Author/Authors :
Manuel J. Cases-Thomas، نويسنده , , John J. Masters، نويسنده , , Magnus W. Walter، نويسنده , , Gordon Campbell، نويسنده , , Louise Haughton، نويسنده , , Peter T. Gallagher، نويسنده , , David R. Dobson، نويسنده , , Vincent Mancuso، نويسنده , , Benjamin Bonnier، نويسنده , , Thierry Giard، نويسنده , , Thierry Defrance، نويسنده , , Michel Vanmarsenille، نويسنده , , Andrew Ledgard، نويسنده , , Craig White ، نويسنده , , Sivi Ouwerkerk-Mahadevan، نويسنده , , Francoise J. Brunelle، نويسنده , , Nancy A. Dezutter، نويسنده , , Camy A. Herbots، نويسنده , , Joel Y. Lienard، نويسنده , , Jeremy Findlay، نويسنده , , et al.، نويسنده ,
Abstract :
A novel series of tertiary alcohol containing 2-substituted benzyl morpholines have been discovered as potent and selective inhibitors of the norepinephrine transporter. Efficient synthetic routes were developed featuring a highly diastereoselective nucleophilic addition of benzyl Grignard reagents to enantiopure (4-benzylmorpholin-2-yl)phenylmethanone (11) as the key synthetic step. In vitro binding affinity for the norepinephrine, dopamine and serotonin transporters and in vivo examination of a select compound (16) in a pharmacodynamic animal model for norepinephrine reuptake inhibition are presented.
Keywords :
depression , Atomoxetine , Attention Deficit Hyperactivity Disorder , ADHD , Norepinephrine , Dopamine , Serotonin , Reuptake , inhibitor , ?-MMT , Metariminol , Morpholine , Tertiary alcohol , Selective norepinephrine reuptake inhibitor
