Potent and selective, sulfamide-based human beta 3-adrenergic receptor agonists

Robert L Dow; Ernest S Paight; Steven R Schneider; John R Hadcock; Diane M Hargrove; Kelly A Martin; Tristan S Maurer; Nancy A Nardone; David A Tess; Paul DaSilva-Jardine

doi:10.1016/j.bmcl.2004.03.089

Potent and selective, sulfamide-based human beta 3-adrenergic receptor agonists

Bioorg Med Chem Lett. 2004 Jun 21;14(12):3235-40. doi: 10.1016/j.bmcl.2004.03.089.

Authors

Robert L Dow¹, Ernest S Paight, Steven R Schneider, John R Hadcock, Diane M Hargrove, Kelly A Martin, Tristan S Maurer, Nancy A Nardone, David A Tess, Paul DaSilva-Jardine

Affiliation

¹ Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton, CT 06340, USA. [email protected]

PMID: 15149682
DOI: 10.1016/j.bmcl.2004.03.089

Abstract

A series of sulfamide-based analogs related to L-796568 were prepared and evaluated for their biological activity at the human beta(3)-adrenergic receptor (AR). This modification allows for a significant reduction in molecular weight, while maintaining single-digit nanomolar potencies at the beta(3)-AR and high selectivities versus the beta(2)- or beta(3)-AR.

MeSH terms

Adrenergic beta-3 Receptor Agonists*
Adrenergic beta-Agonists / chemistry*
Adrenergic beta-Agonists / metabolism
Adrenergic beta-Agonists / pharmacology
Animals
Humans
Oxygen Consumption / drug effects
Oxygen Consumption / physiology
Rats
Receptors, Adrenergic, beta-3 / metabolism
Sulfonamides / chemistry*
Sulfonamides / metabolism
Sulfonamides / pharmacology

Substances

Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists
Receptors, Adrenergic, beta-3
Sulfonamides