4-(5-nitro-1,3-dioxoisoindolin-2-yl)benzenesulfonamide | 324055-22-3

• 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: 4-(5-nitro-1,3-dioxoisoindolin-2-yl)benzenesulfonamide
• 英文别名: 4-(5-Nitro-1,3-dioxoisoindol-2-yl)benzenesulfonamide
• CAS: 324055-22-3
• 化学式: C₁₄H₉N₃O₆S
• 分子量: 347.308
• InChiKey: ODIGCXXQQQBPBI-UHFFFAOYSA-N

物化性质

• 沸点：
  641.3±65.0 °C(Predicted)
• 密度：
  1.673±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  152
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-硝基邻苯二甲酸酐 、 磺胺 以 溶剂黄146 为溶剂， 反应 12.0h， 以88%的产率得到4-(5-nitro-1,3-dioxoisoindolin-2-yl)benzenesulfonamide
  参考文献：
  名称：

  Carbonic anhydrase inhibitors: Synthesis and inhibition of the human carbonic anhydrase isoforms I, II, IX and XII with benzene sulfonamides incorporating 4- and 3-nitrophthalimide moieties

  摘要：

  A series of 4 and 5 nitro-1,3-dioxoisoindolin-2-yl benzenesulfonamide derivatives (compounds 1-8) was synthesized by reaction of benzenesulfonamide derivatives with 4 and 3-nitrophthalic anhydrides. These new sulfonamides were investigated as inhibitors of the zinc metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and more specifically against the human (h) cytosolic isoforms hCA I and II and the transmembrane, tumor-associated hCA IX and XII. Most of the novel compounds were medium potency-weak hCA I inhibitors (K(i)s in the range of 295-10,000 nM), but were more effective hCA II inhibitors (K(i)s of 1.7-887 nM). The tumor-associated hCA IX was also inhibited, with K(i)s in the micromolar range, whereas against hCA XII the inhibition constants were in the range of 90-3746 nM. The structure-activity relationship (SAR) with this series of sulfonamides is straightforward, with the main features leading to good activity for each isoforms being established. The high sequence hCA alignment homology and molecular docking studies was performed in order to rationalize the activities reported and binding mode to different hCA as inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.031

文献信息

• Molecular design, synthesis and biological evaluation of cyclic imides bearing benzenesulfonamide fragment as potential COX-2 inhibitors. Part 2
  作者：Ibrahim A. Al-Suwaidan、Amer M. Alanazi、Adel S. El-Azab、Abdulrahman M. Al-Obaid、Kamal E.H. ElTahir、Azza R. Maarouf、Mohamed A. Abu El-Enin、Alaa A.-M. Abdel-Aziz

  DOI：10.1016/j.bmcl.2013.02.107

  日期：2013.5

  A group of cyclic imides (1-10) was designed for evaluation as a selective COX-2 inhibitors and investigated in vivo for their anti-inflammatory activity. Compounds 6a, 6b, 8a, 8b, 9a, 9b, 10a and 10b were proved to be potent COX-2 inhibitors with IC50 range of 0.1-4.0 mu M. In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 8a as a highly potent (IC50 = 0.1 mu M), and an extremely selective [COX-2 (SI) > 1000] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 = 72.4 mg/kg) relative to diclofenac (ED50 = 114 mg/kg). Molecular modeling was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. The study showed that the homosulfonamide fragment of 8a inserted deep inside the 2 degrees-pocket of the COX-2 active site, where the SO2NH2 group underwent H-bonding interaction with Gln(192)(2.95 angstrom), Phe(518)(2.82 angstrom) and Arg(513)(2.63 and 2.73 angstrom). Docking study of the synthesized compound 8a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. (C) 2013 Elsevier Ltd. All rights reserved.
• Carbonic anhydrase inhibitors: Synthesis and inhibition of the human carbonic anhydrase isoforms I, II, IX and XII with benzene sulfonamides incorporating 4- and 3-nitrophthalimide moieties
  作者：Kalyan K. Sethi、Saurabh M. Verma、Muhammet Tanç、Gaultier Purper、Gaetan Calafato、Fabrizio Carta、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2014.01.031

  日期：2014.3

  A series of 4 and 5 nitro-1,3-dioxoisoindolin-2-yl benzenesulfonamide derivatives (compounds 1-8) was synthesized by reaction of benzenesulfonamide derivatives with 4 and 3-nitrophthalic anhydrides. These new sulfonamides were investigated as inhibitors of the zinc metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and more specifically against the human (h) cytosolic isoforms hCA I and II and the transmembrane, tumor-associated hCA IX and XII. Most of the novel compounds were medium potency-weak hCA I inhibitors (K(i)s in the range of 295-10,000 nM), but were more effective hCA II inhibitors (K(i)s of 1.7-887 nM). The tumor-associated hCA IX was also inhibited, with K(i)s in the micromolar range, whereas against hCA XII the inhibition constants were in the range of 90-3746 nM. The structure-activity relationship (SAR) with this series of sulfonamides is straightforward, with the main features leading to good activity for each isoforms being established. The high sequence hCA alignment homology and molecular docking studies was performed in order to rationalize the activities reported and binding mode to different hCA as inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.