期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 18, 期 7, 页码 2704-2712出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2010.02.023
关键词
5,6-Disubstituted pyrimidines; Lithiation; Positron-emission tomography (PET); Cytostatic evaluations; X-ray diffraction; Hydrogen bonds; pi center dot center dot center dot pi interactions
资金
- Ministry of Science of the Republic of Croatia [125-0982464-2925, 119-1193079-3069, 098-0982464-2514]
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 H-1 NMR, C-13 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 center dot center dot center dot O and one C-H center dot center dot center dot O hydrogen bonds in 4 form three-dimensional network. One O-H center dot center dot center dot N hydrogen bond and one pi center dot center dot center dot pi interaction self-assemble the molecules of 7 into sheets. In supramolecular aggregation of 14, only pi center dot center dot center dot 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-methoxy-tritylethylpyrimidine (9) and 2,4-dichloro-5-chloroethylpyrimidine (14) exhibited the most prominent inhibitory effects. Furthermore, compound 14 showed marked activity against human colon carcinoma (IC50 = 0.4 mu M). (C) 2010 Elsevier Ltd. All rights reserved.
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