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

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.

SUBMITTER: Gavrin LK

PROVIDER: S-EPMC4007968 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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

Gavrin Lori K LK Mahaney Paige E PE Jenkins Douglas D Nogle Lisa M LM Mugford Cheryl A CA Huselton Christine C Leiter Jennifer J Johnston Grace H GH Bray Jenifer A JA Burroughs Kevin D KD Cosmi Scott A SA Alfinito Peter P Ho Douglas M DM Deecher Darlene C DC Trybulski Eugene J EJ

ACS medicinal chemistry letters 20100325 3

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 dysfunc ...[more]

PMID: 24900182

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