8-(3-Hydroxyphenyl)-2-morpholin-4-ylchromen-4-one | 503468-79-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 8-(3-Hydroxyphenyl)-2-morpholin-4-ylchromen-4-one
• CAS: 503468-79-9
• 化学式: C₁₉H₁₇NO₄
• 分子量: 323.348
• InChiKey: WPUKKEMHTVGTFK-UHFFFAOYSA-N

物化性质

• 沸点：
  555.9±50.0 °C(Predicted)
• 密度：
  1.341±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(3-Hydroxyphenyl)-2-morpholin-4-ylchromen-4-one 、 N-苯基双(三氟甲烷磺酰)亚胺 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以77%的产率得到Trifluoro-methanesulfonic acid 3-(2-morpholin-4-yl-4-oxo-4H-chromen-8-yl)-phenyl ester
  参考文献：
  名称：

  8-Biarylchromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK)

  摘要：

  The synthesis and biological evaluation of libraries of 8-biarylchromen-4-ones enabled the elucidation of structure-activity relationships for inhibition of the DNA-dependent protein kinase (DNA-PK), with 8-(3- (thiophen-2-yl) phenyl) chromen-4-one and 8-(3-(thiophen-3-yl)phenyl) chromen-4-one being especially potent inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.066
• 作为产物：
  描述：

  4-乙酰基吗啉 在 四(三苯基膦)钯 、 三氟甲磺酸酐 、 potassium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 二氯甲烷 为溶剂， 反应 96.0h， 生成 8-(3-Hydroxyphenyl)-2-morpholin-4-ylchromen-4-one
  参考文献：
  名称：

  Discovery of Potent Chromen-4-one Inhibitors of the DNA-Dependent Protein Kinase (DNA-PK) Using a Small-Molecule Library Approach

  摘要：

  Structure-activity relationships for inhibition of DNA-dependent protein kinase (DNA-PK) have been defined for substituted chromen-4-ones. For the 2-amino-substituted benzo[h]chromen-4-ones, a morpholine substituent at this position was essential for activity. Small libraries of 6- and 7-alkoxy-substituted chromen-4-ones showed that a number of 7-alkoxysubstituted chromenones displayed improved activity. Focused libraries incorporating 6-, 7-, and 8-aryl and heteroaryl substituents were prepared. In these cases, 6- and 7-substitution was disfavored, whereas 8-substitution was largely tolerated. Surprisingly, two compounds, 2-N-morpholino-8-dibenzofuranyl-chromen-4-one (NU7427, 32{38}) and the 2-N-morpholino-8-dibenzothiophenyl-chromen-4-one (NU7441, 32{26}) were excellent inhibitors (IC50 vs DNAPK = 40 and 13 nM, respectively). The ring-saturated analogue 2-N-morpholino-8-(6',7',8',9'-tetrahydrodibenzothiophene)chromen-4-one, 36, retained potent activity (IC50 vs DNA-PK = 23 nM). The dibenzothiophene 32{38} sensitized HeLa cells to ionizing radiation in vitro, with dose modification factors of 2.5 at 10% survival being observed at 0.5 mu M. The cytotoxicity of the topoisomerase II inhibitor etoposide was also potentiated.

  DOI：

  10.1021/jm050444b

文献信息

• DNA-PK inhibitors
  申请人：Smith Cameron Murray Graeme

  公开号：US20060264623A1

  公开（公告）日：2006-11-23

  Compounds of formula l: wherein A, B and D are respectively selected from the group consisting of: (i) CH, NH, C; (ii) CH, N, N;and (iii) CH, O, C; are disclosed for use in inhibiting DNA-PK.

  本发明公开了化学式为l的化合物，其中A、B和D分别选自以下组中的一组：(i) CH、NH、C；(ii) CH、N、N；以及(iii) CH、O、C；用于抑制DNA-PK。
• DNA-PK INHIBITORS
  申请人：Kudos Pharmaceuticals Ltd

  公开号：EP1869040A1

  公开（公告）日：2007-12-26
• [EN] DNA-PK INHIBITORS<br/>[FR] INHIBITEURS D'ADN-PK
  申请人：KUDOS PHARM LTD

  公开号：WO2006109084A1

  公开（公告）日：2006-10-19

  [EN] Compounds of formula (I) wherein A, B and D are respectively selected from the group consisting of : (i) CH, NH, C; (ii) CH, N, N;and (iii)CH, O, C; are disclosed for use in inhibiting DNA-PK.
  [FR] Composés de formule (I) dans laquelle A, B et D sont respectivement choisis parmi le groupe composé de : (i) CH, NH, C; (ii) CH, N, N ; et (iii)CH, O, C. Les composés sont décrits pour une utilisation dans l'inhibition de l'ADN-PK.
• Discovery of Potent Chromen-4-one Inhibitors of the DNA-Dependent Protein Kinase (DNA-PK) Using a Small-Molecule Library Approach
  作者：Ian R. Hardcastle、Xiaoling Cockcroft、Nicola J. Curtin、Marine Desage El-Murr、Justin J. J. Leahy、Martin Stockley、Bernard T. Golding、Laurent Rigoreau、Caroline Richardson、Graeme C. M. Smith、Roger J. Griffin

  DOI：10.1021/jm050444b

  日期：2005.12.1

  Structure-activity relationships for inhibition of DNA-dependent protein kinase (DNA-PK) have been defined for substituted chromen-4-ones. For the 2-amino-substituted benzo[h]chromen-4-ones, a morpholine substituent at this position was essential for activity. Small libraries of 6- and 7-alkoxy-substituted chromen-4-ones showed that a number of 7-alkoxysubstituted chromenones displayed improved activity. Focused libraries incorporating 6-, 7-, and 8-aryl and heteroaryl substituents were prepared. In these cases, 6- and 7-substitution was disfavored, whereas 8-substitution was largely tolerated. Surprisingly, two compounds, 2-N-morpholino-8-dibenzofuranyl-chromen-4-one (NU7427, 3238}) and the 2-N-morpholino-8-dibenzothiophenyl-chromen-4-one (NU7441, 3226}) were excellent inhibitors (IC50 vs DNAPK = 40 and 13 nM, respectively). The ring-saturated analogue 2-N-morpholino-8-(6',7',8',9'-tetrahydrodibenzothiophene)chromen-4-one, 36, retained potent activity (IC50 vs DNA-PK = 23 nM). The dibenzothiophene 3238} sensitized HeLa cells to ionizing radiation in vitro, with dose modification factors of 2.5 at 10% survival being observed at 0.5 mu M. The cytotoxicity of the topoisomerase II inhibitor etoposide was also potentiated.
• 8-Biarylchromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK)
  作者：Marine Desage-El Murr、Celine Cano、Bernard T. Golding、Ian R. Hardcastle、Marc Hummersome、Mark Frigerio、Nicola J. Curtin、Keith Menear、Caroline Richardson、Graeme C.M. Smith、Roger J. Griffin

  DOI：10.1016/j.bmcl.2008.07.066

  日期：2008.9

  The synthesis and biological evaluation of libraries of 8-biarylchromen-4-ones enabled the elucidation of structure-activity relationships for inhibition of the DNA-dependent protein kinase (DNA-PK), with 8-(3- (thiophen-2-yl) phenyl) chromen-4-one and 8-(3-(thiophen-3-yl)phenyl) chromen-4-one being especially potent inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.