A Profound Insight into the Structure-activity Relationship of Ubiquitous Scaffold Piperazine: An Explicative Review

Abstract: Despite extensive research in the field of drug discovery and development, still there is a need to develop novel molecular entities. Literature reveals a substantial heterocyclic nucleus named, piperazine, which shows an immense therapeutic voyage. For several decades, molecules having the piperazine nucleus have entered the market as a drug exhibiting biological potential. It was known to possess antipsychotic, antihistamine, antianginal, antidepressant, anticancer, antiviral, cardioprotective, and anti-inflammatory activity with a specific basis for structural activity relationship. Thus, it is regarded as a key structural feature in most of the already available therapeutic drugs in the market. Reports also suggest that the extensive utilization of these currently available drugs having a piperazine nucleus shows increasing tolerance significantly day by day. In addition to this, various other factors like solubility, low bioavailability, cost-effectiveness, and imbalance between pharmacokinetics and pharmacodynamics profile limit their utilization. Focusing on that issues, various structural modification studies were performed on the piperazine moiety to develop new derivatives/analogs to overcome the problems associated with available marketed drugs. Thus, this review article aims to gain insight into the number of structural modifications at the N-1 and N-4 positions of the piperazine scaffold. This SAR approach may prove to be the best way to overcome the above-discussed drawbacks and lead to the design of drug molecules with better efficacy and affinity. Hence, there is an urgent need to focus on the structural features of this scaffold which paves further work for deeper exploration and may help medicinal chemists as well as pharmaceutical industries.