2. Academic Validation
  3. 3-Pyridyloxypropanolamine agonists of the beta 3 adrenergic receptor with improved pharmacokinetic properties

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

Affiliation

  • 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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