{4-[6-(4-Hydrazinocarbonylmethyl-5-phenyl-thiophene-2-carbonyl)-2-phenyl-indol-1-yl]-butyl}-carbamic acid tert-butyl ester | 917079-03-9

• 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: {4-[6-(4-Hydrazinocarbonylmethyl-5-phenyl-thiophene-2-carbonyl)-2-phenyl-indol-1-yl]-butyl}-carbamic acid tert-butyl ester
• CAS: 917079-03-9
• 化学式: C₃₆H₃₈N₄O₄S
• 分子量: 622.788
• InChiKey: FXENPQLBHYJQOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.11
• 重原子数：
  45.0
• 可旋转键数：
  11.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  115.45
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  {4-[6-(4-Hydrazinocarbonylmethyl-5-phenyl-thiophene-2-carbonyl)-2-phenyl-indol-1-yl]-butyl}-carbamic acid tert-butyl ester 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 17.0h， 以20%的产率得到{5-[1-(4-aminobutyl)-2-phenyl-1H-indole-6-carbonyl]-2-phenylthiophene-3-yl}acetic acid hydrazide dihydrochloride
  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：

  {5-[3-amino-4-(phenylethynyl)benzoyl]-2-phenylthiophene-3-yl}acetic acid methyl ester 在 二(氰基苯)二氯化钯 一水合肼 、 cesium fluoride 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 53.0h， 生成 {4-[6-(4-Hydrazinocarbonylmethyl-5-phenyl-thiophene-2-carbonyl)-2-phenyl-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