3-(1H-benzo[d]imidazol-6-yl)-5-(4-nitrophenyl)-1,2,4-oxadiazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(1H-benzo[d]imidazol-6-yl)-5-(4-nitrophenyl)-1,2,4-oxadiazole
• 英文别名: 3-(3H-benzimidazol-5-yl)-5-(4-nitrophenyl)-1,2,4-oxadiazole
• 化学式: C₁₅H₉N₅O₃
• 分子量: 307.268
• InChiKey: YXVCDQHOBQJKRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,4-二氨基苯甲腈 在 盐酸 、 盐酸羟胺 、 potassium carbonate 、 N,N'-羰基二咪唑 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 3-(1H-benzo[d]imidazol-6-yl)-5-(4-nitrophenyl)-1,2,4-oxadiazole
  参考文献：
  名称：

  Discovery and Modification of in Vivo Active Nrf2 Activators with 1,2,4-Oxadiazole Core: Hits Identification and Structure–Activity Relationship Study

  摘要：

  Induction of phase II antioxidant enzymes by activation of Nrf2/ARE pathway has been recognized as a promising strategy for the regulation of oxidative stress-related diseases. Herein we report our effort on the discovery and optimization of Nrf2 activators with 1,2,4-oxadiazole core. Screening of an in-house collection containing 7500 compounds by ARE-luciferase reporter assay revealed a moderate Nrf2 activator, 1. Aimed at obtaining more derivatives efficiently, molecular similarity search by the combination of 2D fingerprint-based and 3D shape-based search was applied to virtually screening the Chemdiv collection. Three derivatives with the same core were identified to have better inductivity of Nrf2 than 1 The best hit 4 was selected as starting point for structurally optimization, leading to a much more potent derivative 32. It in vitro upregulated gene and protein level of Nrf2 as well as its downstream markers such as NQO1, GCLM, and HO-1. It remarkably suppressed inflammation in the in vivo LPS-challenged mouse model. Our results provide a new chemotype as Nrf2-ARE activators which deserve further optimization with the aim to obtain active anti-inflammatory agents through Nrf2-ARE pathway.

  DOI：

  10.1021/acs.jmedchem.5b00170

文献信息

• Discovery and Modification of in Vivo Active Nrf2 Activators with 1,2,4-Oxadiazole Core: Hits Identification and Structure–Activity Relationship Study
  作者：Li-Li Xu、Jun-Feng Zhu、Xiao-Li Xu、Jie Zhu、Li Li、Mei-Yang Xi、Zheng-Yu Jiang、Ming-Ye Zhang、Fang Liu、Meng-chen Lu、Qi-Chao Bao、Qi Li、Chao Zhang、Jin-Lian Wei、Xiao-Jin Zhang、Lian-Shan Zhang、Qi-Dong You、Hao-Peng Sun

  DOI：10.1021/acs.jmedchem.5b00170

  日期：2015.7.23

  Induction of phase II antioxidant enzymes by activation of Nrf2/ARE pathway has been recognized as a promising strategy for the regulation of oxidative stress-related diseases. Herein we report our effort on the discovery and optimization of Nrf2 activators with 1,2,4-oxadiazole core. Screening of an in-house collection containing 7500 compounds by ARE-luciferase reporter assay revealed a moderate Nrf2 activator, 1. Aimed at obtaining more derivatives efficiently, molecular similarity search by the combination of 2D fingerprint-based and 3D shape-based search was applied to virtually screening the Chemdiv collection. Three derivatives with the same core were identified to have better inductivity of Nrf2 than 1 The best hit 4 was selected as starting point for structurally optimization, leading to a much more potent derivative 32. It in vitro upregulated gene and protein level of Nrf2 as well as its downstream markers such as NQO1, GCLM, and HO-1. It remarkably suppressed inflammation in the in vivo LPS-challenged mouse model. Our results provide a new chemotype as Nrf2-ARE activators which deserve further optimization with the aim to obtain active anti-inflammatory agents through Nrf2-ARE pathway.