(E)-1-(4-bromophenyl)-3-(2-chloro-7-ethoxyquinolin-3-yl)prop-2-en-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (E)-1-(4-bromophenyl)-3-(2-chloro-7-ethoxyquinolin-3-yl)prop-2-en-1-one
• 化学式: C₂₀H₁₅BrClNO₂
• 分子量: 416.702
• InChiKey: PWGHICBKSBFTEX-UXBLZVDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-1-(4-bromophenyl)-3-(2-chloro-7-ethoxyquinolin-3-yl)prop-2-en-1-one 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以77%的产率得到3-(3-(4-bromophenyl)-4,5-dihydro-1H-pyrazol-5-yl)-2-chloro-7-ethoxyquinoline
  参考文献：
  名称：

  Structure-Guided Optimization of Replication Protein A (RPA)–DNA Interaction Inhibitors

  摘要：

  Replication protein A (RPA) is the major human single stranded DNA (ssDNA)-binding protein, playing essential roles in DNA replication, repair, recombination, and DNA-damage response (DDR). Inhibition of RPA-DNA interactions represents a therapeutic strategy for cancer drug discovery and has great potential to provide single agent anticancer activity and to synergize with both common DNA damaging chemotherapeutics and newer targeted anticancer agents. In this letter, a new series of analogues based on our previously reported TDRL-551 (4) compound were designed to improve potency and physicochemical properties. Molecular docking studies guided molecular insights, and further SAR exploration led to the identification of a series of novel compounds with low micromolar RPA inhibitory activity, increased solubility, and excellent cellular up-take. Among a series of analogues, compounds 43, 44, 45, and 46 hold promise for further development of novel anticancer agents.

  DOI：

  10.1021/acsmedchemlett.9b00440
• 作为产物：
  描述：

  间氨基苯乙醚 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 6.34h， 生成 (E)-1-(4-bromophenyl)-3-(2-chloro-7-ethoxyquinolin-3-yl)prop-2-en-1-one
  参考文献：
  名称：

  Structure-Guided Optimization of Replication Protein A (RPA)–DNA Interaction Inhibitors

  摘要：

  Replication protein A (RPA) is the major human single stranded DNA (ssDNA)-binding protein, playing essential roles in DNA replication, repair, recombination, and DNA-damage response (DDR). Inhibition of RPA-DNA interactions represents a therapeutic strategy for cancer drug discovery and has great potential to provide single agent anticancer activity and to synergize with both common DNA damaging chemotherapeutics and newer targeted anticancer agents. In this letter, a new series of analogues based on our previously reported TDRL-551 (4) compound were designed to improve potency and physicochemical properties. Molecular docking studies guided molecular insights, and further SAR exploration led to the identification of a series of novel compounds with low micromolar RPA inhibitory activity, increased solubility, and excellent cellular up-take. Among a series of analogues, compounds 43, 44, 45, and 46 hold promise for further development of novel anticancer agents.

  DOI：

  10.1021/acsmedchemlett.9b00440

文献信息

• [EN] REPLICATION PROTEIN A (RPA)-DNA INTERACTION INHIBITORS<br/>[FR] INHIBITEURS DE L'INTERACTION PROTÉINE A DE RÉPLICATION (RPA)-ADN
  申请人：UNIV INDIANA TRUSTEES

  公开号：WO2021119242A1

  公开（公告）日：2021-06-17

  This invention relates to RPA compounds or pharmaceutically acceptable salts thereof, and for the use of the compounds to treat cancer.

  这项发明涉及RPA化合物或其药用盐，以及利用这些化合物治疗癌症的用途。
• MATERIALS AND METHOD FOR INHIBITING REPLICATION PROTEIN A AND USES THEREOF
  申请人：Indiana University Research and Technology Corporation

  公开号：EP2531032B1

  公开（公告）日：2019-04-10
• MATERIALS AND METHOD FOR INHIBITING REPLICATION PROTEIN A AND USES THEREOF
  申请人：Turchi John J.

  公开号：US20130028989A1

  公开（公告）日：2013-01-31

  Targeting uncontrolled cell proliferation and resistance to DNA damaging chemotherapeutics with at least one reagent has significant potential in cancer treatment. Replication Protein A, the eukaryotic single-strand (ss) DNA binding protein, is essential for genomic maintenance and stability via roles in both DNA replication and repair. Reported herein are small molecules that inhibits the in vitro, in vivo, and cellular ssDNA binding activity of RPA, thereby disrupting the eukaryotic cell cycle, inducing cytotoxicity and increasing the efficacy of chemotherapeutic agents damage DNA, and/or disrupt its replication and/or function. These results provide new insights into the mechanism of RPA-ssDNA interactions in chromosome maintenance and stability. This represents a molecularly targeted eukaryotic DNA binding inhibitor and demonstrates the utility of targeting a protein-DNA interaction as a means of studying the cell cycle and providing a therapeutic strategy for cancer treatment.
• US8859532B2
  申请人：——

  公开号：US8859532B2

  公开（公告）日：2014-10-14
• US9533969B2
  申请人：——

  公开号：US9533969B2

  公开（公告）日：2017-01-03