2-((1H-indol-3-yl)methyl)-1H-benzo[d]imidazole | 18382-16-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-((1H-indol-3-yl)methyl)-1H-benzo[d]imidazole
• 英文别名: 2-(Indol-3-ylmethyl)benzimidazole；2-(1H-indol-3-ylmethyl)-1H-benzimidazole
• CAS: 18382-16-6
• 化学式: C₁₆H₁₃N₃
• 分子量: 247.299
• InChiKey: KNWCOKXQOGGRMQ-UHFFFAOYSA-N

物化性质

• 熔点：
  193-193.5 °C(Solvent: Nitromethane)
• 沸点：
  583.8±33.0 °C(Predicted)
• 密度：
  1.322±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 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：
  44.5
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-((1H-indol-3-yl)methyl)-1H-benzo[d]imidazole 在 selenium(IV) oxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 生成 (1H-benzo[d]imidazol-2-yl)(1H-indol-3-yl)methanone
  参考文献：
  名称：

  From methylene bridged diindole to carbonyl linked benzimidazoleindole: Development of potent and metabolically stable PCSK9 modulators

  摘要：

  Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently validated therapeutic target for lowering low-density lipoprotein cholesterol (LDL-C). Through phenotypic screening, we previously discovered a class of small-molecules with a 2,3'-diindolymethane (DIM) skeleton that can decrease the expression of PCSK9. But these compounds have low potency and low metabolically stability. After performing structure-activity relationship (SAR) optimization by nitrogen scan, deuterium substitution and fluorine scan, we identified a series of much more potent and metabolically stable PCSK9 modulators. A preliminary in vivo pharmacokinetic study was performed for representative analogues difluorodiindolyketone (DFDIK) 12 and difluorobenzoimidazolylindolylketone (DFBIIK-1) 13. The in vitro metabolic stability correlate well with the in vivo data. The most potent compound 21 has the EC50 of 0.15 nM. Our SAR studies also indicated that the NH on the indole ring of 21 can tolerate more function groups, which may facilitate the mechanism of action studies and also allow further improvement of the pharmacological properties. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112678
• 作为产物：
  描述：

  吲哚-3-乙腈 在 盐酸 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 21.0h， 生成 2-((1H-indol-3-yl)methyl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  唑及其衍生物的合成和性质。32.吲哚羧酸亚氨基酯盐酸盐的合成及部分转化

  摘要：

  DOI：

  10.1007/bf00561348

文献信息

• A General Approach to Substituted Benzimidazoles and Benzoxazoles <i>via</i> Heterogeneous Palladium‐Catalyzed Hydrogen‐Transfer with Primary Amines
  作者：Marianna Pizzetti、Elisa De Luca、Elena Petricci、Andrea Porcheddu、Maurizio Taddei

  DOI：10.1002/adsc.201200253

  日期：2012.9.17

  employed. Primary amines are the most suitable reagents for the atom economy of the overall process that resulted to be general as several different substituted benzimidazoles were obtained in good yield. Benzoxazoles can be also prepared starting from primary amines and o‐aminophenol. The reaction is also highly selective as no (poly)‐alkylated phenylenediamines or cross‐contaminated benzimidazoles are

  据报道，在钯/炭存在下，以邻苯二胺和胺为原料合成苯并咪唑。在微波电介质加热，可以使用叔胺，仲，和甚至伯胺作为底物为钯-介导的过程中得到的2-取代的或1,2-二取代的苯并咪唑，取决于性质ø -使用的苯二胺。对于整个过程的原子经济性而言，伯胺是最合适的试剂，由于获得了数种不同的取代苯并咪唑类，它们的收率很高，因此普遍使用。苯并恶唑也可以从伯胺和邻氨基苯甲酸开始制备氨基苯酚 由于没有从（N-单烷基苯二胺）获得（多）烷基化的苯二胺或交叉污染的苯并咪唑，该反应的选择性也很高。这种行为被解释为与N-烷基芳基胺的芳族NH键连接的亚甲基脱氢的稀缺性。实验进行了同意，以画出过程中发生的反应路径的几乎完整图景。催化剂可以循环使用几次，尽管远未达到最佳性能，但催化剂TON = 90对于进一步的大规模优化方案是令人鼓舞的。此外，上的木炭催化微波辅助反应在钯Ò苯二胺使叔胺脱烷基并转化为仲胺。
• BENZOIMIDAZOLE INDOLYL METHANES AND METHODS OF USING THEM TO INHIBIT PCKS9 AND PCKS9-MEDIATED AILMENTS
  申请人：Wisconsin Alumni Research Foundation

  公开号：US20200262819A1

  公开（公告）日：2020-08-20

  Described are benzoimidazole indolyl methane compounds, pharmaceutical compositions containing them, and use of the compounds to inhibit PCSK9-mediated ailments. The compounds have the structure:

  描述了苯并咪唑吲哚甲烷化合物，含有它们的药物组合物，以及利用这些化合物抑制PCSK9介导的疾病。这些化合物具有以下结构：
• Synthesis and biological evaluation of benzimidazole derivatives as potent AMP-activated protein kinase activators
  作者：Julie Charton、Sophie Girault-Mizzi、Marie-Ange Debreu-Fontaine、Fabienne Foufelle、Isabelle Hainault、Jean-Guy Bizot-Espiard、Daniel-Henri Caignard、Christian Sergheraert

  DOI：10.1016/j.bmc.2006.02.028

  日期：2006.7

  Design, synthesis and structure-activity relationships of beU:/AP/DTD501/BMC/4818nzimidazole derivatives as activators of the AMP-activated protein kinase (AMPK) are presented in this paper. AMPK is the central component of a protein kinase cascade that plays a key role in the regulation of energy balance. Once activated, AMPK initiates a series of responses that are aimed at restoring the energy balance of the cell and recent studies have indicated that AMPK plays an important role in regulation of the whole-body energy metabolism. The following study based on the lead compound S27847 involved modification of three regions of this compound. Preliminary structure activity relationships are being described. (c) 2006 Elsevier Ltd. All rights reserved.
• Antiinflammatory activity of novel indole derivatives
  作者：M Verma、M Tripathi、AK Saxena、K Shanker

  DOI：10.1016/0223-5234(94)90193-7

  日期：1994.1

  3-[(2-Imidazolyl, benzimidazolyl or benzoxazolyl)alkyl]indoles 2a-h were synthesized by cyclizing the carboxylic group of (3-indolyl)alkanoic acids 1 with ethylenediamine, o-phenylenediamine or o-aminophenol, respectively. Reaction of 1 with p-aminoacetophenone or aryl-substituted thiosemicarbazones yielded N-(4-acetylphenyl)-(2 or 4)-(indol-3-yl)alkylcarboxamides 3a-b or l-arylidene 4-[2-(indol-3-yl)(acetyl or propionyl)]thiosemicarbazides 5a-h; 3a-b were cyclized into N-[4-(2-aminothiazol-4-yl)phenyl]-(2 or 4)-(indol-3-yl)alkylcarboxamides 4a-b. Cyclization of 5a-h with malonic acid yielded 1-[2-(indol-3-yl)(acetyl or propionyl)]-3-arylideneamino-2-thiobarbituric acids 6a-h, which were finally converted into corresponding Mannich bases 7a-f. Compounds 2a-h, 4a-b, 6a-h and 7a-f were evaluated for their antiinflammatory activity. Compounds 2e, 2g, 4b, 6c and 6d exhibited promising antiinflammatory activity with a lower ulcerogenic liability than indomethacin.
• KELAREV V. I.; SHVEXGEJMER G. A., XIMIYA GETEROTSIKL. SOEDIN., 1980, HO 5, 645-650
  作者：KELAREV V. I.、 SHVEXGEJMER G. A.

  DOI：——

  日期：——