Structure-activity relationships of chiral selective norepinephrine reuptake inhibitors (sNRI) with increased oxidative stability.

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Hudson S, Kiankarimi M, Eccles W, Dwight W, Mostofi YS, Genicot MJ, Fleck BA, Gogas K, Aparicio A, Wang H, Wen J, Wade WS

Structure-activity relationships of chiral selective norepinephrine reuptake inhibitors (sNRI) with increased oxidative stability.

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4491-4. doi: 10.1016/j.bmcl.2008.07.049. Epub 2008 Jul 17.

PubMed ID
18672364 [ View in PubMed
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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 (IC(50)s<10 nM), selectivity against the other monoamine transporters, and inhibition of CYP2D6 (IC(50)s>1 microM). In addition, the compounds are generally more stable than atomoxetine to oxidative metabolism and thus are likely to have lower clearance in humans.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AtomoxetineCytochrome P450 2D6IC 50 (nM)2000N/AN/ADetails
AtomoxetineSodium-dependent noradrenaline transporterIC 50 (nM)5N/AN/ADetails
AtomoxetineSodium-dependent serotonin transporterIC 50 (nM)180N/AN/ADetails