替芬泰 | 934264-38-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 替芬泰
• 英文名称: N-[N-benzoyl-O-(2-dimethylaminoethyl)-L-tyrosyl]-L-phenylalaninol
• 英文别名: N-[(2S)-3-[4-[2-(dimethylamino)ethoxy]phenyl]-1-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]benzamide
• CAS: 934264-38-7
• 化学式: C₂₉H₃₅N₃O₄
• 分子量: 489.615
• InChiKey: XWEMGJQQCSSGPN-BDYUSTAISA-N

物化性质

• 沸点：
  763.5±60.0 °C(Predicted)
• 密度：
  1.169±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  90.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  替芬泰 在 4-二甲氨基吡啶 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Process development of clinical anti-HBV drug Y101: identification and synthesis of novel impurities

  摘要：

  本文介绍了在实验室优化过程中以及后来在批量合成过程中观察到的 N-[N-苯甲酰基-O-(2-二甲基氨基乙基)-l-酪氨酰]-l-苯丙氨醇（Y101）的九种新型工艺杂质。对这些杂质进行了高效液相色谱监测，并根据 LC-MS/MS 和 NMR 光谱的碎片模式初步确定了它们的结构。对所有杂质进行了合成，并通过 HPLC 联用进样确认了它们的结构。除了研究杂质的形成、合成和表征外，还介绍了将这些杂质降至国际协调会议（ICH）认可水平的策略。

  DOI：

  10.1007/s11164-015-2169-0
• 作为产物：
  描述：

  N-(N-benzoyl-O-benzoyl-L-tyrosyl)-L-phenylalaninol 在 potassium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 替芬泰
  参考文献：
  名称：

  Identification, Synthesis, and Strategy for Minimization of Potential Impurities in the Preclinical Anti-HBV Drug Y101

  摘要：

  The identification of actual, potential, and theoretical impurities of N-W-benzoyl-O-(2-dimethylaminoethyl)-L-tyrosyl]-L-phenylalaninol (Y101), a preclinical anti-HBV drug, is described in this article. The impurities were monitored by HPLC, and their structures were established on the basis of NMR, IR, and MS. Most of the impurities were synthesized, and their assigned constitutions were confirmed by HPLC co-injection with an ordinary column (Phenomenex Gemini, 250 mm x 4.6 mm, 5 mu m) or a chiral column (DAICEL Chiralcel OD-H). According to the synthetic route, the origins of all of these related impurities were analyzed, and some practical strategies were applied for minimizing these impurities to the level accepted by the International Conference on Harmonization (ICH), and therefore, these strategies can be well applied to the quality control in Y101 clinical sample manufacture.

  DOI：

  10.1021/op400119b

文献信息

• Development of a practical and scalable synthesis of anti-HBV drug Y101
  作者：Zhan-Xing Hu、Yan-Gong Zhang、Qiao An、Bi-Xue Xu、Wei-Dong Pan、Pei-Xue Cao、Chang-Xiao Liu、Zheng-Ming Huang、Wen Xia、Jing-Ying Qiu、Guang-Yi Liang

  DOI：10.1016/j.tet.2014.11.019

  日期：2014.12

  The process research and development of a practical and scalable synthetic method towards Anti-HBV Drug N-[N-benzoyl-O-(2-dimethylaminoethyl)-l-tyrosyl]-l-phenylalaninol (Y101) was described. Initial synthetic routes of Y101 in milligram quantities were unsuitable for large-scale synthesis to provide bulk material. As part of the collaboration between Medicinal Chemistry and Research active pharmaceutical

  描述了针对抗HBV药物N- [ N-苯甲酰基-O-（2-二甲基氨基乙基）-1-酪氨酰基] -1-苯基丙氨醇（Y101）的实用且可扩展的合成方法的工艺研究和开发。Y101的最初合成路线（毫克量）不适合大规模合成以提供块状材料。作为药物化学与研究活性药物成分（API）之间合作的一部分，Y101千克级合成的合适途径发展了。相反，这里描述的改进的路线不需要所有步骤都通过柱色谱法纯化，并且有效地抑制了杂质的形成。Y101的大规模合成成功地证明了这种高效且可扩展的过程。
• Identification, Synthesis, and Strategy for Minimization of Potential Impurities in the Preclinical Anti-HBV Drug <b>Y101</b>
  作者：Zhanxing Hu、Qiao An、Kunfeng Li、Yangong Zhang、Jingying Qiu、Bixue Xu、Weidong Pan、Peixue Cao、Changxiao Liu、Zhengming Huang、Wen Xia、Guangyi Liang

  DOI：10.1021/op400119b

  日期：2013.9.20

  The identification of actual, potential, and theoretical impurities of N-W-benzoyl-O-(2-dimethylaminoethyl)-L-tyrosyl]-L-phenylalaninol (Y101), a preclinical anti-HBV drug, is described in this article. The impurities were monitored by HPLC, and their structures were established on the basis of NMR, IR, and MS. Most of the impurities were synthesized, and their assigned constitutions were confirmed by HPLC co-injection with an ordinary column (Phenomenex Gemini, 250 mm x 4.6 mm, 5 mu m) or a chiral column (DAICEL Chiralcel OD-H). According to the synthetic route, the origins of all of these related impurities were analyzed, and some practical strategies were applied for minimizing these impurities to the level accepted by the International Conference on Harmonization (ICH), and therefore, these strategies can be well applied to the quality control in Y101 clinical sample manufacture.
• Process development of clinical anti-HBV drug Y101: identification and synthesis of novel impurities
  作者：Zhanxing Hu、HaiJian Liao、Qiao An、Weidong Pan、Peixue Cao、Changxiao Liu、Zhengming Huang、Wen Xia、Bixue Xu、Guangyi Liang

  DOI：10.1007/s11164-015-2169-0

  日期：2016.3

  Nine novel process impurities of N-[N-benzoyl-O-(2-dimethylaminoethyl)-l-tyrosyl]-l-phenylalaninol (Y101) observed during the laboratory optimization and later during its bulk synthesis are described in this article. The impurities were monitored by HPLC, and their structures were tentatively assigned on the basis of fragmentation patterns in LC−MS/MS and NMR spectroscopies. All of the impurities were synthesized, and their assigned constitutions were confirmed by co-injection in HPLC. In addition to the formation, synthesis, and characterization, the strategy for minimizing these impurities to a level accepted by the International Conference on Harmonisation (ICH) was also described.

  本文介绍了在实验室优化过程中以及后来在批量合成过程中观察到的 N-[N-苯甲酰基-O-(2-二甲基氨基乙基)-l-酪氨酰]-l-苯丙氨醇（Y101）的九种新型工艺杂质。对这些杂质进行了高效液相色谱监测，并根据 LC-MS/MS 和 NMR 光谱的碎片模式初步确定了它们的结构。对所有杂质进行了合成，并通过 HPLC 联用进样确认了它们的结构。除了研究杂质的形成、合成和表征外，还介绍了将这些杂质降至国际协调会议（ICH）认可水平的策略。