2-(4-adamantan-1-yl-phenoxymethyl)-1H-benzoimidazole-5-carboxylic acid methyl ester

• 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: 2-(4-adamantan-1-yl-phenoxymethyl)-1H-benzoimidazole-5-carboxylic acid methyl ester
• 英文别名: methyl 2-[[4-(1-adamantyl)phenoxy]methyl]-3H-benzimidazole-5-carboxylate
• 化学式: C₂₆H₂₈N₂O₃
• 分子量: 416.52
• InChiKey: DDSDQTSUZNQOAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  64.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-adamantan-1-yl-phenoxymethyl)-1H-benzoimidazole-5-carboxylic acid methyl ester 在 盐酸 、 水 、 溶剂黄146 、 碳酸氢钠 作用下， 以 水 为溶剂， 反应 3.0h， 以84%的产率得到2-(4-adamantan-1-yl-phenoxymethyl)-1H-benzoimidazole-5 carboxylic acid
  参考文献：
  名称：

  COMPOUNDS THAT INHIBIT HIF-1 ACTIVITY, THE METHOD FOR PREPARATION THEREOF AND THE PHARMACEUTICAL COMPOSITION CONTAINING THEM AS AN EFFECTIVE COMPONENT

  摘要：

  本文披露了一种HIF-1抑制剂，其制备方法，以及包含其作为活性成分的药物组合物。该HIF-1抑制剂显示抗癌活性，这归功于其对HIF-1的抑制活性，HIF-1是一种在癌症生长和转移中起重要作用的转录因子，但不具有一般细胞毒性。因此，HIF抑制剂及其药用可接受的盐可用作治疗各种癌症，如肝癌、胃癌和乳腺癌的治疗药物。此外，具有对HIF-1抑制活性的化合物在治疗由HIF-1介导的VEGF表达加重的糖尿病视网膜病变和关节炎方面是有用的。

  公开号：

  US20090306078A1
• 作为产物：
  描述：

  4-(1-金刚烷基)苯酚 在 lithium hydroxide monohydrate 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 2-(4-adamantan-1-yl-phenoxymethyl)-1H-benzoimidazole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors

  摘要：

  A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC50 = 4.4 mu M) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.046

文献信息

• COMPOUNDS THAT INHIBIT HIF-1 ACTIVITY, THE METHOD FOR PREPARATION THEREOF AND THE PHARMACEUTICAL COMPOSITION CONTAINING THEM AS AN EFFECTIVE COMPONENT
  申请人：Lee Jung Joon

  公开号：US20090306078A1

  公开（公告）日：2009-12-10

  Disclosed herein are an HIF-1 inhibitor, a method for the preparation thereof, and a pharmaceutical composition comprising the same as an active ingredient. The HIF-1 inhibitor shows anticancer activity thanks to the inhibition activity against HIF-1, a transcription factor which plays an important role in the growth and metastasis of cancer, but not to general cytotoxicity. Thus, the HIF-inhibitor and a pharmaceutically acceptable salt thereof can be used as a therapeutic for various cancers such as liver cancer; stomach cancer and breast cancer. Also, the compound having inhibition activity against HIF-1 is useful in the treatment of diabetic retinopathy and arthritis, which are aggravated by HIF-1-mediated VEGF expression.

  本文披露了一种HIF-1抑制剂，其制备方法，以及包含其作为活性成分的药物组合物。该HIF-1抑制剂显示抗癌活性，这归功于其对HIF-1的抑制活性，HIF-1是一种在癌症生长和转移中起重要作用的转录因子，但不具有一般细胞毒性。因此，HIF抑制剂及其药用可接受的盐可用作治疗各种癌症，如肝癌、胃癌和乳腺癌的治疗药物。此外，具有对HIF-1抑制活性的化合物在治疗由HIF-1介导的VEGF表达加重的糖尿病视网膜病变和关节炎方面是有用的。
• Anti‐Tumoural [NHC(thiolato)] Gold(I) Complexes Derived from HIF‐1α Inhibitor AC1‐004 Target the Mitochondrial Redox System and Show Antiangiogenic Effects in vivo
  作者：Sebastian W. Schleser、Leonhard H. F. Köhler、Florian Riethmüller、Sebastian Reich、Robin Fertig、Luca Schlotte、Jonathan Seib、Alexander Goller、Gerrit Begemann、Rhett Kempe、Rainer Schobert

  DOI：10.1002/cplu.202300167

  日期：2023.5

  AC1‐004 is a potent inhibitor of the hypoxia‐inducible factor alpha (HIF‐1α) pathway, essential for tumour growth, angiogenesis and metastasis. We modelled a series of gold(I) complexes on AC1‐004, retaining its 5‐carboalkoxybenzimidazole as an NHC ligand while replacing its 2‐aryloxymethyl residue with modified thiolato gold(I) fragments. The intention was to augment a potential HIF‐1α inhibition by conducive effects typical of NHC gold complexes, such as an inhibition of tumoural thioredoxin reductase (TrxR), an increase in reactive oxygen species (ROS), and cytotoxic and antiangiogenic effects. We report on the synthesis and biological effects of twelve such N,N’‐dialkylbenzimidazol‐2‐ylidene gold(I) complexes, obtained in average yields of 65 % for the thiophenolato and 45 % for the novel 4‐(adamant‐2‐yl)benzenethiol complexes. The structure of one complex was validated via single‐crystal X‐ray diffraction. Structure‐activity relationships (SAR) were derived by variation of the N‐substituents (Me, Et, iPr, pentyl, Bn) and the thiolato ligand. Their cytotoxicity against various human cancer cell lines of different entities reached IC₅₀ values in the single‐digit micromolar range. The complexes were also assayed for the induction of tumour cell apoptosis (activation of caspase‐3/7), TrxR inhibition and antiangiogenic effects in zebrafish. Cyclopropene‐bearing congeners were employed in click reactions to examine the subcellular accumulation of the complexes.

  摘要AC1-004 是缺氧诱导因子α（HIF-1α）通路的强效抑制剂，对肿瘤生长、血管生成和转移至关重要。我们在 AC1-004 的基础上模拟了一系列金（I）复合物，保留其 5-羧基烷氧基苯并咪唑作为 NHC 配体，同时用改性硫醇金（I）片段取代其 2-芳氧基甲基残基。这样做的目的是通过 NHC 金复合物的典型效应（如抑制肿瘤硫氧还原酶 (TrxR)、增加活性氧 (ROS)、细胞毒性和抗血管生成效应）来增强潜在的 HIF-1α 抑制作用。我们报告了 12 种此类 N,N'-二烷基苯并咪唑-2-亚基金（I）复合物的合成和生物效应，其中噻吩酚复合物的平均产率为 65%，新型 4-（金刚烷-2-基）苯硫酚复合物的平均产率为 45%。通过单晶 X 射线衍射验证了一种复合物的结构。通过改变 N-取代基（Me、Et、iPr、戊基、Bn）和硫醇配体，得出了结构-活性关系（SAR）。它们对不同实体的各种人类癌细胞株的细胞毒性 IC50 值达到了个位数微摩尔范围。这些复合物还在斑马鱼体内进行了诱导肿瘤细胞凋亡（激活 caspase-3/7）、抑制 TrxR 和抗血管生成作用的检测。在点击反应中使用了含环丙烯的同系物，以检测复合物的亚细胞积累情况。
• WO2008/4798
  申请人：——

  公开号：——

  公开（公告）日：——
• COMPOSITION FOR THE PREVENTION AND TREATMENT OF METABOLIC DISORDER CONTAINING BENZAZOLE DERIVATIVES AS AN ACTIVE INGREDIENT
  申请人：Lee Hyun Sun

  公开号：US20100076039A1

  公开（公告）日：2010-03-25

  Disclosed is a composition for the prevention and treatment of metabolic diseases, which comprises a benzazole derivative as an active ingredient. The benzazole derivative has inhibitory activity against DGAT (diacylglycerol acyltransferase), which causes metabolic diseases such as obesity and diabetes in the process of lipid metabolism. With the ability to effectively control lipid metabolism and energy metabolism, thus, the composition is useful in the prevention and treatment of metabolic diseases, such as obesity and diabetes.
• US8304448B2
  申请人：——

  公开号：US8304448B2

  公开（公告）日：2012-11-06