Dual serotonin transporter/histamine H 3 ligands: Optimization of the H 3 pharmacophore

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 3; pp. 702 - 706
• Main Authors: Keith, John M., Gomez, Leslie A., Letavic, Michael A., Ly, Kiev S., Jablonowski, Jill A., Seierstad, Mark, Barbier, Ann J., Wilson, Sandy J., Boggs, Jamin D., Fraser, Ian C., Mazur, Curt, Lovenberg, Timothy W., Carruthers, Nicholas I.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.02.2007
• Subjects: 5-HTP potentiation; Histamine H 3; Ring-closure; Serotonin transporter; Ring-closure; 5-HTP potentiation; Serotonin transporter; Histamine H 3
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.10.089

A series of tetrahydroisoquinolines acting as dual histamine H 3/serotonin transporter ligands is described. A highly regio-selective synthesis of the tetrahydroisoquinoline core involving acid mediated ring-closure of an acetophenone intermediate followed by reduction with NaCNBH 3 was developed. In vitro and in vivo data are discussed. A series of tetrahydroisoquinolines acting as dual histamine H 3/serotonin transporter ligands is described. A highly regio-selective synthesis of the tetrahydroisoquinoline core involving acid mediated ring-closure of an acetophenone intermediate followed by reduction with NaCNBH 3 was developed. In vitro and in vivo data are discussed.