4-nitrophenyl [N-triphenylmethyl-4-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]pentanamide-5-yl]carbonate | 1189357-99-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 4-nitrophenyl [N-triphenylmethyl-4-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]pentanamide-5-yl]carbonate
• 英文别名: [(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-5-oxo-5-(tritylamino)pentyl] (4-nitrophenyl) carbonate
• CAS: 1189357-99-0
• 化学式: C₄₆H₃₉N₃O₈
• 分子量: 761.831
• InChiKey: DSNDAYWMRHPWOL-DHUJRADRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.1
• 重原子数：
  57
• 可旋转键数：
  16
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  149
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-(di-tert-butylphosphoryl)cinnamic acid 、 4-nitrophenyl [N-triphenylmethyl-4-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]pentanamide-5-yl]carbonate 、 Fmoc-L-亮氨酸 、 Fmoc-L-脯氨酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Structure−Affinity Relationships of Glutamine Mimics Incorporated into Phosphopeptides Targeted to the SH2 Domain of Signal Transducer and Activator of Transcription 3

  摘要：

  In cancer cells, signal transducer and activator of transcription 3 (Stat3) participates in aberrant growth, survival, angiogenesis, and invasion signals 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. One of the important elements of the recognition sequence, pTyr-Xxx-Xxx-Gln, is glutamine. We incorporated novel Gin mimics into a lead peptide, pCinn-Leu-Pro-Gln-NHBn, and found that a linear, unconstrained side chain and carboxamide are necessary for high affinity, and the benzamide can be eliminated. Replacement of Gln-NHBn with (R)-4-aminopentanamide or 2-aminoethylurea produced inhibitors with equal or greater potency than that of the lead, as judged by fluorescence polarization (IC50 values were 110 and 130 nM, respectively). When Pro was replaced with cis-3,4-methanoproline, the glutamine mimic, (4R,5S)-4-amino-5-benzyloxyhexanamide resulted in an IC50 of 69 nM, the highest affinity Stat3 inhibitor reported to date.

  DOI：

  10.1021/jm901105k
• 作为产物：
  描述：

  N-triphenylmethyl 4-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-hydroxypentanamide 、 对硝基苯基氯甲酸酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以62%的产率得到4-nitrophenyl [N-triphenylmethyl-4-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]pentanamide-5-yl]carbonate
  参考文献：
  名称：

  Structure−Affinity Relationships of Glutamine Mimics Incorporated into Phosphopeptides Targeted to the SH2 Domain of Signal Transducer and Activator of Transcription 3

  摘要：

  In cancer cells, signal transducer and activator of transcription 3 (Stat3) participates in aberrant growth, survival, angiogenesis, and invasion signals 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. One of the important elements of the recognition sequence, pTyr-Xxx-Xxx-Gln, is glutamine. We incorporated novel Gin mimics into a lead peptide, pCinn-Leu-Pro-Gln-NHBn, and found that a linear, unconstrained side chain and carboxamide are necessary for high affinity, and the benzamide can be eliminated. Replacement of Gln-NHBn with (R)-4-aminopentanamide or 2-aminoethylurea produced inhibitors with equal or greater potency than that of the lead, as judged by fluorescence polarization (IC50 values were 110 and 130 nM, respectively). When Pro was replaced with cis-3,4-methanoproline, the glutamine mimic, (4R,5S)-4-amino-5-benzyloxyhexanamide resulted in an IC50 of 69 nM, the highest affinity Stat3 inhibitor reported to date.

  DOI：

  10.1021/jm901105k

文献信息

• Structure−Affinity Relationships of Glutamine Mimics Incorporated into Phosphopeptides Targeted to the SH2 Domain of Signal Transducer and Activator of Transcription 3
  作者：Pijus K. Mandal、Zhiyong Ren、Xiaomin Chen、Chiyi Xiong、John S. McMurray

  DOI：10.1021/jm901105k

  日期：2009.10.8

  In cancer cells, signal transducer and activator of transcription 3 (Stat3) participates in aberrant growth, survival, angiogenesis, and invasion signals 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. One of the important elements of the recognition sequence, pTyr-Xxx-Xxx-Gln, is glutamine. We incorporated novel Gin mimics into a lead peptide, pCinn-Leu-Pro-Gln-NHBn, and found that a linear, unconstrained side chain and carboxamide are necessary for high affinity, and the benzamide can be eliminated. Replacement of Gln-NHBn with (R)-4-aminopentanamide or 2-aminoethylurea produced inhibitors with equal or greater potency than that of the lead, as judged by fluorescence polarization (IC50 values were 110 and 130 nM, respectively). When Pro was replaced with cis-3,4-methanoproline, the glutamine mimic, (4R,5S)-4-amino-5-benzyloxyhexanamide resulted in an IC50 of 69 nM, the highest affinity Stat3 inhibitor reported to date.