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.
A E Weber  1 ,  H O Ok ,  R F Alvaro ,  M R Candelore ,  M A Cascieri ,  S H Chiu ,  L Deng ,  M J Forrest ,  G J Hom ,  J E Hutchins ,  J Kao ,  D E MacIntyre ,  R J Mathvink ,  D McLoughlin ,  R R Miller ,  R C Newbold ,  T V Olah ,  E R Parmee ,  L Perkins ,  R A Stearns ,  C D Strader ,  J Szumiloski ,  Y S Tang ,  L Tota ,  M H Fisher
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
PMID: 9873496 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.

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