2-[(3-hydroxy-4-methoxyphenyl)methylidene]-N-phenylhydrazine-1-carbothioamide | 468087-08-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-[(3-hydroxy-4-methoxyphenyl)methylidene]-N-phenylhydrazine-1-carbothioamide
• 英文别名: 2-(3-hydroxy-4-methoxybenzylidene)-N-phenylhydrazine-1-carbothioamide；1-[(3-Hydroxy-4-methoxyphenyl)methylideneamino]-3-phenylthiourea
• CAS: 468087-08-3
• 化学式: C₁₅H₁₅N₃O₂S
• 分子量: 301.369
• InChiKey: VAFMLBCDPJEIKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  98
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(3-hydroxy-4-methoxyphenyl)methylidene]-N-phenylhydrazine-1-carbothioamide 在 iron(III) chloride 、 sodium acetate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 N¹-benzylidene-N²-[3-(3-hydroxy-4-methoxyphenyl)-4-(1,4-benzoquinon-2-yl)-1,3-thiazol-2-ylidene]hydrazine
  参考文献：
  名称：

  Synthesis and biological evaluation of novel benzoquinones as potential antimicrobial agents

  摘要：

  New series of 2,5-dihydroxyphenyl-1,3-thiazoles 4a-l was synthesized by reacting 2,5-dihydroxyphenacyl bromide with various 4-aryl thiosemicarbazones 3a-l that on oxidation with ferric chloride yielded the corresponding N (1)-substituted benzylidene-N (2)-[3-aryl-4-(1,4-benzoquinon-2-yl)-1,3-thiazol-2-ylidene]hydrazines 5a-l. They were evaluated for antibacterial activity against Staphylococcus aureus and Bacillus subtilis as Gram-positive bacteria, Escherichia coli and Pseudomonas aeruginosa as Gram-negative bacteria. They were also evaluated for their in vitro antifungal potential against Candida albicans. Almost all tested compounds were found to possess variable degrees of antimicrobial activity. The obtained data revealed that compounds 4b-h and 5e, 5f and 5l exhibited promising antimicrobial activity against the tested organisms of which compound 4b proved to be the most active.

  DOI：

  10.1007/s00044-012-0076-0
• 作为产物：
  描述：

  异香兰素 、 4-苯基-3-硫代氨基脲 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 以88.6%的产率得到2-[(3-hydroxy-4-methoxyphenyl)methylidene]-N-phenylhydrazine-1-carbothioamide
  参考文献：
  名称：

  发现新型溴酚-硫代氨基脲杂化物作为用于癌症的聚（ADP-核糖）聚合酶-1（PARP-1）的强效选择性抑制剂。

  摘要：

  聚（ADP-核糖）聚合酶-1（PARP-1）是抗癌药物发现的新潜在目标。设计，合成并评估了一系列作为PARP-1抑制剂的溴酚-硫代半碳杂zone杂化物的抗肿瘤活性。其中，最有前途的化合物11对PARP-2（IC50> 1000 nM）表现出优异的选择性PARP-1抑制活性（IC50 = 29.5 nM），并对SK-OV-3，Bel-7402和在体内SK-OV-3细胞异种移植模型中，HepG2癌细胞系（IC50 = 2.39、5.45和4.60μM）以及肿瘤生长的抑制作用。进一步的研究表明，化合物11通过多种抗癌机制发挥了抗肿瘤作用，包括诱导凋亡和细胞周期停滞，DNA双链断裂的细胞蓄积，DNA修复改变，抑制H2O2触发的PARylation，通过产生细胞毒性活性氧而产生的抗增殖作用以及自噬。另外，化合物11显示出良好的药代动力学特性和良好的安全性。这些观察表明，化合物11可以用作发现新的抗癌药物的先导化合物。

  DOI：

  10.1021/acs.jmedchem.8b01946

文献信息

• Design and Synthesis of Novel Thiosemicarbazones as Potent Anti-breast Cancer Agents
  作者：Mashooq Ahmad Bhat、M. Al-Tahhan、Mohamed A. Al-Omar、Ahmed M. Naglah、Abdullah Al-Dhfyan

  DOI：10.2174/1570180815666181008100944

  日期：2019.3.8

  Thiosemicarbazones and its derivatives received a great pharmaceutical importance due to their prominent biological activities. Methods: A series of disubstituted thiosemicarbazone derivatives (1-12) were designed and synthesized as pure compounds in good yield. All the synthesized compounds were analyzed by spectral data. The anticancer activity of all the compounds was performed against breast cancer MCF-7

  背景：硫代氨基咔唑及其衍生物因其突出的生物活性而在制药上具有重要意义。 方法：设计并合成了一系列双取代的硫代半碳酰胺衍生物（1-12），其收率为纯净。通过光谱数据分析所有合成的化合物。所有化合物的抗癌活性均针对乳腺癌MCF-7和MDA-MB-231细胞系进行。 结果：大多数化合物显示出对乳腺癌MCF-7和MDA-MB-231细胞系的活性，分别为（IC50 = 12.25 µM ‒ 185.35 µM）和（IC50 = 12.97 µM ‒ 107.33 µM）。化合物9分别针对MCF-7和MDA-MB-231细胞系（IC50 = 12.76 µM和12.97 µM）。 结论：发现化合物9具有显着的抗乳腺癌活性。进一步评估该化合物在5和10 µM浓度下对乳腺癌细胞MCF-7的侧群抑制百分比测定。与参考药物维拉帕米相比，在5μM浓度下，它显示出对阻止侧群的优势超过80％。
• One-pot and catalyst-free synthesis of thiosemicarbazones via multicomponent coupling reactions
  作者：Silvio Cunha、Tiago Lima da Silva

  DOI：10.1016/j.tetlet.2009.02.134

  日期：2009.5

  A novel and efficient procedure for the synthesis of thiosemicarbazones has been achieved via a multi-component and catalyst-free reaction of phenyl or p-chlorophenyl isothiocyanate, hydrazine, and aldehydes or ketones. The method afforded 20 thiosemicarbazones in good yields and short reaction time. (c) 2009 Elsevier Ltd. All rights reserved.
• Discovery of Novel Bromophenol–Thiosemicarbazone Hybrids as Potent Selective Inhibitors of Poly(ADP-ribose) Polymerase-1 (PARP-1) for Use in Cancer
  作者：Chuanlong Guo、Lijun Wang、Xiuxue Li、Shuaiyu Wang、Xuemin Yu、Kuo Xu、Yue Zhao、Jiao Luo、Xiangqian Li、Bo Jiang、Dayong Shi

  DOI：10.1021/acs.jmedchem.8b01946

  日期：2019.3.28

  Poly(ADP-ribose) polymerase-1 (PARP-1) is a new potential target for anticancer drug discovery. A series of bromophenol-thiosemicarbazone hybrids as PARP-1 inhibitors were designed, synthesized, and evaluated for their antitumor activities. Among them, the most promising compound, 11, showed excellent selective PARP-1 inhibitory activity (IC50 = 29.5 nM) over PARP-2 (IC50 > 1000 nM) and potent anticancer

  聚（ADP-核糖）聚合酶-1（PARP-1）是抗癌药物发现的新潜在目标。设计，合成并评估了一系列作为PARP-1抑制剂的溴酚-硫代半碳杂zone杂化物的抗肿瘤活性。其中，最有前途的化合物11对PARP-2（IC50> 1000 nM）表现出优异的选择性PARP-1抑制活性（IC50 = 29.5 nM），并对SK-OV-3，Bel-7402和在体内SK-OV-3细胞异种移植模型中，HepG2癌细胞系（IC50 = 2.39、5.45和4.60μM）以及肿瘤生长的抑制作用。进一步的研究表明，化合物11通过多种抗癌机制发挥了抗肿瘤作用，包括诱导凋亡和细胞周期停滞，DNA双链断裂的细胞蓄积，DNA修复改变，抑制H2O2触发的PARylation，通过产生细胞毒性活性氧而产生的抗增殖作用以及自噬。另外，化合物11显示出良好的药代动力学特性和良好的安全性。这些观察表明，化合物11可以用作发现新的抗癌药物的先导化合物。
• Synthesis and biological evaluation of novel benzoquinones as potential antimicrobial agents
  作者：Ibrahim Chaaban、El Sayeda M. El Khawass、Mona A. Mahran、Heba A. Abd El Razik、Nehad S. El Salamouni、Abeer E. Abdel Wahab

  DOI：10.1007/s00044-012-0076-0

  日期：2013.2

  New series of 2,5-dihydroxyphenyl-1,3-thiazoles 4a-l was synthesized by reacting 2,5-dihydroxyphenacyl bromide with various 4-aryl thiosemicarbazones 3a-l that on oxidation with ferric chloride yielded the corresponding N (1)-substituted benzylidene-N (2)-[3-aryl-4-(1,4-benzoquinon-2-yl)-1,3-thiazol-2-ylidene]hydrazines 5a-l. They were evaluated for antibacterial activity against Staphylococcus aureus and Bacillus subtilis as Gram-positive bacteria, Escherichia coli and Pseudomonas aeruginosa as Gram-negative bacteria. They were also evaluated for their in vitro antifungal potential against Candida albicans. Almost all tested compounds were found to possess variable degrees of antimicrobial activity. The obtained data revealed that compounds 4b-h and 5e, 5f and 5l exhibited promising antimicrobial activity against the tested organisms of which compound 4b proved to be the most active.