1-(2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-oxoethyl)pyridinium bromide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 1-(2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-oxoethyl)pyridinium bromide
• 英文别名: 1-(2,3-Dihydro-1,4-benzodioxin-6-yl)-2-pyridin-1-ium-1-ylethanone;bromide
• 化学式: Br*C₁₅H₁₄NO₃
• 分子量: 336.185
• InChiKey: BLJBKWJHHLKBQC-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.37
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-oxoethyl)pyridinium bromide 在 草酰氯 、 ammonium acetate 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 lithium hydroxide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Mining a Kröhnke Pyridine Library for Anti-Arenavirus Activity

  摘要：

  Several arenaviruses cause hemorrhagic fever (HF) disease in humans and represent important public health problems in their endemic regions. In addition, evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus is a neglected human pathogen of clinical significance. There are no licensed arenavirus vaccines, and current antiarenavirus therapy is limited to an off-label use of ribavirin that is only partially effective. Therefore, there is an unmet need for novel therapeutics to combat human pathogenic arenaviruses, a task that will be facilitated by the identification of compounds with antiarenaviral activity that could serve as probes to identify arenavirus-host interactions suitable for targeting, as well as lead compounds to develop future antiarenaviral drugs. Screening of a combinatorial library of Kronhke pyridines identified compound KP-146 [(5-(5-(2,3-dihydrobenzo[b] [1,4] dioxin-6-yl)-4'-methoxy-[1,1'-biphenyl]-3-yl)thiophene-2-carboxamide] as having strong anti-lymphocytic choriomeningitis virus (LCMV) activity in cultured cells. KP-146 did not inhibit LCMV cell entry but rather interfered with the activity of the LCMV ribonucleoprotein (vRNP) responsible for directing virus RNA replication and gene transcription, as well as with the budding process mediated by the LCMV matrix Z protein. LCMV variants with increased resistance to KP-146 did not emerge after serial passages in the presence of KP-146. Our findings support the consideration of Krohnke pyridine scaffold as a valuable source to identify compounds that could serve as tools to dissect arenavirus-host interactions, as well as lead candidate structures to develop antiarenaviral drugs.

  DOI：

  10.1021/acsinfecdis.7b00236
• 作为产物：
  描述：

  吡啶 、 2-溴-1-(2,3-二氢-1,4-苯并二氧)乙酮 以 四氢呋喃 为溶剂， 以2.5 g的产率得到1-(2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-oxoethyl)pyridinium bromide
  参考文献：
  名称：

  Mining a Kröhnke Pyridine Library for Anti-Arenavirus Activity

  摘要：

  Several arenaviruses cause hemorrhagic fever (HF) disease in humans and represent important public health problems in their endemic regions. In addition, evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus is a neglected human pathogen of clinical significance. There are no licensed arenavirus vaccines, and current antiarenavirus therapy is limited to an off-label use of ribavirin that is only partially effective. Therefore, there is an unmet need for novel therapeutics to combat human pathogenic arenaviruses, a task that will be facilitated by the identification of compounds with antiarenaviral activity that could serve as probes to identify arenavirus-host interactions suitable for targeting, as well as lead compounds to develop future antiarenaviral drugs. Screening of a combinatorial library of Kronhke pyridines identified compound KP-146 [(5-(5-(2,3-dihydrobenzo[b] [1,4] dioxin-6-yl)-4'-methoxy-[1,1'-biphenyl]-3-yl)thiophene-2-carboxamide] as having strong anti-lymphocytic choriomeningitis virus (LCMV) activity in cultured cells. KP-146 did not inhibit LCMV cell entry but rather interfered with the activity of the LCMV ribonucleoprotein (vRNP) responsible for directing virus RNA replication and gene transcription, as well as with the budding process mediated by the LCMV matrix Z protein. LCMV variants with increased resistance to KP-146 did not emerge after serial passages in the presence of KP-146. Our findings support the consideration of Krohnke pyridine scaffold as a valuable source to identify compounds that could serve as tools to dissect arenavirus-host interactions, as well as lead candidate structures to develop antiarenaviral drugs.

  DOI：

  10.1021/acsinfecdis.7b00236

文献信息

• Mining a Kröhnke Pyridine Library for Anti-Arenavirus Activity
  作者：Pedro O. Miranda、Beatrice Cubitt、Nicholas T. Jacob、Kim D. Janda、Juan C. de la Torre

  DOI：10.1021/acsinfecdis.7b00236

  日期：2018.5.11

  Several arenaviruses cause hemorrhagic fever (HF) disease in humans and represent important public health problems in their endemic regions. In addition, evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus is a neglected human pathogen of clinical significance. There are no licensed arenavirus vaccines, and current antiarenavirus therapy is limited to an off-label use of ribavirin that is only partially effective. Therefore, there is an unmet need for novel therapeutics to combat human pathogenic arenaviruses, a task that will be facilitated by the identification of compounds with antiarenaviral activity that could serve as probes to identify arenavirus-host interactions suitable for targeting, as well as lead compounds to develop future antiarenaviral drugs. Screening of a combinatorial library of Kronhke pyridines identified compound KP-146 [(5-(5-(2,3-dihydrobenzo[b] [1,4] dioxin-6-yl)-4'-methoxy-[1,1'-biphenyl]-3-yl)thiophene-2-carboxamide] as having strong anti-lymphocytic choriomeningitis virus (LCMV) activity in cultured cells. KP-146 did not inhibit LCMV cell entry but rather interfered with the activity of the LCMV ribonucleoprotein (vRNP) responsible for directing virus RNA replication and gene transcription, as well as with the budding process mediated by the LCMV matrix Z protein. LCMV variants with increased resistance to KP-146 did not emerge after serial passages in the presence of KP-146. Our findings support the consideration of Krohnke pyridine scaffold as a valuable source to identify compounds that could serve as tools to dissect arenavirus-host interactions, as well as lead candidate structures to develop antiarenaviral drugs.