{5-[1-(4-N-boc-aminobutyl)-2-phenyl-1H-indol-6-carbonyl]-2-phenylthiophen-3-yl}acetic acid methyl ester | 875271-90-2

• 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: {5-[1-(4-N-boc-aminobutyl)-2-phenyl-1H-indol-6-carbonyl]-2-phenylthiophen-3-yl}acetic acid methyl ester
• 英文别名: Methyl 2-[5-[1-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]-2-phenylindole-6-carbonyl]-2-phenylthiophen-3-yl]acetate
• CAS: 875271-90-2
• 化学式: C₃₇H₃₈N₂O₅S
• 分子量: 622.785
• InChiKey: BLHFBZDRAVRQOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  {5-[1-(4-N-boc-aminobutyl)-2-phenyl-1H-indol-6-carbonyl]-2-phenylthiophen-3-yl}acetic acid methyl ester 在 盐酸 、 sodium hydroxide 、 1-羟基苯并三唑 、 溶剂黄146 、 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 甲醇 、 二氯甲烷 、 2,2,2-三氟乙醇 、 乙酸乙酯 为溶剂， 反应 51.5h， 生成 2-{5-[1-(4-aminobutyl)-2-phenyl-1H-indole-6-carbonyl]-2-phenylthiophene-3-yl}-N-hydroxyacetamide hydrochloride
  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
• 作为产物：
  描述：

  (2-苯基噻吩-3-基)乙酸乙酯 在 二(氰基苯)二氯化钯 、 四(三苯基膦)钯 盐酸 、 氢氧化钾 、 copper(l) iodide 、 三氯化铝 、 二乙胺 、 cesium fluoride 、 tin(ll) chloride 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 61.0h， 生成 {5-[1-(4-N-boc-aminobutyl)-2-phenyl-1H-indol-6-carbonyl]-2-phenylthiophen-3-yl}acetic acid methyl 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

文献信息

• SMALL-MOLECULE BOTULINUM TOXIN INHIBITORS
  申请人：Pang Yuan-Ping

  公开号：US20100260778A1

  公开（公告）日：2010-10-14

  Small-molecule inhibitors of Botulinum toxin, including BoNTA, BoNTD and BoNTE are provided, as well as methods of using the inhibitors.

  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。
• US8492428B2
  申请人：——

  公开号：US8492428B2

  公开（公告）日：2013-07-23