12b-hydroxy-3-methoxy-5,12b-dihydro-6H-isoindolo[1,2-a]isoquinolin-8-one | 1250264-78-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 12b-hydroxy-3-methoxy-5,12b-dihydro-6H-isoindolo[1,2-a]isoquinolin-8-one
• 英文别名: CRR-204；12b-Hydroxy-3-methoxy-5,6-dihydroisoindolo[1,2-a]isoquinolin-8-one
• CAS: 1250264-78-8
• 化学式: C₁₇H₁₅NO₃
• 分子量: 281.311
• InChiKey: BALDTJMJEIRONH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(3-methoxyphenethyl)isoindoline-1,3-dione 在 三氟甲磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以93%的产率得到12b-hydroxy-3-methoxy-5,12b-dihydro-6H-isoindolo[1,2-a]isoquinolin-8-one
  参考文献：
  名称：

  Brønsted acid assisted activation of imide carbonyl group: regioselective synthesis of isoindoloisoquinolinone alkaloid (±)-nuevamine

  摘要：

  用三氟甲磺酸活化酰亚胺羰基有助于苯乙基邻苯二甲酰亚胺的分子内环化，从而得到融合的异吲哚异喹啉酮骨架。利用这种方法，首次成功地进行了异吲哚异喹啉酮生物碱 (±)-nuevamine 的一锅区域选择性合成。

  DOI：

  10.1039/c1ob06349a

文献信息

• An unusual reactivity of BBr3: Accessing tetrahydroisoquinoline units from N-phenethylimides
  作者：Jayaraman Selvakumar、Alexandros Makriyannis、Chinnasamy Ramaraj Ramanathan

  DOI：10.1039/c0ob00269k

  日期：——

  Isoindoloisoquinalinone, pyrroloisoquinolinone and benzo[a]quinolizinone units are constructed via intramolecular cyclization of the methoxy substituted N-phenethylimides using BBr3.

  异吲哚异喹啉酮、吡咯异喹啉酮和苯并[a]喹嗪酮单元是通过使用 BBr3 对甲氧基取代的 N-苯乙基亚酰胺进行分子内环化而构建的。
• P₄O₁₀/TfOH mediated domino condensation–cyclization of amines with diacids: a route to indolizidine alkaloids under catalyst- and solvent-free conditions
  作者：Ketan S. Mandrekar、Santosh G. Tilve

  DOI：10.1039/d2ra02534e

  日期：——

  employment of either a catalyst or solvent. The use of a few aliphatic and aromatic dicarboxylic acids is shown along with various primary amines. This method is suitable for synthesizing pyrrolo[2,1-a]isoquinolines, pyrido[2,1-a]isoquinolines, and isoindolo[1,2-a]isoquinolinones in excellent yields. When phthalic acid is used, a workup with either NaBH4 or a saturated NaHCO3 solution provided 12b-H or 12b-OH

  开发了一种多米诺缩合环化方法，使用 P 4 O 10 /TfOH 试剂系统合成吲哚里西啶生物碱，无需使用催化剂或溶剂。显示了一些脂肪族和芳香族二羧酸以及各种伯胺的使用。该方法适用于合成吡咯并[2,1- a ]异喹啉、吡啶并[2,1- a ]异喹啉和异吲哚[1,2- a ]异喹啉酮，收率良好。当使用邻苯二甲酸时，使用 NaBH 4或饱和 NaHCO 3溶液进行后处理得到 12 b -H 或 12 b -OH 异吲哚[1,2- a]异喹啉酮，分别。
• Synthesis and biological evaluation of isoindoloisoquinolinone, pyroloisoquinolinone and benzoquinazolinone derivatives as poly(ADP-ribose) polymerase-1 inhibitors
  作者：Arumugam Suyavaran、Chitteti Ramamurthy、Ramachandran Mareeswaran、Yagna Viswa Shanthi、Jayaraman Selvakumar、Selvaraj Mangalaraj、Muthuvel Suresh Kumar、Chinnasamy Ramaraj Ramanathan、Chinnasamy Thirunavukkarasu

  DOI：10.1016/j.bmc.2014.12.017

  日期：2015.2

  A series of novel fused isoquinolinones with isoindoloisoquinolinone, pyroloisoquinolinone, and benzoquinalizinone skeletons were synthesized from corresponding phenethylimides. The isoquinolinone derivatives were evaluated for their protective effect on chicken erythrocytes subjected to oxidative damage. The effect of isoquinolinone derivatives were analysed by estimation of cell viability, antioxidant enzyme activities, DNA damage (comet assay), PARP-1 inhibition assay and molecular docking of the compounds with PARP-1 active site. The compounds CRR-271, CRR-288 and CRR-224+225 showed significant protective effect at 100 mu M concentration. The PARP-1 inhibition assay revealed the IC50 values of CRR-271, CRR-288 and CRR-224+225 as <200 nM, further molecular docking studies shows higher binding energies with PARP-1 active site. Interesting findings in this study suggest that the novel isoquinolinone derivatives inhibit PARP-1 activity and protect cells against oxidative DNA damage, which could be implemented in the treatment of inflammatory diseases. (C) 2014 Elsevier Ltd. All rights reserved.