2. Academic Validation
  3. Discovery of WAY-260022, a Potent and Selective Inhibitor of the Norepinephrine Transporter

Discovery of WAY-260022, a Potent and Selective Inhibitor of the Norepinephrine Transporter

  • ACS Med Chem Lett. 2010 Mar 25;1(3):91-5. doi: 10.1021/ml100009p.
Lori K Gavrin 1,  Paige E Mahaney 2,  Douglas Jenkins 2,  Lisa M Nogle 2,  Cheryl A Mugford 3,  Christine Huselton 3,  Jennifer Leiter 4,  Grace H Johnston 4,  Jenifer A Bray 4,  Kevin D Burroughs 4,  Scott A Cosmi 4,  Peter Alfinito 4,  Douglas M Ho 5,  Darlene C Deecher 4,  Eugene J Trybulski 2
Affiliations

Affiliations

  • 1 Worldwide Medicinal Chemistry, Pfizer Global Research and Development, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140.
  • 2 Worldwide Medicinal Chemistry.
  • 3 Drug Safety and Metabolism.
  • 4 Women's Health and Musculoskeletal Biology.
  • 5 Department of Chemistry, Princeton University, Princeton, New Jersey 08544.
PMID: 24900182 DOI: 10.1021/ml100009p
Abstract

The potency and selectivity of a series of 1-{(1S)-2-[amino]-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol analogues are described. These compounds were prepared to improve in vitro metabolic stability and achieve brain penetration. Compound 13 (WAY-260022, NRI-022) was found to be a potent inhibitor of norepinephrine reuptake and demonstrated excellent selectivity over the serotonin and dopamine transporters. Additionally, 13 exhibited oral efficacy in a rat model of thermoregulatory dysfunction.

Keywords

WAY-260022; brain penetration, vasomotor symptoms; dopamine transporter; norepinephrine reuptake inhibitor; serotonin transporter.

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