methyl 4-[2-(1-benzhydryl-5-chloro-2-{2-[({[(2,4-dichlorophenyl)sulfanyl]methyl}sulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoate | 1125597-70-7

• 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: methyl 4-[2-(1-benzhydryl-5-chloro-2-{2-[({[(2,4-dichlorophenyl)sulfanyl]methyl}sulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoate
• 英文别名: Methyl 4-[2-[1-benzhydryl-5-chloro-2-[2-[(2,4-dichlorophenyl)sulfanylmethylsulfonylamino]ethyl]indol-3-yl]ethoxy]benzoate
• CAS: 1125597-70-7
• 化学式: C₄₀H₃₅Cl₃N₂O₅S₂
• 分子量: 794.219
• InChiKey: SJWIEAHOBWYSHU-UHFFFAOYSA-N

物化性质

• 沸点：
  902.0±75.0 °C(predicted)
• 密度：
  1.34±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.7
• 重原子数：
  52
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 4-[2-(1-benzhydryl-5-chloro-2-{2-[({[(2,4-dichlorophenyl)sulfanyl]methyl}sulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoate 在 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以100%的产率得到4-[2-(1-benzhydryl-5-chloro-2-{2-[({[(2,4-dichlorophenyl)sulfanyl]methyl}sulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoic acid
  参考文献：
  名称：

  Reactions of Functionalized Sulfonamides: Application to Lowering the Lipophilicity of Cytosolic Phospholipase A₂α Inhibitors

  摘要：

  The cPLA(2)alpha inhibitors we reported earlier were potent in both isolated enzyme and rat whole blood assays but have high plogD(7.4). To address these issues, reactions of electrophilic sulfonamides 9-12 were employed to incorporate various heterocyclic or heterciatom-based reagents into cPLA(2)alpha inhibitors. For example, reactions of 9 with sulfur nucleophiles such as thiophenol allowed rapid assembly of thioether analogues that were converted into the corresponding sulfoxides to afford less lipophilic derivatives. Reactions of 10 and 11 with various nitrogen nucleophiles, including aromatic heterocycles and aliphatic an-fines, provided an efficient way to introduce polarity into cPLA(2)alpha inhibitors. Finally, we report the first application of (2-formylphenyl)methanesulfonyl chloride, 13. Reductive amination of 2-formylphenylmethane sulfonamides allowed the introduction of various nitrogen nucleophiles. Several inhibitors obtained herein have plogD(7.4) values 3-4 units lower than previously synthesized compounds and yet maintain in vitro potency.

  DOI：

  10.1021/jm8009876
• 作为产物：
  描述：

  methyl 4-{2-[1-benzhydryl-5-chloro-2-(2-{[(chloromethyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoate 、 2,4-二氯苯硫酚 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 methyl 4-[2-(1-benzhydryl-5-chloro-2-{2-[({[(2,4-dichlorophenyl)sulfanyl]methyl}sulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoate
  参考文献：
  名称：

  Reactions of Functionalized Sulfonamides: Application to Lowering the Lipophilicity of Cytosolic Phospholipase A₂α Inhibitors

  摘要：

  The cPLA(2)alpha inhibitors we reported earlier were potent in both isolated enzyme and rat whole blood assays but have high plogD(7.4). To address these issues, reactions of electrophilic sulfonamides 9-12 were employed to incorporate various heterocyclic or heterciatom-based reagents into cPLA(2)alpha inhibitors. For example, reactions of 9 with sulfur nucleophiles such as thiophenol allowed rapid assembly of thioether analogues that were converted into the corresponding sulfoxides to afford less lipophilic derivatives. Reactions of 10 and 11 with various nitrogen nucleophiles, including aromatic heterocycles and aliphatic an-fines, provided an efficient way to introduce polarity into cPLA(2)alpha inhibitors. Finally, we report the first application of (2-formylphenyl)methanesulfonyl chloride, 13. Reductive amination of 2-formylphenylmethane sulfonamides allowed the introduction of various nitrogen nucleophiles. Several inhibitors obtained herein have plogD(7.4) values 3-4 units lower than previously synthesized compounds and yet maintain in vitro potency.

  DOI：

  10.1021/jm8009876