methyl 4-(2-{1-benzhydryl-5-chloro-2-[2-({[(phenylsulfanyl)methyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoate | 683813-68-5

• 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-({[(phenylsulfanyl)methyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoate
• 英文别名: Methyl 4-[2-[1-benzhydryl-5-chloro-2-[2-(phenylsulfanylmethylsulfonylamino)ethyl]indol-3-yl]ethoxy]benzoate
• CAS: 683813-68-5
• 化学式: C₄₀H₃₇ClN₂O₅S₂
• 分子量: 725.329
• InChiKey: RJHQGBCRWGPXAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.4
• 重原子数：
  50
• 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-({[(phenylsulfanyl)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93%的产率得到4-(2-{1-benzhydryl-5-chloro-2-[2-({[(phenylsulfanyl)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 、 苯硫酚 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 84.0h， 生成 methyl 4-(2-{1-benzhydryl-5-chloro-2-[2-({[(phenylsulfanyl)methyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoate
  参考文献：
  名称：

  Methods for the use of inhibitors of cytosolic phospholipase A2 in the treatment of thrombosis

  摘要：

  这项发明提供了一种使用通式所示的取代吲哚化合物及其药用盐形式的方法。该发明提供了一种在哺乳动物中治疗或预防血栓形成，或预防血栓形成症状进展的化合物使用方法。

  公开号：

  US20080009485A1

文献信息

• Process for making an aldehyde
  申请人：Wyeth

  公开号：US20040082785A1

  公开（公告）日：2004-04-29

  A process for making an aromatic aldehyde in which a sulfoxide is reacted with a dihalogenated aromatic compound in the absence of an effective amount of an activating reagent. The aldehyde may then be used to make other compounds, such as a compound that acts as a cPLA inhibitor.

  一种制备芳香醛的过程，其中亚砜与双卤代芳香化合物在缺乏有效量活化试剂的情况下发生反应。然后可以使用该醛制备其他化合物，例如作为cPLA抑制剂的化合物。