2-溴-1,3,4,5-四氢-6H-吡咯并[4,3,2-ef][2]苯并氮杂卓-6-酮 | 283173-72-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: 2-溴-1,3,4,5-四氢-6H-吡咯并[4,3,2-ef][2]苯并氮杂卓-6-酮
• 中文别名: 瑞卡帕布杂质
• 英文名称: 2-bromo-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-one
• 英文别名: 5-bromo-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indol-1-one；2-bromo-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one
• CAS: 283173-72-8
• 化学式: C₁₁H₉BrN₂O
• 分子量: 265.109
• InChiKey: ZRRIVOUCCUFNDH-UHFFFAOYSA-N

物化性质

• 熔点：
  204-206 °C (decomp)
• 沸点：
  559.1±50.0 °C(Predicted)
• 密度：
  1.684±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-溴-1,3,4,5-四氢-6H-吡咯并[4,3,2-ef][2]苯并氮杂卓-6-酮 在 氯化锌 、 三苯基膦钯 sodium cyanoborohydride 、 sodium carbonate 、 lithium chloride 作用下， 以 甲醇 、 乙醇 、 水 、 甲苯 为溶剂， 生成 2-(3-(N,N-dimethylamino)methylphenyl)-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-one
  参考文献：
  名称：

  Tricyclic inhibitors of poly(ADP-ribose) polymerases

  摘要：

  以下公式化合物是聚(ADP核糖基)转移酶（PARP）抑制剂，可用于治疗癌症并改善中风、头部创伤和神经退行性疾病的影响。作为癌症治疗药物，本发明的化合物可与细胞毒性药物和/或放射线结合使用。

  公开号：

  US06495541B1
• 作为产物：
  描述：

  3-吲哚丙酸 在 aluminum (III) chloride 、 正丁基锂 、 氯化亚砜 、 盐酸羟胺 、 水 、 sodium acetate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 氯乙酰氯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 为溶剂， 反应 38.5h， 生成 2-溴-1,3,4,5-四氢-6H-吡咯并[4,3,2-ef][2]苯并氮杂卓-6-酮
  参考文献：
  名称：

  Poly(ADP-ribose) Polymerase in Neurodegeneration: Radiosynthesis and Radioligand Binding in ARC-SWE tg Mice

  摘要：

  We report the synthesis, radiosynthesis, and characterization of a radioligand for poly(ADP-ribose) polymerase (PARP). PARP is of central importance in cell homeostasis, neuroplasticity, and neurodegeneration in the brain. A radiolabeled PARP inhibitor was developed and used for autoradiographic quantification of PARP protein concentration in wild-type and transgenic rodent brains ex vivo in high resolution. The binding of [H-3]rucaparib was found to be confined to PARP-expressing domains, for example, cerebellar cortex or hippocampal regions in both models. Saturation binding experiments confirmed selective and reversible binding to a single site (K-d = 1.1 +/- 0.2 nM).

  DOI：

  10.1021/acschemneuro.8b00053

文献信息

• Copper-Mediated Radiosynthesis of [¹⁸F]Rucaparib
  作者：Zijun Chen、Gianluca Destro、Florian Guibbal、Chung Ying Chan、Bart Cornelissen、Véronique Gouverneur

  DOI：10.1021/acs.orglett.1c02770

  日期：2021.9.17

  poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is used in the clinic to treat BRCA-mutated cancers. Herein, we report two strategies to access the 18F-isotopologue of rucaparib by applying a copper-mediated nucleophilic 18F-fluorodeboronation. The most successful approach features an aldehydic boronic ester precursor that is subjected to reductive amination post-18F-labeling and affords [18F]rucaparib

  聚（ADP-核糖）聚合酶（PARP）抑制剂rucaparib在临床上用于治疗BRCA突变的癌症。在此，我们报告了两种通过应用铜介导的亲核18 F-氟脱硼来获得 rucaparib 的18 F-同位素体的策略。最成功的方法是采用醛硼酸酯前体，在18 F 标记后进行还原胺化，得到 [ 18 F]rucaparib，其活性产率为 11% ± 3% ( n = 3) 和摩尔活性 ( A m ) 高达 30 GBq/μmol。提出了初步体外研究。
• [EN] TRICYCLIC INHIBITORS OF POLY(ADP-RIBOSE) POLYMERASES<br/>[FR] INHIBITEURS TRICYCLIQUES DE POLY(ADP-RIBOSE) POLYMERASES
  申请人：AGOURON PHARMA

  公开号：WO2000042040A1

  公开（公告）日：2000-07-20

  Compounds of formula (I) are poly(ADP-ribosyl)transferase (PARP) inhibitors, and are useful as therapeutics in treatment of cancers and the amelioration of the effects of stroke, head trauma, and neurodegenerative disease. As cancer therapeutics, the compounds of the invention may be used, e.g., in combination with cytotoxic agents and/or radiation.

  公式（I）的化合物是聚(ADP-核糖基)转移酶（PARP）抑制剂，并可用于治疗癌症和改善中风、头部创伤和神经退行性疾病的影响，作为治疗剂。作为癌症治疗剂，本发明的化合物可以与细胞毒性剂和/或放射线结合使用。
• Novel Tricyclic Poly(ADP-ribose) Polymerase-1 Inhibitors with Potent Anticancer Chemopotentiating Activity:  Design, Synthesis, and X-ray Cocrystal Structure
  作者：Stacie S. Canan Koch、Lars H. Thoresen、Jayashree G. Tikhe、Karen A. Maegley、Robert J. Almassy、Jianke Li、Xiao-Hong Yu、Scott E. Zook、Robert A. Kumpf、Cathy Zhang、Theodore J. Boritzki、Rena N. Mansour、Kanyin E. Zhang、Anne Ekker、Chris R. Calabrese、Nicola J. Curtin、Suzanne Kyle、Huw D. Thomas、Lan-Zhen Wang、A. Hilary Calvert、Bernard T. Golding、Roger J. Griffin、David R. Newell、Stephen E. Webber、Zdenek Hostomsky

  DOI：10.1021/jm020259n

  日期：2002.11.1

  A series of novel compounds have been designed that are potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1), and the activity and physical properties have been characterized. The new structural classes, 3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-ones and 3,4-dihydropyrrolo[4,3,2-de]isoquinolin-5-(1H)-ones, have conformationally locked benzamide cores that specifically interact with the PARP-1 protein. The compounds have been evaluated with in vitro cellular assays that measure the ability of the PARP-1 inhibitors to enhance the effect of cytotoxic agents against cancer cell lines.
• TRICYCLIC INHIBITORS OF POLY(ADP-RIBOSE) POLYMERASES
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP1140936B1

  公开（公告）日：2004-03-17
• Pharmaceutical Compositions and Method for Treating, Reducing, Ameliorating, Alleviating, or Preventing Dry Eye
  申请人：Zhang Jinzhong

  公开号：US20080305994A1

  公开（公告）日：2008-12-11

  A composition for treating, reducing, ameliorating, alleviating, or preventing a dry eye condition or an opthalmologic disorder that has an etiology in inflammation comprises an inhibitor of activity of poly(ADP-ribose) polymerase (“PARP”). The composition can also include a modulator of pro-inflammatory gene expression.