77181-69-2

• 常用中文名：索立夫定
• 常用英文名：Sorivudine
• CAS号：77181-69-2
• 分子式：C₁₁H₁₃BrN₂O₆
• 分子量：349.13500
• 相关类别： 信号通路 细胞周期/DNA损伤 DNA/RNA合成
• 发布时间：2018-07-23 18:34:09
• 更新时间：2024-01-11 22:23:38
• Sorivudine (BV-araU) 是一种口服活性的,合成的嘧啶核苷抗代谢 (pyrimidine nucleoside antimetabolite) 药物。Sorivudine 的抗病毒活性来自某些 DNA 病毒中存在的特定胸苷激酶 (thymidine kinase) 选择性转化为核苷酸,从而反过来会干扰病毒 DNA 合成 (DNA synthesis)。

名称

• 中文名: 索立夫定
• 英文名: Sorivudine
• 英文别名: Bravavir; Bravavir (tn); Sorivudin; YN-72; Brovavir; BV-araU

物化性质

• 密度: 1.979g/cm3
• 熔点: 182 °C
• 分子式: C₁₁H₁₃BrN₂O₆
• 分子量: 349.13500
• 精确质量: 347.99600
• PSA: 124.78000
• 折射率: 1.746
• 储存条件: 2-8°C

生物活性

• 描述: Sorivudine (BV-araU) 是一种口服活性的,合成的嘧啶核苷抗代谢 (pyrimidine nucleoside antimetabolite) 药物。Sorivudine 的抗病毒活性来自某些 DNA 病毒中存在的特定胸苷激酶 (thymidine kinase) 选择性转化为核苷酸,从而反过来会干扰病毒 DNA 合成 (DNA synthesis)。
• 相关类别:
  研究领域 >> 感染
  信号通路 >> 细胞周期/DNA损伤 >> DNA/RNA合成
• 体外研究: 索里夫定(BV-araU)对ID50s(50%抑制剂量)分别为0.39μM和0.67μM的HSV-1和HSV-2(野生型VR-3和UW-268)的抑制作用[1]。索里夫定对水痘-带状疱疹病毒、单纯疱疹1型病毒和爱泼斯坦-巴尔病毒等几种病毒具有抗病毒活性[1]。索里夫定(BV-araU)是一种嘧啶核苷类似物,对水痘带状疱疹病毒(VZV)有体外抑制作用,其浓度为00001-0.004 mg/ml,比阿昔洛韦3抑制VZV复制所需浓度低1000倍以上浓度范围为0.03-0.1 mg/ml[2]。
• 体内研究: 索里夫定(BV-araU)经口给药治疗HSV-l脑炎。当剂量超过12.5mg/kg时,治疗小鼠的存活时间延长。当剂量超过50mg/kg时,死亡率显著降低(we1l),一个更相关的模型是非洲绿猴(cerophiccus aethiops)的猴水痘病毒感染。在这个系统中,索里夫定的治疗剂量低至20毫克/千克/天肌肉注射或100毫克/千克/天口服完全防止病毒血症和死亡率。在进行这些研究时,没有证据表明血液学或临床化学方面存在神经毒性或异常。低至每天0.2毫克/千克的剂量是有效的；然而,低剂量时出现突破性病毒血症[2]。
• 参考文献:

  [1]. Diasio RB, et al. Sorivudine and 5-fluorouracil; a clinically significant drug-drug interaction due to inhibition of dihydropyrimidine dehydrogenase. Br J Clin Pharmacol. 1998 Jul;46(1):1-4.

  [2]. Whitley RJ, et al. Sorivudine: a potent inhibitor of varicella zoster virus replication.Adv Exp Med Biol. 1996;394:41-4.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : UV9009810 CHEMICAL NAME : 2,4(1H,3H)-Pyrimidinedione, 1-beta-D-arabinofuranosyl-5-(2-bromoethenyl)-, (E)- CAS REGISTRY NUMBER : 77181-69-2 LAST UPDATED : 199503 DATA ITEMS CITED : 15 MOLECULAR FORMULA : C11-H13-Br-N2-O6 MOLECULAR WEIGHT : 349.17 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >8 gm/kg TOXIC EFFECTS : Gastrointestinal - other changes TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Kidney, Ureter, Bladder - other changes in urine composition TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Kidney, Ureter, Bladder - other changes in urine composition TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >3 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 72800 mg/kg/26W-C TOXIC EFFECTS : Liver - other changes Endocrine - hyperglycemia Blood - changes in cell count (unspecified) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 112 gm/kg/4W-I TOXIC EFFECTS : Liver - changes in liver weight Kidney, Ureter, Bladder - changes in bladder weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 45 gm/kg/4W-C TOXIC EFFECTS : Cardiac - EKG changes not diagnostic of specified effects TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 182 gm/kg/26W-C TOXIC EFFECTS : Endocrine - other changes Blood - changes in spleen Related to Chronic Data - death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 22 gm/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - other developmental abnormalities TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 500 mg/kg SEX/DURATION : female 17-20 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Newborn - live birth index (measured after birth) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1625 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death MUTATION DATA TYPE OF TEST : Sister chromatid exchange TEST SYSTEM : Human Lymphocyte DOSE/DURATION : 200 mg/L REFERENCE : LIFSAK Life Sciences. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1-8, 1962-69; V.14- 1974- Volume(issue)/page/year: 38,281,1986

合成路线

95119-95-2 ~22% 77181-69-2

文献：RESprotech GmbH Patent: US2010/227834 A1, 2010 ; Location in patent: Page/Page column 20 ;

87877-27-8 ~% 77181-69-2

文献：Baraldi, Pier G.; Bazzanini, Rita; Manfredini, Stefano; Simoni, Daniele; Robins, Morris J. Tetrahedron Letters, 1993 , vol. 34, # 19 p. 3177 - 3180

132054-88-7 ~% 77181-69-2

文献：Baraldi, Pier G.; Bazzanini, Rita; Manfredini, Stefano; Simoni, Daniele; Robins, Morris J. Tetrahedron Letters, 1993 , vol. 34, # 19 p. 3177 - 3180

86359-94-6 ~% 77181-69-2

文献：Robins; Manfredini Tetrahedron Letters, 1990 , vol. 31, # 39 p. 5633 - 5636

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