(E)-isopropyl 3-(3,4-dihydroxyphenyl)acrylate

• 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)-isopropyl 3-(3,4-dihydroxyphenyl)acrylate
• 英文别名: isopropyl caffeate；propan-2-yl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
• 化学式: C₁₂H₁₄O₄
• 分子量: 222.241
• InChiKey: HUBVPNVELDTWJF-GQCTYLIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-isopropyl 3-(3,4-dihydroxyphenyl)acrylate 在 silver(l) oxide 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 28.0h， 以6%的产率得到(±)-isopropyl trans-(E)-2-(3,4-dihydroxyphenyl)-7-hydroxy-5-(3-isopropoxy-3-oxo-prop-1-en-1-yl)-2,3-dihydrobenzofuran-3-carboxylate
  参考文献：
  名称：

  （±）-反式-2-苯基-2,3-二氢苯并呋喃类杀菌剂：合成，体外评估和SAR分析。

  摘要：

  利什曼病是由利什曼原虫属的寄生虫引起的一种被忽视的热带病，在世界范围内造成了严重的疾病负担，对数百万人的生命构成了威胁，因此是主要的公共卫生问题。需要更有效且无毒的新疗法，特别是对于内脏利什曼病（一种最严重的疾病）。在二氢苯并呋喃以前具有抗霉菌活性的背景下，我们在此介绍一组70种反式-2-苯基-2,3-二氢苯并呋喃的合成及其对利什曼原虫donovani的体外活性的评估，并讨论结构-活动关系。化合物8m-o和8r表现出最高的效价（IC 50  <2μmol/ L）和抗真菌活性相对于对哺乳动物细胞的细胞毒性的有趣的选择性（SI> 4.6）。尽管如此，从体外代谢测定中观察到的最有效化合物（8m）的高清除率可以推断出结构优化是进一步的要求。另一方面，手性分离8m并随后对其对映异构体进行生物学评估表明，手性对活性和细胞毒性没有影响。通过简单的评分函数估算药物相似性对计算机模拟ADME的性质和配体效率

  DOI：

  10.1016/j.ejmech.2020.112493
• 作为产物：
  描述：

  TRANS-咖啡酸 在 碘 、 zinc trifluoromethanesulfonate 作用下， 以 乙腈 为溶剂， 反应 8.17h， 生成 (E)-isopropyl 3-(3,4-dihydroxyphenyl)acrylate
  参考文献：
  名称：

  Zn(OTf)₂-Promoted Chemoselective Esterification of Hydroxyl Group Bearing Carboxylic Acids

  摘要：

  Selective esterification of aliphatic and aromatic carboxylic acids with various alcohols is studied using triphenylphosphine, I-2, and a catalytic amount of Zn(OTf)(2). Use of this catalyst allows the formation of esters at a faster rate with good to excellent yield by activating the in situ generated acyloxyphosphonium ion intermediate. During the esterification process, both their aromatic and aliphatic hydroxyl groups are fully preserved from trans-esterification. The results show that the bulkiness and the reactivity of this doubly activated intermediate III control the selectivity and the rate of the reaction, respectively. The method is also useful for direct amidation reactions.

  DOI：

  10.1021/jo302502r

文献信息

• Design and Synthesis of Novel Aspirin-Caffeic Acid Ester Hybrids for Cardioprotection with Reduced Risk of Hemorrhagic Stroke
  作者：Zhi-Hao Shi、Nian-Guang Li、Yu-Ping Tang、Qian-Ping Shi、Wei Zhang、Peng-Xuan Zhang、Ze-Xi Dong、Wei Li、Jin-Ao Duan

  DOI：10.14233/ajchem.2015.17896

  日期：——

  A series of novel aspirin-caffeic acid ester hybrids for cardioprotection with reduced risk of hemorrhagic stroke were designed and synthesized by coupling aspirin and caffeic acid esters inspired by NCX-4016. The synthesized compounds were evaluated for their in vitro antiplatelet aggregations induced by ADP and antioxidant activity of the caffeic acid esters which could be released from the hybrids by esterases in vivo like NCX 4016 were determined by DPPH assay. The results showed that compound 3d exhibited potent antiplatelet activity than aspirin and its intermediate caffeic acid isopropyl ester (2d) showed good antioxidant activity and thus could be considered to be novel potent cardioprotectic drug candidates with reduced risk of hemorrhagic stroke.

  一系列新型阿司匹林-咖啡酸酯杂合体被设计并合成为降低出血性卒中风险的护心药物，灵感来自NCX-4016。通过ADP诱导的体外抗血小板聚集和DPPH试验测定了所合成化合物中能够被酯酶如NCX 4016在体内释放的咖啡酸酯的抗氧化活性。结果显示，化合物3d展现出了比阿司匹林及其中间体咖啡酸异丙酯（2d）更强的抗血小板活性，而且表现出良好的抗氧化活性，因而可被认为是降低出血性卒中风险的新型高效护心药物候选者。
• Design, Synthesis, and Preliminary Evaluation of Substituted Cinnamic Acid Esters as Selective Matrix Metalloproteinase Inhibitors
  作者：Zhi-Hao Shi、Nian-Guang Li、Qian-Ping Shi、Hao-Tang、Yu-Ping Tang

  DOI：10.1002/ddr.21015

  日期：2012.9

  Strategy, Management and Health Policy Preclinical Research

  战略，管理与卫生政策 临床前研究
• Mechanism of toxicity of esters of Caffeic and dihydrocaffeic acids
  作者：Beth Etzenhouser、Corwin Hansch、Sanjay Kapur、C.Dias Selassie

  DOI：10.1016/s0968-0896(00)00238-8

  日期：2001.1

  Ten esters each of caffeic acid and dihydrocaffeic acid have recently been synthesized. Cytotoxicity evaluations of these esters versus L1210 leukemia and MCF-7 breast cancer cells in culture have led to the delineation of substantially different QSAR for each series. The L1210 QSAR for dihydrocaffeic acid esters resembles the QSAR obtained for simple phenols and estrogenic phenols. However, the QSAR

  最近已合成了咖啡酸和二氢咖啡酸的十种酯。这些酯对培养中的L1210白血病和MCF-7乳腺癌细胞的细胞毒性评估已导致每个系列的QSAR均存在明显差异。二氢咖啡因酸酯的L1210 QSAR与简单酚和雌激素酚获得的QSAR相似。但是，与咖啡酸酯有关的QSAR与它的姊妹QSAR有很大不同。该差异可以归因于侧链中烯烃键的存在。咖啡酸的辛酯对白血病细胞的毒性是广泛研究的苯乙酯CAPE的十倍。
• Process for Producing an Aromatic Unsaturated Compound
  申请人：Wang Weiqi

  公开号：US20080221337A1

  公开（公告）日：2008-09-11

  The present invention provides a process for producing an aromatic unsaturated compound of the formula (4) wherein Ar represents an optionally substituted aromatic group or an optionally substituted heteroaromatic group, and Y represents an electron withdrawing group, which comprises reacting (a) a compound of the formula (1) Ar—H  (1) wherein Ar has the same meaning as defined above with (b) a compound of the formula (2) wherein Y has the same meaning as defined above, and Z represents a lower alkoxy, or a compound of the formula (3) wherein Y and Z have the same meanings as defined above, in the presence of (c) an acid or a compound which generates a mineral acid by its hydrolysis.

  本发明提供了一种制备公式（4）的芳香不饱和化合物的方法，其中Ar代表可选择取代的芳香基团或可选择取代的杂环芳香基团，Y代表电子提取基团，包括以下步骤：(a)将公式（1）的化合物Ar-H（1）与(b)公式（2）的化合物反应，其中Y具有与上述定义相同的含义，Z代表低级烷氧基，或公式（3）的化合物，其中Y和Z具有与上述定义相同的含义，在(c)酸或通过其水解生成矿酸的化合物的存在下。
• ANTICANCER USE OF CAFFEIC ACID AND ITS DERIVATIVES
  申请人：Joshi Kalpana Sanjay

  公开号：US20100010002A1

  公开（公告）日：2010-01-14

  The present invention relates to the use of caffeic acid or a derivative thereof represented by the following general formula (1) wherein X is O, NH, or heterocyclyl; R may be present or absent and if present, is H, alkyl, aryl, or heterocyclyl; in all its stereoisomeric and tautomeric forms, and mixtures thereof in all ratios, and a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, pharmaceutically acceptable polymorph or a prodrug, in the treatment of chronic myeloid leukemia (CML) which is resistant to treatment with GLEEVEC. The invention also relates to a method for reducing the proliferation of cells that are resistant to GLEEVEC by contacting the cells with a compound of general formula (1). The present invention also relates to pharmaceutical compositions (for the manufacture of the medicament) including caffeic acid or a derivative or a salt thereof represented by the general formula (1) for the treatment of chronic myeloid leukemia (CML) that is resistant to treatment with GLEEVEC, or for reducing the proliferation of cells that are resistant to GLEEVEC. The present invention further relates to a method of treatment of chronic myeloid leukemia (CML) that is resistant to treatment with GLEEVEC.

  本发明涉及使用咖啡酸或其衍生物在治疗对GLEEVEC治疗具有抗药性的慢性髓细胞白血病（CML）方面的应用，该衍生物由以下通式（1）表示： 其中X为O、NH或杂环基；R可以存在或不存在，如果存在，则为H、烷基、芳基或杂环基；在其立体异构体和互变异构体形式中，以及在所有比例的混合物中，以及药学上可接受的盐、药学上可接受的溶剂化合物、药学上可接受的多晶形或前药。本发明还涉及通过接触一般式（1）的化合物来减少对GLEEVEC具有抗药性的细胞的增殖的方法。本发明还涉及包括咖啡酸或一般式（1）所表示的其衍生物或其盐的制药组合物（用于制造药物），用于治疗对GLEEVEC治疗具有抗药性的慢性髓细胞白血病（CML）或减少对GLEEVEC具有抗药性的细胞的增殖。本发明还涉及治疗对GLEEVEC治疗具有抗药性的慢性髓细胞白血病（CML）的方法。