[2-Phenyl-5-(2-phenyl-1H-indole-6-carbonyl)thiophene-3-yl]acetic acid | 875271-72-0

• 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: [2-Phenyl-5-(2-phenyl-1H-indole-6-carbonyl)thiophene-3-yl]acetic acid
• 英文别名: [2-phenyl-5-(2-phenyl-1H-indol-6-carbonyl)thiophen-3-yl]acetic acid；2-[2-phenyl-5-(2-phenyl-1H-indole-6-carbonyl)thiophen-3-yl]acetic acid
• CAS: 875271-72-0
• 化学式: C₂₇H₁₉NO₃S
• 分子量: 437.519
• InChiKey: VFJZUZKXAZBIKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  98.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [2-Phenyl-5-(2-phenyl-1H-indole-6-carbonyl)thiophene-3-yl]acetic acid 在 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 二氯甲烷 、 2,2,2-三氟乙醇 为溶剂， 反应 24.5h， 生成 N-Hydroxy-2-[2-phenyl-5-(2-phenyl-1H-indole-6-carbonyl)thiophene-3-yl]acetamide
  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 、 sodium hydroxide 、 copper(l) iodide 、 三氯化铝 、 二乙胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 [2-Phenyl-5-(2-phenyl-1H-indole-6-carbonyl)thiophene-3-yl]acetic acid
  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。
• Small-molecule botulinum toxin inhibitors
  申请人：Pang Yuan-Ping

  公开号：US08492428B2

  公开（公告）日：2013-07-23

  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
• Serotype-selective, small-molecule inhibitors of the zinc endopeptidase of botulinum neurotoxin serotype A
  作者：Jewn Giew Park、Peter C. Sill、Edward F. Makiyi、Alfonso T. Garcia-Sosa、Charles B. Millard、James J. Schmidt、Yuan-Ping Pang

  DOI：10.1016/j.bmc.2005.08.018

  日期：2006.1

  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.