benzofuran-2-carboxylic acid (2-hydroxyethyl)amide | 306956-34-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: benzofuran-2-carboxylic acid (2-hydroxyethyl)amide
• 英文别名: N-(2-hydroxyethyl)-1-benzofuran-2-carboxamide
• CAS: 306956-34-3
• 化学式: C₁₁H₁₁NO₃
• mdl: MFCD12177917
• 分子量: 205.213
• InChiKey: ARJKZMYWWRWKPB-UHFFFAOYSA-N

物化性质

• 沸点：
  464.1±25.0 °C(Predicted)
• 密度：
  1.276±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  62.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzofuran-2-carboxylic acid (2-hydroxyethyl)amide 在 sodium hydride 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 WAY-170523
  参考文献：
  名称：

  Structure-Based Design of a Novel, Potent, and Selective Inhibitor for MMP-13 Utilizing NMR Spectroscopy and Computer-Aided Molecular Design

  摘要：

  The high-resolution NMR solution structure of the catalytic fragment of human collagenase-3 (MMP-13) was used as a starting point for structure-based design of selective inhibitors for MMP-13. The major structural difference observed between the MMP structures is the relative size and shape of the S1' pocket where this pocket is significantly longer for MMP-13, nearly reaching the surface of the protein. On the basis of the extended nature of the MMP-13 S1' pocket an inhibitor potent and selective for MMP-13 was designed from an initial high throughput screening (HTS) lead. CL-82198 was identified as a weak (10 muM) inhibitor against MMP-13 while demonstrating no activity against MMP-1, MMP-9, or the related enzyme TACE. The drug-Like properties of CL-82198 made it an ideal candidate for optimization of enzyme potency and selectivity. On the basis of NMR binding studies, it was shown that inhibitor CL-82198 bound within the entire S1' pocket of MMP-13 which is the basis of its selectivity against MMP-1, MMP-9, and TACE. A strategy utilizing this information was devised for designing new inhibitors that showed enhanced selectivity toward MMP-13. Our design strategy combined the critical selectivity features of CL-82198 with the known potency features of a nonspecific MMP inhibitor (WAY-152177) to generate a potent and selective MMP-13 inhibitor (WAY-170523). WAY-170523 has an IC50 of 17 nM for MMP-13 and showed > 5800-, 56-, and >500-fold selectivity against MMP-1 MMP-9, and TACE, respectively.

  DOI：

  10.1021/ja001547g
• 作为产物：
  描述：

  苯并呋喃-2-羧酸 、 C.I.酸性橙108 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.17h， 以43%的产率得到benzofuran-2-carboxylic acid (2-hydroxyethyl)amide
  参考文献：
  名称：

  Structure-Based Design of a Novel, Potent, and Selective Inhibitor for MMP-13 Utilizing NMR Spectroscopy and Computer-Aided Molecular Design

  摘要：

  The high-resolution NMR solution structure of the catalytic fragment of human collagenase-3 (MMP-13) was used as a starting point for structure-based design of selective inhibitors for MMP-13. The major structural difference observed between the MMP structures is the relative size and shape of the S1' pocket where this pocket is significantly longer for MMP-13, nearly reaching the surface of the protein. On the basis of the extended nature of the MMP-13 S1' pocket an inhibitor potent and selective for MMP-13 was designed from an initial high throughput screening (HTS) lead. CL-82198 was identified as a weak (10 muM) inhibitor against MMP-13 while demonstrating no activity against MMP-1, MMP-9, or the related enzyme TACE. The drug-Like properties of CL-82198 made it an ideal candidate for optimization of enzyme potency and selectivity. On the basis of NMR binding studies, it was shown that inhibitor CL-82198 bound within the entire S1' pocket of MMP-13 which is the basis of its selectivity against MMP-1, MMP-9, and TACE. A strategy utilizing this information was devised for designing new inhibitors that showed enhanced selectivity toward MMP-13. Our design strategy combined the critical selectivity features of CL-82198 with the known potency features of a nonspecific MMP inhibitor (WAY-152177) to generate a potent and selective MMP-13 inhibitor (WAY-170523). WAY-170523 has an IC50 of 17 nM for MMP-13 and showed > 5800-, 56-, and >500-fold selectivity against MMP-1 MMP-9, and TACE, respectively.

  DOI：

  10.1021/ja001547g

文献信息

• Structure-Based Design of a Novel, Potent, and Selective Inhibitor for MMP-13 Utilizing NMR Spectroscopy and Computer-Aided Molecular Design
  作者：James M. Chen、Frances C. Nelson、Jeremy I. Levin、Dominick Mobilio、Franklin J. Moy、Ramaswamy Nilakantan、Arie Zask、Robert Powers

  DOI：10.1021/ja001547g

  日期：2000.10.1

  The high-resolution NMR solution structure of the catalytic fragment of human collagenase-3 (MMP-13) was used as a starting point for structure-based design of selective inhibitors for MMP-13. The major structural difference observed between the MMP structures is the relative size and shape of the S1' pocket where this pocket is significantly longer for MMP-13, nearly reaching the surface of the protein. On the basis of the extended nature of the MMP-13 S1' pocket an inhibitor potent and selective for MMP-13 was designed from an initial high throughput screening (HTS) lead. CL-82198 was identified as a weak (10 muM) inhibitor against MMP-13 while demonstrating no activity against MMP-1, MMP-9, or the related enzyme TACE. The drug-Like properties of CL-82198 made it an ideal candidate for optimization of enzyme potency and selectivity. On the basis of NMR binding studies, it was shown that inhibitor CL-82198 bound within the entire S1' pocket of MMP-13 which is the basis of its selectivity against MMP-1, MMP-9, and TACE. A strategy utilizing this information was devised for designing new inhibitors that showed enhanced selectivity toward MMP-13. Our design strategy combined the critical selectivity features of CL-82198 with the known potency features of a nonspecific MMP inhibitor (WAY-152177) to generate a potent and selective MMP-13 inhibitor (WAY-170523). WAY-170523 has an IC50 of 17 nM for MMP-13 and showed > 5800-, 56-, and >500-fold selectivity against MMP-1 MMP-9, and TACE, respectively.