(Z)-1-((2-hydroxynaphthalen-3-yl)methyl)-3-(1-methyl-2-oxoindolin-3-ylidene) thiourea

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (Z)-1-((2-hydroxynaphthalen-3-yl)methyl)-3-(1-methyl-2-oxoindolin-3-ylidene) thiourea
• 英文别名: (3Z)-1-[(3-hydroxynaphthalen-2-yl)methyl]-3-(1-methyl-2-oxoindol-3-ylidene)thiourea
• 化学式: C₂₁H₁₇N₃O₂S
• 分子量: 375.451
• InChiKey: MZOQJWDNYAZPNA-NMWGTECJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  97
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 1-甲基靛红 、 硫脲 、 2-萘酚 在 对甲苯磺酸 作用下， 以 乙醇 为溶剂， 反应 36.0h， 以75%的产率得到(Z)-1-((2-hydroxynaphthalen-3-yl)methyl)-3-(1-methyl-2-oxoindolin-3-ylidene) thiourea
  参考文献：
  名称：

  N-取代的羟基萘亚氨基-羟吲哚衍生物作为新型的PI3-激酶抑制剂和乳腺癌药物：分子验证和结构-活性关系研究

  摘要：

  N-取代的羟基亚氨基亚氨基-羟吲哚衍生物（5a–g）作为磷酸肌醇3-激酶（PI3K）的抑制剂出现，PI3K是细胞凋亡或程序性细胞死亡的重要调节剂。获得了电子供体/受体取代的吲哚亚胺（5a–g），并通过FTIR，1H NMR，13C NMR和HRMS阐明了结构。通过竞争性ELISA评估PI3K的抑制能力。随后，评估了对乳腺癌（MCF-7）细胞系的抗癌活性。在两种活性中，化合物5c，5d和5f显示出最有效的活性。抗癌活性的抑制百分比为78.​​22±1.02（5c）和78.98±1.08（5f），并且IC 50为2.02±0.92μ米（图5c）和1.98±0.18μ米（图5f）。发现化合物5a和5g对两种活性均无活性，其余的均显示中等活性。为了更深入地了解结合模式和抑制剂的结合亲和力，将5a–g对接至PI3Ksp110α（PDB ID：2ENQ）的活性位点。结果表明，PI3Ks的结合口袋中的疏

  DOI：

  10.1111/cbdd.13079

文献信息

• Therapeutic investigations of novel indoxyl-based indolines: A drug target validation and Structure-Activity Relationship of angiotensin-converting enzyme inhibitors with cardiovascular regulation and thrombolytic potential
  作者：A. Manikandan、Pearl Moharil、M. Sathishkumar、C. Muñoz-Garay、A. Sivakumar

  DOI：10.1016/j.ejmech.2017.09.076

  日期：2017.12

  A family of 12 members of Naphthalene-2-ol-indolin-2-one-thiocarbamides (5a-1) with pharmacological potentials of cardiovascular modulator were efficiently synthesized and evaluated. These compounds show inhibitory activity on angiotensin-converting enzyme (ACE), which is a principal constituent of the renin angiotensin system and causative source for hypertension (HTN) (elevated blood pressure) and congestive heart failure (CHF), a parameter that was tested in this report. Prior to this, to get more insight into the binding mode and inhibition of human ACE C-domain (PDB ID: 2XY9) and N-domain (PDB ID: 3NXQ) compounds 5a-1 was docked into the active site of them. The established inhibitory constant (Ki) (range 40-500 nM) and least binding affinities (-18.52 to 30.57 kcal/mol) indicated the therapeutic selectivity of compounds 5a-1 towards ACE C-domain inhibition over ACE N-domain. The cytotoxicity effect of most potent compounds among 5a-1 were tested in normal breast cells and MCF-7 cell lines. Simultaneously, H2O2 induced antioxidant and DNA damage assessment was executed. Eventually, a thrombolytic activity followed by a human red blood cell (HRBC) membrane stabilization study to ensure the relaxation of blood and stabilization of RBC was executed. Structure-Activity Relationship (SAR) study discloses the potential of 5c, 5h, and 5k as cardiovascular protective therapeutic agents among 5a-1. (C) 2017 Elsevier Masson SAS. All rights reserved.
• N-substituted hydroxynaphthalene imino-oxindole derivatives as new class of PI3-kinase inhibitor and breast cancer drug: Molecular validation and structure-activity relationship studies
  作者：M. Rajesh Kumar、Manikandan Alagumuthu、V. Violet Dhayabaran

  DOI：10.1111/cbdd.13079

  日期：2018.1

  N-substituted hydroxynaphthalene imino-oxindole derivatives (5a–g) were emerged as the inhibitors of the phosphoinositide 3-kinase (PI3K), which is a crucial regulator of apoptosis or programmed cell death. Electron donor-/acceptor-substituted indole-imine (5a–g) was achieved, and the structures were elucidated by FTIR, 1H NMR, 13C NMR and HRMS. Inhibition potency of PI3Ks was assessed by competitive

  N-取代的羟基亚氨基亚氨基-羟吲哚衍生物（5a–g）作为磷酸肌醇3-激酶（PI3K）的抑制剂出现，PI3K是细胞凋亡或程序性细胞死亡的重要调节剂。获得了电子供体/受体取代的吲哚亚胺（5a–g），并通过FTIR，1H NMR，13C NMR和HRMS阐明了结构。通过竞争性ELISA评估PI3K的抑制能力。随后，评估了对乳腺癌（MCF-7）细胞系的抗癌活性。在两种活性中，化合物5c，5d和5f显示出最有效的活性。抗癌活性的抑制百分比为78.​​22±1.02（5c）和78.98±1.08（5f），并且IC 50为2.02±0.92μ米（图5c）和1.98±0.18μ米（图5f）。发现化合物5a和5g对两种活性均无活性，其余的均显示中等活性。为了更深入地了解结合模式和抑制剂的结合亲和力，将5a–g对接至PI3Ksp110α（PDB ID：2ENQ）的活性位点。结果表明，PI3Ks的结合口袋中的疏