1-(3-methoxyphenyl)-2-(4-methoxyphenyl)-1H-benzo[d]imidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-(3-methoxyphenyl)-2-(4-methoxyphenyl)-1H-benzo[d]imidazole
• 英文别名: 1-(3-Methoxyphenyl)-2-(4-methoxyphenyl)benzimidazole；1-(3-methoxyphenyl)-2-(4-methoxyphenyl)benzimidazole
• 化学式: C₂₁H₁₈N₂O₂
• 分子量: 330.386
• InChiKey: UEYMOKVOOUGEOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  间氨基苯甲醚 、 4-甲氧基苯甲醛 、 1-氟-2-硝基苯 在 sodium dithionite 作用下， 以 二甲基亚砜 为溶剂， 反应 3.0h， 以63%的产率得到1-(3-methoxyphenyl)-2-(4-methoxyphenyl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Discovery of new leads against Mycobacterium tuberculosis using scaffold hopping and shape based similarity

  摘要：

  BM212 [1,5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)-methyl-pyrrole] is a pyrrole derivative with strong inhibitory activity against drug resistant Mycobacterium tuberculosis and mycobacteria residing in macrophages. However, it was not pursued because of its poor pharmacokinetics and toxicity profile. Our goal was to design and synthesize new antimycobacterial BM212 analogs with lower toxicity and better pharmacokinetic profile. Using the scaffold hopping approach, three structurally diverse heterocycles - 2,3-disubstituted imidazopyridines, 2,3-disubstituted benzimidazoles and 1,2,4-trisubstituted imidazoles emerged as promising antitubercular agents. All compounds were synthesized through easy and convenient methods and their structures confirmed by IR, H-1 NMR, C-11 NMR and MS. In-vitro cytotoxicity studies on normal kidney monkey cell lines and HepG2 cell lines, as well as metabolic stability studies on rat liver microsomes for some of the most active compounds, established that these compounds have negligible cytotoxicity and are metabolically stable. Interestingly the benzimidazole compound (4a) is as potent as the parent molecule BM212 (MIC 2.3 mu g/ml vs 0.7-1.5 mu g/ml), but is devoid of the toxicity against HepG2 cell lines (IC50 203.10 mu M vs 7.8 mu M). (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.07.034

文献信息

• Discovery of new leads against Mycobacterium tuberculosis using scaffold hopping and shape based similarity
  作者：Ravindra D. Wavhale、Elvis A.F. Martis、Premlata K. Ambre、Baojie Wan、Scott G. Franzblau、Krishna R. Iyer、Kavita Raikuvar、Katarzyna Macegoniuk、Łukasz Berlicki、Santosh R. Nandan、Evans C. Coutinho

  DOI：10.1016/j.bmc.2017.07.034

  日期：2017.9

  BM212 [1,5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)-methyl-pyrrole] is a pyrrole derivative with strong inhibitory activity against drug resistant Mycobacterium tuberculosis and mycobacteria residing in macrophages. However, it was not pursued because of its poor pharmacokinetics and toxicity profile. Our goal was to design and synthesize new antimycobacterial BM212 analogs with lower toxicity and better pharmacokinetic profile. Using the scaffold hopping approach, three structurally diverse heterocycles - 2,3-disubstituted imidazopyridines, 2,3-disubstituted benzimidazoles and 1,2,4-trisubstituted imidazoles emerged as promising antitubercular agents. All compounds were synthesized through easy and convenient methods and their structures confirmed by IR, H-1 NMR, C-11 NMR and MS. In-vitro cytotoxicity studies on normal kidney monkey cell lines and HepG2 cell lines, as well as metabolic stability studies on rat liver microsomes for some of the most active compounds, established that these compounds have negligible cytotoxicity and are metabolically stable. Interestingly the benzimidazole compound (4a) is as potent as the parent molecule BM212 (MIC 2.3 mu g/ml vs 0.7-1.5 mu g/ml), but is devoid of the toxicity against HepG2 cell lines (IC50 203.10 mu M vs 7.8 mu M). (C) 2017 Elsevier Ltd. All rights reserved.