Fialuridine and its metabolites inhibit DNA polymerase γ at sites of multiple adjacent analog incorporation, decrease mtDNA abundance, and cause mitochondrial structural defects in cultured hepatoblasts was written by Lewis, William; Levine, Eric S.; Griniuviene, Brone; Tankersley, Kevin O.; Colacino, Joseph M.; Sommadossi, Jean-Pierre; Watanabe, Kyoichi A.; Perrino, Fred W.. And the article was included in Proceedings of the National Academy of Sciences of the United States of America on April 16,1996.Synthetic Route of C10H13FN2O5 The following contents are mentioned in the article:
The thymidine analog fialuridine [1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodouracil (FIAU)] was toxic in trials for chronic hepatitis B infection. One mechanism postulated that defective mtDNA replication was mediated through inhibition of DNA polymerase-γ (DNA pol-γ) by FIAU triphosphate (FIAUTP) or by triphosphates of FIAU metabolites. Inhibition kinetics and primer-extension analyses determined biochem. mechanisms of FIAU, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-methyluracil (FAU), and 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil triphosphate (TP) inhibition of DNA pol-γ. DTMP incorporation by DNA poly-γ was inhibited competitively by FIAUTP, FMAUTP, and FAUTP (Ki = 0.015, 0.03, and 1.0 μM, resp.). By using oligonucleotide template-primers, DNA poly-γ incorporated each analog into DNA opposite a single adenosine efficiently without effects on DNA chain elongation. Incorporation of multiple adjacent analogs at positions of consecutive adenosines dramatically impaired chain elongation by DNA pol-γ. Effects of FIAU, FMAU, and FAU on HepG2 cell mtDNA abundance and ultrastructure were determined After 14 days, mtDNA decreased by 30% with 20 μM FIAU or 20 μM FMAU and decreased less than 10% with 100 μM FAU. FIAU and FMAU disrupted mitochondria and caused accumulation of intracytoplasmic lipid droplets. Biochem. and cell biol. findings suggest that FIAU and its metabolites inhibit mtDNA replication, most likely at positions of adenosine tracts, leading to decreased mtDNA and mitochondrial ultrastructural defects. This study involved multiple reactions and reactants, such as 1-((2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione (cas: 69256-17-3Synthetic Route of C10H13FN2O5).
1-((2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione (cas: 69256-17-3) belongs to pyrimidine derivatives. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Synthetic Route of C10H13FN2O5
69256-17-3;1-((2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione;The future of 69256-17-3;New trend of C10H13FN2O5;function of 69256-17-3