2-(5,6-dimethyl-1H-benzimidazol-2-yl)-3-(4-diethylaminophenyl)acrylonitrile

• 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: 2-(5,6-dimethyl-1H-benzimidazol-2-yl)-3-(4-diethylaminophenyl)acrylonitrile
• 化学式: C₂₂H₂₄N₄
• 分子量: 344.459
• InChiKey: IKDGVIKUVOFOPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.09
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55.71
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  4，5-二甲基-1，2-苯二胺 在 哌嗪 作用下， 以 乙醇 为溶剂， 反应 4.5h， 生成 2-(5,6-dimethyl-1H-benzimidazol-2-yl)-3-(4-diethylaminophenyl)acrylonitrile
  参考文献：
  名称：

  Development of benzimidazole derivatives to inhibit HIV-1 replication through protecting APOBEC3G protein

  摘要：

  Human APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G, MG) is a potent restriction factor against human immunodeficiency virus type 1 (HIV-1) by inducing hypermutation of G to A in viral genome after its incorporation into virions. HIV-1 Vif (Virion Infectivity Factor) counteracts A3G by inducing ubiquitination and proteasomal degradation of MG protein. Vif-A3G axis therefore is a promising therapeutic target of HIV-1. Here we report the screening, synthesis and SAR studies of benzimidazole derivatives as potent inhibitors against HIV-1 replication via protecting MG protein. Based on the steep SAR of the benzimidazole scaffold, we identified compound 14 and 26 which provided the best potency, with IC50 values of 3.45 nM and 58.03 nM respectively in the anti-HIV-1 replication assay in H9 cells. Compound 14 and 26 also afforded protective effects on MG protein level. Both compounds have been proved to be safe in acute toxicological studies. Taken together, we suggest that these two benzimidazole derivatives can be further developed as a new category of anti-HIV-1 leads. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.050

文献信息

• Development of benzimidazole derivatives to inhibit HIV-1 replication through protecting APOBEC3G protein
  作者：Ting Pan、Xin He、Bing Chen、Hui Chen、Guannan Geng、Haihua Luo、Hui Zhang、Chuan Bai

  DOI：10.1016/j.ejmech.2015.03.050

  日期：2015.5

  Human APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G, MG) is a potent restriction factor against human immunodeficiency virus type 1 (HIV-1) by inducing hypermutation of G to A in viral genome after its incorporation into virions. HIV-1 Vif (Virion Infectivity Factor) counteracts A3G by inducing ubiquitination and proteasomal degradation of MG protein. Vif-A3G axis therefore is a promising therapeutic target of HIV-1. Here we report the screening, synthesis and SAR studies of benzimidazole derivatives as potent inhibitors against HIV-1 replication via protecting MG protein. Based on the steep SAR of the benzimidazole scaffold, we identified compound 14 and 26 which provided the best potency, with IC50 values of 3.45 nM and 58.03 nM respectively in the anti-HIV-1 replication assay in H9 cells. Compound 14 and 26 also afforded protective effects on MG protein level. Both compounds have been proved to be safe in acute toxicological studies. Taken together, we suggest that these two benzimidazole derivatives can be further developed as a new category of anti-HIV-1 leads. (C) 2015 Elsevier Masson SAS. All rights reserved.