5-(2-ethoxyethyl)-5-(6-(4-fluorophenoxy)pyridin-3-yloxy)pyrimidine-2,4,6(1H,3H,5H)-trione | 959985-16-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(2-ethoxyethyl)-5-(6-(4-fluorophenoxy)pyridin-3-yloxy)pyrimidine-2,4,6(1H,3H,5H)-trione
• 英文别名: 5-(2-ethoxyethyl)-5-[6-(4-fluorophenoxy)pyridin-3-yl]oxy-1,3-diazinane-2,4,6-trione
• CAS: 959985-16-1
• 化学式: C₁₉H₁₈FN₃O₆
• 分子量: 403.367
• InChiKey: VPVGVAGTYSVBFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  6-(4-氟苯氧基)吡啶-3-醇 、 5-bromo-5-(2-ethoxy-ethyl)-pyrimidine-2,4,6-trione 生成 5-(2-ethoxyethyl)-5-(6-(4-fluorophenoxy)pyridin-3-yloxy)pyrimidine-2,4,6(1H,3H,5H)-trione
  参考文献：
  名称：

  Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13

  摘要：

  Explorations in the pyrimidinetrione series of MMP-13 inhibitors led to the discovery of a series of spiro-fused compounds that are potent and selective inhibitiors of MMP-13. While other spiro-fused motifs are hydrolytically unstable, presumably due to electronic destabilization of the pyrimidinetrione ring, the spiropyrrolidine series does not share this liability. Greater than 100-fold selectivity versus other MMP family members was achieved by incorporation of an extended aryl-heteroaryl P1' group. When dosed as the sodium salt, these compounds displayed excellent oral absorption and pharmacokinetic properties. Despite the selectivity, a representative of this series produced fibroplasia in a 14 day rat study. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.09.085

文献信息

• Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13
  作者：Kevin D. Freeman-Cook、Lawrence A. Reiter、Mark C. Noe、Amy S. Antipas、Dennis E. Danley、Kaushik Datta、James T. Downs、Shane Eisenbeis、James D. Eskra、David J. Garmene、Elaine M. Greer、Richard J. Griffiths、Roberto Guzman、Joel R. Hardink、Fouad Janat、Christopher S. Jones、Gary J. Martinelli、Peter G. Mitchell、Ellen R. Laird、Jennifer L. Liras、Lori L. Lopresti-Morrow、Jayvardhan Pandit、Usa D. Reilly、Donald Robertson、Marcie L. Vaughn-Bowser、Lilli A. Wolf-Gouviea、Sue A. Yocum

  DOI：10.1016/j.bmcl.2007.09.085

  日期：2007.12

  Explorations in the pyrimidinetrione series of MMP-13 inhibitors led to the discovery of a series of spiro-fused compounds that are potent and selective inhibitiors of MMP-13. While other spiro-fused motifs are hydrolytically unstable, presumably due to electronic destabilization of the pyrimidinetrione ring, the spiropyrrolidine series does not share this liability. Greater than 100-fold selectivity versus other MMP family members was achieved by incorporation of an extended aryl-heteroaryl P1' group. When dosed as the sodium salt, these compounds displayed excellent oral absorption and pharmacokinetic properties. Despite the selectivity, a representative of this series produced fibroplasia in a 14 day rat study. (c) 2007 Elsevier Ltd. All rights reserved.