methyl 2-(quinolin-2-ylthio)acetate | 52131-60-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl 2-(quinolin-2-ylthio)acetate
• 英文别名: methyl (S-2-quinolinoyl)mercaptoacetate；quinolin-2-ylsulfanyl-acetic acid methyl ester；Methyl 2-quinolin-2-ylsulfanylacetate
• CAS: 52131-60-9
• 化学式: C₁₂H₁₁NO₂S
• 分子量: 233.291
• InChiKey: ZYWCPBUXYWIYRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  64.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-(quinolin-2-ylthio)acetate 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 5.0h， 生成 (2-quinolinylthio)acetic acid
  参考文献：
  名称：

  Discovery of an Inhibitor for the TREK-1 Channel Targeting an Intermediate Transition State of Channel Gating

  摘要：

  Modulators can be designed to stabilize the inactive and active states of ion channels, but whether intermediate (IM) states of channel gating are druggable remains underexplored. In this study, using molecular dynamics simulations of the TWIK-related potassium channel 1 (TREK-1) channel, a two-pore domain potassium channel, we captured an IM state during the transition from the down (inactive) state to the up (active-like) state. The IM state contained a druggable allosteric pocket that was not present in the down or up state. Drug design targeting the pocket led to the identification of the TKIM compound as an inhibitor of TREK-1. Using integrated methods, we verified that TKIM binds to the pocket of the IM state of TREK-1, which differs from the binding of common inhibitors, which bind to channels in the inactive state. Overall, this study identified an allosteric ligand-binding site and a new mechanistic inhibitor for TREK-1, suggesting that IM states of ion channels may be promising druggable targets for use in discovering allosteric modulators.

  DOI：

  10.1021/acs.jmedchem.0c00842
• 作为产物：
  描述：

  2-氯喹啉 、 巯基乙酸甲酯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 生成 methyl 2-(quinolin-2-ylthio)acetate
  参考文献：
  名称：

  Discovery of an Inhibitor for the TREK-1 Channel Targeting an Intermediate Transition State of Channel Gating

  摘要：

  Modulators can be designed to stabilize the inactive and active states of ion channels, but whether intermediate (IM) states of channel gating are druggable remains underexplored. In this study, using molecular dynamics simulations of the TWIK-related potassium channel 1 (TREK-1) channel, a two-pore domain potassium channel, we captured an IM state during the transition from the down (inactive) state to the up (active-like) state. The IM state contained a druggable allosteric pocket that was not present in the down or up state. Drug design targeting the pocket led to the identification of the TKIM compound as an inhibitor of TREK-1. Using integrated methods, we verified that TKIM binds to the pocket of the IM state of TREK-1, which differs from the binding of common inhibitors, which bind to channels in the inactive state. Overall, this study identified an allosteric ligand-binding site and a new mechanistic inhibitor for TREK-1, suggesting that IM states of ion channels may be promising druggable targets for use in discovering allosteric modulators.

  DOI：

  10.1021/acs.jmedchem.0c00842

文献信息

• Discovery of an Inhibitor for the TREK-1 Channel Targeting an Intermediate Transition State of Channel Gating
  作者：Yuqin Ma、Qichao Luo、Jie Fu、Yanxin Che、Fei Guo、Lianghe Mei、Qiansen Zhang、Yang Li、Huaiyu Yang

  DOI：10.1021/acs.jmedchem.0c00842

  日期：2020.10.8

  Modulators can be designed to stabilize the inactive and active states of ion channels, but whether intermediate (IM) states of channel gating are druggable remains underexplored. In this study, using molecular dynamics simulations of the TWIK-related potassium channel 1 (TREK-1) channel, a two-pore domain potassium channel, we captured an IM state during the transition from the down (inactive) state to the up (active-like) state. The IM state contained a druggable allosteric pocket that was not present in the down or up state. Drug design targeting the pocket led to the identification of the TKIM compound as an inhibitor of TREK-1. Using integrated methods, we verified that TKIM binds to the pocket of the IM state of TREK-1, which differs from the binding of common inhibitors, which bind to channels in the inactive state. Overall, this study identified an allosteric ligand-binding site and a new mechanistic inhibitor for TREK-1, suggesting that IM states of ion channels may be promising druggable targets for use in discovering allosteric modulators.