew T Taber, Jie Zhang, Gene M Dubowchik

Affiliation

¹ Pharmaceutical Research Institute, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA. [email protected]

PMID: 15990298
DOI: 10.1016/j.bmcl.2005.05.117

Abstract

7-Aryl-6,7-dihydroimidazoimidazoles represent a novel series of high-affinity corticotropin-releasing factor 1 receptor antagonists. Here, we report their synthesis and SAR as well as behavioral activity of two exemplary compounds, 7b and 7k, in a mouse canopy model of anxiety.

MeSH terms

Animals
Anti-Anxiety Agents / chemical synthesis*
Anti-Anxiety Agents / pharmacokinetics
Anti-Anxiety Agents / pharmacology
Anxiety / drug therapy
Blood-Brain Barrier
CRF Receptor, Type 1
Corticotropin-Releasing Hormone
Humans
Imidazoles / chemical synthesis*
Imidazoles / pharmacokinetics
Imidazoles / pharmacology
Mice
Rats
Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Anti-Anxiety Agents
Imidazoles
Receptors, Corticotropin-Releasing Hormone
CRF Receptor, Type 1
Corticotropin-Releasing Hormone