phenyl[1,1']pyridyl[4',1'']phenyl-4,4''-bis-carbonitrile | 168426-35-5

• 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-carbonitrile
• 英文别名: 2,5-bis(4-cyanophenyl)pyridine；4,4'-(Pyridine-2,5-diyl)dibenzonitrile；4-[6-(4-cyanophenyl)pyridin-3-yl]benzonitrile
• CAS: 168426-35-5
• 化学式: C₁₉H₁₁N₃
• 分子量: 281.316
• InChiKey: IPUBOJHKMVZIOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  60.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  phenyl[1,1']pyridyl[4',1'']phenyl-4,4''-bis-carbonitrile 在 盐酸羟胺 、 potassium tert-butylate 、 溶剂黄146 作用下， 以 二甲基亚砜 为溶剂， 5.0~20.0 ℃ 、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：

  2,5-二溴吡啶 、 4-氰基苯硼酸 在 四(三苯基膦)钯 sodium carbonate 作用下， 以 甲醇 、 甲苯 为溶剂， 以84%的产率得到phenyl[1,1']pyridyl[4',1'']phenyl-4,4''-bis-carbonitrile
  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 of dicationic diarylpyridines as nucleic-acid binding agents
  作者：A Kumar、RA Rhodes、J Spychala、WD Wilson、DW Boykin、RR Tidwell、CC Dykstra、JE Hall、SK Jones、RF Schinazi

  DOI：10.1016/0223-5234(96)88214-6

  日期：1995.1

  4-bromoacetophenone in six steps is presented. The dications bind to poly dA.dT in the order 7 > 13 > 18 > 8 > 9; the order of binding to poly A.U is 7 > 13 > 8 > 9; 18 essentially does not bind to the RNA model. Only 7 inhibits topoisomerase II at millimolar concentrations. The dicationic compounds that were tested against Pneumonocystis carinii in the immuno-suppressed rat model show only modest activity

  2,6-双[4-(4,5-二氢-1H-咪唑-2-基)苯基]吡啶7, 2-[4-(4,5-二氢-1H-咪唑-2-基)的合成)-苯基]-6-[3-(4,5-二氢-1H-咪唑-2-基)苯基]吡啶8和2,6-双[3-(4,5-二氢-1H-咪唑-描述了来自适当取代的溴苯乙酮的五个步骤中的 2-基)苯基]吡啶 9。还报道了 3,5-双[4-(4,5-二氢-1H-咪唑-2-基)苯基]吡啶 13，由 4-溴苯基乙腈分四步制备。2,5-双[4-(4,5-二氢-1H-咪唑-2-基)-苯基]吡啶 18 由 4-溴苯乙酮分六步制备。指示以 7 > 13 > 18 > 8 > 9 的顺序与聚 dA.dT 结合；与poly AU的结合顺序为7>13>8>9；18 基本上不与 RNA 模型结合。只有 7 在毫摩尔浓度下抑制拓扑异构酶 II。在免疫抑制大鼠模型中针对卡氏肺囊虫测试的双阳离子化合物仅显示出中等活性并且具有中
• Azaterphenyl diamidines as antileishmanial agents
  作者：Laixing Hu、Reem K. Arafa、Mohamed A. Ismail、Tanja Wenzler、Reto Brun、Manoj Munde、W. David Wilson、Sandra Nzimiro、Serene Samyesudhas、Karl A. Werbovetz、David W. Boykin

  DOI：10.1016/j.bmcl.2007.10.091

  日期：2008.1

  Eighteen diamidino azaterphenyls and analogues were evaluated as anti-leishmanials; nine of the compounds gave IC50 values less than 1 mu M, five exhibited values less than 0.40 mu M, and two gave values less than 0.10 mu M in a Leishmania donovani axenic amastigote assay. The activity of the diamidines strongly depends on the ring N-atom location relative to the amidine groups and correlates with DNA affinity. Transmission electron microscopy studies showed a dramatic dilation of the mitochondrion and evidence of disintegration of the kinetoplast of the amastigotes. (C) 2007 Elsevier Ltd. All rights reserved.
• 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.