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

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.
Sarah Hudson 1,  Mehrak Kiankarimi,  Wendy Eccles,  Wesley Dwight,  Yalda S Mostofi,  Marc J Genicot,  Beth A Fleck,  Kathleen Gogas,  Anna Aparicio,  Hua Wang,  Jenny Wen,  Warren S Wade
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA. [email protected]
PMID: 18672364 DOI: 10.1016/j.bmcl.2008.07.049
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.

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