(2SR,3S)-3-(Boc-amino)-3-<3-(tert-butylsulfamoyl)phenyl>-2-<(4-methoxybenzyl)sulfanyl>propanoic acid | 224822-78-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (2SR,3S)-3-(Boc-amino)-3-<3-(tert-butylsulfamoyl)phenyl>-2-<(4-methoxybenzyl)sulfanyl>propanoic acid
• 英文别名: (3S)-3-[3-(tert-butylsulfamoyl)phenyl]-2-[(4-methoxyphenyl)methylsulfanyl]-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 224822-78-0
• 化学式: C₂₆H₃₆N₂O₇S₂
• 分子量: 552.713
• InChiKey: MNPJXYXVABRWSH-HMTLIYDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  37
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  165
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2SR,3S)-3-(Boc-amino)-3-<3-(tert-butylsulfamoyl)phenyl>-2-<(4-methoxybenzyl)sulfanyl>propanoic acid 在 氢氟酸 、 间甲酚 、 N,N-二异丙基乙胺 、 三氟乙酸 、 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 为溶剂， 反应 6.0h， 生成 N-<(2R,3S)-3-amino-3-(3-sulfamoylphenyl)-2-sulfanylpropanoyl>-L-tyrosyl-N-benzyl-L-histidinamide
  参考文献：
  名称：

  Metallopeptidase Inhibitors of Tetanus Toxin:  A Combinatorial Approach

  摘要：

  The bacterial protein tetanus toxin (TeNt), which belongs to the family of zinc endopeptidases, cleaves synaptobrevin, an essential synaptic protein component of the neurotransmitter exocytosis apparatus, at a single peptide bond (Gln(76)-Phe(77)). This protease activity is a particularly attractive target for designing potent and selective synthetic inhibitors as a possible drug therapy for tetanus. beta-Aminothiols mimicking Gln(76) of synaptobrevin have been previously shown to inhibit the tetanus neurotoxin enzymatic activity in the 35-250 mu M range. These compounds have now been modified to interact with S' subsites of the TeNt active site, with the aim of increasing their inhibitory potencies. Combinatorial libraries of pseudotripeptides, containing an ethylene sulfonamide or an m-sulfonamidophenyl moiety as the P-1 side chain and natural amino acids in P-1' and P-2' positions, were synthesized. The best inhibitory activity was observed with Tyr and His as P-1' and P-2' components, respectively. This led to new inhibitors of TeNt with K-i values in the 3-4 mu M range. These molecules are the most potent inhibitors of TeNt described so far.

  DOI：

  10.1021/jm981066w
• 作为产物：
  描述：

  ethyl (2S,3S)-3-(Boc-amino)-3-<3-(tert-butylsulfamoyl)phenyl>-2-<(4-methoxybenzyl)sulfanyl>propanoate 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以98%的产率得到(2SR,3S)-3-(Boc-amino)-3-<3-(tert-butylsulfamoyl)phenyl>-2-<(4-methoxybenzyl)sulfanyl>propanoic acid
  参考文献：
  名称：

  Metallopeptidase Inhibitors of Tetanus Toxin:  A Combinatorial Approach

  摘要：

  The bacterial protein tetanus toxin (TeNt), which belongs to the family of zinc endopeptidases, cleaves synaptobrevin, an essential synaptic protein component of the neurotransmitter exocytosis apparatus, at a single peptide bond (Gln(76)-Phe(77)). This protease activity is a particularly attractive target for designing potent and selective synthetic inhibitors as a possible drug therapy for tetanus. beta-Aminothiols mimicking Gln(76) of synaptobrevin have been previously shown to inhibit the tetanus neurotoxin enzymatic activity in the 35-250 mu M range. These compounds have now been modified to interact with S' subsites of the TeNt active site, with the aim of increasing their inhibitory potencies. Combinatorial libraries of pseudotripeptides, containing an ethylene sulfonamide or an m-sulfonamidophenyl moiety as the P-1 side chain and natural amino acids in P-1' and P-2' positions, were synthesized. The best inhibitory activity was observed with Tyr and His as P-1' and P-2' components, respectively. This led to new inhibitors of TeNt with K-i values in the 3-4 mu M range. These molecules are the most potent inhibitors of TeNt described so far.

  DOI：

  10.1021/jm981066w

文献信息

• Metallopeptidase Inhibitors of Tetanus Toxin:  A Combinatorial Approach
  作者：Loïc Martin、Fabrice Cornille、Serge Turcaud、Hervé Meudal、Bernard P. Roques、Marie-Claude Fournié-Zaluski

  DOI：10.1021/jm981066w

  日期：1999.2.1

  The bacterial protein tetanus toxin (TeNt), which belongs to the family of zinc endopeptidases, cleaves synaptobrevin, an essential synaptic protein component of the neurotransmitter exocytosis apparatus, at a single peptide bond (Gln(76)-Phe(77)). This protease activity is a particularly attractive target for designing potent and selective synthetic inhibitors as a possible drug therapy for tetanus. beta-Aminothiols mimicking Gln(76) of synaptobrevin have been previously shown to inhibit the tetanus neurotoxin enzymatic activity in the 35-250 mu M range. These compounds have now been modified to interact with S' subsites of the TeNt active site, with the aim of increasing their inhibitory potencies. Combinatorial libraries of pseudotripeptides, containing an ethylene sulfonamide or an m-sulfonamidophenyl moiety as the P-1 side chain and natural amino acids in P-1' and P-2' positions, were synthesized. The best inhibitory activity was observed with Tyr and His as P-1' and P-2' components, respectively. This led to new inhibitors of TeNt with K-i values in the 3-4 mu M range. These molecules are the most potent inhibitors of TeNt described so far.