N-[2-[3',6'-bis(diethylamino)-3-oxospiro[isoindole-1,9'-xanthene]-2-yl]ethyl]-4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide | 1416368-41-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-[2-[3',6'-bis(diethylamino)-3-oxospiro[isoindole-1,9'-xanthene]-2-yl]ethyl]-4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
• CAS: 1416368-41-6
• 化学式: C₄₇H₄₇F₃N₆O₄S
• 分子量: 848.989
• InChiKey: QDSLXGWLJMBQRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9
• 重原子数：
  61
• 可旋转键数：
  13
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  罗丹明B 在 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 19.0h， 生成 N-[2-[3',6'-bis(diethylamino)-3-oxospiro[isoindole-1,9'-xanthene]-2-yl]ethyl]-4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
  参考文献：
  名称：

  Hybrid fluorescent conjugates of COX-2 inhibitors: Search for a COX-2 isozyme imaging cancer biomarker

  摘要：

  The observation that the cyclooxygenase-2 (COX-2) isozyme is over-expressed in multiple types of cancer, relative to that in adjacent non-cancerous tissue, prompted this investigation to prepare a group of hybrid fluorescent conjugates wherein the COX inhibitors ibuprofen, (S)-naproxen, acetyl salicylic acid, a chlororofecoxib analog and celecoxib were coupled via a linker group to an acridone, dansyl or rhodamine B fluorophore. Within this group of compounds, the ibuprofen-acridone conjugate (10) showed potent and selective COX-2 inhibition (COX-2 IC50 = 0.67 mu M; SI = 110.6), but its fluorescence emission (lambda(em) = 417, 440 nm) was not suitable for fluorescent imaging of cancer cells that over-express the COX-2 isozyme. In comparison, the celecoxib-dansyl conjugate (25) showed a slightly lower COX-2 potency and selectivity (COX-2 IC50 = 1.1 mu M; SI > 90) than the conjugate 10, and it possesses a better fluorescence emission (lambda(em) = 500 nm). Ultimately, a celecoxib-rhodamine B conjugate (28) that exhibited moderate COX-2 potency and selectivity (COX-2 IC50 = 3.9 mu M; SI > 25) having the best fluorescence emission (lambda(em) = 580 nm) emerged as the most promising biomarker for fluorescence imaging using a colon cancer cell line that over-expresses the COX-2 isozyme. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.131

文献信息

• Hybrid fluorescent conjugates of COX-2 inhibitors: Search for a COX-2 isozyme imaging cancer biomarker
  作者：Atul Bhardwaj、Jatinder Kaur、Sai Kiran Sharma、Zhangjian Huang、Frank Wuest、Edward E. Knaus

  DOI：10.1016/j.bmcl.2012.10.131

  日期：2013.1

  The observation that the cyclooxygenase-2 (COX-2) isozyme is over-expressed in multiple types of cancer, relative to that in adjacent non-cancerous tissue, prompted this investigation to prepare a group of hybrid fluorescent conjugates wherein the COX inhibitors ibuprofen, (S)-naproxen, acetyl salicylic acid, a chlororofecoxib analog and celecoxib were coupled via a linker group to an acridone, dansyl or rhodamine B fluorophore. Within this group of compounds, the ibuprofen-acridone conjugate (10) showed potent and selective COX-2 inhibition (COX-2 IC50 = 0.67 mu M; SI = 110.6), but its fluorescence emission (lambda(em) = 417, 440 nm) was not suitable for fluorescent imaging of cancer cells that over-express the COX-2 isozyme. In comparison, the celecoxib-dansyl conjugate (25) showed a slightly lower COX-2 potency and selectivity (COX-2 IC50 = 1.1 mu M; SI > 90) than the conjugate 10, and it possesses a better fluorescence emission (lambda(em) = 500 nm). Ultimately, a celecoxib-rhodamine B conjugate (28) that exhibited moderate COX-2 potency and selectivity (COX-2 IC50 = 3.9 mu M; SI > 25) having the best fluorescence emission (lambda(em) = 580 nm) emerged as the most promising biomarker for fluorescence imaging using a colon cancer cell line that over-expresses the COX-2 isozyme. (C) 2012 Elsevier Ltd. All rights reserved.