Human beta3-adrenergic receptor agonists containing 1,2,3-triazole-substituted benzenesulfonamides

Bioorg Med Chem Lett. 2000 Sep 18;10(18):2111-4. doi: 10.1016/s0960-894x(00)00422-4.

Abstract

Compounds containing a 1,2,3-triazole-substituted benzenesulfonamide were prepared and found to be potent and selective human beta3-adrenergic receptor agonists. The most interesting compound, trifluoromethylbenzyl analogue 12e (beta3 EC50 = 3.1 nM with >1500-fold selectivity over binding to both beta1- and beta2 receptors), stimulates lipolysis in the rhesus monkey (ED50 = 0.36 mg/kg) and is 25% orally bioavailable in the dog.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Adrenergic beta-3 Receptor Agonists*
  • Animals
  • Benzenesulfonamides
  • Biological Availability
  • CHO Cells
  • Cricetinae
  • Cyclic AMP / metabolism
  • Dogs
  • Dose-Response Relationship, Drug
  • Humans
  • Infusions, Parenteral
  • Isoproterenol / pharmacology
  • Lipolysis / drug effects
  • Macaca mulatta
  • Protein Binding
  • Receptors, Adrenergic, beta-3 / metabolism
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / metabolism
  • Sulfonamides / pharmacokinetics
  • Tachycardia / chemically induced
  • Triazoles / chemical synthesis
  • Triazoles / metabolism
  • Triazoles / pharmacokinetics

Substances

  • Adrenergic beta-3 Receptor Agonists
  • Receptors, Adrenergic, beta-3
  • Sulfonamides
  • Triazoles
  • Cyclic AMP
  • Isoproterenol