(2S,5S)-5-[[(9H-芴-9-基甲氧基)羰基]氨基]-1,2,4,5,6,7-六氢-4-氧代-氮杂卓并[3,2,1-hi]吲哚-2-羧酸 | 204326-24-9

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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
• 中文名称: (2S,5S)-5-[[(9H-芴-9-基甲氧基)羰基]氨基]-1,2,4,5,6,7-六氢-4-氧代-氮杂卓并[3,2,1-hi]吲哚-2-羧酸
• 中文别名: 腺苷13C5
• 英文名称: (2S,11S)-11-([[(9H-fluoren-9-yl)methoxy]carbonyl]amino)-12-oxo-1-azatricyclo[6.4.1.0^[4,13]]trideca-4(13),5,7-triene-2-carboxylic acid
• 英文别名: (3S,6S)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-oxo-1,2,3,4,6,7-hexahydroazepino[3,2,1-hi]indole-6-carboxylic acid；Fmoc-Haic-OH；(2S-cis)-5-(9H-fluoren-9-yl)methoxycarbonylamino-4-oxo-1,2,4,5,6,7-hexahydro-azepino[3,2,1-hi]indole-2-carboxylic acid；(2S,5S)-FMOC-5-amino-1,2,4,5,6,7-hexahydroazepino[3,2,1-Hi]indol-4-one-2-carboxylic acid；(2S,5S)-5-(((9H-fluoren-9-yl)methoxy)carbonylamino)-4-oxo-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxylic acid；Fmoc-(2S,5S)-5-amino-1,2,4,5,6,7-hexahydroazepino[3,2,1-Hi]indole-4-one-2-carboxylic acid；(2S,11S)-11-(9H-fluoren-9-ylmethoxycarbonylamino)-12-oxo-1-azatricyclo[6.4.1.04,13]trideca-4,6,8(13)-triene-2-carboxylic acid
• CAS: 204326-24-9
• 化学式: C₂₈H₂₄N₂O₅
• 分子量: 468.509
• InChiKey: NHNOPJNRVODSCV-ZEQRLZLVSA-N

物化性质

• 沸点：
  765.2±60.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  (2S,5S)-5-[[(9H-芴-9-基甲氧基)羰基]氨基]-1,2,4,5,6,7-六氢-4-氧代-氮杂卓并[3,2,1-hi]吲哚-2-羧酸 在 哌啶 、 sodium carbonate 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (2S,5S)-5-(methoxycarbonylamino)-4-oxo-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxylic acid
  参考文献：
  名称：

  ANTIVIRAL COMPOUNDS

  摘要：

  本发明提供了用于治疗丙型肝炎病毒（HCV）感染的化合物、组合物和方法。还公开了含有这些化合物的药物组合物以及使用这些化合物治疗HCV感染的方法。

  公开号：

  US20120230951A1
• 作为产物：
  描述：

  9-芴甲基-N-琥珀酰亚胺基碳酸酯 、 methyl (2S,11S)-9,12-dioxo-11-(2,2,2-trifluoroacetamido)-1-azatricyclo[6.4.1.0Λ[4,13]]trideca-4,6,8(13)-triene-2-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 lithium hydroxide 作用下， 生成 (2S,5S)-5-[[(9H-芴-9-基甲氧基)羰基]氨基]-1,2,4,5,6,7-六氢-4-氧代-氮杂卓并[3,2,1-hi]吲哚-2-羧酸
  参考文献：
  名称：

  Conformationally Constrained Peptidomimetic Inhibitors of Signal Transducer and Activator of Transcription 3: Evaluation and Molecular Modeling

  摘要：

  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.

  DOI：

  10.1021/jm801491w

文献信息

• [EN] MALONAMIDE DERIVATIVES AS GAMMA-SECRETASE INHIBITORS<br/>[FR] DERIVES DE MALONAMIDE UTILISES COMME INHIBITEURS DE LA GAMMA-SECRETASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004069826A1

  公开（公告）日：2004-08-19

  The invention relates to malonamide derivatives of formula (IA) or (IB) and to pharmaceutically suitable acid addition salts thereof. The compounds are Ϝ-secretase inhibitors and the related compounds may be useful in the treatment of Alzheimer's disease.

  这项发明涉及公式（IA）或（IB）的马隆酰胺衍生物及其药用适宜的酸盐。这些化合物是Ϝ-分泌酶抑制剂，相关化合物可能在治疗阿尔茨海默病方面有用。
• [EN] STAT DEGRADERS AND USES THEREOF<br/>[FR] AGENTS DE DÉGRADATION DE STAT ET LEURS UTILISATIONS
  申请人：KYMERA THERAPEUTICS INC

  公开号：WO2020206424A1

  公开（公告）日：2020-10-08

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用方法。
• INHIBITORS OF HCV NS5A
  申请人：Hoffman-La Roche Inc.

  公开号：US20150166514A1

  公开（公告）日：2015-06-18

  The present invention provides compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

  本发明提供了用于治疗丙型肝炎病毒（HCV）感染的化合物、组合物和方法。还公开了含有这些化合物的药物组合物以及使用这些化合物治疗HCV感染的方法。
• Inhibitors of signal transduction and activator of transcription 3
  申请人：McMurray S. John

  公开号：US20070010428A1

  公开（公告）日：2007-01-11

  Stat3 inhibitor compounds are disclosed, wherein the compounds are structural analogs of Ac-pTyr-Leu-Pro-Gln-Thr-NH 2 and bind to the SH2 domain of Stat3 under physiological conditions to inhibit a cellular signaling activity of Stat3.

  抑制剂化合物Stat3被披露，其中这些化合物是Ac-pTyr-Leu-Pro-Gln-Thr-NH2的结构类似物，并在生理条件下与Stat3的SH2结构域结合，从而抑制Stat3的细胞信号活性。
• Preparation of amides from acids and resin bound azides: Suppression of intramolecular lactam formation
  作者：Zhilian Tang、Jeffrey C. Pelletier

  DOI：10.1016/s0040-4039(98)00905-8

  日期：1998.7

  A new method for the formation of amides on solid phase has been developed. The procedure involves the reaction between activated acids in solution and resin bound iminophosphoranes generated from the corresponding azides and tributylphosphine. The method is particularly attractive when starting from δ azido acids since amides can form without internal cyclization to the lactam.

  已经开发了在固相上形成酰胺的新方法。该过程涉及溶液中的活化酸与由相应的叠氮化物和三丁基膦生成的树脂结合的亚氨基正膦之间的反应。当从δ叠氮酸开始时，该方法特别有吸引力，因为可以形成酰胺而没有内部环化成内酰胺。