[1-[(4-Fluorophenyl)methyl]benzimidazol-2-yl]hydrazine | 388574-83-2

• 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: [1-[(4-Fluorophenyl)methyl]benzimidazol-2-yl]hydrazine
• CAS: 388574-83-2
• 化学式: C₁₄H₁₃FN₄
• 分子量: 256.282
• InChiKey: SYEJOGDHENTYAT-UHFFFAOYSA-N

物化性质

• 沸点：
  435.3±47.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  55.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [1-[(4-Fluorophenyl)methyl]benzimidazol-2-yl]hydrazine 在 盐酸 、 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 生成 2-[10-[(4-Fluorophenyl)methyl]-3,4-dioxo-[1,2,4]triazino[4,3-a]benzimidazol-2-yl]acetic acid
  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：

  2-氯苯并咪唑 在 sodium hydride 、 一水合肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 [1-[(4-Fluorophenyl)methyl]benzimidazol-2-yl]hydrazine
  参考文献：
  名称：

  含有苯并咪唑/吡唑啉酮/1,3,4-恶二唑基序的吡咯杂芳唑的合成和细胞毒性评价。

  摘要：

  合成了含有苯并咪唑/吡唑酮/1,3,4-恶二唑的偶氮甲碱连接的吡咯二杂芳唑，收率令人满意。其结构经IR、1H-NMR、13C-NMR和元素分析证实。对一组乳腺癌细胞系（MDA-AB-231、BT-474 和 Ishikawa 细胞）的体外细胞毒活性评估表明，吡咯-苯并咪唑杂合体比吡唑啉酮和 1,3,4-恶二唑更有效所有细胞系中的杂种。化合物 (9) 对 BT-474 细胞系表现出良好的细胞毒性，IC50 值为 7.7 µM。

  DOI：

  10.1002/jhet.2501

文献信息

• Study of Oxidative Cyclization Using PhI(OAc)2 in the Formation of Benzo[4,5]thiazolo[2,3-c][1,2,4]triazoles and Related Heterocycles – Scope and Limitations
  作者：Charles Demmer、Morten Jørgensen、Jan Kehler、Lennart Bunch

  DOI：10.1055/s-0033-1341159

  日期：——

  the synthesis of benzo[4,5]thiazolo[2,3- c ][1,2,4]triazoles and related heterocycles under mild conditions was herein developed. The key step of this transformation is an oxidative cyclization employing PhI(OAc) 2 as reagent. Scope and limitations (group functionality tolerance and sterics) were studied showing the robustness of the present methodology which can be used as potential access to new fused

  本文开发了一种在温和条件下合成苯并[4,5]噻唑并[2,3-c][1,2,4]三唑和相关杂环的一锅两步反应。这种转化的关键步骤是使用 PhI(OAc) 2 作为试剂的氧化环化。研究了范围和限制（基团功能耐受性和空间），显示了本方法的稳健性，可用作获取新的融合杂环库的潜在途径。
• [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.
• Synthesis and Cytotoxic Evaluation of Pyrrole Hetarylazoles Containing Benzimidazole/Pyrazolone/1,3,4-Oxadiazole Motifs
  作者：Bereket Mochona、Timothy Jackson、DeCoria McCauley、Elizabeth Mazzio、Kinfe K. Redda

  DOI：10.1002/jhet.2501

  日期：2016.11

  Azomethine linked pyrrole bishetarylazoles containing benzimidazole/pyrazolone/1,3,4-oxadiazole were synthesized in satisfactory yields. Their structures were confirmed by IR, 1H-NMR, 13C-NMR and elemental analysis. Evaluation for the cytotoxic activities In vitro against a panel of breast cancer cell lines (MDA-AB-231, BT-474 and Ishikawa cells) revealed that the pyrrole-benzimidazole hybrids are

  合成了含有苯并咪唑/吡唑酮/1,3,4-恶二唑的偶氮甲碱连接的吡咯二杂芳唑，收率令人满意。其结构经IR、1H-NMR、13C-NMR和元素分析证实。对一组乳腺癌细胞系（MDA-AB-231、BT-474 和 Ishikawa 细胞）的体外细胞毒活性评估表明，吡咯-苯并咪唑杂合体比吡唑啉酮和 1,3,4-恶二唑更有效所有细胞系中的杂种。化合物 (9) 对 BT-474 细胞系表现出良好的细胞毒性，IC50 值为 7.7 µM。