2-benzyl-5-(hydroxymethylidene)-1-phenyl-2,5,6,7-tetrahydro-4H-isoindol-4-one | 1575822-09-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-benzyl-5-(hydroxymethylidene)-1-phenyl-2,5,6,7-tetrahydro-4H-isoindol-4-one
• CAS: 1575822-09-1
• 化学式: C₂₂H₁₉NO₂
• 分子量: 329.398
• InChiKey: DEGYLJGHCTWSIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.77
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  42.23
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-benzyl-5-(hydroxymethylidene)-1-phenyl-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 25.5h， 生成 8-benzyl-N,7-diphenyl-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：

  溴甲苯 在 potassium tert-butylate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 、 mineral oil 为溶剂， 反应 29.0h， 生成 2-benzyl-5-(hydroxymethylidene)-1-phenyl-2,5,6,7-tetrahydro-4H-isoindol-4-one
  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

文献信息

• Preclinical Activity of New [1,2]Oxazolo[5,4-<i>e</i>]isoindole Derivatives in Diffuse Malignant Peritoneal Mesothelioma
  作者：Virginia Spanò、Marzia Pennati、Barbara Parrino、Anna Carbone、Alessandra Montalbano、Vincenzo Cilibrasi、Valentina Zuco、Alessia Lopergolo、Denis Cominetti、Patrizia Diana、Girolamo Cirrincione、Paola Barraja、Nadia Zaffaroni

  DOI：10.1021/acs.jmedchem.6b00777

  日期：2016.8.11

  series of 22 derivatives of the [1,2]oxazolo[5,4-e]isoindole system were synthesized through an efficient and versatile procedure that involves the annelation of the [1,2]oxazole moiety to the isoindole ring, producing derivatives with a wide substitution pattern. The structure–activity relationship indicates that the N-4-methoxybenzyl group appears crucial for potent activity. In addition, the presence

  [1,2]恶唑并[5,4- e ]异吲哚体系的一系列22种衍生物是通过一种有效且通用的方法合成的，该方法涉及将[1,2]恶唑部分与异吲哚环进行脱环反应，从而制得衍生物具有广泛的替代模式。结构-活性关系表明Ñ-4-甲氧基苄基似乎对有效活性至关重要。另外，6-苯基部分的存在是重要的，并且用3,4,5-三甲氧基取代基达到最佳活性。当对完整的NCI人肿瘤细胞系进行测试时，具有这两个结构特征的最具活性的化合物能够在纳摩尔浓度下抑制肿瘤细胞的增殖。有趣的是，由于微管蛋白聚合的抑制作用，在弥漫性恶性腹膜间皮瘤（DMPM）（一种快速致死性疾病）的实验模型中，该化合物可有效降低体外和体内细胞生长，削弱细胞周期进程并诱导凋亡。 ，对常规治疗策略的反应较差。