2-(3,4,5-trimethoxyphenyl)-5-(3,4-methylenedioxy)phenylamino-1,3,4-oxadiazole | 893766-08-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 2-(3,4,5-trimethoxyphenyl)-5-(3,4-methylenedioxy)phenylamino-1,3,4-oxadiazole
• 英文别名: N-(1,3-benzodioxol-5-yl)-5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-amine
• CAS: 893766-08-0
• 化学式: C₁₈H₁₇N₃O₆
• 分子量: 371.349
• InChiKey: KUORWAAAEAKOLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  97.1
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-(1,3-benzodioxol-5-yl)-2-[(3,4,5-trimethoxyphenyl)carbonyl]hydrazinecarbothioamide 在 N,N'-二环己基碳二亚胺 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 2-(3,4,5-trimethoxyphenyl)-5-(3,4-methylenedioxy)phenylamino-1,3,4-oxadiazole
  参考文献：
  名称：

  Novel derivatives of 1,3,4-oxadiazoles are potent mitostatic agents featuring strong microtubule depolymerizing activity in the sea urchin embryo and cell culture assays

  摘要：

  A series of novel 1,3,4-oxadiazole derivatives based on structural and electronic overlap with combretastatins have been designed and synthesized. Initially, we tested all new compounds in vivo using the phenotypic sea urchin embryo assay to yield a number of agents with anti-proliferative, anti-mitotic, and microtubule destabilizing activities. The experimental data led to identification of 1,3,4-oxadiazole derivatives with isothiazole (5-8) and phenyl (9-12) pharmacophores featuring activity profiles comparable to that of combretastatins, podophyllotoxin and nocodazole. Cytotoxic effects of the two lead molecules, namely 6 and 12, were further confirmed and evaluated by conventional assays with the A549 human cancer cell line including cell proliferation, cell cycle arrest at the G2/M phase, cellular microtubule distribution, and finally in vitro microtubule assembly with purified tubulin. The modeling results using 3D similarity (ROCS) and docking (FRED) correlated well with the observed activity of the molecules. Docking data suggested that the most potent molecules are likely to target the colchicine binding site. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.12.072

文献信息

• Novel derivatives of 1,3,4-oxadiazoles are potent mitostatic agents featuring strong microtubule depolymerizing activity in the sea urchin embryo and cell culture assays
  作者：Alex S. Kiselyov、Marina N. Semenova、Natalya B. Chernyshova、Andrei Leitao、Alexandr V. Samet、Konstantine A. Kislyi、Mikhail M. Raihstat、Tudor Oprea、Heiko Lemcke、Margaréta Lantow、Dieter G. Weiss、Nazli N. Ikizalp、Sergei A. Kuznetsov、Victor V. Semenov

  DOI：10.1016/j.ejmech.2009.12.072

  日期：2010.5

  A series of novel 1,3,4-oxadiazole derivatives based on structural and electronic overlap with combretastatins have been designed and synthesized. Initially, we tested all new compounds in vivo using the phenotypic sea urchin embryo assay to yield a number of agents with anti-proliferative, anti-mitotic, and microtubule destabilizing activities. The experimental data led to identification of 1,3,4-oxadiazole derivatives with isothiazole (5-8) and phenyl (9-12) pharmacophores featuring activity profiles comparable to that of combretastatins, podophyllotoxin and nocodazole. Cytotoxic effects of the two lead molecules, namely 6 and 12, were further confirmed and evaluated by conventional assays with the A549 human cancer cell line including cell proliferation, cell cycle arrest at the G2/M phase, cellular microtubule distribution, and finally in vitro microtubule assembly with purified tubulin. The modeling results using 3D similarity (ROCS) and docking (FRED) correlated well with the observed activity of the molecules. Docking data suggested that the most potent molecules are likely to target the colchicine binding site. (C) 2010 Elsevier Masson SAS. All rights reserved.