5-(hydroxymethylene)-2-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one | 1148040-70-3

• 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: 5-(hydroxymethylene)-2-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one
• 英文别名: 5-(Hydroxymethylidene)-2-methyl-6,7-dihydroisoindol-4-one；5-(hydroxymethylidene)-2-methyl-6,7-dihydroisoindol-4-one
• CAS: 1148040-70-3
• 化学式: C₁₀H₁₁NO₂
• 分子量: 177.203
• InChiKey: BSANAHUPQFLHFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(hydroxymethylene)-2-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 26.0h， 生成 8-methyl-N-phenyl-6,8-dihydro-5H-pyrrolo[3,4-h]quinazolin-2-amine
  参考文献：
  名称：

  Synthesis of a new class of pyrrolo[3,4-h]quinazolines with antimitotic activity

  摘要：

  A new series of pyrrolo[3,4-h]quinazolines was conveniently prepared with a broad substitution pattern. A large number of derivatives was obtained and the cellular cytotoxicity was evaluated in vitro against 5 different human tumor cell lines with GI(50) values reaching the low micromolar level (1.3-19.8 mu M). These compounds were able to induce cell death mainly by apoptosis through a mitochondrial dependent pathway. Selected compounds showed antimitotic activity and a reduction of tubulin polymerization in a concentration-dependent manner. Moreover, they showed anti-angiogenic properties since reduced in vitro endothelial cell migration and disrupted HUVEC capillary-like tube network in Matrigel. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.014
• 作为产物：
  描述：

  2-methyl-6,7-dihydro-2H-isoindol-4(5H)-one 、 甲酸乙酯 在 potassium tert-butylate 作用下， 以 苯 为溶剂， 反应 26.0h， 以60%的产率得到5-(hydroxymethylene)-2-methyl-2,5,6,7-tetrahydro-4H-isoindol-4-one
  参考文献：
  名称：

  吡咯并[3,4- h ]喹啉酮类新型光化学治疗剂

  摘要：

  合成吡咯并[3,4- h ]喹啉-2-酮作为角呋喃香豆素当归的氮等价物，目的是获得具有增加的抗增殖活性和较低的不良毒性作用的新型光化学治疗剂。寻求一种通用的合成途径以分离具有在吡咯部分上的良好取代模式的新环系统的衍生物。新化合物的光生物学筛选显示出强大的光毒性作用和很大的UVA剂量依赖性，在亚微摩尔水平下达到IC 50值。诱导的细胞光细胞毒性与线粒体和溶酶体的参与，细胞周期谱的改变和膜脂质过氧化的凋亡有关。

  DOI：

  10.1016/j.bmc.2011.02.023

文献信息

• [1,2]Oxazolo[5,4- e ]isoindoles as promising tubulin polymerization inhibitors
  作者：Virginia Spanò、Marzia Pennati、Barbara Parrino、Anna Carbone、Alessandra Montalbano、Alessia Lopergolo、Valentina Zuco、Denis Cominetti、Patrizia Diana、Girolamo Cirrincione、Nadia Zaffaroni、Paola Barraja

  DOI：10.1016/j.ejmech.2016.09.013

  日期：2016.11

  A series of [1,2]Oxazolo [5,4-e]isoindoles has been synthesized through a versatile and high yielding sequence. All the new structures showed in the 1HNMR spectra, the typical signal in the 8.34–8.47 ppm attributable to the H-3 of the [1,2]oxazole moiety. Among all derivatives, methoxy benzyl substituents at positions 3 and 4 or/and 5 were very effective in reducing the growth of different tumor cell

  通过通用和高产率的序列合成了一系列的[1,2]]唑啉[5,4- e ]异吲哚。所有新结构均在1 HNMR光谱中显示，在8.34–8.47 ppm中的典型信号归因于[1,2]恶唑部分的H-3。在所有衍生物中，位置3和4或/和5处的甲氧基苄基取代基在减少不同肿瘤细胞系的生长方面非常有效，包括弥漫性恶性腹膜间皮瘤（DMPM），这是一种对可用治疗方案反应较差且不常见的恶性肿瘤。活性最高的化合物6j 被发现会破坏微管蛋白聚合，导致细胞周期停滞在G2 / M期并诱导DMPM细胞凋亡，使其成为发现新的有效抗有丝分裂药物的新线索。
• Pyrano[2,3-e]isoindol-2-ones, new angelicin heteroanalogues
  作者：Paola Barraja、Virginia Spanò、Diana Patrizia、Anna Carbone、Girolamo Cirrincione、Daniela Vedaldi、Alessia Salvador、Giampietro Viola、Francesco Dall’Acqua

  DOI：10.1016/j.bmcl.2009.01.096

  日期：2009.3

  synthesis of the pyrano[2,3-e]isoindol-2-one ring system, an heteroanalogue of angelicin, is reported. Our synthetic approach consists of the annelation of the pyran ring on the isoindole moiety using 5-dialkylamino- or 5-hydroxymethylene intermediates as building blocks. The photoantiproliferative activity of the new derivatives was studied. Some of them bearing the benzyl group at the 8 position

  据报道，吡喃并[2,3 - e ] isoindol-2-one环系统，即当归的杂类似物，可以方便地合成。我们的合成方法包括使用5-二烷基氨基-或5-羟基亚甲基中间体作为结构单元，使吡喃环在异吲哚部分上的成环反应。研究了新衍生物的光抗增殖活性。其中一些在8位带有苄基的化合物在微摩尔范围内具有IC 50活性。细胞的细胞毒性涉及细胞凋亡，细胞周期概况的改变和膜的光损伤。
• Convenient synthesis of pyrrolo[3,4-g]indazole
  作者：Virginia Spanò、Alessandra Montalbano、Anna Carbone、Barbara Parrino、Patrizia Diana、Girolamo Cirrincione、Paola Barraja

  DOI：10.1016/j.tet.2013.09.003

  日期：2013.11

  The synthesis of a novel class of tetrahydropyrrolo[3,4-g]indazoles is reported, by annelation of the pyrazole ring on the isoindole moiety by means of 5-hydroxymethylene tetrahydroisoindole-4-ones key intermediates, with good regioselectivity. Dihydroderivatives were also obtained by oxidation with DDQ of the corresponding tetrahydropyrrolo[3,4-g]indazoles. The growth inhibitory effect was evaluated at the National Cancer Institute of Bethesda and some derivatives showed modest activity. (C) 2013 Elsevier Ltd. All rights reserved.
• Pyrrolo[3,4-h]quinolinones a new class of photochemotherapeutic agents
  作者：Paola Barraja、Patrizia Diana、Alessandra Montalbano、Anna Carbone、Giampietro Viola、Giuseppe Basso、Alessia Salvador、Daniela Vedaldi、Francesco Dall’Acqua、Girolamo Cirrincione

  DOI：10.1016/j.bmc.2011.02.023

  日期：2011.4

  nitrogen isosters of the angular furocoumarin angelicin, with the aim of obtaining new photochemotherapeutic agents with increased antiproliferative activity and lower undesired toxic effects. A versatile synthetic pathway was approached to allow the isolation of derivatives of the new ring system with a good substitution pattern on the pyrrole moiety. Photobiological screenings of the new compounds

  合成吡咯并[3,4- h ]喹啉-2-酮作为角呋喃香豆素当归的氮等价物，目的是获得具有增加的抗增殖活性和较低的不良毒性作用的新型光化学治疗剂。寻求一种通用的合成途径以分离具有在吡咯部分上的良好取代模式的新环系统的衍生物。新化合物的光生物学筛选显示出强大的光毒性作用和很大的UVA剂量依赖性，在亚微摩尔水平下达到IC 50值。诱导的细胞光细胞毒性与线粒体和溶酶体的参与，细胞周期谱的改变和膜脂质过氧化的凋亡有关。
• Synthesis of a new class of pyrrolo[3,4-h]quinazolines with antimitotic activity
  作者：Virginia Spanò、Alessandra Montalbano、Anna Carbone、Barbara Parrino、Patrizia Diana、Girolamo Cirrincione、Ignazio Castagliuolo、Paola Brun、Olaf-Georg Issinger、Silvia Tisi、Irina Primac、Daniela Vedaldi、Alessia Salvador、Paola Barraja

  DOI：10.1016/j.ejmech.2013.10.014

  日期：2014.3

  A new series of pyrrolo[3,4-h]quinazolines was conveniently prepared with a broad substitution pattern. A large number of derivatives was obtained and the cellular cytotoxicity was evaluated in vitro against 5 different human tumor cell lines with GI(50) values reaching the low micromolar level (1.3-19.8 mu M). These compounds were able to induce cell death mainly by apoptosis through a mitochondrial dependent pathway. Selected compounds showed antimitotic activity and a reduction of tubulin polymerization in a concentration-dependent manner. Moreover, they showed anti-angiogenic properties since reduced in vitro endothelial cell migration and disrupted HUVEC capillary-like tube network in Matrigel. (C) 2013 Elsevier Masson SAS. All rights reserved.