5H-[1,3]Dioxolo[4,5-f]indole-6-carbonyl chloride | 1025925-62-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5H-[1,3]Dioxolo[4,5-f]indole-6-carbonyl chloride
• CAS: 1025925-62-5
• 化学式: C₁₀H₆ClNO₃
• 分子量: 223.616
• InChiKey: IYEWPLVEZUUFMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5H-[1,3]Dioxolo[4,5-f]indole-6-carbonyl chloride 在 三溴化硼 作用下， 以 1,4-二氧六环 、 乙醚 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 N-(3,4-dihydroxyphenethyl)-5,6-dihydroxy-1H-indole-2-carboxamide
  参考文献：
  名称：

  Virtual Screening and Biological Validation of Novel Influenza Virus PA Endonuclease Inhibitors

  摘要：

  The influenza virus RNA-dependent RNA polymerase complex (RdRp), a heterotrimeric protein complex responsible for viral RNA transcription and replication, represents a primary target for antiviral drug development. One particularly attractive approach is interference with the endonucleolytic "cap-snatching" reaction by the RdRp subunit PA, more precisely by inhibiting its metal-dependent catalytic activity which resides in the N-terminal part of PA (PA-Nter). Almost all PA inhibitors (PAIs) thus far discovered bear pharmacophoric fragments with chelating motifs able to bind the bivalent metal ions in the catalytic core of PA-Nter. More recently, the availability of crystallographic structures of PA-Nter has enabled rational design of original PAIs with improved binding properties and antiviral potency. We here present a coupled pharmacophore/docking virtual screening approach that allowed us to identify PAIs with interesting inhibitory activity in a PA-Nter enzymatic assay. Moreover, antiviral activity in the low micromolar range was observed in cell-based influenza virus assays.

  DOI：

  10.1021/acsmedchemlett.5b00109
• 作为产物：
  描述：

  ethyl 5H-[1,3]dioxolo[4,5-f]indole-6-carboxylate 在 氢氧化钾 、 氯化亚砜 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 0.5h， 生成 5H-[1,3]Dioxolo[4,5-f]indole-6-carbonyl chloride
  参考文献：
  名称：

  Indoles and pyridazino[4,5-b]indoles as nonnucleoside analog inhibitors of HIV-1 reverse transcriptase

  摘要：

  The synthesis and the study of the activity of new indol-2-carboxamides and pyridazino[4,5-b]indoles as inhibitors of HIV-1 reverse transcriptase (RT) are presented. The activity of the compounds synthesized as inhibitors of different types of HIV-1 RT (wild type enzyme and mutant forms P236L, Y181C and P236L/Y181C) was evaluated. The activity of the most active compounds was investigated in the syncytia reduction in vitro assay, in HIV-1(IIIB)-infected HT4lacZ-1 cells. Their potential cytotoxicity was determined in parallel. Two lead compounds, N-[1-[2-(3-isopropylamino)pyridyl]piperazin]-5,6-methylenedioxy indol-2-carboxamide 7q and N-[1-[2-(3-ethylamino)pyridyl]piperazin] 7s have been identified.

  DOI：

  10.1016/0223-5234(96)88316-4

文献信息

• Indoles and pyridazino[4,5-b]indoles as nonnucleoside analog inhibitors of HIV-1 reverse transcriptase
  作者：M Font、A Monge、A Cuartero、A Elorriaga、J.J. Martínez-Irujo、E Alberdi、E Santiago、I Prieto、J.J. Lasarte、P Sarobe、F Borrás

  DOI：10.1016/0223-5234(96)88316-4

  日期：1995.1

  The synthesis and the study of the activity of new indol-2-carboxamides and pyridazino[4,5-b]indoles as inhibitors of HIV-1 reverse transcriptase (RT) are presented. The activity of the compounds synthesized as inhibitors of different types of HIV-1 RT (wild type enzyme and mutant forms P236L, Y181C and P236L/Y181C) was evaluated. The activity of the most active compounds was investigated in the syncytia reduction in vitro assay, in HIV-1(IIIB)-infected HT4lacZ-1 cells. Their potential cytotoxicity was determined in parallel. Two lead compounds, N-[1-[2-(3-isopropylamino)pyridyl]piperazin]-5,6-methylenedioxy indol-2-carboxamide 7q and N-[1-[2-(3-ethylamino)pyridyl]piperazin] 7s have been identified.
• Virtual Screening and Biological Validation of Novel Influenza Virus PA Endonuclease Inhibitors
  作者：Nicolino Pala、Annelies Stevaert、Roberto Dallocchio、Alessandro Dessì、Dominga Rogolino、Mauro Carcelli、Vanna Sanna、Mario Sechi、Lieve Naesens

  DOI：10.1021/acsmedchemlett.5b00109

  日期：2015.8.13

  The influenza virus RNA-dependent RNA polymerase complex (RdRp), a heterotrimeric protein complex responsible for viral RNA transcription and replication, represents a primary target for antiviral drug development. One particularly attractive approach is interference with the endonucleolytic "cap-snatching" reaction by the RdRp subunit PA, more precisely by inhibiting its metal-dependent catalytic activity which resides in the N-terminal part of PA (PA-Nter). Almost all PA inhibitors (PAIs) thus far discovered bear pharmacophoric fragments with chelating motifs able to bind the bivalent metal ions in the catalytic core of PA-Nter. More recently, the availability of crystallographic structures of PA-Nter has enabled rational design of original PAIs with improved binding properties and antiviral potency. We here present a coupled pharmacophore/docking virtual screening approach that allowed us to identify PAIs with interesting inhibitory activity in a PA-Nter enzymatic assay. Moreover, antiviral activity in the low micromolar range was observed in cell-based influenza virus assays.