Author/Authors :
Sarah Hudson، نويسنده , , Mehrak Kiankarimi، نويسنده , , Wendy Eccles، نويسنده , , Wesley Dwight، نويسنده , , Yalda S. Mostofi، نويسنده , , Marc J. Genicot، نويسنده , , Beth A. Fleck، نويسنده , , Kathleen Gogas، نويسنده , , Anna Aparicio، نويسنده , , Hua Wang، نويسنده , , Jenny Wen، نويسنده , , Warren S. Wade، نويسنده ,
Abstract :
The synthesis and SAR of a series of chiral heterocyclic ring-constrained norepinephrine reuptake inhibitors are described. The best compounds compare favorably with atomoxetine in potency (IC50s < 10 nM), selectivity against the other monoamine transporters, and inhibition of CYP2D6 (IC50s > 1 μM). In addition, the compounds are generally more stable than atomoxetine to oxidative metabolism and thus are likely to have lower clearance in humans.
