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The Novel C-6 Alkylated Pyrimidine Derivatives: Synthesis, X-Ray Crystal Structure Study, Antiviral and Cytostatic Evaluations

New types of C-6 alkylated pyrimidine derivatives 3-7 were prepared via lithiation of 2, 4-dimethoxy-5, 6-dimethyl pyrimidine and subsequent nucleophilic addition or substitution reactions of the organolithium intermediate with acetaldehyde, fluoroacetone, trifluoroacetone and epichlorhydrine as electrophiles. An unequivocal proof of the stereostructure of piperido[1, 2-c]pyrimidine-1-one derivative 17 was obtained by the single crystal X-ray diffraction method. Novel compounds 3-6, 8-13 and 15-17 were evaluated against their cytostatic and antiviral activities. Amongst all evaluated compounds, fluorinated acyclic pyrimidine derivatives 6 and 9 showed the best cytostatic activities. Compound 6 exhibited a pronounced effect against breast carcinoma (MCF-7, IC50 = 8.38 ug/ml), while compound 9 exhibited moderate effect against cervical carcinoma (HeLa, IC50 = 19.73 ug/ml). Fluorinated pyrimidine derivatives 5 and 9 showed the best and selective activities against Davis strains of cytomegalovirus (CMV, 5: EC50 = 4 ug/ml and 9: EC50 = 8 ug/ml). Compound 5 appears to demonstrate sufficient anti-CMV potency and selectivity to justify its structure optimization and further biological evaluation.

C-6 Alkylated Pyrimidine Derivatives; Synthesis; X-Ray Crystal Structure Study; Antiviral and Cytostatic Evaluations

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