(4-{2-Phenyl-6-[5-phenyl-4-(trityloxycarbamoyl-methyl)-thiophene-2-carbonyl]-indol-1-yl}-butyl)-carbamic acid tert-butyl ester | 875272-00-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (4-{2-Phenyl-6-[5-phenyl-4-(trityloxycarbamoyl-methyl)-thiophene-2-carbonyl]-indol-1-yl}-butyl)-carbamic acid tert-butyl ester
• CAS: 875272-00-7
• 化学式: C₅₅H₅₁N₃O₅S
• 分子量: 866.093
• InChiKey: YIMMRFJBRDWBCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.16
• 重原子数：
  64.0
• 可旋转键数：
  16.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  98.66
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (4-{2-Phenyl-6-[5-phenyl-4-(trityloxycarbamoyl-methyl)-thiophene-2-carbonyl]-indol-1-yl}-butyl)-carbamic acid tert-butyl ester 在 2,2,2-三氟乙醇 、 溶剂黄146 作用下， 反应 48.0h， 以92%的产率得到2-{5-[1-(4-N-Boc-aminobutyl)-2-phenyl-1H-indol-6-carbonyl]-2-phenylthiophen-3-yl}-N-hydroxyacetamide
  参考文献：
  名称：

  SMALL-MOLECULE BOTULINUM TOXIN INHIBITORS

  摘要：

  本发明提供了肉毒毒素的小分子抑制剂，包括BoNTA、BoNTD和BoNTE，以及使用这些抑制剂的方法。

  公开号：

  US20100260778A1
• 作为产物：
  描述：

  [2-phenyl-5-(2-phenyl-1H-indole-6-carbonyl)thiophene-3-yl]acetic acid methyl ester 在 sodium hydroxide 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 cesium fluoride 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 51.0h， 生成 (4-{2-Phenyl-6-[5-phenyl-4-(trityloxycarbamoyl-methyl)-thiophene-2-carbonyl]-indol-1-yl}-butyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Serotype-selective, small-molecule inhibitors of the zinc endopeptidase of botulinum neurotoxin serotype A

  摘要：

  Botulinum neurotoxin serotype A (BoNTA) is one of the most toxic substances known. Currently, there is no antidote to BoNTA. Small molecules identified from high-throughput screening reportedly inhibit the endopeptidase-the zinc-bound, catalytic domain of BoNTA-at a drug concentration of 20 mu M. However, optimization of these inhibitors is hampered by challenges including the computational evaluation of the ability of a zinc ligand to compete for coordination with nearby residues in the active site of BoNTA. No improved inhibitor of the endopeptidase has been reported. This article reports the development of a serotype-selective, small-molecule inhibitor of BoNTA with a K-i of 12 mu M. This inhibitor was designed to coordinate the zinc ion embedded in the active site of the enzyme for affinity and to interact with a species-specific residue in the active site for selectivity. It is the most potent small-molecule inhibitor of BoNTA reported to date. The results suggest that multiple molecular dynamics simulations using the cationic dummy atom approach are useful to structure-based design of zinc protease inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.08.018