(E)-3-(2,3-dimethoxyphenyl)prop-2-enoyl chloride | 185253-63-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(2,3-dimethoxyphenyl)prop-2-enoyl chloride
• CAS: 185253-63-8
• 化学式: C₁₁H₁₁ClO₃
• 分子量: 226.66
• InChiKey: VRLJVOPVODJEEG-VOTSOKGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-(2,3-dimethoxyphenyl)prop-2-enoyl chloride 在 sodium carbonate 、 palladium dichloride 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 23.0h， 生成 (E)-methyl 2-acetylamino-5-(6-(2,3-dimethoxystyryl)-2-methylpyrimidin-4-yl)benzoate
  参考文献：
  名称：

  具有邻氨基苯甲酸酯部分的2,4,6-三取代嘧啶的设计，合成，细胞毒性和分子建模研究

  摘要：

  通过使用一锅多组分方法，由5-（乙炔基）邻氨基苯甲酸甲酯，芳酰基或肉桂酰基氯和各种am设计并合成了一系列具有邻氨基苯甲酸酸酯部分的2,4,6-三取代的嘧啶。使用常规MTT测定法评估所有化合物对模型癌细胞系（CEM-13，U-937，MDA-MB-231，BT-474，DU-145）的细胞毒性活性。结构-活性关系分析表明，4,6- diarylpyrimidines 13 - 17，具有吡啶或在2位嘧啶环取代的显示相比，2-甲基或2-苯基取代的嘧啶的活性的增加。2-氨基取代的化合物9对人单核细胞样细胞U-937具有选择性。三取代的嘧啶18 - 21中，含有（E） -苯乙烯基取代基的嘧啶核的6位，表现出活性的针对乳腺癌细胞系MDA-MB-231，BT-474的增加，并且还针对人前列腺细胞系DU-145。化合物18和20显示出对癌细胞系MDA-MB-231的最佳效力；它们的活性与阿霉素在该细胞系

  DOI：

  10.1007/s00044-019-02314-8
• 作为产物：
  描述：

  2,3-二甲氧基肉桂酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 以100%的产率得到(E)-3-(2,3-dimethoxyphenyl)prop-2-enoyl chloride
  参考文献：
  名称：

  一种通过二氮杂苯吡唑-3-酮的简单方法

  摘要：

  描述了从首先被转化成相应的酰肼的丙烯酸开始有效地进入吡唑-3-酮。酰肼的氧化产生了二氮烯，并且在用ZrCl 4处理时将其环化成吡唑-3-酮。在温和的反应条件下，容易除去吡唑啉酮衍生物的N-1的甲氧基羰基保护基。

  DOI：

  10.1016/j.tet.2009.08.047

文献信息

• Design and synthesis novel di-carbonyl analogs of curcumin (DACs) act as potent anti-inflammatory agents against LPS-induced acute lung injury (ALI)
  作者：Jianchang Qian、Xianxin Chen、Sheng Shu、Wenxin Zhang、Bo Fang、Xiaojing Chen、Yunjie Zhao、Zhiguo Liu、Guang Liang

  DOI：10.1016/j.ejmech.2019.02.042

  日期：2019.4

  A novel series of di-carbonyl analogs of curcumin (DACs) were prepared and evaluated for their anti-inflammatory properties. Preliminary results showed that a vast majority of compounds tested in this study could effectively suppress LPS-induced production of tumor necrosis factor (TNF)-α and interleukin (IL)-6. Structure-activity relationships of the compounds were discussed. Compounds 5a27 and 5a28

  制备了一系列新的姜黄素二羰基类似物（DACs），并评估了它们的抗炎特性。初步结果表明，本研究中测试的绝大多数化合物都可以有效抑制LPS诱导的肿瘤坏死因子（TNF）-α和白介素（IL）-6的产生。讨论了化合物的构效关系。化合物5a27和5a28显示出最有效的抗炎活性和具有比姜黄素更高的结构稳定性和生物利用度口服体外。从机制上讲，它们通过抑制有丝分裂原激活的蛋白激酶（MAPK）信号传导和NF-κB的核易位来抑制巨噬细胞的激活。在体内，5a275a28和5a28可以显着减轻脂多糖（LPS）诱导的急性肺损伤（ALI）。活性化合物使肺的干/湿比显着标准化，这与中性粒细胞浸润的抑制和促炎性细胞因子的产生是一致的。总的来说，这些结果提出了一系列新的姜黄素类似物，作为有望用于治疗ALI的抗炎药。
• Dual-tail approach to discovery of novel carbonic anhydrase IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site
  作者：Zhuang Hou、Bin Lin、Yu Bao、Hai-ning Yan、Miao Zhang、Xiao-wei Chang、Xin-xin Zhang、Zi-jie Wang、Gao-fei Wei、Mao-sheng Cheng、Yang Liu、Chun Guo

  DOI：10.1016/j.ejmech.2017.03.023

  日期：2017.5

  novel Carbonic Anhydrase (CA) IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site, which also contains a zinc ion as part of the catalytic center. The classic sulfanilamide moiety was used as the zinc binding group. An amino glucosamine fragment was chosen as the hydrophilic part and a cinnamamide fragment as the hydrophobic part in order to draw favorable

  通过同时匹配活性位的疏水和亲水部分，双尾法设计新颖的碳酸酐酶（CA）IX抑制剂，活性位也包含锌离子作为催化中心的一部分。经典的磺胺基部分被用作锌结合基团。选择氨基葡糖胺片段作为亲水部分，而肉桂酰胺片段作为疏水部分，以便与活性部位的相应一半进行有利的相互作用。与基本上没有与两半活性位点发生亲水和疏水相互作用的磺胺相比，本研究中设计和合成的化合物在结合亲和力方面提高了1000倍。大多数化合物可有效抑制CA，IC50值为7-152 nM。化合物14e（IC50：7 nM）比参考药物乙酰唑酰胺（IC50：30 nM）更有效。结果证明，通过连接疏水性和亲水性片段同时匹配活性位的疏水性和亲水性两部分的双尾法对于设计新型CA抑制剂是有用的。实验数据和分子对接模拟都阐明了这些化合物的有效性。这项工作为进一步开发用于癌症治疗的新型CA IX抑制剂奠定了坚实的基础。结果证明，通过连接疏水性和亲水性片段同时匹配
• Synthesis and leishmanicidal activity of cinnamic acid esters: structure–activity relationship
  作者：Elver Otero、Sara M. Robledo、Santiago Díaz、Miguel Carda、Diana Muñoz、Julian Paños、Ivan D. Vélez、Wilson Cardona

  DOI：10.1007/s00044-013-0741-y

  日期：2014.3

  Several cinnamic acid esters were obtained via Fischer esterification of cinnamic acids derivatives with aliphatic alcohols. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes and cytotoxic activity was evaluated against mammalian U-937 cells. The compounds 11, 15-17, and 23, were active against Leishmania parasite and although toxic for mammalian cells, they still are potential candidates for antileishmanial drug development. A SAR analysis indicates that first, while smaller alkyl chains lead to higher selectivity indices (10, 11 vs. 12-17); second, the degree of oxygenation is essential for activity, primarily in positions 3 and 4 (17 vs. 18-20 and 22); and third, hydroxyl groups increase both activity and cytotoxicity (14 vs. 23). On the other hand, the presence of a double bond in the side chain is crucial for cytotoxicity and leishmanicidal activity (12 vs. 21). However, further studies are required to optimize the structure of the promising molecules and to validate the in vitro activity against Leishmania demonstrated here with in vivo studies.
• Ligustrazine derivatives. Part 3: Design, synthesis and evaluation of novel acylpiperazinyl derivatives as potential cerebrocardiac vascular agents
  作者：Xian-Chao Cheng、Xin-Yong Liu、Wen-Fang Xu、Xiu-Li Guo、Ning Zhang、Yu-Ning Song

  DOI：10.1016/j.bmc.2009.03.012

  日期：2009.4

  A series of novel acylpiperazinyl Ligustrazine derivatives was designed, synthesized, and their protective effects on damaged ECV-304 cells and antiplatelet aggregation activities were evaluated. The results showed that compound E33 displayed most potential protective effects on the ECV-304 cells damaged by hydrogen peroxide, and compound E1 was found to be the most active antiplatelet aggregation agent. Structure-activity relationships were briefly discussed. (C) 2009 Elsevier Ltd. All rights reserved.
• A novel sorbicillinoid compound as a potent anti‐inflammation agent through inducing NLRP3 protein degradation
  作者：Fangfang Wang、Meng Zhang、Meng Yuan、Zixuan Xia、Fengge Yang、Sihao Zhang、Tengyu Lin、Lianxiang Luo、Jinshan Tang、Youwei Zhang

  DOI：10.1111/bph.16058

  日期：——

  Background and PurposeChronic inflammation is pathogenic and contributes to human diseases, causing a significant threat to public health. The NLR family pyrin domain‐containing protein 3 (NLRP3) is the best‐characterized factor regulating inflammation. Therefore, targeting NLRP3 has the potential to treat inflammatory diseases and improve human health.Experimental ApproachLipopolysaccharide was used to induce inflammation in cell cultures. Lipopolysaccharide/d‐galactosamine and dextran sulfate sodium salt were used to induce acute liver inflammation and ulcerative colitis respectively in C57BL/6J mice. Western blotting, immunofluorescence, immunoprecipitation, quantitative PCR and enzyme‐linked immunosorbent assay (ELISA) were used to evaluate the activation of the inflammatory response in cell cultures and in mice.Key ResultsJNUTS013, a novel sorbicillinoid compound recently synthesized by us, significantly inhibited inflammation both in cell cultures and in mouse models. Mechanistically, JNUTS013 induced proteasome‐dependent degradation of NLRP3. Hence, it suppressed the formation of the NLRP3 inflammasome and the production of downstream inflammatory cytokines and chemokines. The inhibitory effect of JNUTS013 on NLRP3 protein expression was confirmed in mice. Importantly, JNUTS013 failed to ameliorate bowel inflammation in Nlrp3‐/‐ knockout mice, supporting NLRP3 as the biological target by which JNUTS013 inhibits inflammation. Further studies revealed critical chemical moieties of JNUTS013 required for inducing NLRP3 degradation.Conclusion and ImplicationsThis study identifies a novel compound JNUTS013 that inhibits inflammation through inducing NLRP3 protein degradation in vitro and in vivo, which not only supports the development of JNUTS013 as an anti‐inflammation agent but also creates a new way for the treatment of inflammation by chemically inducing NLRP3 degradation.