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.
White
James D
JD
Department of Chemistry, Oregon State University, Corvallis, Oregon 97331, USA. james.white@oregonstate.edu
Juniku
Rajan
R
Huang
Kun
K
Yang
Jongtae
J
Wong
David T
DT
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