sodium 2-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-1-yloxy)acetate | 881375-86-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: sodium 2-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-1-yloxy)acetate
• 英文别名: sodium [4-(2-morpholin-4-yl-4-oxo-4H-chromen-8-yl)-dibenzothiophen-1-yloxy]-acetate；Sodium;2-[4-(2-morpholin-4-yl-4-oxochromen-8-yl)dibenzothiophen-1-yl]oxyacetate
• CAS: 881375-86-6
• 化学式: C₂₇H₂₀NO₆S*Na
• 分子量: 509.515
• InChiKey: BQDVJYOEKHAUFB-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  116
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-异丙基哌嗪 、 sodium 2-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-1-yloxy)acetate 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 8-(1-(2-(4-isopropylpiperazin-1-yl)-2-oxoethoxy)dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-one
  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
• 作为产物：
  描述：

  2-[4-(2-Morpholin-4-yl-4-oxochromen-8-yl)dibenzothiophen-1-yl]oxyacetic acid 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 生成 sodium 2-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-1-yloxy)acetate
  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

• [EN] DNA-PK INHIBITORS<br/>[FR] INHIBITEURS D'ADN-PK
  申请人：KUDOS PHARM LTD

  公开号：WO2006032869A1

  公开（公告）日：2006-03-30

  A compound of formula I: and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein: R1 and R2 are independently selected from hydrogen, an optionally substituted C1-7 alkyl group, C3-20 heterocyclyl group, or C5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; Q is -NH-C(=O)- or -O-; Y is an optionally substituted C1-5 alkylene group; X is selected from SR3 or NR4R5, wherein, R3, or R4 and R5 are independently selected from hydrogen, optionally substituted C1-7 alkyl, C5-20 aryl, or C3-20 heterocyclyl groups, or R4 and R5 may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; if Q is -O-, X is additionally selected from -C(=O)-NR6R7, wherein R6 and R7 are independently selected from hydrogen, optionally substituted C1-7 alkyl, C5-20 aryl, or C3-20 heterocyclyl groups, or R6 and R7 may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; and if Q is -NH-C(=O)-, -Y-X may additionally be selected from C1-7 alkyl.

  化合物I的分子式为：及其异构体、盐、溶剂和化学保护形式、以及其前药，其中：R1和R2独立选择氢、可选取代的C1-7烷基、C3-20杂环基或C5-20芳基，或者与它们连接的氮原子一起形成一个可选取代的杂环环，其具有4至8个环原子；Q为-NH-C（=O）-或-O-；Y为可选取代的C1-5烷基；X选自SR3或NR4R5，其中R3，或R4和R5独立选择氢、可选取代的C1-7烷基、C5-20芳基或C3-20杂环基，或者R4和R5可以与它们连接的氮原子一起形成一个可选取代的杂环环，其具有4至8个环原子；如果Q为-O-，X还被选自-C（=O）-NR6R7，其中R6和R7独立选择氢、可选取代的C1-7烷基、C5-20芳基或C3-20杂环基，或者R6和R7可以与它们连接的氮原子一起形成一个可选取代的杂环环，其具有4至8个环原子；如果Q为-NH-C（=O）-，-Y-X还可以被选自C1-7烷基。
• 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.