Design, Synthesis, and Evaluation of the Kinase Inhibition Potential of Pyridylpyrimidinylaminophenyl Derivatives

作者：Manchanda Priyanka; Parshad Badri; Kumar Amit; Tiwari Rakesh K; Shirazi Amir N; Parang Keykavous; Sharma Sunil K^*

来源：Archiv der Pharmazie, 2017, 350(3-4): e1600390.

DOI：10.1002/ardp.201600390

• Amide derivatives
• Imatinib
• Kinase inhibitors
• Pyridin-2(1H)-one
• Pyridylpyrimidinylaminophenyl

In view of potent kinase inhibitors for the treatment of myriad human disorders, we synthesized some structurally variant amide/cyclic amide derivatives based on pyridylpyrimidinylaminophenyl amine, the key pharmacophore of the kinase inhibitor drug molecule, imatinib, and evaluated their kinase inhibition potency. Among the various synthesized amides, compound 20, a cyclic amide/pyridin-2(1H)-one derivative, exhibited an IC50 value comparable to that of the drug imatinib against c-Src kinase, and another compound (14) containing a 2-((4-methyl-2-oxo-2H-chromen-6-yl)oxy)acetamide demonstrated an IC50 value of 8.39M. Furthermore, the constitution of the cyclic amide derivative was confirmed by the single-crystal X-ray diffraction technique. These results may serve as a gateway for developing novel next-generation kinase inhibitors.

• 出版日期2017-4