1-(4-cyanophenyl)-3-methyltriazene | 51029-20-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-cyanophenyl)-3-methyltriazene
• 英文别名: 1-p-Cyanophenyl-3-methyltriazen；1(3)-(p-Cyanophenyl)-3(1)-methyltriazen；4-(2-methyliminohydrazinyl)benzonitrile
• CAS: 51029-20-0
• 化学式: C₈H₈N₄
• 分子量: 160.178
• InChiKey: MOOVONBFLRIJPF-UHFFFAOYSA-N

物化性质

• 沸点：
  287.8±42.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  60.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-cyanophenyl)-3-methyltriazene 在 吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 72.0h， 生成 ditert-butyl (2S)-2-[[[(4-cyanophenyl)diazenyl]-methylcarbamoyl]amino]pentanedioate
  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-cyanophenyl)-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-cyanophenyl)-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

• Triazene drug metabolites. Part 17: synthesis and plasma hydrolysis of acyloxymethyl carbamate derivatives of antitumour triazenes
  作者：Emı́lia Carvalho、Ana Paula Francisco、Jim Iley、Eduarda Rosa

  DOI：10.1016/s0968-0896(00)00100-0

  日期：2000.7

  contribute to the hydrolysis reaction. The sensitivity of the hydrolysis reaction to various structural parameters in the substrates indicates that hydrolysis occurs at the ester rather than the carbamate functionality. In plasma, the rates of hydrolysis correlate with partition coefficients, the most lipophilic compounds being the most stable. An aspirin derivative suffers two consecutive enzymatic reactions

  通过1-芳基-3-甲基三氮烯与（i）氯甲基氯甲酸酯，（ii）NaI在无水丙酮中和（iii）的顺序反应合成一系列3-酰氧基甲氧基羰基-1-芳基-3-甲基三氮烯5在碳酸银存在下的羧酸银或羧酸。在pH 7.7等渗磷酸盐缓冲液和人体血浆中研究了这些化合物的水解。三氮烯酰氧基氨基甲酸酯显示出其充当血浆酶底物的能力。对于化合物5f，获得pH速率曲线，其显示水解涉及酸碱催化。该反应也是缓冲液催化的。因此，在pH 7.7时，非pH依赖性，碱催化和缓冲液催化过程均有助于水解反应。水解反应对底物中各种结构参数的敏感性表明水解发生在酯而不是氨基甲酸酯官能团上。在血浆中，水解速率与分配系数相关，亲脂性最高的化合物最稳定。阿司匹林衍生物经历两个连续的酶促反应，阿斯匹林乙酰基的断裂随后是酰氧基酯基的断裂。这些结果表明三氮烯酰氧基甲基氨基甲酸酯是抗肿瘤单甲基三氮烯的前药。它们将化学稳定性与快速酶水解结合在一起，因此是进
• 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）。
• Targeting Gliomas: Can a New Alkylating Hybrid Compound Make a Difference?
  作者：Rui Pinheiro、Cláudia Braga、Gisela Santos、Maria R. Bronze、Maria J. Perry、Rui Moreira、Dora Brites、Ana S. Falcão

  DOI：10.1021/acschemneuro.6b00169

  日期：2017.1.18

  highly invasive and resistant nature of GBM. Hybrid compounds may open new horizons within this challenge. The multicomponent therapeutic strategy here used resides on a combination of two repurposing drugs acting by different but potentially synergistic mechanisms, improved efficacy, and lower resistance effects. We synthesized a new hybrid compound (HYBCOM) by covalently binding a TMZ analogue to valproic

  胶质母细胞瘤（GBM）是成人中最常见和侵略性的脑肿瘤。三氮唑替莫唑胺（TMZ）是一种烷基化药物，是胶质瘤的经典化学治疗剂，但对于GBM的高度侵袭性和耐药性一直令人失望。杂化化合物可能会在这一挑战中开辟新的视野。此处使用的多组分治疗策略取决于两种通过不同但潜在的协同机制起作用，具有更高疗效和更低抗药性的再利用药物的组合。我们通过将TMZ类似物与丙戊酸共价结合而合成了一种新的杂合化合物（HYBCOM），丙戊酸是一种组蛋白脱乙酰基酶抑制剂药物，已被证明对TMZ耐药神经胶质瘤细胞敏感。就化疗功效而言，研究了这种新分子与TMZ相比的优势。我们的结果证明，HYBCOM可以更有效地降低GL261神经胶质瘤细胞的活力和增殖，同时表现出比功能正常的星形胶质细胞更好地靶向肿瘤细胞。HYBCOM增加的细胞毒性可能是观察到的自噬过程改善的结果。此外，HYBCOM将GL261细胞的形态改变为非极性，更圆的形状，从而