3-Pyridyloxypropanolamine agonists of the beta 3 adrenergic receptor with improved pharmacokinetic properties

Bioorg Med Chem Lett. 1998 Aug 18;8(16):2111-6. doi: 10.1016/s0960-894x(98)00381-3.

Abstract

Pyridyloxypropanolamines L-749,372 (8, beta 3 EC50 = 3.6 nM) and L-750,355 (29, beta 3 EC50 = 13 nM) are selective partial agonists of the human receptor, with 33% and 49% activation, respectively. Both stimulate lipolysis in rhesus monkeys (ED50 = 2 and 0.8 mg/kg, respectively), with minimal effects on heart rate. Oral bioavailability in dogs, 41% for L-749,372 and 47% for L-750,355, is improved relative to phenol analogs.

MeSH terms

  • Adrenergic beta-Agonists / chemical synthesis*
  • Adrenergic beta-Agonists / chemistry
  • Adrenergic beta-Agonists / pharmacokinetics
  • Animals
  • Binding, Competitive
  • Biological Availability
  • Dogs
  • Humans
  • Kinetics
  • Lipolysis / drug effects
  • Macaca mulatta
  • Molecular Structure
  • Propanolamines / chemical synthesis*
  • Propanolamines / chemistry
  • Propanolamines / pharmacokinetics*
  • Propanolamines / pharmacology
  • Pyridines
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology*
  • Receptors, Adrenergic, beta-3
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacokinetics
  • Sulfonamides / pharmacology

Substances

  • Adrenergic beta-Agonists
  • Propanolamines
  • Pyridines
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-3
  • Sulfonamides