2-(1H-benzimidazol-2-yl)-3-(4-diethylamino-2-hydroxyphenyl)acrylonitrile | 95425-62-0

• 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-(1H-benzimidazol-2-yl)-3-(4-diethylamino-2-hydroxyphenyl)acrylonitrile
• 英文别名: 2-(2-benzimidazolyl)-3-(4-N,N-diethylamino-2-hydroxyphenyl)acrylonitrile；2-(1H-benzoimidazol-2-yl)-3-(4-diethylamino-2-hydroxy-phenyl)-acrylonitrile；2-(1H-benzimidazol-2-yl)-3-[4-(diethylamino)-2-hydroxyphenyl]prop-2-enenitrile
• CAS: 95425-62-0
• 化学式: C₂₀H₂₀N₄O
• 分子量: 332.405
• InChiKey: YTESDRRNKUOQGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.9
• 氢给体数：
  2
• 氢受体数：
  4

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 香豆素 7 、 2-(1H-benzimidazol-2-yl)-3-(4-diethylamino-2-hydroxyphenyl)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

• Benzimidazole derivatives related to 2,3-acrylonitriles, benzimidazo[1,2-a]quinolines and fluorenes: Synthesis, antitumor evaluation in vitro and crystal structure determination
  作者：Marijana Hranjec、Gordana Pavlović、Marko Marjanović、Marijeta Kralj、Grace Karminski-Zamola

  DOI：10.1016/j.ejmech.2010.02.022

  日期：2010.6

  A synthesis and biological evaluation of new benzimidazole derivatives, related to 2,3-disubstituted acrylonitriles, benzimidazo[1,2-a]quinoline-6-carbonitriles and heteroaromatic fluorenes was described. The molecular and crystal structures of three compounds 4, 16 and 17 reveal that non-fused fluoro derivative, 4, deviates from planarity by 13.11(2)°, while fused methyl, 16, and fluoro, 17, derivatives

  描述了与2,3-二取代的丙烯腈，苯并咪唑并[1,2 - a ]喹啉-6-腈和杂芳族芴有关的新苯并咪唑衍生物的合成和生物学评价。三种化合物的分子和晶体结构4，16和17表明，非稠合的氟代衍生物，4，平面的偏离由13.11（2）°，而稠合甲基，16，和氟，17，衍生物是内4平面°表现出能够插入双链DNA的平面芳香表面。化合物4以E-异构体存在。 晶体结构证实，氢键的模式主要由弱的C–H⋯N（F）键表征，但在4的情况下，存在的乙醇分子结晶导致N–H⋯O和O–H ⋯N氢键形成。在16和17的晶体结构中，氰基参与氢键的形成，而在4中并非如此。除16和14外，所有化合物均对五种肿瘤细胞系具有显着的抗增殖活性，其中2-苯并咪唑基-3- N-甲基吡咯基-丙烯腈13及其稠合类似物23在所有细胞系中发挥最高的活性（IC 50  = 0.8–30μM），并显示出对HeLa细胞的特殊选择性。非融合的和融合的类似物