3-(2-bromoacetyl)-6-chloro-8-methoxy-2H-chromen-2-one | 1355025-88-5

• 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: 3-(2-bromoacetyl)-6-chloro-8-methoxy-2H-chromen-2-one
• 英文别名: 3-(2-Bromoacetyl)-6-chloro-8-methoxychromen-2-one；3-(2-bromoacetyl)-6-chloro-8-methoxychromen-2-one
• CAS: 1355025-88-5
• 化学式: C₁₂H₈BrClO₄
• 分子量: 331.55
• InChiKey: PHPSSFZWPPNGIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2-bromoacetyl)-6-chloro-8-methoxy-2H-chromen-2-one 、 间氨基苯甲酸 在 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以72%的产率得到6-chloro-3-(2-(3-hydroxycarbonyl)phenylamino)acetyl-8-methoxy-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：

  3-acetyl-6-chloro-8-methoxy-2H-chromen-2-one 在 copper(ll) bromide 作用下， 以 氯仿 、 乙酸乙酯 为溶剂， 以59%的产率得到3-(2-bromoacetyl)-6-chloro-8-methoxy-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.