[5-(4-iodo-3-nitrobenzoyl)-2-phenylthiophen-3-yl]acetic acid | 875271-81-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [5-(4-iodo-3-nitrobenzoyl)-2-phenylthiophen-3-yl]acetic acid
• 英文别名: [5-(4-Iodo-3-nitrobenzoyl)-2-phenylthiophene-3-yl]acetic acid；2-[5-(4-Iodo-3-nitrobenzoyl)-2-phenylthiophen-3-yl]acetic acid
• CAS: 875271-81-1
• 化学式: C₁₉H₁₂INO₅S
• 分子量: 493.278
• InChiKey: HFLXXYXILULAJK-UHFFFAOYSA-N

物化性质

• 熔点：
  100-103 °C
• 沸点：
  678.4±55.0 °C(Predicted)
• 密度：
  1.738±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [5-(4-iodo-3-nitrobenzoyl)-2-phenylthiophen-3-yl]acetic acid 在 N-甲基吗啉 Kaiser oxime PS resin 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 羟胺 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 生成 2-[5-(3-Nitro-4-iodobenzoyl)-2-phenylthiophene-3-yl]-N-hydroxyacetamide
  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-Phenyl-3-thienylacetic acid 在 盐酸 、 sodium hydroxide 、 三氯化铝 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 [5-(4-iodo-3-nitrobenzoyl)-2-phenylthiophen-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。