2. Academic Validation
  3. Synthesis, cytostatic activity and ADME properties of C-5 substituted and N-acyclic pyrimidine derivatives

Synthesis, cytostatic activity and ADME properties of C-5 substituted and N-acyclic pyrimidine derivatives

  • Bioorg Med Chem Lett. 2012 Jan 1;22(1):308-12. doi: 10.1016/j.bmcl.2011.11.009.
Tatjana Gazivoda Kraljević 1,  Mateja Klika,  Marijeta Kralj,  Irena Martin-Kleiner,  Stella Jurmanović,  Astrid Milić,  Jasna Padovan,  Silvana Raić-Malić
Affiliations

Affiliation

  • 1 Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, HR-10000 Zagreb, Croatia.
PMID: 22130132 DOI: 10.1016/j.bmcl.2011.11.009
Abstract

The synthesis of the novel 5-alkyl pyrimidine derivatives, 5,6-dihydrofuro[2,3-d]pyrimidines and 5-alkyl N-methoxymethyl pyrimidine derivatives and evaluation of their cytostatic activities are described. The mechanism of antiproliferative effect of 5-(2-chloroethyl)-substituted pyrimidine 3 that exerted the pronounced cytostatic activity was studied in further details on colon carcinoma (HCT116) cells. The cell cycle perturbation analysis demonstrated severe DNA damage (G2/M arrest) pointing to a potential DNA alkylating ability of 3. Preliminary ADME data of 3 and its 6-methylated structural congener (6-Me-3) showed their high permeability and good metabolic stability.

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