US EPA

7456344 

Journal Article 

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

Muthuraja, P; Himesh, M; Prakash, S; Venkatasubramanian, U; Manisankar, P 

2018 

Yes 

European Journal of Medicinal Chemistry
ISSN: 0223-5234
EISSN: 1768-3254 

Elsevier Masson SAS 

148 

106-115 

English 

10.1016/j.ejmech.2018.02.010 

Kinesin Spindle Protein (KSP) or Eg5 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-5-phenylpyrimidin-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 π-π stacking and hydrogen bond efficiently with the Eg5. © 2018 

Kinesin spindle protein; Molecular docking; Pyrimidine derivatives; acetamide derivative; kinesin; kinesin inhibitor; kinesin spindle protein; n [1 (6 acetamido 5 phenylpyrimidin 4 yl)piperdin 3 yl] 2 (2 fluorophenyl)acetamide; n [1 (6 acetamido 5 phenylpyrimidin 4 yl)piperdin 3 yl] 2 (3 chlorophenoxy)acetamide; n [1 (6 acetamido 5 phenylpyrimidin 4 yl)piperdin 3 yl] 2 (trifluoromethyl)benzamide; n [1 (6 acetamido 5 phenylpyrimidin 4 yl)piperdin 3 yl] 2 phenylacetamide; n [1 (6 acetamido 5 phenylpyrimidin 4 yl)piperdin 3 yl] 2,2,2 trifluoroacetamide; n [1 (6 acetamido 5 phenylpyrimidin 4 yl)piperdin yl] 2 (2 chlorophenoxy)acetamide; n [1 (6 acetamido 5 phenylpyrimidin 4 yl)piperdin yl] 2 (3 fluorophenyl)acetamide; n [1 (6 acetamido 5 phenylpyrimidin 4 yl)piperdin yl] 2 (3 methoxyphenoxy)acetamide; n [1 (6 acetamido 5 phenylpyrimidin 4 yl)piperdin yl] 3 (trifluoromethyl)benzamide; n [1 (6 acetamido 5 phenylpyrimidin 4 yl)piperidin 3 yl]amide derivative; n [6 (3 aminopiperdin 1 yl) 5 phenylpyrimidin 4 yl]acetamide; n [6 [3 (4 methylphenylsulfonamido)piperidin 1 yl] 5 phenylpyrimidin 4 yl]acetamide; piperidine derivative; pyrimidine derivative; tert butyl [1 (6 acetamido 5 phenylpyrimidin 4 yl)piperidin 3 yl]carbamate; tert butyl [1 (6 amino 5 phenylpyrimidin 4 yl)piperidin 3 yl]carbamate; unclassified drug; amide; antineoplastic agent; enzyme inhibitor; KIF11 protein, human; kinesin; pyrimidine derivative; Article; ATPase activity assay; computer model; crystal structure; drug efficacy; drug mechanism; drug screening; drug synthesis; enzyme inhibition; human; hydrogen bond; hydrophobicity; IC50; mitosis; molecular cloning; molecular docking; molecular interaction; protein expression; protein purification; software; steady state; structure activity relation; allosteric site; antagonists and inhibitors; chemical phenomena; chemistry; HeLa cell line; synthesis; Allosteric Site; Amides; Antineoplastic Agents; Enzyme Inhibitors; HeLa Cells; Humans; Hydrophobic and Hydrophilic Interactions; Kinesin; Molecular Docking Simulation; Pyrimidines; Structure-Activity Relationship