2-chloro-N-(3,4,5-trimethoxybenzyl)acetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-chloro-N-(3,4,5-trimethoxybenzyl)acetamide
• 英文别名: 2-chloro-N-[(3,4,5-trimethoxyphenyl)methyl]acetamide
• 化学式: C₁₂H₁₆ClNO₄
• mdl: MFCD08444153
• 分子量: 273.716
• InChiKey: YZWMCMKHKYSDGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(3,4,5-trimethoxybenzyl)acetamide 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 14.0h， 生成 5-((5-methoxy-1H-indol-3-yl)methylene)-2-((3,4,5-trimethoxybenzyl)imino)thiazolidin-4-one
  参考文献：
  名称：

  Discovery of certain benzyl/phenethyl thiazolidinone-indole hybrids as potential anti-proliferative agents: Synthesis, molecular modeling and tubulin polymerization inhibition study

  摘要：

  A series of certain benzyl/phenethyl thiazolidinone-indole hybrids were synthesized for the study of anti-proliferative activity against A549, NCI-H460 (lung cancer), MDA-MB-231 (breast cancer), HCT-29 and HCT-15 (colon cancer) cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). We found that compound G37 displayed highest cytotoxicity with IC50 value of 0.92 +/- 0.12 mu M towards HCT-15 cancer cell line among all the synthesized compounds. Moreover, compound G37 was also tested on normal human lung epithelial cells (L132) and was found to be safe in contrast to HCT-15 cells. The lead compound G37 showed significant G2/M phase arrest in HCT-15 cells. Additionally, compound G37 significantly inhibited tubulin polymerization with IC50, value of 2.92 +/- 0.23 mu M. Mechanistic studies such as acridine orange/ethidium bromide (AO/EB) dual staining, DAPI nuclear staining, annexinV/propidium iodide dual staining, donogenic growth inhibition assays inferred that compound G37 induced apoptotic cell death in HCT-15 cells. Moreover, loss of mitochondrial membrane potential with elevated intracellular ROS levels was observed by compound G37. These compounds bind at the active pocket of the alpha/beta-tubulin with higher number of stable hydrogen bonds, hydrophobic and arene-cation interactions confirmed by molecular modeling studies.

  DOI：

  10.1016/j.bioorg.2019.103188
• 作为产物：
  描述：

  3,4,5-三甲氧基苄胺 、 氯乙酰氯 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-chloro-N-(3,4,5-trimethoxybenzyl)acetamide
  参考文献：
  名称：

  作为微管蛋白聚合抑制剂的新型色烯基 2-iminothiazolidin-4-one 衍生物：设计、合成、生物学评价和分子建模研究

  摘要：

  摘要 在此，我们介绍了作为微管蛋白聚合抑制剂的新型色烯基 2-iminothiazolidin-4-one 衍生物的分子设计、化学合成和评价。通过 MTT 测定评估新合成的化合物对 A549（肺癌）、MDA-MB-231 和 BT-471（乳腺癌）、HepG2（肝癌）和 HCT-116（结肠癌）细胞系的体外细胞毒性. 在合成的化合物中，化合物12b对MDA-MB-231细胞系显示出优异的抗癌活性，IC50值为0.95±1.88 μM，并在正常人支气管上皮细胞（Beas-2B）中被证实是安全的。使用形态学观察、AO/EB 和 DAPI 染色程序观察由铅 12b 诱导的细胞凋亡。更多，通过 JC-1 染色还观察到线粒体膜去极化的剂量依赖性增加。膜联蛋白 V-FITC/PI 测定证实 12b 诱导早期细胞凋亡。此外，细胞周期分析表明，MDA-MB-231 细胞在亚 G2/M 期停滞，并抑制微管蛋白聚合，IC50

  DOI：

  10.1016/j.molstruc.2020.128847

文献信息

• Synthesis, anti-inflammatory, analgesic and COX-1/2 inhibition activities of anilides based on 5,5-diphenylimidazolidine-2,4-dione scaffold: Molecular docking studies
  作者：Alaa A.-M. Abdel-Aziz、Adel S. El-Azab、Laila A. Abou-Zeid、Kamal Eldin H. ElTahir、Naglaa I. Abdel-Aziz、Rezk R. Ayyad、Abdulrahman M. Al-Obaid

  DOI：10.1016/j.ejmech.2016.03.011

  日期：2016.6

  The design, synthesis and pharmacological activities of a group of 5,5-diphenylimidazolidine-2,4-dione bearing anilide, phenacyl and benzylidene fragments 2-27 were reported. The prepared 5,5-diphenylimidazolidine-2,4-dione derivatives were evaluated in vivo for anti-inflammatory, analgesic activities and in vitro for COX-1/2 inhibition assay. Among the tested compounds, derivatives 5, 9, 10, 13, and

  报道了一组5,5-二苯基咪唑烷-2,4-二酮带有苯胺，苯甲酰基和亚苄基片段2-27的设计，合成和药理活性。体内评估了制备的5,5-二苯基咪唑烷-2,4-二酮衍生物的抗炎，镇痛活性，体外评估了COX-1 / 2抑制作用。在所测试的化合物中，衍生物5、9、10、13和14表现出显着和有效的抗炎和镇痛活性，几乎等同于参考药物塞来昔布。在COX-1 / 2抑制试验中，化合物5、9、10和14表现出较高的COX-2抑制活性（IC50分别为0.70μM，0.44μM，0.61μM和0.41μM），选择性指数（SI）范围为142 -243可比塞来昔布[COX-2（SI）> 333]。这些有效的COX-2抑制剂9、10、13
• Novel chromenyl-based 2-iminothiazolidin-4-one derivatives as tubulin polymerization inhibitors: Design, synthesis, biological evaluation and molecular modelling studies
  作者：Dilep Kumar Sigalapalli、Venkatesh Pooladanda、Manasa Kadagathur、Sravanthi Devi Guggilapu、Jaya Lakshmi Uppu、Chandraiah Godugu、Nagendra Babu Bathini、Neelima D. Tangellamudi

  DOI：10.1016/j.molstruc.2020.128847

  日期：2021.2

  Abstract Here-in, we present molecular design, chemical synthesis and evaluation of novel chromenyl-based 2-iminothiazolidin-4-one derivatives as tubulin polymerization inhibitors. The newly synthesized compounds were evaluated for their in vitro cytotoxicities against A549 (lung cancer), MDA-MB-231 and BT-471 (breast cancer), HepG2 (liver cancer) and HCT-116 (colon cancer) cell lines by MTT assay

  摘要 在此，我们介绍了作为微管蛋白聚合抑制剂的新型色烯基 2-iminothiazolidin-4-one 衍生物的分子设计、化学合成和评价。通过 MTT 测定评估新合成的化合物对 A549（肺癌）、MDA-MB-231 和 BT-471（乳腺癌）、HepG2（肝癌）和 HCT-116（结肠癌）细胞系的体外细胞毒性. 在合成的化合物中，化合物12b对MDA-MB-231细胞系显示出优异的抗癌活性，IC50值为0.95±1.88 μM，并在正常人支气管上皮细胞（Beas-2B）中被证实是安全的。使用形态学观察、AO/EB 和 DAPI 染色程序观察由铅 12b 诱导的细胞凋亡。更多，通过 JC-1 染色还观察到线粒体膜去极化的剂量依赖性增加。膜联蛋白 V-FITC/PI 测定证实 12b 诱导早期细胞凋亡。此外，细胞周期分析表明，MDA-MB-231 细胞在亚 G2/M 期停滞，并抑制微管蛋白聚合，IC50
• Synthesis, <i>in vitro</i> antitumour activity, and molecular docking study of novel 2-substituted mercapto-3-(3,4,5-trimethoxybenzyl)-4(3H)-quinazolinone analogues
  作者：Adel S. El-Azab、Alaa A.-M. Abdel-Aziz、Hazem A. Ghabbour、Manal A. Al-Gendy

  DOI：10.1080/14756366.2017.1368504

  日期：2017.1.1

  A novel series of 2-substituted mercapto-3-(3,4,5-trimethoxybenzyl)-4(3H)-quinazolinones 1-20 was synthesised and evaluated for in vitro antitumour activity. N-(4-Chlorophenyl)-2-[(3-(3,4,5-trimethoxybenzyl)-4(3H)-quinazolinon-2-yl)thio)acetamide (7) and N-(3,4,5 trimethoxybenzyl)-2-[(3-(3,4,5-trimethoxybenzyl)-4(3H)-quinazolinon-2-yl)thio]propanamide (19) exhibited excellent antitumour properties

  合成了一系列新的2-取代的巯基-3-（3,4,5-三甲氧基苄基）-4（3H）-喹唑啉酮1-20，并评估了其体外抗肿瘤活性。N-（4-氯苯基）-2-[（3-（3,4,5-三甲氧基苄基）-4（3H）-喹唑啉酮-2-基）硫基）乙酰胺（7）和N-（3,4,5三甲氧基苄基）-2-[（3-（3,4,5-三甲氧基苄基）-4（3H）-喹唑啉酮-2-基）硫基]丙酰胺（19）表现出优异的抗肿瘤特性，平均抑制生长浓度（GI50）为与5-氟尿嘧啶5-FU，吉非替尼和厄洛替尼的分别相比，分别为17.90和6.33 µM（平均GI50：分别为18.60、3.24和7.29 µM）。化合物7和19的GI50（µM）值与5-FU，吉非替尼，厄洛替尼和厄洛替尼对肿瘤细胞株体外亚群的研究表明，化合物7和19的活性几乎等于或高于那些标准药物的活性，尤其是对肺，中枢神经系统和乳腺癌细胞的活性。然而，化合物5、10、14、14、1
• Probing Structural Requirements of Positive Allosteric Modulators of the M₄ Muscarinic Receptor
  作者：Tracey Huynh、Celine Valant、Ian T. Crosby、Patrick M. Sexton、Arthur Christopoulos、Ben Capuano

  DOI：10.1021/jm401032k

  日期：2013.10.24

  The M, mAChR is implicated in several CNS disorders and possesses an allosteric binding site for which ligands modulating the affinity and/or efficacy of ACh may be exploited for selective receptor targeting. We report the synthesis of a focused library of putative M-4 PAMs derived from VU0152100 and VU10005. These compounds investigate the pharmacological effects of previously identified methoxy and fluoro substituents, providing useful estimates of affinity (K-B), cooperativity (alpha beta), and direct agonist properties (tau(B)).
• Discovery of certain benzyl/phenethyl thiazolidinone-indole hybrids as potential anti-proliferative agents: Synthesis, molecular modeling and tubulin polymerization inhibition study
  作者：Dilep Kumar Sigalapalli、Venkatesh Pooladanda、Priti Singh、Manasa Kadagathur、Sravanthi Devi Guggilapu、Jaya Lakshmi Uppu、Neelima D. Tangellamudi、Pavan Kumar Gangireddy、Chandraiah Godugu、Nagendra Babu Bathini

  DOI：10.1016/j.bioorg.2019.103188

  日期：2019.11

  A series of certain benzyl/phenethyl thiazolidinone-indole hybrids were synthesized for the study of anti-proliferative activity against A549, NCI-H460 (lung cancer), MDA-MB-231 (breast cancer), HCT-29 and HCT-15 (colon cancer) cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). We found that compound G37 displayed highest cytotoxicity with IC50 value of 0.92 +/- 0.12 mu M towards HCT-15 cancer cell line among all the synthesized compounds. Moreover, compound G37 was also tested on normal human lung epithelial cells (L132) and was found to be safe in contrast to HCT-15 cells. The lead compound G37 showed significant G2/M phase arrest in HCT-15 cells. Additionally, compound G37 significantly inhibited tubulin polymerization with IC50, value of 2.92 +/- 0.23 mu M. Mechanistic studies such as acridine orange/ethidium bromide (AO/EB) dual staining, DAPI nuclear staining, annexinV/propidium iodide dual staining, donogenic growth inhibition assays inferred that compound G37 induced apoptotic cell death in HCT-15 cells. Moreover, loss of mitochondrial membrane potential with elevated intracellular ROS levels was observed by compound G37. These compounds bind at the active pocket of the alpha/beta-tubulin with higher number of stable hydrogen bonds, hydrophobic and arene-cation interactions confirmed by molecular modeling studies.