tert-butyl 6-cyano-2-(4-(2,4-dichlorophenoxy)phenyl)-1H-indole-1-carboxylate | 1207731-19-8

• 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: tert-butyl 6-cyano-2-(4-(2,4-dichlorophenoxy)phenyl)-1H-indole-1-carboxylate
• 英文别名: Tert-butyl 6-cyano-2-[4-(2,4-dichlorophenoxy)phenyl]indole-1-carboxylate
• CAS: 1207731-19-8
• 化学式: C₂₆H₂₀Cl₂N₂O₃
• 分子量: 479.362
• InChiKey: BQSQXNPRMPECOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  64.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 6-cyano-2-(4-(2,4-dichlorophenoxy)phenyl)-1H-indole-1-carboxylate 、 乙二胺 在 tetraphosphorus decasulfide 作用下， 反应 2.0h， 以64%的产率得到2-(4-(2,4-dichlorophenoxy)phenyl)-6-(4,5-dihydro-1H-imidazol-2-yl)-1H-indole
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Botulinum Neurotoxin A Protease Inhibitors

  摘要：

  NSC 240898 was previously identified as a botulinum neurotoxin A light chain (BoNT/A LC) endopeptidase inhibitor by screening the National Cancer Institute Open Repository diversity set. Two types of analogues have been synthesized and shown to inhibit BoNT/A LC in a FRET-based enzyme assay, with confirmation in an HPLC-based assay. These two series of compounds have also been evaluated for inhibition of anthrax lethal factor (LF), an unrelated metalloprotease, to examine enzyme specificity of the BoNT/A LC inhibition. The most potent inhibitor against BoNT/A LC in these two series is compound 12 (IC50 = 2.5 mu M, FRET assay), which is 4.4-fold more potent than the lead structure and 11.2-fold more selective for BoNT/A LC versus the anthrax LF metalloproteinase. Structure-activity relationship studies have revealed structural features important to potency and enzyme specificity.

  DOI：

  10.1021/jm901852f
• 作为产物：
  描述：

  1-Boc-6-氰基吲哚-2-硼酸 、 1-(4-bromophenoxy)-2,4-dichlorobenzene 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 1.5h， 以49%的产率得到tert-butyl 6-cyano-2-(4-(2,4-dichlorophenoxy)phenyl)-1H-indole-1-carboxylate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Botulinum Neurotoxin A Protease Inhibitors

  摘要：

  NSC 240898 was previously identified as a botulinum neurotoxin A light chain (BoNT/A LC) endopeptidase inhibitor by screening the National Cancer Institute Open Repository diversity set. Two types of analogues have been synthesized and shown to inhibit BoNT/A LC in a FRET-based enzyme assay, with confirmation in an HPLC-based assay. These two series of compounds have also been evaluated for inhibition of anthrax lethal factor (LF), an unrelated metalloprotease, to examine enzyme specificity of the BoNT/A LC inhibition. The most potent inhibitor against BoNT/A LC in these two series is compound 12 (IC50 = 2.5 mu M, FRET assay), which is 4.4-fold more potent than the lead structure and 11.2-fold more selective for BoNT/A LC versus the anthrax LF metalloproteinase. Structure-activity relationship studies have revealed structural features important to potency and enzyme specificity.

  DOI：

  10.1021/jm901852f

文献信息

• Synthesis and Biological Evaluation of Botulinum Neurotoxin A Protease Inhibitors
  作者：Bing Li、Ramdas Pai、Steven C. Cardinale、Michelle M. Butler、Norton P. Peet、Donald T. Moir、Sina Bavari、Terry L. Bowlin

  DOI：10.1021/jm901852f

  日期：2010.3.11

  NSC 240898 was previously identified as a botulinum neurotoxin A light chain (BoNT/A LC) endopeptidase inhibitor by screening the National Cancer Institute Open Repository diversity set. Two types of analogues have been synthesized and shown to inhibit BoNT/A LC in a FRET-based enzyme assay, with confirmation in an HPLC-based assay. These two series of compounds have also been evaluated for inhibition of anthrax lethal factor (LF), an unrelated metalloprotease, to examine enzyme specificity of the BoNT/A LC inhibition. The most potent inhibitor against BoNT/A LC in these two series is compound 12 (IC50 = 2.5 mu M, FRET assay), which is 4.4-fold more potent than the lead structure and 11.2-fold more selective for BoNT/A LC versus the anthrax LF metalloproteinase. Structure-activity relationship studies have revealed structural features important to potency and enzyme specificity.