Application in Particular Diseases
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Azathioprine

Application in Particular Diseases
Product Name
Azathioprine
CAS No.
446-86-6
Chemical Name
Azathioprine
Synonyms
IMURAN;muran;Imrel;azamun;azanin;imurek;imurel;Zytrim;Azasan;bw57-322
CBNumber
CB2170327
Molecular Formula
C9H7N7O2S
Formula Weight
277.26
MOL File
446-86-6.mol
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Azathioprine Property

Melting point:
243-244°C
Boiling point:
521.0±60.0 °C(Predicted)
Density 
1.5379 (rough estimate)
refractive index 
1.7400 (estimate)
storage temp. 
2-8°C
solubility 
Soluble in Dichloromethane and dimethyl sulfoxide.
pka
8.2(at 25℃)
color 
Pale-yellow crystals from Me2CO (aq)
Water Solubility 
<0.1 g/100 mL at 23 ºC
Merck 
14,902
BCS Class
4
Stability:
Stable. Incompatible with strong oxidizing agents, strong bases.
InChIKey
LMEKQMALGUDUQG-UHFFFAOYSA-N
CAS DataBase Reference
446-86-6(CAS DataBase Reference)
IARC
1 (Vol. 26, Sup 7, 100A) 2012
EPA Substance Registry System
Azathioprine (446-86-6)
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Safety

Hazard Codes 
Xi,T,Xn
Risk Statements 
45-22-36/37/38-20/21/22
Safety Statements 
53-22-26-36/37-45-36
WGK Germany 
3
RTECS 
UO8925000
HazardClass 
IRRITANT
HS Code 
29339900
Hazardous Substances Data
446-86-6(Hazardous Substances Data)
Toxicity
LD50 orl-rat: 535 mg/kg NIIRDN 6,3,82
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Danger
Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

H350May cause cancer

Precautionary statements

P202Do not handle until all safety precautions have been read and understood.

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P308+P313IF exposed or concerned: Get medical advice/attention.

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
A4638
Product name
Azathioprine
Purity
≥98%
Packaging
1g
Price
$128
Updated
2024/03/01
Sigma-Aldrich
Product number
1046001
Product name
Azathioprine
Purity
United States Pharmacopeia (USP) Reference Standard
Packaging
200mg
Price
$393
Updated
2024/03/01
TCI Chemical
Product number
A2069
Product name
Azathioprine
Purity
>98.0%(HPLC)(T)
Packaging
5g
Price
$175
Updated
2024/03/01
TCI Chemical
Product number
A2069
Product name
Azathioprine
Purity
>98.0%(HPLC)(T)
Packaging
25g
Price
$524
Updated
2024/03/01
Alfa Aesar
Product number
J62314
Product name
Azathioprine
Packaging
1g
Price
$102.65
Updated
2024/03/01
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Azathioprine Chemical Properties,Usage,Production

Application in Particular Diseases

In Rheumatic Arthritis:
Azathioprine is a purine analog that is converted to 6-mercaptopurine and is thought to interfere with DNA and RNA synthesis. Antirheumatic effects may be seen in 3 to 4 weeks. It should be discontinued if no response is observed after 12 weeks at maximal doses. Its major adverse effects are bone marrow suppression (leukopenia, macrocytic anemia, thrombocytopenia, pancytopenia), stomatitis, GI intolerance, infections, drug fever, hepatotoxicity, and oncogenic potential.

Description

This immunosuppressive and antineoplastic drug is derived from 6-mercaptopurine. It caused occupational dermatitis in a pharmaceutical worker, reconditioner of old tablet packaging machines and in a production mechanic, working in packaging for a pharmaceutical company.

Chemical Properties

Yellow Solid

Chemical Properties

Azathioprine is a complex heterocyclic compound which forms pale yellow crystals.

Originator

Imuran,Wellcome,UK,1964

Uses

Azathioprine is an immunosuppressive purine antimetabolite. The mechanism of action of azathioprine is as a nucleic acid synthesis inhibitor. It has shown promise in treatment of alopecia areata (autoimmune hair loss), with no difference in effectiveness between genders.

Uses

immunosuppressant, antineoplastic, antirheumatic

Uses

An immunosuppressive antimetabolite. Also active as disease modifying antirheumatic drug (DMARD). Azathioprine is a purine analog with immunosuppressive effects.

Definition

ChEBI: A thiopurine that is 6-mercaptopurine in which the mercapto hydrogen is replaced by a 1-methyl-4-nitroimidazol-5-yl group. It is a prodrug for mercaptopurine and is used as an immunosuppressant, prescribed for the treatment of inflammatory conditions and a ter organ transplantation and also for treatment of Crohn's didease and MS.

Indications

Azathioprine (Imuran) is a cytotoxic agent that preferentially destroys any rapidly dividing cell. Since immunologically competent cells are generally rapidly dividing cells, azathioprine is very effective as an immunosuppressive drug. Unfortunately, any cell that is replicating is a target for this action. This lack of specificity leads to serious side effects. Azathioprine, in combination with corticosteroids, has historically been used more widely than any other drug in immunosuppressive therapy. It is classified as a purine antimetabolite and is a derivative of 6-mercaptopurine.

Manufacturing Process

N,N'-Dimethyloxaldiamide is reacted with PCl5, to give 4-chloro-1-methyl imidazole. This is nitrated with HNO3 to give 5-nitro-1-methyl-4- chloroimidazole. Then, a mixture of 4.6 grams of anhydrous 6- mercaptopurine, 5 grams of 1-methyl-4-chloro-5-nitroimidazole and 2.5 grams of anhydrous sodium acetate in 100 ml of dry dimethyl sulfoxide was heated at 100°C for 7 hours.
After standing overnight at room temperature, the mixture was poured into 200 ml of cold water and the yellow precipitate of 6-(1'-methyl-4'-nitro-5'- imidazolyl)mercaptopurine (7.0 grams) collected. After recrystallization from 50% aqueous acetone, the product melted at 243-244°C, dec., and had an UV spectrum with λ maximum = 280 nm at pH 1 and λ max. = 285 nm at pH 11.

brand name

Imuran (Promethus).

Therapeutic Function

Immunosuppressive

General Description

Pale yellow crystals or yellowish powder. Decomposes at 243-244°C. Used for the treatment of rheumatoid arthritis. A known carcinogen.

Air & Water Reactions

Sensitive to oxidation in the air. Insoluble in water.

Reactivity Profile

Azathioprine may react exothermically with acids. Incompatible with isocyanates, peroxides, phenols, epoxides, anhydrides, and acid halides. Hydrolyzed by strongly basic solutions . May react with strong reducing agents to generate flammable gaseous hydrogen or hydrogen sulfide.

Hazard

Confirmed carcinogen.

Fire Hazard

Flash point data for Azathioprine are not available. Azathioprine is probably combustible.

Contact allergens

This immunosuppressive and antineoplastic drug is derived from 6-mercaptopurine. It caused allergic contact dermatitis in a mother crushing tablets for her leukemic son, and occupational dermatitis in a pharmaceutical reconditioner of old tablet packaging machines, and in a production mechanic working in packaging for a pharmaceutical company.

Biochem/physiol Actions

Has shown promise in treatment of alopecia areata (autoimmune hair loss), with no difference in effectiveness between genders.

Mechanism of action

Azathioprine is a phase-specific drug that is toxic to cells during nucleic acid synthesis. Phase-specific drugs are toxic during a specific phase of the mitotic cycle, usually the S-phase, when DNA synthesis is occurring, as opposed to cycle-specific drugs that kill both cycling and intermitotic cells.
Azathioprine is converted in vivo to thioinosinic acid, which competitively inhibits the synthesis of inosinic acid, the precursor to adenylic acid and guanylic acid. In this way, azathioprine inhibits DNA synthesis and therefore suppresses lymphocyte proliferation.This effectively inhibits both humoral and cell-mediated immune responses.

Pharmacology

Azathioprine is well absorbed following oral administration, with peak blood levels occurring within 1 to 2 hours. It is rapidly and extensively metabolized to 6- mercaptopurine, which is further converted in the liver and erythrocytes to a variety of metabolites, including 6- thiouric acid. Metabolites are excreted in the urine.The half-life of azathioprine and its metabolites in the blood is about 5 hours.

Clinical Use

Azathioprine is a relatively powerful antiinflammatory agent. Although its beneficial effect in various conditions is principally attributable to its direct immunosuppressive action, the antiinflammatory properties of the drug play an important role in its overall therapeutic effectiveness.
Azathioprine has been used widely in combination with corticosteroids to inhibit rejection of organ transplants, particularly kidney and liver allografts. However, it is usually reserved for patients who do not respond to cyclosporine plus corticosteroids alone.
Azathioprine also has applications in certain disorders with autoimmune components, most commonly rheumatoid arthritis. It is as effective as cyclophosphamide in the treatment of Wegener’s granulomatosis. It has largely been replaced by cyclosporine in immunosuppressive therapy. Relative to other cytotoxic agents, the better oral absorption of azathioprine is the reason for its more widespread clinical use.

Side effects

The therapeutic use of azathioprine has been limited by the number and severity of adverse effects associated with its administration. Bone marrow suppression resulting in leukopenia, thrombocytopenia, or both may occur. GI toxicity may be a problem. It is also mildly hepatotoxic. Because of its immunosuppressive activity, azathioprine therapy can lead to serious infections. It has been shown to be mutagenic in animals and humans and carcinogenic in animals.

Safety Profile

Confirmed human carcinogen producing bladder tumors and leukemia. Poison by subcutaneous, intradermal, and intraperitoneal routes. Moderately toxic by ingestion. Human systemic effects: liver changes, hypermotility, diarrhea, nausea or vomiting, increased body temperature, BP lowering, decreased urine volume or anuria, normocytic anemia, bone marrow changes. An experimental teratogen. Other experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits very toxic fumes of NO,xand SOx. An immunosuppressant.

Synthesis

Azathioprine, 6-[(1-methyl-4-nitroimidazol-5-yl)thio]purine (31.2.1), is synthesized by heteroarylation of the sulfhydrile group of 6-mercaptopurine (30.1.2.9) with 5-chloro-1-methyl-4-nitroimidazol in the presence of sodium acetate as a weak base.

Potential Exposure

Azathioprine is an immunosuppressive agent, generally used in combination with a corticosteroid to prevent rejection following renal homotransplantations. It also is used following transplantation of other organs. Other uses of azathioprine include the treatment of a variety of presumed autoimmune diseases, including rheumatoid arthritis; ankylosing spondylitis; systemic lupus erythematosus; dermatonyositis, periarteritis nodosa, scleroderma, refractory thombocytopenic purpura; autoimmune hemolytic anemia; chronic active liver disease; regional enteritis; ulcerative colitis; various autoimmune diseases of the eye; acute and chronic glomerulonephritis; the nephritic syndrome; Wegener’s granulomatosis; and multiple sclerosis.

Veterinary Drugs and Treatments

In veterinary medicine, azathioprine is used primarily as an immunosuppressive agent in the treatment of immune-mediated diseases in dogs. See Doses below for more information. For autoagglutinizing immune mediated hemolytic anemia, azathioprine is generally recommended to start at the time of diagnosis. When used in combination with cyclosporine, azathioprine has been used to prevent rejection of MHC-matched renal allografts in dogs.
Although the drug can be very toxic to bone marrow in cats, it is sometimes used to treat feline autoimmune skin diseases.

Drug interactions

Potentially hazardous interactions with other drugs
Allopurinol: enhances effect with increased toxicity. Reduce azathioprine dose by 50-75% if administered concomitantly - ideally avoid.
Antibacterials: increased risk of haematological toxicity with co-trimoxazole.
Anticoagulants: possibly reduced anticoagulant effect of coumarins.
Antipsychotics: avoid with clozapine.
Antivirals: myelosuppressive effects enhanced by ribavirin.
Ciclosporin: decreased ciclosporin absorption and bioavailability.
Cytotoxics may be additive or synergistic in producing toxicity, particularly on the bone marrow.
Febuxostat: avoid concomitant use.
Vaccines: risk of generalised infections with live vaccines - avoid.

First aid

If this chemical gets into the eyes, remove anycontact lenses at once and irrigate with water or normalsaline immediately for at least 20°30 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts the skin, removecontaminated clothing and wash immediately with soap andwater. Seek medical attention immediately. If this chemicalhas been inhaled, remove from exposure, begin rescuebreathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPR if heart actionhas stopped. Transfer promptly to a medical facility. Whenthis chemical has been swallowed, get medical attention.Give large quantities of water and induce vomiting. Do notmake an unconscious person vomit.

Carcinogenicity

Azathioprine is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans.

Metabolism

Azathioprine is extensively metabolised to its active moiety mercaptopurine, which in turn is activated intracellularly by conversion to nucleotide derivatives. Mercaptopurine is rapidly and extensively metabolised in the liver, by methylation, oxidation and by the formation of inorganic sulfates. Thiol methylation is catalysed by the enzyme thiopurine methyltransferase (TPMT). TPMT activity is highly variable in patients because of a genetic polymorphism in the TPMT gene. About 10% of a dose of azathioprine is reported to be split between the sulfur and the purine ring to give 1-methyl-4-nitro-5-thioimidazole. The proportion of different metabolites is reported to vary between patients. Metabolites and small amounts of unchanged azathioprine and mercaptopurine are eliminated in the urine.

storage

Color Code—Blue: Health Hazard/Poison: Store ina secure poison location. Prior to working with this chemicalyou should be trained on its proper handling and storage.Store in a refrigerator under an inert atmosphere. A regulated, marked area should be established where this chemicalis handled, used, or stored in compliance with OSHAStandard 1910.1045.

Shipping

UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required.

Incompatibilities

Incompatible with reducing agents, such as hydrides (may cause the release of explosive gases), oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong acids (violent exothermic reaction), strong bases.

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Azathioprine Suppliers

Changzhou Yabang Pharmaceutical Co., LTD.
Tel
0519-86388158
Fax
0086-519-86388160
Email
xujian@yabangpharma.com
Country
China
ProdList
80
Advantage
51
Shanghai Boyle Chemical Co., Ltd.
Tel
021-50182298 021-50180596
Fax
+86-21-57758967
Email
sales@boylechem.com
Country
China
ProdList
2210
Advantage
55
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Fax
86-10-82849933
Email
jkinfo@jkchemical.com
Country
China
ProdList
96815
Advantage
76
Meryer (Shanghai) Chemical Technology Co., Ltd.
Tel
4006608290; 18621169109
Fax
86-21-61259102
Email
market03@meryer.com
Country
China
ProdList
40241
Advantage
62
3B Pharmachem (Wuhan) International Co.,Ltd.
Tel
821-50328103-801 18930552037
Fax
86-21-50328109
Email
3bsc@sina.com
Country
China
ProdList
15848
Advantage
69
TCI (Shanghai) Development Co., Ltd.
Tel
021-67121386
Fax
021-67121385
Email
Sales-CN@TCIchemicals.com
Country
China
ProdList
24539
Advantage
81
Energy Chemical
Tel
021-021-58432009 400-005-6266
Fax
021-58436166
Email
sales8178@energy-chemical.com
Country
China
ProdList
44751
Advantage
61
Wuhan Chemwish Technology Co., Ltd
Tel
86-027-67849912
Fax
86-027-87531808
Email
sales@chemwish.com
Country
China
ProdList
35906
Advantage
56
Capot Chemical Co., Ltd
Tel
+86 (0) 571 85 58 67 18
Fax
0086-571-85864795
Email
sales@capotchem.com
Country
China
ProdList
18217
Advantage
66
LGM Pharma
Tel
1-(800)-881-8210
Fax
615-250-9817
Email
inquiries@lgmpharma.com
Country
United States
ProdList
2127
Advantage
70
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View Lastest Price from Azathioprine manufacturers

WUHAN FORTUNA CHEMICAL CO., LTD
Product
Azathioprine 446-86-6
Price
US $0.00/kg
Min. Order
1kg
Purity
98%min
Supply Ability
1000kg
Release date
2023-01-13
Hebei Guanlang Biotechnology Co., Ltd.
Product
Azathioprine 446-86-6
Price
US $0.00-0.00/KG
Min. Order
1KG
Purity
99%
Supply Ability
500000kg
Release date
2023-03-31
Hebei Guanlang Biotechnology Co,.LTD
Product
Azathioprine 446-86-6
Price
US $5.00-2.00/KG
Min. Order
1KG
Purity
99%
Supply Ability
10000kg
Release date
2023-04-26

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