Antitumor activity of FTC-092, a masked 5-trifluoromethyl-2′-deoxyuridine derivative

@article{Takeda2004AntitumorAO,
  title={Antitumor activity of FTC-092, a masked 5-trifluoromethyl-2′-deoxyuridine derivative},
  author={Setsuo Takeda and Jun-ichi Yamashita and Hitoshi Saito and Junji Uchida and Hiroyasu Satake and Yuji Yamada and Norio Unemi and Yusuke Wataya and Hikoya Hayatsu},
  journal={Cancer Chemotherapy and Pharmacology},
  year={2004},
  volume={29},
  pages={122-126}
}
Summary1-(3-O-Benzyl-2-deoxy-β-d-ribofuranosyl)-5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione (FTC-092), a fluorinated pyrimidine derivative, appeared to be effective against various transplantable tumors in mice following oral administration, and its activity was superior to that of several other antitumor fluorinated pyrimidines. The ED50 value for FTC-092 the dose effective in achieving 50% inhibition of tumor growth against the solid form of sarcoma 180 was 13.3 mg/kg daily, whereas those… 
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Fluorine-Containing Diazines in Medicinal Chemistry and Agrochemistry
The combination of a fluorine atom and a diazine ring, which both possess unique structural and chemical features, can generate new relevant building blocks for the discovery of efficient fluorinated

References

SHOWING 1-10 OF 38 REFERENCES
Studies on antitumor agents. 8. Antitumor activities of O-alkyl derivatives of 2'-deoxy-5-(trifluoromethyl)uridine and 2'-deoxy-5-fluorouridine.
TLDR
O-Benzyl and O-ethyl derivatives of 2'-deoxy-5-(trifluoromethyl)uridine and FUdR were synthesized and the oral antitumor activity of the compounds against sarcoma 180 in mice was examined.
FLUORINATED PYRIMIDINES. XXI. THE TUMOR-INHIBITORY ACTIVITY OF 5-TRIFLUOROMETHYL-2'-DEOXYURIDINE.
TLDR
The tumor-inhibitory activity of 5-trifluoromethyluracil and F3TDR has been studied in four transplanted mouse neoplasms and the mechanism of tumor inhibition appears to be primarily a result of the inhibition of thymidylate synthetase.
Studies on antitumor agents. VI. Syntheses and antitumor activities of acyl derivatives of 2'-deoxy-5-trifluoromethyluridine.
TLDR
Various O-ACYl and N-acyl derivatives of 2'-deoxy-5-trifluoromethyluridine (F3Thd) were synthesized and among the 5'-and 3', 5'-diester compounds with aliphatic acids, the 5'O-hexanoyl compound showed the highest activity.
Comparative studies of fluorinated pyrimidines with various cell lines.
TLDR
The effects of a number of pyrimidine nucleoside analogs on the growth of HeLa, Novikoff hepatoma, and L 5178 leukemia cells in culture have been determined, suggesting that the irreversible toxicity was the consequence of incorporation of these analogs into nucleic acids.
The clinical pharmacology of 5-trifluoromethyl-2'-deoxyuridine.
TLDR
There is no correlation between the extent of catabolism of F3TdR and its clinical efficacy and the 1st- and 2nd-hr urines of eight pediatric patients were studied, and the children metabolized the drug less rapidly than did adults.
In vivo kinetics of thymidylate synthetase inhibition of 5-fluorouracil-sensitive and -resistant murine colon adenocarcinomas.
TLDR
Levels of free TS in the tumor after 5-FUra treatment are predictive of chemotherapeutic response in these murine models of human colonic adenocarcinoma, and could not be explained by the small differences among the tumors in total perchloric acid-soluble metabolites of 5-UFra or drug incorporation into RNA.
Fluorinated pyrimidines. XXXVII. Effects of 5-trifluoromethyl-2'-deoxyuridine on the synthesis of deoxyribonucleic acid of mammalian cells in culture.
TLDR
Alkaline sucrose gradient sedimentation revealed that the molecules of DNA containing F3TdR are smaller than normal DNA, suggesting that the rate of growth or joining of chains of DNA is inhibited as a result of the incorporation of the analogue.
EXPERIMENTAL AND CLINICAL USE OF FLUORINATED PYRIMIDINES IN CANCER CHEMOTHERAPY.
TLDR
A critical review of the literature on the chemotherapeutic trials of these compounds has been made, and it is concluded that 5-FU and 4-FU are clinically useful in the palliation of patients suffering from advanced cancer.
The incorporation of 5-fluoro-2'-deoxyuridine into DNA of mammalian tumor cells.
Fluorinated pyrimidines. XXVI. Mammalian thymidylate synthetase: its mechanism of action and inhibition by fluorinated nucleotides.
Thymidylate synthetase from Ehrlich ascites carcinomna cells has been assayed by a spectrophotometric method, and several new properties of this enzyme have been discovered. Thymidylate produces a
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