(2R,3R,4R)-2-(2-chloro-6-(3-fluorobenzylamino)-9H-purin-9-yl)-tetrahydrofuran-3,4-diol | 1166277-96-8

• 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-(2-chloro-6-(3-fluorobenzylamino)-9H-purin-9-yl)-tetrahydrofuran-3,4-diol
• 英文别名: (2R,3R,4R)-2-[2-chloro-6-[(3-fluorophenyl)methylamino]purin-9-yl]oxolane-3,4-diol
• CAS: 1166277-96-8
• 化学式: C₁₆H₁₅ClFN₅O₃
• 分子量: 379.778
• InChiKey: JFCMTERYFDMKKL-IXPVHAAZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  26
• 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：

  2,6-dichloro-9-((3aR,4R,6aR)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purine 在 盐酸 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 15.0h， 生成 (2R,3R,4R)-2-(2-chloro-6-(3-fluorobenzylamino)-9H-purin-9-yl)-tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  A3腺苷受体结合亲和力与截短腺苷衍生物抗肾间质纤维化活性的相关性研究

  摘要：

  截短的 4'-硫代核苷 1-4 和 4'-氧代核苷 5-8 作为有效和选择性的 A3AR 拮抗剂分别由 d-甘露糖和 d-赤藓酸γ-内酯合成。评估了这些核苷在 TGF-β1 处理的小鼠近端肾小管 (mProx) 细胞中的抗纤维化肾脏保护活性。它们对 A3AR 的拮抗活性与它们对 mProx 细胞中 TGF-β1 诱导的胶原 I 上调的抑制活性成正比。该结果表明 A3AR 拮抗剂的结合亲和力与其抗纤维化活性密切相关。因此，A3AR 拮抗剂可能是治疗慢性肾病的新型候选药物。

  DOI：

  10.1007/s12272-018-1079-2

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.
• Correlation study between A3 adenosine receptor binding affinity and anti-renal interstitial fibrosis activity of truncated adenosine derivatives
  作者：Jinha Yu、Gyudong Kim、Dnyandev B. Jarhad、Hyuk Woo Lee、Jiyoun Lee、Chong Woo Park、Hunjoo Ha、Lak Shin Jeong

  DOI：10.1007/s12272-018-1079-2

  日期：2019.9

  (mProx) cells. Their antagonistic activities for A3AR were proportional to their inhibitory activities against TGF-β1-induced collagen I upregulation in mProx cells. This result suggests that the binding affinity of A3AR antagonists is closely correlated with their anti-fibrotic activity. Thus, A3AR antagonists might be novel therapeutic candidates for treating chronic kidney disease.

  截短的 4'-硫代核苷 1-4 和 4'-氧代核苷 5-8 作为有效和选择性的 A3AR 拮抗剂分别由 d-甘露糖和 d-赤藓酸γ-内酯合成。评估了这些核苷在 TGF-β1 处理的小鼠近端肾小管 (mProx) 细胞中的抗纤维化肾脏保护活性。它们对 A3AR 的拮抗活性与它们对 mProx 细胞中 TGF-β1 诱导的胶原 I 上调的抑制活性成正比。该结果表明 A3AR 拮抗剂的结合亲和力与其抗纤维化活性密切相关。因此，A3AR 拮抗剂可能是治疗慢性肾病的新型候选药物。