6-Methyl-1H-imidazo[1,2-a][1,3,5]triazine-2,4-dione | 899822-41-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 6-Methyl-1H-imidazo[1,2-a][1,3,5]triazine-2,4-dione
• 英文别名: 6-methylimidazo[1,2-a][1,3,5]triazine-2,4(1H,3H)-dione；6-methyl-1H-imidazo[1,2-a][1,3,5]triazine-2,4-dione
• CAS: 899822-41-4
• 化学式: C₆H₆N₄O₂
• 分子量: 166.139
• InChiKey: HTNSGUAKEYEURZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-Methyl-1H-imidazo[1,2-a][1,3,5]triazine-2,4-dione 在 sodium hydroxide 、 sodium hydride 、 二甲基亚砜 作用下， 以 丙酮 为溶剂， 反应 24.0h， 生成 Acetic acid (R)-5-(1,6-dimethyl-2,4-dioxo-1,2-dihydro-imidazo[1,2-a][1,3,5]triazin-3-yl)-1-methyl-pentyl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of lisofylline (LSF) analogs as a potential treatment for Type 1 diabetes

  摘要：

  Lisofylline (LSF, 1-(5-R-hydroxyhexyl)-3,7-dimethylxanthine) is an anti-inflammatory agent that protects beta-cells from Th1 cytokine-induced dysfunction and reduces the onset of Type I diabetes in non-obese diabetic (NOD) mice. Due to its low potency, poor oral bioavailability, and short half-life, the widespread clinical utility of LSF may be limited. Our goal has been to develop new agents based on the LSF structural motif that resolve the potency and pharmacokinetic liabilities of LSF. In this study, we have generated a focused library of LSF analogs that maintain the side chain (5-R-hydroxyhexyl) constant, while substituting a variety of nitrogen-containing heterocyclic substructures for the xanthine moiety of LSF. This library includes the xanthine-like (5-aza-7-deazaxanthine), as well as non-xanthine-like skeletons. The LSF analogs were evaluated in a pancreatic P-cell line for the effects on apoptosis protection and insulin release. The metabolic stability of selected compounds was also tested. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.036
• 作为产物：
  描述：

  6-(2-Oxo-propylamino)-1H-[1,3,5]triazine-2,4-dione 在 硫酸 作用下， 反应 1.5h， 以35%的产率得到6-Methyl-1H-imidazo[1,2-a][1,3,5]triazine-2,4-dione
  参考文献：
  名称：

  Synthesis and biological evaluation of lisofylline (LSF) analogs as a potential treatment for Type 1 diabetes

  摘要：

  Lisofylline (LSF, 1-(5-R-hydroxyhexyl)-3,7-dimethylxanthine) is an anti-inflammatory agent that protects beta-cells from Th1 cytokine-induced dysfunction and reduces the onset of Type I diabetes in non-obese diabetic (NOD) mice. Due to its low potency, poor oral bioavailability, and short half-life, the widespread clinical utility of LSF may be limited. Our goal has been to develop new agents based on the LSF structural motif that resolve the potency and pharmacokinetic liabilities of LSF. In this study, we have generated a focused library of LSF analogs that maintain the side chain (5-R-hydroxyhexyl) constant, while substituting a variety of nitrogen-containing heterocyclic substructures for the xanthine moiety of LSF. This library includes the xanthine-like (5-aza-7-deazaxanthine), as well as non-xanthine-like skeletons. The LSF analogs were evaluated in a pancreatic P-cell line for the effects on apoptosis protection and insulin release. The metabolic stability of selected compounds was also tested. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.036

文献信息

• Synthesis and biological evaluation of lisofylline (LSF) analogs as a potential treatment for Type 1 diabetes
  作者：Peng Cui、Timothy L. Macdonald、Meng Chen、Jerry L. Nadler

  DOI：10.1016/j.bmcl.2006.04.036

  日期：2006.7

  Lisofylline (LSF, 1-(5-R-hydroxyhexyl)-3,7-dimethylxanthine) is an anti-inflammatory agent that protects beta-cells from Th1 cytokine-induced dysfunction and reduces the onset of Type I diabetes in non-obese diabetic (NOD) mice. Due to its low potency, poor oral bioavailability, and short half-life, the widespread clinical utility of LSF may be limited. Our goal has been to develop new agents based on the LSF structural motif that resolve the potency and pharmacokinetic liabilities of LSF. In this study, we have generated a focused library of LSF analogs that maintain the side chain (5-R-hydroxyhexyl) constant, while substituting a variety of nitrogen-containing heterocyclic substructures for the xanthine moiety of LSF. This library includes the xanthine-like (5-aza-7-deazaxanthine), as well as non-xanthine-like skeletons. The LSF analogs were evaluated in a pancreatic P-cell line for the effects on apoptosis protection and insulin release. The metabolic stability of selected compounds was also tested. (c) 2006 Elsevier Ltd. All rights reserved.