4-formyl-2-methoxyphenyl chloroethanoate | 305-00-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 4-formyl-2-methoxyphenyl chloroethanoate
• 英文别名: 4-formyl-2-methoxyphenyl chloroacetate；vanillin chloroacetyl chloride；Chloracetylvanillin；Acetic acid, 2-chloro-, 4-formyl-2-methoxyphenyl ester；(4-formyl-2-methoxyphenyl) 2-chloroacetate
• CAS: 305-00-0
• 化学式: C₁₀H₉ClO₄
• 分子量: 228.632
• InChiKey: YIWJDTGZFZJZPI-UHFFFAOYSA-N

物化性质

• 沸点：
  121 °C(Press: 0.19 Torr)
• 密度：
  1.313±0.06 g/cm3(Predicted)
• 熔点：
  82-84 °C(Solv: ligroine (8032-32-4); ethyl acetate (141-78-6))

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-formyl-2-methoxyphenyl chloroethanoate 在 三乙胺 、 氧化硼 作用下， 以 乙醇 为溶剂， 反应 13.0h， 生成
  参考文献：
  名称：

  Synthesis of curcumin and ethylcurcumin bioconjugates as potential antitumor agents

  摘要：

  Some new curcumin and ethylcurcumin bioconjugates with various functionalities supported on the curcumin skeleton were synthesized and evaluated for antitumor activity. Most of the newly synthesized compounds are more active than curcumin and ethyl curcumin but are less cytotoxic than the reference compound doxorubicin. Surprisingly, many of these compounds are not cytotoxic to noncancer cells. Compounds 5c, 5e, 5g, 5j, 6b, and 6g having 5-methylthiadiazole, 6-methoxy-benzothiazole, diethylaminoethyl and the usual alkylating bis(2-chloroethyl)amino moieties showed the highest cytotoxic activity against SK-MEL cancer cells. Compounds 5k, 6c, and 6g are less cytotoxic to KB cancer cells. Moreover, compounds 5c, 5e, 5j, 5k, 6d, 6e, 6f, and 6g showed cytotoxicity against BT-549 cancer cells with 5j being the most active compound. Curcumin and the new intermediate di-O-chloroacetylcurcumin (3a) were also cytotoxic against the same cell line but are less active than the target compounds. Compound 6b is the only one exhibiting cytotoxicity against SK-OV-3 cancer cells.

  DOI：

  10.1007/s00044-011-9587-3
• 作为产物：
  描述：

  香草醛 、 氯乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 4-formyl-2-methoxyphenyl chloroethanoate
  参考文献：
  名称：

  取代的苯基[（5-苄基-1,3,4-恶二唑-2-基）硫烷基]乙酸酯/乙酰胺为碱性磷酸酶抑制剂：合成，计算研究，酶抑制动力学和DNA结合研究。

  摘要：

  合成了取代的苯基[（5-苄基-1,3,4-恶二唑-2-基）硫烷基]乙酸酯/乙酰胺9a-j，作为碱性磷酸酶抑制剂。通过一系列反应将苯乙酸1转化为5-苄基-1,3,4-恶二唑-2-硫酮4。然后使中间体恶二唑4与苯酚6a-f的氯乙酰基衍生物和苯胺衍生物8a-d反应得到标题的恶二唑衍生物9a-j。评价所有标题化合物9a-j对人碱性磷酸酶（ALP）的抑制活性。发现化合物9a-j表现出良好至优异的碱性磷酸酶抑制活性，尤其是9h显示出有效活性，IC50值为0.420±0.012μM，而标准品（KH2PO4）的IC50值为2.80μM。最有效的抑制剂9h的酶抑制动力学是通过Line-weaever Burk图确定的，该图显示了与酶结合的非竞争性模式。针对碱性磷酸酶（1EW2）进行了分子对接研究，以检查合成的化合物9a-j对靶蛋白的结合亲和力。与其他衍生物相比，化合物9h表现出优异的结合亲和力，具有结合能值（-7

  DOI：

  10.1016/j.bioorg.2019.103108

文献信息

• Preparative Synthesis of Vanillin and Vanillal Alkanoates
  作者：E. A. Dikusar、O. G. Vyglazov、K. L. Moiseichuk、N. A. Zhukovskaya、N. G. Kozlov

  DOI：10.1007/s11167-005-0242-y

  日期：2005.1

  Procedures for preparing vanillin and vanillal alkanoates were developed.

  制备香草醛及其烷酸酯的工艺流程被开发出来。
• Synthesis and Evaluation of Prodrugs of Ketoprofen with Antioxidants as Gastroprotective NSAIDs
  作者：Shikha Sehajpal、Deo Nandan Prasad、Rajesh K. Singh

  DOI：10.14233/ajchem.2018.21495

  日期：——

  Ketoprofen-antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal effects associated with ketoprofen. For reducing the gastrointestinal toxicity, the free carboxylic group (–COOH) was temporarily masked by esterification with alcoholic/phenolic –OH of natural antioxidants thymol, guaiacol, menthol and vanillin. In order to obtain the derivatives with improved in vivo lability, the double ester prodrugs i.e. ketoprofen-antioxidant through the glycolic acid spacer (-CH2COO-) have been synthesized. These mutual prodrugs were evaluated for their anti-inflammatory, analgesic and antiulcer properties. The results indicate that there is merit to extend the therapeutic utility of this potential NSAID by developing the ketoprofen-antioxidant mutual prodrugs as gastroprotective NSAIDs.

  齐多普芬-抗氧化剂互作前药被合成以减少与齐多普芬相关的胃肠道效应。为降低胃肠道毒性，自由羧基（-COOH）被暂时通过酯化与天然抗氧化剂百里香酚、愈创木酚、薄荷醇和香草醛的醇/酚-OH所掩盖。为了获得体内不稳定性改善的衍生物，双酯前药，即通过甘醇酸间隔基（-CH2COO-）的齐多普芬-抗氧化剂，已被合成。这些互作前药在抗炎、镇痛和抗溃疡特性方面进行了评估。结果表明，通过开发作为胃保护性非甾体抗炎药的齐多普芬-抗氧化剂互作前药，扩展这种潜在非甾体抗炎药的治疗用途是有价值的。
• Novel ketoprofen–antioxidants mutual codrugs as safer nonsteroidal anti‐inflammatory drugs: Synthesis, kinetic and pharmacological evaluation
  作者：Shikha Sehajpal、Deo Nandan Prasad、Rajesh K. Singh

  DOI：10.1002/ardp.201800339

  日期：2019.7

  the double ester codrugs, that is, ketoprofen–antioxidant through the glycolic acid spacer (–CH2COO; IIIa–h), have also been designed and synthesized. The synthesized codrugs were characterized by IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analysis. The in vitro hydrolysis studies showed the lowest hydrolysis (highest stability) in acidic pH 1.2, whereas moderate hydrolysis was seen at pH

  酮洛芬属于最常见的非甾体抗炎药（NSAIDs）之一，但由于胃肠道并发症的发生率高，其临床应用受到限制。NSAIDs 治疗中活性氧 (ROS) 的释放在引起胃部并发症中起主要作用。抗氧化剂不仅可以防止胃溃疡和脂质过氧化，还可以保持谷胱甘肽型过氧化物酶 (GPO) 的活性。因此，本研究调查了在单个分子中结合两种不同化合物的抗炎和抗氧化特性以形成一系列 16 种酮洛芬-抗氧化互药的效用。游离羧基，被认为是酮洛芬胃毒性的原因之一，通过与天然抗氧化剂的醇/酚-OH 的简单和双酯化作用暂时掩盖。在简单的酯化中，酮洛芬与天然抗氧化剂（IIa-h）直接相连，希望获得无胃毒副作用的药物。为了改善体内不稳定性以及胃部副作用，还设计并合成了双酯协同药物，即酮洛芬-通过乙醇酸间隔物（–CH2COO；IIIa–h）的抗氧化剂。合成的共药通过IR、1H NMR、13C NMR、质谱和元素分析表征。体外水解研究表明，在酸性
• Synthesis, kinetic mechanism and docking studies of vanillin derivatives as inhibitors of mushroom tyrosinase
  作者：Zaman Ashraf、Muhammad Rafiq、Sung-Yum Seo、Mustafeez Mujtaba Babar、Najam-us-Sahar Sadaf Zaidi

  DOI：10.1016/j.bmc.2015.06.068

  日期：2015.9

  their mushroom tyrosinase inhibitory activity was explored. The kinetics of inhibition on mushroom tyrosinase by these esters was also investigated. It was found that hydroxyl substituted benzoic acid derivatives were weak inhibitors; however hydroxy or chloro substituted cinnamic acid and piperazine substituted derivatives were able to induce significant tyrosinase inhibition. The mushroom tyrosinase

  本研究的目的是通过向香兰素中添加羟基取代的苯甲酸，肉桂酸和哌嗪残基来发现对抗酪氨酸酶活性的贡献程度。研究表明，香兰素已转化为酯，如（4a - 4d），（6a - 6b）和（8a - 8b）所示。）。此外，探讨了这些酯的结构与其蘑菇酪氨酸酶抑制活性之间的关系。还研究了这些酯对蘑菇酪氨酸酶的抑制动力学。发现羟基取代的苯甲酸衍生物是弱抑制剂。然而，羟基或氯取代的肉桂酸和哌嗪取代的衍生物能够诱导显着的酪氨酸酶抑制作用。蘑菇酪氨酸酶（PDBID 2ZWE）与合成的香兰素衍生物对接，并将其计算的结合能与提供正相关性的实验IC 50值进行比较。最有效的衍生物2-（4-甲酰基-2-甲氧基苯氧基）-2-氧乙基（2 E）-3-（4-羟苯基）丙-2-烯酸酯（6a）具有IC 50值为16.13μM，结合能为-7.2 kcal / mol的羟基取代的肉桂酸支架。（6a）的酪氨酸酶抑制活性与标准曲酸相当。动力学分析表明，化合物6a是抑制常数为K
• Novel thiosemicarbazone and thiazolidin‐4‐one derivatives containing vanillin core: Synthesis, characterization, and anticancer activity studies
  作者：Feyzi Sinan Tokalı、Halil Şenol、Tuğba Gençoğlu Katmerlikaya、Aydan Dağ、Kıvılcım Şendil

  DOI：10.1002/jhet.4619

  日期：——

  most common and lethal disease in the world, therefore, patients need new and potent anticancer agents for treatment. In this study, starting from vanillin, 24 new compounds, which are 12 thiosemicarbazone (4a-h, 5i-j, 6k) and 12 thiazolidin-4-one (7a-h, 8i-j and 9k) derivatives, were synthesized and characterized by Nuclear Magnetic Resonance (NMR), High-Resolution Mass Spectroscopy (HRMS), and Fourier-transform

  癌症是世界上最常见和最致命的疾病之一，因此，患者需要新的强效抗癌药物进行治疗。本研究以香草醛为原料，合成了24个新化合物，即12个缩氨基硫脲(4a-h, 5i-j, 6k)和12个噻唑烷-4-酮( 7a-h, 8i-j和9k)衍生物，并以核磁共振 (NMR)、高分辨率质谱 (HRMS) 和傅立叶变换红外 (FTIR) 技术为特征。研究了 CCD-1079Sk 人类健康成纤维细胞和 MDA-MB-231 人类乳腺癌细胞系的体外细胞毒性作用。对于 MDA-MB-231，分子显示 IC 50范围为 88.08 ± 0.027–16.54 ± 0.031 μM（多柔比星：61.70 ± 0.021 μM），对于 CCD-1079Sk，分子显示 IC 50范围为 192.36 ± 0.018–13.58 ± 0.035 μM（多柔比星：52.01 ± 0.028 μM）。与用作标准药物的多柔比星相比