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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
American Journal of Heterocyclic Chemistry
Volume 5, Issue 4, December 2019, Pages: 76-80
Received: Aug. 27, 2019; Accepted: Sep. 10, 2019; Published: Oct. 11, 2019
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Dina Abed Bakhotmah, Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
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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.
Barbituric, Thiobarbituric, 1,2,4-triazine, CDK2, Malonate Ester, Trifluoroacylation
To cite this article
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, American Journal of Heterocyclic Chemistry. Vol. 5, No. 4, 2019, pp. 76-80. doi: 10.11648/j.ajhc.20190504.11
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