6-[(1-methyl-4-nitro-1H-imidazol-5-yl)sulfanyl]-7H-purine

• ChemBase ID: 867
• Molecular Formular: C9H7N7O2S
• Molecular Mass: 277.26258
• Monoisotopic Mass: 277.0381935
• SMILES: S(c1n(cnc1[N+](=O)[O-])C)c1ncnc2nc[nH]c12
• Canonical SMILES: Cn1cnc(c1Sc1ncnc2c1[nH]cn2)[N+](=O)[O-]
• InChI: InChI=1S/C9H7N7O2S/c1-15-4-14-7(16(17)18)9(15)19-8-5-6(11-2-10-5)12-3-13-8/h2-4H,1H3,(H,10,11,12,13)
• InChIKey: LMEKQMALGUDUQG-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 6-[(1-methyl-4-nitro-1H-imidazol-5-yl)sulfanyl]-7H-purine; 6-[(1-methyl-4-nitro-1H-imidazol-5-yl)sulfanyl]-9H-purine
• IUPAC Traditional name: azathioprine; AZA; immuran
• Brand Name: Azasan; Ccucol; Imuran; Imurek; Imurel; Muran; Azamun; Azanin; Azasan, Imuran and others
• Synonyms: 6-[(1-Methyl-4-nitro-1H-imidazol-5-yl)thio]-1H-purine; Azanin; Imurek; Imurel; Zytrim; Azathioprine Sodium; Azathioprin; Azothioprine; Azatioprin; Azathioprine; Azasan; Imuran; Azamun; BW-57-322; NSC-39084; 6-[(1-Methyl-4-nitroimidazol-5-yl)-thio] purine; Azathioprine; 6-[(1-甲基-4-硝基-1H-咪唑-5-基)硫代]-1H-嘌呤; 硫唑嘌呤

Database IDs

• CAS Number: 446-86-6
• EC Number: 207-175-4
• MDL Number: MFCD00055974; MFCD00069203
• PubChem SID: 24890673; 160964330; 24278074; 46508252
• PubChem CID: 2265
• CHEBI ID: 2948
• ATC CODE: L04AX01
• CHEMBL: 1542
• Chemspider ID: 2178
• DrugBank ID: DB00993
• KEGG ID: D00238
• Unique Ingredient Identifier: MRK240IY2L
• Wikipedia Title: Azathioprine
• Medline Plus: a682167

CALCULATED PROPERTIES

JChem

• Acid pKa: 8.645115
• H Acceptors: 6
• H Donor: 1
• LogD (pH = 5.5): 1.1594115
• LogD (pH = 7.4): 1.1514583
• Log P: 1.173144
• Molar Refractivity: 70.9462 cm^3
• Polarizability: 25.458958 Å^3
• Polar Surface Area: 118.1 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.84
• LOG S: -2.41
• Solubility (Water): 1.07e+00 g/l

PROPERTIES

Physical Property

• Solubility: 272 mg/L; DMSO
• Apperance: Yellow Solid
• Melting Point: 238-245 °C (460.4-473°F); 251-253°C
• Hydrophobicity(logP): 0.7

Safety Information

• Storage Condition: 0°C, Protect from light; -20°C; -20°C Freezer
• Storage Warning: IRRITANT
• RTECS: UO8925000
• European Hazard Symbols: Toxic (T)
• UN Number: 2811
• German water hazard class: 3
• Hazard Class: 6.1
• Packing Group: III
• Australian Hazchem: 2X
• Risk Statements: 45-22-36/37/38; R:22-45
• Safety Statements: 22-26-36/37-45; S:28-36/37/39-45-53
• EU Classification: T2
• EU Hazard Identification Number: 6.1B
• Emergency Response Guidebook(ERG) Number: 154
• TSCA Listed: false
• GHS Pictograms: GHS07; GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H302-H315-H319-H335-H350
• GHS Precautionary statements: P201-P261-P305 + P351 + P338-P308 + P313
• Personal Protective Equipment: Eyeshields, Faceshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• Storage Temperature: -20°C

Pharmacology Properties

• Admin Routes: Mainly oral (sometimes initially intravenous)
• Bioavailability: 60±31%
• Excretion: Renal, 98% as metabolites
• Half Life: 26–80 minutes (azathioprine); 3–5 hours (drug plus metabolites)
• Metabolism: Activated non-enzymatically, deactivated mainly by xanthine oxidase
• Protein Bound: 20–30%
• Legal Status: Rx-only
• Pregnancy Category: D (Australia); D (US)
• US Licence: azathioprine

Product Information

• Purity: >95%; ≥98%
• Salt Data: Free Base
• Suitability: meets USP testing specifications

DETAILS

MP Biomedicals - 02191364

Crystalline
Immunosuppresive and cytostatic agent.

DrugBank - DB00993

• Drug Groups: approved
• Description: An immunosuppressive pro-drug. It is converted into 6-mercaptopurine in the body where it blocks purine metabolism and DNA synthesis.
• Indication: For use in rheumatoid arthritis, preventing renal transplant rejection, Crohn's disease, and colitis.
• Pharmacology: Azathioprine is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation and autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease or Crohn's disease. It is a pro-drug, converted in the body to the active metabolite 6-mercaptopurine. Azathioprine acts to inhibit purine synthesis necessary for the proliferation of cells, especially leukocytes and lymphocytes. It is a safe and effective drug used alone in certain autoimmune diseases, or in combination with other immunosuppressants in organ transplantation. Its most severe side effect is bone marrow suppression, and it should not be given in conjunction with purine analogues such as allopurinol. The enzyme thiopurine S-methyltransferase (TPMT) deactivates 6-mercaptopurine. Genetic polymorphisms of TPMT can lead to excessive drug toxicity, thus assay of serum TPMT may be useful to prevent this complication.
• Toxicity: The oral LD₅₀ for single doses of azathioprine in mice and rats are 2500 mg/kg and 400 mg/kg, respectively. Very large doses of this antimetabolite may lead to marrow hypoplasia, bleeding, infection, and death.
• Affected Organisms: Humans and other mammals
• Biotransformation: Primarily converted to the active metabolites 6-mercaptopurine and 6-thioinosinic acid via a non-enzymatica process. 6-mercaptopurine is subsequently metabolized primarily by xanthine oxidase.
• Absorption: Well absorbed following oral administration.
• Half Life: Approximately 5 hours for the unchanged drug and its metabolites.
• Protein Binding: Azathioprine and the metabolite mercaptopurine are moderately bound to serum proteins (30%).
• References: Konstantopoulou M, Belgi A, Griffiths KD, Seale JR, Macfarlane AW: Azathioprine-induced pancytopenia in a patient with pompholyx and deficiency of erythrocyte thiopurine methyltransferase. BMJ. 2005 Feb 12;330(7487):350-1. [Pubmed] ; Woodroffe R, Yao GL, Meads C, Bayliss S, Ready A, Raftery J, Taylor RS: Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study. Health Technol Assess. 2005 May;9(21):1-179, iii-iv. [Pubmed] ; Gombar VK, Enslein K, Blake BW: Carcinogenicity of azathioprine: an S-AR investigation. Mutat Res. 1993 May;302(1):7-12. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1721

Research Area: Immunology
Biological Activity:
Azathioprine(Azasan, Imuran) is a drug that suppresses the immune system. Azathioprine is used in organ transplantation and autoimmune disease. Azathioprine is used in organ transplantation and autoimmune disease. Azathioprine interferes with the synthesis of purines (adenine and guanine), which is required for DNA synthesis. Fast-growing cells, including T-cells and B-cells, are particularly affected by the inhibition of purine synthesis. [1]

Sigma Aldrich - A4638

Biochem/physiol Actions
Has shown promise in treatment of alopecia areata (autoimmune hair loss), with no difference in effectiveness between genders.1

Toronto Research Chemicals - A803350

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

REFERENCES

• Konstantopoulou M, Belgi A, Griffiths KD, Seale JR, Macfarlane AW: Azathioprine-induced pancytopenia in a patient with pompholyx and deficiency of erythrocyte thiopurine methyltransferase. BMJ. 2005 Feb 12;330(7487):350-1. Pubmed
• Woodroffe R, Yao GL, Meads C, Bayliss S, Ready A, Raftery J, Taylor RS: Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study. Health Technol Assess. 2005 May;9(21):1-179, iii-iv. Pubmed
• Gombar VK, Enslein K, Blake BW: Carcinogenicity of azathioprine: an S-AR investigation. Mutat Res. 1993 May;302(1):7-12. Pubmed
• http://en.wikipedia.org/wiki/Azathioprine
• Mitrou, P.S., et al.: Arzneim.-Forsch., 29, 483, 662 (1979)
• Ding, T.L., et al.: Drug. Metab. Dispos., 7, 373 (1979)
• Chan, G.L.C., et al.: Pharmacotherapy, 7, 165 (1979)
• Sandborn, W.J., et al.: : Scand. J. Gastroenterol., 33, Suppl. 225, 92 (1998,)