5-Fluor-2'-desoxyuridin

Bezeichnung:5-Fluor-2'-desoxyuridin

CAS-Nr50-91-9

Englisch Name:Floxuridine

CBNumberCB3210097

SummenformelC9H11FN2O5

Molgewicht246.19

MOL-Datei50-91-9.mol

Synonyma

Floxuridin

5-Fluor-2'-desoxyuridin

5-Fluor-2'-desoxyuridin physikalisch-chemischer Eigenschaften

Schmelzpunkt	148 °C(lit.)
Siedepunkt	150 °C
alpha	35.9 º (c=1, water)
Dichte	1.3751 (estimate)
storage temp.	room temp
Löslichkeit	Soluble to 100 mM in water and to 100 mM in DMSO
pka	pKa 7.44 (Uncertain)
Aggregatzustand	Powder
Farbe	White to almost white
Wasserlöslichkeit	soluble
Merck	14,4112
BRN	2645818
Stabilität	Stable. Incompatible with strong oxidizing agents.
InChIKey	ODKNJVUHOIMIIZ-GFCOJPQKSA-N
CAS Datenbank	50-91-9(CAS DataBase Reference)
NIST chemische Informationen	Uridine, 2'-deoxy-5-fluoro-(50-91-9)
EPA chemische Informationen	Floxuridine (50-91-9)

Sicherheit

Kennzeichnung gefährlicher	Xn,T,Xi
R-Sätze:	22-68-36/37/38-40-20/21/22
S-Sätze:	22-36-36/37/39-26
RIDADR	UN 2811 6.1/PG 3
WGK Germany	3
RTECS-Nr.	YU7525000
F	10-23
Hazard Note	Toxic
HazardClass	6.1
PackingGroup	III
HS Code	29349990
Giftige Stoffe Daten	50-91-9(Hazardous Substances Data)
Toxizität	LD50 oral in rat: 215mg/kg

Gefahreninformationscode (GHS)

Floxuridine Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
R68:Irreversibler Schaden möglich.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
R40:Verdacht auf krebserzeugende Wirkung.
R20/21/22:Gesundheitsschädlich beim Einatmen,Verschlucken und Berührung mit der Haut.
S-Sätze Betriebsanweisung:
S22:Staub nicht einatmen.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
Beschreibung
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.
Chemische Eigenschaften
White Solid
Originator
FUDR,Roche,US ,1971
Verwenden
Antiviral; antineoplastic.
Verwenden
renal function diagnosis
Verwenden
Floxuridine USP is used in Palliative treatment of gastrointestinal adenocarcinoma with liver metastases.
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.
Trademarks
Fudr (Mayne).
Therapeutic Function
Antiviral, Cancer chemotherapy
Allgemeine Beschreibung
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.
Allgemeine Beschreibung
Inhibits DNA synthesis.
Health Hazard
ACUTE/CHRONIC HAZARDS: Floxuridine is highly toxic by ingestion.
Brandgefahr
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.
Sicherheitsprofil
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.
Synthese
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 Upstream-Materialien And Downstream Produkte

5-Fluor-2'-desoxyuridin Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

50-91-9, Floxuridine Verwandte Suche:

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