3-(4-(1H-imidazol-1-yl)phenyl)-2-(1H-benzo[d]imidazol-2-yl)acrylonitrile | 1353056-56-0

• 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-(4-(1H-imidazol-1-yl)phenyl)-2-(1H-benzo[d]imidazol-2-yl)acrylonitrile
• 英文别名: 2-(1H-benzimidazol-2-yl)-3-[4-(1H-imidazol-1-yl)phenyl]acrylonitrile；2-(1H-benzimidazol-2-yl)-3-(4-imidazol-1-ylphenyl)prop-2-enenitrile
• CAS: 1353056-56-0
• 化学式: C₁₉H₁₃N₅
• 分子量: 311.346
• InChiKey: RQRVRUFJJJUVPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.81
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.29
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  邻苯二胺 在 哌嗪 作用下， 以 乙醇 为溶剂， 反应 4.5h， 生成 3-(4-(1H-imidazol-1-yl)phenyl)-2-(1H-benzo[d]imidazol-2-yl)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

• Time-dependent botulinum neurotoxin serotype A metalloprotease inhibitors
  作者：Bing Li、Steven C. Cardinale、Michelle M. Butler、Ramdas Pai、Jonathan E. Nuss、Norton P. Peet、Sina Bavari、Terry L. Bowlin

  DOI：10.1016/j.bmc.2011.10.062

  日期：2011.12

  Botulinum neurotoxins (BoNTs) are the most lethal of biological substances, and are categorized as class A biothreat agents by the Centers for Disease Control and Prevention. There are currently no drugs to treat the deadly flaccid paralysis resulting from BoNT intoxication. Among the seven BoNT serotypes, the development of therapeutics to counter BoNT/A is a priority (due to its long half-life in the neuronal cytosol and its ease of production). In this regard, the BoNT/A enzyme light chain (LC) component, a zinc metalloprotease responsible for the intracellular cleavage of synaptosomal-associated protein of 25 kDa, is a desirable target for developing post-BoNT/A intoxication rescue therapeutics. In an earlier study, we reported the high throughput screening of a library containing 70,000 compounds, and uncovered a novel class of benzimidazole acrylonitrile-based BoNT/A LC inhibitors. Herein, we present both structure-activity relationships and a proposed mechanism of action for this novel inhibitor chemotype. (C) 2011 Elsevier Ltd. All rights reserved.