4-(4-fluoro-3-(4-(4-fluorophenyl)piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one | 848135-90-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(4-fluoro-3-(4-(4-fluorophenyl)piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one
• 英文别名: 4-[[4-fluoro-3-[4-(4-fluorophenyl)piperazine-1-carbonyl]phenyl]methyl]-2H-phthalazin-1-one
• CAS: 848135-90-0
• 化学式: C₂₆H₂₂F₂N₄O₂
• 分子量: 460.483
• InChiKey: SWYJKASXUDOUHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-[(3,4-二氢-4-氧代-1-酞嗪基)甲基]-2-氟苯甲酸 、 1-(4-氟苯基)哌嗪 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以52%的产率得到4-(4-fluoro-3-(4-(4-fluorophenyl)piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one
  参考文献：
  名称：

  Synthesis and evaluation of an AZD2461 [18F]PET probe in non-human primates reveals the PARP-1 inhibitor to be non-blood-brain barrier penetrant

  摘要：

  Poly(ADP-ribose)polymerase-1 inhibitor (PARPi) AZD2461 was designed to be a weak P-glycoprotein (P-gp) analogue of FDA approved olaparib. With this chemical property in mind, we utilized the AZD2461 ligand architecture to develop a CNS penetrant and PARP-1 selective imaging probe, in order to investigate PARP-1 mediated neuroinflammation and neurodegenerative diseases, such as Alzheimer's and Parkinson's. Our work led to the identification of several high-affinity PARPi, including AZD2461 congener 9e (PARP-1 IC50, = 3.9 +/- 1.2 nM), which was further evaluated as a potential F-18-PET brain imaging probe. However, despite the similar molecular scaffolds of 9e and AZD2461, our studies revealed non-appreciable brain-uptake of [F-18]9e in non-human primates, suggesting AZD2461 to be non-CNS penetrant.

  DOI：

  10.1016/j.bioorg.2018.10.015

文献信息

• LOW AFFINITY POLY(AD-RIBOSE) POLYMERASE 1 DEPENDENT CYTOTOXIC AGENTS
  申请人：THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

  公开号：US20200407374A1

  公开（公告）日：2020-12-31

  The present disclosure provides compounds of Formula (I) or (II), pharmaceutically acceptable salt, isotopic variant, stereoisomer, or a mixture thereof. Also provided are pharmaceutical compositions comprising a compound, methods of treating a poly(ADP-ribose)polymerase-1-mediated disease or disorder in a subject, methods of detecting a poly(ADP-ribose)polymerase-1-mediated neurodegenerative disease or disorder, or methods of monitoring cancer treatment in a subject. In some embodiments, the poly(ADP-ribose)polymerase-1-mediated disease or disorder is a neurodegenerative disease or cancer.