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

Article abstract of DOI:10.1016/j.bmcl.2007.08.017

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.