(2,3-dihydrobenzo[1,4]dioxin-6-yl)-[5-(3-methyl-5-nitro-3H-imidazol-4-yl)-[1,3,4]oxadiazol-2-yl]amine | 900014-55-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (2,3-dihydrobenzo[1,4]dioxin-6-yl)-[5-(3-methyl-5-nitro-3H-imidazol-4-yl)-[1,3,4]oxadiazol-2-yl]amine
• 英文别名: 2-(1-methyl-4-nitroimidazol-5-yl)-5-(3,4-ethylenedioxy)phenylamino-1,3,4-oxadiazole；N-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-(1-methyl-4-nitro-1H-imidazol-5-yl)-1,3,4-oxadiazol-2-amine；N-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-(3-methyl-5-nitroimidazol-4-yl)-1,3,4-oxadiazol-2-amine
• CAS: 900014-55-3
• 化学式: C₁₄H₁₂N₆O₅
• mdl: MFCD07657587
• 分子量: 344.286
• InChiKey: FYBXYSKIUQRBHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  133
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2,3-dihydrobenzo[1,4]dioxin-6-yl)-[5-(3-methyl-5-nitro-3H-imidazol-4-yl)-[1,3,4]oxadiazol-2-yl]amine 在 palladium on activated charcoal sodium tetrahydroborate 、 氢气 作用下， 以 甲醇 、 乙醇 为溶剂， 20.0~50.0 ℃ 、5.07 MPa 条件下， 反应 2.25h， 生成 (2,3-dihydrobenzo[1,4]dioxin-6-yl)-(5-{3-methyl-5-[(pyridin-2-ylmethyl)amino]-3H-imidazol-4-yl}-[1,3,4]oxadiazol-2-yl)amine
  参考文献：
  名称：

  Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines

  摘要：

  Oxadiazole derivatives were synthesized and evaluated for their ability to inhibit tubulin polymerization and to cause mitotic arrest in tumor cells. The most potent compounds inhibited tubulin polymerization at concentrations below 1 mu M. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (10, EC50 = 7.8 nM). Competition for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure-activity relationships for this novel series of antimitotic agents. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.11.094
• 作为产物：
  描述：

  3-methyl-5-nitro-3H-imidazole-4-carboxylic acid hydrazide 在 2,3-二脱氧胞啶 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 5.0h， 生成 (2,3-dihydrobenzo[1,4]dioxin-6-yl)-[5-(3-methyl-5-nitro-3H-imidazol-4-yl)-[1,3,4]oxadiazol-2-yl]amine
  参考文献：
  名称：

  Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines

  摘要：

  Oxadiazole derivatives were synthesized and evaluated for their ability to inhibit tubulin polymerization and to cause mitotic arrest in tumor cells. The most potent compounds inhibited tubulin polymerization at concentrations below 1 mu M. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (10, EC50 = 7.8 nM). Competition for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure-activity relationships for this novel series of antimitotic agents. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.11.094

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.
• Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines
  作者：Xiaohu Ouyang、Evgueni L. Piatnitski、Vatee Pattaropong、Xiaoling Chen、Hai-Ying He、Alexander S. Kiselyov、Avdhoot Velankar、Joel Kawakami、Marc Labelle、Leon Smith、Julia Lohman、Sui Ping Lee、Asra Malikzay、James Fleming、Jason Gerlak、Ying Wang、Robin L. Rosler、Kai Zhou、Stan Mitelman、Margarita Camara、David Surguladze、Jacqueline F. Doody、M. Carolina Tuma

  DOI：10.1016/j.bmcl.2005.11.094

  日期：2006.3

  Oxadiazole derivatives were synthesized and evaluated for their ability to inhibit tubulin polymerization and to cause mitotic arrest in tumor cells. The most potent compounds inhibited tubulin polymerization at concentrations below 1 mu M. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (10, EC50 = 7.8 nM). Competition for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure-activity relationships for this novel series of antimitotic agents. (C) 2005 Elsevier Ltd. All rights reserved.