Piperazine, a Key Substructure for Antidepressants: Its Role in Developments and Structure-Activity Relationships.

Ravi Ranjan KumarBhupinder Kumar


Depression is the single largest contributor to global disability with a huge economic and social burden on the world. There are a number of antidepressant drugs on the market, but treatment-resistant depression and relapse of depression in a large number of patients have increased problems for clinicians. One peculiarity observed in most of the marketed antidepressants is the presence of a piperazine substructure. Although piperazine is also used in the optimization of other pharmacological agents, it is almost extensively used for the development of novel antidepressants. One common understanding is that this is due to its favorable CNS pharmacokinetic profile; however, in the case of antidepressants, piperazine plays a much bigger role and is involved in specific binding conformations of these agents. Therefore, in this review, a critical analysis of the significance of the piperazine moiety in the development of antidepressants has been performed. An overview of current developments in the designing and synthesis of piperazine-based antidepressants (2015 onwards) along with SAR studies is also provided. The various piperazine-based therapeutic agents in early- or late-phase human testing for depression are also discussed. T...Continue Reading


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