(E)-2'-demethylaplysinopsin | 72479-09-5

• 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)-2'-demethylaplysinopsin
• 英文别名: (E)-5-((1H-indol-3-yl)methylene)-2-amino-1-methyl-1H-imidazol-4(5H)-one；(5E)-2-amino-5-(1H-indol-3-ylmethylidene)-1-methylimidazol-4-one
• CAS: 72479-09-5
• 化学式: C₁₃H₁₂N₄O
• 分子量: 240.264
• InChiKey: AAMOMFNMMXXVGM-IZZDOVSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.51
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  71.98
• 氢给体数：
  3.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (E)-2'-demethylaplysinopsin 以 甲醇 为溶剂， 反应 3.0h， 生成 8Z-4'-demethylaplysinopsin
  参考文献：
  名称：

  Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator

  摘要：

  Chemical analysis of a specimen of the sponge lanthella cf. flabelliformis returned two new sesquiterpene glycinyl lactams, ianthellalactams A (1) and B (2), the known sponge sesquiterpene dictyodendrillin (3) and its ethanolysis artifact ethyl dictyodendrillin (4), and five known sponge indole alkaloids, aplysinopsin (5), 8E-3'-deimino-3'-oxoaplysinopsin (6), 8Z-3'-deimino-3'-oxoaplysinopsin (7), dihydroaplysinopsin (8) and tubastrindole B (9). The equilibrated mixture 6/7 exhibited glycine-gated chloride channel receptor (GlyR) antagonist activity with a bias towards alpha 3 over alpha 1 GlyR, while tubastrindole B (9) exhibited a bias towards alpha 1 over alpha 3 GlyR. At low- to sub-micromolar concentrations, 9 was also a selective potentiator of alpha 1 GlyR, with no effect on alpha 3 GlyR-a pharmacology that could prove useful in the treatment of movement disorders such as spasticity and hyperekplexia. Our investigations into the GlyR modulatory properties of 1-9 were further supported by the synthesis of a number of structurally related indole alkaloids. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.061
• 作为产物：
  描述：

  肌酸酐 、 3-吲哚甲醛 反应 0.75h， 以42%的产率得到(E)-2'-demethylaplysinopsin
  参考文献：
  名称：

  Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator

  摘要：

  Chemical analysis of a specimen of the sponge lanthella cf. flabelliformis returned two new sesquiterpene glycinyl lactams, ianthellalactams A (1) and B (2), the known sponge sesquiterpene dictyodendrillin (3) and its ethanolysis artifact ethyl dictyodendrillin (4), and five known sponge indole alkaloids, aplysinopsin (5), 8E-3'-deimino-3'-oxoaplysinopsin (6), 8Z-3'-deimino-3'-oxoaplysinopsin (7), dihydroaplysinopsin (8) and tubastrindole B (9). The equilibrated mixture 6/7 exhibited glycine-gated chloride channel receptor (GlyR) antagonist activity with a bias towards alpha 3 over alpha 1 GlyR, while tubastrindole B (9) exhibited a bias towards alpha 1 over alpha 3 GlyR. At low- to sub-micromolar concentrations, 9 was also a selective potentiator of alpha 1 GlyR, with no effect on alpha 3 GlyR-a pharmacology that could prove useful in the treatment of movement disorders such as spasticity and hyperekplexia. Our investigations into the GlyR modulatory properties of 1-9 were further supported by the synthesis of a number of structurally related indole alkaloids. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.061

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
• 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.
• Metabolites of the marine sponge Dercitus species
  作者：Peter Djura、D. John Faulkner

  DOI：10.1021/jo01292a043

  日期：1980.2
• GUELLA, GRAZIANO;MANCINI, INES;ZIBROWIUS, HELMUT;PIETRA, FRANCESCO, HELV. CHIM. ACTA, 71,(1988) N 4, 773-782
  作者：GUELLA, GRAZIANO、MANCINI, INES、ZIBROWIUS, HELMUT、PIETRA, FRANCESCO

  DOI：——

  日期：——