Multi-targeted pharmacological properties of cinnamyl piperazine derivatives: a comprehensive review

The cinnamyl piperazine motif is a crucial element in drugs targeting various biological targets. Medicinal chemistry researchers have designed and synthesized drug-like cinnamyl piperazine candidates with multiple medicinal properties, including activities in the central nervous system (CNS), antitumor, antiviral, anti-inflammatory, antimicrobial, cardiovascular, and enzyme inhibitory effects. Structure-activity relationship (SAR) investigations have been a focus for medicinal chemists, and several derivatives have been developed for different targets. In this article, we comprehensively summarize the biological activities and SAR of cinnamyl piperazine derivatives, as well as the notable clinical candidates reported in patents and the co-crystal structure between cinnamyl piperazine derivatives and potential targets, aiming to provide an overall retrospective and prospective view of cinnamyl piperazine analogs.