Studies on a series of milnacipran analogs containing a heteroaromatic group as potent norepinephrine and serotonin transporter inhibitors

Bioorg Med Chem Lett. 2008 Jun 1;18(11):3230-5. doi: 10.1016/j.bmcl.2008.04.045. Epub 2008 Apr 25.

Abstract

A series of milnacipran analogs containing a heteroaromatic group were synthesized and studied as monoamine transporter inhibitors. Many compounds exhibited higher potency than milnacipran at NET and NET/SERT with no significant change in lipophilicity. For example, compound R-26f was about 10-fold more potent than milnacipran with IC(50) values of 8.7 and 26nM at NET and SERT, respectively.

MeSH terms

  • Combinatorial Chemistry Techniques
  • Cyclopropanes / chemical synthesis*
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology*
  • Humans
  • Milnacipran
  • Molecular Structure
  • Norepinephrine / metabolism
  • Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors*
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis*
  • Selective Serotonin Reuptake Inhibitors / chemistry
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Cyclopropanes
  • Norepinephrine Plasma Membrane Transport Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Milnacipran
  • Norepinephrine