2-氯-1-(4-三氟甲基苄基)-1H-苯并咪唑 | 388574-65-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-氯-1-(4-三氟甲基苄基)-1H-苯并咪唑
• 英文名称: 2-chloro-1-((4-trifluoromethyl)benzyl)benzo[d]imidazole
• 英文别名: 2-Chloro-1-(4-trifluoromethyl-benzyl)-1H-benzoimidazole；2-chloro-1-[[4-(trifluoromethyl)phenyl]methyl]benzimidazole
• CAS: 388574-65-0
• 化学式: C₁₅H₁₀ClF₃N₂
• 分子量: 310.706
• InChiKey: UAQRXZZAJWUUDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-氯-1-(4-三氟甲基苄基)-1H-苯并咪唑 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 5.0h， 生成 Ethyl 2-[3,4-dioxo-10-[[4-(trifluoromethyl)phenyl]methyl]-[1,2,4]triazino[4,3-a]benzimidazol-2-yl]acetate
  参考文献：
  名称：

  [1,2,4]Triazino[4,3-a]benzimidazole Acetic Acid Derivatives:  A New Class of Selective Aldose Reductase Inhibitors

  摘要：

  Acetic acid derivatives of [1,2,4]triazino[4,3-alpha ]benzimidazole (TBI) were synthesized and tested in vitro and in vivo as a novel class of aldose reductase (ALR2) inhibitors. Compound 3, (10-benzyl[1,2,4]triazino[4,3-alpha ]benzimidazol-3,4(10H)-dion-2-yl)acetic acid, displayed the highest inhibitory activity (IC50 = 0.36 muM) and was found to be effective in preventing cataract development in severely galactosemic rats when administered as an eyedrop solution. All the compounds investigated were selective for ALR2, since none of them inhibited appreciably aldehyde reductase, sorbitol dehydrogenase, or glutathione reductase. The activity of 3 was lowered by inserting various substituents on the pendant phenyl ring, by shifting the acetic acid moiety from the 2 to the 3 position of the TBI nucleus, or by cleaving the TBI system to yield benzimidazolylidenehydrazines as open-chain analogues. A three-dimensional model of human ALR2 was built, taking into account the conformational. changes induced by the binding of inhibitors such as zopolrestat, to simulate the docking of 3 into the enzyme active site. The theoretical binding mode of 3 was fully consistent with the structure-activity relationships in the TBI series and will guide the design of novel ALR2 inhibitors.

  DOI：

  10.1021/jm0109210
• 作为产物：
  描述：

  1-(4-trifluoromethylbenzyl)-1,3-dihydro-benzoimidazol-2-one 在 盐酸 、 三氯氧磷 作用下， 以 水 为溶剂， 反应 3.0h， 生成 2-氯-1-(4-三氟甲基苄基)-1H-苯并咪唑
  参考文献：
  名称：

  Synthesis and biological evaluation of 2,3-dihydroimidazo[1,2-a]benzimidazole derivatives against Leishmania donovani and Trypanosoma cruzi

  摘要：

  A high-throughput (HTS) and high-content screening (HCS) campaign of a commercial library identified 2,3-dihydroimidazo[1,2-a]benzimidazole analogues as a novel class of anti-parasitic agents. A series of synthetic derivatives were evaluated for their in vitro anti-leishmanial and anti-trypanosomal activities against Leishmania donovani and Trypanosoma cruzi, which have been known as the causative parasites for visceral leishmaniasis and Chagas disease, respectively. In the case of Leishmania, the compounds were tested in both intracellular amastigote and extracellular promastigote assays. Compounds 4 and 24 showed promising anti-leishmanial activity against intracellular L. donovani (3.05 and 5.29 μM, respectively) and anti-trypanosomal activity against T. cruzi (1.10 and 2.10 μM, respectively) without serious cytotoxicity toward THP-1 and U2OS cell lines.

  DOI：

  10.1016/j.ejmech.2014.07.038

文献信息

• Antimalarial Benzimidazole Derivatives Incorporating Phenolic Mannich Base Side Chains Inhibit Microtubule and Hemozoin Formation: Structure–Activity Relationship and <i>In Vivo</i> Oral Efficacy Studies
  作者：Godwin Akpeko Dziwornu、Dina Coertzen、Meta Leshabane、Constance M. Korkor、Cleavon K. Cloete、Mathew Njoroge、Liezl Gibhard、Nina Lawrence、Janette Reader、Mariëtte van der Watt、Sergio Wittlin、Lyn-Marie Birkholtz、Kelly Chibale

  DOI：10.1021/acs.jmedchem.1c00354

  日期：2021.4.22

  A novel series of antimalarial benzimidazole derivatives incorporating phenolic Mannich base side chains at the C2 position, which possess dual asexual blood and sexual stage activities, is presented. Structure–activity relationship studies revealed that the 1-benzylbenzimidazole analogues possessed submicromolar asexual blood and sexual stage activities in contrast to the 1H-benzimidazole analogues

  提出了一系列新的抗疟疾苯并咪唑衍生物，该衍生物在C2位上结合了酚类曼尼希碱侧链，具有无性血液和有性的双重活动。结构与活性之间的关系研究表明，与1 H-苯并咪唑类似物相比，1-苄基苯并咪唑类似物具有亚微摩尔无性血液和性阶段活动，而1 H-苯并咪唑类似物仅对无性血液阶段（ABS）寄生虫具有活性。此外，前者在ABS寄生虫中表现出微管抑制活性，但在II / III期配子细胞中表现出更显着的抑制作用。1 H-苯并咪唑类似物除了是血红蛋白形成的真正抑制剂外，还显示出对微管的抑制作用。体内对伯氏疟原虫感染的小鼠进行的功效研究表明，当以4×50 mg / kg口服给药时，领先的化合物41表现出很高的功效（寄生虫血症减少98％）。通常，该化合物对哺乳动物细胞无细胞毒性。
• Synthesis and biological evaluation of 2,3-dihydroimidazo[1,2-a]benzimidazole derivatives against Leishmania donovani and Trypanosoma cruzi
  作者：Sangmi Oh、Sungbum Kim、Sunju Kong、Gyongseon Yang、Nakyung Lee、Dawoon Han、Junghyun Goo、Jair L. Siqueira-Neto、Lucio H. Freitas-Junior、Rita Song

  DOI：10.1016/j.ejmech.2014.07.038

  日期：2014.9

  A high-throughput (HTS) and high-content screening (HCS) campaign of a commercial library identified 2,3-dihydroimidazo[1,2-a]benzimidazole analogues as a novel class of anti-parasitic agents. A series of synthetic derivatives were evaluated for their in vitro anti-leishmanial and anti-trypanosomal activities against Leishmania donovani and Trypanosoma cruzi, which have been known as the causative parasites for visceral leishmaniasis and Chagas disease, respectively. In the case of Leishmania, the compounds were tested in both intracellular amastigote and extracellular promastigote assays. Compounds 4 and 24 showed promising anti-leishmanial activity against intracellular L. donovani (3.05 and 5.29 μM, respectively) and anti-trypanosomal activity against T. cruzi (1.10 and 2.10 μM, respectively) without serious cytotoxicity toward THP-1 and U2OS cell lines.
• [1,2,4]Triazino[4,3-<i>a</i>]benzimidazole Acetic Acid Derivatives:  A New Class of Selective Aldose Reductase Inhibitors
  作者：Federico Da Settimo、Giampaolo Primofiore、Antonio Da Settimo、Concettina La Motta、Sabrina Taliani、Francesca Simorini、Ettore Novellino、Giovanni Greco、Antonio Lavecchia、Enrico Boldrini

  DOI：10.1021/jm0109210

  日期：2001.12.1

  Acetic acid derivatives of [1,2,4]triazino[4,3-alpha ]benzimidazole (TBI) were synthesized and tested in vitro and in vivo as a novel class of aldose reductase (ALR2) inhibitors. Compound 3, (10-benzyl[1,2,4]triazino[4,3-alpha ]benzimidazol-3,4(10H)-dion-2-yl)acetic acid, displayed the highest inhibitory activity (IC50 = 0.36 muM) and was found to be effective in preventing cataract development in severely galactosemic rats when administered as an eyedrop solution. All the compounds investigated were selective for ALR2, since none of them inhibited appreciably aldehyde reductase, sorbitol dehydrogenase, or glutathione reductase. The activity of 3 was lowered by inserting various substituents on the pendant phenyl ring, by shifting the acetic acid moiety from the 2 to the 3 position of the TBI nucleus, or by cleaving the TBI system to yield benzimidazolylidenehydrazines as open-chain analogues. A three-dimensional model of human ALR2 was built, taking into account the conformational. changes induced by the binding of inhibitors such as zopolrestat, to simulate the docking of 3 into the enzyme active site. The theoretical binding mode of 3 was fully consistent with the structure-activity relationships in the TBI series and will guide the design of novel ALR2 inhibitors.