6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-[5-[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy]pyridin-2-yl]-1H-indole | 1207731-09-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-[5-[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy]pyridin-2-yl]-1H-indole
• CAS: 1207731-09-6
• 化学式: C₂₇H₂₆N₆O
• 分子量: 450.543
• InChiKey: FQSGYUOFFSDKSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  86.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(5-(4-cyanophenoxy)pyridin-2-yl)-1H-indole-6-carbonitrile 、 1,3-丙二胺 在 tetraphosphorus decasulfide 作用下， 反应 2.0h， 生成 6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-[5-[4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy]pyridin-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

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.