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Zalcitabine

Zalcitabine
Zalcitabine structure
CAS No.
7481-89-2
Chemical Name:
Zalcitabine
Synonyms
DDC;D 2C;Hivid;ddCyd;I-livid;2',3'-ddC;NSC 606170;ZALCITABINE;Ro 24-2027/000;Dideoxycytidin
CBNumber:
CB2369466
Molecular Formula:
C9H13N3O3
Formula Weight:
211.22
MOL File:
7481-89-2.mol

Zalcitabine Properties

Melting point:
217-218 °C(lit.)
Boiling point:
350.9°C (rough estimate)
alpha 
D25 +81° (c = 0.635 in water)
Density 
1.2605 (rough estimate)
refractive index 
78 ° (C=0.5, H2O)
storage temp. 
Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
form 
powder
pka
14.44±0.10(Predicted)
color 
colorless
Water Solubility 
5-10 g/100 mL at 19 ºC
Merck 
14,10109
BRN 
654956
Stability:
Stable. Combustible. Incompatible with strong oxidizing agents.
InChIKey
WREGKURFCTUGRC-POYBYMJQSA-N
CAS DataBase Reference
7481-89-2(CAS DataBase Reference)
FDA UNII
6L3XT8CB3I
Proposition 65 List
Zalcitabine
NCI Drug Dictionary
Hivid
IARC
2B (Vol. 76) 2000
EPA Substance Registry System
Cytidine, 2',3'-dideoxy- (7481-89-2)
SAFETY
  • Risk and Safety Statements
Symbol(GHS) 
GHS08
Signal word  Warning
Hazard statements  H361-H351
Precautionary statements  P201-P202-P308+P313-P405-P501a-P280-P281
Hazard Codes  Xn,C
Risk Statements  40-36/37-34
Safety Statements  22-36-45-36/37/39-27-26
WGK Germany  3
RTECS  HA3870000
10-23
HS Code  2934990002

Zalcitabine price More Price(10)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich D5782 2′,3′-Dideoxycytidine ≥98% (HPLC) 7481-89-2 100mg $148 2021-03-22 Buy
Sigma-Aldrich 1724306 Zalcitabine United States Pharmacopeia (USP) Reference Standard 7481-89-2 200mg $366 2021-03-22 Buy
Alfa Aesar L10619 2',3'-Dideoxycytidine, 98+% 7481-89-2 50mg $58.9 2021-03-22 Buy
Alfa Aesar L10619 2',3'-Dideoxycytidine, 98+% 7481-89-2 250mg $207 2021-03-22 Buy
Cayman Chemical 16019 Zalcitabine ≥95% 7481-89-2 25mg $25 2021-03-22 Buy

Zalcitabine Chemical Properties,Uses,Production

Description

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.

Chemical Properties

White to Off-White Cyrstalline Powder

Originator

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

Uses

ammonia detoxicant, diagnostic aid

Uses

A pyrimidine nucleoside analogue with antiviral activity

Definition

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

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.

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 zinc-copper couple. The mixture was stirred under argon at room temperature overnight. The mixture was deoxygenated by evacuation followed by filling the reaction vessel with argon (oxygen-free nitrogen may be used); this procedure was repeated three times. It was filtered over Celite, the flask was rinsed out with of acetonitrile, and the rinse was used to wash the Celite. The combined filtrate and washing were evaporated (40°C), and the residue was dissolved in of methylene chloride. This was added to a previously prepared solution of ethylenediaminetetraacetic acid disodium salt dihydrate (Fluka) in deionized water containing of sodium bicarbonate. The mixture was stirred vigorously for 1.5 hr, and filtered over Celite, which was washed with methylene chloride. The organic phase was separated and the aqueous phase was re-extracted with of methylene chloride. The combined organic was washed with of saturated sodium bicarbonate, which was back-extracted with of methylene chloride. The combined organic was dried (MgSO 4 ), filtered, and concentrated. To this was added of acetic anhydride followed by 40 g of poly- 4-vinylpyridine, and the mixture was stirred under nitrogen for 3 hr. It was filtered over Celite, which was washed with methylene chloride. The combined filtrate and washing were evaporated, toluene was added, and the mixture was evaporated again, ether was added with vigorous stirring for 15 minutes. The mixture was filtered (some scraping of the flask was necessary) and washed with ether to give 570 mg of after crystallization from hot tetrahydrofuran, melting point 125°C; [α] D 25 +119.04°(c=0.25, CHCl 3 ).
Preparation of [2R-[2α,5α(S*)]]-N-[1-[5-[[2-(acetyloxy)-1-oxopropoxy] methyl]tetrahydro-2-furanyl]-1,2-dihydro-2-oxo-4-pyrimidinyl]acetamide.
A solution of 720 mg 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 set forth in 10 ml L of methanol and 10 ml of tetrahydrofuran was hydrogenated over 200 mg of 10% palladium on charcoal at room temperature and atmospheric pressure until hydrogen uptake ceased (10 ml). The mixture was filtered over Celite and the filtrate was evaporated to give a gum. Chromatography on 10 g of silica (70-230 mesh) with 10% methanol in methylene chloride, gave 290 mg of the product as a foam, [α] D 25 +88.43° (C=0.99, CHCl 3 ).
Preparation of 2',3'-dideoxycytidine.
A solution of 20.7 g of [2R-[2α,5α(S*)]]-N-[1-[5-[[2-(acetyloxy)-1- oxopropoxy]methyl]tetrahydro-2-furanyl]-1,2-dihydro-2-oxo-4-pyrimidinyl] acetamide in 100 ml of ethanol was treated with 10.0 ml of Triton B (N- benzyltrimethyl-ammonium hydroxide), and the mixture was stirred at room temperature overnight. The mixture was concentrated to 20 ml, cooled to 0°C, and the product was collected by filtration. It was washed with 10 ml of cold ethanol to give 4.48 g of 2',3'-dideoxycytidine, melting point 215°-218°C, as an white solid.

brand name

Hivid (Roche).

Therapeutic Function

Antiviral, Immunosuppressive

General Description

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.

General Description

White crystalline powder. Odorless.

Air & Water Reactions

Water soluble.

Reactivity Profile

Zalcitabine may be sensitive to prolonged exposure to light.

Fire Hazard

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

Pharmacokinetics

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.

Pharmacology

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.

Side effects

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

Metabolism

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 Preparation Products And Raw materials

Raw materials

Preparation Products


Zalcitabine Suppliers

Global( 254)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
career henan chemical co
+86-371-86658258
sales@coreychem.com CHINA 29960 58
Jinan Carbotang Biotech Co.,Ltd.
+86 15866703830
figo.gao@foxmail.com CHINA 2778 58
Hubei Jusheng Technology Co.,Ltd.
86-18871470254
027-59599243 linda@hubeijusheng.com CHINA 28229 58
Chongqing Chemdad Co.,Ltd
+86-19923101450
sales@chemdad.com CHINA 4000 58
Nanjing Baifuli Technology Co., Ltd.
+86-15335185688
sales@unisyn.cn CHINA 332 58
Hubei xin bonus chemical co. LTD
86-13657291602
027-59338440 linda@hubeijusheng.com CHINA 23035 58
BOC Sciences
1-631-485-4226
1-631-614-7828 inquiry@bocsci.com United States 19753 58
Chongqing Chemdad Co., Ltd
+86-13650506873
sales@chemdad.com CHINA 37282 58
Alchem Pharmtech,Inc.
8485655694
sales@alchempharmtech.com United States 63726 58
CONIER CHEM AND PHARMA LIMITED
86-18523575427
sales@conier.com CHINA 47496 58

View Lastest Price from Zalcitabine manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2021-07-02 Zalcitabine
7481-89-2
US $15.00-10.00 / KG 1KG 99%+ HPLC Monthly supply of 1 ton Zhuozhou Wenxi import and Export Co., Ltd
2020-05-26 Zalcitabine
7481-89-2
US $0.00-0.00 / Kg 1KG 99.0% 500 MT Shaanxi Dideu Medichem Co. Ltd
2019-07-06 Zalcitabine
7481-89-2
US $2.00 / KG 1KG 98% 1ton career henan chemical co

Zalcitabine Spectrum


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