3-[2-(acetylamino)-3-(4-hydroxyphenyl)propanoyl]-1-(4-cyanophenyl)-3-methyltriazene

• 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
• 英文名称: 3-[2-(acetylamino)-3-(4-hydroxyphenyl)propanoyl]-1-(4-cyanophenyl)-3-methyltriazene
• 英文别名: (2S)-2-acetamido-N-[(4-cyanophenyl)diazenyl]-3-(4-hydroxyphenyl)-N-methylpropanamide
• 化学式: C₁₉H₁₉N₅O₃
• 分子量: 365.392
• InChiKey: RJZIDTKXPLXVGL-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[2-(acetylamino)-3-(4-hydroxyphenyl)propanoyl]-1-(4-cyanophenyl)-3-methyltriazene 在 4-二甲氨基吡啶 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 酪氨酸酶 作用下， 以 aq. phosphate buffer 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 3-[2-(N-Boc)-3-(4-hydroxyphenyl)propanoyl]-1-(4-cyanophenyl)-3-methyltriazene
  参考文献：
  名称：

  Synthesis and evaluation of N-acylamino acids derivatives of triazenes. Activation by tyrosinase in human melanoma cell lines

  摘要：

  In this research work we report the synthesis of a new series of triazene prodrugs designed for Melanocyte-Directed Enzyme Prodrug Therapy (MDEPT). These compounds are derived from the N-acyltyrosine amino acid a good enzyme substrate for the tyrosinase enzyme, which is significantly overexpressed in melanoma cells. We analysed their chemical stability and plasma enzymatic hydrolysis, and we also evaluated the release of the antitumoral drug in the presence of the tyrosinase. Subsequently, we performed the evaluation of the prodrug cytotoxicity in melanoma cell lines with different levels of tyrosinase activity. Prodrug 5c showed the highest cytotoxicity against melanoma cell lines, and this effect correlated well with the tyrosinase activity suggesting that prodrug cytotoxicity is tyrosinase-dependent. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.040
• 作为产物：
  描述：

  N-乙酰-L-酪氨酸 在 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 49.0h， 生成 3-[2-(acetylamino)-3-(4-hydroxyphenyl)propanoyl]-1-(4-cyanophenyl)-3-methyltriazene
  参考文献：
  名称：

  Synthesis and evaluation of N-acylamino acids derivatives of triazenes. Activation by tyrosinase in human melanoma cell lines

  摘要：

  In this research work we report the synthesis of a new series of triazene prodrugs designed for Melanocyte-Directed Enzyme Prodrug Therapy (MDEPT). These compounds are derived from the N-acyltyrosine amino acid a good enzyme substrate for the tyrosinase enzyme, which is significantly overexpressed in melanoma cells. We analysed their chemical stability and plasma enzymatic hydrolysis, and we also evaluated the release of the antitumoral drug in the presence of the tyrosinase. Subsequently, we performed the evaluation of the prodrug cytotoxicity in melanoma cell lines with different levels of tyrosinase activity. Prodrug 5c showed the highest cytotoxicity against melanoma cell lines, and this effect correlated well with the tyrosinase activity suggesting that prodrug cytotoxicity is tyrosinase-dependent. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.040

文献信息

• Synthesis and evaluation of N-acylamino acids derivatives of triazenes. Activation by tyrosinase in human melanoma cell lines
  作者：Ana Sofia Monteiro、Joana Almeida、Guadalupe Cabral、Paulo Severino、Paula A. Videira、Ana Sousa、Rafael Nunes、João D. Pereira、Ana Paula Francisco、M. Jesus Perry、Eduarda Mendes

  DOI：10.1016/j.ejmech.2013.09.040

  日期：2013.12

  In this research work we report the synthesis of a new series of triazene prodrugs designed for Melanocyte-Directed Enzyme Prodrug Therapy (MDEPT). These compounds are derived from the N-acyltyrosine amino acid a good enzyme substrate for the tyrosinase enzyme, which is significantly overexpressed in melanoma cells. We analysed their chemical stability and plasma enzymatic hydrolysis, and we also evaluated the release of the antitumoral drug in the presence of the tyrosinase. Subsequently, we performed the evaluation of the prodrug cytotoxicity in melanoma cell lines with different levels of tyrosinase activity. Prodrug 5c showed the highest cytotoxicity against melanoma cell lines, and this effect correlated well with the tyrosinase activity suggesting that prodrug cytotoxicity is tyrosinase-dependent. (C) 2013 Elsevier Masson SAS. All rights reserved.