tert-butyl 4-(3-(1H-indole-2-carboxamido)phenyl)-2-(methylamino)-1H-imidazole-1-carboxylate | 1574306-31-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl 4-(3-(1H-indole-2-carboxamido)phenyl)-2-(methylamino)-1H-imidazole-1-carboxylate
• 英文别名: tert-butyl 4-[3-(1H-indole-2-carbonylamino)phenyl]-2-(methylamino)imidazole-1-carboxylate
• CAS: 1574306-31-2
• 化学式: C₂₄H₂₅N₅O₃
• 分子量: 431.494
• InChiKey: DUNUNNPYKPJKDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3-(1H-indole-2-carboxamido)phenyl)-2-(methylamino)-1H-imidazole-1-carboxylate 在 盐酸 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 5.0h， 以95%的产率得到4-(3-(1H-indole-2-carboxamido)phenyl)-2-(methylamino)-1H-imidazol-3-ium chloride
  参考文献：
  名称：

  Analogues of the marine alkaloids oroidin, clathrodin, and hymenidin induce apoptosis in human HepG2 and THP-1 cancer cells

  摘要：

  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。

  DOI：

  10.1039/c4md00286e
• 作为产物：
  描述：

  2-(methylamino)-4-(3-nitrophenyl)-1H-imidazolium bromide 在 N-甲基吗啉 、 palladium on activated charcoal 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 32.5h， 生成 tert-butyl 4-(3-(1H-indole-2-carboxamido)phenyl)-2-(methylamino)-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

• Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues
  作者：Nace Zidar、Sofia Montalvão、Žiga Hodnik、Dorota Nawrot、Aleš Žula、Janez Ilaš、Danijel Kikelj、Päivi Tammela、Lucija Mašič

  DOI：10.3390/md12020940

  日期：——

  fungal strain (Candida albicans), and oroidin was found to possess promising Gram-positive antibacterial activity. Using oroidin as a scaffold, 34 new analogues were designed, prepared and screened for their antimicrobial properties. Of these compounds, 12 exhibited >80% inhibition of the growth of at least one microorganism at a concentration of 50 µM. The most active derivative was found to be 4-phenyl-2-aminoimidazole

  海洋生物产生的次级代谢物可能对开发新的药物先导物很有价值，也可以为设计和合成新的生物活性化合物提供结构支架。海洋生物碱、clathrodin 和 oroidin 最初是从 Agelas 属的海绵中分离出来的，它们被制备并评估了它们对三种细菌菌株（粪肠球菌、金黄色葡萄球菌和大肠杆菌）和一种真菌菌株（白色念珠菌）的抗菌活性，并且发现 oroidin 具有有希望的革兰氏阳性抗菌活性。使用 oroidin 作为支架，设计、制备了 34 种新类似物并筛选了它们的抗菌特性。在这些化合物中，12 种在 50 µM 的浓度下表现出对至少一种微生物生长的抑制 > 80%。发现活性最强的衍生物是 4-苯基-2-氨基咪唑 6 小时，其对革兰氏阳性菌的 MIC₉₀（最低抑制浓度）值为 12.5 µM，对大肠杆菌为 50 µM。发现金黄色葡萄球菌和哺乳动物细胞之间的选择性指数对于化合物 6h 为 2.9，这在评估化合物作为抗菌先导物的潜力时很重要。
• Substituted 4-phenyl-2-aminoimidazoles and 4-phenyl-4,5-dihydro-2-aminoimidazoles as voltage-gated sodium channel modulators
  作者：Nace Zidar、Žiga Jakopin、David J. Madge、Fiona Chan、Jan Tytgat、Steve Peigneur、Marija Sollner Dolenc、Tihomir Tomašić、Janez Ilaš、Lucija Peterlin Mašič、Danijel Kikelj

  DOI：10.1016/j.ejmech.2013.12.034

  日期：2014.3

  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.
• 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。