(+/-)-2-furan-2-yl-5-(octahydro-pyrido[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: (+/-)-2-furan-2-yl-5-(octahydro-pyrido[1,2-a]pyrazin-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ylamine
• 英文别名: 5-(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: C₁₆H₂₀N₈O
• 分子量: 340.388
• InChiKey: AXRFXIIGLMCJFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  八氢吡啶并[1,2-a]吡嗪 、 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 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以90%的产率得到(+/-)-2-furan-2-yl-5-(octahydro-pyrido[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

• A2a adenosine receptor antagonists
  申请人：Peng Hairuo

  公开号：US20070173505A1

  公开（公告）日：2007-07-26

  The invention is based on the discovery that compounds of formula (I) possess unexpectedly high affinity for the A 2a adenosine receptor, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including Parkinson's disease. In one embodiment, the invention features a compound of formula (I).

  本发明基于发现，式（I）化合物具有意外的高亲和力，可用作A2a腺苷受体的拮抗剂，用于预防和/或治疗多种疾病，包括帕金森病。在一种实施例中，本发明涉及式（I）化合物。
• A2A ADENOSINE RECEPTOR ANTAGONISTS
  申请人：Biogen Idec MA Inc.

  公开号：EP1633756A2

  公开（公告）日：2006-03-15
• US7834014B2
  申请人：——

  公开号：US7834014B2

  公开（公告）日：2010-11-16
• [EN] A2A ADENOSINE RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RECEPTEUR D'ADENOSINE A2A
  申请人：BIOGEN IDEC INC

  公开号：WO2004092173A2

  公开（公告）日：2004-10-28

  The invention is based on the discovery that compounds of formula (I) possess unexpectedly high affinity for the A2a adenosine receptor, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including Parkinson's disease. In one embodiment, the invention features a compound of formula (I).
• 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.