2’,5’-二氯联苯-3-羧酸 | 1049036-18-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2’,5’-二氯联苯-3-羧酸
• 英文名称: 2',5'-dichloro-[1,1'-biphenyl]-3-carboxylic acid
• 英文别名: 3-(2,5-dichlorophenyl)benzoic acid
• CAS: 1049036-18-1
• 化学式: C₁₃H₈Cl₂O₂
• 分子量: 267.111
• InChiKey: DSHFQBLSASSQRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2916399090

反应信息

• 作为反应物：
  描述：

  2’,5’-二氯联苯-3-羧酸 在 4-二甲氨基吡啶 、 potassium cyanide 、 羟胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 (2S,3S)-2-((2',5'-dichloro-[1,1'-biphenyl]-3-yl)formamido)-N-hydroxy-3-methylpentanamide
  参考文献：
  名称：

  Synthesis and activity of isoleucine sulfonamide derivatives as novel botulinum neurotoxin serotype A light chain inhibitors

  摘要：

  The botulinum neurotoxin (BoNT) is the most lethal protein known to man causing the deadly disease botulinum. The neurotoxin, composed of a heavy (HC) and light (LC) chain, work in concert to cause muscle paralysis. A therapeutic strategy to treat individuals infected with the neurotoxin is inhibiting the catalytic activity of the BoNT LC. We report the synthesis, inhibition study and computational docking analysis of novel small molecule BoNT/A LC inhibitors. A structure activity relationship study resulted in the discovery of D-isoleucine functionalized with a hydroxamic acid on the C-terminal and a biphenyl with chlorine at C- 2 connected by a sulfonamide linker at the N-terminus. This compound has a measured IC50 of 0.587 mu M for the BoNT/A LC. Computational docking analysis indicates the sulfonamide linker adopts a geometry that is advantageous for binding to the BoNT LC active site. In addition, Arg363 is predicted to be involved in key binding interactions with the scaffold in this study.

  DOI：

  10.1016/j.bmc.2020.115659
• 作为产物：
  描述：

  2,5-二氯苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 24.17h， 生成 2’,5’-二氯联苯-3-羧酸
  参考文献：
  名称：

  Synthesis and activity of isoleucine sulfonamide derivatives as novel botulinum neurotoxin serotype A light chain inhibitors

  摘要：

  The botulinum neurotoxin (BoNT) is the most lethal protein known to man causing the deadly disease botulinum. The neurotoxin, composed of a heavy (HC) and light (LC) chain, work in concert to cause muscle paralysis. A therapeutic strategy to treat individuals infected with the neurotoxin is inhibiting the catalytic activity of the BoNT LC. We report the synthesis, inhibition study and computational docking analysis of novel small molecule BoNT/A LC inhibitors. A structure activity relationship study resulted in the discovery of D-isoleucine functionalized with a hydroxamic acid on the C-terminal and a biphenyl with chlorine at C- 2 connected by a sulfonamide linker at the N-terminus. This compound has a measured IC50 of 0.587 mu M for the BoNT/A LC. Computational docking analysis indicates the sulfonamide linker adopts a geometry that is advantageous for binding to the BoNT LC active site. In addition, Arg363 is predicted to be involved in key binding interactions with the scaffold in this study.

  DOI：

  10.1016/j.bmc.2020.115659

文献信息

• Synthesis and activity of isoleucine sulfonamide derivatives as novel botulinum neurotoxin serotype A light chain inhibitors
  作者：Jordan C. Thompson、Wendy T. Dao、Alex Ku、Sandra L. Rodriguez-Beltran、Martin Amezcua、Alejandra Y. Palomino、Thanh Lien、Nicholas T. Salzameda

  DOI：10.1016/j.bmc.2020.115659

  日期：2020.9

  The botulinum neurotoxin (BoNT) is the most lethal protein known to man causing the deadly disease botulinum. The neurotoxin, composed of a heavy (HC) and light (LC) chain, work in concert to cause muscle paralysis. A therapeutic strategy to treat individuals infected with the neurotoxin is inhibiting the catalytic activity of the BoNT LC. We report the synthesis, inhibition study and computational docking analysis of novel small molecule BoNT/A LC inhibitors. A structure activity relationship study resulted in the discovery of D-isoleucine functionalized with a hydroxamic acid on the C-terminal and a biphenyl with chlorine at C- 2 connected by a sulfonamide linker at the N-terminus. This compound has a measured IC50 of 0.587 mu M for the BoNT/A LC. Computational docking analysis indicates the sulfonamide linker adopts a geometry that is advantageous for binding to the BoNT LC active site. In addition, Arg363 is predicted to be involved in key binding interactions with the scaffold in this study.