Azathioprine Basic information
Application in Particular Diseases
Product Name: Azathioprine
Synonyms: 6-((1-methyl-4-nitro-1h-imidazol-5-yl)thio)-1h-purin;6-((1-methyl-4-nitroimidazol-5-yl)thio)-purin;6-(1’-methyl-4’-nitro-5’-imidazolyl)-mercaptopurine;6-(1-Methyl-4-nitro-5-imidazolythio)-9H-pur-ine;6-(1-methyl-4-nitroimidazol-5-ylthio)purin;6-(1-methyl-p-nitro-5-imidazolyl)-thiopurine;azamun;azanin
CAS: 446-86-6
MF: C9H7N7O2S
MW: 277.27
EINECS: 207-175-4
Product Categories: Sulphur Derivatives;Purine;Biochemistry;Chemical Reagents for Pharmacology Research;Nucleobases and their analogs;Nucleosides, Nucleotides & Related Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;API's;Miscellaneous Compounds;AZANIN;Pharmaceutical intermediates
Mol File: 446-86-6.mol

Azathioprine Chemical Properties
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.  Freezer
solubility  Soluble in Dichloromethane and dimethyl sulfoxide.
pka 8.2(at 25℃)
form  neat
color  Pale-yellow crystals from Me2CO (aq)
Water Solubility  <0.1 g/100 mL at 23 ºC
Merck  14,902
Stability: Stable. Incompatible with strong oxidizing agents, strong bases.
InChIKey LMEKQMALGUDUQG-UHFFFAOYSA-N
CAS DataBase Reference 446-86-6(CAS DataBase Reference)
EPA Substance Registry System Azathioprine (446-86-6)

Safety Information
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
Hazard Note  Irritant
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

Azathioprine Usage And Synthesis
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.
Chemical Properties Yellow Solid
Chemical Properties Azathioprine is a complex heterocyclic compound which forms pale yellow crystals.
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.
Brand name Imuran (Promethus).
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.
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.
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.
Carcinogenicity Azathioprine is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans.
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.