478182-28-4

• 常用中文名：盐酸茚罗西生
• 常用英文名：R-1479
• CAS号：478182-28-4
• 分子式：C₉H₁₂N₆O₅
• 分子量：284.229
• 相关类别： 化学试剂 有机试剂 叠氮
• 发布时间：2018-08-26 18:38:15
• 更新时间：2024-01-09 00:15:03
• R-1479 是一种特异性的HCV复制 (HCV replication) 抑制剂，在HCV亚基因组复制体系中，IC₅₀ 为 1.28 μM。

名称

• 中文名: 盐酸茚罗西生
• 英文名: 4-amino-1-[(2R,3R,4S,5R)-5-azido-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
• 英文别名: 4-amino-1-[(2R,3R,4S,5R)-5-azido-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2(1H)-one (non-preferred name); R-1479||4'-Azidocytidine|R1479; CS-0362; 4'-azidocytidine; 4'azidocytidine; R1479; 4-Amino-1-[(2R,3R,4S,5R)-5-azido-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyrimidinone; R-1479

物化性质

• 分子式: C₉H₁₂N₆O₅
• 分子量: 284.229
• 精确质量: 284.086914
• PSA: 181.57000
• LogP: -0.20
• 储存条件: -20°C

生物活性

• 描述: R-1479 是一种特异性的HCV复制 (HCV replication) 抑制剂,在HCV亚基因组复制体系中,IC50 为 1.28 μM。
• 相关类别:
  信号通路 >> 抗感染 >> HCV
  研究领域 >> 感染
• 靶点:

  IC50: 1.28 μM (HCV replication)[1]

• 体外研究: 当在增殖的复制子细胞孵育72小时后作为剂量依赖性的Renillaluciferase活性降低测量时,R-1479(R1479)抑制HCV RNA复制,平均IC 50值为1.28μM。 R-1479对浓度高达2mM的HCV复制子或Huh-7细胞的细胞存活率或增殖没有影响[1]。最有效和非细胞毒性的衍生物是R-1479,在HCV复制子系统中IC50为1.28μM。制备R-1479的三磷酸盐,并显示其是由NS5B介导的RNA合成的抑制剂(IC50 = 320nM),由HCV编码的RNA聚合酶。 R-1479在复制子测定中显示出良好的活性,没有可测量的细胞毒性或细胞抑制作用[2]。
• 激酶实验: 膜结合的天然HCV复制酶复合物从2209-23 HCV复制子细胞和携带HCV复制子RNA的衍生细胞系中分离，所述HCV复制子RNA在NS5B编码序列中具有S282T突变。体外复制酶测定包含10μL细胞质膜级分，50 mM HEPES（pH 7.5），10 mM KCl，10 mM二硫苏糖醇，5 mM MgCl2,20μg/ mL放线菌素D，1 mM ATP，1 mM GTP，1 mM UTP，30μCi[α-33P] CTP（3000 Ci / mmol，10 mCi / mL），1单位/μLSUPERase•In，10 mM肌酸磷酸盐和200μg/ mL肌酸磷酸激酶，终体积25μL 。确定核苷酸类似物的抑制[1]。
• 细胞实验: 使用[3H]胸苷掺入闪烁亲近测定系统测量R-1479对氚标记的胸苷掺入细胞DNA的影响。 MTT和WST-1测定系统用于测量细胞活力。 ATP生物发光检测试剂盒HSII用于测量细胞内ATP水平[1]。
• 参考文献:

  [1]. Klumpp K, et al. The novel nucleoside analog R1479 (4'-azidocytidine) is a potent inhibitor of NS5B-dependent RNA synthesis and hepatitis C virus replication in cell culture. J Biol Chem. 2006 Feb 17;281(7):3793-9.

  [2]. Smith DB, et al. Design, synthesis, and antiviral properties of 4'-substituted ribonucleosides as inhibitors of hepatitis C virus replication: the discovery of R1479. Bioorg Med Chem Lett. 2007 May 1;17(9):2570-6.

合成路线

690270-27-0 ~% 478182-28-4

文献：Smith, David B.; Martin, Joseph A.; Klumpp, Klaus; Baker, Stewart J.; Blomgren, Peter A.; Devos, Rene; Granycome, Caroline; Hang, Julie; Hobbs, Christopher J.; Jiang, Wen-Rong; Laxton, Carl; Pogam, Sophie Le; Leveque, Vincent; Ma, Han; Maile, Graham; Merrett, John H.; Pichota, Arkadius; Sarma, Keshab; Smith, Mark; Swallow, Steven; Symons, Julian; Vesey, David; Najera, Isabel; Cammack, Nick Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 9 p. 2570 - 2576

690271-25-1 ~% 478182-28-4

文献：Smith, David B.; Martin, Joseph A.; Klumpp, Klaus; Baker, Stewart J.; Blomgren, Peter A.; Devos, Rene; Granycome, Caroline; Hang, Julie; Hobbs, Christopher J.; Jiang, Wen-Rong; Laxton, Carl; Pogam, Sophie Le; Leveque, Vincent; Ma, Han; Maile, Graham; Merrett, John H.; Pichota, Arkadius; Sarma, Keshab; Smith, Mark; Swallow, Steven; Symons, Julian; Vesey, David; Najera, Isabel; Cammack, Nick Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 9 p. 2570 - 2576

478182-26-2 ~% 478182-28-4

文献：Smith, David B.; Martin, Joseph A.; Klumpp, Klaus; Baker, Stewart J.; Blomgren, Peter A.; Devos, Rene; Granycome, Caroline; Hang, Julie; Hobbs, Christopher J.; Jiang, Wen-Rong; Laxton, Carl; Pogam, Sophie Le; Leveque, Vincent; Ma, Han; Maile, Graham; Merrett, John H.; Pichota, Arkadius; Sarma, Keshab; Smith, Mark; Swallow, Steven; Symons, Julian; Vesey, David; Najera, Isabel; Cammack, Nick Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 9 p. 2570 - 2576

139442-01-6 ~% 478182-28-4

文献：Smith, David B.; Martin, Joseph A.; Klumpp, Klaus; Baker, Stewart J.; Blomgren, Peter A.; Devos, Rene; Granycome, Caroline; Hang, Julie; Hobbs, Christopher J.; Jiang, Wen-Rong; Laxton, Carl; Pogam, Sophie Le; Leveque, Vincent; Ma, Han; Maile, Graham; Merrett, John H.; Pichota, Arkadius; Sarma, Keshab; Smith, Mark; Swallow, Steven; Symons, Julian; Vesey, David; Najera, Isabel; Cammack, Nick Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 9 p. 2570 - 2576

139419-04-8 ~% 478182-28-4

文献：Smith, David B.; Martin, Joseph A.; Klumpp, Klaus; Baker, Stewart J.; Blomgren, Peter A.; Devos, Rene; Granycome, Caroline; Hang, Julie; Hobbs, Christopher J.; Jiang, Wen-Rong; Laxton, Carl; Pogam, Sophie Le; Leveque, Vincent; Ma, Han; Maile, Graham; Merrett, John H.; Pichota, Arkadius; Sarma, Keshab; Smith, Mark; Swallow, Steven; Symons, Julian; Vesey, David; Najera, Isabel; Cammack, Nick Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 9 p. 2570 - 2576

139419-02-6 ~% 478182-28-4

文献：Smith, David B.; Martin, Joseph A.; Klumpp, Klaus; Baker, Stewart J.; Blomgren, Peter A.; Devos, Rene; Granycome, Caroline; Hang, Julie; Hobbs, Christopher J.; Jiang, Wen-Rong; Laxton, Carl; Pogam, Sophie Le; Leveque, Vincent; Ma, Han; Maile, Graham; Merrett, John H.; Pichota, Arkadius; Sarma, Keshab; Smith, Mark; Swallow, Steven; Symons, Julian; Vesey, David; Najera, Isabel; Cammack, Nick Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 9 p. 2570 - 2576

14365-63-0 ~% 478182-28-4

文献：Smith, David B.; Martin, Joseph A.; Klumpp, Klaus; Baker, Stewart J.; Blomgren, Peter A.; Devos, Rene; Granycome, Caroline; Hang, Julie; Hobbs, Christopher J.; Jiang, Wen-Rong; Laxton, Carl; Pogam, Sophie Le; Leveque, Vincent; Ma, Han; Maile, Graham; Merrett, John H.; Pichota, Arkadius; Sarma, Keshab; Smith, Mark; Swallow, Steven; Symons, Julian; Vesey, David; Najera, Isabel; Cammack, Nick Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 9 p. 2570 - 2576

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