aplysinopsin | 63153-56-0

• 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: aplysinopsin
• 英文别名: (E)-5-((1H-indol-3-yl)methylene)-2-imino-1,3-dimethylimidazolidin-4-one；(5E)-2-imino-5-(1H-indol-3-ylmethylidene)-1,3-dimethylimidazolidin-4-one
• CAS: 63153-56-0
• 化学式: C₁₄H₁₄N₄O
• 分子量: 254.291
• InChiKey: AZGOVLGMSGAOMP-FZYUQVBKSA-N

物化性质

• 沸点：
  425.5±55.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.85
• 重原子数：
  19.0
• 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

• 作为反应物：
  描述：

  aplysinopsin 、 2-萘磺酰氯 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以34%的产率得到(E)-2-imino-1,3-dimethyl-5-((1-(naphthalen-2-ylsulfonyl)-1H-indol-3-yl)methylene)imidazolidin-4-one
  参考文献：
  名称：

  鉴定 aplysinopsin 作为抗胆碱酯酶和抗 BACE-1 活性的血脑屏障可渗透支架

  摘要：

  Aplysinopsins 是一组海洋衍生的吲哚生物碱，具有多种药理作用。然而，尚未报道它们对抗阿尔茨海默病靶点的影响。在此，我们报告了 aplysinopsin ( 1 )的合成及其对胆碱酯酶和 β 位点淀粉样前体蛋白裂解酶 1 (BACE-1) 的影响。它抑制电鳗乙酰胆碱酯酶 (AChE)、马血清丁酰胆碱酯酶 (BChE) 和人 BACE-1，IC 50值分别为 33.9、30.3 和 33.7 µM，具有出色的 BBB 渗透性 ( P e 8.92 × 10 -6 cm/ s)。为了优化其亚微摩尔活性，制备并筛选了第一代类似物。两个最活跃的类似物5b和 (Z)-发现8g有效渗透 BBB（P e  > 5 × 10 -6 cm/s）。所述Ñ磺酰胺衍生物5b中显示更好的胆碱酯酶抑制，而其它类似物（Z） - 8克强烈抑制BACE-1（IC 50 0.78μM）活性。类似物5b主要与 AChE

  DOI：

  10.1016/j.bioorg.2020.104568
• 作为产物：
  描述：

  3-吲哚甲醛 在 氢氧化钾 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 aplysinopsin
  参考文献：
  名称：

  Synthesis of 2-dimethylaminoimidazole derivatives: a new access to indolyl-imidazole alkaloids of marine origin.

  摘要：

  The first preparation of 2-dimethylaminoimidazole 1a, a structural feature of several marine products was undertaken and its reactivity investigated. The synthesis of natural alkaloids 5 and 12b was achieved by direct coupling of the easily accessible oxidized 2-dimethylaminoimidazoles 7 and 8 with indole-3-carboxaldehyde and indole respectively, demonstrating the usefulness of this approach for other structurally related natural products.

  DOI：

  10.1016/s0040-4039(00)92376-1

文献信息

• Novel Aplysinopsin-Type Alkaloids from Scleractinian Corals of the Family Dendrophylliidae of the Mediterranean and the Philippines. Configurational-assignment criteria, stereospecific synthesis, and photoisomerization
  作者：Graziano Guella、Ines Mancini、Helmut Zibrowius、Francesco Pietra

  DOI：10.1002/hlca.19880710412

  日期：1988.6.15

  scleractinian coral Tubastraea sp. (Dendrophylliidae) collected at Palawan, Philippines, 3′-deimino-3′-oxoaplysinopsin (4) and 6-bromo-3′-deimino-3′-oxoaplysinopsin (6) are now isolated as 5:2 mixtures of (E/Z) stereoisomers. The 3′-deimino-2′,4′-bis(demethyl)-3′-oxoaplysinopsin (7) and 6-bromo-3′-demino-2′,4-bis(demethyl)-3′-oxoaplysinopsin (5) are isolated as 2:3 and 1:1 (E/Z) mixtures, respectively

  来自巩膜珊瑚Tubastraea sp。（3）-deimino-3'-oxoaplysinopsin（4）和6-bromo-3'-deimino-3'-oxoaplysinopsin（6）收集于菲律宾巴拉望岛（Dendrophylliidae），现以（E / Z）立体异构体。3'-deimino-2'，4'-双（去甲基）-3'-氧皂甙酶（7）和6-bromo-3'-demino-2'，4-双（去甲基）-3'-氧皂甙酶（5）分别以2：3和1：1（E / Z）混合物的形式从另一种树突藻（Leptopsammia pruvoti）中分离出来，收集在法国地中海沿岸的马赛附近。通过合成可获得用于完整结构确定所需的大量这些化合物和相关化合物。因此，吲哚-3-羧甲醛（9）或其6-溴衍生物14与乙内酰脲（15），3-甲基乙内酰脲（11）或1，3-二甲基乙内酰脲（10）的缩合产生具有高立体特异性的普遍的天然
• 5-(Indol-3-ylmethylene)-1,3-dimethyl-2-methylamino-4-imidazolidinone
  申请人：Hoffmann-La Roche Inc.

  公开号：US04195179A1

  公开（公告）日：1980-03-25

  5-(Indol-3-ylmethylene)-1,3-dimethyl-2-methylimino-4-imidazolidinone and its geometric isomers, prepared, inter alia, from indole-3-aldehyde and 1,3-dimethyl-2-methylimino-4-imidazolidinone, are described. The end products are useful as antidepressants.

  描述了5-（吲哚-3-基甲烯基）-1,3-二甲基-2-甲基亚胺-4-咪唑啉酮及其几何异构体，其中包括从吲哚-3-醛和1,3-二甲基-2-甲基亚胺-4-咪唑啉酮制备的。最终产品可用作抗抑郁剂。
• Gulati, Deepa; Chauhan, P. M. S.; Pratap, Ram, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1994, vol. 33, # 1, p. 4 - 9
  作者：Gulati, Deepa、Chauhan, P. M. S.、Pratap, Ram、Bhakuni, D. S.

  DOI：——

  日期：——
• 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.