Azepines and Piperidines with Dual Norepinephrine Dopamine Uptake Inhibition and Antidepressant Activity

Azepines and Piperidines with Dual Norepinephrine Dopamine Uptake Inhibition and Antidepressant Activity

Herein, we describe the discovery of inhibitors of norepinephrine (NET) and dopamine (DAT) transporters with reduced activity relative to serotonin transporters (SERT). Two compounds, 8b and 21a, along with nomifensine were tested in a rodent receptor occupancy study and demonstrated dose-dependent...

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Veröffentlicht in:ACS medicinal chemistry letters 2013-01, Vol.4 (1), p.46-51
Hauptverfasser: Brown, Dean G, Bernstein, Peter R, Wu, Ye, Urbanek, Rebecca A, Becker, Christopher W, Throner, Scott R, Dembofsky, Bruce T, Steelman, Gary B, Lazor, Lois A, Scott, Clay W, Wood, Michael W, Wesolowski, Steven S, Nugiel, David A, Koch, Stephanie, Yu, Jian, Pivonka, Donald E, Li, Shuang, Thompson, Carol, Zacco, Anna, Elmore, Charles S, Schroeder, Patricia, Liu, JianWei, Hurley, Christopher A, Ward, Stuart, Hunt, Hazel J, Williams, Karen, McLaughlin, Joseph, Hoesch, Valerie, Sydserff, Simon, Maier, Donna, Aharony, David
Format: Artikel
Sprache:eng
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Letter
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Zusammenfassung:Herein, we describe the discovery of inhibitors of norepinephrine (NET) and dopamine (DAT) transporters with reduced activity relative to serotonin transporters (SERT). Two compounds, 8b and 21a, along with nomifensine were tested in a rodent receptor occupancy study and demonstrated dose-dependent displacement of radiolabeled NET and DAT ligands. These compounds were efficacious in a rat forced swim assay (model of depression) and also had activity in rat spontaneous locomotion assay.
ISSN:1948-5875
1948-5875
DOI:10.1021/ml300262e