Docking and quantitative structure–activity relationship studies for imidazo[1,2-a]pyrazines as inhibitors of checkpoint kinase-1


We have performed docking of imidazo[1,2-a]pyrazines complexed with checkpoint kinase1 (Chk1) to better understand the structural requirements and preferred conformations of these inhibitors. The study was performed on a selected set of 33 compounds with variation in structure and activity. In addition, the predicted inhibitor concentrations (IC50) of the imidazo[1,2-a]pyrazines as Chk1 inhibitors were obtained by comparative molecular similarity analysis (CoMSIA). The best CoMSIA model included electrostatic and hydrophobic fields, had a good Q 2 value of 0.589, and adequately predicted the compounds contained in the test set. Furthermore, plots of the CoMSIA fields allowed conclusions to be drawn for the selection of suitable inhibitors.

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Julio Caballero thanks “Becas Universidad de Talca” for financial support through doctoral fellowship. Part of this work has been supported by Fondecyt, Grant 11090431, Proyecto interno DI-13-10/R, Universidad Andres Bello.

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Correspondence to Julio Caballero.

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Caballero, J., Zilocchi, S., Tiznado, W. et al. Docking and quantitative structure–activity relationship studies for imidazo[1,2-a]pyrazines as inhibitors of checkpoint kinase-1. Med Chem Res 21, 1912–1920 (2012).

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  • Checkpoint kinase-1 inhibitors
  • Molecular docking
  • Quantitative structure–activity relationships
  • CoMSIA