5-(3,4,5-trimethoxyphenyl)-[1,3]dioxolo[4,5-g]isoquinoline | 6289-71-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-(3,4,5-trimethoxyphenyl)-[1,3]dioxolo[4,5-g]isoquinoline
• 英文别名: 5-(3,4,5-trimethoxy-phenyl)-[1,3]dioxolo[4,5-g]isoquinoline；5-(3,4,5-Trimethoxy-phenyl)-[1,3]dioxolo[4,5-g]isochinolin
• CAS: 6289-71-0
• 化学式: C₁₉H₁₇NO₅
• 分子量: 339.348
• InChiKey: BRORELUZNXUCNK-UHFFFAOYSA-N

物化性质

• 熔点：
  112-115 °C
• 沸点：
  470.9±45.0 °C(Predicted)
• 密度：
  1.279±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-(3,4,5-trimethoxy-phenyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]isoquinoline 在 potassium permanganate 、 叔丁醇 作用下， 生成 5-(3,4,5-trimethoxyphenyl)-[1,3]dioxolo[4,5-g]isoquinoline
  参考文献：
  名称：

  Synthesis of Some Isoquinoline Derivatives Related to Podophyllotoxin

  摘要：

  DOI：

  10.1021/ja01167a114

文献信息

• ISOQUINOLINE BIARYL COMPOUNDS, A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, AND USES THEREOF
  申请人：Ludwig-Maximilians-Universität München

  公开号：EP3653608A1

  公开（公告）日：2020-05-20

  The present invention provides a compound having the formula (I) which is suitable as a tubulin polymerization inhibitor and/or an antimitotic cytotoxin. Thus, it can be employed in the treatment, amelioration or prevention of a disorder selected from a neoplastic disorder, atherosclerosis, psoriasis, restenosis, idiopathic pulmonary fibrosis, scleroderma, wet age-related macular degeneration, and cirrhosis of the liver.

  本发明提供了一种具有化学式(I)的化合物，适用作微管聚合抑制剂和/或抗有丝分裂细胞毒素。因此，它可用于治疗、改善或预防从肿瘤性疾病、动脉粥样硬化、牛皮癣、再狭窄、特发性肺纤维化、硬皮病、湿性年龄相关性黄斑变性和肝硬化中选择的疾病。
• Isoquinoline-based biaryls as a robust scaffold for microtubule inhibitors
  作者：Yvonne Kraus、Carina Glas、Benedikt Melzer、Li Gao、Constanze Heise、Monique Preuße、Julia Ahlfeld、Franz Bracher、Oliver Thorn-Seshold

  DOI：10.1016/j.ejmech.2019.111865

  日期：2020.1

  We here report the discovery of isoquinoline-based biaryls as a new scaffold for colchicine domain tubulin inhibitors. Colchicinoid inhibitors offer highly desirable cytotoxic and vascular disrupting bioactivities, but their further development requires improving in vivo robustness and tolerability: properties that both depend on the scaffold structure employed. We have developed isoquinoline-based biaryls as a novel scaffold for high-potency tubulin inhibitors, with excellent robustness, druglikeness, and facile late-stage structural diversification, accessible through a tolerant synthetic route. We confirmed their bioactivity mechanism in vitro, developed soluble prodrugs, and established safe in vivo dosing in mice. By addressing several problems facing the current families of inhibitors, we expect that this new scaffold will find a range of in vivo applications towards translational use in cancer therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.