title: Synthesis, X-ray crystal structure study and antitumoral evaluations of 5,6-disubstituted pyrimidine derivatives.
abstract: 5,6-Disubstituted pyrimidine derivatives (3-20) were prepared by intramolecular cyclization reaction of alpha-(1-carbamyliminomethylene)-gamma-butyrolactone (2) with sodium ethoxide and subsequent chemical transformation of 2-hydroxy group in C-5 side chain as well as lithiation reaction for introduction of acyclic side chain at C-6. All compounds were characterized by (1)H NMR, (13)C NMR and mass spectra. Structures of compounds 4, 7 and 14 were unambiguously confirmed by X-ray crystal structural analysis. Supramolecular structures of these three compounds differ significantly. Two N-H...O and one C-H...O hydrogen bonds in 4 form three-dimensional network. One O-H...N hydrogen bond and one pi...pi interaction self-assemble the molecules of 7 into sheets. In supramolecular aggregation of 14, only pi...pi stacking interactions participate, so forming chains. The compounds were evaluated for their cytostatic activities against human malignant cell lines. Of all tested compounds, 2,4-dimethoxy-5-methoxytritylethylpyrimidine (9) and 2,4-dichloro-5-chloroethylpyrimidine (14) exhibited the most prominent inhibitory effects. Furthermore, compound 14 showed marked activity against human colon carcinoma (IC(50)=0.4microM).
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, PO Box 177, HR-10000 Zagreb, Croatia.
authors.forename: Tatjana Gazivoda
authors.initials: TG
authors.lastname: Kraljević
authors.forename: Svjetlana
authors.initials: S
authors.lastname: Kristafor
authors.forename: Lidija
authors.initials: L
authors.lastname: Suman
authors.forename: Marijeta
authors.initials: M
authors.lastname: Kralj
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
authors.forename: Mario
authors.initials: M
authors.lastname: Cetina
authors.forename: Silvana
authors.initials: S
authors.lastname: Raić-Malić
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D011743:Pyrimidines