2. Academic Validation
  3. Synthesis and structure-activity relationships of selective norepinephrine reuptake inhibitors (sNRI) with improved pharmaceutical characteristics

Synthesis and structure-activity relationships of selective norepinephrine reuptake inhibitors (sNRI) with improved pharmaceutical characteristics

  • Bioorg Med Chem Lett. 2008 Dec 1;18(23):6151-5. doi: 10.1016/j.bmcl.2008.10.013.
Joseph Pontillo 1,  Dongpei Wu,  Brett Ching,  Sarah Hudson,  Marc J Genicot,  Yinghong Gao,  Todd Ewing,  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.
PMID: 18954981 DOI: 10.1016/j.bmcl.2008.10.013
Abstract

The design synthesis and SAR of a series of chiral ring-constrained norepinephrine reuptake inhibitors with improved physicochemical properties is described. Typical compounds are potent (IC(50)s<10 nM), selective against the Other monoamine transporters, weak CYP2D6 inhibitors (IC(50)s>1 microM) and stable to oxidation by human liver microsomes. In addition, the compounds exhibit a favorable polarity profile.

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