Design, synthesis and activity evaluation of novel selective serotonin reuptake inhibitors

Depression is a kind of common and severe mental illness.' During the past two decades, selective serotonin reuptake inhibitors (SSRIs) have been proved to be a safer and more effective resistance than the first-generation antidepressants (TCAs and MAOIs), and have gained incredible popularity. Based on the conformation analysis and pharmacophore information of SSRIs, flexible database searching from the NCI-3D and Maybridge-3D database was performed. Three classes of the new compounds structures were designed and 27 analogues were prepared and evaluated as potential antidepressant agents. Biphenylbenzamidine derivative I-19 showed good activity of affinity to the 5-HT transporter. It can be used as the lead structure for drug design with the objective of making more potent inhibitors against 5-HT transporter.