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

Liming Shao; 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

doi:10.1016/j.bmcl.2011.01.019

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

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1434-7. doi: 10.1016/j.bmcl.2011.01.019. Epub 2011 Jan 12.

Authors

Liming Shao¹, 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

Affiliation

¹ Discovery and Early Clinical Research, Sunovion Pharmaceuticals Inc., Marlborough, MA 01752, USA. liming.shao@sunovion.com

PMID: 21310612
DOI: 10.1016/j.bmcl.2011.01.019

Abstract

Novel chiral cyclohexylaryl amines were developed with potent reuptake inhibition against the serotonin, norepinephrine and dopamine transporters and activity at 10 and 30 mpk PO in the mouse tail suspension test. Prototype compound 31 (SERT, NET, DAT IC(50) ≤ 1, 21, 28 nM) was highly brain penetrant, had minimal CYP and hERG inhibition, and represents a previously undisclosed architecture with potential for treatment of major depressive disorder.

MeSH terms

Amines / chemical synthesis*
Amines / chemistry
Amines / pharmacology
Animals
Cyclization
Dopamine Uptake Inhibitors* / chemical synthesis
Dopamine Uptake Inhibitors* / chemistry
Dopamine Uptake Inhibitors* / pharmacology
Drug Design*
Inhibitory Concentration 50
Mice
Molecular Structure
Norepinephrine* / chemical synthesis
Norepinephrine* / chemistry
Norepinephrine* / pharmacology
Serotonin* / chemical synthesis
Serotonin* / chemistry
Serotonin* / pharmacology
Stereoisomerism

Substances

Amines
Dopamine Uptake Inhibitors
Serotonin
Norepinephrine