3-(tert-Butoxycarbonylamino-ethoxycarbonyl-methyl)-benzoic acid ethyl ester | 213487-96-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-(tert-Butoxycarbonylamino-ethoxycarbonyl-methyl)-benzoic acid ethyl ester
• 英文别名: Ethyl 3-[2-ethoxy-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxoethyl]benzoate
• CAS: 213487-96-8
• 化学式: C₁₈H₂₅NO₆
• 分子量: 351.4
• InChiKey: PGCFIGRUADTDDK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(tert-Butoxycarbonylamino-ethoxycarbonyl-methyl)-benzoic acid ethyl ester 在 N-甲基吗啉 、 sodium hydroxide 、 sodium tetrahydroborate 、 三异丙基硅烷 、 氨 、 碘 、 三乙胺 、 三氟乙酸 、 lithium chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 3,3'-[(disulfanediyl)bis((2SR)-2-aminoethylene)]bis(benzamide)
  参考文献：
  名称：

  β-Amino-thiols Inhibit the Zinc Metallopeptidase Activity of Tetanus Toxin Light Chain

  摘要：

  Tetanus neurotoxin is a 150-kDa protein produced by Clostridium tetani, which causes the lethal spastic paralytic syndromes of tetanus by blocking inhibitory neurotransmitter release at central synapses. The toxin light chain (50 kDa) has a zinc endopeptidase activity specific for synaptobrevin, an essential component of the neuroexocytosis apparatus. Previous unsuccessful attempts to block the proteolytic activity of this neurotoxin with well-known inhibitors of other zinc proteases led us to study the design of specific inhibitors as a possible drug therapy to prevent the progressive evolution of tetanus following infection. Starting from the synaptobrevin sequence at the level of the cleavage site by tetanus neurotoxin (Gln(76)-Phe(77)), a thiol analogue of glutamine demonstrated inhibitory activities in the millimolar range. A structure-activity relationship performed with this compound led us to determine the requirement for the correct positioning of the thiol group, the primary amino group, and a carboxamide or sulfonamide group on the side chain. This resulted in the design of a beta-amino-(4-sulfamoylphenyl)glycine-thiol, the first significantly efficient inhibitor of tetanus neurotoxin with a K-i value of 35 +/- 5 mu M.

  DOI：

  10.1021/jm981015z
• 作为产物：
  描述：

  3-[氨基(羧基)甲基]苯甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-(tert-Butoxycarbonylamino-ethoxycarbonyl-methyl)-benzoic acid ethyl ester
  参考文献：
  名称：

  β-Amino-thiols Inhibit the Zinc Metallopeptidase Activity of Tetanus Toxin Light Chain

  摘要：

  Tetanus neurotoxin is a 150-kDa protein produced by Clostridium tetani, which causes the lethal spastic paralytic syndromes of tetanus by blocking inhibitory neurotransmitter release at central synapses. The toxin light chain (50 kDa) has a zinc endopeptidase activity specific for synaptobrevin, an essential component of the neuroexocytosis apparatus. Previous unsuccessful attempts to block the proteolytic activity of this neurotoxin with well-known inhibitors of other zinc proteases led us to study the design of specific inhibitors as a possible drug therapy to prevent the progressive evolution of tetanus following infection. Starting from the synaptobrevin sequence at the level of the cleavage site by tetanus neurotoxin (Gln(76)-Phe(77)), a thiol analogue of glutamine demonstrated inhibitory activities in the millimolar range. A structure-activity relationship performed with this compound led us to determine the requirement for the correct positioning of the thiol group, the primary amino group, and a carboxamide or sulfonamide group on the side chain. This resulted in the design of a beta-amino-(4-sulfamoylphenyl)glycine-thiol, the first significantly efficient inhibitor of tetanus neurotoxin with a K-i value of 35 +/- 5 mu M.

  DOI：

  10.1021/jm981015z