4-(2-(1H-benzo[d]imidazol-1-yl)ethoxy)benzaldehyde

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 4-(2-(1H-benzo[d]imidazol-1-yl)ethoxy)benzaldehyde
• 英文别名: 4-[2-(Benzimidazol-1-yl)ethoxy]benzaldehyde
• 化学式: C₁₆H₁₄N₂O₂
• 分子量: 266.299
• InChiKey: QBQPDGSJMGDAPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-(1H-benzo[d]imidazol-1-yl)ethoxy)benzaldehyde 在 哌啶 、 sodium tetrahydroborate 、 cobalt dimethylglyoxime 、 苯甲酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 24.0h， 生成 5-(4-(2-(1H-benzo[d]imidazol-1-yl)ethoxy)benzyl)thiazolidine-2,4-dione
  参考文献：
  名称：

  Synthesis, biological evaluation, and molecular docking investigation of benzhydrol- and indole-based dual PPAR-γ/FFAR1 agonists

  摘要：

  Type-2 diabetes mellitus is a progressive cluster of metabolic disorders, representing a global public health burden affecting more than 366 million people worldwide. We recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome proliferator activated receptor-gamma (PPAR-gamma) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures. To further investigate this concept, two new scaffolds, the benzhydrol- and indole-based chemotypes, were introduced here in. Our optimization campaign resulted in three compounds; 15a, 15c, and 15d, with affinities in the low micromolar range on both targets. In vivo study of selected test compounds, revealed that 15c possesses a significant anti-hyperglycemic and anti-hyperlipidemic activities superior to rosiglitazone in fat-fed animal models. Molecular docking analysis was conducted to explain the binding modes of both series. These compounds could lead to the development of the unique antidiabetic agent acting as insulin sensitizer as well as insulin secretagogue. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.03.051
• 作为产物：
  描述：

  对羟基苯甲醛 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-(2-(1H-benzo[d]imidazol-1-yl)ethoxy)benzaldehyde
  参考文献：
  名称：

  α-淀粉酶异二聚体和抑制剂作为降糖药的设计、合成和分子建模

  摘要：

  设计并合成了一系列基于罗格列酮的异二聚体，并评估了它们的 α-淀粉酶和抗氧化活性。采用MolDock对接法探索化合物在PPARγ和α-淀粉酶活性位点的结合方式。在针对 PPARγ（PDB 代码：1FM6）晶体结构的分子对接研究中，化合物 10 和 13 显示与氨基酸 Arg379、Asp379、Asn385、Ala387、Glu388、Val389、Glu390 和 Lys438 相互作用。α-淀粉酶（PDB 代码：5EOF）与化合物 10 和 13 的对接结果显示与氨基酸 Ala169、Lys172、Asp173、Tyr174、Val175、Arg176 和 Lys178 具有良好的相互作用。根据对接分数，设计的化合物被选择性地优先合成。所有合成的化合物都进行了体外 α-淀粉酶活性和抗氧化活性。化合物 10 和 13 具有比阿卡波糖更高的效力，并且大多数化合物显示出抗氧化活性。此外，还评估了活性最强的化合物

  DOI：

  10.1007/s11030-022-10414-8

文献信息

• Novel Euglycemic and Hypolipidemic Agents. 1
  作者：Braj B. Lohray、Vidya Bhushan、Bheema P. Rao、Gurram R. Madhavan、Nagabelli Murali、Krovvidi N. Rao、Ananth K. Reddy、Bagepalli M. Rajesh、Pamulapati G. Reddy、Ranjan Chakrabarti、Reeba K. Vikramadithyan、Ramanujam Rajagopalan、Rao N. V. S. Mamidi、Hemant K. Jajoo、Swaminathan Subramaniam

  DOI：10.1021/jm970444e

  日期：1998.5.1

  A series of [[(heterocyclyl)ethoxy]benzyl]-2,4-thiazolidinediones have been synthesized by the condensation of corresponding aldehyde 1 and 2,4-thiazolidinedione followed by hydrogenation. Both unsaturated thiazolidinedione 2 and its saturated counterpart 3 have shown antihyperglycemic activity. Many of these compounds have shown superior euglycemic and hypolipidemic activity compared to troglitazone (CS 045). The indole analogue DRF-2189 (3g) was found to be a very potent insulin sensitizer, comparable to BRL-49653 in genetically obese C57BL/6J-ob/ob and 57BL/KsJ-db/db mice. Pharmacokinetic and tissue distribution studies conducted on BRL-49653 and DRF-2189 (3g) indicate that these drugs are well-distributed in target tissues. On the basis of euglycemic activity as well as enhanced selectivity against reduction of triglycerides in plasma, DRF-2189 (3g) has been selected for further evaluation.
• Novel indole containing thiazolidinedione derivatives as potent euglycemic and hypolipidaemic agents
  作者：Braj B. Lohray、V. Bhushan、P.Bheema Rao、G.R. Madhavan、N. Murali、K.Narasimha Rao、G.R. Madhavan、N. Murali、K.Narasimha Rao、K. Anantha Reddy、B.M. Rajesh、P. Ganpathy Reddy、R. Chakrabarti、R. Rajagopalan

  DOI：10.1016/s0960-894x(97)00118-2

  日期：1997.1

  Several thiazolidinediones having indol as heterocyclic moiety have been synthesized and evaluated for euglycemic properties. A few of them have been found to be superior to troglitazone. (C) 1997 Elsevier Science Ltd.
• Synthesis, biological evaluation, and molecular docking investigation of benzhydrol- and indole-based dual PPAR-γ/FFAR1 agonists
  作者：Khaled M. Darwish、Ismail Salama、Samia Mostafa、Mohamed S. Gomaa、El-Sayed Khafagy、Mohamed A. Helal

  DOI：10.1016/j.bmcl.2018.03.051

  日期：2018.5

  Type-2 diabetes mellitus is a progressive cluster of metabolic disorders, representing a global public health burden affecting more than 366 million people worldwide. We recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome proliferator activated receptor-gamma (PPAR-gamma) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures. To further investigate this concept, two new scaffolds, the benzhydrol- and indole-based chemotypes, were introduced here in. Our optimization campaign resulted in three compounds; 15a, 15c, and 15d, with affinities in the low micromolar range on both targets. In vivo study of selected test compounds, revealed that 15c possesses a significant anti-hyperglycemic and anti-hyperlipidemic activities superior to rosiglitazone in fat-fed animal models. Molecular docking analysis was conducted to explain the binding modes of both series. These compounds could lead to the development of the unique antidiabetic agent acting as insulin sensitizer as well as insulin secretagogue. (C) 2018 Elsevier Ltd. All rights reserved.
• Design, synthesis, and molecular modeling of heterodimer and inhibitors of α-amylase as hypoglycemic agents
  作者：Ved Prakash Singh、Manisha Nidhar、Pratima Yadav、Ranjeet Kumar、Priyanka Sonker、Ashish Kumar Tewari

  DOI：10.1007/s11030-022-10414-8

  日期：2023.2

  docking score, the designed compounds were selectively prioritized for synthesis. All synthesized compounds were subjected to in vitro α-amylase activity and antioxidant activity. Compounds 10 and 13 were to possess higher potency than acarbose, and most of the compounds showed antioxidant activity. Additionally, the most active compound 10 was evaluated for in vivo anti-diabetic activity. Graphical

  设计并合成了一系列基于罗格列酮的异二聚体，并评估了它们的 α-淀粉酶和抗氧化活性。采用MolDock对接法探索化合物在PPARγ和α-淀粉酶活性位点的结合方式。在针对 PPARγ（PDB 代码：1FM6）晶体结构的分子对接研究中，化合物 10 和 13 显示与氨基酸 Arg379、Asp379、Asn385、Ala387、Glu388、Val389、Glu390 和 Lys438 相互作用。α-淀粉酶（PDB 代码：5EOF）与化合物 10 和 13 的对接结果显示与氨基酸 Ala169、Lys172、Asp173、Tyr174、Val175、Arg176 和 Lys178 具有良好的相互作用。根据对接分数，设计的化合物被选择性地优先合成。所有合成的化合物都进行了体外 α-淀粉酶活性和抗氧化活性。化合物 10 和 13 具有比阿卡波糖更高的效力，并且大多数化合物显示出抗氧化活性。此外，还评估了活性最强的化合物