(Z)-2-amino-4-((4-bromo-1H-indol-3-yl)methylene)-1-methyl-1H-imidazol-5(4H)-one | 1393483-95-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (Z)-2-amino-4-((4-bromo-1H-indol-3-yl)methylene)-1-methyl-1H-imidazol-5(4H)-one
• 英文别名: (5Z)-2-amino-5-[(4-bromo-1H-indol-3-yl)methylidene]-3-methylimidazol-4-one
• CAS: 1393483-95-8
• 化学式: C₁₃H₁₁BrN₄O
• 分子量: 319.161
• InChiKey: ADEZIYQYXOGZGX-YHYXMXQVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  74.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-溴吲哚-3-甲醛 、 isocreatinine 生成 (Z)-2-amino-4-((4-bromo-1H-indol-3-yl)methylene)-1-methyl-1H-imidazol-5(4H)-one
  参考文献：
  名称：

  Synthesis and evaluation of aplysinopsin analogs as inhibitors of human monoamine oxidase A and B

  摘要：

  Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms. Previous studies have shown aplysinopsin analogs to possess a variety of biological activities, including modulation of neurotransmissions. A series of fifty aplysinopsin analogs was synthesized and assayed for monoamine oxidase A and B inhibitory activity. Three compounds displayed significant MAO inhibitory activity and selectivity. The compound (E)-5-[(6-bromo-1H-indol-3-yl) methylene]-2-imino-1,3-dimethylimidazolidin-4-one (3x) possessed an IC50 of 5.6 nM at MAO-A and had a selectivity index of 80.24. An SAR study revealed that multiple N-methylations, one of which should be at position N-2', and bromination at C-5 or C-6 are important factors for MAO-A potency and selectivity. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.058

文献信息

• Synthesis and evaluation of aplysinopsin analogs as inhibitors of human monoamine oxidase A and B
  作者：Kevin Lewellyn、Dobroslawa Bialonska、Narayan D. Chaurasiya、Babu L. Tekwani、Jordan K. Zjawiony

  DOI：10.1016/j.bmcl.2012.06.058

  日期：2012.8

  Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms. Previous studies have shown aplysinopsin analogs to possess a variety of biological activities, including modulation of neurotransmissions. A series of fifty aplysinopsin analogs was synthesized and assayed for monoamine oxidase A and B inhibitory activity. Three compounds displayed significant MAO inhibitory activity and selectivity. The compound (E)-5-[(6-bromo-1H-indol-3-yl) methylene]-2-imino-1,3-dimethylimidazolidin-4-one (3x) possessed an IC50 of 5.6 nM at MAO-A and had a selectivity index of 80.24. An SAR study revealed that multiple N-methylations, one of which should be at position N-2', and bromination at C-5 or C-6 are important factors for MAO-A potency and selectivity. (c) 2012 Elsevier Ltd. All rights reserved.
• In vitro structure–activity relationships of aplysinopsin analogs and their in vivo evaluation in the chick anxiety–depression model
  作者：Kevin Lewellyn、Dobroslawa Bialonska、Melissa J. Loria、Stephen W. White、Kenneth J. Sufka、Jordan K. Zjawiony

  DOI：10.1016/j.bmc.2013.09.011

  日期：2013.11

  Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms and have been shown to possess a range of biological activities. In vitro receptor binding assays showed that of the 12 serotonin receptor subtypes, analogues showed a high affinity for the 5-HT2B and 5-HT2C receptor subtypes, with selectivity for 5-HT2B over 5-HT2C. While no conclusions could be drawn about the number and position of N-methylations, bromination at C-4 and C-5 of the indole ring resulted in greater binding affinities, with K-i's as low as 35 nM. This data, combined with previous knowledge of the CNS activity of aplysinopsin analogs, suggested that these compounds may have potential as leads for antidepressant drugs. Compounds 3c, 3u, and 3x were evaluated in the chick anxiety-depression model to assess their in vivo efficacy. Compound 3c showed a modest antidepressant effect at a dose of 30 nM/kg in the animal model. (C) 2013 Elsevier Ltd. All rights reserved.