(E)-5-((5-bromo-1H-indol-3-yl)methylene)-2-imino-1,3-dimethylimidazolidin-4-one | 97480-14-3

• 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: (E)-5-((5-bromo-1H-indol-3-yl)methylene)-2-imino-1,3-dimethylimidazolidin-4-one
• 英文别名: (E)-5-[(5-bromo-1H-indol-3-yl)methylene]-2-imino-1,3-dimethylimidazolidin-4-one；5-bromoaplysinopsin；(5E)-5-[(5-bromo-1H-indol-3-yl)methylidene]-2-imino-1,3-dimethylimidazolidin-4-one
• CAS: 97480-14-3
• 化学式: C₁₄H₁₃BrN₄O
• 分子量: 333.187
• InChiKey: DICVBGGIAAPPNV-ZSUDRMHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.61
• 重原子数：
  20.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  63.19
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  5-bromo-3-(2'-imino-1',3'-dimethyl-5'-oxo-4'-imidazolinylidenemethyl)-1-(p-toluenesulphonyl)-1H-indole 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以50%的产率得到(E)-5-((5-bromo-1H-indol-3-yl)methylene)-2-imino-1,3-dimethylimidazolidin-4-one
  参考文献：
  名称：

  Gulati, Deepa; Chauhan, P. M. S.; Pratap, Ram, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1994, vol. 33, # 1, p. 10 - 16

  摘要：

  DOI：

文献信息

• Constituents of morphologically similar sponges
  作者：Adrienne A. Tymiak、Kenneth L. Rinehart、Gerald J. Bakus

  DOI：10.1016/s0040-4020(01)96471-3

  日期：1985.1

  the marine sponge Smenospongia aurea have been isolated and characterized as 5-bromo- and 5,6-dibromo-N,N-dimethyltryptamines (1 and 2), aureol (3), and two new aplysinopsin derivatives (6-bromoaplysinopsin and 6-bromo-4'-N-demethylaplysinopsin, 4 and 5, respectively). Morphologically similar species from the Caribbean have been surveyed and found to contain either mixtures of these metabolites or

  已从海洋海绵金黄色葡萄球菌中分离出化合物，并将其表征为5-溴和5,6-二溴-N，N-二甲基色胺（1和2），金黄色酚（3）和两种新的皂素衍生物（6-溴皂素和6-溴-4'-N-去甲基aplysinopsin ，分别为4和5）。已经对加勒比地区形态相似的物种进行了调查，发现它们既包含这些代谢物的混合物，也包含溴酪氨酸衍生的化合物。讨论了含溴吲哚的代谢物的1 H NMR光谱。
• 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.
• Synthesis and structure–affinity relationships of novel small molecule natural product derivatives capable of discriminating between serotonin 5-HT1A, 5-HT2A, 5-HT2C receptor subtypes
  作者：David F. Cummings、Diana C. Canseco、Pratikkumar Sheth、James E. Johnson、John A. Schetz

  DOI：10.1016/j.bmc.2010.05.017

  日期：2010.7

  Efforts to develop ligands that distinguish between clinically relevant 5-HT2A and 5-HT2C serotonin receptor subtypes have been challenging, because their sequences have high homology. Previous studies reported that a novel aplysinopsin belonging to a chemical class of natural products isolated from a marine sponge was selective for the 5-HT2C over the 5-HT2A receptor subtype. Our goal was to explore the 5-HT2A/2C receptor structure-affinity relationships of derivatives based on the aplysinopsin natural product pharmacophore. Twenty aplysinopsin derivatives were synthesized, purified and tested for their affinities for cloned human serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptor subtypes. Four compounds in this series had >30-fold selectivity for 5-HT2A or 5-HT2C receptors. The compound (E)-5-((5,6-dichloro-1H-indol-3-yl) methylene)-2-imino-1,3-dimethylimidazolidin-4-one (UNT-TWU-22, 16) had approximately 2100-fold selectivity for the serotonin 5-HT2C receptor subtype: an affinity for 5-HT2C equal to 46 nM and no detectable affinity for the 5-HT1A or 5-HT2A receptor subtypes. The two most important factors controlling 5-HT2A or 5-HT2C receptor subtype selectivity were the combined R1,R3-alkylation of the imidazolidinone ring and the type and number of halogens on the indole ring of the aplysinopsin pharmacophore. (C) 2010 Elsevier Ltd. All rights reserved.
• Gulati, Deepa; Chauhan, P. M. S.; Pratap, Ram, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1994, vol. 33, # 1, p. 10 - 16
  作者：Gulati, Deepa、Chauhan, P. M. S.、Pratap, Ram、Bhakuni, D. S.

  DOI：——

  日期：——