N-(3,4,5-trimethoxybenzoyl)imidazole

• 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: N-(3,4,5-trimethoxybenzoyl)imidazole
• 英文别名: imidazol-1-yl-(3,4,5-trimethoxyphenyl)methanone
• 化学式: C₁₃H₁₄N₂O₄
• 分子量: 262.265
• InChiKey: IMEZTARHGGCYHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3,4,5-trimethoxybenzoyl)imidazole 在 正丁基锂 、 tetra-n-butylammoniumfluoride trihydrate 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 乙腈 为溶剂， 反应 21.5h， 生成 phenstatin
  参考文献：
  名称：

  Application of plant allylpolyalkoxybenzenes in synthesis of antimitotic phenstatin analogues

  摘要：

  Phenstatin and its derivatives with the modified ring A have been synthesized, using plant allylpolyalkoxybenzenes as a starting material. The targeted molecules were evaluated in a phenotypic sea urchin embryo assay for antiproliferative activity. It was found that phenstatin ring A modifications yielded antimitotic compounds. The most effective myristicin derivative 7d (combretastatin A-2 analogue) was determined to be ca. 10 times more potent than phenstatin, displaying antimitotic tubulin-destabilizing activity at the same concentration range as combretastatins. In contrast to combretastatins, 7d featured the steric stability with potential for further design as anticancer agent. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.124
• 作为产物：
  描述：

  咪唑 、 3,4,5-三甲氧基苯甲酰氯 以 氯仿 为溶剂， 以77%的产率得到N-(3,4,5-trimethoxybenzoyl)imidazole
  参考文献：
  名称：

  Study of the Reaction of Hydroxybenzoyl Chlorides and Their Derivatives with Imidazole

  摘要：

  The reaction of hydroxybenzoyl chlorides with imidazole was studied on an example of the Schotten-Baumann reaction of salicyloyl and acetylsalicyloyl chlorides with imidazole, which, according to soe published data, can take two different ways. It was shown that the Schotten-Baumann reaction with imidazole involves imidazole ring opening (Bamberger cleavage) to form l,2-bis(salicyloylamino)ethylene and l,2-bis(acetylsalicyloylamino)ethylene rather than N-salicyloylimidazole and N-acetylsalicyloylimidazole. N-Hydroxybenzoylimidazoles were synthesized by the reaction of hydroxybenzoyl chlorides (and derivatives) with a double excess of imidazole in an aprotic solvent (chloroform, benzene, or diethyl ether) at room temperature. The highest yields (about 80%) of N-hydroxybenzoylimidazoles were obtained in chloroform. Some of the newly synthesized compounds were tested for psychotropic (open field and passive avoidance response tests) and analgesic activities (vocalization threshold test). The best results were obtained with N-(2-hydroxybenzoyl)imidazole, which showed an evident analgesic activity, and, therewith, the motor score and oriented exploratory activity parameters were higher than in the control group.

  DOI：

  10.1134/s1070428019050026

文献信息

• Expedient synthesis of 3-hydroxyisoquinolines and 2-hydroxy-1,4-naphthoquinones via one-pot aryne acyl-alkylation/condensation
  作者：Kevin M. Allan、Boram D. Hong、Brian M. Stoltz

  DOI：10.1039/b913336d

  日期：——

  A convenient method is disclosed for the synthesis of both 3-hydroxyisoquinolines and 2-hydroxy-1,4-naphthoquinones from β-ketoesters using a one-pot aryne acyl-alkylation/condensation procedure. When performed in conjunction with a one-step method for the synthesis of the β-ketoester substrates, this method provides a new route to these polyaromatic structures in only two steps from commercially available carboxylic acid starting materials. The utility of this approach is demonstrated in the synthesis of the atropisomeric P,N-ligand, QUINAP.

  公开了一种方便的方法，可以通过一锅法将β-酮酯合成3-羟基异喹啉和2-羟基-1,4-萘醌，采用芳烯酰基-烷基化/缩合步骤。当与一步法合成β-酮酯底物结合进行时，该方法仅需从商业可得的羧酸起始材料出发，通过两个步骤即可提供这些多芳香结构的新路线。该方法的实用性在于合成了具 atropisomer 的 P,N-配体 QUINAP。
• Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes
  作者：Zi-Long Song、Feifei Bai、Baoxin Zhang、Jianguo Fang

  DOI：10.1021/acs.jafc.9b06360

  日期：2020.2.19

  Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine- or H2O2 -induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.
• An Improved Process for Trimethobenzamide Hydrochloride
  作者：K. Neelakandan、H. Manikandan、N. Santosha、B. Prabhakaran

  DOI：10.1021/op400113a

  日期：2013.7.19

  An improved process for the preparation of trimethobenzamide hydrochloride conforming to regulatory specification is reported. Specifically, a process for the preparation of trimethobenzamide hydrochloride, which is free from the associated impurities that are normally encountered during coupling of 4-(2-dimethylaminoethoxy)benzyl amine with 3,4,5-trimethoxy benzoic acid is described.
• Design and synthesis of 3,5-disubstituted boron-containing 1,2,4-oxadiazoles as potential combretastatin A-4 (CA-4) analogs
  作者：Bhaskar C. Das、Xiang-Ying Tang、Patrick Rogler、Todd Evans

  DOI：10.1016/j.tetlet.2012.02.110

  日期：2012.8

  We have designed and synthesized a small library of 3,5-disubstituted-1,2,4-oxadiazole containing combretastatin A-4 (CA-4) analogs. Our objective is to increase the efficacy of the CA-4 as an anti-tubulin and antimitotic agent by substituting the cis-alkene bond with one of its bioisosteres, the 1,2,4-oxadiazole ring. We also modified the substituents attached to both of the phenyl rings (ring A and B in Fig. 1) of CA-4 for the purpose of diversifying our analogs based on SAR. These compounds were synthesized via a coupling reaction between an amidoxime and a carboxylic acid in DMF solvent, with HOBt as a base, and utilizing EDCI as a coupling reagent. Using this protocol, we synthesized a small library of 10 compounds with moderate to good yields. A detailed biological study is currently undergoing in our laboratory to evaluate the activity of these compounds. (C) 2012 Elsevier Ltd. All rights reserved.
• Reactions of Some 1-(4,5-Dihydroimidaol-2-yl)azoles with Aroyl and Ethoxycarbonyl Isothiocyanates
  作者：Franciszek Saczewski

  DOI：10.3987/com-93-s75

  日期：——

  Three components cyclocondensations of the imidazole derivative (1c) with aroyl isothiocyanates afforded 6,7,8,8a-tetrahydro-3-aroylimidazo[1,2-a][1,3,5]triazine-2,4(3H, 8H)-dithiones (5a-e), while similar reaction with ethoxycarbonyl isothiocyanate led to the formation of ethyl 5-thioxo-2,3,8,9-tetrahydro-5H-diimidazo[1,2-a:1',2;-c][1,3,5]triazine-6-carboxylate (10).