(E)-N-(5-(benzylsulfanyl)-1,3,4-thiadiazol-2-yl)-3-(1-((2,4-bis(tri-fluoromethyl)phenyl)methyl)-1H-indol-3-yl)-2-cyanoprop-2-enamide

• 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: (E)-N-(5-(benzylsulfanyl)-1,3,4-thiadiazol-2-yl)-3-(1-((2,4-bis(tri-fluoromethyl)phenyl)methyl)-1H-indol-3-yl)-2-cyanoprop-2-enamide
• 英文别名: (E)-N-(5-benzylsulfanyl-1,3,4-thiadiazol-2-yl)-3-[1-[[2,4-bis(trifluoromethyl)phenyl]methyl]indol-3-yl]-2-cyanoprop-2-enamide
• 化学式: C₃₀H₁₉F₆N₅OS₂
• 分子量: 643.636
• InChiKey: IJLHAFBTKOUZKT-UDWIEESQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  137
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2,4-双(三氟甲基)溴苄 在 哌啶 、 sodium methylate 、 sodium hydride 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 (E)-N-(5-(benzylsulfanyl)-1,3,4-thiadiazol-2-yl)-3-(1-((2,4-bis(tri-fluoromethyl)phenyl)methyl)-1H-indol-3-yl)-2-cyanoprop-2-enamide
  参考文献：
  名称：

  Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease

  摘要：

  Dengue virus is endemic throughout tropical and subtropical regions, and cause severe epidemic diseases. The NS2B/NS3 protease is a promising drug target for dengue virus. Herein, we report the discovery and modification of a novel class of thiadiazoloacrylamide derivatives with potent inhibitory activity against the NS2B/NS3 protease. Thiadiazolopyrimidinone 1 was firstly determined as a new chemical structure against NS2B/NS3 from a commercial compound library. Then, we sought to identify similar compounds with the thiadiazoloacrylamide core that would exhibit better activity. A series of analogues were synthesized and fourteen of them were identified with strong inhibitory activities, in which the nitrile group in the linker part was discovered as an essential group for the inhibitory activity. The best of these (8b) demonstrated an IC50 at 2.24 mu M based on in vitro DENV2 NS2B-NS3pro assays. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.09.057

文献信息

• Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease
  作者：Hailong Liu、Ruoming Wu、Yanyan Sun、Yan Ye、Jing Chen、Xiaomin Luo、Xu Shen、Hong Liu

  DOI：10.1016/j.bmc.2014.09.057

  日期：2014.11

  Dengue virus is endemic throughout tropical and subtropical regions, and cause severe epidemic diseases. The NS2B/NS3 protease is a promising drug target for dengue virus. Herein, we report the discovery and modification of a novel class of thiadiazoloacrylamide derivatives with potent inhibitory activity against the NS2B/NS3 protease. Thiadiazolopyrimidinone 1 was firstly determined as a new chemical structure against NS2B/NS3 from a commercial compound library. Then, we sought to identify similar compounds with the thiadiazoloacrylamide core that would exhibit better activity. A series of analogues were synthesized and fourteen of them were identified with strong inhibitory activities, in which the nitrile group in the linker part was discovered as an essential group for the inhibitory activity. The best of these (8b) demonstrated an IC50 at 2.24 mu M based on in vitro DENV2 NS2B-NS3pro assays. (C) 2014 Published by Elsevier Ltd.