Synthesis of 1,1-[1-naphthyloxy-2-thiophenyl]-2-methylaminomethylcyclopropanes and their evaluation as inhibitors of serotonin, norepinephrine, and dopamine transporters

James D White; Rajan Juniku; Kun Huang; Jongtae Yang; David T Wong

doi:10.1021/jm900847b

Synthesis of 1,1-[1-naphthyloxy-2-thiophenyl]-2-methylaminomethylcyclopropanes and their evaluation as inhibitors of serotonin, norepinephrine, and dopamine transporters

J Med Chem. 2009 Oct 8;52(19):5872-9. doi: 10.1021/jm900847b.

Authors

James D White¹, Rajan Juniku, Kun Huang, Jongtae Yang, David T Wong

Affiliation

¹ Department of Chemistry, Oregon State University, Corvallis, Oregon 97331, USA. james.white@oregonstate.edu

PMID: 19791802
DOI: 10.1021/jm900847b

Abstract

Stereodefined trisubstituted cyclopropanes bearing naphthyloxy, thiophenyl, and (N-methylamino)methyl groups were synthesized in enantiopure form employing asymmetric cyclopropanation of (E)- and (Z)-allylic alcohols as the key step. In vitro assays of the synthesized cyclopropanes revealed that the K(i) of one of the enantiomers as a dual inhibitor of serotonin and norepinephrine transporters is in the low nanomolar range and is comparable to that of duloxetine.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Cyclopropanes / chemical synthesis*
Cyclopropanes / pharmacology*
Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors
Duloxetine Hydrochloride
Humans
Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors
Plasma Membrane Neurotransmitter Transport Proteins / antagonists & inhibitors*
Serotonin Antagonists
Serotonin Plasma Membrane Transport Proteins / drug effects
Stereoisomerism
Structure-Activity Relationship
Thiophenes

Substances

Cyclopropanes
Dopamine Plasma Membrane Transport Proteins
Norepinephrine Plasma Membrane Transport Proteins
Plasma Membrane Neurotransmitter Transport Proteins
Serotonin Antagonists
Serotonin Plasma Membrane Transport Proteins
Thiophenes
Duloxetine Hydrochloride