9-(3,4-dimethoxyphenyl)-6,9-dihydro-[1,3]dioxolo[4,5-g]furo[3,4-b]quinolin-8(5H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 9-(3,4-dimethoxyphenyl)-6,9-dihydro-[1,3]dioxolo[4,5-g]furo[3,4-b]quinolin-8(5H)-one
• 英文别名: (+/-)-9-(3,4-Dimethoxyphenyl)-6,7-methylenedioxy-4,9-dihydrofuro[3,4-b]quinolin-1(3H)-one；9-(3,4-Dimethoxyphenyl)-6,9-dihydro[1,3]dioxolo[4,5-g]furo[3,4-b]quinolin-8(5H)-one；8-(3,4-dimethoxyphenyl)-5,12,14-trioxa-2-azatetracyclo[7.7.0.03,7.011,15]hexadeca-1(16),3(7),9,11(15)-tetraen-6-one
• 化学式: C₂₀H₁₇NO₆
• 分子量: 367.358
• InChiKey: BBMOVSVMXDPQAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  75.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(3,4-dimethoxyphenyl)-2-hydroxymethyl-6,7-methylenedioxyquinoline-3-carboxylic acid lactone 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以93%的产率得到9-(3,4-dimethoxyphenyl)-6,9-dihydro-[1,3]dioxolo[4,5-g]furo[3,4-b]quinolin-8(5H)-one
  参考文献：
  名称：

  植物中的聚烷氧基苯。5.在海胆胚胎中具有强微管蛋白去稳定活性的氮杂鬼臼毒素合成中的欧芹种子提取物和细胞培养分析

  摘要：

  使用欧芹种子油中的烯丙基聚烷氧基苯合成了一系列带有修饰的环B和E的4-氮杂鬼臼毒素衍生物。在表型海胆胚胎试验中体内评估了靶向分子的抗有丝分裂和微管蛋白去稳定活性。通过体内海胆胚胎测定法鉴定出的最具活性的化合物的特征是肉豆蔻酸衍生的环E（4e，6e和8e）。确定这些分子比鬼臼毒素更有效。通过使用A549和Jurkat人类白血病T细胞系的常规测定法进一步证实和评估了所选分子的细胞毒性作用，包括细胞生长抑制，细胞周期停滞，细胞微管破坏和凋亡诱导。B环的修饰产生6-OMe取代的分子8e，其为最具活性的化合物。最后，在Jurkat细胞中，化合物8e诱导了由顶端caspases-2和-9而不是caspase-8介导的caspase依赖性凋亡，这暗示了caspase-9依赖性内在凋亡途径的参与。

  DOI：

  10.1021/jm200737s

文献信息

• Synthesis and antibacterial activity of new lactone 1,4-dihydroquinoline derivatives
  作者：Rosangela S. Laurentiz、Willian P. Gomes、Ana P. R. Pissurno、Fernanda A. Santos、Vinicius Cristian O. Santos、Carlos H. G. Martins

  DOI：10.1007/s00044-017-2129-x

  日期：2018.4

  and 4ci displayed moderate antibacterial activity against P. gingivalis. 4bi was the most active compound against the three strains of Mycobacterium. Based on structure–activity relationship studies, we observed that the presence of a nitro group on the benzylic ring and a methylenedioxy group on the dihydroquinoline ring enhanced the antibacterial activity of the derivatives.

  在这项工作中，有效地合成了一系列内酯1,4-二氢喹啉衍生物4并通过1 H和13 C NMR进行了表征。评价了所合成的化合物对细菌菌株牙龈卟啉单胞菌，黑线菌，血链球菌和血链球菌以及对结核分枝杆菌，鸟分枝杆菌和堪萨斯分枝杆菌的体外抗菌活性。结果表明，所评价的化合物对革兰氏阴性细菌更具活性。化合物4ba，4bb，4BG，4bi，40亿，4CH，和4 Cl显示温和的抗菌活性对牙龈卟啉菌。4bi是对三种分枝杆菌最具活性的化合物。根据结构-活性关系研究，我们观察到苄基环上存在硝基，二氢喹啉环上存在亚甲基二氧基，可以增强衍生物的抗菌活性。
• Insecticidal heterolignans—Tubuline polymerization inhibitors with activity against chewing pests
  作者：Jens Frackenpohl、Isabelle Adelt、Horst Antonicek、Christian Arnold、Patricia Behrmann、Nicole Blaha、Jutta Böhmer、Oliver Gutbrod、Roman Hanke、Sabine Hohmann、Marc van Houtdreve、Peter Lösel、Olga Malsam、Martin Melchers、Valentina Neufert、Elisabeth Peschel、Udo Reckmann、Thomas Schenke、Hans-Peter Thiesen、Robert Velten、Kathrin Vogelsang、Hans-Christoph Weiss

  DOI：10.1016/j.bmc.2009.01.042

  日期：2009.6

  Starting from natural product podophyllotoxin 1 substituted heterolignans were identified with promising insecticidal in vivo activity. The impact of substitution in each segment of the core structure was investigated in a detailed SAR study, and variation of substituents in both aromatic moieties afforded derivatives 5 and 43 with broad insecticidal activity against lepidopteran and coleopteran species. In vitro measurements supported by modeling studies indicate that heterolignans 3-134 act as tubuline polymerization inhibitors interacting with the colchicine-binding site. Insect specific structure-activity effects were observed showing that the insecticidal SAR described herein differs from reported cytotoxicity studies. (C) 2009 Elsevier Ltd. All rights reserved.
• 4-Aza-2,3-dehydro-4-deoxypodophyllotoxins: simple aza-podophyllotoxin analogues possessing potent cytotoxicity
  作者：Yukio Hitotsuyanagi、Masamoto Fukuyo、Kyoko Tsuda、Masatsugu Kobayashi、Akira Ozeki、Hideji Itokawa、Koichi Takeya

  DOI：10.1016/s0960-894x(99)00693-9

  日期：2000.2

  4-Aza-2,3-dehydro-4-deoxypodophyllotoxin analogues 3a-n were synthesized through quinolines 2a-n. Comparison of their cytotoxicity against P-388 leukemia cells revealed that the steric effects of the ring B substituents on the activity are greater than the electronic effects, while the presence of a methoxy group on the ring E is not essential to exhibit potent cytotoxicity. Analogues 3a and 3b proved to be more than twice as cytotoxic as natural podophyllotoxin (1). (C) 2000 Elsevier Science Ltd. All rights reserved.
• US6548515B1
  申请人：——

  公开号：US6548515B1

  公开（公告）日：2003-04-15
• Polyalkoxybenzenes from Plants. 5. Parsley Seed Extract in Synthesis of Azapodophyllotoxins Featuring Strong Tubulin Destabilizing Activity in the Sea Urchin Embryo and Cell Culture Assays
  作者：Marina N. Semenova、Alex S. Kiselyov、Dmitry V. Tsyganov、Leonid D. Konyushkin、Sergei I. Firgang、Roman V. Semenov、Oleg R. Malyshev、Mikhail M. Raihstat、Fabian Fuchs、Anne Stielow、Margareta Lantow、Alex A. Philchenkov、Michael P. Zavelevich、Nikolay S. Zefirov、Sergei A. Kuznetsov、Victor V. Semenov

  DOI：10.1021/jm200737s

  日期：2011.10.27

  targeted molecules were evaluated in vivo in a phenotypic sea urchin embryo assay for antimitotic and tubulin destabilizing activity. The most active compounds identified by the in vivo sea urchin embryo assay featured myristicin-derived ring E (4e, 6e, and 8e). These molecules were determined to be more potent than podophyllotoxin. Cytotoxic effects of selected molecules were further confirmed and evaluated

  使用欧芹种子油中的烯丙基聚烷氧基苯合成了一系列带有修饰的环B和E的4-氮杂鬼臼毒素衍生物。在表型海胆胚胎试验中体内评估了靶向分子的抗有丝分裂和微管蛋白去稳定活性。通过体内海胆胚胎测定法鉴定出的最具活性的化合物的特征是肉豆蔻酸衍生的环E（4e，6e和8e）。确定这些分子比鬼臼毒素更有效。通过使用A549和Jurkat人类白血病T细胞系的常规测定法进一步证实和评估了所选分子的细胞毒性作用，包括细胞生长抑制，细胞周期停滞，细胞微管破坏和凋亡诱导。B环的修饰产生6-OMe取代的分子8e，其为最具活性的化合物。最后，在Jurkat细胞中，化合物8e诱导了由顶端caspases-2和-9而不是caspase-8介导的caspase依赖性凋亡，这暗示了caspase-9依赖性内在凋亡途径的参与。