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

Cynthia D Jesudason; James E Baker; Robert D Bryant; Jack W Fisher; Libbey S O'Farrell; Gregory A Gaich; Minxia M He; Steven D Kahl; Aidas V Kriauciunas; Mark L Heiman; Mary A Peters; Christopher J Rito; Julie H Satterwhite; Frank C Tinsley; William G Trankle; Anthony J Shuker

doi:10.1021/ml200071k

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. eCollection 2011 Aug 11.

Authors

Cynthia D Jesudason¹, James E Baker¹, Robert D Bryant¹, Jack W Fisher¹, Libbey S O'Farrell¹, Gregory A Gaich¹, Minxia M He¹, Steven D Kahl¹, Aidas V Kriauciunas¹, Mark L Heiman¹, Mary A Peters¹, Christopher J Rito¹, Julie H Satterwhite¹, Frank C Tinsley¹, William G Trankle¹, Anthony J Shuker¹

Affiliation

¹ Lilly Research Laboratories, Eli Lilly & Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.

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.