3-[2,3-(dihydro-3-(3-ethoxycarbonylphenyl)-2-thioxo-1H-imidazol-5-yl)]-2H-chromen-2-one | 1355025-98-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-[2,3-(dihydro-3-(3-ethoxycarbonylphenyl)-2-thioxo-1H-imidazol-5-yl)]-2H-chromen-2-one
• 英文别名: ethyl 3-[5-(2-oxochromen-3-yl)-2-sulfanylidene-1H-imidazol-3-yl]benzoate
• CAS: 1355025-98-7
• 化学式: C₂₁H₁₆N₂O₄S
• 分子量: 392.435
• InChiKey: DYILTSUXJXXNBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氨基苯甲酸乙酯 、 3-(溴乙酰基)香豆素 在 碳酸氢钠 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 6.5h， 生成 3-[2,3-(dihydro-3-(3-ethoxycarbonylphenyl)-2-thioxo-1H-imidazol-5-yl)]-2H-chromen-2-one
  参考文献：
  名称：

  Identification of novel molecular scaffolds for the design of MMP-13 inhibitors: A first round of lead optimization

  摘要：

  Osteoarthritis (OA) is the leading cause of joint pain and disability in middle-aged and elderly patients, and is characterized by progressive loss of articular cartilage. Among the various matrix metalloproteinases (MMPs), MMP-13 is specifically expressed in the cartilage of human OA patients and is not present in normal adult cartilage. Thus. MMP-13-selective inhibitors are promising candidates in ostearthritis therapy. Recently, we designed an N-isopropoxy-arylsulfonamide-based hydroxamate inhibitor, which showed low nanomolar activity and high selectivity for MMP-13. In parallel to further studies aiming to assess the in vivo activity of our compound, we screened the Life Chemicals database through computational docking to seek for novel scaffolds as zinc-chelating non-hydroxamate inhibitors. Experimental evaluation of 20 selected candidate compounds verified five novel leads with IC50 in the low mu M range. These newly discovered inhibitors are structurally unrelated to the ones known so far and provide useful scaffolds to develop compounds with more desirable properties. Finally, a first round of structure-based optimization on lead 1 was accomplished and led to an increase in potency of more than 5 fold. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.035

文献信息

• Identification of novel molecular scaffolds for the design of MMP-13 inhibitors: A first round of lead optimization
  作者：Valeria La Pietra、Luciana Marinelli、Sandro Cosconati、Francesco Saverio Di Leva、Elisa Nuti、Salvatore Santamaria、Isabella Pugliesi、Matteo Morelli、Francesca Casalini、Armando Rossello、Concettina La Motta、Sabrina Taliani、Robert Visse、Hideaki Nagase、Federico da Settimo、Ettore Novellino

  DOI：10.1016/j.ejmech.2011.10.035

  日期：2012.1

  Osteoarthritis (OA) is the leading cause of joint pain and disability in middle-aged and elderly patients, and is characterized by progressive loss of articular cartilage. Among the various matrix metalloproteinases (MMPs), MMP-13 is specifically expressed in the cartilage of human OA patients and is not present in normal adult cartilage. Thus. MMP-13-selective inhibitors are promising candidates in ostearthritis therapy. Recently, we designed an N-isopropoxy-arylsulfonamide-based hydroxamate inhibitor, which showed low nanomolar activity and high selectivity for MMP-13. In parallel to further studies aiming to assess the in vivo activity of our compound, we screened the Life Chemicals database through computational docking to seek for novel scaffolds as zinc-chelating non-hydroxamate inhibitors. Experimental evaluation of 20 selected candidate compounds verified five novel leads with IC50 in the low mu M range. These newly discovered inhibitors are structurally unrelated to the ones known so far and provide useful scaffolds to develop compounds with more desirable properties. Finally, a first round of structure-based optimization on lead 1 was accomplished and led to an increase in potency of more than 5 fold. (C) 2011 Elsevier Masson SAS. All rights reserved.