2-(4-phenoxyphenylsulfonamido)acetic acid | 885269-07-8

• 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: 2-(4-phenoxyphenylsulfonamido)acetic acid
• 英文别名: 2-[(4-Phenoxyphenyl)sulfonylamino]acetic acid
• CAS: 885269-07-8
• 化学式: C₁₄H₁₃NO₅S
• 分子量: 307.327
• InChiKey: IOCNHGZCHKITDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-phenoxyphenylsulfonamido)acetic acid 在 N-甲基吗啉 、 5%-palladium/activated carbon 、 氢气 、 1-丙基磷酸酐 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 20.0 ℃ 、150.0 kPa 条件下， 反应 3.0h， 生成 2-[(4-phenoxyphenyl)sulfonylamino]ethanehydroxamic acid
  参考文献：
  名称：

  New bifunctional metalloproteinase inhibitors: an integrated approach towards biological improvements and cancer therapy

  摘要：

  The key role of some matrix metalloproteinases (MMPs) on several pathological processes, including carcinogenesis and tumor growth, makes the development of MMP inhibitors (MMPIs) an attractive approach for cancer therapy. We present herein an integrated approach for the development of a new series of inhibitors of MMP2 and MMP14, two enzymes over-expressed by human ovarian cancer. As a first step, a new series of single model compounds bearing different zinc-binding groups (ZBGs), such as carboxylic, hydroxamic acid, hydrazide and sulfonylhydrazide groups, were studied and revealed reasonably good capacity for the Zn(II) chelation in solution and for the MMP inhibition. Aimed at further reinforcing the biological activity of these MMPIs as anti-cancer agents, a selection of those models was extra-functionalized with benzothiazole (BTA), a group with recognized antitumor activity. Analysis of the results obtained for these bifunctional compounds, in particular the inhibitory activity against MMP2 and MMP14 as well as the anti-proliferative activity on the A2780 ovarian cancer cell line, allowed to understand the activity dependence on the type of ZBG, as well as the relevance of the ETA moiety. Overall, the evidenced BTA-associated activity improvements on enzyme inhibition and cell antiproliferactivity, combined with the hydrolytic stability revealed by the hydrazide group, suggest that these new bifunctional BTA-hydrazide derivatives should be taken in consideration for the development of new generations of MMPIs with anti-cancer activity. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jinorgbio.2013.03.003
• 作为产物：
  描述：

  4-苯氧基苯磺酰氯 在 三乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 28.0h， 生成 2-(4-phenoxyphenylsulfonamido)acetic acid
  参考文献：
  名称：

  New bifunctional metalloproteinase inhibitors: an integrated approach towards biological improvements and cancer therapy

  摘要：

  The key role of some matrix metalloproteinases (MMPs) on several pathological processes, including carcinogenesis and tumor growth, makes the development of MMP inhibitors (MMPIs) an attractive approach for cancer therapy. We present herein an integrated approach for the development of a new series of inhibitors of MMP2 and MMP14, two enzymes over-expressed by human ovarian cancer. As a first step, a new series of single model compounds bearing different zinc-binding groups (ZBGs), such as carboxylic, hydroxamic acid, hydrazide and sulfonylhydrazide groups, were studied and revealed reasonably good capacity for the Zn(II) chelation in solution and for the MMP inhibition. Aimed at further reinforcing the biological activity of these MMPIs as anti-cancer agents, a selection of those models was extra-functionalized with benzothiazole (BTA), a group with recognized antitumor activity. Analysis of the results obtained for these bifunctional compounds, in particular the inhibitory activity against MMP2 and MMP14 as well as the anti-proliferative activity on the A2780 ovarian cancer cell line, allowed to understand the activity dependence on the type of ZBG, as well as the relevance of the ETA moiety. Overall, the evidenced BTA-associated activity improvements on enzyme inhibition and cell antiproliferactivity, combined with the hydrolytic stability revealed by the hydrazide group, suggest that these new bifunctional BTA-hydrazide derivatives should be taken in consideration for the development of new generations of MMPIs with anti-cancer activity. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jinorgbio.2013.03.003

文献信息

• Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: Synthesis and biological evaluation
  作者：Elisa Nuti、Salvatore Santamaria、Francesca Casalini、Kazuhiro Yamamoto、Luciana Marinelli、Valeria La Pietra、Ettore Novellino、Elisabetta Orlandini、Susanna Nencetti、Anna Maria Marini、Silvia Salerno、Sabrina Taliani、Federico Da Settimo、Hideaki Nagase、Armando Rossello

  DOI：10.1016/j.ejmech.2012.12.058

  日期：2013.4

  Aggrecanases, in particular aggrecanase-2 (ADAMTS-5), are considered the principal proteases responsible for aggrecan degradation in osteoarthritis. For this reason, considerable effort has been put on the discovery and development of aggrecanase inhibitors able to slow down or halt the progression of osteoarthritis. We report herein the synthesis and biological evaluation of a series of arylsulfonamido-based hydroxamates as aggrecanase inhibitors. Compound 18 was found to have a nanomolar activity for ADAMTS-5, ADAMTS-4 and MMP-13 and high selectivity over MMP-1 and MMP-14. Furthermore, this compound proved to be effective in blocking ex vivo cartilage degradation without having effect on cell cytotoxicity. (C) 2013 Elsevier Masson SAS. All rights reserved.
• New bifunctional metalloproteinase inhibitors: an integrated approach towards biological improvements and cancer therapy
  作者：Sérgio M. Marques、Claudia C. Abate、Sílvia Chaves、Fernanda Marques、Isabel Santos、Elisa Nuti、Armando Rossello、M. Amélia Santos

  DOI：10.1016/j.jinorgbio.2013.03.003

  日期：2013.10

  The key role of some matrix metalloproteinases (MMPs) on several pathological processes, including carcinogenesis and tumor growth, makes the development of MMP inhibitors (MMPIs) an attractive approach for cancer therapy. We present herein an integrated approach for the development of a new series of inhibitors of MMP2 and MMP14, two enzymes over-expressed by human ovarian cancer. As a first step, a new series of single model compounds bearing different zinc-binding groups (ZBGs), such as carboxylic, hydroxamic acid, hydrazide and sulfonylhydrazide groups, were studied and revealed reasonably good capacity for the Zn(II) chelation in solution and for the MMP inhibition. Aimed at further reinforcing the biological activity of these MMPIs as anti-cancer agents, a selection of those models was extra-functionalized with benzothiazole (BTA), a group with recognized antitumor activity. Analysis of the results obtained for these bifunctional compounds, in particular the inhibitory activity against MMP2 and MMP14 as well as the anti-proliferative activity on the A2780 ovarian cancer cell line, allowed to understand the activity dependence on the type of ZBG, as well as the relevance of the ETA moiety. Overall, the evidenced BTA-associated activity improvements on enzyme inhibition and cell antiproliferactivity, combined with the hydrolytic stability revealed by the hydrazide group, suggest that these new bifunctional BTA-hydrazide derivatives should be taken in consideration for the development of new generations of MMPIs with anti-cancer activity. (C) 2013 Elsevier Inc. All rights reserved.