N-(t-butoxycarbonyl)-(2S)-aminobutyryl-L-proline | 185212-61-7

• 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: N-(t-butoxycarbonyl)-(2S)-aminobutyryl-L-proline
• 英文别名: 1-(N-(tert-butoxycarbonyl)-2(S)-aminobutyryl)-L-proline；(2S)-1-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]pyrrolidine-2-carboxylic acid
• CAS: 185212-61-7
• 化学式: C₁₄H₂₄N₂O₅
• 分子量: 300.355
• InChiKey: VWOBXTNLHNUEPH-UWVGGRQHSA-N

物化性质

• 沸点：
  500.0±45.0 °C(Predicted)
• 密度：
  1.194±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(t-butoxycarbonyl)-(2S)-aminobutyryl-L-proline 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 2.5h， 生成 (S)-1-((S)-2-Amino-butyryl)-pyrrolidine-2-carboxylic acid isobutyl-amide; compound with trifluoro-acetic acid
  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：

  methyl (2S)-1-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]pyrrolidine-2-carboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 N-(t-butoxycarbonyl)-(2S)-aminobutyryl-L-proline
  参考文献：
  名称：

  首次合成astin G

  摘要：

  环五肽的astin家族包含几种非编码氨基酸，包括β-苯丙氨酸，α-氨基丁酸和几种取代的脯氨酸。本文讨论了大环的困难环化和该家族成员astin G的随后的首次全合成。该合成为包含高度敏感的3，4-二氯脯氨酸的stins的合成提供了模型。

  DOI：

  10.1016/s0040-4039(98)02423-x
• 作为试剂：
  描述：

  3-(甲基三)丙烯酸呋喃 、 氯甲酸异丁酯 在 N-乙基吗啉 作用下， 以 四氢呋喃 、 N-(t-butoxycarbonyl)-(2S)-aminobutyryl-L-proline 为溶剂， 生成 N-(t-butoxycarbonyl)-(2S)-aminobutyryl-L-proline 3-methylthiopropylamide
  参考文献：
  名称：

  Tripeptidylpeptidase inhibitors

  摘要：

  公式为的化合物，其中取代基的定义如规范中所述，以及治疗与胆囊收缩素失活或过度降解相关的疾病的方法也被披露。

  公开号：

  US06403561B1

文献信息

• INHIBITEURS DE TRIPEPTIDYLPEPTIDASES
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP0828851B1

  公开（公告）日：2005-07-20
• US6403561B1
  申请人：——

  公开号：US6403561B1

  公开（公告）日：2002-06-11
• [EN] TRIPEPTIDYLPEPTIDASE INHIBITORS<br/>[FR] INHIBITEURS DE TRIPEPTIDYLPEPTIDASES
  申请人：——

  公开号：WO1996035805A2

  公开（公告）日：1996-11-14

  [EN] Inhibitors of a membrane tripeptidylpeptidase responsible for the inactivation of endogenous neuropeptides such as cholecystokinin are described.
  [FR] L'invention concerne des inhibiteurs d'une tripeptidylpeptidase membranaire responsable pour l'inactivation de neuropeptides endogènes notamment la cholécystokinine.
• Tripeptidylpeptidase inhibitors
  申请人：Institut National de la Sante et de la Recherche Medicale (Inserm)

  公开号：US06403561B1

  公开（公告）日：2002-06-11

  A compound of formula 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.

  公式为的化合物，其中取代基的定义如规范中所述，以及治疗与胆囊收缩素失活或过度降解相关的疾病的方法也被披露。
• Inhibitors of Tripeptidyl Peptidase II. 3. Derivation of Butabindide by Successive Structure Optimizations Leading to a Potential General Approach to Designing Exopeptidase Inhibitors
  作者：C. Robin Ganellin、Paul B. Bishop、Ramesh B. Bambal、Suzanne M. T. Chan、Bertrand Leblond、Andrew N. J. Moore、Lihua Zhao、Pierre Bourgeat、Christiane Rose、Froylan Vargas、Jean-Charles Schwartz

  DOI：10.1021/jm0500830

  日期：2005.11.1

  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.