tert-butyl 2-amino-4-(4-aminophenyl)-1H-imidazole-1-carboxylate | 1574306-18-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 2-amino-4-(4-aminophenyl)-1H-imidazole-1-carboxylate
• CAS: 1574306-18-5
• 化学式: C₁₄H₁₈N₄O₂
• 分子量: 274.323
• InChiKey: HZFCFTKSWSAZGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  96.16
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-amino-4-(4-aminophenyl)-1H-imidazole-1-carboxylate 在 N-甲基吗啉 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 乙酰氯 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 25.5h， 生成 (S)-2-amino-4-(4-(pyrrolidin-1-ium-2-carboxamido)phenyl)-1H-imidazol-3-ium chloride
  参考文献：
  名称：

  Substituted 4-phenyl-2-aminoimidazoles and 4-phenyl-4,5-dihydro-2-aminoimidazoles as voltage-gated sodium channel modulators

  摘要：

  Voltage-gated sodium channels play an integral part in neurotransmission and their dysfunction is frequently a cause of various neurological disorders. On the basis of the structure of marine alkaloid clathrodin, twenty eight new analogs were designed, synthesized and tested for their ability to block human Na(v)1.3, Na(v)1.4 and Na(v)1.7 channels, as well as for their selectivity against human cardiac isoform Na(v)1.5, using automated patch clamp electrophysiological assay. Several compounds exhibited promising activities on different Na-v channel isoforms in the medium micromolar range and some of the compounds showed also moderate isoform selectivities. The most promising results were obtained for the Na(v)1.3 channel, for which four compounds were found to possess IC50 values lower than 15 mu M. All of the active compounds bind to the open-inactivated states of the channels and therefore act as state-dependent modulators. The obtained results validate the approach of using natural products driven chemistry for drug discovery starting points and represent a good foundation for future design of selective Na-v modulators. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.034
• 作为产物：
  描述：

  2-溴-4'-硝基苯乙酮 在 4-二甲氨基吡啶 、 palladium on activated charcoal 、 氢气 、 一水合肼 作用下， 以 四氢呋喃 、 甲醇 、 乙醇-D1 、 乙腈 为溶剂， 反应 13.67h， 生成 tert-butyl 2-amino-4-(4-aminophenyl)-1H-imidazole-1-carboxylate
  参考文献：
  名称：

  Substituted 4-phenyl-2-aminoimidazoles and 4-phenyl-4,5-dihydro-2-aminoimidazoles as voltage-gated sodium channel modulators

  摘要：

  Voltage-gated sodium channels play an integral part in neurotransmission and their dysfunction is frequently a cause of various neurological disorders. On the basis of the structure of marine alkaloid clathrodin, twenty eight new analogs were designed, synthesized and tested for their ability to block human Na(v)1.3, Na(v)1.4 and Na(v)1.7 channels, as well as for their selectivity against human cardiac isoform Na(v)1.5, using automated patch clamp electrophysiological assay. Several compounds exhibited promising activities on different Na-v channel isoforms in the medium micromolar range and some of the compounds showed also moderate isoform selectivities. The most promising results were obtained for the Na(v)1.3 channel, for which four compounds were found to possess IC50 values lower than 15 mu M. All of the active compounds bind to the open-inactivated states of the channels and therefore act as state-dependent modulators. The obtained results validate the approach of using natural products driven chemistry for drug discovery starting points and represent a good foundation for future design of selective Na-v modulators. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.034

文献信息

• Analogues of the marine alkaloids oroidin, clathrodin, and hymenidin induce apoptosis in human HepG2 and THP-1 cancer cells
  作者：Tihomir Tomašič、Dominik Nabergoj、Sanja Vrbek、Nace Zidar、Žiga Jakopin、Aleš Žula、Žiga Hodnik、Marko Jukič、Marko Anderluh、Janez Ilaš、Marija Sollner Dolenc、Jean Peluso、Geneviève Ubeaud-Séquier、Christian D. Muller、Lucija Peterlin Mašič、Danijel Kikelj

  DOI：10.1039/c4md00286e

  日期：——

  Structural modification of the marine alkaloid oroidin resulted in improved apoptosis inducing activity in HepG2 and THP-1 cell lines.

  海洋生物碱oroidin的结构修改导致在HepG2和THP-1细胞系中的凋亡诱导活性得到改善。
• Inhibition of biofilm formation by conformationally constrained indole-based analogues of the marine alkaloid oroidin
  作者：Žiga Hodnik、Joanna M. Łoś、Aleš Žula、Nace Zidar、Žiga Jakopin、Marcin Łoś、Marija Sollner Dolenc、Janez Ilaš、Grzegorz Węgrzyn、Lucija Peterlin Mašič、Danijel Kikelj

  DOI：10.1016/j.bmcl.2014.03.094

  日期：2014.6

  Herein, we describe indole-based analogues of oroidin as a novel class of 2-aminoimidazole-based inhibitors of methicillin-resistant Staphylococcus aureus biofilm formation and, to the best of our knowledge, the first reported 2-aminoimidazole-based inhibitors of Streptococcus mutans biofilm formation. This study highlighted the indole moiety as a dibromopyrrole mimetic for obtaining inhibitors of S. aureus and S. mutans biofilm formation. The most potent compound in the series, 5-(trifluoromethoxy) indole-based analogue 4b (MBIC50 = 20 mu M), emerged as a promising hit for further optimisation of novel inhibitors of S. aureus and S. mutans biofilms. (C) 2014 Elsevier Ltd. All rights reserved.