Novel and potent human and rat beta3-adrenergic receptor agonists containing substituted 3-indolylalkylamines

Bioorg Med Chem Lett. 2003 Apr 7;13(7):1301-5. doi: 10.1016/s0960-894x(03)00073-8.


A novel series of 2-(3-indolyl)alkylamino-1-(3-chlorophenyl)ethanols was prepared and evaluated for in vitro ability to stimulate cAMP production in Chinese hamster ovary cells expressing cloned human beta(3)-AR. The optically active 30a was found to be the most potent and selective human beta(3)-AR agonist in this series with an EC(50) value of 0.062nM. In addition, 30a selectivity for human beta(3)-AR was 210-fold and 103-fold that for human beta(2)-AR and beta(1)-AR, respectively. Furthermore, 30a showed potent agonistic activity at rat beta(3)-AR.

MeSH terms

  • Adrenergic beta-3 Receptor Agonists*
  • Adrenergic beta-Agonists / chemical synthesis*
  • Adrenergic beta-Agonists / pharmacology*
  • Alkanes / chemical synthesis*
  • Alkanes / pharmacology*
  • Animals
  • CHO Cells
  • Cloning, Molecular
  • Cricetinae
  • Cyclic AMP / metabolism
  • Ethanolamines / pharmacology
  • Humans
  • Indoles / pharmacology*
  • Models, Molecular
  • Molecular Conformation
  • Rats
  • Structure-Activity Relationship
  • Tryptamines / chemical synthesis
  • Tryptamines / pharmacology


  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-Agonists
  • Alkanes
  • Ethanolamines
  • Indoles
  • Tryptamines
  • BRL 37344
  • Cyclic AMP