Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D02259 (NaI)
 1,823 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1-(Tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU), which is named Ftorafur or FT-207 and is used clinically as an antitumor agent, was conveniently synthesized by condensation of the trimethylsilyl derivative of 5-fluorouracil with 2-acetoxytetrahydrofuran using NaI as a catalyst. This optically inactive Thf-FU was resolved into optically active (R)-(+)- and (S)-(-)-Thf-FU in high optical purity and excellent yield by formation of diastereoisomers with brucine. 13C NMR data were obtained on Thf-FU and related compounds and the antibacterial activities and in vivo antitumor activities of these isomers were tested. The degradations of these isomers to 5-fluorouracil by liver microsomes were also examined. No significant differences were found in any of these properties of these isomers.
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PMID:Studies of antitumor agents. 1. Resolution of racemic 1-(tetrahydro-2-furanyl)-k-fluorouracil into the R and S isomers and examination of the biological activities of the isomers. 33

Convenient and efficient methods were developed for preparing 1-(tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU, 3) [trade name, Futraful (Ftorafur) or FT-207], which is used clinically as an antitumor agent, and 1,3-bis(tetrahydro-2-furanyl)-5-fluorouracil (Thf2-FU, 4). For the syntheses, 2,4-bis(trimethylsily)-5-fluorouracil (Me3Si-FU, 1) and 2-acetoxytetrahydrofuran (Thf-OAc, 2) were condensed in the presence of Friedel-Crafts catalysts, such as SnCl4 and BF3-Et2O in dichloromethane, or in the presence of NaI in acetonitrile to give Thf-Fu or Thf2-FU depending on the reaction conditions and workup procedure. A trace of 3-(tetrahydro-2-furanyl)-5-fluorouracil (3-Thf-FU, 5) was formed in these reactions. Thf2-FU was easily hydrolyzed to Thf-FU. 2-Methoxytetrahydrofuran can be used instead of Thf-OAc for preparation of Thf-FU under similar conditions. The optimal ratios of Me3Si-FU, Thf-OAc, and SnCl4 or NaI for preparation of Thf-FU and Thf2-FU were determined. In all cases, 2-2.5 equiv of Thf-OAc with respect to Me3Si-FU gave the best results. The yields of Thf-FU and more especially of Thf2-FU were greatly dependent on the relative amount of SnCl4, and 0.01-0.1 equiv of the catalyst with respect to Me3Si-FU gave the best results. Thf2-FU was found to be effective against murine solid tumors and it was less toxic than Thf-FU when given orally. The antitumor activity of 3-Thf-FU is also reported.
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PMID:Studies on antitumor agents, 2. Syntheses and antitumor activities of 1-(tetrahydro-2-furanyl)-5-fluorouracil and 1,3-bis(tetrahydro-2-furanyl)-5-fluorouracil. 35 21