(E)-N'-(4-hydroxybenzylidene)benzohydrazide | 31083-62-2

• 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: (E)-N'-(4-hydroxybenzylidene)benzohydrazide
• 英文别名: N-[(E)-(4-hydroxyphenyl)methylideneamino]benzamide
• CAS: 31083-62-2
• 化学式: C₁₄H₁₂N₂O₂
• 分子量: 240.261
• InChiKey: SOGSNJSJOSFZAI-XNTDXEJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  61.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-N'-(4-hydroxybenzylidene)benzohydrazide 在 chloroamine-T 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以75%的产率得到2-(4-hydroxyphenyl)-5-phenyl-1,3,4-oxadiazole
  参考文献：
  名称：

  新型双(1,3,4-恶二唑)的合成、抗菌活性和计算机研究

  摘要：

  摘要 在目前的研究中，高效地制备了与脂肪核相连的新型双（2,5-二取代 1,3,4-恶二唑）。为此，适当的双（醛）和苯甲酰肼反应生成相应的双（N-苯甲酰腙）。使用不同的试剂、溶剂和反应温度优化了先前中间体的氧化环化。在 80 °C 下，三当量氯胺-T 在乙醇中 3 小时产生目标双 (1,3,4-恶二唑) 的良好收率。使用环丙沙星作为参考（MIC 值为 2.9 µM），筛选了新的双（1,3,4-恶二唑）对六种革兰氏阳性和阴性菌株的抗菌活性。混合动力车4a和4b对金黄色葡萄球菌菌株的 MIC 值分别为 7.3 和 7.2 µM，对铜绿假单胞菌菌株的 MIC 值分别为 14.7 和 14.3 µM 。SwissADME、药物相似性模型评分、生物活性评分和分子对接也用于验证一些新杂种作为潜在抗菌药物和 DNA 促旋酶抑制剂的活性。

  DOI：

  10.1080/00397911.2022.2095211
• 作为产物：
  描述：

  苯甲酸 在 硫酸 、 一水合肼 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 2.0h， 生成 (E)-N'-(4-hydroxybenzylidene)benzohydrazide
  参考文献：
  名称：

  Modulation of estrogen-related receptors subtype selectivity: Conversion of an ERRβ/γ selective agonist to ERRα/β/γ pan agonists

  摘要：

  Estrogen Related Receptors (ERRs) are key regulators of energy homeostasis and play important role in the etiology of metabolic disorders, skeletal muscle related disorders, and neurodegenerative diseases. Among the three ERR isoforms, ERR alpha emerged as a potential drug target for metabolic and neurodegenerative diseases. Although ERR beta/gamma selective agonist chemical tools have been identified, there are no chemical tools that effectively target ERR alpha agonism. We successfully engineered high affinity ERR alpha agonism into a chemical scaffold that displays selective ERR beta/gamma agonist activity (GSK4716), providing novel ERR alpha/beta/gamma pan agonists that can be used as tools to probe the physiological roles of these nuclear receptors. We identified the structural requirements to enhance selectivity toward ERR alpha. Molecular modeling shows that our novel modulators have favorable binding modes in the LBP of ERR alpha and can induce conformational changes where Phe328 that originally occupies the pocket is dislocated to accommodate the ligands in a rather small cavity. The best agonists up-regulated the expression of target genes PGC-1 alpha and PGC-1 beta, which are necessary to achieve maximal mitochondrial biogenesis. Moreover, they increased the mRNA levels of PDK4, which play an important role in energy homeostasis.

  DOI：

  10.1016/j.bioorg.2020.104079

文献信息

• Synthesis, biological evaluation, drug-likeness, and in silico screening of novel benzylidene-hydrazone analogues as small molecule anticancer agents
  作者：Mohammad Sayed Alam、Dong-Ung Lee

  DOI：10.1007/s12272-015-0699-z

  日期：2016.2

  A series of fifteen benzylidene-hydrazone analogues (3a–o), including eight new compounds, were synthesized and evaluated for their cytotoxic activities in four human cancer cell lines and for their antioxidant activities using DPPH. Of the tested compounds 3e, which possesses two methoxy substituents in its benzylidene phenyl ring, was found to be potently cytotoxic to all cancer cell lines tested with IC50 values of 0.12 (lung), 0.024 (ovarian), 0.097 (melanoma), and 0.05 μM (colon), and these IC50 values were comparable to those of the doxorubicin standard (IC50 = 0.021, 0.074, 0.001, and 0.872 μM, respectively). DPPH assay showed compounds 3f, 3i, and 3g had IC50 values of 0.60, 0.99, and 1.30 μM, respectively, which were comparable to that of ascorbic acid (IC50 = 0.87 μM). Computational parameters such as, drug-likeness, ADME properties, toxicity effects, and drug scores were evaluated, and none of the fifteen compounds violated Lipinski’s rule of five or Veber’s rule, and thus they demonstrated good drug-likeness properties. In addition, all fifteen compounds had a higher drug score than the doxorubicin and BIBR1532. In silico screening was also conducted by docking of the active compounds on the active site of telomerase reverse transcriptase catalytic subunit, an important therapeutic target of anticancer agents, to determine the probable binding properties. The total binding energies of docked compounds are correlated well with cytotoxic potencies (pIC50) against lung, ovarian, melanoma, and colon cancer cell lines indicating that the benzylidene-hydrazones could use for the development of new anticancer agents as a telomerase inhibitor.

  一系列十五种苯亚甲基酰肼类似物（3a-o），包括八种新化合物，被合成并评估了它们在四种人类癌细胞系中的细胞毒活性和使用DPPH的抗氧化活性。在测试的化合物中，3e在苯亚甲基苯环上有两个甲氧基取代基，被发现对所有测试的癌细胞系都有很强的细胞毒性，IC50值分别为0.12（肺），0.024（卵巢），0.097（黑色素瘤）和0.05μM（结肠），这些IC50值与多柔比星标准（IC50=0.021，0.074，0.001，和0.872μM，分别）相当。DPPH实验显示化合物3f，3i和3g的IC50值分别为0.60，0.99和1.30μM，与抗坏血酸（IC50=0.87μM）相当。评估了计算参数，如药物相似性，ADME性质，毒性效应和药物得分，十五种化合物都没有违反利普斯基的五规则或维伯规则，因此它们显示出良好的药物相似性。此外，所有十五种化合物的药物得分都高于多柔比星和BIBR1532。还通过将活性化合物对接在端粒酶逆转录酶催化亚基的活性位点上，这是抗癌药物的重要治疗靶点，以确定可能的结合性质。对接化合物的总结合能与对肺，卵巢，黑色素瘤和结肠癌细胞系的细胞毒性强度的对数（pIC50）很好地相关，表明苯亚甲基酰肼可以作为端粒酶抑制剂用于新抗癌药物的开发。
• Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity
  作者：Leandro da Costa Clementino、Guilherme Felipe Santos Fernandes、Igor Muccilo Prokopczyk、Wilquer Castro Laurindo、Danyelle Toyama、Bruno Pereira Motta、Amanda Martins Baviera、Flávio Henrique-Silva、Jean Leandro dos Santos、Marcia A. S. Graminha

  DOI：10.1371/journal.pone.0259008

  日期：——

  Leishmaniasis is a neglected disease that affects 12 million people living mainly in developing countries. Herein, 24 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antileishmanial activity. Compound 4f, a furoxan derivative, was particularly remarkable in this regard, with EC₅₀ value of 3.6 μM against L. infantum amastigote forms and CC₅₀ value superior to 500 μM against murine peritoneal macrophages. In vitro studies suggested that 4f may act by a dual effect, by releasing nitric oxide after biotransformation and by inhibiting cysteine protease CPB (IC₅₀: 4.5 μM). In vivo studies using an acute model of infection showed that compound 4f at 7.7 mg/Kg reduced ~90% of parasite burden in the liver and spleen of L. infantum-infected BALB/c mice. Altogether, these outcomes highlight furoxan 4f as a promising compound for further evaluation as an antileishmanial agent.

  利什曼病是一种影响主要发展中国家居民的1200万人的被忽视的疾病。在这项研究中，合成了24种新的含氧化物的化合物，随后评估了它们的抗利什曼病活性。其中，一种呋喃氧化物衍生物4f在这方面表现尤为出色，对婴儿利什曼体形式的EC50值为3.6μM，对小鼠腹膜巨噬细胞的CC50值超过500μM。体外研究表明，4f可能通过双重作用发挥作用，经生物转化后释放一氧化氮，并抑制半胱氨酸蛋白酶CPB（IC50：4.5μM）。使用急性感染模型的体内研究表明，7.7毫克/千克的4f化合物可使感染婴儿利什曼体的BALB/c小鼠肝脏和脾脏中的寄生虫负担减少约90%。总的来说，这些结果突出了呋喃氧化物4f作为一种有前途的化合物，值得进一步评估其作为抗利什曼病药物的潜力。
• Aza-Michael Addition Reactions of Hydrazones with Activated Alkynes Catalyzed by Nitrogen-Containing Organic Bases
  作者：Zhi-Liang Yuan、Yin Wei、Min Shi

  DOI：10.1002/ejoc.201000365

  日期：2010.7

  2]-octane)-catalyzed Michael-type reactions of hydrazones with activated alkynes are described in this paper. This aza-Michael addition reaction can be applied to different types of hydrazones, such as hydrazones 1 and hydroxy-bearing hydrazones 5. The corresponding adducts are achieved in high yields under mild reaction conditions. DABCO-promoted aza-Michael addition reactions were successfully applied to

  本文描述了几种高效的 DABCO（1,4-二氮杂双环 [2.2.2]-辛烷）催化腙与活化炔烃的迈克尔型反应。这种氮杂-迈克尔加成反应可以应用于不同类型的腙，如腙1和含羟基的腙5。相应的加合物在温和的反应条件下以高产率获得。DABCO 促进的氮杂-迈克尔加成反应成功地应用于一系列具有活化炔烃的腙，以中等至良好的产率提供相应的加合物。
• Analogs of Nitrofuran Antibiotics to Combat Resistance
  申请人：The Trustees of Indiana University

  公开号：US20220009914A1

  公开（公告）日：2022-01-13

  Novel compounds and methods of killing or inhibiting the growth of bacteria.

  小说化合物及杀死或抑制细菌生长的方法。
• RUBBER COMPOSITION AND PNEUMATIC TIRES
  申请人：Bridgestone Corporation

  公开号：EP0909788A1

  公开（公告）日：1999-04-21

  A rubber composition prepared by compounding 0.05 to 20 parts by weight of at least one selected from substituted hydrazide compounds represented by the following Formulas (I) to (IV) per 100 parts by weight of a rubber component comprising at least one rubber selected from the group consisting of natural rubber and synthetic rubber, and a pneumatic tire using the same: wherein A represents one selected from the group consisting of an aromatic group which may have a substituent, a hydantoin ring which may have a substituent, and a saturated or unsaturated linear hydrocarbon having 1 to 18 carbon atoms; Y represents hydrogen, an amino group, an alkyl group having 1 to 18 carbon atoms, a cycloalkyl group, an alkenyl group, an aromatic group, a pyridyl group or hydrazino group; and R1 to R11 each represent hydrogen, an alkyl group having 1 to 18 carbon atoms, a cycloalkyl group or an aromatic group.

  一种橡胶组合物，其制备方法是每 100 重量份由至少一种选自天然橡胶和合成橡胶组的橡胶组成的橡胶组分中混入 0.05 至 20 重量份的至少一种选自下式(I)至(IV)所代表的取代酰肼化合物，以及使用该组合物的充气轮胎： 其中 A 代表选自芳香基团（可具有取代基）、海因环（可具有取代基）和具有 1 至 18 个碳原子的饱和或不饱和线性烃；Y 代表氢、氨基、具有 1 至 18 个碳原子的烷基、环烷基、烯基、芳香基、吡啶基或肼基；R1 至 R11 分别代表氢、具有 1 至 18 个碳原子的烷基、环烷基或芳香基。