Antiviral, antitumor, and thymidylate synthetase inhibition studies of 5-substituted styryl derivatives of 2′-deoxyuridine and their 5′-phosphates

Synthesis, X-ray crystal structure study and antitumoral evaluations of 5,6-disubstituted pyrimidine derivatives

“…25 Therefore, biological activities by both 5-substituted and 6-substituted uracil derivatives encouraged us to explore chemistry and biological activities of novel 5,6-disubstituted uracil derivatives. In this paper we present syntheses, X-ray crystal structural study and cytostatic evaluations of pyrimidine derivatives (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) bearing substituents at positions C-5 and C-6 of pyrimidine ring (Figure 1). a-(1-Carbamyliminomethylene)-c-butyrolactone (2) was prepared by condensation of a-acetyl-c-butyrolactone (1) with urea in ethanol.…”

“…5-Substituted uracil analogs have been investigated extensively for use in cancer 1,2 and viral chemotherapy, 3,4 as enzyme inhibitors [5][6][7][8] and in the synthesis of modified nucleotides. 9,10 In addition, pyrimidines substituted at position C-6, as for example, 1-[(2-hydroxyethyl)-methyl]-6-(phenylthio)thymine (HEPT) 11,12 or 3,4-dihydro-2-alkoxy-6-benzyl-4-oxopyrimidines (DABOs) 13 and their derivatives [14][15][16] exhibited a potent and selective activity against human immunodeficiency virus type-1 (HIV-1).…”

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a b s t r a c t 5,6-Disubstituted pyrimidine derivatives (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were prepared by intramolecular cyclization reaction of a-(1-carbamyliminomethylene)-c-butyrolactone (2) with sodium ethoxide and subsequent chemical transformation of 2-hydroxy group in C-5 side chain as well as lithiation reaction for introduction of acyclic side chain at C-6. All compounds were characterized by 1 H NMR, 13 C NMR and mass spectra.

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Synthetic nucleosides and nucleotides. XXVII. Selective inhibition of deoxyribonucleic acid polymerase .ALPHA. by 1-.BETA.-D-arabinofuranosyl-5-styryluracil 5'-triphosphates and related nucleotides: Influence of hydrophobic and steric factors on the inhibitory action.

“…Ninhydrin positive (violet). 5-Phenethyl araUTP (11) A mixture of 1800 01)308 units (0.10 mmol) of 8 in 1 ml of water and 0.1 g of palladium-carbon was stirred under 1 atm pressure of hydrogen for 24 h at room temperature. The solution was filtered through celite, and the filter was washed with 200 ml of 50% aqueous ethanol-3% NH4OH.…”

Design, Synthesis, and Evaluation of Antineoplastic Activity of Novel Carbocyclic Nucleosides

“…We recognized an excellent opportunity when we could assemble a set of over 200 NA compounds, previously synthesized in one of our laboratories [3,[6][7][8][9] or elsewhere , all measured in a single, consistent cytotoxic assay against murine leukemia L1210/0 cells [32] . With the desire to build statistical sound and predictive models from such data, we have recently presented a detailed QSAR analysis covering the most important two-dimensional (2D) structural features that rule the anticancer activity within NAs.…”