2-(2-methoxybenzylidene)hydrazinecarboximidamide | 42452-51-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(2-methoxybenzylidene)hydrazinecarboximidamide
• 英文别名: 2-[(2-Methoxyphenyl)methylideneamino]guanidine
• CAS: 42452-51-7
• 化学式: C₉H₁₂N₄O
• mdl: MFCD00989411
• 分子量: 192.22
• InChiKey: NWNHXWIPOLXCLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  86
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-methoxybenzylidene)hydrazinecarboximidamide 、 1,1,1-trifluoro-4-methoxypent-3-en-2-one 以 乙醇 为溶剂， 反应 4.0h， 以94%的产率得到2-(N'-2-methoxy-benzylidenehydrazino)-6-methyl-4-trifluoromethyl-pyrimidine
  参考文献：
  名称：

  Convergent synthesis and cruzain inhibitory activity of novel 2-(N′-benzylidenehydrazino)-4-trifluoromethyl-pyrimidines

  摘要：

  To search for new cruzain inhibitors, the synthesis of a series of novel 2-(N'-benzylidenehydrazino)-4-trifluoromethyl-pyrimidines in a convergent manner is presented. The cruzain inhibitory activity of some of these compounds was evaluated and a binding model was proposed. All derivatives tested were active and the most significant inhibitory effect (80% at 100 mu M) and IC(50) value (85 mu M) were obtained from the 2-(N'-4-chloro-benzylidenehydrazino)-4-trifluoromethyl-pyrimidine. Although further structural optimization to improve solubility is necessary, the molecular docking studies suggest that these inhibitors occupy the S2 pocket without irreversible enzyme inactivation, through hydrophobic interactions, thus, indicating a desirable mode of interaction for the design of novel inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.10.052
• 作为产物：
  描述：

  邻甲氧基苯甲醛 、 氨基胍媒染剂 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 2-(2-methoxybenzylidene)hydrazinecarboximidamide
  参考文献：
  名称：

  Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes

  摘要：

  背景：利什曼病是全球性健康问题，在发展中国家高度流行。在该病的四种主要临床形式中，内脏利什曼病是最严重的，95%的病例会致命。由于一线化疗药物的不良副作用和报道的药物耐药性，迫切需要寻找可以替代或补充当前使用的有效药物。氨基胍脒肼酮（AGH）已被探索用于展示多样的生物活性，特别是MGBG的抗利什曼病活性。生物同功异构体硫脲半胱氨酮（TSC）提供类似的生物活性多样性，包括对利什曼病和克氏锥虫的抗原虫效应。 目的：考虑到利什曼病在全球范围内的影响，本研究旨在设计、合成并对L. chagasi阿马斯蒂果虫进行筛选，以及对小型“内部”AGH和TSC衍生物及其结构相关化合物的细胞毒性进行评估。 方法：首先合成了一组AGH（3-7）、TSC（9, 10）和半胱氨酮（11）。随后，设计并制备了不同的半约束类似物，包括噻唑烷（12）、二氢噻嗪（13）、咪唑烷（15）、嘧啶（16, 18）、吲哚烷（19, 20）和苯并三唑环酮（23-25）。所有中间体和目标化合物均以满意的收率获得，并展示了与其结构一致的光谱数据。所有最终化合物均对L. chagasi阿马斯蒂果虫和J774.A1细胞系进行了评估。使用GOLD®软件对其进行了针对巯基还原酶的分子对接。 结果：AGH的3i、4a和5d以及TSC的9i、9k和9o被选为有价值的命中物。这些化合物与五环胺相比具有抗利什曼病活性，IC50值范围从0.6到7.27μM，最大效果高达55.3％，满意的SI值（范围从11到87）。另一方面，大多数结果的半约束类似物被发现具有细胞毒性或具有降低的抗利什曼病活性。总体而言，TSC类比其同功异构AGH类更有前景，而有益的芳香族取代作用在两个系列中并不相似。计算机模拟研究表明这些命中物能够抑制阿马斯蒂果虫的巯基还原酶。 结论：三种AGH和三种TSC的有前景的抗利什曼病活性得到了表征。这些化合物与PTD相比具有抗利什曼病活性，IC50值范围从0.6到7.27μM，SI值满意。正在进行涉及其他利什曼病菌株的进一步药理学评估，这将有助于选择最佳的命中物进行体内实验。

  DOI：

  10.2174/1573406417666210216154428

文献信息

• Iodine Catalyzed Oxidative Coupling of Diaminoazines and Amines for the Synthesis of 3,5-Disubstituted-1,2,4-Triazoles
  作者：Aabid A. Wani、Sumit S. Chourasiya、Deepika Kathuria、Subash C. Sahoo、Uwe Beifuss、Prasad V. Bharatam

  DOI：10.1021/acs.joc.1c00704

  日期：2021.6.4

  A simple, convenient, transition metal-free one pot synthesis of 3,5-disubstituted-1,2,4-triazoles has been established. The innovation in this reaction is the use of easily available 1,1-diaminoazines as substrates. This method provides the products with wider substrate scope, at an expedited rate, and with relatively better yields in comparison to the reported methods. The reaction mechanism involves

  已经建立了一种简单、方便、不含过渡金属的 3,5-二取代-1,2,4-三唑的一锅合成方法。该反应的创新之处在于使用容易获得的 1,1-二氨基嗪作为底物。与报道的方法相比，该方法以更快的速度为产品提供了更广泛的底物范围和相对更好的产量。反应机理包括初始分子间亲核加成（由 I 2促进），然后是分子内亲核环化。
• Synthesis, Biological Activity Evaluation and Molecular Docking of Imidazole Derivatives Possessing Hydrazone Moiety
  作者：Hüseyin Kekeçmuhammed、Michael Tapera、Ekrem Aydoğdu、Emin Sarıpınar、Elanur Aydin Karatas、Eda Mehtap Uc、Mesut Akyuz、Burak Tüzün、İlhami Gulcin、Rıfat Emin Bora、İlhan Özer İlhan

  DOI：10.1002/cbdv.202200886

  日期：2023.6

  Synthesized compounds were evaluated for their in vitro anticancer (prostate cell lines; PC3) and CA inhibitory (hCA I and hCA II) activity. Among them, some compound displayed remarkable anticancer activity and CA inhibitory activity with Ki values in range of 17.53±7.19–150.50±68.87 nM against cytosolic hCA I isoform associated with epilepsy, and 28.82±14.26–153.27±55.80 nM against dominant cytosolic

  为了鉴定具有低细胞毒性的潜在活性抗癌剂和CA抑制剂，通过氮杂-迈克尔加成反应和分子内环化合成了一系列新的杂化化合物，其中包含咪唑环和腙部分作为其结构的一部分。使用各种光谱技术阐明了合成化合物的结构。评估了合成化合物的体外抗癌（前列腺细胞系；PC3）和 CA 抑制（hCA I 和 hCA II）活性。其中，一些化合物表现出显着的抗癌活性和CA抑制活性，对与癫痫相关的胞质hCA I亚型的K i值在17.53±7.19–150.50±68.87 nM范围内，对主要胞质hCA的K i 值在28.82±14.26–153.27±55.80 nM范围内。与青光眼相关的 II 亚型。此外，还计算了生物活性分子的理论参数以确定其药物相似性。用于计算的蛋白质是前列腺癌蛋白质（PDB ID：3RUK 和 6XXP）。进行 ADME/T 分析以检查所研究分子的药物特性。
• Synthesis, carbonic anhydrase inhibitory activity, anticancer activity and molecular docking studies of new imidazolyl hydrazone derivatives
  作者：Michael Tapera、Hüseyin Kekeçmuhammed、Burak Tüzün、Emin Sarıpınar、Ümit M. Koçyiğit、Ebrar Yıldırım、Murat Doğan、Yunus Zorlu

  DOI：10.1016/j.molstruc.2022.133816

  日期：2022.12
• Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes
  作者：Thiago M. de Aquino、Paulo H. B. França、Érica E. E. S. Rodrigues、Igor. J.S. Nascimento、Paulo F. S. Santos-Júnior、Pedro G. V. Aquino、Mariana S. Santos、Aline C. Queiroz、Morgana V. Araújo、Magna S. Alexandre-Moreira、Raiza R. L. Rodrigues、Klinger A. F. Rodrigues、Johnnatan D. Freitas、Jacques Bricard、Mario R. Meneghetti、Jean-Jacques Bourguignon、Martine Schmitt、Edeildo F. da Silva-Júnior、João X. de Araújo-Júnior

  DOI：10.2174/1573406417666210216154428

  日期：2022.2

  Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi.

  Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "in-house" library of both AGH and TSC derivatives and their structurally-related compounds.

  A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD® software.

  The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC50 values ranged from 0.6 to 7.27 μM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms.

  The promising antileishmanial activity of three AGH’s and three TSC’s was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 μM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are under progress, which will help to choose the best hits for in vivo experiments.

  背景：利什曼病是全球性健康问题，在发展中国家高度流行。在该病的四种主要临床形式中，内脏利什曼病是最严重的，95%的病例会致命。由于一线化疗药物的不良副作用和报道的药物耐药性，迫切需要寻找可以替代或补充当前使用的有效药物。氨基胍脒肼酮（AGH）已被探索用于展示多样的生物活性，特别是MGBG的抗利什曼病活性。生物同功异构体硫脲半胱氨酮（TSC）提供类似的生物活性多样性，包括对利什曼病和克氏锥虫的抗原虫效应。 目的：考虑到利什曼病在全球范围内的影响，本研究旨在设计、合成并对L. chagasi阿马斯蒂果虫进行筛选，以及对小型“内部”AGH和TSC衍生物及其结构相关化合物的细胞毒性进行评估。 方法：首先合成了一组AGH（3-7）、TSC（9, 10）和半胱氨酮（11）。随后，设计并制备了不同的半约束类似物，包括噻唑烷（12）、二氢噻嗪（13）、咪唑烷（15）、嘧啶（16, 18）、吲哚烷（19, 20）和苯并三唑环酮（23-25）。所有中间体和目标化合物均以满意的收率获得，并展示了与其结构一致的光谱数据。所有最终化合物均对L. chagasi阿马斯蒂果虫和J774.A1细胞系进行了评估。使用GOLD®软件对其进行了针对巯基还原酶的分子对接。 结果：AGH的3i、4a和5d以及TSC的9i、9k和9o被选为有价值的命中物。这些化合物与五环胺相比具有抗利什曼病活性，IC50值范围从0.6到7.27μM，最大效果高达55.3％，满意的SI值（范围从11到87）。另一方面，大多数结果的半约束类似物被发现具有细胞毒性或具有降低的抗利什曼病活性。总体而言，TSC类比其同功异构AGH类更有前景，而有益的芳香族取代作用在两个系列中并不相似。计算机模拟研究表明这些命中物能够抑制阿马斯蒂果虫的巯基还原酶。 结论：三种AGH和三种TSC的有前景的抗利什曼病活性得到了表征。这些化合物与PTD相比具有抗利什曼病活性，IC50值范围从0.6到7.27μM，SI值满意。正在进行涉及其他利什曼病菌株的进一步药理学评估，这将有助于选择最佳的命中物进行体内实验。
• Convergent synthesis and cruzain inhibitory activity of novel 2-(N′-benzylidenehydrazino)-4-trifluoromethyl-pyrimidines
  作者：Nilo Zanatta、Simone S. Amaral、Josiane M. dos Santos、Débora L. de Mello、Liana da S. Fernandes、Helio G. Bonacorso、Marcos A.P. Martins、Adriano D. Andricopulo、Deise M. Borchhardt

  DOI：10.1016/j.bmc.2008.10.052

  日期：2008.12.15

  To search for new cruzain inhibitors, the synthesis of a series of novel 2-(N'-benzylidenehydrazino)-4-trifluoromethyl-pyrimidines in a convergent manner is presented. The cruzain inhibitory activity of some of these compounds was evaluated and a binding model was proposed. All derivatives tested were active and the most significant inhibitory effect (80% at 100 mu M) and IC(50) value (85 mu M) were obtained from the 2-(N'-4-chloro-benzylidenehydrazino)-4-trifluoromethyl-pyrimidine. Although further structural optimization to improve solubility is necessary, the molecular docking studies suggest that these inhibitors occupy the S2 pocket without irreversible enzyme inactivation, through hydrophobic interactions, thus, indicating a desirable mode of interaction for the design of novel inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.