RESUMO
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).
Assuntos
Zidovudina/análogos & derivados , Azóis/química , Pirimidinonas/química , Zidovudina/síntese químicaRESUMO
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.
Assuntos
Citosina/análogos & derivados , Divisão Celular/efeitos dos fármacos , Citosina/toxicidade , Células HeLa/efeitos dos fármacos , Humanos , Células KB/efeitos dos fármacos , Estrutura Molecular , Solubilidade , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Citosina/análogos & derivados , Isótopos de Carbono , Deutério , Hidrogênio , Indicadores e Reagentes , Marcação por Isótopo/métodos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , FotoquímicaRESUMO
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.
Assuntos
Fluoruracila/efeitos da radiação , Oligorribonucleotídeos/efeitos da radiação , Cinética , Modelos Químicos , Fotoquímica , Raios UltravioletaRESUMO
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.
Assuntos
Fluoruracila/análogos & derivados , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação de Ácido Nucleico , Fotoquímica , Teoria Quântica , Relação Estrutura-AtividadeRESUMO
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.
