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The synthetic route for introduction of a fluoroalkyl (7-12, 14), fluoroalkenyl (15 and 16), fluorophenylalkyl (17, 19, 20, and 22), and fluorophenylalkenyl (18, 21) side chain at C-6 of the pyrimidine involved the lithiation of the pyrimidine derivatives 3 and 3a and subsequent nucleophilic addition or substitution reactions of the organolithium intermediate thus obtained with various electrophiles. Conformational properties of the novel fluorinated pyrimidine derivatives were assessed by the use of 1D difference NOE enhancements and C-F coupling constants. Compounds 4-22 were evaluated for their antiviral and cytostatic activities. Of all compounds evaluated, the 5-bromopyrimidine derivatives 5 and 6 showed the highest inhibitory activities. Among the series of fluoroalkylated pyrimidines, which is generally more active than the series of fluorophenylalkylated pyrimidines, compounds 8 and 14 displayed moderate cytostatic activities against the tested tumor cell lines. Moreover, compound 8 containing a 2-fluoromethylpropyl side chain expressed some but not highly specific activity against varicella-zoster virus (VZV). From C-6 fluorophenylalkylated pyrimidine derivatives, 17a and 21 showed a slight activity against cytomegalovirus (CMV), VZV, and Coxsackie B4 virus, respectively. Besides, compounds 17a and 21 showed no cytotoxic effect.

In the title compound, C10H14N2O3, a pyrimidine ring is fused with a piperidine ring. The pyrimidine ring is planar, whereas the piperidine ring adopts a half-chair conformation. The molecules of the title compound are connected via O-H...O intermolecular hydrogen bonds into infinite zigzag chains. The pyrimidine ring is involved in three C-H...pi interactions, which link the hydrogen-bonded chains into a three-dimensional framework.

A series of the novel 5-methyl pyrimidine derivatives with an acyclic side chain at the C-6 position were synthesized using lithiation of a 2,4-dimethoxy-5,6-dimethyl pyrimidine and subsequent nucleophilic addition or substitution reactions of the organolithium intermediate thus obtained with acetaldehyde, epichlorhydrine, fluorinated ketones and fluorinated ester. The novel compounds were evaluated for their cytostatic and antiviral activities. Among all the compounds evaluated, two fluorinated acyclic pyrimidine derivatives showed the highest cytostatic activities. The compound containing a 2-hydroxy-3,3,3-trifluoro-1-propenyl side chain exhibited a pronounced effect against breast carcinoma (MCF-7, IC50=8.38 micorg/ml), while the compound with a 2-fluoromethyl-2-acetoxypropyl chain exhibited moderate effect against cervical carcinoma (HeLa, IC50=19.73 microg/ml).