engleski

The Novel 6-Fluoroalkylated Side Chain Substituted Pyrimidine Derivatives: Synthesis, 1H and 13C NMR Conformational Analysis, Antiviral and Cytostatic Evaluation

New types of C-6 alkylated pyrimidine derivatives were prepared via lithiation of 2, 4-dimethoxy-5, 6-dimethyl pyrimidine and 2, 4-dimethoxy-6-methyl pyrimidine and subsequent nucleophilic addition or substitution reactions of the organolithium intermediate with acetaldehyde, epichlorhydrine and fluorinated ketones and fluorinated esters as electrophiles. Novel compounds were evaluated against their cytostatic and antiviral activities. Amongst all evaluated compounds, fluorinated acyclic pyrimidine derivatives 6 showed the best cytostatic activity. [1] Compound 6 exhibited a pronounced effect against breast carcinoma (MCF-7, IC50 = 8.38  g/ml). Fluorinated pyrimidine derivatives 5 and 9 showed the best and selective activities against Davis strains of cytomegalovirus (CMV, 5: EC50 = 4  g/ml and 9: EC50 = 8  g/ml). Compound 5 appears to demonstrate sufficient anti-CMV potency and selectivity to justify its structure optimization and further biological evaluation.

C-6 fluoroalkylated pyrimidine derivatives; antiviral activities; NMR conformational analysis

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