2-(4-methoxybenzylidene)-2,3-dihydro-5,6-dimethoxyinden-1-one | 222965-37-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-(4-methoxybenzylidene)-2,3-dihydro-5,6-dimethoxyinden-1-one
• 英文别名: 5,6-dimethoxy-2-(4-methoxybenzylidene)-2,3-dihydro-1H-inden-1-one；5,6-dimethoxy-2-[(4-methoxyphenyl)methylidene]-3H-inden-1-one
• CAS: 222965-37-9
• 化学式: C₁₉H₁₈O₄
• 分子量: 310.35
• InChiKey: SMEWWRJXXCTEDX-UHFFFAOYSA-N

物化性质

• 沸点：
  515.4±50.0 °C(Predicted)
• 密度：
  1.217±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-methoxybenzylidene)-2,3-dihydro-5,6-dimethoxyinden-1-one 在 盐酸 、 sodium tetrahydroborate 、 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 生成 2-(4-methoxybenzyl)-5,6-dimethoxy-1H-indene
  参考文献：
  名称：

  Syntheses of 2-methoxyestradiol and eugenol template based diarylpropenes as non-steroidal anticancer agents

  摘要：

  基于2-甲氧基雌二醇（1）和丁子香酚（6）模板，合成了构象灵活和刚性的二芳基丙烯类化合物14(a–l)与20(a–e)，作为非甾体抗肿瘤药物。采用SRB法评估了这些合成化合物在体外对人癌细胞系MCF-7、A549、DU 145、KB和MDA-MB-231的抗肿瘤活性。化合物14i、14k和15a在不同癌细胞系中显示显著的抗肿瘤活性，IC50值介于10.27 μM至27.91 μM之间。活性最高的分子14k通过诱导凋亡和阻滞细胞周期于G2/M期来抑制细胞增殖。在正常肝单核细胞（THP-1）中进行的体外毒性测试显示，这些化合物（14i、14k和15a）对癌细胞与健康细胞具有高度的选择性。

  DOI：

  10.1039/c4ra03823a
• 作为产物：
  描述：

  5,6-二甲氧基茚酮 、 4-甲氧基苯甲醛 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 2-(4-methoxybenzylidene)-2,3-dihydro-5,6-dimethoxyinden-1-one
  参考文献：
  名称：

  A Facile Ionic Liquid Promoted Synthesis, Cholinesterase Inhibitory Activity and Molecular Modeling Study of Novel Highly Functionalized Spiropyrrolidines

  摘要：

  在离子液体[bmim]Br中合成了一系列新型二甲基氧代茚满嵌段螺吡咯烷，并评估了其对胆碱酯酶的抑制活性。在螺吡咯烷中，化合物4f对乙酰胆碱酯酶（AChE）表现出最强的活性，IC50值为1.57 µM。对活性最高的化合物进行了分子对接模拟，以揭示其与AChE受体活性位点的结合机制。

  DOI：

  10.3390/molecules20022296

文献信息

• Ionic Liquid-Promoted Synthesis and Cholinesterase Inhibitory Activity of Highly Functionalized Spiropyrrolidines
  作者：Raju Suresh Kumar、Abdulrahman I. Almansour、Natarajan Arumugam、Alireza Basiri、Yalda Kia、Raju Ranjith Kumar

  DOI：10.1071/ch14370

  日期：——

  A library of novel, highly functionalized spiropyrrolidines has been synthesized stereoselectively for the first time in ionic liquid medium employing [3+2] cycloaddition of a series of 2-arylmethylidene-5,6-dimethoxy-2,3-dihydro-1H-inden-1-ones with an unexplored azomethine ylide derived from acenaphthenequinone or isatin and tryptophan. These compounds were evaluated in vitro for their acetylcholinesterase and butyrylcholinesterase inhibitory activities. Molecular modelling simulation was performed to determine the binding interaction and orientation of these molecules in the active site gorge of the respective receptors.

  我们首次在离子液体介质中利用一系列 2-芳基亚甲基-5,6-二甲氧基-2,3-二氢-1H-茚-1-酮与源自苊醌或异atin 和色氨酸的一种未探索的偶氮甲基醯化物的[3+2]环加成，立体选择性地合成了一批新型、高官能度的螺吡咯烷类化合物。对这些化合物的乙酰胆碱酯酶和丁酰胆碱酯酶抑制活性进行了体外评估。进行了分子建模模拟，以确定这些分子在各自受体活性位点峡谷中的结合相互作用和取向。
• Multifunctional indanone–chalcone hybrid compounds with anti-β-amyloid (Aβ) aggregation, monoamine oxidase B (MAO-B) inhibition and neuroprotective properties against Alzheimer’s disease
  作者：Keren Wang、Lintao Yu、Jian Shi、Wenmin Liu、Zhipei Sang

  DOI：10.1007/s00044-019-02423-4

  日期：2019.11

  discover multifunctional agents for the treatment of Alzheimer’s disease (AD), a series of indanone–chalcone hybrid compounds were designed and synthesized based on the multitarget-directed ligand strategy. Their monoamino oxidases (MAO-A and MAO-B) and Aβ1–42 aggregation inhibitory activities were evaluated. The results were shown that all synthetic compounds exhibited mostly good multifunctional activities

  为了发现用于治疗阿尔茨海默氏病（AD）的多功能药物，基于多靶标定向配体策略设计并合成了一系列茚满酮-查尔酮杂化化合物。评估了它们的单氨基氧化酶（MAO-A和MAO-B）和Aβ1–42聚集抑制活性。结果表明，所有合成化合物均表现出良好的多功能活性。它们之中，化合物TM-11表示的最好的甲β 1-42聚集抑制效力（IC 50  〜1.8μM）和良好的解聚作用的活性（IC 50  〜7.9微米）。TEM图像和对接研究都为该假设提供了良好的合理解释。同时，化合物TM-11是一种选择性MAO-B抑制剂，以及针对A中的神经保护剂β 1-42诱导的毒性。基于结构上的考虑，化合物TM-11的亲脂性可根据Lipinski的5法则在体外穿过血脑屏障（BBB）。总之，这些结果表明，化合物TM-11可能是治疗AD的潜在多功能剂。
• POMA analyses as new efficient bioinformatics’ platform to predict and optimise bioactivity of synthesized 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues
  作者：Mohamed Jawed Ahsan、Jeyabalan Govindasamy、Habibullah Khalilullah、Govind Mohan、James P. Stables、Christophe Pannecouque、Eric De Clercq

  DOI：10.1016/j.bmcl.2012.09.108

  日期：2012.12

  A series of 43, 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues (D01-D43) were analysed using Petra, Osiris, Molinspiration and ALOGPS (POMA) to identify pharmacophore, toxicity prediction, lipophilicity and bioactivity. All the compounds were evaluated for anti-HIV activity. 3-(4-Chlorophenyl)-N-(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D07) was found to be the most active with IC50 > 4.83 mu M and CC50 4.83 mu M. 3-(4-Fluorophenyl)-6,7-dimethoxy-3a, 4-dihydro-3H-indeno[1,2-c]pyrazole-2-carbothioamide (D41) was found to be the most active compound against bacterial strains with MIC of 4 mu g/ml, comparable to the standard drug ciprofloxacin while 3-(4-methoxyphenyl)-6,7-dimethoxy-3a, 4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D38) was found to be the most active compound against fungal strains with MIC 2-4 mu g/ml, however less active than standard fluconazole. Toxicities prediction by Osiris were well supported and experimentally verified with exception of some compounds. In anticonvulsant screening, 3-(4-fluorophenyl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D09) showed maximum activity showing 100% (4/4, 0.25-0.5 h) and 75% (3/4, 1.0 h) protection against minimal clonic seizure test without any toxicity. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis and anticonvulsant activity of 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues
  作者：Mohamed Jawed Ahsan、Habibullah Khalilullah、James P. Stables、Jeyabalan Govindasamy

  DOI：10.3109/14756366.2012.663364

  日期：2013.6.1

  A series of fourteen 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues were synthesized and evaluated for anticonvulsant activity according to the Antiepileptic Drug Development Programme (ADD) protocol. Some of the synthesized compounds showed significant activity in minimal clonic seizure model (6 Hz psychomotor seizure test). 3-(4-Fluorophenyl)-N-(4-bromophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c] pyrazole-2-carboxamide (4c) was found to be the most active compound of the series showing 75% (3/4, 0.25-2.0 h) and 50% (2/4, 4.0 h) protection against minimal clonic seizure at 100 mg/kg without any toxicity. 3-(Pyridin-4-yl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a, 4-dihydro-3H-indeno[1,2-c] pyrazole-2-carboxamide (4f) showed protection in maximal electroshock (MES) seizure and subcutaneous metrazol (scMET) seizure at 300 mg/kg.
• Synthesis and antimycobacterial evaluation of 3a,4-dihydro-3H-indeno [1,2-c] pyrazole-2-carboxamide analogues
  作者：Mohamed Jawed Ahsan、Jeyabalan Govinda Samy、Habibullah Khalilullah、Mohamed Afroz Bakht、Mohd. Zaheen Hassan

  DOI：10.1016/j.ejmech.2011.09.035

  日期：2011.11

  In the present investigation, a series of 3a,4-dihydro-3H-indeno [1,2-c] pyrazole-2-carboxamide analogues were synthesized and were evaluated for antitubercular activity by two fold serial dilution technique. All the newly synthesized compounds showed low to good inhibitory activities against Mycobacterium tuberculosis H(37)Rv and multi-drug resistant M. tuberculosis (MDR-TB). 3-(4-fluorophenyl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno [1,2-c] pyrazole-2-carboxamide (4c) was found to be the most promising compound active against M. tuberculosis, H37Rv and MDR-TB with minimum inhibitory concentrations 0.83 mu M and 332 mu M respectively. (C) 2011 Elsevier Masson SAS. All rights reserved.