4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors.

Anthony D Pechulis,James P Beck,Matt A Curry,Mark A Wolf,Arthur E Harms,Ning Xi,Chet Opalka,Mark P Sweet,Zhicai Yang,A Samuel Vellekoop,Andrew M Klos,Peter J Crocker,Carla Hassler,Mia Laws,Douglas B Kitchen,Mark A Smith,Richard E Olson, Shuang Liu,Bruce F Molino

Bioorganic & Medicinal Chemistry Letters（2012）

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Abstract

Novel 4-phenyl tetrahydroisoquinolines that inhibit both dopamine and norepinephrine transporters were designed and prepared. In this Letter, we describe the synthesis, in vitro activity and associated structure–activity relationships of this series. We also report the ex vivo NET occupancy of a representative compound, 41.

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Key words

Norepinephrine reuptake inhibitor,Dopamine reuptake inhibitor,Dual dopamine and norepinephrine reuptake inhibitors,DAT,NET,ADHD,Depression

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