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

• ChemBase编号: 867
• 分子式: C9H7N7O2S
• 平均质量: 277.26258
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 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传统名: azathioprine; AZA; immuran
• 商标名: Azasan; Ccucol; Imuran; Imurek; Imurel; Muran; Azamun; Azanin; Azasan, Imuran and others
• 别名: 6-[(1-甲基-4-硝基-1H-咪唑-5-基)硫代]-1H-嘌呤; 硫唑嘌呤; 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

登记号

• CAS号: 446-86-6
• EC号: 207-175-4
• MDL号: MFCD00055974; MFCD00069203
• PubChem SID: 24278074; 24890673; 160964330; 46508252
• PubChem CID: 2265
• CHEBI ID: 2948
• ATC码: L04AX01
• CHEMBL: 1542
• Chemspider ID: 2178
• DrugBank ID: DB00993
• KEGG ID: D00238
• 美国药典/FDA物质标识码: MRK240IY2L
• 维基百科标题: Azathioprine
• Medline Plus: a682167

理论计算性质

JChem

• Acid pKa: 8.645115
• 质子受体: 6
• 质子供体: 1
• LogD (pH = 5.5): 1.1594115
• LogD (pH = 7.4): 1.1514583
• Log P: 1.173144
• 摩尔折射率: 70.9462 cm^3
• 极化性: 25.458958 Å^3
• 极化表面积: 118.1 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 0.84
• LOG S: -2.41
• 溶解度: 1.07e+00 g/l

分子性质

理化性质

• 溶解度: 272 mg/L; DMSO
• 外观: Yellow Solid
• 熔点: 238-245 °C (460.4-473°F); 251-253°C
• 疏水性(logP): 0.7

安全信息

• 保存条件: 0°C, Protect from light; -20°C; -20°C Freezer
• 保存注意事项: IRRITANT
• RTECS编号: UO8925000
• 欧盟危险性物质标志: 有毒(Toxic) (T)
• 联合国危险货物编号: 2811
• 德国WGK号: 3
• 联合国危险货物等级: 6.1
• 联合国危险货物包装类别(PG): III
• 澳大利亚Hazchem: 2X
• 危险公开号: 45-22-36/37/38; R:22-45
• 安全公开号: 22-26-36/37-45; S:28-36/37/39-45-53
• 欧盟危险货物分类: T2
• 欧盟危险识别号(EUHIN): 6.1B
• 美国ERG指导号: 154
• TSCA收录: false
• GHS危险品标识: GHS07; GHS08
• GHS警示词: Danger
• GHS危险声明: H302-H315-H319-H335-H350
• GHS警示性声明: P201-P261-P305 + P351 + P338-P308 + P313
• 个人保护装置: 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
• 保存温度: -20°C

药理学性质

• 给药途径: Mainly oral (sometimes initially intravenous)
• 生物利用度: 60±31%
• 排泄: Renal, 98% as metabolites
• 半衰期: 26–80 minutes (azathioprine); 3–5 hours (drug plus metabolites)
• 代谢: Activated non-enzymatically, deactivated mainly by xanthine oxidase
• 蛋白结合率: 20–30%
• 法定药品分级: Rx-only
• 妊娠期药物分类: D (Australia); D (US)
• 美国（FDA）药品许可证: azathioprine

产品相关信息

• 纯度: >95%; ≥98%
• 成盐信息: Free Base
• 适用性: meets USP testing specifications

详细说明

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.

参考文献

• 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,)