Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Design, Synthesis and in-vitro Screening of New 1H-Pyrazole and 1,2-Isoxazole Derivatives as Potential Inhibitors for ROS and MAPK14 Kinases

  • Al-Sanea, Mohammad M. (Department of Biomolecular Science, University of Science and Technology) ;
  • El-Deeb, Ibrahim M. (Institute for Glycomics, Griffith University, Gold Coast Campus, QLD) ;
  • Lee, So Ha (Chemical Kinomics Research Center, Korea Institute of Science and Technology)
  • Received : 2012.08.08
  • Accepted : 2012.11.14
  • Published : 2013.02.20
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Abstract

A new series of 4-(2-(substituted)pyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazoles (4a-f) and their 1,2-isoxazole analogues (5a-f) has been rationally designed, synthesized and screened against both ROS and MAPK14 kinases. Compounds 4b, 4c and 4e showed moderate inhibitions against both ROS and MAPK14 kinases. Compound 4e has showed the strongest inhibitions with IC50 values of 1.25 ${\mu}M$ and 3.00 ${\mu}M$ against ROS and MAPK14 kinases, respectively. A brief structure-activity relationship study and a molecular modeling study were made revealing a group of essential structural features for good kinase inhibitory activity within this new class of kinase inhibitors.

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References

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