Zidovudine
- Iupac Name：1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
- CAS No.: 30516-87-1
- Molecular Weight：267.24132
- Modify Date.: 2022-11-01 22:40
- Introduction: Zidovudine, also known as azidothymidine (AZT), is an antiviral agent acting via reversetranscnptase inhibition. It was first launched in the U.K. and subsequently introduced inover a dozen countries for the management of severe manifestations of HIV infection. Inpatients with AIDS and ARC, zidovudine reduces the risk of opportunistic infections andprolongs survival time. In symptom-free patients it shows promise in halting furtherimmunological deterioration.
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1. Names and Identifiers
- 1.1 Name
- Zidovudine
- 1.2 Synonyms
1-(3-Azido-2,3-Dideoxy-Beta-D-Ribofuranosyl)Thymine 1-(3-Azido-2,3-dideoxy-Β-D-glycero-pentofuranosyl)-5-methylpyrimidine-2,4(1H,3H)-dione 1-(3-Azido-2,3-dideoxy-Β-D-ribofuranosyl)thymine 1-[(2R,4S,5S)-4-azido-5-(hydroxyméthyl)tétrahydrofuran-2-yl]-5-méthylpyrimidine-2,4(1H,3H)-dione 1-[(2R,4S,5S)-4-Azido-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-methylpyrimidin-2,4(1H,3H)-dion 1-[4-azido-5-(hydroxymethyl)-2-tetrahydrofuranyl]-5-methylpyrimidine-2,4-dione 1-[4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-pyrimidine-2,4-dione 1-[4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione 1-[4-azido-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione 1-[4-azido-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione 2,4(1H,3H)-pyrimidinedione, 1-(3-azido-2,3-dideoxy-Β-D-glycero-pentofuranosyl)-5-methyl- 3'-Azido-3'-deoxythymidine 3'-azido-3'-droxythymidine 3'-Deoxy-3'-azidothymi Azidothymidine Azitidin AZT BE-AS09U bwa509u BW-A509U MFCD00006536 retrovir Retrovis Thymidine, 3'-azido-3'-deoxy- Timazid ZDV Zidovudine solution ZVD
- 1.3 CAS No.
- 30516-87-1
- 1.4 CID
- 35370
- 1.5 EINECS(EC#)
- 623-849-4
- 1.6 Molecular Formula
- C10H13N5O4 (isomer)
- 1.7 Inchi
- InChI=1S/C10H13N5O4/c1-5-3-15(10(18)12-9(5)17)8-2-6(13-14-11)7(4-16)19-8/h3,6-8,16H,2,4H2,1H3,(H,12,17,18)/t6-,7+,8+/m0/s1
- 1.8 InChkey
- HBOMLICNUCNMMY-XLPZGREQSA-N
- 1.9 Canonical Smiles
- CC1=CN(C(=O)NC1=O)C2CC(C(O2)CO)N=[N+]=[N-]
- 1.10 Isomers Smiles
- CC1=CN(C(=O)NC1=O)[C@H]2C[C@@H]([C@H](O2)CO)N=[N+]=[N-]
2. Properties
- 2.1 Density
- 1.3382 (rough estimate)
- 2.1 Melting point
- 106-112℃
- 2.1 Refractive index
- 47 ° (C=1, H2O)
- 2.1 Flash Point
- 9℃
- 2.1 Precise Quality
- 267.09700
- 2.1 PSA
- 134.07000
- 2.1 logP
- -0.74354
- 2.1 Solubility
- H2O: 50?mg/mL
- 2.2 Appearance
- White to off-white Crystals
- 2.3 Storage
- Store at -20°C. Very Hygroscopic. Light Sensitive.
- 2.4 Chemical Properties
- Off White Crystalline Powder
- 2.5 Color/Form
- Powder
- 2.6 Odor
- Odorless
- 2.7 pKa
- pKa 9.53(H2O
t = 25.0±0.1
I = 0.00) (Uncertain)
- 2.8 Water Solubility
- 1-5 g/100 mL at 17 oC
- 2.9 Spectral Properties
- UV max in water = 226 nm (epsilon=11,650)
- 2.10 StorageTemp
- 2-8°C
3. Use and Manufacturing
- 3.1 Definition
- ChEBI: A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase.
- 3.2 General Description
- Slightly off-white odorless powdery solid.
- 3.3 Usage
- A potent and selective inhibitor of HIV-1 replication
4. Safety and Handling
- 4.1 Symbol
- GHS08;
- 4.1 Hazard Codes
- Xn
- 4.1 Signal Word
- Warning
- 4.1 Risk Statements
- R40
- 4.1 Safety Statements
- S36/37/39;S45
- 4.1 Exposure Standards and Regulations
- Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).
Zidovudine, used as a anti-infective agent, was approved by FDA for marketing in the United States on 3/19/87.
Zidovudine is designated an orphan drug by the US Food and Drug Administration (FDA) for use in the management of human immunodeficiency virus (HIV; formerly HTLV-III/LAV) infections. Zidovudine currently is labeled by the FDA for the management of HIV infections in certain adults with an absolute helper/inducer (CD4+, T4+) T-cell count from peripheral blood of 500/cu mm or less at the time therapy with the drug is initiated and who are asymptomatic, have early symptomatic HIV infections, or have advanced symptomatic infections (eg, acquired immunodeficiency syndrome AIDS or advanced AIDS related complex ARC). Zidovudine also is labeled by the FDA for the management of HIV infections in children 3 months of age or older who have HIV related symptoms or who are asymptomatic but have abnormal laboratory values indicating substantial HIV related immunosuppression.
The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl zidovudine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
- 4.2 Octanol/Water Partition Coefficient
- log Kow = 0.05
- 4.3 Fire Hazard
- Flash point data for Zidovudine are not available; however, Zidovudine is probably combustible.
- 4.4 Other Preventative Measures
- PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Principles that apply to chem or biochem lab also apply to microbiological & cell-culture labs ... Special consideration should be given to route of admin. ... Safest method of administering volatile carcinogen is by injection of a soln. Admin by topical application, gavage, or intratracheal instillation should be performed under hood. If chem will be exhaled, animals should be kept under hood during this period. Inhalation exposure requires special equipment. ... Unless specifically required, routes of admin other than in the diet should be used. Mixing of carcinogen in diet should be carried out in sealed mixers under fume hood, from which the exhaust is fitted with an efficient particulate filter. Techniques for cleaning mixer & hood should be devised before expt begun. When mixing diets, special protective clothing &, possibly, respirators may be required. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to skin, animals should be kept in cages with solid bottoms & sides & fitted with a filter top. When volatile carcinogens are given, filter tops should not be used. Cages which have been used to house animals that received carcinogens should be decontaminated. Cage-cleaning facilities should be installed in area in which carcinogens are being used, to avoid moving of ... contaminated /cages/. It is difficult to ensure that cages are decontaminated, & monitoring methods are necessary. Situations may exist in which the use of disposable cages should be recommended, depending on type & amt of carcinogen & efficiency with which it can be removed. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ... contamination in lab could build up during conduct of expt, periodic checks should be carried out on lab atmospheres, surfaces, such as walls, floors & benches, & ... interior of fume hoods & airducts. As well as regular monitoring, check must be carried out after cleaning-up of spillage. Sensitive methods are required when testing lab atmospheres. ... Methods ... should ... where possible, be simple & sensitive. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination has occurred, such as spillage, should be decontaminated by lab personnel engaged in expt. Design of expt should ... avoid contamination of permanent equipment. ... Procedures should ensure that maintenance workers are not exposed to carcinogens. ... Particular care should be taken to avoid contamination of drains or ventilation ducts. In cleaning labs, procedures should be used which do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner equipped with high-efficiency particulate filter on exhaust, which are avail commercially, should be used. Sweeping, brushing & use of dry dusters or mops should be prohibited. Grossly contaminated cleaning materials should not be re-used ... If gowns or towels are contaminated, they should not be sent to laundry, but ... decontaminated or burnt, to avoid any hazard to laundry personnel. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where carcinogens are used ... should be marked distinctively with appropriate labels. Access ... limited to persons involved in expt. ... A prominently displayed notice should give the name of the Scientific Investigator or other person who can advise in an emergency & who can inform others (such as firemen) on the handling of carcinogenic substances. /Chemical Carcinogens/
- 4.5 Hazard Declaration
- H351
- 4.5 Cleanup Methods
- PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/
- 4.6 DisposalMethods
- SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.
PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can be destroyed using chem reactions ... but no general rules can be given. ... As a general technique ... treatment with sodium dichromate in strong sulfuric acid can be used. The time necessary for destruction ... is seldom known ... but 1-2 days is generally considered sufficient when freshly prepd reagent is used. ... Carcinogens that are easily oxidizable can be destroyed with milder oxidative agents, such as saturated soln of potassium permanganate in acetone, which appears to be a suitable agent for destruction of hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or acylating agents per se can be destroyed by reaction with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols & thiosulfate. The reactivity of various alkylating agents varies greatly ... & is also influenced by sol of agent in the reaction medium. To facilitate the complete reaction, it is suggested that the agents be dissolved in ethanol or similar solvents. ... No method should be applied ... until it has been thoroughly tested for its effectiveness & safety on material to be inactivated. For example, in case of destruction of alkylating agents, it is possible to detect residual compounds by reaction with 4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/
- 4.7 RIDADR
- UN1230 - class 3 - PG 2 - Methanol, solution
- 4.7 Safety Profile
- Moderately toxic by intravenousroute. Human systemic effects by ingestion: aplasticanemia, changes in blood cell count, convulsions or effect on seizure threshold, headache, nails, retinal changes.Human mutation data reported.
- 4.8 Caution Statement
- P280
- 4.8 Formulations/Preparations
- Oral capsules, 100 mg, Retrovir; GlaxoSmithKline; solution, 50 mg/5 ml, Retrovir syrup, GlaxoSmithKline; tablets, film-coated, 300 mg, Retrovir, GlaxoSmithKline; parenteral injection for iv infusion, 10 mg/ml, Retrovir iv Infusion, GlaxoSmithKline
- 4.9 WGK Germany
- 3
- 4.9 RTECS
- XP2072000
- 4.9 Toxicity
-
CHEMICAL IDENTIFICATION
- RTECS NUMBER :
- XP2072000
- CHEMICAL NAME :
- Thymidine, 3'-azido-3'-deoxy-
- CAS REGISTRY NUMBER :
- 30516-87-1
- LAST UPDATED :
- 199712
- DATA ITEMS CITED :
- 36
- MOLECULAR FORMULA :
- C10-H13-N5-O4
- MOLECULAR WEIGHT :
- 267.28
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Human - woman
- DOSE/DURATION :
- 1 gm/kg/6W-I
- TOXIC EFFECTS :
- Skin and Appendages - nails
- TYPE OF TEST :
- LDLo - Lowest published lethal dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Human - man
- DOSE/DURATION :
- 86 mg/kg/1W-I
- TOXIC EFFECTS :
- Behavioral - convulsions or effect on seizure threshold
Behavioral - headache
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Human - man
- DOSE/DURATION :
- 434 mg/kg/38D-I
- TOXIC EFFECTS :
- Blood - changes in cell count (unspecified)
Blood - aplastic anemia
Blood - changes in bone marrow (not otherwise specified)
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Unreported
- SPECIES OBSERVED :
- Human - man
- DOSE/DURATION :
- 69 mg/kg
- TOXIC EFFECTS :
- Sense Organs and Special Senses (Eye) - retinal changes (pigmentary
depositions, retinitis, other)
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 3084 mg/kg
- TOXIC EFFECTS :
- Sense Organs and Special Senses (Eye) - ptosis
Behavioral - somnolence (general depressed activity)
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- >70 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Unreported
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- >750 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 3062 mg/kg
- TOXIC EFFECTS :
- Sense Organs and Special Senses (Eye) - ptosis
Behavioral - somnolence (general depressed activity)
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- >70 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Unreported
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- >750 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 54600 mg/kg/1Y-I
- TOXIC EFFECTS :
- Blood - pigmented or nucleated red blood cells
Blood - changes in erythrocyte (RBC) count
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 91 gm/kg/26W-I
- TOXIC EFFECTS :
- Blood - normocytic anemia
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 47 gm/kg/94D-I
- TOXIC EFFECTS :
- Blood - pigmented or nucleated red blood cells
Blood - changes in bone marrow (not otherwise specified)
Blood - changes in erythrocyte (RBC) count
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 4700 mg/kg/94D-I
- TOXIC EFFECTS :
- Blood - pigmented or nucleated red blood cells
Blood - changes in bone marrow (not otherwise specified)
Blood - changes in erythrocyte (RBC) count
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 14500 mg/kg/29D-I
- TOXIC EFFECTS :
- Blood - pigmented or nucleated red blood cells
Blood - changes in erythrocyte (RBC) count
Blood - changes in leukocyte (WBC) count
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 6800 mg/kg/17D-I
- TOXIC EFFECTS :
- Kidney, Ureter, Bladder - changes in tubules (including acute renal failure,
acute tubular necrosis)
Blood - pigmented or nucleated red blood cells
Blood - changes in erythrocyte (RBC) count
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- 7 gm/kg/2W-I
- TOXIC EFFECTS :
- Blood - leukopenia
Blood - thrombocytopenia
Nutritional and Gross Metabolic - weight loss or decreased weight gain
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Primate - monkey
- DOSE/DURATION :
- 3094 mg/kg/13W-I
- TOXIC EFFECTS :
- Blood - normocytic anemia
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Primate - monkey
- DOSE/DURATION :
- 18200 mg/kg/26W-I
- TOXIC EFFECTS :
- Blood - pigmented or nucleated red blood cells
Blood - changes in other cell count (unspecified)
Blood - changes in erythrocyte (RBC) count
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Primate - monkey
- DOSE/DURATION :
- 12740 mg/kg/1Y-I
- TOXIC EFFECTS :
- Blood - pigmented or nucleated red blood cells
Blood - changes in erythrocyte (RBC) count
Blood - changes in platelet count
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 4200 mg/kg
- SEX/DURATION :
- male 4 week(s) pre-mating
- TOXIC EFFECTS :
- Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland,
accessory glands
Reproductive - Paternal Effects - other effects on male
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 23 gm/kg
- SEX/DURATION :
- male 85 day(s) pre-mating
female 26 day(s) pre-mating - 3 week(s) post-birth
- TOXIC EFFECTS :
- Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured
before birth)
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 69 gm/kg
- SEX/DURATION :
- male 85 day(s) pre-mating
female 26 day(s) pre-mating - 3 week(s) post-birth
- TOXIC EFFECTS :
- Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
Reproductive - Effects on Newborn - live birth index (measured after birth)
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 27900 mg/kg
- SEX/DURATION :
- female 26 day(s) pre-mating - 15 day(s) post-birth
- TOXIC EFFECTS :
- Reproductive - Effects on Newborn - live birth index (measured after birth)
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 910 mg/kg
- SEX/DURATION :
- female 1-13 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured
before birth)
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 6500 mg/kg
- SEX/DURATION :
- female 6-18 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
- TYPE OF TEST :
- Micronucleus test
- TYPE OF TEST :
- Cytogenetic analysis
MUTATION DATA
- TYPE OF TEST :
- Sister chromatid exchange
- TEST SYSTEM :
- Rodent - hamster Ovary
- DOSE/DURATION :
- 500 mg/L
- REFERENCE :
- MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 321,113,1994
5. MSDS
2.Hazard identification
2.1 Classification of the substance or mixture
Germ cell mutagenicity, Category 2
Carcinogenicity, Category 1B
Reproductive toxicity, Category 2
Specific target organ toxicity \u2013 repeated exposure, Category 1
2.2 GHS label elements, including precautionary statements
| Pictogram(s) |  |
| Signal word | Danger |
| Hazard statement(s) | H341 Suspected of causing genetic defects H350 May cause cancer H361 Suspected of damaging fertility or the unborn child H372 Causes damage to organs through prolonged or repeated exposure |
| Precautionary statement(s) | |
| Prevention | P201 Obtain special instructions before use. P202 Do not handle until all safety precautions have been read and understood. P280 Wear protective gloves/protective clothing/eye protection/face protection. P260 Do not breathe dust/fume/gas/mist/vapours/spray. P264 Wash ... thoroughly after handling. P270 Do not eat, drink or smoke when using this product. |
| Response | P308+P313 IF exposed or concerned: Get medical advice/ attention. P314 Get medical advice/attention if you feel unwell. |
| Storage | P405 Store locked up. |
| Disposal | P501 Dispose of contents/container to ... |
2.3 Other hazards which do not result in classification
none
7. Synthesis Route
30516-87-1Total: 91 Synthesis Route
9. Other Information
- 9.0 Merck
- 14,10123
- 9.1 BRN
- 3595791
- 9.2 Description
- Zidovudine, also known as azidothymidine (AZT), is an antiviral agent acting via reverse transcnptase inhibition. It was first launched in the U.K. and subsequently introduced in over a dozen countries for the management of severe manifestations of HIV infection. In patients with AIDS and ARC, zidovudine reduces the risk of opportunistic infections and prolongs survival time. In symptom-free patients it shows promise in halting further immunological deterioration.
- 9.3 Chemical Properties
- Off White Crystalline Powder
- 9.4 Originator
- Detroit Inst. Cancer Res. (USA)
- 9.5 Uses
- A potent and selective inhibitor of HIV-1 replication
- 9.6 Uses
- antibacterial
- 9.7 Uses
- Zidovudine is an antiretroviral drug that is clinically active against HIV-1 and is intended to treat HIV-infected patients. Zidovudine is an analog of thymidine that inhibits replication of the AIDS virus. It also turned into mono-, di-, and triphosphates by the same cellular enzymes that catalyze phosphorylation of thymidine and thymidine nucleosides. Zidovudine-triphosphate is then included in the terminal fragment of the growing chain of viral DNA by viral reverse transcriptase, thus causing the viral DNA chain to break apart in cells infected with the virus.
Zidovudine has been authorized for treating patients with AIDS. It significantly prolongs the life of the patient, although it has a number of toxic effects. Synonyms of this drug are azidothymidine and retrovir.
- 9.8 Definition
- ChEBI: A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase.
- 9.9 Indications
- Zidovudine was the first agent to be used to prevent the transmission of HIV from a pregnant woman to her child. It was given to the mother at 14 to 34 weeks’ gestation and to the child for the first 6 weeks of life. Current combination therapies employ zidovudine with another NRTI and a protease inhibitor.
- 9.10 Manufacturing Process
- Preparation of 2,3'-anhydrothymidine
Thymidine (85.4 g; 0.353 mol) was dissolved in 500 mL dry DMF (dimethyl formamide) and added to N-(2-chloro-1,1,2-trifluoroethyl)diethylamine (100.3 g; 0.529 mol) [prepared according to the method of D. E. Ayer, J. Med. Chem. 6, 608 (1963)]. This solution was heated at 70°C for 30 minutes then poured into 950 mL ethanol with vigorous stirring. The product precipitated from this solution and was filtered. The ethanol supernatant was refrigerated then filtered to yield a total of 47.75 g (0.213 mol; 60.3%) of 2,3'- anhydrothymidine; melting point 228°-230°C.
Preparation for 3'-azido-3'-deoxythymidine
2,3'-Anhydrothymidine (25 g; 0.1115 mol) and NaN 3 (29 g; 0.446 mol) was suspended in a mixture of 250 mL DMF and 38 mL H 2 O. The reaction was refluxed for 5 hours at which time it was poured into 1 liter of H 2 O. This aqueous solution was extracted with ethyl acetate (EtOAc) (3x700 ml). The EtOAc was dried over Na 2 SO 4 , filtered, and then EtOAc was removed in vacuo to yield a viscous oil. This oil was stirred with 200 mL water resulting in a solid, 3'-azido-3'-deoxythymidine, 9.15 g (0.0342 mol); 30.7%; melting point 116°-118°C.
- 9.11 Brand name
- Retrovir (GlaxoSmithKline).
- 9.12 Therapeutic Function
- Antiviral, Antineoplastic
- 9.13 Antimicrobial activity
- Zidovudine is active against HIV-1, HIV-2 and HTLV-1.
- 9.14 Acquired resistance
- As with stavudine, mutations at position 41, 67 and 70, and positions 210, 215 and 219 (the ‘thymidine analog mutations’) of the reverse transcriptase genes are associated with diminished antiretroviral efficacy.
- 9.15 General Description
- Slightly off-white odorless powdery solid.
- 9.16 General Description
- Zidovudine, 3'-azido-3'-deoxythymidine or AZT, is ananalog of thymidine that possesses antiviral activityagainst HIV-1, HIV-2, HTLV-1, and several other retroviruses.This nucleoside was synthesized in 1978 by Linand Prusoff as an intermediate in the preparation ofamino acid analogs of thymidine. A screening program directedtoward the identification of agents potentially effectivefor the treatment of patients with AIDS led to the discoveryof its unique antiviral properties 7 years later.
Zidovudine is recommended for the management of adultpatients with symptomatic HIV infection (AIDS or ARC)who have a history of confirmed Pneumocystis carinii pneumoniaor an absolute CD4+(T4 or TH cell) lymphocytecount below 200/mm3 before therapy. The hematologicaltoxicity of the drug precludes its use in asymptomatic patients.Anemia and granulocytopenia are the most commontoxic effects associated with AZT.
- 9.17 Air & Water Reactions
- Dust may form an explosive mixture in air. Water soluble. Hydrolysis occurs in strongly basic solutions .
- 9.18 Reactivity Profile
- Zidovudine is a azido compound. Azo, diazo, azido compounds can detonate. This applies in particular to organic azides that have been sensitized by the addition of metal salts or strong acids. Toxic gases are formed by mixing materials of this class with acids, aldehydes, amides, carbamates, cyanides, inorganic fluorides, halogenated organics, isocyanates, ketones, metals, nitrides, peroxides, phenols, epoxides, acyl halides, and strong oxidizing or reducing agents. Flammable gases are formed by mixing materials in this group with alkali metals. Explosive combination can occur with strong oxidizing agents, metal salts, peroxides, and sulfides.
- 9.19 Fire Hazard
- Flash point data for Zidovudine are not available; however, Zidovudine is probably combustible.
- 9.20 Pharmaceutical Applications
- An analog of thymidine formulated for oral or intravenous use.
- 9.21 Biochem/physiol Actions
- Reverse transcriptase inhibitor active against HIV-1 virus.
- 9.22 Mechanism of action
- Zidovudine (AZT , ZDV) is an analogue of thymidine in which the azido group is substituted at the 3-carbon atom of the dideoxyribose moiety. It is active against RNA tumor viruses (retroviruses) that are the causative agents of AIDS and T-cell leukemia. Retroviruses, by virtue of RT, direct the synthesis of a provirus (DNA copy of a viral RNA genome). Proviral DNA integrates into the normal cell DNA, leading to the HIV infection. Zidovudine is converted to 5′-mono-, di-, and triphosphates by the cellular thymidine kinase. These phosphates are then incorporated into proviral DNA, because RT uses ZDV-triphosphate as a substrate. This process prevents normal 5′,3′-phosphodiester bonding, resulting in termination of DNA chain elongation because of the presence of an azido group in ZDV. The multiplication of HIV is halted by selective inhibition of RT and, thus, viral DNA polymerase by ZDV-triphosphate at the required dose concentration. Zidovudine is a potent inhibitor of HIV-1, but it also inhibits HIV-2 and EBV.
- 9.23 Pharmacokinetics
- Oral absorption: 65%
Cmax 300 mg twice daily: 2.3 mg/L
Plasma half-life: 1.1 h
Volume of distribution: 1.6 L/kg
Plasma protein binding; 34–38%
Absorption and distribution
It is absorbed rapidly and almost completely following oral administration. Absorption is not significantly affected by food. It appears to undergo widespread body distribution. CNS penetration is fairly good. The semen:plasma ratio varies from 0.95 to 13.5 (mean 5.9). It is secreted into breast milk.
Metabolism and excretion
Following hepatic metabolism (glucuronidation), elimination is primarily renal. After oral administration, urinary recovery of zidovudine and its glucuronide metabolite accounted for 14% and 74% respectively of the dose, with a total urinary recovery of 90%.
In severe renal impairment, clearance was about half that reported in subjects with normal renal function Accumulation may occur in patients with hepatic impairment due to decreased glucuronidation.
- 9.24 Clinical Use
- Treatment of HIV infection in adults and children (in combination with other antiretroviral drugs)
Reduction of maternal transmission of HIV to the fetus
- 9.25 Side effects
- In common with other drugs in this class, use has been associated with episodes of fatal and non-fatal lactic acidosis and hepatomegaly with steatosis. Careful clinical evaluation is needed in patients with evidence of hepatic abnormality. Myelosuppression may occur within the first 4–6 weeks of therapy. Hematological parameters should be monitored during this period, with prompt dose modification or switch if abnormalities are observed. Treatment with reduced doses may be attempted in some patients once bone marrow recovery has been observed. Myopathy is rarely seen with the use of the current dosing regimens.
Co-administration with drugs known to cause nephrotoxicity, cytotoxicity or which interfere with red or white blood cell number and function may increase the risk of toxicity. Probenecid and trimethoprim may reduce renal clearance of zidovudine, and other drugs that are metabolized by glucuronidation may interfere with its metabolism.
- 9.26 Safety Profile
- Moderately toxic by intravenousroute. Human systemic effects by ingestion: aplasticanemia, changes in blood cell count, convulsions or effect on seizure threshold, headache, nails, retinal changes.Human mutation data reported.
- 9.27 Chemical Synthesis
- Zidovudine is 3-azido-3-deoxytimidine (36.1.26), is synthesized from 1-(2-deoxy-5-O-trityl-β-D-lyxosyl)thymine, which is treated with methansulfonyl chloride in pyridine to make the corresponding mesylate 36.1.24. Replacing the methyl group with an azide group using lithium azide in dimethylformamaide makes the product 36.1.25 with inverted configuration at C3 of the furanosyl ring. Heating this in 80% acetic acid removes the trityl protection, giving zidovudine.
- 9.28 Veterinary Drugs and Treatments
- In veterinary medicine, zidovudine may be useful for treating feline immunodeficiency virus (FIV) or feline leukemia virus (FeLV). While zidovudine can reduce the viral load in infected cats and improve clinical signs, it may not alter the natural course of the disease to a great extent.
- 9.29 Usage
- 3'-Azido-3'-deoxythymidine is a Anti-viral agent, and also used as a reverse transcriptase inhibitor active against HIV-1 virus that blocks the incorporation of nucleotides into growing DNA strands. Useful for antiviral and anticancer studies. 3?-Azido-3?-deoxythymidine enters CNS by diffusion and causes irreversible telomere shortening.
10. Computational chemical data
- Molecular Weight: 267.24132g/mol
- Molecular Formula: C10H13N5O4
- Compound Is Canonicalized: True
- XLogP3-AA: null
- Exact Mass: 267.09675391
- Monoisotopic Mass: 267.09675391
- Complexity: 484
- Rotatable Bond Count: 3
- Hydrogen Bond Donor Count: 2
- Hydrogen Bond Acceptor Count: 6
- Topological Polar Surface Area: 93.2
- Heavy Atom Count: 19
- Defined Atom Stereocenter Count: 3
- Undefined Atom Stereocenter Count: 0
- Defined Bond Stereocenter Count: 0
- Undefined Bond Stereocenter Count: 0
- Isotope Atom Count: 0
- Covalently-Bonded Unit Count: 1
- CACTVS Substructure Key Fingerprint: AAADccBzuAAAAAAAAAAAAAAAAAAAASAAAAAgAAAAAAAAAAAAAAAAHgAYCAAADDzhgAYDAAPABgCKAgFWUACAAAAAAAAAAAEIAECDEAIAwQAPQAAOByIDAMCwMAIAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA==
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