5-methoxy-2-naphthalen-2-yl-1H-benzoimidazole | 3367-03-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-methoxy-2-naphthalen-2-yl-1H-benzoimidazole
• 英文别名: 6-methoxy-2-naphthalen-2-yl-1H-benzimidazole
• CAS: 3367-03-1
• 化学式: C₁₈H₁₄N₂O
• 分子量: 274.322
• InChiKey: IELZCDPZIQCECK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-methoxy-2-naphthalen-2-yl-1H-benzoimidazole 在 tris-(dibenzylideneacetone)dipalladium(0) 、 BINAP 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 16.0h， 生成 N-cyclohexyl-4-(6-methoxy-2-(naphthalen-2-yl)-1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Syntheses and biological evaluation of 1-heteroaryl-2-aryl-1 H -benzimidazole derivatives as c-Jun N-terminal kinase inhibitors with neuroprotective effects

  摘要：

  1-Heteroaryl-2-aryl-1H-benzimidazole derivatives were synthesized as inhibitors of c-Jun N-terminal kinases, JNK3. Their activities were evaluated through measurement of K-d using SPR, JNK3 kinase assay, and cell-viability of human neuroblastoma cells. Most tested compounds showed high affinity (10 mu M-46 nM) to JNK3. Among them, compound 16f exhibited potent activities (K-d = 46 nM). Especially, 16f was also found to present a potent cell protective effect (IC50 = 1.09 mu M) against toxicity induced by anisomycin, showing a possibility as protective therapeutics in neuronal cell apoptosis. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.021
• 作为产物：
  描述：

  4-methoxyphenylene-1,2-diamine dihydrochloride 、 2-萘甲醛 在 三乙胺 、 双氧水 作用下， 以 甲醇 为溶剂， 反应 3.5h， 以33%的产率得到5-methoxy-2-naphthalen-2-yl-1H-benzoimidazole
  参考文献：
  名称：

  Syntheses and biological evaluation of 1-heteroaryl-2-aryl-1 H -benzimidazole derivatives as c-Jun N-terminal kinase inhibitors with neuroprotective effects

  摘要：

  1-Heteroaryl-2-aryl-1H-benzimidazole derivatives were synthesized as inhibitors of c-Jun N-terminal kinases, JNK3. Their activities were evaluated through measurement of K-d using SPR, JNK3 kinase assay, and cell-viability of human neuroblastoma cells. Most tested compounds showed high affinity (10 mu M-46 nM) to JNK3. Among them, compound 16f exhibited potent activities (K-d = 46 nM). Especially, 16f was also found to present a potent cell protective effect (IC50 = 1.09 mu M) against toxicity induced by anisomycin, showing a possibility as protective therapeutics in neuronal cell apoptosis. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.021

文献信息

• Biologically Potent Benzimidazole-Based-Substituted Benzaldehyde Derivatives as Potent Inhibitors for Alzheimer’s Disease along with Molecular Docking Study
  作者：Bushra Adalat、Fazal Rahim、Wajid Rehman、Zarshad Ali、Liaqat Rasheed、Yousaf Khan、Thoraya A. Farghaly、Sulaiman Shams、Muhammad Taha、Abdul Wadood、Syed A. A. Shah、Magda H. Abdellatif

  DOI：10.3390/ph16020208

  日期：——

  Twenty-one analogs were synthesized based on benzimidazole, incorporating a substituted benzaldehyde moiety (1–21). These were then screened for their acetylcholinesterase and butyrylcholinesterase inhibition profiles. All the derivatives except 13, 14, and 20 showed various inhibitory potentials, ranging from IC50 values of 0.050 ± 0.001 µM to 25.30 ± 0.40 µM against acetylcholinesterase, and 0.080 ± 0.001 µM to 25.80 ± 0.40 µM against butyrylcholinesterase, when compared with the standard drug donepezil (0.016 ± 0.12 µM and 0.30 ± 0.010 µM, against acetylcholinesterase and butyrylcholinesterase, respectively). Compound 3 in both cases was found to be the most potent compound due to the presence of chloro groups at the 3 and 4 positions of the phenyl ring. A structure-activity relationship study was performed for all the analogs except 13, 14, and 20, further, molecular dynamics simulations were performed for the top two compounds as well as the reference compound in a complex with acetylcholinesterase and butyrylcholinesterase. The molecular dynamics simulation analysis revealed that compound 3 formed the most stable complex with both acetylcholinesterase and butyrylcholinesterase, followed by compound 10. As compared to the standard inhibitor donepezil both compounds revealed greater stabilities and higher binding affinities for both acetylcholinesterase and butyrylcholinesterase.

  以苯并咪唑为基础，结合取代的苯甲醛分子，合成了 21 种类似物（1-21）。然后对这些衍生物进行了乙酰胆碱酯酶和丁酰胆碱酯酶抑制谱的筛选。除 13、14 和 20 外，所有衍生物都显示出不同的抑制潜力，对乙酰胆碱酯酶的 IC50 值从 0.050 ± 0.001 µM 到 25.30 ± 0.40 µM，对丁酰胆碱酯酶的 IC50 值从 0.080 ± 0.001 µM 到 25.与标准药物多奈哌齐（对乙酰胆碱酯酶和丁酰胆碱酯酶的作用分别为 0.016 ± 0.12 µM 和 0.30 ± 0.010 µM）相比，化合物 3 对丁酰胆碱酯酶的作用为 0.080 ± 0.001 µM 至 25.30 ± 0.40 µM。在这两种情况下，化合物 3 都是最有效的化合物，这是因为在苯环的 3 和 4 位上存在氯基。对除 13、14 和 20 之外的所有类似物进行了结构-活性关系研究，并对前两种化合物以及参考化合物与乙酰胆碱酯酶和丁酰胆碱酯酶的复合物进行了分子动力学模拟。分子动力学模拟分析表明，化合物 3 与乙酰胆碱酯酶和丁酰胆碱酯酶形成的复合物最为稳定，其次是化合物 10。与标准抑制剂多奈哌齐相比，这两种化合物对乙酰胆碱酯酶和丁酰胆碱酯酶都具有更高的稳定性和结合亲和力。
• Syntheses and biological evaluation of 1-heteroaryl-2-aryl-1 H -benzimidazole derivatives as c-Jun N-terminal kinase inhibitors with neuroprotective effects
  作者：Mi-hyun Kim、Junghun Lee、Kyungjin Jung、Minjung Kim、Yun-Jin Park、Heechul Ahn、Young Hye Kwon、Jung-Mi Hah

  DOI：10.1016/j.bmc.2013.02.021

  日期：2013.4

  1-Heteroaryl-2-aryl-1H-benzimidazole derivatives were synthesized as inhibitors of c-Jun N-terminal kinases, JNK3. Their activities were evaluated through measurement of K-d using SPR, JNK3 kinase assay, and cell-viability of human neuroblastoma cells. Most tested compounds showed high affinity (10 mu M-46 nM) to JNK3. Among them, compound 16f exhibited potent activities (K-d = 46 nM). Especially, 16f was also found to present a potent cell protective effect (IC50 = 1.09 mu M) against toxicity induced by anisomycin, showing a possibility as protective therapeutics in neuronal cell apoptosis. (C) 2013 Elsevier Ltd. All rights reserved.