1-(4-acetylphenyl)-3-methyltriazene | 51029-21-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-acetylphenyl)-3-methyltriazene
• 英文别名: 1-p-Acetylphenyl-3-methyltriazen；1(3)-(p-Acetylphenyl)-3-methyltriazen；1-[4-(2-methyliminohydrazinyl)phenyl]ethanone
• CAS: 51029-21-1
• 化学式: C₉H₁₁N₃O
• 分子量: 177.206
• InChiKey: ZMVPYGSBZJKCAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  53.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2914399090

反应信息

• 作为反应物：
  描述：

  1-(4-acetylphenyl)-3-methyltriazene 在 吡啶 、 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 77.0h， 生成 (2S)-2-[[[(4-acetylphenyl)diazenyl]-methylcarbamoyl]amino]pentanedioic acid
  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：

  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

文献信息

• Targeting gliomas with triazene-based hybrids: Structure-activity relationship, mechanistic study and stability
  作者：Cláudia Braga、Ana R. Vaz、M. Conceição Oliveira、M. Matilde Marques、Rui Moreira、Dora Brites、Maria J. Perry

  DOI：10.1016/j.ejmech.2019.03.048

  日期：2019.6

  Herein we report novel hybrid compounds based on valproic acid and DNA-alkylating triazene moieties, 1, with therapeutic potential for glioblastoma multiforme chemotherapy. We identified hybrid compounds 1d and 1e to be remarkably more potent against glioma and more efficient in decreasing invasive cell properties than temozolomide and endowed with chemical and plasma stability. In contrast to temozolomide

  本文中，我们报告了基于丙戊酸和DNA-烷基化三氮烯部分1的新型杂合化合物，具有治疗成胶质细胞瘤多形式化学疗法的潜力。我们确定杂合化合物1d和1e与替莫唑胺相比，对神经胶质瘤的效力显着增强，并且在降低侵袭性细胞特性方面更有效，并且具有化学和血浆稳定性。与替莫唑胺发生水解以释放出烷基化代谢产物相反，丙戊酸酯杂化物显示出低的烷基化DNA潜力。关键的理化特性与CNS的最佳渗透率相吻合，突显了这些有效的基于三氮烯的杂化物在增强抗癌化学疗法方面的潜力。
• Towards an efficient prodrug of the alkylating metabolite monomethyltriazene: Synthesis and stability of N-acylamino acid derivatives of triazenes
  作者：Maria de Jesus Perry、Emília Carvalho、Eduarda Rosa、Jim Iley

  DOI：10.1016/j.ejmech.2008.06.022

  日期：2009.3

  A series of 3-[α-(acylamino)acyl]-1-aryl-3-methyltriazenes 6a–l, potential cytotoxic triazene prodrugs, were synthesised by coupling 1-aryl-3-methyltriazenes to N-acylamino acids. Their hydrolysis was studied in isotonic pH 7.4 phosphate buffer and in human plasma, while hydrolysis of the derivative 6a was studied in more depth across a range of pH values. Prodrugs 6a–l hydrolyse by cleavage of the

  通过将1-芳基-3-甲基三氮烯与N-酰基氨基酸偶联，合成了一系列3- [α-（酰基氨基）酰基] -1-芳基-3-甲基三氮烯6a - 1，潜在的细胞毒性三氮烯前药。在等渗pH 7.4磷酸盐缓冲液和人血浆中研究了它们的水解，而在一系列pH值范围内更深入地研究了衍生物6a的水解。前药6a – l通过裂解三氮烯酰基水解得到相应的单甲基三氮烯。在人体血浆中的研究表明，氨基酸载体的α-氨基的酰化是降低α-氨基酰基衍生物的化学反应性同时保持快速酶水解速率的有效手段。这些衍生物显示出log  P值，表明它们应该被生物膜很好地吸收。
• The selective cytotoxicity of new triazene compounds to human melanoma cells
  作者：Ana Sousa、Fábio Santos、Maria Manuela Gaspar、Susana Calado、João D. Pereira、Eduarda Mendes、Ana Paula Francisco、Maria Jesus Perry

  DOI：10.1016/j.bmc.2017.04.049

  日期：2017.8

  human plasma (1.5 ≤ t½ (h) ≤ 161). Compounds 3c–n revealed to be excellent tyrosinase substrates (0.74 ≤ t½ (min) ≤ 6) with the best tyrosinase substrate 3l releasing MMT 45 s after tyrosinase activation. Structure-activity relationship studies allowed the identification of the better structural features for enzyme affinity. Furthermore, the derivatives 3l and 3m showed cell selectivity with significant

  转移性黑色素瘤仍然是最难克服的癌症之一。我们研究的目的是设计用于黑素瘤特异性疗法的抗肿瘤三氮烯化合物3。该策略利用了黑色素生物合成的独特酶途径，将无毒前药转化为黑素瘤细胞中的有毒药物。通过偶联两个活性部分，烷基化三氮烯和不同的酪氨酸酶底物来设计化合物3。所有化合物3在生理pH（t½≥48  h）时在等渗磷酸盐缓冲液（PBS）中化学稳定，并且大多数化合物在人血浆中缓慢水解（1.5≤t½（h）≤161）。化合物3c –n显示出优异的酪氨酸酶底物（0.74≤t1 /2（min）≤6），最佳酪氨酸酶底物3l在酪氨酸酶活化后释放MMT 45s。结构-活性关系研究允许鉴定更好的酶亲和力结构特征。此外，衍生物3l和3m对具有酪氨酸酶过表达MNT-1和B16F10的黑色素瘤细胞系具有明显的细胞毒性作用（IC 50值为46–65μM）。
• Suzuki Coupling of Activated Aryltriazenes for Practical Synthesis of Biaryls from Anilines
  作者：Dongsheng Guo、Weijia Shi、Gang Zou

  DOI：10.1002/adsc.202200433

  日期：2022.7.19

  palladium-catalyzed Suzuki coupling of aryltriazenes activated by a sulfonyl group at N3 atom under the common basic conditions. Benefiting from elimination of stoichiometric acid activators, activated aryltriazenes could efficiently couple with arylboronic acids to afford diaryls in modest to excellent yields by using a simple catalyst at low loading, 0.3 mol% Pd(PPh3)2Cl2. Scope and limitation of the coupling are

  除非使用化学计量的布朗斯台德或路易斯酸活化剂，否则芳基三氮烯几乎不能参与生产性有机转化。我们在这里首次报道了在普通碱性条件下由 N3 原子上的磺酰基活化的芳基三氮烯的钯催化 Suzuki 偶联。得益于化学计量酸活化剂的消除，活化的芳基三氮烯可以有效地与芳基硼酸偶联，通过使用低负载量的简单催化剂（0.3 mol% Pd(PPh 3 ) 2 Cl 2 ）以中等至优异的产率提供二芳基化合物。通过 26 个示例演示了耦合的范围和限制。
• 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