phenyl[1,1']pyridyl[4',1'']phenyl-4,4''-bis-N-hydroxyamidine | 910547-45-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: phenyl[1,1']pyridyl[4',1'']phenyl-4,4''-bis-N-hydroxyamidine
• 英文别名: phenyl[1,1']pyridyl[4',1'']phenyl-4,4''-bis-N-hydroxycarboxamidine；N'-hydroxy-4-[6-[4-[(Z)-N'-hydroxycarbamimidoyl]phenyl]pyridin-3-yl]benzenecarboximidamide
• CAS: 910547-45-4
• 化学式: C₁₉H₁₇N₅O₂
• 分子量: 347.376
• InChiKey: YOGNYUSOLBXXLD-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C
• 沸点：
  585.9±60.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  130
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  phenyl[1,1']pyridyl[4',1'']phenyl-4,4''-bis-N-hydroxyamidine 、 乙酸酐 在 palladium on activated charcoal 溶剂黄146 、 氢气 作用下， 20.0 ℃ 、344.74 kPa 条件下， 生成 acetic acid;4-[6-(4-carbamimidoylphenyl)pyridin-3-yl]benzenecarboximidamide
  参考文献：
  名称：

  Synthesis, DNA Affinity, and Antiprotozoal Activity of Linear Dications:  Terphenyl Diamidines and Analogues

  摘要：

  Diamidines 10a-g and 18a, b were obtained from dinitriles 9a-g and 15a, b by treatment with lithium trimethylsilylamide or upon hydrogenation of bis-O-acetoxyamidoximes. Dinitriles 9a-g were prepared via Suzuki reactions between arylboronic acids and arylnitriles. Potential prodrugs 12a-f and 17 were prepared via methylation of the diamidoximes 11a-f and 16a. Significant DNA affinities for rigid-rod molecules were observed. Compounds 10a, 10b, 10d, 18a, and 18b show IC50 values of 5 nM or less against Trypanosoma brucei rhodesiense ( T. b. r.) and 10a, 10b, 10e, 18a, and 18b gave similar ones against Plasmodium falciparum ( P. f.). The dications, 10a, 10d, 10f, and 10g are more active than furamidine in vivo. The prodrugs are only moderately effective on oral administration. Mouse liver microsome bioconversion of the methamidoxime prodrugs is significantly reduced from that of pafuramidine and suggests that the in vivo efficacy of these prodrugs is, in part, due to poor bioconversion.

  DOI：

  10.1021/jm060470p
• 作为产物：
  描述：

  phenyl[1,1']pyridyl[4',1'']phenyl-4,4''-bis-carbonitrile 在 盐酸羟胺 、 potassium tert-butylate 作用下， 以 二甲基亚砜 为溶剂， 以97%的产率得到phenyl[1,1']pyridyl[4',1'']phenyl-4,4''-bis-N-hydroxyamidine
  参考文献：
  名称：

  Synthesis, DNA Affinity, and Antiprotozoal Activity of Linear Dications:  Terphenyl Diamidines and Analogues

  摘要：

  Diamidines 10a-g and 18a, b were obtained from dinitriles 9a-g and 15a, b by treatment with lithium trimethylsilylamide or upon hydrogenation of bis-O-acetoxyamidoximes. Dinitriles 9a-g were prepared via Suzuki reactions between arylboronic acids and arylnitriles. Potential prodrugs 12a-f and 17 were prepared via methylation of the diamidoximes 11a-f and 16a. Significant DNA affinities for rigid-rod molecules were observed. Compounds 10a, 10b, 10d, 18a, and 18b show IC50 values of 5 nM or less against Trypanosoma brucei rhodesiense ( T. b. r.) and 10a, 10b, 10e, 18a, and 18b gave similar ones against Plasmodium falciparum ( P. f.). The dications, 10a, 10d, 10f, and 10g are more active than furamidine in vivo. The prodrugs are only moderately effective on oral administration. Mouse liver microsome bioconversion of the methamidoxime prodrugs is significantly reduced from that of pafuramidine and suggests that the in vivo efficacy of these prodrugs is, in part, due to poor bioconversion.

  DOI：

  10.1021/jm060470p

文献信息

• Synthesis, DNA Affinity, and Antiprotozoal Activity of Linear Dications:  Terphenyl Diamidines and Analogues
  作者：Mohamed A. Ismail、Reem K. Arafa、Reto Brun、Tanja Wenzler、Yi Miao、W. David Wilson、Claudia Generaux、Arlene Bridges、James E. Hall、David W. Boykin

  DOI：10.1021/jm060470p

  日期：2006.8.1

  Diamidines 10a-g and 18a, b were obtained from dinitriles 9a-g and 15a, b by treatment with lithium trimethylsilylamide or upon hydrogenation of bis-O-acetoxyamidoximes. Dinitriles 9a-g were prepared via Suzuki reactions between arylboronic acids and arylnitriles. Potential prodrugs 12a-f and 17 were prepared via methylation of the diamidoximes 11a-f and 16a. Significant DNA affinities for rigid-rod molecules were observed. Compounds 10a, 10b, 10d, 18a, and 18b show IC50 values of 5 nM or less against Trypanosoma brucei rhodesiense ( T. b. r.) and 10a, 10b, 10e, 18a, and 18b gave similar ones against Plasmodium falciparum ( P. f.). The dications, 10a, 10d, 10f, and 10g are more active than furamidine in vivo. The prodrugs are only moderately effective on oral administration. Mouse liver microsome bioconversion of the methamidoxime prodrugs is significantly reduced from that of pafuramidine and suggests that the in vivo efficacy of these prodrugs is, in part, due to poor bioconversion.