1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)ethanone | 1393921-62-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)ethanone
• 英文别名: 1-(5-methoxy-2,2-dimethylchromen-8-yl)ethanone
• CAS: 1393921-62-4
• 化学式: C₁₄H₁₆O₃
• 分子量: 232.279
• InChiKey: JDGBKMXPPYUNKE-UHFFFAOYSA-N

物化性质

• 沸点：
  368.2±42.0 °C(Predicted)
• 密度：
  1.082±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2914509090

反应信息

• 作为反应物：
  描述：

  1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)ethanone 在 盐酸 、 sodium hydride 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 15.0h， 生成 (E)-1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)-3-(4-methoxy-3-(2-morpholinoethoxy)phenyl)prop-2-en-1-one
  参考文献：
  名称：

  Synthesis and biological evaluation of novel pyranochalcone derivatives as a new class of microtubule stabilizing agents

  摘要：

  Twenty-five novel pyranochalcone derivatives were synthesized and evaluated for their in vitro and in vivo antiproliferative activities. Among them, compound 10i exhibited superior potent activity against 21 tumor cell lines including multidrug resistant phenotype with the IC50 values ranged from 0.09 to 1.30 mu M. In addition, 10i significantly induced cell cycle arrest in G2/M phase, promoted tubulin polymerization into microtubules and caused microtubule stabilization. Further studies confirmed that 10i significantly suppressed the growth of tumor volume in HepG2 xenograft tumor model. Our study demonstrated that 10i could have beneficial antitumor activity as a novel microtubule stabilizing agent. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.007
• 作为产物：
  描述：

  丹皮酚 在 吡啶 、 copper(II) choride dihydrate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 17.0h， 生成 1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)ethanone
  参考文献：
  名称：

  基于米帕钦的双微管蛋白/HDAC抑制剂治疗前列腺癌的设计和生物学评价

  摘要：

  本工作基于天然产物米勒帕钦的结构，设计并合成了一种新型微管蛋白/HDAC双抑制剂，该抑制剂已被鉴定为微管蛋白聚合抑制剂。生物学评估表明，该化合物对 PC-3 细胞表现出令人印象深刻的效力，IC 值为 16 nM，并有效抑制微管聚合和 HDAC 活性。此外，化合物不仅诱导细胞周期阻滞在G2/M期，而且诱导PC-3细胞凋亡。进一步的研究表明，PC-3细胞中PC-3细胞凋亡的诱导伴随着线粒体膜电位的降低和活性氧水平的升高。此外，对肿瘤细胞迁移和血管生成具有抑制作用。在PC-3异种移植模型中，取得了显着的抑瘤率90.07%@20 mg/kg，显着超越CA-4（55.62%@20 mg/kg）。同时，表现出良好的体内药物代谢特性。所有结果表明，它是一种很有前途的前列腺癌化疗双微管蛋白/HDAC抑制剂，值得进一步研究。

  DOI：

  10.1016/j.ejmech.2024.116301

文献信息

• Synthesis and biological evaluation of novel chalcone derivatives as a new class of microtubule destabilizing agents
  作者：Xiaochao Huang、Rizhen Huang、Lingxue Li、Shaohua Gou、Hengshan Wang

  DOI：10.1016/j.ejmech.2017.03.031

  日期：2017.5

  A series of novel chalcone derivatives were designed and synthesized as potential antitumor agents. Structures of target molecules were confirmed by 1H NMR, 13C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. Among them, compound 12k displayed potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC50

  设计并合成了一系列新颖的查耳酮衍生物作为潜在的抗肿瘤剂。通过1 H NMR，13 C NMR和HR-MS确认目标分子的结构，并使用MTT分析评估其体外抗增殖活性。其中，化合物12k对测试肿瘤细胞系（包括多药耐药性人类癌症系）表现出强效活性，IC50值为3.75至8.42μM。此外，发现化合物12k通过线粒体途径诱导NCI-H460细胞凋亡，包括ROS水平升高，线粒体膜电位丧失，细胞色素c释放，Bcl-2下调，上调Bax的激活，分别激活caspase-9和caspase-3。此外，细胞周期分析表明12k有效地导致细胞周期停滞在G2 / M期。微管蛋白聚合测定的结果表明，12k可以抑制微管蛋白的体外聚合。此外，分子对接研究表明12k可以与微管蛋白的秋水仙碱位点结合。
• (E)-1-(5-METHOXY-2,2-DIMETHYL-2H-CHROMEN-8-YL)-3-(4-METHOXYPHENYL)PROP-2-EN-1-ONE AND ANALOGS THEREOF, AS WELL AS PREPARATION METHOD AND USE THEREOF
  申请人：Chen Lijuan

  公开号：US20150133659A1

  公开（公告）日：2015-05-14

  The present invention relates to millepachine ((E)-1-(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)-3-(4-methoxyphenyl)prop-2-en-1-one) and its analogues. The present invention provides methods for preparing these compounds, pharmaceutical compositions including these compounds, and methods of treating diseases utilizing pharmaceutical compositions including these compounds.

  本发明涉及米勒帕辛（（E）-1-(5-甲氧基-2,2-二甲基-2H-香豆素-8-基)-3-(4-甲氧基苯基)丙-2-烯-1-酮）及其类似物。本发明提供了制备这些化合物的方法，包括这些化合物的药物组合物，以及利用包括这些化合物的药物组合物治疗疾病的方法。
• Natural Products‐Based Fungicides: Synthesis and Antifungal Activity against Plant Pathogens of 2 <i>H</i> ‐Chromene Derivatives
  作者：Wenjing Liu、Yong Li、Judi Fan、Lei Tang、Bing Guo、Wei Xue、Lingling Fan

  DOI：10.1002/cbdv.202200802

  日期：2022.11

  synthesized and their antifungal activity against some typical plant pathogenic fungi were firstly evaluated. The in vitro antifungal bioassays showed that some of the target compounds exhibited comparable or better inhibition activities than the commercial agricultural fungicide hymexazol. Especially compound 1m displayed more promising fungicidal effect against Alternaria alternate (EC50=9.9 μg/mL) and

  为了寻找新的潜在抗真菌药物，设计、合成了40种 2 H-色烯类似物，并首次评价了它们对一些典型植物病原真菌的抗真菌活性。体外抗真菌生物测定表明，一些目标化合物表现出与商业农业杀真菌剂羟霉唑相当或更好的抑制活性。特别是化合物1m对Alternaria alternate (EC 50 =9.9 μg/mL)和Botrytis cinerea (EC 50 =9.4 μg/mL)表现出更好的杀菌效果，显着优于恶霉灵。此外，体内保护作用结果也表明，化合物1m具有作为新型植物源农药进一步开发的极好潜力。
• Design, synthesis and biological evaluation of a series of pyrano chalcone derivatives containing indole moiety as novel anti-tubulin agents
  作者：Guangcheng Wang、Chunyan Li、Lin He、Kai Lei、Fang Wang、Yuzi Pu、Zhuang Yang、Dong Cao、Liang Ma、Jinying Chen、Yun Sang、Xiaolin Liang、Mingli Xiang、Aihua Peng、Yuquan Wei、Lijuan Chen

  DOI：10.1016/j.bmc.2014.02.028

  日期：2014.4

  A new series of pyrano chalcone derivatives containing indole moiety (3-42, 49a-49r) were synthesized and evaluated for their antiproliferative activities. Among all the compounds, compound 49b with a propionyloxy group at the 4-position of the left phenyl ring and N-methyl-5-indoly on the right ring displayed the most potent cytotoxic activity against all tested cancer cell lines including multidrug resistant phenotype, which inhibits cancer cell growth with IC50 values ranging from 0.22 to 1.80 mu M. Furthermore, 49b significantly induced cell cycle arrest in G2/M phase and inhibited the polymerization of tubulin. Molecular docking analysis demonstrated the interaction of 49b at the colchicine binding site of tubulin. In experiments in vivo, 49b exerted potent anticancer activity in HepG2 human liver carcinoma in BALB/c nude mice. These results indicated these compounds are promising inhibitors of tubulin polymerization for the potential treatment of cancer. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis, Evaluation, and Mechanism Study of Novel Indole-Chalcone Derivatives Exerting Effective Antitumor Activity Through Microtubule Destabilization in Vitro and in Vivo
  作者：Jun Yan、Jie Chen、Shun Zhang、Jinhui Hu、Ling Huang、Xingshu Li

  DOI：10.1021/acs.jmedchem.6b00021

  日期：2016.6.9

  Twenty-nine novel indole-chalcone derivatives were synthesized and evaluated for antiproliferative activity. Among them, 14k exhibited most potent activity, with IC50 values of 3-9 nM against six cancer cells, which displayed a 3.8-8.7-fold increase in activity when compare with compound 2. Further investigation revealed 14k was a novel tubulin polymerization inhibitor binding to the colchicine site. Its low cytotoxicity toward normal human cells and nearly equally potent activity against drug resistant cells revealed the possibility for cancer therapy. Cellular mechanism studies elucidated 14k arrests cell cycle at G(2)/M phase and induces apoptosis along with the decrease of mitochondrial membrane potential. Furthermore, good metabolic stability of 14k was observed in mouse liver microsomes. Importantly, 14k and its phosphate salt 14k-P inhibited tumor growth in xenograft models in vivo without apparent toxicity, which was better than the reference compound CA-4P and 2. In summary, 14k deserves consideration for cancer therapy.