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

Priyanka Manchanda, Badri Parshad, Amit Kumar, Rakesh K. Tiwari, Amir N. Shirazi, Keykavous Parang, Sunil K. Sharma

Research output: Contribution to journalArticlepeer-review

Abstract

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 8.39 μM. 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.

Original languageEnglish (US)
Article number1600390
JournalArchiv der Pharmazie
Volume350
Issue number3-4
DOIs
StatePublished - Apr 1 2017

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery

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