2-benzylidenehydrazinecarboximidamide | 3357-37-7

• 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: 2-benzylidenehydrazinecarboximidamide
• 英文别名: Benzylidenamino-guanidin；Benzaldehyd-guanylhydrazon；benzylidene aminoguanidine；benzaldehyde guanylhydrazone；Benzylideneaminoguanidine；2-(benzylideneamino)guanidine
• CAS: 3357-37-7
• 化学式: C₈H₁₀N₄
• mdl: MFCD00276316
• 分子量: 162.194
• InChiKey: WNPXUCYRKHVMAD-UHFFFAOYSA-N

物化性质

• 熔点：
  182 °C
• 沸点：
  284.3±23.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  76.8
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2928000090

反应信息

• 作为反应物：
  描述：

  2-benzylidenehydrazinecarboximidamide 在 碘甲烷 作用下， 生成 N-benzylidenamino-N-methyl-guanidine
  参考文献：
  名称：

  1-(Alkylamino)-guanidines

  摘要：

  DOI：

  10.1021/ja01132a007
• 作为产物：
  描述：

  1-Benzyl-2-guanyl-1-nitroso-hydrazin 在 盐酸 作用下， 以 乙腈 为溶剂， 生成 2-benzylidenehydrazinecarboximidamide
  参考文献：
  名称：

  Synthesis and Reactions of 1-Nitroso-1-alkyl-2-guanyl-and -2-carbamylhydrazines

  摘要：

  DOI：

  10.1021/jo01013a066
• 作为试剂：
  描述：

  2,4,6-三甲氧基苯甲醛 、 Diphenylphosphine oxide 、 丙二腈 在 2-benzylidenehydrazinecarboximidamide 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以84%的产率得到2-((diphenylphosphoryl)(2,4,6-trimethoxyphenyl)methyl)malononitrile
  参考文献：
  名称：

  1,1-二氨基嗪作为磷-迈克尔加成反应中的有机催化剂

  摘要：

  1,1-二氨基嗪可作为有效的有机催化剂，用于在联苯氧化膦和活化的烯烃（迈克尔受体）之间形成磷-碳键。与早期使用的有机催化剂相比，这些催化剂以更快的速度提供 P-C 加合物，并具有相对更好的产率。显着的优点是 1,1-二氨基嗪即使在水性介质中也能以非常好的产率催化反应。在多组分条件下，亚磷酸二甲酯和亚苄基丙二腈之间也成功地进行了使用 1,1-二氨基嗪的有机催化。

  DOI：

  10.1039/d1cc04657h

文献信息

• Reaktionen des Cumalinsäure-methylesters und Cumalinaldehyds mit ambidenten Nucleophilen
  作者：Vratislav Kvita、Hanspeter Sauter、Brian Tuck

  DOI：10.1002/hlca.19880710610

  日期：1988.9.28

  Reactions of Methyl Coumalate and Coumalaldehyde with Ambident Nucleophiles

  香豆酸甲酯和香豆醛醛与环境亲核试剂的反应
• 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。
• Synthesis of nitrogen-containing heterocycles<b>6</b>. Formation and structures of imidazolinones and related compounds through cyclization of diaminomethylenehydrazones with dimethyl acetylenedicarboxylate
  作者：Yoshiko Miyamoto、Chiji Yamazaki

  DOI：10.1002/jhet.5570310626

  日期：1994.11

  Diaminomethylenehydrazones 1 of aromatic and aliphatic carbonyl compounds react with dimethyl acetylenedicarboxylate (DMAD) at room temperature to give four types of heterocycles, (5-oxoimidazolin-4-ylidene) acetates 2, 3 and 6, (2-imino-5-oxoimidazolidin-4-ylidene) acetate 4 and 6-oxo-1,6-dihydropyrimidine-4-carboxylates 5 according to the substitution patterns of 1 in moderate to high yields. Amino

  Diaminomethylenehydrazones 1芳香族和脂肪族羰基化合物与在室温下乙炔二（DMAD）反应，得到四种类型的杂环，（5-oxoimidazolin -4-亚基）乙酸盐2，3和6，（2-亚氨基-5-氧代咪唑烷根据1的取代模式，乙酸4-亚烷基酯4和6-氧代1,6-二氢嘧啶-4-羧酸酯5具有中等至高收率。酮的氨基（N，N-二甲基氨基）亚甲基hydr仅生成（Z）-和（E）-异构体2和3的（5-氧代咪唑啉-4-基-亚乙基）乙酸酯（Z）-异构体2通常占主导地位，而醛基则为5。二氨基和氨基（N-甲基氨基）亚甲基hydr产生5和/或6，而二（N-甲基氨基）亚甲基gives得到（2-亚氨基-5-氧代咪唑啉丁-4-亚烷基）乙酸酯4作为唯一的环化产物。
• Enriching biologically relevant chemical space around 2-aminothiazole template for anticancer drug development
  作者：Sarah Titus、Kumaran G. Sreejalekshmi

  DOI：10.1007/s00044-017-2039-y

  日期：2018.1

  virtual library in anticancer target proteins- estrogen receptor (3ERT), cyclin dependent kinase (3FDN), and Aurora kinase (3LAU), identified selective binding of the compounds as ATP competitive inhibitors of 3LAU. The synthetic access to the compounds was realized through a facile and economically viable [4 + 1] ring synthesis strategy employing commercially available reagents. The in vitro cytotoxicity

  设计了基于生物学相关核心模板2-氨基噻唑的组合文库，该文库具有广泛的多样性多样性，可用于抗癌治疗。使用异丙基，异丁基，环己基和苄基片段，通过在5-苯甲酰基-2-芳基氨基-1,3-噻唑的C4肼末端上的偶氮甲碱键结合多样性元素，并评估其中的化学空间富集。内部的200个成员的虚拟文库在抗癌靶蛋白-雌激素受体（3ERT），细胞周期蛋白依赖性激酶（3FDN）和Aurora激酶（3LAU）中的分子对接确定了化合物作为3LAU ATP竞争性抑制剂的选择性结合。通过使用市售试剂的简便且经济可行的[4 +1]环合成策略可实现对化合物的合成访问。发现2b，3b和4b在小于十微摩尔浓度下对MCF-7和A549细胞系具有活性。此外，预测的理化性质表明这些分子中的大多数都适用于药物，它们遵循5规则（RO5）。因此，我们提出了2-烷基/芳基氨基-4-亚烷基/亚芳基肼基-5-苯甲酰基-1，3-噻唑类化合物作为用于定向合
• 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。