(E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-4,5-dichloro-1H-pyrrole-2-carboxamide | 1370448-91-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-4,5-dichloro-1H-pyrrole-2-carboxamide
• 英文别名: dichloroclathrodin；N-[(E)-3-(2-amino-1H-imidazol-5-yl)prop-2-enyl]-4,5-dichloro-1H-pyrrole-2-carboxamide
• CAS: 1370448-91-1
• 化学式: C₁₁H₁₁Cl₂N₅O
• 分子量: 300.147
• InChiKey: MYEOSEFRVAPSCL-OWOJBTEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  99.6
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-4,5-dichloro-1H-pyrrole-2-carboxamide 在 acetone extract of Stylissa caribica, live sponges, Bahamas, Sweetings Cay, diced and homogenized with crushed dry ice and acetone and then filtered with filter paper 、 水 、 双氧水 、 sodium hydroxide 作用下， 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  海洋海绵 Agelas conifera 和 Stylissa caribica 的吡咯氨基咪唑生物碱代谢合成

  摘要：

  游戏-设置-匹配：吡咯氨基咪唑生物碱 (PAI) 是通过来自产生 PAI 的海绵的无细胞酶制剂，从 oroidin 的氯化类似物代谢合成的。 PAI 生物合成的证据和意义包括推定的单电子转移 (SET)，它促进前体的 C - C 键形成反应。

  DOI：

  10.1002/anie.201108119
• 作为产物：
  描述：

  N-benzyloxycarbonyl-1,2-dihydropyridine 在 N-甲基吗啉 、 溴 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.75h， 生成 (E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-4,5-dichloro-1H-pyrrole-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

• Pyrrole Aminoimidazole Alkaloid Metabiosynthesis with Marine Sponges Agelas conifera and Stylissa caribica
  作者：E. Paige Stout、Yong-Gang Wang、Daniel Romo、Tadeusz F. Molinski

  DOI：10.1002/anie.201108119

  日期：2012.5.14

  Game‐SET‐match: Pyrrole aminoimidazole alkaloids (PAIs) are metabiosynthesized from chlorinated analogues of oroidin by cell‐free enzyme preparations from PAI‐producing sponges. Evidence and implications for the biosynthesis of PAIs include putative single‐electron transfers (SETs) that promote CC bond‐forming reactions of precursors.

  游戏-设置-匹配：吡咯氨基咪唑生物碱 (PAI) 是通过来自产生 PAI 的海绵的无细胞酶制剂，从 oroidin 的氯化类似物代谢合成的。 PAI 生物合成的证据和意义包括推定的单电子转移 (SET)，它促进前体的 C - C 键形成反应。
• 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.