N-(4-bromo-2-methylphenyl)-2-naphthamide | 429627-41-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(4-bromo-2-methylphenyl)-2-naphthamide
• 英文别名: N-(4-bromo-2-methylphenyl)naphthalene-2-carboxamide
• CAS: 429627-41-8
• 化学式: C₁₈H₁₄BrNO
• 分子量: 340.219
• InChiKey: QDOYRUBXBHREAH-UHFFFAOYSA-N

物化性质

• 熔点：
  168-170 °C
• 沸点：
  397.5±35.0 °C(Predicted)
• 密度：
  1.448±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  2-甲基-4-溴苯胺 、 2-萘甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以49%的产率得到N-(4-bromo-2-methylphenyl)-2-naphthamide
  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.