2-(Biphenyl-3-ylaminomethylene)-malonic acid diethyl ester | 35957-51-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(Biphenyl-3-ylaminomethylene)-malonic acid diethyl ester
• 英文别名: Diethyl [(biphenyl-3-ylamino)methylidene]propanedioate；diethyl 2-[(3-phenylanilino)methylidene]propanedioate
• CAS: 35957-51-8
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: OIXUYKLSAZTIDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(Biphenyl-3-ylaminomethylene)-malonic acid diethyl ester 在 sodium hydroxide 作用下， 以 二苯醚 、 水 为溶剂， 反应 0.08h， 生成 4-Oxo-7-phenyl-1,4-dihydro-quinoline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and antiplatelet activity of phenyl quinolones

  摘要：

  In our search for novel antiplatelet agents, seven positional phenyl quinolone isomers were synthesized. Preliminary screening confirmed their inhibitory effects against arachidonic acid (AA)-induced platelet aggregation. Varying the substitutional position of the phenyl group had a profound effect on the antiplatelet activity of these isomers. 3-Phenyl-4-quinolone showed the greatest potency and was superior to indomethacin, although the two structures are quite different. The mechanism and pharmacological action of 3-phenyl-4-quinolone are currently under investigation. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00141-2
• 作为产物：
  描述：

  苯硼酸 在 palladium diacetate 三苯基膦 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 2-(Biphenyl-3-ylaminomethylene)-malonic acid diethyl ester
  参考文献：
  名称：

  Design and Synthesis of Potent Inhibitors of the Malaria Parasite Dihydroorotate Dehydrogenase

  摘要：

  Pyrimidine biosynthesis presents an attractive drug target in malaria parasites due to the absence of a pyrimidine salvage pathway. A set of compounds designed to inhibit the Plasmodium falciparum pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (PfDHODH) was synthesized. PfDHODH-specific inhibitors with low nanomolar binding affinities were identified that bind in the N-terminal hydrophobic channel of dihydroorotate dehydrogenase, the presumed site of ubiquinone binding during oxidation of dihydroorotate to orotate. These compounds also prevented growth of cultured parasites at low micromolar concentrations. Models that suggest the mode of inhibitor binding is based on shape complementarity, matching hydrophobic regions of inhibitor and enzyme, and interaction of inhibitors with amino acid residues F188, H185, and R265 are supported by mutagenesis data. These results further highlight PfDHODH as a promising new target for chemotherapeutic intervention in prevention of malaria and provide better understanding of the factors that determine specificity over human dihydroorotate dehydrogenase.

  DOI：

  10.1021/jm060687j

文献信息

• Design and Synthesis of Potent Inhibitors of the Malaria Parasite Dihydroorotate Dehydrogenase
  作者：Timo Heikkilä、Christopher Ramsey、Matthew Davies、Christophe Galtier、Andrew M. W. Stead、A. Peter Johnson、Colin W. G. Fishwick、Andrew N. Boa、Glenn A. McConkey

  DOI：10.1021/jm060687j

  日期：2007.1.1

  Pyrimidine biosynthesis presents an attractive drug target in malaria parasites due to the absence of a pyrimidine salvage pathway. A set of compounds designed to inhibit the Plasmodium falciparum pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (PfDHODH) was synthesized. PfDHODH-specific inhibitors with low nanomolar binding affinities were identified that bind in the N-terminal hydrophobic channel of dihydroorotate dehydrogenase, the presumed site of ubiquinone binding during oxidation of dihydroorotate to orotate. These compounds also prevented growth of cultured parasites at low micromolar concentrations. Models that suggest the mode of inhibitor binding is based on shape complementarity, matching hydrophobic regions of inhibitor and enzyme, and interaction of inhibitors with amino acid residues F188, H185, and R265 are supported by mutagenesis data. These results further highlight PfDHODH as a promising new target for chemotherapeutic intervention in prevention of malaria and provide better understanding of the factors that determine specificity over human dihydroorotate dehydrogenase.
• Synthesis and antiplatelet activity of phenyl quinolones
  作者：Li-Jiau Huang、Ming-Chieh Hsieh、Che-Ming Teng、Kuo-Hsiung Lee、Sheng-Chu Kuo

  DOI：10.1016/s0968-0896(98)00141-2

  日期：1998.10

  In our search for novel antiplatelet agents, seven positional phenyl quinolone isomers were synthesized. Preliminary screening confirmed their inhibitory effects against arachidonic acid (AA)-induced platelet aggregation. Varying the substitutional position of the phenyl group had a profound effect on the antiplatelet activity of these isomers. 3-Phenyl-4-quinolone showed the greatest potency and was superior to indomethacin, although the two structures are quite different. The mechanism and pharmacological action of 3-phenyl-4-quinolone are currently under investigation. (C) 1998 Elsevier Science Ltd. All rights reserved.