4-benzyl-3-isobutyl-5-((4-methoxybenzyl)thio)-4H-1,2,4-triazole

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-benzyl-3-isobutyl-5-((4-methoxybenzyl)thio)-4H-1,2,4-triazole
• 英文别名: 3-[(4-Methoxyphenyl)methylsulfanyl]-5-(2-methylpropyl)-4-(phenylmethyl)-1,2,4-triazole；4-benzyl-3-[(4-methoxyphenyl)methylsulfanyl]-5-(2-methylpropyl)-1,2,4-triazole
• 化学式: C₂₁H₂₅N₃OS
• 分子量: 367.515
• InChiKey: WYMPXNJKMFASMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  65.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  异戊酸甲酯 在 caesium carbonate 、 一水合肼 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 2.0h， 生成 4-benzyl-3-isobutyl-5-((4-methoxybenzyl)thio)-4H-1,2,4-triazole
  参考文献：
  名称：

  Fragment-based drug discovery of triazole inhibitors to block PDEδ-RAS protein-protein interaction

  摘要：

  Although mutated Ras protein is well recognized as an important drug target, direct targeting Ras has proven to be a daunting task. Recent studies demonstrated that Ras protein needs PDE delta to relocate to plasma membrane to execute its signaling transduction function, which provides a new avenue for modulating the Ras protein. To find small molecules antagonizing the interactions between PDE delta and Ras, here we presented a successful application of fragment-based drug discovery of PDE delta inhibitors. Under the guidance of crystal structures, we are able to quickly optimize the initial fragment into highly potent inhibitors, with more than 2000-fold improvement in binding activity, which further adds to the arsenal towards the inhibition of Ras signaling in cancer therapy. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.12.018