(E)-3-(benzo[d][1,3]dioxol-5-yl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one | 114021-54-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-(benzo[d][1,3]dioxol-5-yl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one
• 英文别名: 2'-hydroxy-4'-methoxy-3,4-methylenedioxychalcone；2'-hydroxy-4'-methoxy-3,4-methylenedioxychalkone；3-benzo[1,3]dioxol-5-yl-1-(2-hydroxy-4-methoxy-phenyl)-propenone；3-Benzo[1,3]dioxol-5-yl-1-(2-hydroxy-4-methoxy-phenyl)-propenon；3-(Benzo[1,3]dioxol-5-yl)-1-(2-hydroxy-4-methoxyphenyl)-2-propen-1-one；3-(1,3-Benzodioxol-5-yl)-1-(2-hydroxy-4-methoxyphenyl)-2-propen-1-one；(E)-3-(1,3-benzodioxol-5-yl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one
• CAS: 114021-54-4
• 化学式: C₁₇H₁₄O₅
• 分子量: 298.295
• InChiKey: VZZSETBKCYRDTI-QHHAFSJGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-3-(benzo[d][1,3]dioxol-5-yl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 以79%的产率得到3-(benzo[d][1,3]dioxol-5-yl)-1-(2-hydroxy-4-methoxyphenyl)propan-1-one
  参考文献：
  名称：

  查尔酮，二氢查耳酮和1,3-二芳基丙烷类似物作为抗炎剂的合成和生物学评估。

  摘要：

  通过醛醇缩合制备二十一个查耳酮，随后将这些化合物还原，得到相应的二氢查耳酮和1，3-二苯基丙烷衍生物。检查了合成产物对LPS活化的小鼠腹膜巨噬细胞中NO抑制的影响。在测试的化合物中，1,3-二芳基丙烷类似物2-（3-（3,4-二甲氧基苯基）丙基）-5-甲氧基苯酚（3p）对NO的产生表现出最显着的抑制作用。为了研究作用机理，通过免疫印迹研究了3p对iNOS和COX-2蛋白表达的影响。结果得出结论，3p能够通过ERK，p38和JNK减弱NF-κB信号传导而抑制LPS诱导的RAW264.7细胞中的iNOS表达。

  DOI：

  10.1016/j.bmcl.2017.02.038
• 作为产物：
  描述：

  丹皮酚 、 胡椒醛 生成 (E)-3-(benzo[d][1,3]dioxol-5-yl)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  1,3-二苯基丙-2-烯酮的13C核磁共振研究

  摘要：

  已经记录了 48 个不同取代的查耳酮（1,3-二苯基丙-2 烯酮）的 13C NMR 光谱并讨论了结果。该数据将有助于识别新的/天然查耳酮。

  DOI：

  10.1002/mrc.1260280516

文献信息

• Discovery of efficient stimulators for adult hippocampal neurogenesis based on scaffolds in dragon's blood
  作者：Jian-Hua Liang、Liang Yang、Si Wu、Si-Si Liu、Mark Cushman、Jing Tian、Nuo-Min Li、Qing-Hu Yang、He-Ao Zhang、Yun-Jie Qiu、Lin Xiang、Cong-Xuan Ma、Xue-Meng Li、Hong Qing

  DOI：10.1016/j.ejmech.2017.05.025

  日期：2017.8

  discovered to efficiently stimulate adult rats' neurogenesis. In-depth structure-activity relationship studies proved the necessity of a stilbene scaffold that is absent in highly cytotoxic analogs such as chalcones and heteroaryl rings and inactive analogs such as diphenyl acetylene and diphenyl ethane, and validated the importance of an NH in the carboxamide and a methylenedioxy substituent on the

  由衰老和神经系统疾病引起的海马神经发生减少会损害神经回路并导致记忆丧失。一种新的铅化合物（ñ -反式-3'，4'- methylenedioxystilben -4-基乙酰胺27）已发现有效地刺激成年大鼠的神经发生。深入的结构-活性关系研究证明，在高度细胞毒性类似物（如查耳酮和杂芳基环）和无活性类似物（如二苯乙炔和二苯乙烷）中不存在二苯乙烯骨架的必要性，并验证了氨甲酰胺和苯环上的亚甲二氧基取代基。免疫组织化学染色和生化分析表明，与先前报道的神经保护化学物质相比，N-二苯乙烯基羧酰胺具有神经增殖型神经发生的额外能力，从而为提高成年哺乳动物脑的可塑性提供了基础。
• Condensation reactions in water of active methylene compounds with arylaldehydes. One-pot synthesis of flavonols.
  作者：Francesco Fringuelli、Giosanna Pani、Oriana Piermatti、Ferdinando Pizzo

  DOI：10.1016/s0040-4020(01)89287-5

  日期：1994.1

  with benzaldehyde were studied in water in heterogeneous phase in the presence and absence of anionic and cationic surfactants such as SLS, CTACl, (CTA)2SO4 and CTAOH. All the reactions occur with excellent yields. The cationic surfactants favour the reaction and the comparison with the corresponding tetrabutylammonium salts show that the micellar catalysis is effective mainly towards the dehydration

  在存在和不存在阴离子表面活性剂和阳离子表面活性剂（例如SLS，CTACl，（CTA））的情况下，研究了苯乙醛，环己酮，异佛尔酮，苯乙腈，对硝基苯乙腈，（苯磺酰基）乙腈和茚与苯甲醛在异相水中的缩合反应。2 SO 4和CTAOH。所有反应均以优异的产率进行。阳离子表面活性剂有利于该反应，并且与相应的四丁基铵盐的比较表明，胶束催化主要对缩合之后的脱水反应有效。阴离子表面活性剂SLS是无活性的。在水性介质中以优异的产率制备了2'-羟基查耳酮，并且实现了一锅合成7-和3'，4'-取代的黄酮醇。
• SAR Studies and Biological Characterization of a Chromen-4-one Derivative as an Anti-<i>Trypanosoma brucei</i> Agent
  作者：Chiara Borsari、Nuno Santarem、Sara Macedo、María Dolores Jiménez-Antón、Juan J. Torrado、Ana Isabel Olías-Molero、María J. Corral、Annalisa Tait、Stefania Ferrari、Luca Costantino、Rosaria Luciani、Glauco Ponterini、Sheraz Gul、Maria Kuzikov、Bernhard Ellinger、Birte Behrens、Jeanette Reinshagen、José María Alunda、Anabela Cordeiro-da-Silva、Maria Paola Costi

  DOI：10.1021/acsmedchemlett.8b00565

  日期：2019.4.11

  Chemical modulation of the flavonol 2-(benzo[d] [1,3]dioxo1-5-y1)-chromen-4-one (1), a promising anti-Trypanosomatid agent previously identified, was evaluated through a phenotypic screening approach. Herein, we have performed structure activity relationship studies around hit compound 1. The pivaloyl derivative (13) showed significant anti-T. brucei activity (EC50 = 1.1 1iM) together with a selectivity index higher than 92. The early in vitro ADME-tox properties (cytotoxicity, mitochondria] toxicity, cytochrome P450 and hERG inhibition) were determined for compound 1 and its derivatives, and these led to the identification of some liabilities. The 1,3-benzodioxole moiety in the presented compounds confers better in vivo pharmacokinetic properties than those of classical flavonols. Further studies using different delivery systems could lead to an increase of compound blood levels.
• Discovery of a benzothiophene-flavonol halting miltefosine and antimonial drug resistance in Leishmania parasites through the application of medicinal chemistry, screening and genomics
  作者：Chiara Borsari、María Dolores Jiménez-Antón、Julia Eick、Eugenia Bifeld、Juan José Torrado、Ana Isabel Olías-Molero、María Jesús Corral、Nuno Santarem、Catarina Baptista、Leda Severi、Sheraz Gul、Markus Wolf、Maria Kuzikov、Bernhard Ellinger、Jeanette Reinshagen、Gesa Witt、Pasquale Linciano、Annalisa Tait、Luca Costantino、Rosaria Luciani、Paloma Tejera Nevado、Dorothea Zander-Dinse、Caio H. Franco、Stefania Ferrari、Carolina B. Moraes、Anabela Cordeiro-da-Silva、Glauco Ponterini、Joachim Clos、José María Alunda、Maria Paola Costi

  DOI：10.1016/j.ejmech.2019.111676

  日期：2019.12

  Leishmaniasis, a major health problem worldwide, has a limited arsenal of drugs for its control. The appearance of resistance to first- and second-line anti-leishmanial drugs confirms the need to develop new and less toxic drugs that overcome spontaneous resistance. In the present study, we report the design and synthesis of a novel library of 38 flavonol-like compounds and their evaluation in a panel of assays encompassing parasite killing, pharmacokinetics, genomics and ADME-Toxicity resulting in the progression of a compound in the drug discovery value chain. Compound 19, 2-(benzo[b]thiophen-3-yl)3-hydroxy-6-methoxy-4H-chromen-4-one, exhibited a broad-spectrum activity against Leishmania spp. (EC50 1.9 mu M for Leishmania infantum, 3.4 mu M 4 for L. donovani, 6.7 mu M for L. major), Trypanosoma cruzi (EC50 7.5 mu M) and T. brucei (EC50 0.8 mu M). Focusing on anti-Leishmania activity, compound 19 challenge in vitro did not select for resistance markers in L donovani, while a Cos-Seq screening for dominant resistance genes identified a gene locus on chromosome 36 that became ineffective at concentrations beyond EC50 Thus, compound 19 is a promising scaffold to tackle drug resistance in Leishmania infection. In vivo pharmacokinetic studies indicated that compound 19 has a long half-life (intravenous (IV): 63.2 h; per os (PO): 46.9 h) with an acceptable ADME-Toxicity profile. When tested in Leishmania infected hamsters, no toxicity and limited efficacy were observed. Low solubility and degradation were investigated spectroscopically as possible causes for the sub-optimal pharmacokinetic properties. Compound 19 resulted a specific compound based on the screening against a protein set, following the intrinsic fluorescence changes. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Singh, Om V.; Muthukrishnan; Sunderavadivelu, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2005, vol. 44, # 12, p. 2575 - 2581
  作者：Singh, Om V.、Muthukrishnan、Sunderavadivelu

  DOI：——

  日期：——

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