Novel C-6 fluorinated acyclic side chain pyrimidine derivatives: Synthesis, H-1 and C-13 NMR conformational studies, and antiviral and cytostatic evaluations (CROSBI ID 132729)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Prekupec, Svjetlana ; Makuc, Damjan ; Plavec, Janez ; Šuman, Lidija ; Kralj, Marijeta ; Pavelić, Krešimir ; Balzarini, Jan ; De Clercq, Erik ; Mintas, Mladen ; Raić-Malić, Silvana
engleski
Novel C-6 fluorinated acyclic side chain pyrimidine derivatives: Synthesis, H-1 and C-13 NMR conformational studies, and antiviral and cytostatic evaluations
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.
fluoroalkylated pyrimidines ; positron-emission tomography ; NMR conformational analysis ; antiviral and cytostatic activity evaluations
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Podaci o izdanju
50 (13)
2007.
3037-3045
objavljeno
0022-2623
1520-4804
10.1021/jm0614329
Povezanost rada
Kemija, Temeljne medicinske znanosti