5-氟-2'-脱氧尿苷,

2'-Deoxy-5-fluorouridine

2'-Deoxy-5-fluorouridine is a nucleoside analog that inhibits the enzyme ribonucleotide reductase, which is involved in the synthesis of DNA. It has been shown to inhibit the growth of cancer cells and induce apoptosis in vivo. 2'-Deoxy-5-fluorouridine has also been shown to inhibit tumor growth in animal models by inhibiting the production of reactive oxygen species and upregulating tumor suppressor genes, such as p53. This drug also has inhibitory effects on enzymes that are involved in cell proliferation, such as protein kinase C and tyrosine kinases. 2'-Deoxy-5-fluorouridine is metabolized by water vapor, so it must be administered with a humidifier or nebulizer. 2'-Deoxy-5-fluorouridine may cause side effects such as nausea, vomiting, and diarrhea.

Floxuridine is a prodrug that is rapidly catabolized in vivo to 5-fluorouracil when administered by rapid injection. In addition, floxuridine inhibits thymidylate synthase (EC50 = 0.6 nM), interfering with DNA synthesis. It has been used to treat various cancers, particularly metastases to the liver.

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.

Floxuridine is a fluorinated pyrimidine monophosphate analogue of 5-fluoro-2'-deoxyuridine-5'-phosphate (FUDR-MP) with antineoplastic activity. As an antimetabolite, floxuridine inhibits thymidylate synthase, resulting in disruption of DNA synthesis and cytotoxicity. This agent is also metabolized to fluorouracil and other metabolites that can be incorporated into RNA and inhibit the utilization of preformed uracil in RNA synthesis. (NCI04)

Floxuridine (FUDR) is a pyrimidine analogue used as an antineoplastic agent, usually as a continuous hepatic arterial infusion to treat hepatic metastases from colon cancer. Intraarterial floxuridine is associated with a very high rate of serum enzyme and bilirubin elevations during therapy, and with frequent biliary damage that can result in a secondary sclerosing cholangitis, which can be severe and lead to cirrhosis.

Floxuridine, also known as fudr or 5FDU, belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. Pyrimidine 2'-deoxyribonucleosides are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2. Floxuridine is a drug which is used for palliative management of gastrointestinal adenocarcinoma metastatic to the liver, when given by continuous regional intra-arterial infusion in carefully selected patients who are considered incurable by surgery or other means. also for the palliative management of liver cancer (usually administered by hepatic intra-arterial infusion). Floxuridine exists as a solid, soluble (in water), and a very weakly acidic compound (based on its pKa). Floxuridine has been found in human liver and kidney tissues, and has also been detected in multiple biofluids, such as urine and blood.

Title: Floxuridine

CAS Registry Number: 50-91-9

CAS Name: 2'-Deoxy-5-fluorouridine

Additional Names: 1-(2-deoxy-b-D-ribofuranosyl)-5-fluorouracil; 5-fluoro-2'-deoxy-b-uridine

Manufacturers' Codes: NSC-27640

Trademarks: FUDR (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: Prepn: Hoffer et al., J. Am. Chem. Soc. 81, 4112 (1959); Heidelberger, Duschinsky, US 2885396 (1959); Duschinsky et al., US 2970139 (1961); Hoffer, US 2949451; US 3041335 (1960, 1962 both to Hoffmann-La Roche). Structure: Lemieux, Hoffer, Can. J. Chem. 39, 110 (1961). Crystal and molecular structure: Harris, Diss. Abstr. 24, 4425 (1964); Harris, McIntyre, Biophys. J. 4, 203 (1964). Conformation of furanose ring in molecule: Sundaralingam, J. Am. Chem. Soc. 87, 599 (1965).

Properties: Crystals from butyl acetate, mp 150-151° (Hoffer, 1959); also reported as mp 145° (US 3041335). [a]D +37° (water), +48.6° (DMF). uv max (pH 7.2): 268 nm (e 7570); (pH 14): 270 nm (e 6480).

Melting point: mp 150-151° (Hoffer, 1959); mp 145° (US 3041335)

Optical Rotation: [a]D +37° (water), +48.6° (DMF)

Absorption maximum: uv max (pH 7.2): 268 nm (e 7570); (pH 14): 270 nm (e 6480)

Derivative Type: a-Anomer

Additional Names: 1-(2-Deoxy-a-D-erythro-pentofuranosyl)-5-fluorouracil

Properties: Crystals from butyl acetate, mp 150-151°. [a]D25 -21° (c = 2 in water).

Melting point: mp 150-151°

Optical Rotation: [a]D25 -21° (c = 2 in water)

Therap-Cat: Antiviral; antineoplastic.

Keywords: Antineoplastic; Antimetabolites; Pyrimidine Analogs; Antiviral; Purines/Pyrimidinones.

COA:

Product name: 2'-Deoxy-5-fluorouridine           CAS: 50-91-9 

References:

1. Harris M, et al., Biophys. J. 1964, 4, p203