8-hydroxy-3-(2-(3-hydroxycarbonyl)phenylamino)acetyl-2H-chromen-2-one | 1355025-93-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 8-hydroxy-3-(2-(3-hydroxycarbonyl)phenylamino)acetyl-2H-chromen-2-one
• CAS: 1355025-93-2
• 化学式: C₁₈H₁₃NO₆
• 分子量: 339.304
• InChiKey: WZCSFLIVISXMTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.49
• 重原子数：
  25.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  116.84
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  硫氰酸铵 、 8-hydroxy-3-(2-(3-hydroxycarbonyl)phenylamino)acetyl-2H-chromen-2-one 在 溶剂黄146 作用下， 反应 1.5h， 以67%的产率得到3-[2,3-(dihydro-3-(3-hydroxycarbonylphenyl)-2-thioxo-1H-imidazol-5-yl)]-8-hydroxy-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
• 作为产物：
  描述：

  2,3-二羟基苯甲醛 在 哌啶 、 碳酸氢钠 、 copper(ll) bromide 作用下， 以 乙醇 、 氯仿 、 乙酸乙酯 为溶剂， 反应 10.0h， 生成 8-hydroxy-3-(2-(3-hydroxycarbonyl)phenylamino)acetyl-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