Discovery of 1-(3,4-dichlorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydroquinolin-4-amine, a dual serotonin and dopamine reuptake inhibitor

Bioorg Med Chem Lett. 2011 Jan 1;21(1):520-3. doi: 10.1016/j.bmcl.2010.10.086. Epub 2010 Oct 28.

Abstract

The present work describes a series of novel tetrahydroquinoline amines that potently inhibit the in vitro reuptake of serotonin and dopamine (dual reuptake inhibitors). The compounds are structurally related to a series we disclosed previously, but are improved with respect to cytochrome P-450 enzyme (CYP) and potassium ion channel Kv11.1 (hERG) inhibition and synthetic accessibility. The detailed synthesis and in vitro activity and ADME profile of the compounds is described, which represent a previously undisclosed dual reuptake inhibitor chemotype.

MeSH terms

  • Animals
  • Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopamine Uptake Inhibitors / chemical synthesis
  • Dopamine Uptake Inhibitors / chemistry*
  • Dopamine Uptake Inhibitors / pharmacokinetics
  • Drug Evaluation, Preclinical
  • Humans
  • Mice
  • Microsomes / metabolism
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacokinetics
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis
  • Selective Serotonin Reuptake Inhibitors / chemistry*
  • Selective Serotonin Reuptake Inhibitors / pharmacokinetics
  • Serotonin Plasma Membrane Transport Proteins / chemistry*
  • Serotonin Plasma Membrane Transport Proteins / metabolism

Substances

  • 1-(3,4-dichlorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydroquinolin-4-amine
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • Quinolines
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors