Discovery of a potent, selective, and less flexible selective norepinephrine reuptake inhibitor (sNRI)

  • Bioorg Med Chem Lett. 2008 Jul 15;18(14):4224-7. doi: 10.1016/j.bmcl.2008.05.057.
Dongpei Wu  1 ,  Joseph Pontillo ,  Brett Ching ,  Sarah Hudson ,  Yinghong Gao ,  Beth A Fleck ,  Kathleen Gogas ,  Warren S Wade
Affiliations
  • 1. Department of Medicinal Chemistry, Neurocrine Biosciences Inc. 12790 El Camino Real, San Diego, CA 92130, USA.
PMID: 18550369 DOI: 10.1016/j.bmcl.2008.05.057
Abstract

The design, synthesis, and SAR of a series of ring-constrained norepinephrine reuptake inhibitors are described. A substantially rigid inhibitor with potent functional activity at the transporter (IC(50)=8 nM) was used to develop a model for the distance and orientation of key features necessary for interaction with the norepinephrine transporter (NET).