4-(4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl)benzenesulfonamide | 88062-88-8

• 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-(4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl)benzenesulfonamide
• 英文别名: 4-(4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl) benzenesulphonamide；4-(4,5,6,7-Tetrachloro-1,3-dioxoisoindol-2-yl)benzenesulfonamide
• CAS: 88062-88-8
• 化学式: C₁₄H₆Cl₄N₂O₄S
• 分子量: 440.091
• InChiKey: VOULHARHCIQTLL-UHFFFAOYSA-N

物化性质

• 熔点：
  300 °C(Solv: 1,4-dioxane (123-91-1))
• 沸点：
  684.8±65.0 °C(Predicted)
• 密度：
  1.807±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 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：
  106
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl)benzenesulfonamide 、 phenylmagnesium chloride 以30%的产率得到
  参考文献：
  名称：

  ISLAM, A. M.;EL-SHARIEF, A. M. SH.;EL-MAGHRABY, A. A.;EL-SAID, A. S., EGYPT. J. SCI., 1982, 25, N 6, 513-520

  摘要：

  DOI：
• 作为产物：
  描述：

  四氯苯二甲酸酐 、 磺胺 在 溶剂黄146 作用下， 反应 2.0h， 以98%的产率得到4-(4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl)benzenesulfonamide
  参考文献：
  名称：

  含有单环、双环和三环酰亚胺部分的磺酰胺的合成和人碳酸酐酶 I、II、IX 和 XII 抑制研究

  摘要：

  新的衍生物是通过含氨基的芳香磺酰胺与单、双和三环酸酐反应合成的。这些磺胺类药物被研究为人类碳酸酐酶 (hCAs, EC 4.2.1.1) I、II、IX 和 XII 抑制剂。hCA I 受到抑制常数 (Kis) 范围从 49 到 >10,000 nM 的抑制。生理上占优势的 hCA II 被大多数磺胺显着抑制，Kis 范围在 2.4 和 4515 nM 之间。hCA IX 和 hCA XII 分别在 9.7 至 7766 nM 和 14 至 316 nM 的范围内被这些磺胺类药物抑制。在分子对接研究的帮助下，结构-活性关系（SAR）被合理化。

  DOI：

  10.3390/ph14070693

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 cytosolic mammalian carbonic anhydrase isoforms I, II and VII with benzene sulfonamides incorporating 4,5,6,7-tetrachlorophthalimide moiety
  作者：Kalyan K. Sethi、Saurabh M. Verma、Muhammet Tanç、Fabrizio Carta、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2013.06.035

  日期：2013.9

  A series of 4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl benzenesulfonamide derivatives (compounds 1-8) was synthesized by reaction of benzene sulfonamides incorporating primary amino moieties with 4,5,6,7-tetrachlorophthalic anhydride. These sulfonamides were assayed as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Some of these compounds showed very good in vitro human carbonic anhydrase (hCA) isoforms I, II and VII inhibitory properties, with affinities in the low nanomolar range. Inhibition activities against hCA I were in the range of 159-444 nM; against hCA II in the range of 2.4-4515 nM, and against hCA VII in the range of 1.3-469 nM. The structure-activity relationship (SAR) with this series of sulfonamides is straightforward, with the main features leading to good activity for each isoform being established. (C) 2013 Elsevier Ltd. All rights reserved.