2-(p-Nitro-phenacylmercapto)-benzimidazol | 22794-92-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(p-Nitro-phenacylmercapto)-benzimidazol
• 英文别名: 2-(1H-benzimidazol-2-ylsulfanyl)-1-(4-nitrophenyl)ethanone
• CAS: 22794-92-9
• 化学式: C₁₅H₁₁N₃O₃S
• 分子量: 313.337
• InChiKey: CYLIFSHGFSUXES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(p-Nitro-phenacylmercapto)-benzimidazol 在 一水合肼 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 3-((E)-((E)-(2-(1H-benzo[d]imidazol-2-ylthio)-1-(4-nitrophenyl)ethylidene)hydrazono)methyl)phenol
  参考文献：
  名称：

  Synthesis, in vitro alpha-glucosidase inhibitory potential of benzimidazole bearing bis-Schiff bases and their molecular docking study

  摘要：

  Voglibose and acarbose are distinguished alpha-glucosidase inhibitors used for controlling of diabetes mellitus. Unfortunately, these distinguished and clinically used inhibitors have also numerous side effects. Subsequently, there is still needed to develop safer therapy. Despite of a broad spectrum of biological importance of benzimidazole, it is occasionally evaluated for alpha-glucosidase activity. Current study deals with the synthesis and biological screening of benzimidazole bearing bis-Schiff bases (1-19) for their alpha-glucosidase inhibitory activity. All analogues exhibited excellent to good inhibitory potential (IC50 = 2.20 +/- 0.1to 88.60 +/- 1.70 mu M) when compared with standard drug acarbose (IC50 = 38.45 +/- 0.80 mu M). A structure activity relationship has been established on the basis of electronic effects and position of different substituents present on phenyl ring. In order to rationalize the binding interactions of most active analogues with the active site of alpha-glucosidase enzyme, molecular docking study was conducted.

  DOI：

  10.1016/j.bioorg.2019.103394
• 作为产物：
  描述：

  1H-苯并咪唑-2-硫醇 在 硫酸 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 2.5h， 生成 2-(p-Nitro-phenacylmercapto)-benzimidazol
  参考文献：
  名称：

  2-((Benzimidazol-2-yl)thio)-1-arylethan-1-ones: Synthesis, crystal study and cancer stem cells CD133 targeting potential

  摘要：

  In order to develop a potent anti-tumor agent that can target both cancer stem cells and the bulk of tumor cells, a series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a-o was synthesized. All compounds were evaluated for their anti-proliferative activity towards colon HT-29 cancer cell line. In addition, their inhibitory effect against cell surface expression of CD133, a potent cancer stem cells (CSCs) marker, in the same cells was evaluated by flow cytometry at 10 mu M. Compound 51 emerged as the most active anti-proliferative analog against HT-29 (IC50 = 18.83 +/- 1.37 mu M), that almost equipotent as 5-fluorouracil (IC50 = 15.83 +/- 1.63 mu M) with 50.11 +/- 4.05% inhibition effect on CD133 expression, suggested dual targeted effect. Also, compounds 5h, 5j, 5k and 5m-o inhibited the expression of CD133 with more than 50%. The SAR study pointed out the significance of substitution of the pendent phenyl group with lipophilic electron-donating groups or replacing it by 2-thienyl or 2-furyl groups. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.023

文献信息

• Synthesis of benzimidazole derivatives as potent inhibitors for α-amylase and their molecular docking study in management of type-II diabetes
  作者：Shafqat Hussain、Muhammad Taha、Fazal Rahim、Shawkat Hayat、Khalid Zaman、Naveed Iqbal、Manikandan Selvaraj、Muhammad Sajid、Masroor Ahmad Bangesh、Fahad Khan、Khalid Mohammed Khan、Nizam Uddin、Syed Adnan Ali Shah、Muhammad Ali

  DOI：10.1016/j.molstruc.2021.130029

  日期：2021.5

  standard drug acarbose. While others derivatives of the series showed good inhibitory potentials. All the synthesized compounds were characterized by HREI-MS, 1H and 13C-NMR spectroscopy. Structure activity relationship (SAR) has been established for all newly synthesized analogs. Binding interactions between ligands and active residues of the enzyme were confirmed through molecular docking study.

  在寻找有效的α-淀粉酶抑制剂的过程中，我们合成了十七种带有磺酰胺的2-巯基苯并咪唑衍生物（1-17），并评估了它们的α-淀粉酶抑制潜力。所有合成的化合物显示的可变程度α-淀粉酶活性的具有IC 50值0.90±0.30 11.20 0.05到±测距μ当与标准药物阿卡波糖具有IC相比中号50值1.70±0.10 μ M.化合物1，2，11 ，12和14的IC 50值为1.40±0.10、1.30±0.05、0.90±0.05、1.60±0.05和1.60±0.10 µM分别被发现比标准药物阿卡波糖好很多倍。而该系列的其他衍生物则显示出良好的抑制潜力。所有合成的化合物均通过HREI-MS，1 H和13 C-NMR光谱进行表征。已经为所有新合成的类似物建立了结构活性关系（SAR）。通过分子对接研究证实了配体与酶的活性残基之间的结合相互作用。
• Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2-Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468 Cells as Apoptosis-Inducing Agents
  作者：Hatem Abdel-Aziz、Wagdy Eldehna、Hazem Ghabbour、Ghada Al-Ansary、Areej Assaf、Abdullah Al-Dhfyan

  DOI：10.3390/ijms17081221

  日期：——

  On account of its poor prognosis and deficiency of therapeutic stratifications, triple negative breast cancer continues to form the causative platform of an incommensurate number of breast cancer deaths. Aiming at the development of potent anticancer agents as a continuum of our previous efforts, a novel series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a–w was synthesized and evaluated for its anti-proliferative activity towards triple negative breast cancer (TNBC) MDA-MB-468 cells. Compound 5k was the most active analog against MDA-MB-468 (IC50 = 19.90 ± 1.37 µM), with 2.1-fold increased activity compared to 5-fluorouracil (IC50 = 41.26 ± 3.77 µM). Compound 5k was able to induce apoptosis in MDA-MB-468, as evidenced by the marked boosting in the percentage of florecsein isothiocyanate annexin V (Annexin V–FITC)-positive apoptotic cells (upper right (UR) + lower right (LR)) by 2.8-fold in comparison to control accompanied by significant increase in the proportion of cells at pre-G1 (the first gap phase) by 8.13-fold in the cell-cycle analysis. Moreover, a quantitative structure activity relationship (QSAR) model was established to investigate the structural requirements orchestrating the anti-proliferative activity. Finally, we established a theoretical kinetic study.

  由于其预后不良和治疗分层的不足，三阴性乳腺癌继续成为导致乳腺癌死亡人数不相称的原因平台。作为我们之前努力的连续体，旨在开发有效的抗癌药物，合成了一系列新型 2-((benzimidazol-2-yl)thio)-1-aryllethan-1-ones 5a–w 并评估了其抗癌效果。 -对三阴性乳腺癌（TNBC）MDA-MB-468细胞的增殖活性。化合物 5k 是 MDA-MB-468 活性最强的类似物 (IC50 = 19.90 ± 1.37 µM)，与 5-氟尿嘧啶相比，活性增加了 2.1 倍 (IC50 = 41.26 ± 3.77 µM)。化合物 5k 能够诱导 MDA-MB-468 细胞凋亡，异硫氰酸荧光素膜联蛋白 V (Annexin V–FITC) 阳性凋亡细胞的百分比显着增加（右上 (UR) + 右下 (LR)） ）与对照相比增加了 2.8 倍，同时在细胞周期分析中，G1 前（第一个间隙期）的细胞比例显着增加了 8.13 倍。此外，还建立了定量结构活性关系（QSAR）模型来研究协调抗增殖活性的结构要求。最后，我们建立了理论动力学研究。
• Synthesis of Novel Benzimidazole-Based Thiazole Derivatives as Multipotent Inhibitors of α-Amylase and α-Glucosidase: In Vitro Evaluation along with Molecular Docking Study
  作者：Rafaqat Hussain、Shahid Iqbal、Mazloom Shah、Wajid Rehman、Shoaib Khan、Liaqat Rasheed、Fazal Rahim、Ayed A. Dera、Sana Kehili、Eslam B. Elkaeed、Nasser S. Awwad、Majed A. Bajaber、Mohammed Issa Alahmdi、Hamad Alrbyawi、Hashem O. Alsaab

  DOI：10.3390/molecules27196457

  日期：——

  ability to inhibit α-amylase and α-glucosidase when compared to acarbose as a standard drug. The recently available analogs showed a wide variety of inhibitory potentials that ranged between 1.31 ± 0.05 and 38.60 ± 0.70 µM (against α-amylase) and between 2.71 ± 0.10 and 42.31 ± 0.70 µM (against α-glucosidase) under the positive control of acarbose (IC50 = 10.30 ± 0.20 µM against α-amylase) (IC50 = 9

  在这项研究中，提供了含有噻唑部分 ( 1-17 ) 的苯并咪唑杂合类似物，然后测试了它们与作为标准药物的阿卡波糖相比抑制 α-淀粉酶和 α-葡糖苷酶的能力。最近可用的类似物在阿卡波糖的阳性控制下显示出多种抑制电位，范围在 1.31 ± 0.05 和 38.60 ± 0.70 µM（针对 α-淀粉酶）和 2.71 ± 0.10 和 42.31 ± 0.70 µM（针对 α-葡萄糖苷酶）之间（针对 α-淀粉酶的IC 50 = 10.30 ± 0.20 µM）（IC 50= 9.80 ± 0.20µM 对 α-葡萄糖苷酶）。分别基于环 B 和 C 周围的取代模式对所有类似物进行了构效关系 (SAR) 研究。从 SAR 研究得出的结论是，带有较小尺寸的取代基（-F 和 Cl）或能够与目标酶的催化残基形成氢键（-OH）的取代基的类似物增强了抑制潜力。因此，类似物 2（具有间氟取代）、3（具有对氟取代）和
• Benzimidazole-Based Schiff Base Hybrid Scaffolds: A Promising Approach to Develop Multi-Target Drugs for Alzheimer’s Disease
  作者：Rafaqat Hussain、Shoaib Khan、Hayat Ullah、Farhan Ali、Yousaf Khan、Asma Sardar、Rashid Iqbal、Farid S. Ataya、Nasser M. El-Sabbagh、Gaber El-Saber Batiha

  DOI：10.3390/ph16091278

  日期：——

  A series of benzimidazole-based Schiff base derivatives (1–18) were synthesized and structurally elucidated through 1H NMR, 13C NMR and HREI-MS analysis. Subsequently, these synthetic derivatives were subjected to evaluation for their inhibitory capabilities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). All these derivatives showed significant inhibition against AChE with an IC50 value in the range of 123.9 ± 10.20 to 342.60 ± 10.60 µM and BuChE in the range of 131.30 ± 9.70 to 375.80 ± 12.80 µM in comparison with standard Donepezil, which has IC50 values of 243.76 ± 5.70 µM (AChE) and 276.60 ± 6.50 µM (BuChE), respectively. Compounds 3, 5 and 9 exhibited potent inhibition against both AChE and BuChE. Molecular docking studies were used to validate and establish the structure–activity relationship of the synthesized derivatives.

  通过 1H NMR、13C NMR 和 HREI-MS 分析，合成了一系列基于苯并咪唑的席夫碱衍生物（1-18）并阐明了其结构。随后，对这些合成衍生物对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）的抑制能力进行了评估。所有这些衍生物对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）都有明显的抑制作用，其 IC50 值在 123.9 ± 10.20 至 342.60 ± 10.60 µM 之间，对 BuChE 的抑制作用在 131.30 ± 9.70 至 375.80 ± 12.80 µM 之间，而标准物质多奈哌齐的 IC50 值分别为 243.76 ± 5.70 µM（AChE）和 276.60 ± 6.50 µM（BuChE）。化合物 3、5 和 9 对 AChE 和 BuChE 都有很强的抑制作用。分子对接研究用于验证和建立合成衍生物的结构-活性关系。
• Synthesis, In Vitro α-Amylase Activity, and Molecular Docking Study of New Benzimidazole Derivatives
  作者：Hayat Ullah、Hafeez Ullah、M. Taha、F. Khan、F. Rahim、I. Uddin、M. Sarfraz、S. A. Ali Shah、A. Aziz、S. Mubeen

  DOI：10.1134/s1070428021060130

  日期：2021.6