Synthesis of enantiomerically pure milnacipran analogs and inhibition of dopamine, serotonin, and norepinephrine transporters

Heidi Roggen; Jan Kehler; Tine Bryan Stensbøl; Tore Hansen

doi:10.1016/j.bmcl.2007.02.054

Synthesis of enantiomerically pure milnacipran analogs and inhibition of dopamine, serotonin, and norepinephrine transporters

Bioorg Med Chem Lett. 2007 May 15;17(10):2834-7. doi: 10.1016/j.bmcl.2007.02.054. Epub 2007 Feb 27.

Authors

Heidi Roggen¹, Jan Kehler, Tine Bryan Stensbøl, Tore Hansen

Affiliation

¹ University of Oslo, Department of Chemistry, Sem Saelands vei 26, 0315 Oslo, Norway.

PMID: 17350257
DOI: 10.1016/j.bmcl.2007.02.054

Abstract

A series of Milnacipran analogs with variation in the aromatic moiety were prepared in high enantiomeric excess. Structure-activity relationships for two parallel enantiomeric series are described. The (-)-(1R,2S)-naphthyl analog (8h) showed the highest potency in the two series and is a triple reuptake inhibitor of the SERT, NET, and DAT.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cyclopropanes / chemical synthesis*
Cyclopropanes / pharmacology*
Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors
Drug Design
Membrane Transport Proteins / drug effects*
Milnacipran
Molecular Conformation
Molecular Structure
Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors*
Serotonin Plasma Membrane Transport Proteins / drug effects

Substances

Cyclopropanes
Dopamine Plasma Membrane Transport Proteins
Membrane Transport Proteins
Norepinephrine Plasma Membrane Transport Proteins
Serotonin Plasma Membrane Transport Proteins
Milnacipran