5-(4-phenoxyphenyl)-5-(4-(2-nitrooxy-ethyl)piperazin-1-yl)-pyrimidine-2,4,6(1H,3H,5H)-trione | 1360880-37-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(4-phenoxyphenyl)-5-(4-(2-nitrooxy-ethyl)piperazin-1-yl)-pyrimidine-2,4,6(1H,3H,5H)-trione
• 英文别名: 2-[4-[2,4,6-Trioxo-5-(4-phenoxyphenyl)-1,3-diazinan-5-yl]piperazin-1-yl]ethyl nitrate
• CAS: 1360880-37-0
• 化学式: C₂₂H₂₃N₅O₇
• 分子量: 469.454
• InChiKey: GBVUVWPIAISPTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  5-bromo-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 、 1-哌嗪乙醇硝酸酯 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以42%的产率得到5-(4-phenoxyphenyl)-5-(4-(2-nitrooxy-ethyl)piperazin-1-yl)-pyrimidine-2,4,6(1H,3H,5H)-trione
  参考文献：
  名称：

  Design of Barbiturate–Nitrate Hybrids that Inhibit MMP-9 Activity and Secretion

  摘要：

  We describe a new type of barbiturate-based matrix metalloproteinase (MMP) inhibitor incorporating a nitric oxide (NO) donor/mimetic group (series 1). The compounds were designed to inhibit MMP at enzyme level and to attenuate MMP-9 secretion arising from inflammatory signaling. To detect effects related to the nitrate, we prepared and studied an analogous series of barbiturate C5-alkyl alcohols that were unable to release NO (series 2). Both series inhibited recombinant human MMP-2/9 activity with nanomolar potency. Series 1 consistently inhibited the secretion of MMP-9 from TNF alpha/IL1 beta stimulated Caco-2 cells at 10 mu M, which could be attributed to NO related effects because the non-nitrate panel did not affect enzyme levels. Several compounds from series 1 (10 mu M) inhibited tumor cell invasion but none from the non-nitrate panel did. The work shows that MMP-inhibitory barbiturates are suitable scaffolds for hybrid design, targeting additional facets of MMP pathophysiology, with potential to improve risk-benefit ratios.

  DOI：

  10.1021/jm201352k

文献信息

• Design of Barbiturate–Nitrate Hybrids that Inhibit MMP-9 Activity and Secretion
  作者：Jun Wang、Shane O’Sullivan、Shona Harmon、Ray Keaveny、Marek W. Radomski、Carlos Medina、John F. Gilmer

  DOI：10.1021/jm201352k

  日期：2012.3.8

  We describe a new type of barbiturate-based matrix metalloproteinase (MMP) inhibitor incorporating a nitric oxide (NO) donor/mimetic group (series 1). The compounds were designed to inhibit MMP at enzyme level and to attenuate MMP-9 secretion arising from inflammatory signaling. To detect effects related to the nitrate, we prepared and studied an analogous series of barbiturate C5-alkyl alcohols that were unable to release NO (series 2). Both series inhibited recombinant human MMP-2/9 activity with nanomolar potency. Series 1 consistently inhibited the secretion of MMP-9 from TNF alpha/IL1 beta stimulated Caco-2 cells at 10 mu M, which could be attributed to NO related effects because the non-nitrate panel did not affect enzyme levels. Several compounds from series 1 (10 mu M) inhibited tumor cell invasion but none from the non-nitrate panel did. The work shows that MMP-inhibitory barbiturates are suitable scaffolds for hybrid design, targeting additional facets of MMP pathophysiology, with potential to improve risk-benefit ratios.