去氧氟尿苷, 5'-Deoxy-5-fluorouridine

5'-Deoxy-5-fluorouridine (5FU) is a nucleoside that is used in the treatment of cancer. It is an antimetabolite that inhibits the synthesis of DNA, RNA, and proteins by reversibly inhibiting ribonucleotide reductase. 5FU also inhibits epidermal growth factor receptor (EGFR), which leads to apoptosis in cancerous cells. The concentration–time curve for 5FU has been determined using tissue culture and hl-60 cells as biological samples. This drug has been shown to be effective against metastatic colorectal cancer when administered with other chemotherapeutic drugs.

Fluoropyrimidine. Shows antitumor and antiangiogenic effects in vivo. Activates NF-κB in macrophages. Orally active. Active metabolite 5-fluorouracil also available.

Doxifluridine is an intermediary prodrug of fluorouracil, the pyrimidine analog that inhibits thymidylate synthase selectively in tumor cells, interfering with DNA synthesis. Doxifluridine is one of two intermediary metabolites formed during metabolic conversion of the chemotherapeutic prodrug, capecitabine, to fluorouracil.

Pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards

Doxifluridine is a fluoropyrimidine derivative and oral prodrug of the antineoplastic agent 5-fluorouracil (5-FU) with antitumor activity. Doxifluridine, designed to circumvent the rapid degradation of 5-FU by dihydropyrimidine dehydrogenase in the gut wall, is converted into 5-FU in the presence of pyrimidine nucleoside phosphorylase. 5-FU interferes with DNA synthesis and subsequent cell division by reducing normal thymidine production and interferes with RNA transcription by competing with uridine triphosphate for incorporation into the RNA strand.

Doxifluridine is a pyrimidine 5'-deoxyribonucleoside that is 5-fluorouridine in which the hydroxy group at the 5' position is replaced by a hydrogen. It is an oral prodrug of the antineoplastic agent 5-fluorouracil. Designed to circumvent the rapid degradation of 5-fluorouracil by dihydropyrimidine dehydrogenase in the gut wall, it is converted into 5-fluorouracil in the presence of pyrimidine nucleoside phosphorylase. It has a role as an antimetabolite, an antineoplastic agent and a prodrug. It is an organofluorine compound and a pyrimidine 5'-deoxyribonucleoside.

Doxifluridine has been investigated for the treatment of Stomach Cancer.

Title: Doxifluridine

CAS Registry Number: 3094-09-5

CAS Name: 5'-Deoxy-5-fluorouridine

Additional Names: 1-(b-D-5'-deoxyribofuranosyl)-5-fluorouracil; 5'-DFUR; 5'-dFUrd

Manufacturers' Codes: Ro-21-9738

Trademarks: Flutron (Roche); Furtulon (Roche)

Molecular Formula: C9H11FN2O5

Molecular Weight: 246.19

Percent Composition: C 43.91%, H 4.50%, F 7.72%, N 11.38%, O 32.49%

Literature References: Fluorinated pyrimidine nucleoside with cytostatic activity. Prepn: A. F. Cook, US 4071680 (1978 to Hoffmann-La Roche); H. Hrebabecky, J. Beranek, Nucleic Acids Res. 5, 1029 (1978); A. F. Cook et al., J. Med. Chem. 22, 1330 (1979). Stereospecific synthesis: J. Kiss et al., Helv. Chim. Acta 65, 1522 (1982). Mechanism of action studies: H.-R. Hartmann, A. Matter, Cancer Res. 42, 2412 (1982); R. D. Armstrong et al., Cancer Chemother. Pharmacol. 11, 102 (1983). Kinetics and metabolism in humans: J.-P. Sommadossi et al., Cancer Res. 43, 930 (1983). Clinical trials in colorectal carcinoma: R. Abele et al., J. Clin. Oncol. 1, 750 (1983); S. D. Fossa et al., Cancer Chemother. Pharmacol. 15, 161 (1985). Series of articles on animal toxicology: Yakuri to Chiryo 13, Suppl. 2, 221-430 (1985); acute toxicity: M. Shimizu et al., ibid. 209, C.A. 104, 14673z-14678e (1986). Evaluation of neurotoxicity in humans: M. S. Heier, S. D. Fossa, Acta Neurol. Scand. 73, 449 (1986).

Properties: Crystals from ethyl acetate, mp 189-190° (Cook). Also reported as crystals from 2-propanol, mp 186-188° (Hrebabecky, Beranek); needles from methanol + ethyl acetate, mp 192-193° (Kiss). pKa 7.4. [a]D25 +18.4° (c = 0.419 in water). uv max (in methanol): 268-269 nm (e 8550). LD50 (14 day) in mice or rats (mg/kg): >1000 i.v.: >2000 s.c.; in male, female mice, male, female rats (mg/kg): >5000, >5000, 3471, 3390 orally (Shimizu).

Melting point: mp 189-190° (Cook); mp 186-188° (Hrebabecky, Beranek); mp 192-193° (Kiss)

pKa: pKa 7.4

Optical Rotation: [a]D25 +18.4° (c = 0.419 in water)

Absorption maximum: uv max (in methanol): 268-269 nm (e 8550)

Toxicity data: LD50 (14 day) in mice or rats (mg/kg): >1000 i.v.: >2000 s.c.; in male, female mice, male, female rats (mg/kg): >5000, >5000, 3471, 3390 orally (Shimizu)

Therap-Cat: Antineoplastic.

Keywords: Antineoplastic; Antimetabolites; Pyrimidine Analogs.

COA:

Product name: 5'-Deoxy-5-fluorouridine    CAS: 3094-09-5,38817-29-7 

References:

1. De Cesane, M., et al, Cancer Res., 49, 5969 (1994)
2. Di Bartolomeo, M., et al, Tumori, 81, 147(1995)