4,7-dioxo-5-(R)-(2,2,2-trifluoroacetylamino)-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-(S)-carboxylic acid methyl ester | 160726-07-8

• 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: 4,7-dioxo-5-(R)-(2,2,2-trifluoroacetylamino)-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-(S)-carboxylic acid methyl ester
• 英文别名: methyl (2S,11R)-9,12-dioxo-11-[(2,2,2-trifluoroacetyl)amino]-1-azatricyclo[6.4.1.04,13]trideca-4(13),5,7-triene-2-carboxylate
• CAS: 160726-07-8
• 化学式: C₁₆H₁₃F₃N₂O₅
• 分子量: 370.285
• InChiKey: GLVPHYVCUGOTQR-ZJUUUORDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.75
• 重原子数：
  26.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92.78
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4,7-dioxo-5-(R)-(2,2,2-trifluoroacetylamino)-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-(S)-carboxylic acid methyl ester 在 palladium on activated charcoal 氢气 作用下， 以 溶剂黄146 为溶剂， 生成 (2S,5R)-4-Oxo-5-(2,2,2-trifluoro-acetylamino)-1,2,4,5,6,7-hexahydro-azepino[3,2,1-hi]indole-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Practical syntheses of a novel tricyclic dipeptide mimetic based on a [6H]-azepino indoline nucleus: Application to angiotensin-converting enzyme inhibition

  摘要：

  Two stereocontrolled synthetic approaches towards 5-(S)-amino-1,2,4,5,6,7-hexahydro-azepino [3,2,1-hi] indole-4-one-2-(S)-carboxylic acid 1, based on intramolecular Friedel-Crafts acylations, are reported. This conformationally restricted tricyclic dipeptidomimetic has been applied a the design of a potent and orally active inhibitor of angiotensin-converting enzyme (ACE).

  DOI：

  10.1016/s0040-4039(00)78331-6
• 作为产物：
  描述：

  (S)-(-)-2-(三氟乙酰胺)琥珀酸酐 在 三氯化铝 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 反应 25.0h， 生成 4,7-dioxo-5-(R)-(2,2,2-trifluoroacetylamino)-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-(S)-carboxylic acid methyl ester
  参考文献：
  名称：

  Practical syntheses of a novel tricyclic dipeptide mimetic based on a [6H]-azepino indoline nucleus: Application to angiotensin-converting enzyme inhibition

  摘要：

  Two stereocontrolled synthetic approaches towards 5-(S)-amino-1,2,4,5,6,7-hexahydro-azepino [3,2,1-hi] indole-4-one-2-(S)-carboxylic acid 1, based on intramolecular Friedel-Crafts acylations, are reported. This conformationally restricted tricyclic dipeptidomimetic has been applied a the design of a potent and orally active inhibitor of angiotensin-converting enzyme (ACE).

  DOI：

  10.1016/s0040-4039(00)78331-6

文献信息

• [EN] GRANZYME B DIRECTED IMAGING AND THERAPY<br/>[FR] IMAGERIE DU GRANZYME B ET THÉRAPIE DIRIGÉES CONTRE LE GRANZYME B
  申请人：CYTOSITE BIOPHARMA INC

  公开号：WO2019160916A1

  公开（公告）日：2019-08-22

  Provided herein are heterocyclic compounds useful for imaging Granzyme B. Methods of imaging Granzyme B, combination therapies, and kits comprising the Granzyme B imaging agents are also provided.

  本文提供了用于成像Granzyme B的杂环化合物。还提供了成像Granzyme B的方法、联合疗法以及包含Granzyme B成像试剂的试剂盒。
• Conformationally Constrained Peptidomimetic Inhibitors of Signal Transducer and Activator of Transcription 3: Evaluation and Molecular Modeling
  作者：Pijus K. Mandal、Donald Limbrick、David R. Coleman、Garrett A. Dyer、Zhiyong Ren、J. Sanderson Birtwistle、Chiyi Xiong、Xiaomin Chen、James M. Briggs、John S. McMurray

  DOI：10.1021/jm801491w

  日期：2009.4.23

  Signal transducer and activator of transcription 3 (Stat3) is involved in aberrant growth and survival signals in malignant tumor cells and is a validated target for anticancer drug design. We are targeting its SH2 domain to prevent docking to cytokine and growth factor receptors and subsequent signaling. The amino acids of our lead phosphopeptide, Ac-pTyr-Leu-Pro-Gln-Thr-Val-NH2, were replaced with conformationally constrained mimics. Structure-affinity studies led to the peptidomimetic, pCinn-Haic-Gln-NHBn (21). which had an IC50 of 162 nM (fluorescence polarization), compared to 290 nM for the lead phosphopeptide (pCinn = 4-phosphoryloxycinnamate, Haic = (2S,5S)-5-amino-1,2,4,5,6,7-hexahydro-4-oxo-azepino[3,2,1-hi]indole-2-carboxylic acid). pCinn-Haic-Gln-OH was docked to the SH2 domain (AUTODOCK), and the two highest populated clusters were subjected to molecular dynamics simulations. Both converged to a common peptide conformation. The complex exhibits unique hydrogen bonding between Haic and Gln and Stat3 as well as hydrophobic interactions between the protein and pCinn and Haic.