(2R,3R,4R)-2-(6-(3-fluorobenzylamino)-9H-purin-9-yl)tetrahydrofuran-3,4-diol | 1166277-74-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (2R,3R,4R)-2-(6-(3-fluorobenzylamino)-9H-purin-9-yl)tetrahydrofuran-3,4-diol
• 英文别名: (2R,3R,4R)-2-[6-[(3-fluorophenyl)methylamino]purin-9-yl]oxolane-3,4-diol
• CAS: 1166277-74-2
• 化学式: C₁₆H₁₆FN₅O₃
• 分子量: 345.333
• InChiKey: QPLGLUVUMGUTTI-AXAPSJFSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氟苄胺 、 (2R,3R,4R)-2-(6-chloropurin-9-yl)oxolane-3,4-diol 以 乙醇 为溶剂， 以80%的产率得到(2R,3R,4R)-2-(6-(3-fluorobenzylamino)-9H-purin-9-yl)tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  Structure–activity relationships of truncated adenosine derivatives as highly potent and selective human A3 adenosine receptor antagonists

  摘要：

  On the basis of potent and selective binding affinity of truncated 4'-thioadenosine derivatives at the human A(3) adenosine receptor (AR), their bioisosteric 4'-oxo derivatives were designed and synthesized from commercially available 2,3-O-isopropylidene-D-erythrono lactone. The derivatives tested in AR binding assays were substituted at the C2 and N-6 positions. All synthesized nucleosides exhibited potent and selective binding affinity at the human A(3) AR. They were less potent than the corresponding 4'-thio analogues, but showed still selective to other subtypes. The 2-Cl series generally were better than the 2-H series in view of binding affinity and selectivity. Among compounds tested, compound 5d (X=Cl, R=3-bromobenzyl) showed the highest binding affinity (K-i = 13.0 +/- 6.9 nM) at the hA(3) AR with high selectivity (at least 88-fold) in comparison to other AR subtypes. Like the corresponding truncated 4'-thio series, compound 5d antagonized the action of an agonist to inhibit forskolin-stimulated adenylate cyclase in hA(3) AR-expressing CHO cells. Although the 4'-oxo series were less potent than the 4'-thio series, this class of human A(3) AR antagonists is also regarded as another good template for the design of A(3) AR antagonists and for further drug development. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.03.034

文献信息

• Structure–activity relationships of truncated adenosine derivatives as highly potent and selective human A3 adenosine receptor antagonists
  作者：Shantanu Pal、Won Jun Choi、Seung Ah Choe、Cara L. Heller、Zhan-Guo Gao、Moshe Chinn、Kenneth A. Jacobson、Xiyan Hou、Sang Kook Lee、Hea Ok Kim、Lak Shin Jeong

  DOI：10.1016/j.bmc.2009.03.034

  日期：2009.5

  On the basis of potent and selective binding affinity of truncated 4'-thioadenosine derivatives at the human A(3) adenosine receptor (AR), their bioisosteric 4'-oxo derivatives were designed and synthesized from commercially available 2,3-O-isopropylidene-D-erythrono lactone. The derivatives tested in AR binding assays were substituted at the C2 and N-6 positions. All synthesized nucleosides exhibited potent and selective binding affinity at the human A(3) AR. They were less potent than the corresponding 4'-thio analogues, but showed still selective to other subtypes. The 2-Cl series generally were better than the 2-H series in view of binding affinity and selectivity. Among compounds tested, compound 5d (X=Cl, R=3-bromobenzyl) showed the highest binding affinity (K-i = 13.0 +/- 6.9 nM) at the hA(3) AR with high selectivity (at least 88-fold) in comparison to other AR subtypes. Like the corresponding truncated 4'-thio series, compound 5d antagonized the action of an agonist to inhibit forskolin-stimulated adenylate cyclase in hA(3) AR-expressing CHO cells. Although the 4'-oxo series were less potent than the 4'-thio series, this class of human A(3) AR antagonists is also regarded as another good template for the design of A(3) AR antagonists and for further drug development. (C) 2009 Elsevier Ltd. All rights reserved.