5-(5-(2-chloro-7-ethoxyquinolin-3-yl)-3-(4-(isoxazol-4-yl)phenyl)-4,5-dihydro-1H-pyrazol-1-yl)-5-oxopentanoic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 5-(5-(2-chloro-7-ethoxyquinolin-3-yl)-3-(4-(isoxazol-4-yl)phenyl)-4,5-dihydro-1H-pyrazol-1-yl)-5-oxopentanoic acid
• 英文别名: 5-[3-(2-Chloro-7-ethoxyquinolin-3-yl)-5-[4-(1,2-oxazol-4-yl)phenyl]-3,4-dihydropyrazol-2-yl]-5-oxopentanoic acid；5-[3-(2-chloro-7-ethoxyquinolin-3-yl)-5-[4-(1,2-oxazol-4-yl)phenyl]-3,4-dihydropyrazol-2-yl]-5-oxopentanoic acid
• 化学式: C₂₈H₂₅ClN₄O₅
• 分子量: 532.983
• InChiKey: IDQVAWKATMMUPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.87
• 重原子数：
  38.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  118.12
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  间氨基苯乙醚 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 一水合肼 、 N,N-二异丙基乙胺 、 cesium fluoride 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 38.59h， 生成 5-(5-(2-chloro-7-ethoxyquinolin-3-yl)-3-(4-(isoxazol-4-yl)phenyl)-4,5-dihydro-1H-pyrazol-1-yl)-5-oxopentanoic acid
  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。