4-((2,5-dioxopyrrolidin-1-yl)methyl)benzenesulfonamide | 1429784-70-2

• 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: 4-((2,5-dioxopyrrolidin-1-yl)methyl)benzenesulfonamide
• 英文别名: 4-[(2,5-Dioxopyrrolidin-1-yl)methyl]benzenesulfonamide；4-[(2,5-dioxopyrrolidin-1-yl)methyl]benzenesulfonamide
• CAS: 1429784-70-2
• 化学式: C₁₁H₁₂N₂O₄S
• 分子量: 268.293
• InChiKey: AYNHSSHRIRNWEB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  丁二酸酐 、 磺胺米隆 在 溶剂黄146 作用下， 反应 24.0h， 以76%的产率得到4-((2,5-dioxopyrrolidin-1-yl)methyl)benzenesulfonamide
  参考文献：
  名称：

  Molecular design, synthesis and biological evaluation of cyclic imides bearing benzenesulfonamide fragment as potential COX-2 inhibitors. Part 2

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2013.02.107

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.