(S)-methyl 3-hydroxy-2-(2-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-1-yloxy)ethylamino)propanoate | 881375-56-0

• 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)-methyl 3-hydroxy-2-(2-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-1-yloxy)ethylamino)propanoate
• 英文别名: methyl (2S)-3-hydroxy-2-[2-[4-(2-morpholin-4-yl-4-oxochromen-8-yl)dibenzothiophen-1-yl]oxyethylamino]propanoate
• CAS: 881375-56-0
• 化学式: C₃₁H₃₀N₂O₇S
• 分子量: 574.654
• InChiKey: CESIWBWBPOBRCD-QHCPKHFHSA-N

物化性质

• 沸点：
  828.5±65.0 °C(Predicted)
• 密度：
  1.377±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  二苯并噻吩 在 1,1'-双(二苯基膦)二茂铁 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 tetrafluoroboric acid 、 正丁基锂 、 硝酸 、 potassium acetate 、 吡啶盐酸盐 、 potassium carbonate 、 caesium carbonate 、 溶剂黄146 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 43.75h， 生成 (S)-methyl 3-hydroxy-2-(2-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-1-yloxy)ethylamino)propanoate
  参考文献：
  名称：

  1-Substituted (Dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-ones Endowed with Dual DNA-PK/PI3-K Inhibitory Activity

  摘要：

  Analogues of (dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-one (NU7441), a potent inhibitor of DNA-dependent protein kinase (DNA-PK; IC50 = 42 +/- 2 nM), have been synthesized in which water-solubilizing groups [NHCO(CH2)(n)(NRR2)-R-1, where n = 1 or 2 and the moiety (RRN)-R-1-N-2 was derived from a library of primary and secondary amines, e.g., morpholine] were placed at the 1-position. Several of the newly synthesized compounds exhibited high potency against DNA-PK and potentiated the cytotoxicity of ionizing radiation (IR) in vitro 10-fold or more (e.g., 2-(4-ethyl-piperazin-1-yl)-N-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)-dibenzo[b,d]thio-phen-1-yl)acetamide, 39; DNA-PK IC50 = 5.0 +/- 1 nM, IR dose modification ratio = 13). Furthermore, 39 was shown to potentiate not only IR in vitro but also DNA-inducing cytotoxic anticancer agents, both in vitro and in vivo. Counter-screening against other members of the phosphatidylinositol 3-kinase (PI-3K) related kinase (PIKK) family unexpectedly revealed that some of the compounds were potent mixed DNA-PK and PI-3K inhibitors.

  DOI：

  10.1021/jm400915j

文献信息

• 1-Substituted (Dibenzo[<i>b,d</i>]thiophen-4-yl)-2-morpholino-4<i>H</i>-chromen-4-ones Endowed with Dual DNA-PK/PI3-K Inhibitory Activity
  作者：Céline Cano、Kappusamy Saravanan、Chris Bailey、Julia Bardos、Nicola J. Curtin、Mark Frigerio、Bernard T. Golding、Ian R. Hardcastle、Marc G. Hummersone、Keith A. Menear、David R. Newell、Caroline J. Richardson、K. Shea、Graeme C. M. Smith、Pia Thommes、Attilla Ting、Roger J. Griffin

  DOI：10.1021/jm400915j

  日期：2013.8.22

  Analogues of (dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-one (NU7441), a potent inhibitor of DNA-dependent protein kinase (DNA-PK; IC50 = 42 +/- 2 nM), have been synthesized in which water-solubilizing groups [NHCO(CH2)(n)(NRR2)-R-1, where n = 1 or 2 and the moiety (RRN)-R-1-N-2 was derived from a library of primary and secondary amines, e.g., morpholine] were placed at the 1-position. Several of the newly synthesized compounds exhibited high potency against DNA-PK and potentiated the cytotoxicity of ionizing radiation (IR) in vitro 10-fold or more (e.g., 2-(4-ethyl-piperazin-1-yl)-N-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)-dibenzo[b,d]thio-phen-1-yl)acetamide, 39; DNA-PK IC50 = 5.0 +/- 1 nM, IR dose modification ratio = 13). Furthermore, 39 was shown to potentiate not only IR in vitro but also DNA-inducing cytotoxic anticancer agents, both in vitro and in vivo. Counter-screening against other members of the phosphatidylinositol 3-kinase (PI-3K) related kinase (PIKK) family unexpectedly revealed that some of the compounds were potent mixed DNA-PK and PI-3K inhibitors.