KU0058684 | 623578-11-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: KU0058684
• 英文别名: 1-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]pyrrolidine-2,5-dione；1-(2-Fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)phenyl)pyrrolidine-2,5-dione；1-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]phenyl]pyrrolidine-2,5-dione
• CAS: 623578-11-0
• 化学式: C₁₉H₁₄FN₃O₃
• 分子量: 351.337
• InChiKey: YQSZNYLPVBOGPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  78.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]succinamic acid 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 124.0h， 生成 KU0058684
  参考文献：
  名称：

  [EN] PHTHALAZINONE DERIVATIVES
  [FR] DERIVES DE PHTHALAZINONE

  摘要：

  一种具有化学式（I）的化合物；或其异构体、盐、溶剂合物、化学保护形式、或前药，其中A和B共同代表一个可选择取代的融合芳香环；RL是一个C5-7芳基基团，在邻位由基团R2取代，并可选择进一步取代；其中R2选自化学式（II）和化学式（III）；以及其作为药物的用途，特别用于治疗通过抑制PARP活性改善的疾病。

  公开号：

  WO2003093261A1

文献信息

• Dna damage repair inhibitors for treatment of cancer
  申请人：Kudos Pharmaceuticals Limited

  公开号：EP2305221A1

  公开（公告）日：2011-04-06

  The present invention relates to the recognition that inhibition of the base excision repair pathway is selectively lethal in cells which are deficient in HR dependent DNA DSB repair. Methods and means relating to the treatment of cancers which are deficient in HR dependent DNA DSB repair using inhibitors which target base excision repair components, such as PARP, is provided herein.

  本发明涉及一种认识，即抑制碱基切除修复途径对缺乏 HR 依赖性 DNA DSB 修复的细胞具有选择性致死作用。本发明提供了使用靶向碱基切除修复成分（如 PARP）的抑制剂治疗缺乏 HR 依赖性 DNA DSB 修复的癌症的方法和手段。
• Phthalazinones. Part 1: The design and synthesis of a novel series of potent inhibitors of poly(ADP-ribose)polymerase
  作者：Vincent M. Loh、Xiao-ling Cockcroft、Krystyna J. Dillon、Lesley Dixon、Jan Drzewiecki、Penny J. Eversley、Sylvie Gomez、Janet Hoare、Frank Kerrigan、Ian T.W. Matthews、Keith A. Menear、Niall M.B. Martin、Roger F. Newton、Jane Paul、Graeme C.M. Smith、Julia Vile、Alan J. Whittle

  DOI：10.1016/j.bmcl.2005.03.026

  日期：2005.5

  Screening of the Maybridge compound collection identified 4-arylphthalazinones as micromolar inhibitors of PARP-1 catalytic activity. Subsequent optimisation of both inhibitory activity and metabolic stability led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-ones with low nanomolar, cellular activity as PARP-1 inhibitors and promising metabolic stability in vitro. © 2005 Elsevier Ltd. All rights reserved.
• PHTHALAZINONE DERIVATIVES
  申请人：Kudos Pharmaceuticals Limited

  公开号：EP1501822B1

  公开（公告）日：2010-12-15
• DNA damage repair inhibitors for treatment of cancer
  申请人：Kudos Pharmaceuticals Limited

  公开号：EP2305221B1

  公开（公告）日：2015-05-20
• DNA DAMAGE REPAIR INHIBITORS FOR TREATMENT OF CANCER
  申请人：The Institute of Cancer Research: Royal Cancer Hospital

  公开号：US20170319543A1

  公开（公告）日：2017-11-09

  The present invention relates to the recognition that inhibition of the base excision repair pathway is selectively lethal in cells which are deficient in HR dependent DNA DSB repair. Methods and means relating to the treatment of cancers which are deficient in HR dependent DNA DSB repair using inhibitors which target base excision repair components, such as PARP, is provided herein.