3-[4-nitrophenoxycarbonyl]-1-(4-acetylphenyl)-3-methyltriazene | 1407791-44-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-[4-nitrophenoxycarbonyl]-1-(4-acetylphenyl)-3-methyltriazene
• 英文别名: (4-nitrophenyl) N-[(4-acetylphenyl)diazenyl]-N-methylcarbamate
• CAS: 1407791-44-9
• 化学式: C₁₆H₁₄N₄O₅
• 分子量: 342.311
• InChiKey: YPQJYLVQWDZAEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  117
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-[4-nitrophenoxycarbonyl]-1-(4-acetylphenyl)-3-methyltriazene 在 Pseudomonas sp. E_.C_. 3.4.17.11 carboxypeptidase G₂ 、 苯甲醚 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 53.0h， 生成 1-(4-acetylphenyl)-3-methyltriazene
  参考文献：
  名称：

  Development of triazene prodrugs for ADEPT strategy: New insights into drug delivery system based on carboxypeptidase G2 activation

  摘要：

  Six novel urea triazene prodrugs have been synthesized to apply in antibody-directed enzyme prodrug therapy (ADEPT). The chemical and plasmatic stability of L-glutamate triazene prodrugs were evaluated and the chemical reactivity was mainly attributed to an intramolecular catalysis promoted by the neighbouring carboxylate group of the glutamic moiety. These prodrugs showed an elevated binding to plasma proteins. The L-glutamate triazenes were evaluated as prodrugs of the alkylating agent's monomethyltriazenes, by activation of the bacterial enzyme carboxypeptidase G2 (CPG2). The synthesized prodrugs have been shown to be good substrates for CPG2, and therefore new candidates for ADEPT strategy. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.029
• 作为产物：
  描述：

  1-(4-acetylphenyl)-3-methyltriazene 、 对硝基苯基氯甲酸酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 3-[4-nitrophenoxycarbonyl]-1-(4-acetylphenyl)-3-methyltriazene
  参考文献：
  名称：

  三氮杂化化合物开发中的酪氨酸硫类似物：一种对抗黑色素瘤的新策略

  摘要：

  恶性黑色素瘤是皮肤癌死亡的主要原因。转移性黑色素瘤的治疗仍然是一个巨大的挑战。在这项研究中，我们开发了混合化合物并研究了它们在恶性黑色素瘤化学疗法中的潜在用途。它们被设计为通过双重作用机制发挥作用，由两种药效团组成：酪氨酸硫类似物4- S-半胱氨酚（4-S-CAP，10），具有免疫调节特性和特定的黑素细胞毒性活性，以及​​三氮烯4，具有DNA 烷基化特性。这些化合物的设计旨在通过黑色素瘤细胞中过表达的酪氨酸酶实现选择性激活。化合物11a – e、13a和13b被发现是极好的酪氨酸酶底物 (0.5 min ≤ t 1/2 ≤ 3.7 min)。此外，还评估了衍生物11和13的分子特性、肝毒性、体内毒性特征以及黑色素瘤和非黑色素瘤细胞系中的细胞毒活性评估。将结果与替莫唑胺（一种用于黑色素瘤治疗的三氮烯）获得的结果进行了比较。结果发现，这些杂合体是选择性有效的药物，代表了开发新的多靶点黑色素瘤治

  DOI：

  10.1021/acsmedchemlett.1c00252

文献信息

• Dopamine- and tyramine-based derivatives of triazenes: Activation by tyrosinase and implications for prodrug design
  作者：M. Jesus Perry、Eduarda Mendes、Ana Luísa Simplício、Ana Coelho、Ricardo V. Soares、Jim Iley、Rui Moreira、Ana Paula Francisco

  DOI：10.1016/j.ejmech.2009.03.025

  日期：2009.8

  A range of triazene derivatives were synthesized and investigated as prodrug candidates for melanocyte-directed enzyme prodrug therapy (MDEPT). The prodrugs contained a tyramine or dopamine promoiety required for tyrosinase activation and this was joined via a urea functional group to the cytotoxic triazene. The stability of each of the prodrugs in phosphate buffer, human plasma and in mushroom tyrosinase is discussed. The identification of the main peak formed after the tyrosinase reaction was attempted by LC-MS and the conversion of prodrug to the quinone was confirmed. (C) 2009 Elsevier Masson SAS. All rights reserved.
• Development of triazene prodrugs for ADEPT strategy: New insights into drug delivery system based on carboxypeptidase G2 activation
  作者：Verónica Capucha、Eduarda Mendes、Ana Paula Francisco、M. Jesus Perry

  DOI：10.1016/j.bmcl.2012.09.029

  日期：2012.11

  Six novel urea triazene prodrugs have been synthesized to apply in antibody-directed enzyme prodrug therapy (ADEPT). The chemical and plasmatic stability of L-glutamate triazene prodrugs were evaluated and the chemical reactivity was mainly attributed to an intramolecular catalysis promoted by the neighbouring carboxylate group of the glutamic moiety. These prodrugs showed an elevated binding to plasma proteins. The L-glutamate triazenes were evaluated as prodrugs of the alkylating agent's monomethyltriazenes, by activation of the bacterial enzyme carboxypeptidase G2 (CPG2). The synthesized prodrugs have been shown to be good substrates for CPG2, and therefore new candidates for ADEPT strategy. (C) 2012 Elsevier Ltd. All rights reserved.
• Sulfur Analogues of Tyrosine in the Development of Triazene Hybrid Compounds: A New Strategy against Melanoma
  作者：Margarida Granada、Eduarda Mendes、Maria Jesus Perry、Maria João Penetra、Maria Manuela Gaspar、Jacinta O. Pinho、Sofia Serra、Catarina Teixeira António、Ana Paula Francisco

  DOI：10.1021/acsmedchemlett.1c00252

  日期：2021.11.11

  and 13b were found to be excellent tyrosinase substrates (0.5 min ≤ t1/2 ≤ 3.7 min). Furthermore, derivatives 11 and 13 were evaluated for their molecular properties, hepatotoxicity, in vivo toxicity profile, and assessment of cytotoxic activity in melanoma and non-melanoma cell lines. The results were compared with those obtained for temozolomide, a triazene used in melanoma therapy. It was discovered

  恶性黑色素瘤是皮肤癌死亡的主要原因。转移性黑色素瘤的治疗仍然是一个巨大的挑战。在这项研究中，我们开发了混合化合物并研究了它们在恶性黑色素瘤化学疗法中的潜在用途。它们被设计为通过双重作用机制发挥作用，由两种药效团组成：酪氨酸硫类似物4- S-半胱氨酚（4-S-CAP，10），具有免疫调节特性和特定的黑素细胞毒性活性，以及​​三氮烯4，具有DNA 烷基化特性。这些化合物的设计旨在通过黑色素瘤细胞中过表达的酪氨酸酶实现选择性激活。化合物11a – e、13a和13b被发现是极好的酪氨酸酶底物 (0.5 min ≤ t 1/2 ≤ 3.7 min)。此外，还评估了衍生物11和13的分子特性、肝毒性、体内毒性特征以及黑色素瘤和非黑色素瘤细胞系中的细胞毒活性评估。将结果与替莫唑胺（一种用于黑色素瘤治疗的三氮烯）获得的结果进行了比较。结果发现，这些杂合体是选择性有效的药物，代表了开发新的多靶点黑色素瘤治