Synthesis and evaluation of potent and selective beta3 adrenergic receptor agonists containing heterobiaryl carboxylic acids

Barry G Shearer; Esther Y Chao; David E Uehling; David N Deaton; Conrad Cowan; Bryan W Sherman; Tula Milliken; Walter Faison; Kathleen Brown; Kimberly K Adkison; Frank Lee

doi:10.1016/j.bmcl.2007.05.069

Synthesis and evaluation of potent and selective beta3 adrenergic receptor agonists containing heterobiaryl carboxylic acids

Bioorg Med Chem Lett. 2007 Aug 15;17(16):4670-7. doi: 10.1016/j.bmcl.2007.05.069. Epub 2007 May 25.

Authors

Barry G Shearer¹, Esther Y Chao, David E Uehling, David N Deaton, Conrad Cowan, Bryan W Sherman, Tula Milliken, Walter Faison, Kathleen Brown, Kimberly K Adkison, Frank Lee

Affiliation

¹ Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. barry.g.shearer@gsk.com

PMID: 17560786
DOI: 10.1016/j.bmcl.2007.05.069

Abstract

The design, synthesis, and SAR of a novel series of heterobiaryl phenethanolamine beta3 adrenergic receptor agonists are described. The furan analogue 49 was shown to elicit a significant dose-dependent lowering of plasma glucose in a rodent model of type 2 diabetes.

MeSH terms

Adrenergic beta-3 Receptor Agonists*
Binding Sites
Carboxylic Acids / chemistry*
Carboxylic Acids / pharmacology*
Models, Molecular
Molecular Structure
Structure-Activity Relationship

Substances

Adrenergic beta-3 Receptor Agonists
Carboxylic Acids