G. A. Breault, R. P. A. Ellston, S. Green, S. R. James, P. J. Jewsbury, C. J. Midgley, R. A. Pauptit, C. A. Minshull, J. A. Tucker, and J. E. Pease, “Cyclin-dependent kinase 4 inhibitors as a treatment for cancer. Part 2: Identification and optimisation of substituted 2, 4-bis anilino pyrimidines,” Bioorganic and Medicinal Chemistry Letters, Vol. 13, pp. 2961–2966, 2003.

has been cited by the following article:

• TITLE: Novel Ethyl 2-(1-aminocyclobutyl)-5-(benzoyloxy)-6-hydroxy-pyrimidine-4-carboxylate Derivatives: Synthesis and Anticancer Activities

  AUTHORS: D. Asha, C. V. Kavitha, S. Chandrappa, D. S. Prasanna, K. Vinaya, Sathees C. Raghavan, K. S. Rangappa

  KEYWORDS: Pyrimidine Derivatives, Cytotoxicity, Apoptosis, Leukemia, Cell Cycle Analysis

  JOURNAL NAME: Journal of Cancer Therapy, Vol.1 No.1, March 25, 2010

  ABSTRACT: To explore the anticancer activity of 2, 4, 5, 6-substituted pyrimidines, several ethyl 2-(1-aminocyclobutyl)-5-(benzoyloxy)-6-hydroxy-pyrimidine-4-carboxylatederivatives associated with the different substituted aromatic/aliphatic carboxamidesand sulfonamides were synthesized. Different groups and position on phenyl ring attached to the carboxamideand sulfonamide of the pyrimidine led to two set of compounds. Their chemical structures were confirmed by IR,1H NMR and LC/MS analysis. Cytotoxicity of all the synthesized compounds were examined on human leukemia celllines (K562 and CEM). The preliminary results showed most of the derivatives exhibited good antitumor activity. Compoundwith para chloro substitution among carboxamides and compound with meta dichloro substitution among sulphonamidesexhibited significant antitumor activity with IC50 value of 14.0 μM and 15.0 μM respectively against K562cell line. For comparison among electron donating groups between carboxamides and sulfonamides, compounds withpara tert-butyl substitution were chosen for further studies. Cell cycle analysis suggests that both tert-butyl substitutedcompounds are able to induce apoptosis.