(7RS,9aRS)-2-furan-2-yl-5-[7-(pyridin-3-yloxymethyl)octahydropyrido[1,2-a]pyrazin-2-yl][1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (7RS,9aRS)-2-furan-2-yl-5-[7-(pyridin-3-yloxymethyl)octahydropyrido[1,2-a]pyrazin-2-yl][1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine
• 英文别名: (7RS,9aRS)-2-furan-2-yl-5-[7-(pyridin-3-yloxymethyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine；5-[(7S,9aS)-7-(pyridin-3-yloxymethyl)-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl]-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-amine
• 化学式: C₂₂H₂₅N₉O₂
• 分子量: 447.5
• InChiKey: KHVFGJJNDRNHLI-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  7-氨基-2-(2-呋喃基)-5-甲基磺酰基-[1,2,4]噻唑并[1,5-a][1,3,5]三嗪 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 (7RS,9aRS)-2-furan-2-yl-5-[7-(pyridin-3-yloxymethyl)octahydropyrido[1,2-a]pyrazin-2-yl][1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine
  参考文献：
  名称：

  Novel Bicyclic Piperazine Derivatives of Triazolotriazine and Triazolopyrimidines as Highly Potent and Selective Adenosine A_2A Receptor Antagonists

  摘要：

  A series of bicyclic piperazine derivatives of triazolotriazine and triazolopyrimidines was synthesized. Some of these analogues show high affinity and excellent selectivity for adenosine A(2a) receptor versus the adenosine A(1) receptor. Structure-activity-relationship (SAR) studies based on octahydropyrrolo[1,2-a]pyrazine and octahydropyrido[1,2-a]pyrazine with various capping groups are reported. Among these analogues, the most potent and selective A(2a) antagonist 26h has a K-i value of 0.2 nM and is 16500-fold selective with respect to the A(1) receptor. Among a number of compounds tested, compounds 21a and 21c exhibited significantly improved metabolic stability. Compounds 21a, 21c, and 18a showed good oral efficacy in rodent catalepsy models of Parkinson's disease.

  DOI：

  10.1021/jm0494321

文献信息

• Novel Bicyclic Piperazine Derivatives of Triazolotriazine and Triazolopyrimidines as Highly Potent and Selective Adenosine A₂_A Receptor Antagonists
  作者：Hairuo Peng、Gnanasambandam Kumaravel、Gang Yao、Li Sha、Joy Wang、Herman Van Vlijmen、Tonika Bohnert、Carol Huang、Chi B. Vu、Carol L. Ensinger、Hexi Chang、Thomas M. Engber、Eric T. Whalley、Russell C. Petter

  DOI：10.1021/jm0494321

  日期：2004.12.1

  A series of bicyclic piperazine derivatives of triazolotriazine and triazolopyrimidines was synthesized. Some of these analogues show high affinity and excellent selectivity for adenosine A(2a) receptor versus the adenosine A(1) receptor. Structure-activity-relationship (SAR) studies based on octahydropyrrolo[1,2-a]pyrazine and octahydropyrido[1,2-a]pyrazine with various capping groups are reported. Among these analogues, the most potent and selective A(2a) antagonist 26h has a K-i value of 0.2 nM and is 16500-fold selective with respect to the A(1) receptor. Among a number of compounds tested, compounds 21a and 21c exhibited significantly improved metabolic stability. Compounds 21a, 21c, and 18a showed good oral efficacy in rodent catalepsy models of Parkinson's disease.