2-[3'-fluoro-4'-(N-hydroxyamidino)biphenyl-4-yl]-1H-benzimidazole-5-(N-hydroxy)amidine | 869767-82-8

• 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: 2-[3'-fluoro-4'-(N-hydroxyamidino)biphenyl-4-yl]-1H-benzimidazole-5-(N-hydroxy)amidine
• 英文别名: 2-[3-fluoro-4'-(N-hydroxycarbamimidoyl)-biphenyl-4-yl]-N-hydroxy-1H-benzimidazole-5-carboxamidine；2-[4-[3-fluoro-4-[(Z)-N'-hydroxycarbamimidoyl]phenyl]phenyl]-N'-hydroxy-3H-benzimidazole-5-carboximidamide
• CAS: 869767-82-8
• 化学式: C₂₁H₁₇FN₆O₂
• 分子量: 404.403
• InChiKey: AGALMNSBOBUPKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  146
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[3'-fluoro-4'-(N-hydroxyamidino)biphenyl-4-yl]-1H-benzimidazole-5-(N-hydroxy)amidine 、 溶剂黄146 在 palladium on activated charcoal 乙酸酐 、 氢气 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 4.0h， 以85%的产率得到2-(4'-amidino-3'-fluorobiphenyl-4-yl)-1H-benzimidazole-5-amidine acetic acid salt 1:3
  参考文献：
  名称：

  Dicationic near-linear biphenyl benzimidazole derivatives as DNA-targeted antiprotozoal agents

  摘要：

  A series of near-linear biphenyl benzimidazole diamidines 5a-h were synthesized from their respective diamidoximes (4a-h), through the bis-O-acetoxyamidoxime, followed by hydrogenation in glacial acetic acid/ethanol in the presence of Pd-C. Compounds 4a-h were obtained in three steps, starting with the Suzuki coupling reaction of the appropriate haloarylcarbonitriles la-g or 4-bromo-2-fluorobenzaldehyde with 4-formylphenylboronic acid or 4-cyanophenylboronic acid to form the anticipated 4-formylbiphenyl carbonitrile analogues 2a-h. Subsequent condensation of the formyl derivatives 2a-h with 3,4-diaminobenzonitrile in the presence of sodium bisulfite or 1,4-benzoquinone gave the desired dinitriles 3a-h, the precursors for 4a-h. All the diamidines showed strong DNA affinities, as judged by high Delta T-m values with poly(dA.dT)(2). The compounds were quite active in vitro versus Trypanosoma brucei rhodesiense, giving IC50 values ranging from 3 to 37 nM. These compounds were even more active versus Plasmodium falciparum, exhibiting IC50 values ranging from 0.5 to 23 nM. The compounds showed moderate to good activity in vivo in the STIB900 model for acute African trypanosomiasis. The most active compounds 5b and e gave 3/4 cures on an IP dosage of 20 mg/kg. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.024
• 作为产物：
  描述：

  2-(4'-cyano-3'-fluorobiphenyl-4-yl)-1H-benzimidazole-5-carbonitrile 在 盐酸羟胺 、 potassium tert-butylate 作用下， 以 二甲基亚砜 为溶剂， 以96%的产率得到2-[3'-fluoro-4'-(N-hydroxyamidino)biphenyl-4-yl]-1H-benzimidazole-5-(N-hydroxy)amidine
  参考文献：
  名称：

  Dicationic near-linear biphenyl benzimidazole derivatives as DNA-targeted antiprotozoal agents

  摘要：

  A series of near-linear biphenyl benzimidazole diamidines 5a-h were synthesized from their respective diamidoximes (4a-h), through the bis-O-acetoxyamidoxime, followed by hydrogenation in glacial acetic acid/ethanol in the presence of Pd-C. Compounds 4a-h were obtained in three steps, starting with the Suzuki coupling reaction of the appropriate haloarylcarbonitriles la-g or 4-bromo-2-fluorobenzaldehyde with 4-formylphenylboronic acid or 4-cyanophenylboronic acid to form the anticipated 4-formylbiphenyl carbonitrile analogues 2a-h. Subsequent condensation of the formyl derivatives 2a-h with 3,4-diaminobenzonitrile in the presence of sodium bisulfite or 1,4-benzoquinone gave the desired dinitriles 3a-h, the precursors for 4a-h. All the diamidines showed strong DNA affinities, as judged by high Delta T-m values with poly(dA.dT)(2). The compounds were quite active in vitro versus Trypanosoma brucei rhodesiense, giving IC50 values ranging from 3 to 37 nM. These compounds were even more active versus Plasmodium falciparum, exhibiting IC50 values ranging from 0.5 to 23 nM. The compounds showed moderate to good activity in vivo in the STIB900 model for acute African trypanosomiasis. The most active compounds 5b and e gave 3/4 cures on an IP dosage of 20 mg/kg. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.024