Discovery of potent and orally bioavailable heterocycle-based beta3-adrenergic receptor agonists, potential therapeutics for the treatment of obesity

Bioorg Med Chem Lett. 2007 Sep 15;17(18):5245-50. doi: 10.1016/j.bmcl.2007.06.072. Epub 2007 Jun 30.


A novel series of heterocycle-based analogs were prepared and evaluated for their in vitro and in vivo biological activity as human beta(3)-adrenergic receptor (AR) agonists. Several analogs demonstrated potent agonist activity at the beta(3)-AR, functional selectivity against beta(1)- and beta(2)-ARs, and favorable pharmacokinetic profiles in vivo. Compound 17 increased oxygen consumption in rats, a measure of energy expenditure, with an ED(20%) of 2mg/kg.

MeSH terms

  • Administration, Oral
  • Adrenergic beta-3 Receptor Agonists*
  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / pharmacokinetics
  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Agonists / therapeutic use*
  • Animals
  • Biological Availability
  • Obesity / drug therapy*
  • Rats


  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-Agonists