4-(2-morpholino-4-oxo-4H-chromen-8-yl)benzyl 2-amino-4-methylpentanoate | 1395832-67-3

• 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-(2-morpholino-4-oxo-4H-chromen-8-yl)benzyl 2-amino-4-methylpentanoate
• 英文别名: [4-(2-morpholin-4-yl-4-oxochromen-8-yl)phenyl]methyl (2S)-2-amino-4-methylpentanoate
• CAS: 1395832-67-3
• 化学式: C₂₆H₃₀N₂O₅
• 分子量: 450.535
• InChiKey: PICLEWWEBWSYFG-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  91.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-morpholin-4-yl-4-oxo-4H-chromen-8-yl trifluoromethanesulfonate 在 4-二甲氨基吡啶 、 palladium diacetate 、 potassium carbonate 、 对甲苯磺酸 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 65.0h， 生成 4-(2-morpholino-4-oxo-4H-chromen-8-yl)benzyl 2-amino-4-methylpentanoate
  参考文献：
  名称：

  Synthesis and Characterization of a Novel Prostate Cancer-Targeted Phosphatidylinositol-3-kinase Inhibitor Prodrug

  摘要：

  The phosphatidylinositol-3-kinase/Akt (PI3K/Akt) pathway is constitutively activated in a substantial proportion of prostate tumors and is considered a key mechanism supporting progression toward an androgen-independent status, for which no effective therapy is available. Therefore, PI3K inhibitors, alone or in combination with other cytotoxic drugs, could potentially be used to treat cancer with a constitutive activated PI3K/Akt pathway. To selectively target advanced prostate tumors with a constitutive activated PI3K/Akt pathway, a prostate cancer-specific PI3K inhibitor was generated by coupling the chemically modified form of the quercetin analogue LY294002 (HO-CH2-LY294002, compound 8) with the peptide Mu-LEHSSKLQL, in which the internal sequence HSSKLQ is a substrate for the prostate-specific antigen (PSA) protease. The result is a water-soluble and latent PI3K inhibitor prodrug (compound 11), its activation being dependent on PSA cleavage. Once activated, the L-O-CH2-LY294002 (compound 10) can specifically inhibit PI3K in PSA-secreting prostate cancer cells and induce apoptosis with a potency comparable to that of the original LY294002 compound.

  DOI：

  10.1021/jm300881a

文献信息

• Synthesis and Characterization of a Novel Prostate Cancer-Targeted Phosphatidylinositol-3-kinase Inhibitor Prodrug
  作者：Daniele Baiz、Tanya A. Pinder、Sazzad Hassan、Yelena Karpova、Freddie Salsbury、Mark E. Welker、George Kulik

  DOI：10.1021/jm300881a

  日期：2012.9.27

  The phosphatidylinositol-3-kinase/Akt (PI3K/Akt) pathway is constitutively activated in a substantial proportion of prostate tumors and is considered a key mechanism supporting progression toward an androgen-independent status, for which no effective therapy is available. Therefore, PI3K inhibitors, alone or in combination with other cytotoxic drugs, could potentially be used to treat cancer with a constitutive activated PI3K/Akt pathway. To selectively target advanced prostate tumors with a constitutive activated PI3K/Akt pathway, a prostate cancer-specific PI3K inhibitor was generated by coupling the chemically modified form of the quercetin analogue LY294002 (HO-CH2-LY294002, compound 8) with the peptide Mu-LEHSSKLQL, in which the internal sequence HSSKLQ is a substrate for the prostate-specific antigen (PSA) protease. The result is a water-soluble and latent PI3K inhibitor prodrug (compound 11), its activation being dependent on PSA cleavage. Once activated, the L-O-CH2-LY294002 (compound 10) can specifically inhibit PI3K in PSA-secreting prostate cancer cells and induce apoptosis with a potency comparable to that of the original LY294002 compound.