4-(5-fluoro-1H-benzo[d]imidazol-2-yl)benzonitrile

• 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-(5-fluoro-1H-benzo[d]imidazol-2-yl)benzonitrile
• 英文别名: 4-(6-fluoro-1H-benzimidazol-2-yl)benzonitrile
• 化学式: C₁₄H₈FN₃
• mdl: MFCD11218406
• 分子量: 237.236
• InChiKey: HTSVISSTQLSBSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  52.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(5-fluoro-1H-benzo[d]imidazol-2-yl)benzonitrile 在 盐酸羟胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 18.33h， 以76%的产率得到(Z)-4-(5-fluoro-1H-benzo[d]imidazol-2-yl)-N'-hydroxybenzimidamide
  参考文献：
  名称：

  Synthesis of 2-aryl-1,2,4-oxadiazolo-benzimidazoles: Tubulin polymerization inhibitors and apoptosis inducing agents

  摘要：

  A new series of 2-aryl 1,2,4-oxadiazolo-benzimidazole conjugates have been synthesized and evaluated for their antiproliferative activity in the sixty cancer cell line panel of the National Cancer Institute (NCI). Compounds 5l (NSC: 761109/1) and 5x (NSC: 761814/1) exhibited remarkable cytotoxic activity against most of the cancer cell lines in the one dose assay and were further screened at five dose concentrations (0.01, 0.1, 1, 10 and 100 mu M) which showed GI(50) values in the range of 0.79-28.2 mu M. Flow cytometric data of these compounds showed increased cells in G2/M phase, which is suggestive of G2/M cell cycle arrest. Further, compounds 5l and 5x showed inhibition of tubulin polymerization and disruption of the formation of microtubules. These compounds induce apoptosis byDNAfragmentation and chromatin condensation as well as by mitochondrial membrane depolarization. In addition, structure activity relationship studies within the series are also discussed. Molecular docking studies of compounds 5l and 5x into the colchicine-binding site of the tubulin, revealed the possible mode of interaction by these compounds. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.060
• 作为产物：
  描述：

  4-氟-1,2-苯二胺 、 4-氰基苯甲醛 在 sodium metabisulfite 作用下， 以 乙醇 、 水 为溶剂， 以69%的产率得到4-(5-fluoro-1H-benzo[d]imidazol-2-yl)benzonitrile
  参考文献：
  名称：

  Synthesis of 2-aryl-1,2,4-oxadiazolo-benzimidazoles: Tubulin polymerization inhibitors and apoptosis inducing agents

  摘要：

  A new series of 2-aryl 1,2,4-oxadiazolo-benzimidazole conjugates have been synthesized and evaluated for their antiproliferative activity in the sixty cancer cell line panel of the National Cancer Institute (NCI). Compounds 5l (NSC: 761109/1) and 5x (NSC: 761814/1) exhibited remarkable cytotoxic activity against most of the cancer cell lines in the one dose assay and were further screened at five dose concentrations (0.01, 0.1, 1, 10 and 100 mu M) which showed GI(50) values in the range of 0.79-28.2 mu M. Flow cytometric data of these compounds showed increased cells in G2/M phase, which is suggestive of G2/M cell cycle arrest. Further, compounds 5l and 5x showed inhibition of tubulin polymerization and disruption of the formation of microtubules. These compounds induce apoptosis byDNAfragmentation and chromatin condensation as well as by mitochondrial membrane depolarization. In addition, structure activity relationship studies within the series are also discussed. Molecular docking studies of compounds 5l and 5x into the colchicine-binding site of the tubulin, revealed the possible mode of interaction by these compounds. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.060

文献信息

• Synthesis of 2-aryl-1,2,4-oxadiazolo-benzimidazoles: Tubulin polymerization inhibitors and apoptosis inducing agents
  作者：Ahmed Kamal、T. Srinivasa Reddy、M.V.P.S. Vishnuvardhan、Vijaykumar D. Nimbarte、A.V. Subba Rao、Vunnam Srinivasulu、Nagula Shankaraiah

  DOI：10.1016/j.bmc.2015.05.060

  日期：2015.8

  A new series of 2-aryl 1,2,4-oxadiazolo-benzimidazole conjugates have been synthesized and evaluated for their antiproliferative activity in the sixty cancer cell line panel of the National Cancer Institute (NCI). Compounds 5l (NSC: 761109/1) and 5x (NSC: 761814/1) exhibited remarkable cytotoxic activity against most of the cancer cell lines in the one dose assay and were further screened at five dose concentrations (0.01, 0.1, 1, 10 and 100 mu M) which showed GI(50) values in the range of 0.79-28.2 mu M. Flow cytometric data of these compounds showed increased cells in G2/M phase, which is suggestive of G2/M cell cycle arrest. Further, compounds 5l and 5x showed inhibition of tubulin polymerization and disruption of the formation of microtubules. These compounds induce apoptosis byDNAfragmentation and chromatin condensation as well as by mitochondrial membrane depolarization. In addition, structure activity relationship studies within the series are also discussed. Molecular docking studies of compounds 5l and 5x into the colchicine-binding site of the tubulin, revealed the possible mode of interaction by these compounds. (C) 2015 Elsevier Ltd. All rights reserved.