American Journal of Heterocyclic Chemistry

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Synthesis of Barbituric and Thiobarbituric Acids Bearing 5,6-Diphenyl-1,2,4-Triazin-3-yl Moiety as CDK2 Inhibitors of Tumor Cells

Received: 27 August 2019    Accepted: 10 September 2019    Published: 11 October 2019
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Abstract

Synthesis of several new diphenyl-1',2',4'-triazin-3'-yl barbituric acid are described. The method involves addition reaction of isocyanate and isothiocyanate and 3-amino-5,6-diphenyl-1,2,4-triazine (1) to give N1,N3-disubstituted urea 2 and N1,N3-disubstituted thioureas 3 and 4 respectively. Further, ring closure reactions with malonate ester give barbituric acid 5 and thiobarbituric acid 6 and 7. The Presence of the active methylene in the skeleton of compound 5-7 at C-5 are deduced by condensation with pyridine-4-carboxyladehyde to give barbituric and thiobarbituric acids (8-10). Further fluoroacylation of compounds 5-7, afforded 1-(cyclohexyl/methyl/phenyl)-3-(5',6'-diphenyl-1',2',4'-triazin-3'-yl)-5-(trifluoracetyl)-5H-barbituric/thiobarbituric acids (11-13). Synthesis compounds of the series 5-(trifluoroacetyl) barbituric acid (11) and 5-(trifluoroacetyl) thiobarbituric acids (12 and 13) were able to inhibit activity of CDK2 in a biochemical assay with IC50 values comparable to olomoucine. In addition, a pyridine side chain at C-5 (compound 9 and 10) significantly decreases CDK2 inhibitory activity.

DOI 10.11648/j.ajhc.20190504.11
Published in American Journal of Heterocyclic Chemistry (Volume 5, Issue 4, December 2019)
Page(s) 76-80
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Barbituric, Thiobarbituric, 1,2,4-triazine, CDK2, Malonate Ester, Trifluoroacylation

References
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Author Information
  • Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia

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    Dina Abed Bakhotmah. (2019). Synthesis of Barbituric and Thiobarbituric Acids Bearing 5,6-Diphenyl-1,2,4-Triazin-3-yl Moiety as CDK2 Inhibitors of Tumor Cells. American Journal of Heterocyclic Chemistry, 5(4), 76-80. https://doi.org/10.11648/j.ajhc.20190504.11

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    ACS Style

    Dina Abed Bakhotmah. Synthesis of Barbituric and Thiobarbituric Acids Bearing 5,6-Diphenyl-1,2,4-Triazin-3-yl Moiety as CDK2 Inhibitors of Tumor Cells. Am. J. Heterocycl. Chem. 2019, 5(4), 76-80. doi: 10.11648/j.ajhc.20190504.11

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    AMA Style

    Dina Abed Bakhotmah. Synthesis of Barbituric and Thiobarbituric Acids Bearing 5,6-Diphenyl-1,2,4-Triazin-3-yl Moiety as CDK2 Inhibitors of Tumor Cells. Am J Heterocycl Chem. 2019;5(4):76-80. doi: 10.11648/j.ajhc.20190504.11

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  • @article{10.11648/j.ajhc.20190504.11,
      author = {Dina Abed Bakhotmah},
      title = {Synthesis of Barbituric and Thiobarbituric Acids Bearing 5,6-Diphenyl-1,2,4-Triazin-3-yl Moiety as CDK2 Inhibitors of Tumor Cells},
      journal = {American Journal of Heterocyclic Chemistry},
      volume = {5},
      number = {4},
      pages = {76-80},
      doi = {10.11648/j.ajhc.20190504.11},
      url = {https://doi.org/10.11648/j.ajhc.20190504.11},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.ajhc.20190504.11},
      abstract = {Synthesis of several new diphenyl-1',2',4'-triazin-3'-yl barbituric acid are described. The method involves addition reaction of isocyanate and isothiocyanate and 3-amino-5,6-diphenyl-1,2,4-triazine (1) to give N1,N3-disubstituted urea 2 and N1,N3-disubstituted thioureas 3 and 4 respectively. Further, ring closure reactions with malonate ester give barbituric acid 5 and thiobarbituric acid 6 and 7. The Presence of the active methylene in the skeleton of compound 5-7 at C-5 are deduced by condensation with pyridine-4-carboxyladehyde to give barbituric and thiobarbituric acids (8-10). Further fluoroacylation of compounds 5-7, afforded 1-(cyclohexyl/methyl/phenyl)-3-(5',6'-diphenyl-1',2',4'-triazin-3'-yl)-5-(trifluoracetyl)-5H-barbituric/thiobarbituric acids (11-13). Synthesis compounds of the series 5-(trifluoroacetyl) barbituric acid (11) and 5-(trifluoroacetyl) thiobarbituric acids (12 and 13) were able to inhibit activity of CDK2 in a biochemical assay with IC50 values comparable to olomoucine. In addition, a pyridine side chain at C-5 (compound 9 and 10) significantly decreases CDK2 inhibitory activity.},
     year = {2019}
    }
    

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  • TY  - JOUR
    T1  - Synthesis of Barbituric and Thiobarbituric Acids Bearing 5,6-Diphenyl-1,2,4-Triazin-3-yl Moiety as CDK2 Inhibitors of Tumor Cells
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    JF  - American Journal of Heterocyclic Chemistry
    JO  - American Journal of Heterocyclic Chemistry
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    PB  - Science Publishing Group
    SN  - 2575-5722
    UR  - https://doi.org/10.11648/j.ajhc.20190504.11
    AB  - Synthesis of several new diphenyl-1',2',4'-triazin-3'-yl barbituric acid are described. The method involves addition reaction of isocyanate and isothiocyanate and 3-amino-5,6-diphenyl-1,2,4-triazine (1) to give N1,N3-disubstituted urea 2 and N1,N3-disubstituted thioureas 3 and 4 respectively. Further, ring closure reactions with malonate ester give barbituric acid 5 and thiobarbituric acid 6 and 7. The Presence of the active methylene in the skeleton of compound 5-7 at C-5 are deduced by condensation with pyridine-4-carboxyladehyde to give barbituric and thiobarbituric acids (8-10). Further fluoroacylation of compounds 5-7, afforded 1-(cyclohexyl/methyl/phenyl)-3-(5',6'-diphenyl-1',2',4'-triazin-3'-yl)-5-(trifluoracetyl)-5H-barbituric/thiobarbituric acids (11-13). Synthesis compounds of the series 5-(trifluoroacetyl) barbituric acid (11) and 5-(trifluoroacetyl) thiobarbituric acids (12 and 13) were able to inhibit activity of CDK2 in a biochemical assay with IC50 values comparable to olomoucine. In addition, a pyridine side chain at C-5 (compound 9 and 10) significantly decreases CDK2 inhibitory activity.
    VL  - 5
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