Arylpiperazine-containing pyrimidine 4-carboxamide derivatives targeting serotonin 5-HT2A, 5-HT2C, and the serotonin transporter as a potential antidepressant

Pyrimidine usually has good pharmacokinetic properties as a drug substance and considerable efforts have been devoted to develop pyrimidine derivatives into drug candidates. Arylpiperazine-containing pyrimidine 4-carboxamide derivatives were synthesized and evaluated for binding to serotonin receptors and transporter. Pyrimidine derivatives showed good antidepressant activity in FST (forced swimming test) animal model and also displayed no appreciable inhibitory activity against hERG channel blocking assay. Herein SAR studies of pyrimidine derivatives targeting serotonin receptors and transporter will be disclosed.

Graphical abstractArylpiperazine-containing pyrimidine 4-carboxamide derivatives were synthesized and evaluated as novel antidepressant compounds. The various analogues were prepared and bio-assayed for binding to 5-HT2A, 5HT2C receptor, serotonin transporter. Based on the outcomes of in vitro SAR studies, forced swimming test along with locomotor activities, 16d was identified as a lead compound.Figure optionsDownload full-size imageDownload as PowerPoint slide