2',3'-p-methoxybenzylideneadenosine-5'-carboxylic acid | 1040912-32-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2',3'-p-methoxybenzylideneadenosine-5'-carboxylic acid
• 英文别名: 2',3'-p-anisylideneadenosine-5'-carboxylic acid
• CAS: 1040912-32-0
• 化学式: C₁₈H₁₇N₅O₆
• 分子量: 399.363
• InChiKey: WSFHHGZXKCZAJN-QNPJMSFTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.88
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  143.84
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  2',3'-p-methoxybenzylideneadenosine-5'-carboxylic acid 、 3-aminopropylcarboxamidomethylphosphonic acid diethyl ester hydrochloride 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.02h， 生成
  参考文献：
  名称：

  Selective Nucleoside Triphosphate Diphosphohydrolase-2 (NTPDase2) Inhibitors: Nucleotide Mimetics Derived from Uridine-5′-carboxamide

  摘要：

  Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases, subtypes 1, 2, 3, 8 of NTPDases) dephosphorylate nucleoside tri- and diphosphates to the corresponding di- and monophosphates. In the present study we synthesized adenine and uracil nucleotide mimetics, in which the phosphate residues were replaced by phosphonic acid esters attached to the nucleoside at the 5'-position by amide linkers. Among the synthesized uridine derivatives, we identified the first potent and selective inhibitors of human NTP`Dase2. The most potent compound was 19a (PSB-6426), which was a competitive inhibitor of NTPDase2 exhibiting a Ki value of 8.2,uM and selectivity versus other NTPDases. It was inactive toward uracil nuc leotide- activated P2Y2, P2Y4, and P2Y6 receptor subtypes. Compound 19a was chemically and metabolically highly stable. In contrast to the few known (unselective) NTPDase inhibitors, 19a is an uncharged molecule and may be perorally bioavailable. NTPDase2 inhibitors have potential as novel cardioprotective drugs for the treatment of stroke and for cancer therapy.

  DOI：

  10.1021/jm800175e
• 作为产物：
  描述：

  exo/endo-2',3'-O-p-methoxybenzylideneadenosine 在 2,2,6,6-四甲基哌啶氧化物 、 碘苯二乙酸 作用下， 以 水 、 乙腈 为溶剂， 反应 3.0h， 以71%的产率得到2',3'-p-methoxybenzylideneadenosine-5'-carboxylic acid
  参考文献：
  名称：

  Selective Nucleoside Triphosphate Diphosphohydrolase-2 (NTPDase2) Inhibitors: Nucleotide Mimetics Derived from Uridine-5′-carboxamide

  摘要：

  Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases, subtypes 1, 2, 3, 8 of NTPDases) dephosphorylate nucleoside tri- and diphosphates to the corresponding di- and monophosphates. In the present study we synthesized adenine and uracil nucleotide mimetics, in which the phosphate residues were replaced by phosphonic acid esters attached to the nucleoside at the 5'-position by amide linkers. Among the synthesized uridine derivatives, we identified the first potent and selective inhibitors of human NTP`Dase2. The most potent compound was 19a (PSB-6426), which was a competitive inhibitor of NTPDase2 exhibiting a Ki value of 8.2,uM and selectivity versus other NTPDases. It was inactive toward uracil nuc leotide- activated P2Y2, P2Y4, and P2Y6 receptor subtypes. Compound 19a was chemically and metabolically highly stable. In contrast to the few known (unselective) NTPDase inhibitors, 19a is an uncharged molecule and may be perorally bioavailable. NTPDase2 inhibitors have potential as novel cardioprotective drugs for the treatment of stroke and for cancer therapy.

  DOI：

  10.1021/jm800175e

文献信息

• Ectonucleotidase inhibitors
  申请人：Rheinische Friedrich-Wilhelms-Universität Bonn

  公开号：EP1860113A1

  公开（公告）日：2007-11-28

  Present invention provides ectonucleotidase (ecto-nucleotide triphosphate diphosphohydrolase, NTPDase) inhibitors represented by the following formula, namely nucleotide mimetics as selective NTPDase inhibitors. It also provides methods for preparations of said compounds. Furthermore provided are pharmaceutical and diagnostic compositions comprising said compounds, and the use of said compounds in a medicament for treating diseases associated with ectonucleotidase activity and/or P2 receptors.

  本发明提供了以下公式所代表的细胞核苷酸酶（细胞外核苷酸三磷酸二磷酸水解酶，NTPDase）抑制剂，即作为选择性NTPDase抑制剂的核苷酸类似物。还提供了制备上述化合物的方法。此外，还提供了包含上述化合物的药用和诊断组合物，以及将上述化合物用作治疗与细胞核苷酸酶活性和/或P2受体相关的疾病的药物的用途。