[Development of fluoropyrimidine derivatives].
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.
D000818:Animals; D004261:DNA Replication / Q000187:drug effects; D005467:Floxuridine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D005472:Fluorouracil / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D010766:Phosphorylation; D011742:Pyrimidine Nucleotides / Q000378:metabolism; D051381:Rats; D012513:Sarcoma, Experimental / Q000378:metabolism* / Q000473:pathology; D005641:Tegafur / Q000378:metabolism; D014498:Uracil / Q000378:metabolism
D011742:Pyrimidine Nucleotides; D005467:Floxuridine; D005641:Tegafur; D014498:Uracil; C040250:2'-deoxy-3',5'-di-O-acetyl-5-fluoro-3-(3-methylbenzoyl)uridine; D005472:Fluorouracil; C025034:doxifluridine