7-(3-(4-(2-fluoroethoxy)phenyl)propyl)-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine | 1254187-11-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: 7-(3-(4-(2-fluoroethoxy)phenyl)propyl)-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine
• 英文别名: 10-[3-[4-(2-Fluoroethoxy)phenyl]propyl]-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-7-amine
• CAS: 1254187-11-5
• 化学式: C₂₁H₂₀FN₇O₂
• 分子量: 421.434
• InChiKey: YIXGUARFUYFZQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-(2-呋喃基)-7-[3-(4-甲氧基苯基)丙基]-7H-吡唑并[4,3-e][1,2,4]噻唑并[1,5-c]嘧啶-5-胺 在 三溴化硼 、 caesium carbonate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 7-(3-(4-(2-fluoroethoxy)phenyl)propyl)-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine
  参考文献：
  名称：

  Development of [¹⁸F]-Labeled Pyrazolo[4,3-e]-1,2,4- triazolo[1,5-c]pyrimidine (SCH442416) Analogs for the Imaging of Cerebral Adenosine A_2A Receptors with Positron Emission Tomography

  摘要：

  Cerebral adenosine A2A receptors (A2ARs) are attractive therapeutic targets for the treatment of neurodegenerative and psychiatric disorders. We developed high affinity and selective compound 8 (SCH442416) analogs as in vivo probes for A2ARs using PET. We observed the A2AR-mediated accumulation of [18F]fluoropropyl ([18F]-10b) and [18F]fluoroethyl ([18F]-10a) derivatives of 8 in the brain. The striatum was clearly visualized in PET and in vitro autoradiography images of control animals and was no longer visible after pretreatment with the A2AR subtype-selective antagonist KW6002. In vitro and in vivo metabolite analyses indicated the presence of hydrophilic (radio)metabolite(s), which are not expected to cross the blood-brain-barrier. [18F]-10b and [18F]-10a showed comparable striatum-to- cerebellum ratios (4.6 at 25 and 37 min post injection, respectively) and reversible binding in rat brains. We concluded that these compounds performed equally well, but their kinetics were slightly different. These molecules are potential tools for mapping cerebral A2ARs with PET.

  DOI：

  10.1021/jm500700y

文献信息

• Synthesis and evaluation of 1,2,4-triazolo[1,5-c]pyrimidine derivatives as A2A receptor-selective antagonists
  作者：Bidhan A. Shinkre、T. Santhosh Kumar、Zhan-Guo Gao、Francesca Deflorian、Kenneth A. Jacobson、William C. Trenkle

  DOI：10.1016/j.bmcl.2010.08.021

  日期：2010.10

  Movement disorders such as Parkinson’s disease and Huntington’s disease are serious life-limiting and debilitating movement disorders. Their onset typically occurs from mid-life to late in life, and effective diagnostic techniques for detecting and following the disease course are lacking. Our goal is to develop receptor imaging agents for positron emission tomography (PET) that selectively target

  帕金森病和亨廷顿病等运动障碍是严重的限制生命和使人衰弱的运动障碍。它们的发病通常发生在中年至晚年，并且缺乏用于检测和跟踪病程的有效诊断技术。我们的目标是开发用于正电子发射断层扫描 (PET) 的受体显像剂，它选择性地靶向在纹状体中高度表达的最相关的腺苷受体 (AR) 亚型，即 A 2A AR。为了进一步实现这一目标，我们已经合成并在药理学上表征了一系列高亲和力 A 2A AR 配体，基于已知的拮抗剂 SCH 442416 (R = -Me)，其末端具有结构可变性 (R = -Et, -一世-Pr、-allyl 等）。适合用作PET示踪剂的O-氟乙基类似物的K i值为12.4 nM，并且与A 1和A 3 AR相比对A 2A AR具有高度选择性。
• Development of [¹⁸F]-Labeled Pyrazolo[4,3-<i>e</i>]-1,2,4- triazolo[1,5-<i>c</i>]pyrimidine (SCH442416) Analogs for the Imaging of Cerebral Adenosine A_2A Receptors with Positron Emission Tomography
  作者：Shivashankar Khanapur、Soumen Paul、Anup Shah、Suresh Vatakuti、Michel J. B. Koole、Rolf Zijlma、Rudi A. J. O. Dierckx、Gert Luurtsema、Prabha Garg、Aren van Waarde、Philip H. Elsinga

  DOI：10.1021/jm500700y

  日期：2014.8.14

  Cerebral adenosine A2A receptors (A2ARs) are attractive therapeutic targets for the treatment of neurodegenerative and psychiatric disorders. We developed high affinity and selective compound 8 (SCH442416) analogs as in vivo probes for A2ARs using PET. We observed the A2AR-mediated accumulation of [18F]fluoropropyl ([18F]-10b) and [18F]fluoroethyl ([18F]-10a) derivatives of 8 in the brain. The striatum was clearly visualized in PET and in vitro autoradiography images of control animals and was no longer visible after pretreatment with the A2AR subtype-selective antagonist KW6002. In vitro and in vivo metabolite analyses indicated the presence of hydrophilic (radio)metabolite(s), which are not expected to cross the blood-brain-barrier. [18F]-10b and [18F]-10a showed comparable striatum-to- cerebellum ratios (4.6 at 25 and 37 min post injection, respectively) and reversible binding in rat brains. We concluded that these compounds performed equally well, but their kinetics were slightly different. These molecules are potential tools for mapping cerebral A2ARs with PET.