Synthesis of enantiomerically pure milnacipran analogs and inhibition of dopamine, serotonin, and norepinephrine transporters.
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.
Roggen
Heidi
H
University of Oslo, Department of Chemistry, Sem Saelands vei 26, 0315 Oslo, Norway.
Kehler
Jan
J
Stensbøl
Tine Bryan
TB
Hansen
Tore
T
D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D015195:Drug Design; D026901:Membrane Transport Proteins / Q000187:drug effects*; D000078764:Milnacipran; D008968:Molecular Conformation; D015394:Molecular Structure; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects
D003521:Cyclopropanes; D050483:Dopamine Plasma Membrane Transport Proteins; D026901:Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D000078764:Milnacipran