(2R,3R,4S)-2-(2-chloro-6-(3-chlorobenzylamino)-9H-purin-9-yl)tetrahydrothiophene-3,4-diol | 945457-84-1

• 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,4S)-2-(2-chloro-6-(3-chlorobenzylamino)-9H-purin-9-yl)tetrahydrothiophene-3,4-diol
• 英文别名: (2R,3R,4S)-2-(2-chloro-6-(3-chlorobenzylamino)-9H-purine-9-yl)tetrahydrothiophene-3,4-diol；(2R,3R,4S)-2-[2-chloro-6-[(3-chlorophenyl)methylamino]purin-9-yl]thiolane-3,4-diol
• CAS: 945457-84-1
• 化学式: C₁₆H₁₅Cl₂N₅O₂S
• 分子量: 412.299
• InChiKey: JQUBXCDDRXAMLF-IXPVHAAZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 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：
  121
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-氯苄胺 以83%的产率得到(2R,3R,4S)-2-(2-chloro-6-(3-chlorobenzylamino)-9H-purin-9-yl)tetrahydrothiophene-3,4-diol
  参考文献：
  名称：

  WO2008/108508

  摘要：

  公开号：

文献信息

• Polypharmacology of <i>N</i>⁶-(3-Iodobenzyl)adenosine-5′-<i>N</i>-methyluronamide (IB-MECA) and Related A₃ Adenosine Receptor Ligands: Peroxisome Proliferator Activated Receptor (PPAR) γ Partial Agonist and PPARδ Antagonist Activity Suggests Their Antidiabetic Potential
  作者：Jinha Yu、Seyeon Ahn、Hee Jin Kim、Moonyoung Lee、Sungjin Ahn、Jungmin Kim、Sun Hee Jin、Eunyoung Lee、Gyudong Kim、Jae Hoon Cheong、Kenneth A. Jacobson、Lak Shin Jeong、Minsoo Noh

  DOI：10.1021/acs.jmedchem.7b00805

  日期：2017.9.14

  A3 adenosine receptor (AR) ligands including A3 AR agonist, N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (1a, IB-MECA) were examined for adiponectin production in human bone marrow mesenchymal stem cells (hBM-MSCs). In this model, 1a significantly increased adiponectin production, which is associated with improved insulin sensitivity. However, A3 AR antagonists also promoted adiponectin production

  检查 A3 腺苷受体 (AR) 配体（包括 A3 AR 激动剂、N6-(3-碘苄基)腺苷-5'-N-甲基脲酰胺 (1a, IB-MECA)）在人骨髓间充质干细胞 (hBM-MSC) 中的脂联素生成情况）。在该模型中，1a 显着增加了脂联素的产生，这与胰岛素敏感性的改善有关。然而，A3 AR 拮抗剂也促进 hBM-MSC 中脂联素的产生，表明 A3 AR 途径可能不直接参与脂联素促进活性。在一项靶标解卷积研究中，它们的脂联素促进活性与其与过氧化物酶体增殖物激活受体 (PPAR) γ 和 PPARδ 的结合活性显着相关。它们既充当 PPARγ 部分激动剂又充当 PPARδ 拮抗剂。在糖尿病小鼠模型中，1a 及其结构类似物 A3 AR 拮抗剂显着降低血清葡萄糖和甘油三酯水平，支持其抗糖尿病潜力。这些发现表明，这些化合物的多药效团可以为它们针对各种人类疾病的多效功效提供治疗见解。
• 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。
• ADENOSINE DERIVATIVES, METHOD FOR THE SYNTHESIS THEREOF, AND THE PHARMACEUTICAL COMPOSITIONS FOR THE PREVENTION AND TREATMENT OF THE INFLAMMATORY DISEASES CONTAINING THE SAME AS AN ACTIVE INGREDIENT
  申请人：Jeong Lak Shin

  公开号：US20100137577A1

  公开（公告）日：2010-06-03

  Disclosed are adenosine derivatives, methods for the synthesis thereof, and pharmaceutical compositions for the prevention and treatment of inflammatory diseases, comprising the same as an active ingredient. The adenosine derivatives have high binding affinity and selectivity for adenosine receptors, especially for A3 adenosine receptors and act as A3 adenosine receptor antagonists, and exhibit anti-inflammatory activity. Thus, the adenosine derivatives are useful in the prevention and treatment of inflammatory diseases.

  本发明涉及腺苷衍生物、其合成方法和制备药物组合物，其作为活性成分用于预防和治疗炎症性疾病。该腺苷衍生物具有高结合亲和力和选择性，尤其是对A3腺苷受体具有高亲和力和选择性，并且作为A3腺苷受体拮抗剂，具有抗炎活性。因此，该腺苷衍生物在预防和治疗炎症性疾病方面具有用途。
• PHARMACEUTICAL COMPOSITION FOR PREVENTING AND TREATING NONALCOHOLIC STEATOHEPATITIS, HEPATIC FIBROSIS, AND LIVER CIRRHOSIS, COMPRISING ADENOSINE DERIVATIVES
  申请人：Future Medicine Co., Ltd.

  公开号：EP3533452A1

  公开（公告）日：2019-09-04

  A pharmaceutical composition for preventing or treating liver disease is provided. The pharmaceutical composition comprising a compound represented by formula 1 below or a pharmaceutically acceptable salt of the compound as an active ingredient: where A is S, R is a linear or branched C1-C5 alkyl which is non-substituted or is independently or selectively substituted with one or more C6-C10 aryl groups, a benzyl which is non-substituted or is independently or selectively substituted with halogen or one or more linear or branched C1-C4 alkoxy groups, or a hydroxycarbonyl-substituted benzyl, and Y is H or a halogen atom.

  提供了一种用于预防或治疗肝病的药物组合物。该药物组合物包含下式 1 所代表的化合物或该化合物的药学上可接受的盐作为活性成分： 其中 A 为 S，R 为非取代的或独立或选择性地被一个或多个 C6-C10 芳基取代的直链或支链 C1-C5 烷基，非取代的或独立或选择性地被卤素或一个或多个直链或支链 C1-C4 烷氧基取代的苄基，或羟羰基取代的苄基，Y 为 H 或卤原子。
• PHARMACEUTICAL COMPOSITION FOR PREVENTING AND TREATING GLAUCOMA, CONTAINING ADENOSINE DERIVATIVE
  申请人：Future Medicine Co., Ltd.

  公开号：EP3603647A1

  公开（公告）日：2020-02-05

  A pharmaceutical composition for preventing or treating eye diseases and an oral administration agent for preventing or treating eye diseases are provided. The pharmaceutical composition for preventing or treating eye diseases comprises the compound represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

  本发明提供了一种用于预防或治疗眼疾的药物组合物和一种用于预防或治疗眼疾的口服给药剂。用于预防或治疗眼疾的药物组合物包含化学式 1 所代表的化合物或其药学上可接受的盐作为活性成分。