N-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-1-yl)-2-(piperazin-1-yl)acetamide

• 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: N-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-1-yl)-2-(piperazin-1-yl)acetamide
• 英文别名: N-[4-(2-morpholin-4-yl-4-oxochromen-8-yl)dibenzothiophen-1-yl]-2-piperazin-1-ylacetamide
• 化学式: C₃₁H₃₀N₄O₄S
• 分子量: 554.67
• InChiKey: BTMHRDSTPWZKMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  8

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 、 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 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 丙酮 为溶剂， 反应 54.0h， 生成 N-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-1-yl)-2-(piperazin-1-yl)acetamide
  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

• METHODS FOR IMPROVED HOMOLOGOUS RECOMBINATION AND COMPOSITIONS THEREOF
  申请人：Life Technologies Corporation

  公开号：EP3679144A1

  公开（公告）日：2020-07-15
• [EN] METHODS FOR IMPROVED HOMOLOGOUS RECOMBINATION AND COMPOSITIONS THEREOF<br/>[FR] MÉTHODES DE RECOMBINAISON HOMOLOGUE AMÉLIORÉE ET COMPOSITIONS ASSOCIÉES
  申请人：LIFE TECHNOLOGIES CORP

  公开号：WO2019051316A1

  公开（公告）日：2019-03-14

  The present disclosure relates to methods, kits, and compositions for improving the efficiency of homologous recombination. In particular, the disclosure relates to methods for introducing a nucleic acid cutting entity for DNA editing into cells that are difficult to transfect. Generally, the nucleic acid cutting entity is introduced into the cell without the use of viral vectors. The disclosure also relates to cloning DNA molecules directly into a genome with the combined use of promoter trapping and short homology arms, nuclear localization signal, and/or binding one or more DNA binding agents (TAL effector domain or truncated guide RNA bound by Cas9) to specific sites thereby displacing or restructuring chromatin at the target locus, and/or it increasing the accessibility of the target locus to further enzymatic modifications. The methods and compositions provided herein are, inter alia, useful for genome editing and enhancing enzymatic processes involved therein.
• 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.