1,6-Dimethyl-1H-imidazo[1,2-a][1,3,5]triazine-2,4-dione | 899822-42-5

• 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: 1,6-Dimethyl-1H-imidazo[1,2-a][1,3,5]triazine-2,4-dione
• 英文别名: 1,6-Dimethylimidazo[1,2-a][1,3,5]triazine-2,4-dione
• CAS: 899822-42-5
• 化学式: C₇H₈N₄O₂
• 分子量: 180.166
• InChiKey: YUADJALKCCQTLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,6-Dimethyl-1H-imidazo[1,2-a][1,3,5]triazine-2,4-dione 在 盐酸 、 甲醇 、 sodium hydride 、 二甲基亚砜 作用下， 以 乙醚 为溶剂， 反应 12.0h， 生成 3-((R)-5-Hydroxy-hexyl)-1,6-dimethyl-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
• 作为产物：
  描述：

  6-(2-Oxo-propylamino)-1H-[1,3,5]triazine-2,4-dione 在 sodium hydroxide 、 硫酸 作用下， 以 丙酮 为溶剂， 反应 25.5h， 生成 1,6-Dimethyl-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

• LISOFYLLINE ANALOGS AND METHODS FOR USE
  申请人：Macdonald Timothy L.

  公开号：US20100105690A1

  公开（公告）日：2010-04-29

  Analogs of a Lisofylline (LSF), and synthetic methods for the preparation of such analogs are provided. The analogs of LSF provided have the ability to protect cell viability, particularly the ability to protect pancreatic β-cells.

  提供了Lisofylline（LSF）的类似物以及制备这些类似物的合成方法。所提供的LSF类似物具有保护细胞存活能力，特别是保护胰岛β细胞的能力。
• Lisofylline analogues and their pharmeacuetical uses
  申请人：University Of Virginia Patent Foundation

  公开号：EP2325169A2

  公开（公告）日：2011-05-25

  The present invention provides analogs of a Lysofylline (LSF), and synthetic methods for the preparation of such analogs. The have the active side chain moiety (5-R-hydroxyhexyl) of LSF and can have greater potency and oral bioavailability than LSF.

  本发明提供了 Lysofylline（LSF）的类似物以及制备此类类似物的合成方法。这些类似物具有 LSF 的活性侧链分子（5-R-羟基己基），其效力和口服生物利用度均高于 LSF。
• LISOFYLLINE ANALOGUES AND THEIR PHARMEACUETICAL USES
  申请人：UNIVERSITY OF VIRGINIA PATENT FOUNDATION

  公开号：EP1919867B1

  公开（公告）日：2011-08-17
• US8481580B2
  申请人：——

  公开号：US8481580B2

  公开（公告）日：2013-07-09
• US8871764B2
  申请人：——

  公开号：US8871764B2

  公开（公告）日：2014-10-28