2-(3,4,5-trimethoxybenzyl)isoindoline-1,3-dione | 57944-75-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(3,4,5-trimethoxybenzyl)isoindoline-1,3-dione
• 英文别名: 2-[(3,4,5-Trimethoxyphenyl)methyl]isoindole-1,3-dione
• CAS: 57944-75-9
• 化学式: C₁₈H₁₇NO₅
• 分子量: 327.337
• InChiKey: RPGRHGPHWFRJGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(3,4,5-trimethoxybenzyl)isoindoline-1,3-dione 在 盐酸 、 magnesium 作用下， 以 四氢呋喃 为溶剂， 反应 9.5h， 生成 2-(3,4,5-trimethoxybenzyl)-3-<(E)-2-phenylethylidene>-1-isoindolinone
  参考文献：
  名称：

  前列腺素和相关化合物。七。具有对血栓烷A2类似物（U-46619）诱导的血管收缩具有抑制活性的1-异吲哚啉酮衍生物的合成和抑制活性。

  摘要：

  我们已经合成了一系列新型的1-isoindolinone衍生物，它们抑制了由血栓烷A2类似物U-46619诱导的猪冠状动脉的收缩。

  DOI：

  10.1248/cpb.47.529
• 作为产物：
  描述：

  3,4,5-三甲氧基苄胺 、 苯酐 在 溶剂黄146 作用下， 反应 4.0h， 以90%的产率得到2-(3,4,5-trimethoxybenzyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Structure-based design of phthalimide derivatives as potential cyclooxygenase-2 (COX-2) inhibitors: Anti-inflammatory and analgesic activities

  摘要：

  A group of 30 cyclic imides (1-10a-c) was designed for evaluation as a selective COX-2 inhibitor and investigated in vivo for anti-inflammatory and analgesic activities. Compounds 6a, 6b, 7a and 7b exhibit optimal COX-2 inhibitory potency (IC50 = 0.18, 0.24, 0.28 and 036 AM; respectively) and selectivity index (SI) range of 363-668. In vitro COX-1/COX-2 inhibition structure activity studies identified compound 6a as a highly potent (IC50 = 0.18 AM), and an extremely selective [COX-2 (SI) = 668] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 = 54.0 mg/kg) relative to didofenac (ED50 = 114 mg/kg). Molecular Docking study of the synthesized compound 6a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. Docking study showed that the methoxy moeities of 6a inserted deep inside the 2 degrees-pocket of the COX-2 active site, where the O-atoms of such groups underwent an H-bonding interaction with His(90) (3.02 angstrom), Arg(513) (1.94, 2.83 angstrom), and Gln(192) (3.25 angstrom). (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.039

文献信息

• Extending the structure−activity relationship study of marine natural ningalin B analogues as P-glycoprotein inhibitors
  作者：Chao Yang、Iris L.K. Wong、Kai Peng、Zhen Liu、Peng Wang、Tingfu Jiang、Tao Jiang、Larry M.C. Chow、Sheng Biao Wan

  DOI：10.1016/j.ejmech.2016.09.070

  日期：2017.1

  In the present study, a total of 25 novel ningalin B analogues were synthesized and evaluated for their P-gp modulating activity in a P-gp overexpressed breast cancer cell line LCC6MDR. Preliminary structure-activity study shows that A ring and its two methoxy groups are important pharmacophores for P-gp inhibiting activity. Among all derivatives, 23 is the most potent P-gp modulator with EC50 of 120–165 nM

  在本研究中，总共合成了25种新的宁格灵B类似物，并评估了它们在过表达P-gp的乳腺癌细胞LCC6MDR中的P-gp调节活性。初步的结构活性研究表明，A环及其两个甲氧基是抑制P-gp活性的重要药效团。在所有衍生物中，23是最有效的P-gp调节剂，在逆转紫杉醇，DOX，长春碱和长春新碱的抗性方面，EC 50为120-165 nM。与维拉帕米相比，选择指数至少大于606相对安全。机理研究表明，化合物23通过抑制P-gp的转运活性来逆转P-gp介导的耐药性，从而恢复细胞内药物的积累。总而言之，我们的研究表明，宁格灵B类似物23是一种无细胞毒性且有效的P-gp化学增敏剂，可在将来用于逆转P-gp介导的临床癌症药物耐药性。
• Synthesis and inhibitory activity of isoindolinone derivatives on thromboxane A2 analog (U-46619)-induced vasocontraction.
  作者：Yoshiaki KATO、Hirosato EBIIKE、Kazuo ACHIWA、Naoki ASHIZAWA、Toshio KURIHARA、Fujio KOBAYASHI

  DOI：10.1248/cpb.38.2060

  日期：——

  Newly synthesized isoindolinone derivatives inhibited the contraction of pig coronary artery induced by U-46619, a thromboxane A2 analog.

  新合成的异吲哚酮衍生物可抑制血栓素 A2 类似物 U-46619 诱导的猪冠状动脉收缩。
• CHIMENTI F.; VOMERO S., FARMACO, ED. SCI. <FRPS-AX>, 1975, 30, NO 11, 884-890
  作者：CHIMENTI F.、 VOMERO S.

  DOI：——

  日期：——
• Supported-Pd catalyzed carbonylative synthesis of phthalimides and isoindolinones using Oxalic acid as in situ CO surrogate with 2-iodobenzamides and 2-iodobenzylanilines in ppm-level catalyst loading
  作者：Shankar Ram、Pushkar Mehara、Ashish Kumar、Ajay Kumar Sharma、Arvind Singh Chauhan、Ajay Kumar、Pralay Das

  DOI：10.1016/j.mcat.2022.112606

  日期：2022.9
• Structure-based design of phthalimide derivatives as potential cyclooxygenase-2 (COX-2) inhibitors: Anti-inflammatory and analgesic activities
  作者：Amer M. Alanazi、Adel S. El-Azab、Ibrahim A. Al-Suwaidan、Kamal Eldin H. ElTahir、Yousif A. Asiri、Naglaa I. Abdel-Aziz、Alaa A.-M. Abdel-Aziz

  DOI：10.1016/j.ejmech.2014.12.039

  日期：2015.3

  A group of 30 cyclic imides (1-10a-c) was designed for evaluation as a selective COX-2 inhibitor and investigated in vivo for anti-inflammatory and analgesic activities. Compounds 6a, 6b, 7a and 7b exhibit optimal COX-2 inhibitory potency (IC50 = 0.18, 0.24, 0.28 and 036 AM; respectively) and selectivity index (SI) range of 363-668. In vitro COX-1/COX-2 inhibition structure activity studies identified compound 6a as a highly potent (IC50 = 0.18 AM), and an extremely selective [COX-2 (SI) = 668] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 = 54.0 mg/kg) relative to didofenac (ED50 = 114 mg/kg). Molecular Docking study of the synthesized compound 6a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. Docking study showed that the methoxy moeities of 6a inserted deep inside the 2 degrees-pocket of the COX-2 active site, where the O-atoms of such groups underwent an H-bonding interaction with His(90) (3.02 angstrom), Arg(513) (1.94, 2.83 angstrom), and Gln(192) (3.25 angstrom). (C) 2014 Elsevier Masson SAS. All rights reserved.