(E)-2-(4-(2-(biphenyl-4-yl)vinyl)-N-isopropoxyphenylsulfonamido)-N-hydroxyacetamide | 1178858-48-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (E)-2-(4-(2-(biphenyl-4-yl)vinyl)-N-isopropoxyphenylsulfonamido)-N-hydroxyacetamide
• 英文别名: N-hydroxy-2-[[4-[(E)-2-(4-phenylphenyl)ethenyl]phenyl]sulfonyl-propan-2-yloxyamino]acetamide
• CAS: 1178858-48-4
• 化学式: C₂₅H₂₆N₂O₅S
• 分子量: 466.558
• InChiKey: ZQBRASLBYJYZLM-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (E)-2-(4-(2-(biphenyl-4-yl)vinyl)-N-isopropoxyphenylsulfonamido)-N-(tert-butyldimethylsilyloxy)acetamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以73%的产率得到(E)-2-(4-(2-(biphenyl-4-yl)vinyl)-N-isopropoxyphenylsulfonamido)-N-hydroxyacetamide
  参考文献：
  名称：

  N-O-Isopropyl Sulfonamido-Based Hydroxamates: Design, Synthesis and Biological Evaluation of Selective Matrix Metalloproteinase-13 Inhibitors as Potential Therapeutic Agents for Osteoarthritis

  摘要：

  Matrix metalloproteinase-13 (MMP-13) is a key enzyme implicated in the degradation of the extracellular matrix in osteoarthritis (OA). For this reason, MMP-13 synthetic inhibitors arc being sought as potential therapeutic agents to prevent cartilage degradation and to halt the progression of OA. Herein, we report the synthesis and in vitro evaluation of a new series of selective MMP-13 inhibitors possessing an arylsulfonamidic scaffold. Among these potential inhibitors, a very promising compound was discovered exhibiting nanomolar activity for MMP-13 and was highly selective for this enzyme compared to MMP-1, -14, and TACE. This compound acted as a slow-binding inhibitor of MMP-13 and was demonstrated to be effective in an in vitro Collagen assay and in a model of cartilage degradation. Furthermore, a docking study was conducted for this compound in order to investigate its binding interactions with MMP-13 and the reasons for its selectivity toward MMP-13 versus other MMPs.

  DOI：

  10.1021/jm900261f

文献信息

• <i>N-O-</i>Isopropyl Sulfonamido-Based Hydroxamates: Design, Synthesis and Biological Evaluation of Selective Matrix Metalloproteinase-13 Inhibitors as Potential Therapeutic Agents for Osteoarthritis
  作者：Elisa Nuti、Francesca Casalini、Stanislava I. Avramova、Salvatore Santamaria、Giovanni Cercignani、Luciana Marinelli、Valeria La Pietra、Ettore Novellino、Elisabetta Orlandini、Susanna Nencetti、Tiziano Tuccinardi、Adriano Martinelli、Ngee-Han Lim、Robert Visse、Hideaki Nagase、Armando Rossello

  DOI：10.1021/jm900261f

  日期：2009.8.13

  Matrix metalloproteinase-13 (MMP-13) is a key enzyme implicated in the degradation of the extracellular matrix in osteoarthritis (OA). For this reason, MMP-13 synthetic inhibitors arc being sought as potential therapeutic agents to prevent cartilage degradation and to halt the progression of OA. Herein, we report the synthesis and in vitro evaluation of a new series of selective MMP-13 inhibitors possessing an arylsulfonamidic scaffold. Among these potential inhibitors, a very promising compound was discovered exhibiting nanomolar activity for MMP-13 and was highly selective for this enzyme compared to MMP-1, -14, and TACE. This compound acted as a slow-binding inhibitor of MMP-13 and was demonstrated to be effective in an in vitro Collagen assay and in a model of cartilage degradation. Furthermore, a docking study was conducted for this compound in order to investigate its binding interactions with MMP-13 and the reasons for its selectivity toward MMP-13 versus other MMPs.