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

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White JD, Juniku R, Huang K, Yang J, Wong DT

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.

PubMed ID

19791802 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Desipramine	Sodium-dependent noradrenaline transporter	Ki (nM)	5.11	N/A	N/A	Details
Imipramine	Sodium-dependent serotonin transporter	Ki (nM)	7.57	N/A	N/A	Details