Studies on a series of milnacipran analogs containing a heteroaromatic group as potent norepinephrine and serotonin transporter inhibitors

  • Bioorg Med Chem Lett. 2008 Jun 1;18(11):3230-5. doi: 10.1016/j.bmcl.2008.04.045.
Troy Vickers  1 ,  Brian Dyck ,  Junko Tamiya ,  Mingzhu Zhang ,  Florence Jovic ,  Jonathan Grey ,  Beth A Fleck ,  Anna Aparicio ,  Michael Johns ,  Liping Jin ,  Hui Tang ,  Alan C Foster ,  Chen Chen
Affiliations
  • 1. Department of Medicinal Chemistry, Neurocrine Bioscience, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
PMID: 18468895 DOI: 10.1016/j.bmcl.2008.04.045
Abstract

A series of milnacipran analogs containing a heteroaromatic group were synthesized and studied as Monoamine Transporter inhibitors. Many compounds exhibited higher potency than milnacipran at NET and NET/SERT with no significant change in lipophilicity. For example, compound R-26f was about 10-fold more potent than milnacipran with IC(50) values of 8.7 and 26nM at NET and SERT, respectively.