Floxuridine Chemical Properties

Melting point:

148 °C(lit.)

Boiling point:

150 °C

alpha 

35.9 º (c=1, water)

Density 

1.3751 (estimate)

storage temp. 

room temp

solubility 

Soluble to 100 mM in water and to 100 mM in DMSO

pka

pKa 7.44 (Uncertain)

form 

Powder

color 

White to almost white

Water Solubility 

soluble

Merck 

14,4112

BRN 

2645818

Stability:

Stable. Incompatible with strong oxidizing agents.

InChIKey

ODKNJVUHOIMIIZ-GFCOJPQKSA-N

CAS DataBase Reference

50-91-9(CAS DataBase Reference)

NIST Chemistry Reference

Uridine, 2'-deoxy-5-fluoro-(50-91-9)

EPA Substance Registry System

Floxuridine (50-91-9)

Safety Information

Hazard Codes 

Xn,T,Xi

Risk Statements 

22-68-36/37/38-40-20/21/22

Safety Statements 

22-36-36/37/39-26

RIDADR 

UN 2811 6.1/PG 3

WGK Germany 

3

RTECS 

YU7525000

F 

10-23

Hazard Note 

Toxic

HazardClass 

6.1

PackingGroup 

III

HS Code 

29349990

Hazardous Substances Data

50-91-9(Hazardous Substances Data)

Toxicity

LD50 oral in rat: 215mg/kg

MSDS

• Language:English Provider:Fluorodeoxyuridine
• Language:English Provider:SigmaAldrich
• Language:English Provider:ACROS
• Language:English Provider:ALFA

Floxuridine Usage And Synthesis

Description

Floxuridine is a nucleoside analog that inhibits the enzyme ribonucleotide reductase, which is involved in the synthesis of DNA. Floxuridine has been shown to inhibit the growth of cancer cells and induce apoptosis in vivo. Floxuridine 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.

Chemical Properties

White Solid

Originator

FUDR,Roche,US ,1971

Uses

Floxuridine USP is used in Palliative treatment of gastrointestinal adenocarcinoma with liver metastases.

Uses

Antiviral; antineoplastic.

Uses

renal function diagnosis

Definition

ChEBI: A pyrimidine 2'-deoxyribonucleoside compound having 5-fluorouracil as the nucleobase; used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.

Manufacturing Process

Cells of Streptococcus fecalis (ATCC-8043) were grown in the AOAC folic acid assay medium [Lepper, Official and Tentative Methods of the Association of Official Agricultural Chemists, Washington, D.C., 7th edition, 784 (1950)], supplemented with 2 mg per liter of thymine; following the teachings of Prusoff, Proc. Soc. Exp. Biol. & Med. 85, 564 (1954). After 20 hours of incubation at 37°C, the cells were harvested by centrifugation. The collected cells were washed three times with four volumes of potassium phosphate buffer solution (M/15 aqueous KH2PO4 solution, adjusted to pH 8.0 by addition of 2 N aqueous KOH) and the wet cells were weighed. The cells were finally suspended in the above potassium phosphate buffer solution and ground in a glass tissue homogenizer.
An amount of enzyme preparation equivalent to 900 mg of wet cells was made up to 25 ml with the above potassium phosphate buffer solution. 150 mg (1.15 mmol) of 5-fluorouracil and 1.0 gram of thymidine (4.12 mmol) were dissolved in 15 ml of the above potassium phosphate buffer solution. The mixture was incubated at 37°C for 18 hours. After this time, enzyme action was stopped by the addition of four volumes of acetone and one volume of peroxide-free diethyl ether. The precipitated solids were removed by filtration, and the filtrate was evaporated under nitrogen at reduced pressure until substantially all volatile organic solvent had been removed. About 20 ml of aqueous solution, essentially free of organic solvent, remained. This solution was diluted to 100 ml with distilled water.
Ten microliters of this solution were submitted to descending chromatography on a paper buffered with 0.2 N KH2PO4 (pH 7.8), using a solvent mixture of tertiary amyl alcohol:water:n-butyl ether (80:13:7 by volume). A spot visible under ultraviolet light and having Rf = 0.55 was leached with 0.1 N HCl and assayed for deoxyribose by the method of Stumpf, J. Biol. Chem. 169, 367 (1947). This analysis indicated the presence of a minimum of 85.5 mg (0.35 mmol) of 2'-deoxy-5-fluorouridine in the protein-free reaction mixture according to US Patent 2,885,396. An alternate route from 5-fluorouracil via the mercury derivative, through toluoyl deoxyuridines and then toluoyl removal to give floxuridine is described in US Patent 3,041,335.

brand name

Fudr (Mayne).

Therapeutic Function

Antiviral, Cancer chemotherapy

General Description

The drug is available as a 500-mg vial of lyophilized powder.The drug is used to treat metastatic GI adenocarcinoma.The mechanism of action of this fluoropyrimidine deoxynucleosideanalog involves metabolic conversion to 5-fluorouracil(5-FU) metabolites resulting in inhibition of TSthus disrupting DNA synthesis, function, and repair.Resistance can occur because of increased expression of TS,decreased levels of reduced folate 5,10-methylenetetrahydrofolate,increased activity of DNA repair enzymes, and increasedexpression of dihydropyrimidine dehydrogenase(the major catabolic enzyme). The drug is poorly absorbedfrom the GI tract and is extensive metabolized to 5-FU and5-FU metabolites. Dihydropyrimidine dehydrogenase is themain enzyme responsible for 5-FU catabolism, and it ispresent in liver, GI mucosa, white blood cells, and kidney.The drug interaction and toxicity profiles are equivalent tothose of 5-FU.

General Description

Inhibits DNA synthesis.

Health Hazard

ACUTE/CHRONIC HAZARDS: Floxuridine is highly toxic by ingestion.

Fire Hazard

Flash point data for Floxuridine are not available, but Floxuridine is probably combustible.

Biochem/physiol Actions

Antineoplastic drug that acts as a potent inhibitor of thymidylate synthetase Resistance to FUdR can develop in cancer cell cultures, among other means, by low-level Mycoplasma infection.

Safety Profile

Poison by ingestion. Moderately toxic by intraperitoneal route. An experimental teratogen. Other experimental reproductive effects. Human systemic effects: hypermotitity, diarrhea, nausea, vomiting and other gastrointestinal effects, allergic dermatitis, and bone marrow changes. Human mutation data reported. When heated to decomposition it emits very toxic fumes of Fand NOx.

Synthesis

Fluoxuridine, 5-fluoro-1-(2-deoxyribofuranosyl)-pyrimidin-2,4-(1H,3H)- dione (30.1.3.5), is a pyrimidine nucleotide made by reacting fluorouracil (30.1.3.3) with 2-deoxyribofuranosylbromide in the presence of silver or mercury salts.

Floxuridine(50-91-9)Related Product Information

• 5-Fluorouridine
• Chlorfluazuron
• Hexaflumuron
• 2'-Deoxyuridine
• Fluorine
• Uridine
• 5-Fluorouridine
• Doxifluridine
• 5-Fluorouracil
• Uracil
• 3',5'-DI-O-BENZOYL-5-FLUORO-2'-O-METHYLURIDINE
• 2'-DEOXY-5-FLUOROURIDINE, [3H]-
• T 506
• 3',5'-DI-O-ACETYL-5-FLUORO-2'-O-METHYLURIDINE
• 5'-O-(4,4'-DIMETHOXYTRITYL)-5-FLUORODEOXYURIDINE-3'-(2-CYANOETHYL-N,N-DIISOPROPYL)PHOSPHORAMIDITE
• 5-fluorouridine 5'-triphosphate
• 3',5'-DI-O-ACETYL-5-FLUORO-2'-DEOXYURIDINE
• 5-FLUORO-2'-DEOXYURIDINE 5'-MONOPHOSPHATE SODIUM SALT