N-benzyloxycarbonyl-(2S)-indolinecarboxylic acid ethylamide | 185213-12-1

• 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: N-benzyloxycarbonyl-(2S)-indolinecarboxylic acid ethylamide
• 英文别名: benzyl (2S)-2-(ethylcarbamoyl)-2,3-dihydroindole-1-carboxylate
• CAS: 185213-12-1
• 化学式: C₁₉H₂₀N₂O₃
• 分子量: 324.379
• InChiKey: BNPZHDUGUQJUNH-KRWDZBQOSA-N

物化性质

• 熔点：
  201-201.5 °C
• 沸点：
  543.2±50.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonyl-(2S)-indolinecarboxylic acid ethylamide 在 palladium on activated charcoal N-乙基吗啉 、 氢气 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0~25.0 ℃ 、206.84 kPa 条件下， 反应 3.5h， 生成 N-benzyloxycarbonyl-(2S)-aminobutyryl-(2S)-indolinecarboxylic acid ethylamide
  参考文献：
  名称：

  Inhibitors of Tripeptidyl Peptidase II. 3. Derivation of Butabindide by Successive Structure Optimizations Leading to a Potential General Approach to Designing Exopeptidase Inhibitors

  摘要：

  The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase that has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO(3)H)-Met-OH + GlyTrp-Met-Asp-Phe-NH(2). Starting from Val-Pro-NHBu, a dipeptide of submicromolar affinity that had previously been generated to serve as a lead, successive optimization at P3, P1, and then P2 gave Abu-Pro-NHBu (18, K(i) = 80 nM). Further transformation (by making a benzologue) gave the indoline analogue, butabindide (33) as a reversible inhibitor having nanomolar affinity (Ki = 7 nM). Retrospective analysis suggested the possibility of a general approach to designing exopeptidase inhibitors starting from the structure of the first hydrolysis product. Application of this approach to CCK-8 led to Abu-Phe-NHBu (37), but this only had K(i) = 9.4 mu M. Molecular modeling, to determine the minimum energy conformations and explain the 1000-fold better affinity of butabindide, indicated that 37 cannot access the likely active conformation of butabindide.

  DOI：

  10.1021/jm0500830
• 作为产物：
  描述：

  乙胺 、 (S)-2,3-二氢吲哚-1,2-二甲酸 1-苄酯 在 N-乙基吗啉 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以74%的产率得到N-benzyloxycarbonyl-(2S)-indolinecarboxylic acid ethylamide
  参考文献：
  名称：

  Inhibitors of Tripeptidyl Peptidase II. 3. Derivation of Butabindide by Successive Structure Optimizations Leading to a Potential General Approach to Designing Exopeptidase Inhibitors

  摘要：

  The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase that has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO(3)H)-Met-OH + GlyTrp-Met-Asp-Phe-NH(2). Starting from Val-Pro-NHBu, a dipeptide of submicromolar affinity that had previously been generated to serve as a lead, successive optimization at P3, P1, and then P2 gave Abu-Pro-NHBu (18, K(i) = 80 nM). Further transformation (by making a benzologue) gave the indoline analogue, butabindide (33) as a reversible inhibitor having nanomolar affinity (Ki = 7 nM). Retrospective analysis suggested the possibility of a general approach to designing exopeptidase inhibitors starting from the structure of the first hydrolysis product. Application of this approach to CCK-8 led to Abu-Phe-NHBu (37), but this only had K(i) = 9.4 mu M. Molecular modeling, to determine the minimum energy conformations and explain the 1000-fold better affinity of butabindide, indicated that 37 cannot access the likely active conformation of butabindide.

  DOI：

  10.1021/jm0500830

文献信息

• Tripeptidylpeptidase inhibitors
  申请人：INSERM

  公开号：US20030027743A1

  公开（公告）日：2003-02-06

  A compound of the formula 1 wherein the substituents are defined as in the specification and salts or hydrates thereof is disclosed as well as a method of treating disorders associated with the inactivation or excessive degradation of cholecystokinin.

  本发明揭示了式1的化合物，其中置换基如规范中所定义，以及其盐或水合物，以及一种治疗与胆囊收缩素失活或过度降解相关的疾病的方法。
• US6403561B1
  申请人：——

  公开号：US6403561B1

  公开（公告）日：2002-06-11