1-(4-Fluorophenyl)-2-[2-(2-pyridyl)benzimidazol-1-yl]ethanone | 1355254-68-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-Fluorophenyl)-2-[2-(2-pyridyl)benzimidazol-1-yl]ethanone
• 英文别名: 1-(4-fluorophenyl)-2-(2-pyridin-2-ylbenzimidazol-1-yl)ethanone
• CAS: 1355254-68-0
• 化学式: C₂₀H₁₄FN₃O
• 分子量: 331.349
• InChiKey: NOLNQMFTDAFHCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  47.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-吡啶甲酸 在 polyphosphoric acid 作用下， 以 丙酮 为溶剂， 反应 12.0h， 生成 1-(4-Fluorophenyl)-2-[2-(2-pyridyl)benzimidazol-1-yl]ethanone
  参考文献：
  名称：

  New benzimidazole derivatives as antiplasmodial agents and plasmepsin inhibitors: Synthesis and analysis of structure–activity relationships

  摘要：

  The newly synthesized benzimidazole compounds were suggested to be inhibitors of Plasmodium falciparum plasmepsin II and human cathepsin D by virtual screening of an internal library of synthetic compounds. This was confirmed by enzyme inhibition studies that gave IC50 values in the low micromolar range (2-48 mu M). Ligand docking studies with plasmepsin II predicted binding of benzimidazole compounds at the center of the extended substrate-binding cleft. According to the plausible mode of binding, the pyridine ring of benzimidazole compounds interacted with S1' subsite residues whereas the acetophenone moiety was in contact with S1-S3 subsites of plasmepsin II active center. The benzimidazole derivatives were evaluated for capacity to inhibit the growth of intraerythrocytic P. falciparum in culture. Four benzimidazole compounds inhibited parasite growth at <= 3 mu M. The most active compound 10, 1-(4-phenylphenyl)-2[2-(pyridinyl-2-yl)-1,3-benzdiazol-1-yl]ethanone showed an IC50 of 160 nM. The substitution of a phenyl group and a chlorine atom at the para position of the acetophenone moiety were shown to be crucial for antiplasmodial activity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.018

文献信息

• New benzimidazole derivatives as antiplasmodial agents and plasmepsin inhibitors: Synthesis and analysis of structure–activity relationships
  作者：Zafar Saied Saify、M. Kamran Azim、Waseem Ahmad、Mehrun Nisa、Daniel E. Goldberg、Shaheen A. Hussain、Shamim Akhtar、Arfa Akram、Arshad Arayne、Anna Oksman、Ishtiaq A. Khan

  DOI：10.1016/j.bmcl.2011.10.018

  日期：2012.1

  The newly synthesized benzimidazole compounds were suggested to be inhibitors of Plasmodium falciparum plasmepsin II and human cathepsin D by virtual screening of an internal library of synthetic compounds. This was confirmed by enzyme inhibition studies that gave IC50 values in the low micromolar range (2-48 mu M). Ligand docking studies with plasmepsin II predicted binding of benzimidazole compounds at the center of the extended substrate-binding cleft. According to the plausible mode of binding, the pyridine ring of benzimidazole compounds interacted with S1' subsite residues whereas the acetophenone moiety was in contact with S1-S3 subsites of plasmepsin II active center. The benzimidazole derivatives were evaluated for capacity to inhibit the growth of intraerythrocytic P. falciparum in culture. Four benzimidazole compounds inhibited parasite growth at <= 3 mu M. The most active compound 10, 1-(4-phenylphenyl)-2[2-(pyridinyl-2-yl)-1,3-benzdiazol-1-yl]ethanone showed an IC50 of 160 nM. The substitution of a phenyl group and a chlorine atom at the para position of the acetophenone moiety were shown to be crucial for antiplasmodial activity. (C) 2011 Elsevier Ltd. All rights reserved.