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  • Title: [Development of fluoropyrimidine derivatives].
    Author: Fujii S, Shirasaka T.
    Journal: Gan To Kagaku Ryoho; 1984 Nov; 11(11):2316-28. PubMed ID: 6238573.
    Abstract:
    5-Fluorouracil (5-FU), first synthesized by Heidelberger et al. in 1957 has been used extensively in the treatment of cancer. In the process of development antitumor drugs in fluoropyrimidine, 5-FU and 5-fluorodeoxyuridine (FdUrd) were chosen because these two drugs relatively were incorporated into tumor tissues more than into normal tissues. The toxicity of 5-FU seems to be proportional to its concentration in blood. To be effective clinically, the concentration of a therapeutic drugs (5-FU and FdUrd) should be high in the tumor and low in the blood. In this paper, the characterization of masked forms of 5-FU and FdUrd were described as follows: Metabolism of 5-FU and uracil. Conversion of FT-207 to 5-FU (P-450). Prove in chemotherapy of cancer by oral administration of FT-207. Theory of co-administration of FT-207 with uracil (UFT-therapy). Conversion of 5'DFUR (5'deoxy-5-fluorouridine) to 5-FU (Pyrimidine nucleoside phosphorylase). Conversion of FF-705a 2'-deoxy-3', 5'-O- diacetyl-5-fluoro-3-(3-methylbenzoyl)-uridine to FdUrd and 5-FU, and fluctuation of 5-FU and FdUrd levels in the blood after oral administration of FF-705a.
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