ethyl (3R)-3-(Boc-amino)-3-<3-(tert-butylsulfamoyl)phenyl>propanoate | 222410-26-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl (3R)-3-(Boc-amino)-3-<3-(tert-butylsulfamoyl)phenyl>propanoate
• 英文别名: ethyl (3R)-3-[3-(tert-butylsulfamoyl)phenyl]-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 222410-26-6
• 化学式: C₂₀H₃₂N₂O₆S
• 分子量: 428.55
• InChiKey: SWKCBTKHLMQEGP-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl (3R)-3-(Boc-amino)-3-<3-(tert-butylsulfamoyl)phenyl>propanoate 在 sodium hydroxide 、 lithium diisopropyl amide 作用下， 以 甲醇 、 水 为溶剂， 反应 2.5h， 生成 (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
• 作为产物：
  描述：

  ethyl 3-<3-(tert-butylsulfamoyl)phenyl>propenoate 在 palladium dihydroxide 正丁基锂 、 氢气 作用下， 以 乙酸乙酯 为溶剂， -78.0~25.0 ℃ 、2.0 MPa 条件下， 反应 18.75h， 生成 ethyl (3R)-3-(Boc-amino)-3-<3-(tert-butylsulfamoyl)phenyl>propanoate
  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