ABSTRACT
An efficient method for the preparation of 6-methyltetrazolo-[1,5-c]pyrimidin-5(6H)ones using as the precursors 4-chloro-1,2-dihydro-1-methyl-2-oxopyrimidines is described. The method is also extended to the synthesis of novel tetrazole analogue of 3'-azido-3'-deoxythymidine (AZT).
Subject(s)
Zidovudine/analogs & derivatives , Azoles/chemistry , Pyrimidinones/chemistry , Zidovudine/chemical synthesisABSTRACT
Cytotoxicity of 22 amino acid 4-N-substituted cytosine derivatives was studied on KB and HeLa human tissue cultures. A 4-N-(1H-2-oxo-4 pyrimidyl)-tryptamine with ED50 activity values of 0.145 x 10(-3) mole/l and ED0 = 0.4 x 10(-5) mole/l showed the highest cytotoxic activity and was qualified for further in vivo investigation. The secondary modification of tryptamine substituent seems to be a determining factor of the cytotoxic activity of 4-N-pyrimidinyl amino acids. The activity of the investigated compounds was inversely dependent on their solubility limited by the results of the solubility-activity relationship analysis.
Subject(s)
Cytosine/analogs & derivatives , Cell Division/drug effects , Cytosine/toxicity , HeLa Cells/drug effects , Humans , KB Cells/drug effects , Molecular Structure , Solubility , Structure-Activity RelationshipABSTRACT
A convenient photochemical method of preparation of mono-, di- and trideuterate 4-N-methylcytosines of high isotopic purity is described. These products were obtained by photo-decarboxylation of pyrimidinyl glycines or their alpha, alpha-dideuterated derivatives in water or in deuterium oxide. [2, 2H2]Glycine derivatives were prepared by hydrogen-deuterium exchange in alkaline solution.
Subject(s)
Cytosine/analogs & derivatives , Carbon Isotopes , Deuterium , Hydrogen , Indicators and Reagents , Isotope Labeling/methods , Magnetic Resonance Spectroscopy , Mass Spectrometry , PhotochemistryABSTRACT
5-Fluorouracil residues can form cyclobutane-type photodimers in a direct excitation stacking-controlled process. The stacking also has an important effect on the photohydration of uracil and 5-fluorouracil in our model compounds 5RUra(CH2)35FUra, where R = H, CH3, C2H5, C3H7, F or Cl.
Subject(s)
Fluorouracil/radiation effects , Oligoribonucleotides/radiation effects , Kinetics , Models, Chemical , Photochemistry , Ultraviolet RaysABSTRACT
The structure of internal [2+2] photodimers of 1,1'-trimethylene-bis-(5-fluoro) uracil derivatives has been studied. All investigated compounds have cis-syn geometry with puckered endocyclic cyclobutane ring and chair-like conformation of 1,3-diazacycloheptane ring.
Subject(s)
Fluorouracil/analogs & derivatives , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Models, Molecular , Nucleic Acid Conformation , Photochemistry , Quantum Theory , Structure-Activity RelationshipABSTRACT
The triester method was adapted to the synthesis of uridylyl/3'-5'/5-methylcytidylyl/3'-5'/guanosine. As the protecting groups 4-methoxy-5,6-dihydro-2H-pyran for 2'-OH and 5'-OH groups of uridine and 2'-OH group of 5-methylcytidine, methoxymethylidene for I:3'-cis-diol system of guanosine, and benzoyl for the amino groups of 5-methylcytidine and guanosine were used. The obtained product was characterised by UV, electrophoresis, chromatography, an enzymatic digestion and alkaline hydrolysis.
