Introduction:Piperine is a natural alkaloid found in Piper nigrum. This work aims to perform a virtual screening of 20 synthetic piperine derivatives with potential antileishmanial activity. Methodology: A classificatory prediction model concerning the Leishmania infantum Promastigote cell form in Knime software was built. The compounds were subjected to Molecular Docking in the Molegro Virtual Docker v.6.0.1 software, using the CYP51 target complexed to the inhibitor Fluconazole obtained from the Protein Data Bank. The molecules under study were submitted to a consensus calculation involving the activity probability obtained in the elaborated model, as well as in the molecular docking simulation performed. Results: The prediction model was more than 78% accurate in the test and in the cross-validation, selecting the 20 synthetic derivatives under study as potentially active for the promastigote form. In Docking, only 9 of the molecules of the 20 molecules selected by the model had better energy than the ligand. In the consensus calculation, nine compounds had a probability above 50%. Among the structures, molecule 20 was considered the one with the best performance in the study developed.Conclusions: The virtual screening performed was able to identify the compounds with the highest probability of activity.