Piperonine possesses the chemical structure of pharmacophore, such as hydrogen-bonded acceptor, hydrophobic center and aryl ring center, which can bind to the receptor, and its uncomplicated structure is conducive to structural modification studies. Therefore, piperine not only can be used as a new drug in its own right, but also lays the foundation for further chemical synthesis to obtain highly active and low-toxicity lead compounds.

The derivatives of piperine were prepared by changing the benzene ring substituent, the side chain of the benzene ring and the hexahydropyridine ring substituent of piperine, and the conformational relationship of piperine's anti-hepatic microsomal enzyme activity was investigated. Thirty-eight new congeners or derivatives of piperine were synthesized by modifying the benzene ring, side chain substituents and basic skeleton of piperine, and their activities as inhibitors of the drug metabolizing enzyme CYP450 were investigated. It was shown that, in general, if the structure of the parent compound was changed, the CYP450 inhibition activity would be lost; the saturation degree of the side chain significantly affected the inhibition activity; and the modification of the benzene ring and the basic skeleton could not provide a highly selective CYP450 inhibitor; the study was unable to obtain the new compounds with stronger activity in the end. Another structural modification of piperine was reported using the Diels-Alder reaction to generate piperine dimers, which was not investigated for biological activity.