1,3-dioxo-2-(4-sulfamoylbenzyl)isoindoline-5-carboxylic acid

• 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: 1,3-dioxo-2-(4-sulfamoylbenzyl)isoindoline-5-carboxylic acid
• 英文别名: 1,3-Dioxo-2-[(4-sulfamoylphenyl)methyl]isoindole-5-carboxylic acid；1,3-dioxo-2-[(4-sulfamoylphenyl)methyl]isoindole-5-carboxylic acid
• 化学式: C₁₆H₁₂N₂O₆S
• 分子量: 360.347
• InChiKey: OXXJZVWLYGJXOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.83
• 重原子数：
  25.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  134.84
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  磺胺米隆 、 偏苯三酸酐 在 sodium acetate 、 溶剂黄146 作用下， 反应 24.0h， 以83%的产率得到1,3-dioxo-2-(4-sulfamoylbenzyl)isoindoline-5-carboxylic acid
  参考文献：
  名称：

  Synthesis and anti-inflammatory activity of sulfonamides and carboxylates incorporating trimellitimides: Dual cyclooxygenase/carbonic anhydrase inhibitory actions

  摘要：

  Trimellitimides 6-21 were prepared and investigated in vivo for anti-inflammatory and ulcerogenic effects and in vitro for cytotoxicity. They were subjected to in vitro cyclooxygenase (COX-1/2) and carbonic anhydrase inhibition protocols. Compounds 6-11 and 18 exhibited anti-inflammatory activities and had median effective doses (ED50) of 34.3-49.8 mg kg(-1) and 63.6-86.6% edema inhibition relative to the reference drug celecoxib (ED50 : 33.9 mg kg(-1) and 85.2% edema inhibition). Compounds 6-11 and 18 were weakly cytotoxic at 10 mu M against 59 cell lines compared with the reference standard 5-fluorouracil (5-FU). Compounds 6-11 had optimal selectivity against COX-2. The selectivity index (SI) range was > 200-490 and was comparable to that for celecoxib [COX-2 (SI) > 416.7]. In contrast, compounds 12, 13, and 16-18 were nonselective COX inhibitors with a selectivity index range of 0.92-0.25. The carbonic anhydrase inhibition assay showed that sulfonamide incorporating trimellitimides 6-11 inhibited the cytosolic isoforms hCA I and hCA II, and tumor-associated isoform hCA IX. They were relatively more susceptible to inhibition by compounds 8, 9, and 11. The K-1 ranges were 54.1-81.9 nM for hCA I, 25.9-55.1 nM for hCA II, and 46.0-348.3 nM for hCA IX. (C) 2018 Elsevier Science. All rights reserved.

  DOI：

  10.1016/j.bioorg.2018.11.033

文献信息

• Synthesis and anti-inflammatory activity of sulfonamides and carboxylates incorporating trimellitimides: Dual cyclooxygenase/carbonic anhydrase inhibitory actions
  作者：Alaa A.-M. Abdel-Aziz、Andrea Angeli、Adel S. El-Azab、Mohammed E.A. Hammouda、Magda A. El-Sherbeny、Claudiu T. Supuran

  DOI：10.1016/j.bioorg.2018.11.033

  日期：2019.3

  Trimellitimides 6-21 were prepared and investigated in vivo for anti-inflammatory and ulcerogenic effects and in vitro for cytotoxicity. They were subjected to in vitro cyclooxygenase (COX-1/2) and carbonic anhydrase inhibition protocols. Compounds 6-11 and 18 exhibited anti-inflammatory activities and had median effective doses (ED50) of 34.3-49.8 mg kg(-1) and 63.6-86.6% edema inhibition relative to the reference drug celecoxib (ED50 : 33.9 mg kg(-1) and 85.2% edema inhibition). Compounds 6-11 and 18 were weakly cytotoxic at 10 mu M against 59 cell lines compared with the reference standard 5-fluorouracil (5-FU). Compounds 6-11 had optimal selectivity against COX-2. The selectivity index (SI) range was > 200-490 and was comparable to that for celecoxib [COX-2 (SI) > 416.7]. In contrast, compounds 12, 13, and 16-18 were nonselective COX inhibitors with a selectivity index range of 0.92-0.25. The carbonic anhydrase inhibition assay showed that sulfonamide incorporating trimellitimides 6-11 inhibited the cytosolic isoforms hCA I and hCA II, and tumor-associated isoform hCA IX. They were relatively more susceptible to inhibition by compounds 8, 9, and 11. The K-1 ranges were 54.1-81.9 nM for hCA I, 25.9-55.1 nM for hCA II, and 46.0-348.3 nM for hCA IX. (C) 2018 Elsevier Science. All rights reserved.