Synthesis of N-(1-(6-acetamido-5-phenylpyrimidin-4-y1) piperidin-3-yl) amide derivatives as potential inhibitors for mitotic kinesin spindle protein

摘要

Kinesin Spindle Protein (KSP) or EgS is an essential kinesin that is involved in spindle separation process during mitosis and also unregulated in certain cancer cells. Inhibitors of this enzyme have proved to be effective to block spindle separation followed by mitotic arrest and apoptosis of the cancer cells. Since this enzyme has two allosteric inhibitor binding sites, it's an excellent target for developing drugs for cancer chemotherapy. Many pyrimidine derivatives have been proved to be active against cancer and other enzymes. In this report, we have synthesized a set ten novel N-(1-(6-acetamido-5phenylpyrimidin-4-yl)piperidin-3-yl)amide derivatives and have evaluated their activity against the KSP. The SAR of these active compounds was further analyzed using in silico molecular docking studies using GOLD and AutoDock softwares. All these compounds form hydrophobic interaction, aromatic pi-pi stacking and hydrogen bond efficiently with the EgS. (C) 2018 Published by Elsevier Masson SAS.