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.