Synthesis of 1,1-[1-naphthyloxy-2-thiophenyl]-2-methylaminomethylcyclopropanes and their evaluation as inhibitors of serotonin, norepinephrine, and dopamine transporters.
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.
Department of Chemistry, Oregon State University, Corvallis, Oregon 97331, USA. james.white@oregonstate.edu
James D
JD
White
Rajan
R
Juniku
Kun
K
Huang
Jongtae
J
Yang
David T
DT
Wong
D000818:Animals; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D000068736:Duloxetine Hydrochloride; D006801:Humans; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000037:antagonists & inhibitors*; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes
D003521:Cyclopropanes; D050483:Dopamine Plasma Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050480:Plasma Membrane Neurotransmitter Transport Proteins; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride