Pyrimidine‐based pyrazoles as cyclin‐dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation

@article{Vekariya2018PyrimidinebasedPA,
  title={Pyrimidine‐based pyrazoles as cyclin‐dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation},
  author={Mayur K. Vekariya and Rajesh H. Vekariya and Pathik Subhashchandra Brahmkshatriya and Nisha K Shah},
  journal={Chemical Biology \& Drug Design},
  year={2018},
  volume={92},
  pages={1683 - 1691}
}
A series of new pyrimidine‐pyrazole hybrid molecules were designed as inhibitors of cyclin‐dependent kinase 2. Designed compounds were docked using Glide and the compounds showing good score values and encouraging interactions with the residues were selected for synthesis. They were then evaluated using CDK2‐CyclinA2 enzyme inhibition by a luminescent ADP detection assay. We show that of the 26 compounds synthesized and evaluated, at least 5 compounds were found to be highly potent (IC50 < 20… 
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9 Citations

9 Citations

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References

SHOWING 1-10 OF 26 REFERENCES
Structure-guided discovery of cyclin-dependent kinase inhibitors.
TLDR
Crystal structures of inhibitors containing the related bicyclic heterocycles pyrazolopyrimidines and imidazopyrazine core show that all but one have a common binding mode featuring two hydrogen bonds to the backbone of the kinase hinge region.
Cyclin-Dependent Kinase Inhibitors as Marketed Anticancer Drugs: Where Are We Now? A Short Survey
TLDR
An updated list of compounds under clinical evaluation (phase I/II/III) and their mode of action as ATP- competitive inhibitors are discussed and tentative progress for forthcoming potential ATP non-competitive inhibitors and allosteric inhibitors is briefly described.
Pyrimidoquinazoline-based antitumor agents. Design of topoisomerase II to DNA cross-linkers with activity against protein kinases.
TLDR
It is confirmed that the pyrimidoquinazolines possess inhibitory activity against both topoisomerase II and protein kinases, such as the paullones, a dual property observed in other antineoplastic agents influencing phosphoester transfer.
Synthesis and biological evaluation of novel pyrazole derivatives with anticancer activity.
Synthesis and antiviral activity of new pyrazole and thiazole derivatives.
Design, synthesis and biological evaluation of some pyrazole derivatives as anti-inflammatory-antimicrobial agents.
Cell cycle kinases as therapeutic targets for cancer
TLDR
The potential and limitations of established cell cycle kinases as targets in anticancer drug discovery as well as novel strategies for the design of new agents are discussed.
Synthesis and in vivo diuretic activity of some novel pyrimidine derivatives
TLDR
Overall, compound 3e, 6-(2, 6-dichlorophenyl)-4-(pyridin-2-yl)-1,6-dihydropyrimidine- 2-thiol, was found to be the most promising candidate of the series and showed diuretic properties more than that of standard (acetazolamide) and were long acting.
Synthesis of (1,4)-naphthoquinono-[3,2-c]-1H-pyrazoles and their (1,4)-naphthohydroquinone derivatives as antifungal, antibacterial, and anticancer agents.
Studies on substituted benzo[h]quinazolines, benzo[g]indazoles, pyrazoles, 2,6-diarylpyridines as anti-tubercular agents.
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