Zalcitabine

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H351：Kann vermutlich Krebs verursachen.

• Sicherheit

  P281：Vorgeschriebene persönliche Schutzausrüstung verwenden.

Zalcitabine Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R40:Verdacht auf krebserzeugende Wirkung.
  R36/37:Reizt die Augen und die Atmungsorgane.
  R34:Verursacht Verätzungen.

• S-Sätze Betriebsanweisung:

  S22:Staub nicht einatmen.
  S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
  S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
  S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
  S27:Beschmutzte, getränkte Kleidung sofort ausziehen.
  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.

• Beschreibung

  Zalcitabine is an orally active dideoxynucleoside andog for combination use with zidovudine in advanced HIV infection and also as monotherapy for AIDS patients who cannot tolerate or have not responded to zidovudine. It has a similar mechanism of action (inhibition of reverse transcriptase) to didanosine. Like didanosine, its side effect profile includes peripheral neuropathy. Unlike zidovudine, zalcitabine does not cause bone marrow suppression.

• Beschreibung

  Zalcitabine is an analog of pyrimidine derived from deoxycytidine with the replacement of the hydroxyl group in position 3’ with a hydrogen. In cells, it is phosphorylated to the active triphosphate form, ddCTP, which acts as a substrate for HIV reverse transcriptase (K_i = 51 nM). It incorporates into viral DNA where it terminates chain elongation when the missing hydroxyl group is encountered. Zalcitabine was the third antiretroviral approved by the FDA for treatment of HIV infection and AIDS.

• Chemische Eigenschaften

  White to Off-White Cyrstalline Powder

• Originator

  National Cancer Institute (NIH) (U.S.A.)

• Verwenden

  A pyrimidine nucleoside analogue with antiviral activity.

• Verwenden

  ammonia detoxicant, diagnostic aid

• Indications

  Zalcitabine (ddC, Hivid) is a cytidine analogue active against HIV-1, HIV-2, and hepatitis B virus. It is used for the treatment of HIV infection in adults and asymptomatic children as part of a multidrug regimen. It may be less effective than the other nucleoside inhibitors and is used less frequently.

• Definition

  ChEBI: A pyrimidine 2',3'-dideoxyribonucleoside compound having cytosine as the nucleobase.

• Manufacturing Process

  Bromoacetylation of N-acetylcytidine with 2-acetoxy-2-methylpropanoyl bromide
  A 5 L three-nicked, round-bottomed flask equipped with a mechanical stirrer, thermometer, nitrogen inlet tube, and additional funnel was charge with 142.6 g (0.5 mole) of N-acetylcytidine, and 1.25 L of acetonitrile. The suspension was stirred under nitrogen, cooled to 5°C (ice-bath), and treated dropwise (during 20 min) with 225 ml of 2-acetoxy-2-methylpropanoyl bromide (AIBB) during 30 minutes. At the completion of the addition, a homogeneous solution resulted. It was stirred at room temperature overnight (the reaction was complete within 3 hr), cooled to 5°C, and diluted with 1.25 L of ethyl acetate. After recooling to 5°C, 2.0 L of saturated sodium bicarbonate was added. The mixture was stirred for 5 minutes, the organic phase was separated, and the aqueous phase was back-extracted with 500 ml of ethyl acetate. The combined organic extracts were washed with 1 L of saturated brine, dried (MgSO 4 ), and evaporated to give a gum. Final drying at 40°C (1 mm) for 1 hrgave 264.7 g (102%) of a white solid. High pressure liquid chromatographic analysis gave the following results (major peaks only): 40% of [2R- [2α,3β,4α,5α(S*)]]-N-[1-[3-(acetyloxy)-5-[(2-(acetyloxy)-1-oxopropoxy] methyl]-4-bromotetrahydro-2-furanyl]-1,2-dihydro-2-oxo-4-pyrimidinyl] acetamide (a) and 24% of its regioisomer (b).
  Preparation of [2R-[2α,3β,4α,5α(S*)]]-N-[1-[3-(acetyloxy)-5-[(2-(acetyloxy)- 1-oxopropoxy]methyl]-4-bromotetrahydro-2-furanyl]-1,2-dihydro-2-oxo-4- pyrimidinyl]acetamide (a) and its regioisomer (b).
  A 1-L, three-necked, round-bottomed flask equipped with a mechanical stirrer and argon inlet was charged with 28.52 g of N-acetylcytidine in 250 ml of acetonitrile. The mixture was cooled to 10°C and treated with 48.75 g of (S)- (-)-2-acetoxypropionyl bromide during 15 minutes. It was stirred at room temperature overnight, cooled to 10°C, treated with 400 ml of cold (0°C) saturated sodium bicarbonate, and extracted with 250 ml of ethyl acetate. The extract was washed with 200 ml of saturated brine, dried (MgSO 4 ) and evaporated to give 45.45 g of a white foam. Reversed phase chromatography (C 18 column) with 40% methanol in water gave a pure sample of (a).
  Zinc-copper couple was prepared by the next way:
  A 12 L three-necked, round-bottomed flask equipped with a mechanical stirrer was charged with 4.50 kg of zinc dust. The zinc dust was washed with 3.75 L of 3% aqueous hydrochloric acid by stirring for 3 to 5 minutes. The hydrochloric acid was decanted from the solid. This cycle was repeated with 3x3.75 L of 3% hydrochloric acid. The reaction was slightly exothermic and the volume of the zinc dust increased to double its original volume. The zinc dust was then washed with 4x3.0 L of deionized water to remove any residual hydrochloric acid. After all the water was decanted, the spongy zinc layer was treated with a solution made by dissolving 240.0 g of cupric sulfate dihydrate in 7.5 L of deionized water. The suspension was stirred rapidly as the solution was added. The aquamarine color of the cupric sulfate solution was removed almost immediately and the zinc suspension changed in color from gray to black. The near colorless aqueous layer was decanted and the solid was washed with 4x3.0 L of deionized water. The suspension of zinc-copper couple was filtered through a piece of Whatman No. 1 filter paper, then washed with 4x30 L ethanol and 3x3.0 L of ether. The solid was carefully dried at 25°C and 140 mm overnight to remove ether, then for 3 hr at 130°-140°C (0.5 mm). The solid was cooled to room temperature under vacuum and was stored under argon in amber bottles. The procedure yielded 3.84 kg of zinc-copper couple.
  Preparation of [2R-[2α,5α(S*)]]-N-[1-[5-[[2-(acetyloxy)-1-oxopropoxy] methyl]-2-5-dihydro-2-furanyl]-1,2-dihydro-2-oxo-4-pyrimidinyl]acetamide.
  A total of 1.47 g of a mixture of bromoacetates in acetonitril was reduced with 800 mg of

• Trademarks

  Hivid (Roche).

• Therapeutic Function

  Antiviral, Immunosuppressive

• Allgemeine Beschreibung

  Zalcitabine, 2',3'-dideoxycytidine or ddCyd, is an analog ofcytosine that demonstrates activity against HIV-1 and HIV-2,including strains resistant to AZT. The potency (in peripheralblood mononuclear cells) is similar to that of AZT, but thedrug is more active in populations of monocytes andmacrophages as well as in resting cells.
  The oral bioavailability of zalcitabine is over 80% in adultsand less in children.The major dose-limiting side effect isperipheral neuropathy, characterized by pain, paresthesias,and hypesthesia, beginning in the distal lower extremities.These side effects are typically evident after several months oftherapy with zalcitabine. A potentially fatal pancreatitis is anothertoxic effect of treatment with ddC. The drug has beenapproved for the treatment of HIV infection in adults with advanceddisease who are intolerant to AZT or who have diseaseprogression while receiving AZT. ddC is combined with AZTfor the treatment of advanced HIV infection.

• Allgemeine Beschreibung

  White crystalline powder. Odorless.

• Air & Water Reaktionen

  Water soluble.

• Reaktivität anzeigen

  Zalcitabine may be sensitive to prolonged exposure to light.

• Brandgefahr

  Flash point data for Zalcitabine are not available; however, Zalcitabine is probably combustible.

• Pharmakokinetik

  Zalcitabine (ddC) is a useful alternate drug to ZDV and is given in combination with ZDV when CD4 cell counts fall to less than 300 cells/mm3 . Monotherapy with ddC is more active than ZDV. Its oral bioavailability is 87%, and its plasma half-life is approximately 1 hour. In low doses (0.005 mg/kg every 4 hours), ddC produces sustained decrease in p24 antigen level and increase in CD4 cell counts. The CSF fluid/plasma ratio of ddC is 0.2. Following oral administration, bioavailability of ddC is less than 80%, which is further reduced when taken with food. The mean maximum plasma concentration of the drug also is reduced from 25.2 to 15.5 ng/mL when the drug was taken with food.

• Pharmakologie

  Peripheral neuropathy occurs in up to 50% of patients taking zalcitabine. Stomatitis, esophageal ulceration, hepatotoxicity, rash, and pancreatitis may occur. Zalcitabine should be used with caution in individuals with a history of pancreatitis, liver disease, or alcohol abuse. Dosage adjustment is necessary for individuals with renal impairment. Zalcitabine should not be used in combination with didanosine, lamivudine, or stavudine.

• Nebenwirkungen

  It has side effects, such as stomatitis, rash, fever, malaise, arthritis, and arthralgia.

• Stoffwechsel

  Dideoxyuridine is the major metabolite in urine and feces. The drug penetrates the blood-brain barrier. The major toxicity of ddC is peripheral neuropathy, in which case it should be discontinued. In some cases, pancreatitis occurs when given alone or in combination with ZDV."

Zalcitabine Upstream-Materialien And Downstream Produkte

Zalcitabine Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(350)Suppliers

7481-89-2, Zalcitabine Verwandte Suche: