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The Novel Fluorinated C-6 Substituted Uracil Derivatives: Synthesis, 1H and 13C NMR Conformational and X-Ray Crystal Structure Studies

Pyrimidine derivatives and their nucleosides have great biological significance because they exhibit a wide range of antiviral and anticancer activities. Some uracil and pyrimidinone derivatives substituted at C-5 or C-6 position have emerged in the field of antiviral chemotherapy. The pronounced biological activities exhibited by this class of compounds led us to synthesize the new type of C-6 alkylated pyrimidine derivatives and to evaluate their cytostatic and antiviral activities.1 Among all compounds evaluated, the compound containing a 2-hydroxy-3, 3, 3-trifluoro-1-propenyl side chain exhibited a pronounced effect against breast carcinoma (MCF-7), while the compound with a 2-fluoromethyl-2-acetoxypropyl chain exhibited moderate effect against cervical carcinoma (HeLa).2 A new series of the uracil derivatives (Figure) with an acyclic side chain at the C-6 position were synthesized using lithiation of the 5, 6-dimethyl pyrimidine derivative and subsequent nucleophilic addition or substitution reactions of the organolithium intermediate thus obtained with fluorinated ketones and fluorinated esters. Conformational properties of the novel fluorinated pyrimidine derivatives were assessed with the use of 1D difference NOE enhancements and C-F coupling constants. The compounds will be evaluated for their cytostatic and antiviral activities. 1) Raić-Malić, S. et al., Nucleosides, Nucleotides & Nucleic Acids. 23 (2004) 1707. 2) Prekupec, S. et al., Antiviral Chem. & Chemother. 16 (2005) 327.

Fluorinated C-6 Substituted Uracil Derivatives; 1H and 13C NMR

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