Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohns disease, ulcerative colitis, and systemic lupus erythematosus, and in kidney transplants to prevent rejection. It is listed by the International Agency for Research on Cancer as a group 1 carcinogen (carcinogenic to humans). It is taken by mouth or injected into a vein.Common side effects include bone-marrow suppression and vomiting. Bone-marrow suppression is especially common in people with a genetic deficiency of the enzyme thiopurine S-methyltransferase. Other serious risk factors include an increased risk of certain cancers. Use during pregnancy may result in harm to the baby. Azathioprine is in the purine analogue and antimetabolite family of medications. It works via 6-thioguanine to disrupt the making of RNA and DNA by cells.Azathioprine was first made in 1957. It is on the World Health Organizations List of Essential Medicines. In 2017, it was the 335th-most commonly prescribed medication in the United States, with more than 800,000 prescriptions. Medical uses
Azathioprine is used alone or in combination with other immunosuppressive therapy to prevent rejection following organ transplantation, and to treat an array of autoimmune diseases, including rheumatoid arthritis, pemphigus, systemic lupus erythematosus, Behçets disease, and other forms of vasculitis, autoimmune hepatitis, atopic dermatitis, myasthenia gravis, neuromyelitis optica (Devics disease), restrictive lung disease, and others.
Because actively replicating cells (such as cancer cells and the T cells and B cells of the immune system) are most active in synthesizing purine, making new DNA, these cells are most strongly affected. A portion of the nucleotides is additionally phosphorylated to the triphosphate forms. These  bind to GTP-binding protein Rac1, blocking synthesis of the protein Bcl-xL, thus sending activated T cells and mononuclear cells into apoptosis (programmed cell death). Increased apoptosis of mononuclear cells is seen in inflammatory bowel disease patients treated with azathioprine. Chemistry
Azathioprine is a thiopurine linked to a second heterocycle (an imidazole derivative) via a thioether. It is a pale yellow solid with a slightly bitter taste and a melting point of 238–245 °C. It is practically insoluble in water and only slightly soluble in lipophilic solvents such as chloroform, ethanol, and diethylether. It dissolves in alkaline aqueous solutions, where it hydrolyzes to 6-mercaptopurine.Azathioprine is synthesized from 5-chloro-1-methyl-4-nitro-1H-imidazole and 6-mercaptopurine in dimethyl sulfoxide. The synthesis of the former starts with an amide from methylamine and diethyl oxalate, which is then cyclized and chlorinated with phosphorus pentachloride; the nitro group is introduced with nitric and sulfuric acid. History
Azathioprine was synthesized by George Herbert Hitchings and Gertrude Elion in 1957 (named BW 57-322) to produce 6-MP in a metabolically active, but masked form, and at first used as a chemotherapy drug.Robert Schwartz investigated the effect of 6-MP on the immune response in 1958 and discovered that it profoundly suppresses the formation of antibodies when given to rabbits together with antigens.