2-chloro-3,4,5-trimethoxybenzaldehyde

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-chloro-3,4,5-trimethoxybenzaldehyde
• 化学式: C₁₀H₁₁ClO₄
• 分子量: 230.648
• InChiKey: MRGLRSZJHGAWQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-3,4,5-trimethoxybenzaldehyde 在 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 5.0h， 生成 1-(2-chloro-3,4,5-trimethoxyphenyl)prop-2-yn-1-one
  参考文献：
  名称：

  (Z)-1-Aryl-3-arylamino-2-propen-1-ones, Highly Active Stimulators of Tubulin Polymerization: Synthesis, Structure–Activity Relationship (SAR), Tubulin Polymerization, and Cell Growth Inhibition Studies

  摘要：

  Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. A series of (Z)-1-aryl-3-arylamino-2-propen-1-one (10) were synthesized and evaluated for antiproliferative activity in cell-based assay. The most active compound (Z)-1-(2-bromo-3,4,5-trimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenylamino)prop-2-en-1-one (10ae) was tested in 20 tumor cell lines including multidrug resistant phenotype and was found to induce apoptosis in all these cell lines with similar GI(50) values. Flow cytometry studies showed that 10ae arrested the cells in G2/M phase of cell cycle. In addition to G2/M block, these compounds caused microtubule stabilization like paclitaxel and induced apoptosis via activation of the caspase family. The observations made in this investigation demonstrate that (Z)-1-Aryl-3-arylamino-2-propen-1-one (10) represents a new class of microtubule-stabilizing agents.

  DOI：

  10.1021/jm300176j
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲醛 在 磺酰氯 作用下， 以 二氯甲烷 为溶剂， 以96 %的产率得到2-chloro-3,4,5-trimethoxybenzaldehyde
  参考文献：
  名称：

  通过手性 2,2'-联吡啶配体实现的邻氯代芳基醛的对映选择性 Ullmann 偶联合成轴向手性联芳基化合物

  摘要：

  报道了由 SBpy 型手性 2,2'-联吡啶配体实现的一般且高度对映选择性的 Ni 催化的邻氯代醛的还原自偶联。这种温和且步骤经济的方法允许合成各种轴向手性联芳基表盘，并为各种轴向手性催化剂、配体和天然产物提供多功能中间体。

  DOI：

  10.1002/anie.202212108

文献信息

• Synthesis of Flavokawain Analogues and their Anti-neoplastic Effects on Drug-resistant Cancer Cells Through Hsp90 Inhibition
  作者：Young Ho Seo、Sun You Park

  DOI：10.5012/bkcs.2014.35.4.1154

  日期：2014.4.20

  Hsp90 is an ubiquitous molecular chaperone protein, which plays an important role in regulating maturation and stabilization of many oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 represents great promise as a therapeutic target of cancer. In this study, we synthesized flavokawain analogues and evaluated their biological activities against drug-resistant cancer cells. The study indicated that compound 1i impaired the growth of gefitinib-resistant non-small cell lung cancer (H1975), down-regulated the expression of Hsp90 client proteins including EGFR, Her2, Met, Akt and Cdk4, and upregulated the expression of Hsp70. The result strongly suggested that compound 1i inhibited the proliferation of cancer cells through Hsp90 inhibition. Overall, compound 1i could serve as a potential lead compound to overcome the drug resistance in cancer chemotherapy.

  Hsp90是一种普遍存在的分子伴侣蛋白，在调节多种致癌蛋白的成熟和稳定中起着重要作用。由于其同时禁用多个信号通路的潜力，Hsp90作为癌症的治疗靶点具有巨大前景。在本研究中，我们合成了黄卡瓦醇类似物，并评估了它们对耐药癌细胞的生物活性。研究表明，化合物1i损害了吉非替尼耐药的非小细胞肺癌（H1975）的生长，下调了包括EGFR、Her2、Met、Akt和Cdk4在内的Hsp90客户蛋白的表达，并上调了Hsp70的表达。结果强烈表明，化合物1i通过抑制Hsp90抑制了癌细胞的增殖。总的来说，化合物1i有可能作为一种潜在的先导化合物，克服癌症化疗中的药物耐药性。
• [EN] 2,4,6-TRIALKOXYSTRYL ARYL SULFONES, SULFONAMIDES AND CARBOXAMIDES, AND METHODS OF PREPARATION AND USE<br/>[FR] 2,4,6-TRIALCOXYSTYRYLARYLSULFONES, SULFONAMIDES ET CARBOXAMIDES, ET PROCÉDÉS DE PRÉPARATION ET D'UTILISATION
  申请人：TEMPLE UNIV - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

  公开号：WO2017023912A1

  公开（公告）日：2017-02-09

  Compounds according to Formula (I) are provided and salts thereof, wherein R1, R2, R3, R4, R5, R6, R13, A, X and Y are as defined herein. Methods for preparing compounds of Formula (I) are also provided, as well as methods of treating cellular proliferative disorders, such as cancer, using compounds of Formula (I).

  根据公式（I）提供化合物及其盐，其中R1、R2、R3、R4、R5、R6、R13、A、X和Y的定义如本文所述。还提供了制备公式（I）化合物的方法，以及利用公式（I）化合物治疗细胞增殖性疾病，如癌症的方法。
• Cobalt-Catalyzed Asymmetric Hydrogenation of 1,1-Diarylethenes
  作者：Jianhui Chen、Chenhui Chen、Chonglei Ji、Zhan Lu

  DOI：10.1021/acs.orglett.6b00453

  日期：2016.4.1

  Highly enantioselective cobalt-catalyzed hydrogenation of 1,1-diarylethenes was developed by using bench-stable chiral oxazoline iminopyridine–cobalt complexes as precatalysts. A unique o-chloride effect was observed to achieve high enantioselectivity. Easy removal as well as further transformations of the chloro group make this protocol a potentially useful alternative to synthesize various chiral

  通过使用稳定的手性恶唑啉亚氨基吡啶-钴络合物作为前催化剂，开发了对映体选择性高的钴催化的1,1-二芳烃的氢化反应。观察到独特的邻氯化物效应实现了高对映选择性。易于除去以及氯基团的进一步转化使该方案成为合成各种手性1,1-二芳基乙烷的潜在有用替代品。此过程可以在室温下1克大气压的氢气中以克为单位成功进行。
• Synthesis of Butein Analogues and their Anti-proliferative Activity Against Gefitinib-resistant Non-small Cell Lung Cancer (NSCLC) through Hsp90 Inhibition
  作者：Young Ho Seo、Ju Hui Jeong

  DOI：10.5012/bkcs.2014.35.5.1294

  日期：2014.5.20

  Non-small cell lung cancer (NSCLC) is the most common type of lung cancer representing 85% of lung cancer patients. Despite several EGFR-targeted drugs have been developed in the treatment of NSCLC, the clinical efficacy of these EGFR-targeted therapies is being challenged by the occurrence of drug resistance. In this regard, Hsp90 represents great promise as a therapeutic target of cancerous diseases due to its role in modulating and stabilizing numerous oncogenic proteins. Accordingly, inhibition of single Hsp90 protein simultaneously disables multiple signaling networks so as to overcome drug resistance in cancer. In this study, we synthesized a series of 11 butein analogues and evaluated their biological activities against gefitinibresistant NSCLC cells (H1975). Our study indicated that analogue 1h inhibited the proliferation of H1975 cells, down-regulated the expression of Hsp90 client proteins, including EGFR, Met, Her2, Akt and Cdk4, and upregulated the expression of Hsp70. The result suggested that compound 1h disrupted Hsp90 chaperoning function and could serve a potential lead compound to overcome the drug resistance in cancer chemotherapy.

  非小细胞肺癌（NSCLC）是最常见的肺癌类型，占肺癌患者的85%。尽管针对NSCLC开发了几种EGFR靶向药物，但这些EGFR靶向治疗的临床疗效正受到药物耐药性的挑战。在此背景下，由于Hsp90在调节和稳定多种致癌蛋白中的作用，它作为癌症疾病的潜在治疗靶点展现了巨大希望。相应地，通过抑制单个Hsp90蛋白，可以同时阻断多个信号网络，从而克服癌症中的药物耐药性。在本研究中，我们合成了一系列11个白杨素类似物，并评估了它们对吉非替尼耐药的NSCLC细胞（H1975）的生物活性。我们的研究表明，类似物1h抑制了H1975细胞的增殖，下调了Hsp90客户端蛋白的表达，包括EGFR、Met、Her2、Akt和Cdk4，并上调了Hsp70的表达。这些结果表明，化合物1h破坏了Hsp90的伴侣功能，并可能作为一种潜在的先导化合物，用于克服癌症化疗中的药物耐药性。
• Design, synthesis, and biological evaluation of a series of resorcinol-based N-benzyl benzamide derivatives as potent Hsp90 inhibitors
  作者：Sun You Park、Yong Jin Oh、Yunmee Lho、Ju Hui Jeong、Kwang-Hyeon Liu、Jaeyoung Song、Soong-Hyun Kim、Eunyoung Ha、Young Ho Seo

  DOI：10.1016/j.ejmech.2017.11.054

  日期：2018.1

  Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. Therefore, Hsp90 has emerged as an attractive target in the field of cancer chemotherapy. In this study, we report the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors. In particular, compound 30f shows a significant Hsp90α

  热激蛋白90（Hsp90）是一种普遍存在的分子伴侣，负责许多致癌蛋白的稳定和成熟。因此，Hsp90已成为癌症化学疗法领域中有吸引力的靶标。在这项研究中，我们报告了一系列Hsp90抑制剂的设计，合成和生物学评估。特别是，化合物30F示出了显著的Hsp90 α与IC抑制活性50 5.3纳米的值和优异的生长抑制，GI 50值0.42μM的对非小细胞肺癌细胞，H1975。化合物30f有效降低了Hsp90客户蛋白（包括Her2，EGFR，Met，Akt和c-Raf）的表达水平。因此，复合30f促进了PARP，Caspase 3和Caspase 8的大量切割，表明30f通过凋亡途径诱导癌细胞死亡。此外，细胞色素P450分析表明化合物30f对五种主要P450亚型的活性具有弱抑制作用（ 对于1A2、2C9、2C19、2D6和3A，IC 50 > 5μM），表明30f与底物药物之间存在临床相互作用五种主要的