(S)-(3-tert-butoxycarbonylamino-2-oxo-2,3,4,7-tetrahydroazepin-1-yl)acetic acid ethyl ester | 486439-74-1

• 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: (S)-(3-tert-butoxycarbonylamino-2-oxo-2,3,4,7-tetrahydroazepin-1-yl)acetic acid ethyl ester
• 英文别名: ethyl 2-[(6S)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-7-oxo-5,6-dihydro-2H-azepin-1-yl]acetate
• CAS: 486439-74-1
• 化学式: C₁₅H₂₄N₂O₅
• 分子量: 312.366
• InChiKey: CRYWQNCPJXNNCJ-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-(3-tert-butoxycarbonylamino-2-oxo-2,3,4,7-tetrahydroazepin-1-yl)acetic acid ethyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and evaluation of unsaturated caprolactams as interleukin-1β converting enzyme (ICE) inhibitors

  摘要：

  Peptidomimetic compounds possessing a caprolactam ring constraint were prepared and evaluated as interleukin-1 beta converting enzyme (ICE) inhibitors. The caprolactam ring was used to constrain the P3 region of our inhibitors. This strategy proved to be effective for the synthesis of ICE inhibitors, maintaining key hydrogen bond interactions with the enzyme and invoking a preferred conformation for binding. Several compounds exhibited IC50 values less than 10 nM in a caspase-1 enzyme assay and less than 100 nM in a THP-1 whole cell assay measuring IL-1 beta production. Two compounds, 13c and 13j, were found to have good oral bioavailability (> 50%) in rats when administered as prodrugs. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.011
• 作为产物：
  描述：

  N-(allyl)-N-[(2S)-tert-butoxycarbonylamino-4-pentenoyl]glycine ethyl ester 在 Grubbs catalyst first generation 作用下， 以 1,2-二氯乙烷 为溶剂， 以68%的产率得到(S)-(3-tert-butoxycarbonylamino-2-oxo-2,3,4,7-tetrahydroazepin-1-yl)acetic acid ethyl ester
  参考文献：
  名称：

  脱氢弗莱丁格内酰胺的一般方法：前手性库合成和光谱评估作为潜在的反向诱因。

  摘要：

  从天然的α-氨基酸开始，研究了基于闭环烯烃复分解反应的脱氢弗莱丁格内酰胺9a-h的实际合成。提出的实例包括6元，7元，8元，9元和10元环状二肽模拟物。证明了结构上的变化。我们采用N-烷基化/肽偶联策略研究了复分解前体8a-h。钌基催化剂10a或10b促进了随后的闭环。根据NMR和FT-IR研究显示，所得四残基11d发生分子内氢键键合。因此，证明了脱氢-弗雷丁格内酰胺作为稳定分子内NH（i + 3）... CO（i）氢键的潜在反向诱导剂的发展。

  DOI：

  10.1021/jo0261653

文献信息

• Synthesis and evaluation of unsaturated caprolactams as interleukin-1β converting enzyme (ICE) inhibitors
  作者：Yili Wang、Steven V. O’Neil、John A. Wos、Kofi A. Oppong、Michael C. Laufersweiler、David L. Soper、Christopher D. Ellis、Mark W. Baize、Amy N. Fancher、Wei Lu

  DOI：10.1016/j.bmc.2006.11.011

  日期：2007.2.1

  Peptidomimetic compounds possessing a caprolactam ring constraint were prepared and evaluated as interleukin-1 beta converting enzyme (ICE) inhibitors. The caprolactam ring was used to constrain the P3 region of our inhibitors. This strategy proved to be effective for the synthesis of ICE inhibitors, maintaining key hydrogen bond interactions with the enzyme and invoking a preferred conformation for binding. Several compounds exhibited IC50 values less than 10 nM in a caspase-1 enzyme assay and less than 100 nM in a THP-1 whole cell assay measuring IL-1 beta production. Two compounds, 13c and 13j, were found to have good oral bioavailability (> 50%) in rats when administered as prodrugs. (c) 2006 Elsevier Ltd. All rights reserved.
• A General Approach to Dehydro-Freidinger Lactams:  Ex-Chiral Pool Synthesis and Spectroscopic Evaluation as Potential Reverse Turn Inducers
  作者：Tobias Hoffmann、Reiner Waibel、Peter Gmeiner

  DOI：10.1021/jo0261653

  日期：2003.1.1

  Starting from natural alpha-amino acids, a practical synthesis of the dehydro-Freidinger lactams 9a-h based on the ring-closing olefin metathesis reaction was investigated. The presented examples comprise 6-, 7-, 8-, 9-, and 10-membered cyclic dipeptide mimics. Structural variations were demonstrated. We approached the metathesis precursors 8a-h employing an N-alkylation/peptide-coupling strategy.

  从天然的α-氨基酸开始，研究了基于闭环烯烃复分解反应的脱氢弗莱丁格内酰胺9a-h的实际合成。提出的实例包括6元，7元，8元，9元和10元环状二肽模拟物。证明了结构上的变化。我们采用N-烷基化/肽偶联策略研究了复分解前体8a-h。钌基催化剂10a或10b促进了随后的闭环。根据NMR和FT-IR研究显示，所得四残基11d发生分子内氢键键合。因此，证明了脱氢-弗雷丁格内酰胺作为稳定分子内NH（i + 3）... CO（i）氢键的潜在反向诱导剂的发展。