Dual serotonin transporter inhibitor/histamine H3 antagonists: Development of rigidified H3 pharmacophores

A series of tetrahydroisoquinolines acting as dual serotonin transporter inhibitor/histamine H3 antagonists is described. The introduction of polar aromatic spacers as part of the histamine H3 pharmacophore was explored. A convergent synthesis of the final products allowing late stage introduction of the aromatic side chain was developed. In vitro and in vivo data are discussed.

Graphical abstractA series of tetrahydroisoquinolines acting as dual serotonin transporter inhibitor/histamine H3 antagonists is described. The introduction of polar aromatic spacers as part of the histamine H3 pharmacophore was explored. A convergent synthesis of the final products allowing late stage introduction of the aromatic side chain was developed. In vitro and in vivo data are discussed.Figure optionsDownload full-size imageDownload as PowerPoint slide