(E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-5-fluoro-1H-indole-2-carboxamide | 1609461-55-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-5-fluoro-1H-indole-2-carboxamide
• 英文别名: N-[(E)-3-(2-amino-1H-imidazol-5-yl)prop-2-enyl]-5-fluoro-1H-indole-2-carboxamide
• CAS: 1609461-55-3
• 化学式: C₁₅H₁₄FN₅O
• 分子量: 299.307
• InChiKey: HFMHYLCYABPWMX-OWOJBTEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  99.6
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  吡啶 在 N-甲基吗啉 、 溴 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.75h， 生成 (E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-5-fluoro-1H-indole-2-carboxamide
  参考文献：
  名称：

  Clathrodin, hymenidin and oroidin, and their synthetic analogues as inhibitors of the voltage-gated potassium channels

  摘要：

  We have prepared three alkaloids from the Agelas sponges, clathrodin, hymenidin and oroidin, and a series of their synthetic analogues, and evaluated their inhibitory effect against six isoforms of the KO subfamily of voltage-gated potassium channels, g(v)1.1-K(v)1.6, expressed in Chinese Hamster ovary (CHO) cells using automated patch clamp electrophysiology assay. The most potent inhibitor was the (E)-N-(3(2-amino-1H-imidazol-4-yl)ally1)-4,5-dichloro-1H-pyrrole-2-carboxamide (6g) with IC50 values between 1.4 and 6.1 mu M against K(v)1.3, K(v)1.4, K(v)1.5 and K(v)1.6 channels. All compounds tested displayed selectivity against K(v)1.1 and K(v)1.2 channels. For confirmation of their activity and selectivity, compounds were additionally evaluated in the second independent system against K(v)1.1-K(v)1.6 and K(v)10.1 channels expressed in Xenopus laevis oocytes under voltage clamp conditions where IC50 values against K(v)1.3K(v)1.6 channels for the most active analogues (e.g. 6g) were lower than 1 mu M. Because of the observed low sub-micromolar IC50 values and fairly low molecular weights, the prepared compounds represent good starting points for further optimisation towards more potent and selective voltage-gated potassium channel inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.08.015

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。
• Clathrodin, hymenidin and oroidin, and their synthetic analogues as inhibitors of the voltage-gated potassium channels
  作者：Nace Zidar、Aleš Žula、Tihomir Tomašič、Marc Rogers、Robert W. Kirby、Jan Tytgat、Steve Peigneur、Danijel Kikelj、Janez Ilaš、Lucija Peterlin Mašič

  DOI：10.1016/j.ejmech.2017.08.015

  日期：2017.10

  We have prepared three alkaloids from the Agelas sponges, clathrodin, hymenidin and oroidin, and a series of their synthetic analogues, and evaluated their inhibitory effect against six isoforms of the KO subfamily of voltage-gated potassium channels, g(v)1.1-K(v)1.6, expressed in Chinese Hamster ovary (CHO) cells using automated patch clamp electrophysiology assay. The most potent inhibitor was the (E)-N-(3(2-amino-1H-imidazol-4-yl)ally1)-4,5-dichloro-1H-pyrrole-2-carboxamide (6g) with IC50 values between 1.4 and 6.1 mu M against K(v)1.3, K(v)1.4, K(v)1.5 and K(v)1.6 channels. All compounds tested displayed selectivity against K(v)1.1 and K(v)1.2 channels. For confirmation of their activity and selectivity, compounds were additionally evaluated in the second independent system against K(v)1.1-K(v)1.6 and K(v)10.1 channels expressed in Xenopus laevis oocytes under voltage clamp conditions where IC50 values against K(v)1.3K(v)1.6 channels for the most active analogues (e.g. 6g) were lower than 1 mu M. Because of the observed low sub-micromolar IC50 values and fairly low molecular weights, the prepared compounds represent good starting points for further optimisation towards more potent and selective voltage-gated potassium channel inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.