3-((2-((2-(1H-imidazol-4-yl)ethyl)amino)-9H-purin-6-yl)amino)phenol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 3-((2-((2-(1H-imidazol-4-yl)ethyl)amino)-9H-purin-6-yl)amino)phenol
• 英文别名: 3-[[2-[2-(1H-imidazol-5-yl)ethylamino]-7H-purin-6-yl]amino]phenol
• 化学式: C₁₆H₁₆N₈O
• 分子量: 336.356
• InChiKey: JASWHCDBIHTHFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  127
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2,6-二氯嘌呤 在 三乙胺 作用下， 以 正丁醇 为溶剂， 70.0~130.0 ℃ 、1.79 MPa 条件下， 反应 0.34h， 生成 3-((2-((2-(1H-imidazol-4-yl)ethyl)amino)-9H-purin-6-yl)amino)phenol
  参考文献：
  名称：

  Discovery of Multitarget Antivirals Acting on Both the Dengue Virus NS5-NS3 Interaction and the Host Src/Fyn Kinases

  摘要：

  This study describes the discovery of novel dengue virus inhibitors targeting both a crucial viral protein protein interaction and an essential host cell factor as a strategy to reduce the emergence of drug resistance. Starting from known c-Src inhibitors, a virtual screening was performed to identify molecules able to interact with a recently discovered allosteric pocket on the dengue virus NS5 polymerase. The selection of cheap-to-produce scaffolds and the exploration of the biologically relevant chemical space around them suggested promising candidates for chemical synthesis. A series of purines emerged as the most interesting candidates able to inhibit virus replication at low micromolar concentrations with no Significant toxicity to the host cell. Among the identified antivirals, compound 16i proved to be 10 times More potent than ribavirin, showed a better selectivity index and represents the first-in-class DENV-NS5 allosteric inhibitor able to target both the virus NS5-NS3 interaction and the host kinases c-Src/Fyn.

  DOI：

  10.1021/acs.jmedchem.5b00108

文献信息

• Discovery of Multitarget Antivirals Acting on Both the Dengue Virus NS5-NS3 Interaction and the Host Src/Fyn Kinases
  作者：Paolo Vincetti、Fabiana Caporuscio、Suzanne Kaptein、Antimo Gioiello、Valentina Mancino、Youichi Suzuki、Naoki Yamamoto、Emmanuele Crespan、Andrea Lossani、Giovanni Maga、Giulio Rastelli、Daniele Castagnolo、Johan Neyts、Pieter Leyssen、Gabriele Costantino、Marco Radi

  DOI：10.1021/acs.jmedchem.5b00108

  日期：2015.6.25

  This study describes the discovery of novel dengue virus inhibitors targeting both a crucial viral protein protein interaction and an essential host cell factor as a strategy to reduce the emergence of drug resistance. Starting from known c-Src inhibitors, a virtual screening was performed to identify molecules able to interact with a recently discovered allosteric pocket on the dengue virus NS5 polymerase. The selection of cheap-to-produce scaffolds and the exploration of the biologically relevant chemical space around them suggested promising candidates for chemical synthesis. A series of purines emerged as the most interesting candidates able to inhibit virus replication at low micromolar concentrations with no Significant toxicity to the host cell. Among the identified antivirals, compound 16i proved to be 10 times More potent than ribavirin, showed a better selectivity index and represents the first-in-class DENV-NS5 allosteric inhibitor able to target both the virus NS5-NS3 interaction and the host kinases c-Src/Fyn.