Combination of a Beta adrenoceptor modulator and a norepinephrine-serotonin uptake inhibitor for the treatment of obesity

  • ACS Med Chem Lett. 2011 May 23;2(8):583-6. doi: 10.1021/ml200071k.
Cynthia D Jesudason  1 ,  James E Baker  1 ,  Robert D Bryant  1 ,  Jack W Fisher  1 ,  Libbey S O'Farrell  1 ,  Gregory A Gaich  1 ,  Minxia M He  1 ,  Steven D Kahl  1 ,  Aidas V Kriauciunas  1 ,  Mark L Heiman  1 ,  Mary A Peters  1 ,  Christopher J Rito  1 ,  Julie H Satterwhite  1 ,  Frank C Tinsley  1 ,  William G Trankle  1 ,  Anthony J Shuker  1
Affiliations
  • 1. Lilly Research Laboratories, Eli Lilly & Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
PMID: 24900353 DOI: 10.1021/ml200071k
Abstract

We report the novel combination of a selective beta adrenoceptor modulator and a norepinephrine-serotonin uptake inhibitor (sibutramine) with potential for the treatment of obesity. The synthesis and characterization of 6-[4-[2-[[(2S)-3-(9H-carbazol-4-yloxy)-2-hydroxypropyl]amino]-2-methylpropyl]phenoxy]pyridine-3-carboxamide (LY377604), a human β3-adrenergic receptor agonist and β1- and β2-adrenergic receptor antagonist with no sympathomimetic activity at the β1- and β2-adrenergic receptors, is reported. Some in vivo data in both rats and humans is presented.

Keywords
LY377604; Selective beta adrenoceptor modulator; norepinephrine-serotonin uptake inhibitor; obesity; sibutramine; β3-adrenergic receptor agonist.
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