Discovery of novel and selective tertiary alcohol containing inhibitors of the norepinephrine transporter

MJ Cases-Thomas, JJ Masters, MW Walter…

Index: Cases-Thomas, Manuel J.; Masters, John J.; Walter, Magnus W.; Campbell, Gordon; Haughton, Louise; Gallagher, Peter T.; Dobson, David R.; Mancuso, Vincent; Bonnier, Benjamin; Giard, Thierry; Defrance, Thierry; Vanmarsenille, Michel; Ledgard, Andrew; White, Craig; Ouwerkerk-Mahadevan, Sivi; Brunelle, Francoise J.; Dezutter, Nancy A.; Herbots, Camy A.; Lienard, Joel Y.; Findlay, Jeremy; Hayhurst, Lorna; Boot, John; Thompson, Linda K.; Hemrick-Luecke, Susan Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 7 p. 2022 - 2025

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Citation Number: 16

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 ...