Topochemical models for anti-HIV activity of 1-alkoxy-5-alkyl-6-(arylthio)uracils

Relationship between topochemical indices and anti-HIV-1 (HTLV-III) inhibitory activity of 1-alkoxy-5-alkyl-6-(arylthio)uracils has been studied. Superadjacency, an adjacency-cum-distance-based, topochemical index and Wiener’s, a distance-based, topochemical index were calculated for a set of 36 1-alkoxy-5-alkyl-6-(arylthio)uracils. Resulting data were analyzed and suitable models were developed after identification of the active ranges. Subsequently, a biological activity was assigned to each of the compounds using these models and compared with the reported anti-HIV-1 activity. High accuracy of prediction was observed using these models. Statistical analysis revealed significance of the proposed models as well as a lack of correlation between the topochemical indices employed for the chosen data set.     

Kurze Originalarbeiten: Zur Reindarstellung von tritiummarkierten Pyrimidinderivaten 1. Mitt. Markierung von 5-Hydroxyuracil und 5-Aminouracil durch katalytischen II-T-Austausch

Zur Vervollkommung der strahlenchemischen Technologie für die Herstellung einiger für die Industrie wichtiger silizium-organischer Monomere und zur Durchführung von Forschungs-arbeiten auf diesem Gebiet wurde eine Pilot-Anlage unter Verwendung des Elektronenbeschleunigers EU-0,4 geschaffen, der im Physikalisch-chemischen Forschungsinstitut ?L. J. Karpow“ auf der Grundlago des Rōntgendefektoskopie-Gerātes RUP-400-5 entwickelt wurde.     

Apparent molar heat capacities and volumes of some alkylated derivatives of uracil and adenine in aqueous solution at 25°C

Densities and apparent molar heat capacities of some alkylated derivatives of uracil and adenine: 1-methyluracil, 1,3-dimethyluracil, 1,3-diethylthymine, 5,6-trimethylene-1,3-dimethyluracil, 5,6-tetramethylene-1,3-dimethyluracil, 5,6-pentamethylene-1,3-dimethyluracil, 2,9-dimethyladenine, 2-ethyl-9-methyladenine, 2-propyl-9-methyladenine, 8-ethyl-9-methyladenine, 6,8,9-trimethyladenine and 8-ethyl-6,9-dimethyladenine were determined using flow calorimetry and flow densimetry at 25°C. It was found that the partial molar volumes and heat capacities correlate linearly with the number of substituted methylene groups-CH ₂ -as well as to the number of hydrogen atoms, n _H , belonging to the skeleton of the molecule. In the case of alkylated uracils a difference was observed in the values at infinite dilution V ₂ ^o and C _p2 ^o , depending on the substitution of alkyl and cyclooligomethylene groups.     

Synthesis of Tritiated Components of Nucleic Acids Part 3

At the catalytic tritiation of 5-Formyluracil (5-FU), different compounds are generated. The kind of the species depends on the reaction conditions. 5-FU is one of the derivatives of uracil which are slightly approachable to a catalytic hydrogen isotope exchange. This isotope exchange in the formyl group seems to be favoured above the 6-position in the uracil ring, because of its greater reactivity. After separation of the impurities, we obtained tritiated 5-FU with a specific radioactivity of nearly 1480 GBq/mmol and a radiochemical purity >98%. The pressure of tritium gas was <25 kPa. The catalyst we used was PdO(1.4%)/BaSO₄. With the same catalyst we obtained 5-Hydroxymethyl[hydroxymethyl-³H]- uracil by raising the pressure of tritium gas to 50 kPa. Hydrogenation of the 5.6 double bond occurred by an additional raising of the pressure to 75 kPa and we obtained 5-Hydroxymethyldihydrouracil (5-DHMU) [1].     

Synthesis of 1-(dihydroxypropyl)-5-substituted uracils

Novel 1-(dihydroxypropyl)-5-substituted uracils were synthesized in the reaction of 1-(4-nitrophenyl)-5-substituted uracil derivatives with appropriate aminopropanediols under mild conditions. In the case of 3-amino-1,2-propanediol both racemic and enantiomerically enriched products were obtained. These compounds may be considered as new building blocks for oligonucleotide synthesis.     

Synthesis of some polycyclic noncondensed pyrimidine structures

Methods for the synthesis of compounds containing two or more pyrimidine rings linked through aliphatic chains with different numbers of carbon atoms are described.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 335–340, February, 1995     

Association of Cu2+ with uracil and its thio derivatives: a theoretical study.

The structures and relative stabilities of the complexes between Cu2+ and uracil, 2-thiouracil, 4-thiouracil, and 2,4-dithiouracil were investigated by B3LYP/6-311+G(2df,2p)//B3LYP/6-31G* DFT calculations. In those systems in which both types of basic centers, that is, a carbonyl and a thiocarbonyl group, are present, association of Cu2+ with the oxygen atom is systematically favored, in contrast to what was found for the corresponding Cu+ complexes. This can be understood by considering that association of Cu2+ is immediately followed by oxidation of the base, which accumulates the negative charge at the oxygen atoms. Similarly, for 2,4-dithiouracil the most basic site for Cu+ attachment is the sulfur atom at the 4-position, while for association of Cu2+ it is sulfur at the 2-position. In contrast, differences between uracil-Cu+ and uracil-Cu2+ complexes are very small, and in both cases the oxygen atom at the 4-position is the most basic. Cu2+ binding energies are about 4 and 1.2 times larger than Cu+ binding energies and proton affinities, respectively. Uracil- and thiouracil-Cu2+ complexes are thermodynamically unstable but kinetically stable with respect to their dissociation into uracil*+ + Cu+ or thiouracil*+ + Cu+. The Cu2+ binding energies vary with the difference between the second ionization potential of the metal and the first ionization potential of the base. regardless of the reference acid (H+, Cu+, Cu2+) the basicity trend is 2,4-dithiouracil > 4-thiouracil > 2-thiouracil > uracil.     

MAGIC-LC/FT-IR spectrometry

The FTIR spectra of uracil and thymine were studied at different concentrations in pure Ar matrices as well as in H₂O or HCl doped Ar matrices. The spectral results suggest the presence of open dimers in associated uracil and thymine. The structure of heterodimers of uracils with H₂O and HCl is discussed.     

New type of interaction of 5-iodopyrimidine nucleosides with alkynes

The interaction of 1-(-D-xylofuranosyl)-5-iodo(bromo)uracil derivatives with terminal alkynes in the presence of catalytic amounts of 10% Pd/C and Cul affords the corresponding derivatives of 3-(-D-xylofuranosyl)-6-R-furo[2, 3-d]pyrimidin-2-ones in high yields.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 596–598, March, 1993.