4-[[4-fluoro-3-(2-hydroxy-5-azatricyclo[6.3.1.04,12]dodeca-1(11),8(12),9-triene-5-carbonyl)phenyl]methyl]-2H-phthalazin-1-one | 1428123-27-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 4-[[4-fluoro-3-(2-hydroxy-5-azatricyclo[6.3.1.04,12]dodeca-1(11),8(12),9-triene-5-carbonyl)phenyl]methyl]-2H-phthalazin-1-one
• CAS: 1428123-27-6
• 化学式: C₂₇H₂₂FN₃O₃
• 分子量: 455.488
• InChiKey: IZQGPIIOAMUKOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[[4-fluoro-3-(2-hydroxy-5-azatricyclo[6.3.1.04,12]dodeca-1(11),8(12),9-triene-5-carbonyl)phenyl]methyl]-2H-phthalazin-1-one 在 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 反应 0.08h， 生成 4-[[4-fluoro-3-(2-fluoro-5-azatricyclo[6.3.1.04,12]dodeca-1(11),8(12),9-triene-5-carbonyl)phenyl]methyl]-2H-phthalazin-1-one
  参考文献：
  名称：

  一类哒嗪酮类化合物及其制备方法和用途

  摘要：

  本发明涉及一类如下通式I表示的哒嗪酮类化合物、其制备方法及其在制备预防或治疗与核糖多聚ADP‑核糖聚合酶（PARP）相关的疾病的药物中的用途。

  公开号：

  CN103833756B
• 作为产物：
  描述：

  4,6,7,8-四氢-1H,3H-喹啉-2,5-二酮 在 sodium tetrahydroborate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 4-[[4-fluoro-3-(2-hydroxy-5-azatricyclo[6.3.1.04,12]dodeca-1(11),8(12),9-triene-5-carbonyl)phenyl]methyl]-2H-phthalazin-1-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Series of Benzo[de][1,7]naphthyridin-7(8H)-ones Bearing a Functionalized Longer Chain Appendage as Novel PARP1 Inhibitors

  摘要：

  A series of benzo[de][1,7]naphthyridin-7(8H)-ones possessing a functionalized long-chain appendage have been designed and evaluated as novel PARP1 inhibitors. The initial effort led to the first-generation PARP1 inhibitor 26 bearing a terminal phthalazin-1(2H)-one framework and showing remarkably high PARP1 inhibitory activity (0.31 nM) but only moderate potency in the cell. Further effort generated the second-generation lead 41, showing high potency against both the PARP1 enzyme and BRCA-deficient cells, especially for the BRCA1-deficient MDA-MB-436 cells (CC50 < 0.26 nM). Mechanistic studies revealed that the new PARP1 inhibitors significantly inhibited H2O2-triggered PARylation in SKOV3 cells, induced cellular accumulation of DNA double-strand breaks, and impaired cell-cycle progression in BRCA2-deficient cells. Significant potentiation on the cytotoxicity of Temozolomide was also observed. The unique structural character and exceptionally high potency of 41 made it stand out as a promising drug candidate worthy for further evaluation.

  DOI：

  10.1021/jm301825t