Discovery of N-methyl-1-(1-phenylcyclohexyl)methanamine, a novel triple serotonin, norepinephrine, and dopamine reuptake inhibitor

  • Bioorg Med Chem Lett. 2011 Mar 1;21(5):1438-41. doi: 10.1016/j.bmcl.2011.01.016.
Liming Shao  1 ,  Michael C Hewitt ,  Fengjiang Wang ,  Scott C Malcolm ,  Jianguo Ma ,  John E Campbell ,  Una C Campbell ,  Sharon R Engel ,  Nancy A Spicer ,  Larry W Hardy ,  Rudy Schreiber ,  Kerry L Spear ,  Mark A Varney
Affiliations
  • 1. Discovery and Early Clinical Research, Sunovion Pharmaceuticals Inc., Marlborough, MA 01752, USA. [email protected]
PMID: 21310609 DOI: 10.1016/j.bmcl.2011.01.016
Abstract

The current work discloses a novel cyclohexylarylamine chemotype with potent inhibition of the serotonin, norepinephrine, and dopamine transporters and potential for treatment of major depressive disorder. Optimized compounds 1 (SERT, NET, DAT, IC(50)=169, 85, 21 nM) and 42 (SERT, NET, DAT IC(50)=34, 295, 90 nM) were highly brain penetrant, active in vivo in the mouse tail suspension test at 30 mpk po and were not general motor stimulants.

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