3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine
• 英文别名: [(2s,3s,5r)-3-Azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl pyridine-4-carboxylate；[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl pyridine-4-carboxylate
• 化学式: C₁₆H₁₆N₆O₅
• 分子量: 372.34
• InChiKey: OYFFXILVYKNQTK-YNEHKIRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine 以 phosphate buffer 为溶剂， 生成 异烟酸 、 齐多夫定
  参考文献：
  名称：

  3′-Azido-3′-deoxy-5′-O-isonicotinoylthymidine: A Novel Antiretroviral Analog of Zidovudine. II. Stability in Aqueous Media and Experimental and Theoretical Ionization Constants

  摘要：

  Degradation of 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine (AZT-Iso), an antiretroviral derivative of zidovudine, was investigated in buffer pH 7.4, mu = 300 mOsm at 37, 50 and 60degreesC, and in water (pH 6.6, 37degreesC), giving zidovudine (AZT) and isonicotinic acid (INA) as products. The rate constants were determined by reversed-phase HPLC showing pseudo-first-order kinetics related to the residual amount of AZT-Iso. In this way, the studied compound was demonstrated to be 153 times more stable in water than in buffer solution at 37degreesC. The analytical method was conveniently validated demonstrating to be a rapid and accurate stability-indicating technique. In addition, experimental and theoretical values of pKa were determined.

  DOI：

  10.1081/ncn-120023273
• 作为产物：
  描述：

  齐多夫定 、 氯化异氰盐酸盐 在 吡啶 作用下， 反应 0.25h， 以72.96%的产率得到3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine
  参考文献：
  名称：

  3′-AZIDO-3′-DEOXY-5′-O-ISONICOTINOYLTHYMIDINE, A NEW PRODRUG OF ZIDOVUDINE. SYNTHESIS, SOLID STATE CHARACTERIZATION AND ANTI HIV-1 ACTIVITY

  摘要：

  Synthesis, solid state characterization and anti HIV-1 activity of 3'azido-3'-deoxy-5'-O-isonicotinoylthymidine (2), a new prodrug of zidovudine (AZT, 1), are described. Two solid forms of 2 prepared by crystallization from ethyl acetate-petroleum ether (form x) and from a melt sample of form a (amorphous form) were characterized by X-ray diffractometry, infrared spectroscopy, differential scanning calorimetry (DSC) and thermogravimetry (TGA) techniques. The novel nucleoside exhibited antiviral activity against standard and resistant strain panels of HIV-1 as well as cytotoxicity similar to that of AZT.

  DOI：

  10.1081/ncn-120003287

文献信息

• 3′-Azido-3′-deoxy-5′-O-isonicotinoylthymidine: A Novel Antiretroviral Analog of Zidovudine. II. Stability in Aqueous Media and Experimental and Theoretical Ionization Constants
  作者：Silvina A. Teijeiro、Mónica A. Raviolo、Marisa I. Motura、Margarita C. Briñón

  DOI：10.1081/ncn-120023273

  日期：2003.10

  Degradation of 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine (AZT-Iso), an antiretroviral derivative of zidovudine, was investigated in buffer pH 7.4, mu = 300 mOsm at 37, 50 and 60degreesC, and in water (pH 6.6, 37degreesC), giving zidovudine (AZT) and isonicotinic acid (INA) as products. The rate constants were determined by reversed-phase HPLC showing pseudo-first-order kinetics related to the residual amount of AZT-Iso. In this way, the studied compound was demonstrated to be 153 times more stable in water than in buffer solution at 37degreesC. The analytical method was conveniently validated demonstrating to be a rapid and accurate stability-indicating technique. In addition, experimental and theoretical values of pKa were determined.
• 3′-AZIDO-3′-DEOXY-5′-O-ISONICOTINOYLTHYMIDINE, A NEW PRODRUG OF ZIDOVUDINE. SYNTHESIS, SOLID STATE CHARACTERIZATION AND ANTI HIV-1 ACTIVITY
  作者：Marisa I. Motura、Guillermo N. Moroni、Silvina A. Teijeiro、Horacio Salomón、Margarita C. Briñón

  DOI：10.1081/ncn-120003287

  日期：2002.4.15

  Synthesis, solid state characterization and anti HIV-1 activity of 3'azido-3'-deoxy-5'-O-isonicotinoylthymidine (2), a new prodrug of zidovudine (AZT, 1), are described. Two solid forms of 2 prepared by crystallization from ethyl acetate-petroleum ether (form x) and from a melt sample of form a (amorphous form) were characterized by X-ray diffractometry, infrared spectroscopy, differential scanning calorimetry (DSC) and thermogravimetry (TGA) techniques. The novel nucleoside exhibited antiviral activity against standard and resistant strain panels of HIV-1 as well as cytotoxicity similar to that of AZT.