8-甲烷硫代磺酰基-辛酸 | 1076198-40-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 8-甲烷硫代磺酰基-辛酸
• 英文名称: 8-((methylsulfonyl)thio)octanoic acid
• 英文别名: 8-Methanethiosulfonyl-octanoic Acid；8-methylsulfonylsulfanyloctanoic acid
• CAS: 1076198-40-7
• 化学式: C₉H₁₈O₄S₂
• 分子量: 254.372
• InChiKey: CLHFYHOFMNNBIY-UHFFFAOYSA-N

物化性质

• 熔点：
  56-59?C
• 溶解度：
  可溶于氯仿、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  O-(四氢-2H-吡喃-2-基)羟基胺 、 8-甲烷硫代磺酰基-辛酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.03h， 以81%的产率得到S-(8-oxo-8-(((tetrahydro-2H-pyran-2-yl)oxy)amino)octyl)methanesulfonothioate
  参考文献：
  名称：

  Catch and Anchor Approach To Combat Both Toxicity and Longevity of Botulinum Toxin A

  摘要：

  Botulinum neurotoxins have remarkable persistence (similar to weeks to months in cells), outlasting the small-molecule inhibitors designed to target them. To address this disconnect, inhibitors bearing two pharmacophores.a zinc binding group and a Cys-reactive warhead.were designed to leverage both affinity and reactivity. A series of first-generation bifunctional inhibitors was achieved through structure-based inhibitor design. Through X-ray crystallography, engagement of both the catalytic Zn2+ and Cys165 was confirmed. A second-generation series improved on affinity by incorporating known reversible inhibitor pharmacophores; the mechanism was confirmed by exhaustive dialysis, mass spectrometry, and in vitro evaluation against the C165S mutant. Finally, a third-generation inhibitor was shown to have good cellular activity and low toxicity. In addition to our findings, an alternative method of modeling time-dependent inhibition that simplifies assay setup and allows comparison of inhibition models is discussed.

  DOI：

  10.1021/acs.jmedchem.0c01006
• 作为产物：
  描述：

  8-溴辛酸 、 硫甲磺酸钠 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以91%的产率得到8-甲烷硫代磺酰基-辛酸
  参考文献：
  名称：

  Catch and Anchor Approach To Combat Both Toxicity and Longevity of Botulinum Toxin A

  摘要：

  Botulinum neurotoxins have remarkable persistence (similar to weeks to months in cells), outlasting the small-molecule inhibitors designed to target them. To address this disconnect, inhibitors bearing two pharmacophores.a zinc binding group and a Cys-reactive warhead.were designed to leverage both affinity and reactivity. A series of first-generation bifunctional inhibitors was achieved through structure-based inhibitor design. Through X-ray crystallography, engagement of both the catalytic Zn2+ and Cys165 was confirmed. A second-generation series improved on affinity by incorporating known reversible inhibitor pharmacophores; the mechanism was confirmed by exhaustive dialysis, mass spectrometry, and in vitro evaluation against the C165S mutant. Finally, a third-generation inhibitor was shown to have good cellular activity and low toxicity. In addition to our findings, an alternative method of modeling time-dependent inhibition that simplifies assay setup and allows comparison of inhibition models is discussed.

  DOI：

  10.1021/acs.jmedchem.0c01006