72559-06-9

• 常用中文名：利福布汀
• 常用英文名：Rifabutin
• CAS号：72559-06-9
• 分子式：C₄₆H₆₂N₄O₁₁
• 分子量：847.005
• 相关类别： 原料药 抗生素类药物 利福霉素类药
• 发布时间：2018-05-15 08:00:00
• 更新时间：2024-01-02 19:26:48
• 【用途1】
  原料药（抗结核、抗艾滋病毒抗生素）
  【用途2】
  为利福霉素的螺旋哌啶衍生物，对结核杆菌的抑制作用比利福平约强4倍。主要用于分歧杆菌的肺部感染，对利福平耐药的结核杆菌菌株有效，可用于耐药，复治结核病例，细胞内分歧杆菌感染及爱滋病的治疗。
  【用途3】
  利福霉素衍生物，有抗利福平耐药结核菌株的作用。所需浓度仅为利福平的1/40。毒性小于利福平。日本将其用于非典型结核菌感染的治疗。对耐药麻风病也有效。预防艾滋病人鸟结核分枝杆菌感染。

名称

• 中文名: 利福布丁
• 英文名: Rifabutin
• 中文别名: 利福布汀; 利福布汀(安莎霉素); 4-N-异丁基螺哌啶利福霉素 S; 螺哌啶利福霉素S; 4-脱氧-3,4-[2-螺(N-异丁基-4-哌啶基)]-(1H)-咪唑并-(2,5-双氢)利福霉素S
• 英文别名: Rifabutin; 4-deoxo-3,4-[2-spiro(N-isobutyl-4-piperidyl)-2,5-dihydro-1H-imidazo]-rifamicin S; Ansamycin; RIFABUTINE; Mycobutin; lm427; Rifabatin; antibioticlm427; 1',4-didehydro-1-desoxi-1,4-di-hydro-5'-(2-methyl-propyl)-1-oxo-rifamycin; Ansatipine; 6,9-dihydro-5,17,19,21-tetrahydroxy-8,9-[2-spiro-(N-isobutyl-4-piperidyl)-2,5-dihydro-1H-imidazo]-23-methoxy-2,4,12,16,18,20,22-heptamethyl-6-oxo-2,7-epoxypentadeca-[1,11,13]-trienimine-2H-furo[2',3',7,8]nafto[1,2-d]imidazolo-2,4'-piperidine-5,10,26. (3H,9H)-trione-16-acetate

物化性质

• 密度: 1.3±0.1 g/cm3
• 沸点: 969.6±65.0 °C at 760 mmHg
• 熔点: 169-171ºC
• 分子式: C₄₆H₆₂N₄O₁₁
• 分子量: 847.005
• 闪点: 540.2±34.3 °C
• 精确质量: 846.441528
• PSA: 205.55000
• LogP: 3.45
• 外观性状: 红色-紫罗兰色结晶粉末
• 蒸汽压: 0.0±0.3 mmHg at 25°C
• 折射率: 1.623
• 储存条件: Amber Vial, -20°C Freezer, Under Inert Atmosphere
• 水溶解性: DMSO: >5mg/mL

生物活性

• 描述: Rifabutin (Ansamycin) 是半合成的安莎霉素抗生素,具有抗分枝杆菌特性。
• 相关类别:
  信号通路 >> 抗感染 >> 细菌
  研究领域 >> 感染
• 靶点:

  Antibacterial

• 体外研究: 利福布丁主要是用于治疗结核病的杀菌抗生素药物。它对细菌的作用是基于DNA依赖性RNA聚合酶阻断药物利福霉素S.,一种半合成衍生物。例如,它在高抗性分枝杆菌,革兰氏阳性菌(和一些对革兰氏阴性菌有效)中有效,但也对结核分枝杆菌,麻风杆菌和胞内分枝杆菌有效。利福布丁是一种抗生素;抗肿瘤。利福布汀干扰HSP-90分子伴侣,增强泛素化和蛋白质降解,并使细菌RNA聚合酶失活。
• 参考文献:

  [1]. Review Article: Rifabutin in the Treatment of Refractory Helicobacter pylori Infection J. P. Gisbert, X. Calvet Issue Alimentary Pharmacology & Therapeutics Volume 35, Issue 2, pages 209-221, January 2012

  [2]. Vourvahis M, Davis J, Wang R, Layton G, Choo HW, Chong CL, Tawadrous M.Effect of rifampin and rifabutin on the pharmacokinetics of lersivirine and effect of lersivirine on the pharmacokinetics of rifabutin and 25-o-desacetyl-rifabutin in healthy subjects.Antimicrob Agents Chemother. 2012 Aug;56(8):4303-9.

  [3]. Gisbert JP, Castro-Fernandez M, Perez-Aisa A, Cosme A, Molina-Infante J, Rodrigo L, Modolell I, Cabriada JL, Gisbert JL, Lamas E, Marcos E, Calvet X.Fourth-line rescue therapy with rifabutin in patients with three Helicobacter pylori eradication failures.Aliment Pharmacol Ther. 2012 Apr;35(8):941-7. doi: 10.1111/j.1365-2036.2012.05053.x.

  [4]. Gisbert JP, Calvet X.Review article: rifabutin in the treatment of refractory Helicobacter pylori infection.Aliment Pharmacol Ther. 2012 Jan;35(2):209-21. doi: 10.1111/j.1365-2036.2011.04937.x.

  [5]. Horne DJ, Spitters C, Narita M.Experience with rifabutin replacing rifampin in the treatment of tuberculosis.Int J Tuberc Lung Dis. 2011 Nov;15(11):1485-9, i.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : VJ6700000 CHEMICAL NAME : Rifamycin XIV, 1,4-dihydro-1-deoxy-1',4-didehydro-5'-(2-methylpropyl )-1-oxo- CAS REGISTRY NUMBER : 72559-06-9 LAST UPDATED : 199709 DATA ITEMS CITED : 11 MOLECULAR FORMULA : C46-H62-N4-O11 MOLECULAR WEIGHT : 847.12 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human - man DOSE/DURATION : 60 mg/kg/14D-I TOXIC EFFECTS : Blood - agranulocytosis REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 348,685,1996 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human - woman DOSE/DURATION : 84 mg/kg/14D-I TOXIC EFFECTS : Blood - agranulocytosis REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 348,685,1996 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) REFERENCE : ETPAEK Experimental and Toxicologic Pathology. (Gustav Fischer Verlag Jena, Postfach 100537, D-07705 Jena, Germany) V.44- 1992- Volume(issue)/page/year: 47,1,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 51 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea REFERENCE : ETPAEK Experimental and Toxicologic Pathology. (Gustav Fischer Verlag Jena, Postfach 100537, D-07705 Jena, Germany) V.44- 1992- Volume(issue)/page/year: 47,1,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 3322 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) REFERENCE : ETPAEK Experimental and Toxicologic Pathology. (Gustav Fischer Verlag Jena, Postfach 100537, D-07705 Jena, Germany) V.44- 1992- Volume(issue)/page/year: 47,1,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 266 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea REFERENCE : ETPAEK Experimental and Toxicologic Pathology. (Gustav Fischer Verlag Jena, Postfach 100537, D-07705 Jena, Germany) V.44- 1992- Volume(issue)/page/year: 47,1,1995 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ETPAEK Experimental and Toxicologic Pathology. (Gustav Fischer Verlag Jena, Postfach 100537, D-07705 Jena, Germany) V.44- 1992- Volume(issue)/page/year: 47,1,1995 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE/DURATION : >4 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ETPAEK Experimental and Toxicologic Pathology. (Gustav Fischer Verlag Jena, Postfach 100537, D-07705 Jena, Germany) V.44- 1992- Volume(issue)/page/year: 47,1,1995 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 9100 mg/kg/13W-C TOXIC EFFECTS : Liver - other changes Kidney, Ureter, Bladder - other changes Blood - changes in spleen REFERENCE : ETPAEK Experimental and Toxicologic Pathology. (Gustav Fischer Verlag Jena, Postfach 100537, D-07705 Jena, Germany) V.44- 1992- Volume(issue)/page/year: 47,1,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 29120 mg/kg/1Y-I TOXIC EFFECTS : Blood - normocytic anemia Endocrine - changes in spleen weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases REFERENCE : ETPAEK Experimental and Toxicologic Pathology. (Gustav Fischer Verlag Jena, Postfach 100537, D-07705 Jena, Germany) V.44- 1992- Volume(issue)/page/year: 47,1,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 47 mg/kg/1Y-C TOXIC EFFECTS : Blood - normocytic anemia Blood - changes in spleen Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) REFERENCE : ETPAEK Experimental and Toxicologic Pathology. (Gustav Fischer Verlag Jena, Postfach 100537, D-07705 Jena, Germany) V.44- 1992- Volume(issue)/page/year: 47,1,1995

安全

• 个人防护装备: Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
• 危险品运输编码: NONH for all modes of transport
• RTECS号: VJ6700000
• 海关编码: 2941903000

制备

【方法1】
以1，4-二氢利福霉素S为原料，经溴化，亚硝基取代，氢化，氨化，再和N-异丁基哌啶酮反应，即可得到利福布汀。

海关

海关编码	2941903000