4-phenylamino-N7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸
• 英文名称: 4-phenylamino-N7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
• 英文别名: 2-Hydroxymethyl-5-(4-phenylamino-pyrrolo[2,3-d]pyrimidin-7-yl)-tetrahydro-furan-3,4-diol；(2R,3R,4S,5R)-2-(4-anilinopyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• 化学式: C₁₇H₁₈N₄O₄
• 分子量: 342.354
• InChiKey: BOYZSDZEODWABV-VMUDFCTBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  113
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-chloro-5-iodo-7-(5'-O-tert-butyldimethylsilyl-2',3'-O-isopropylidene-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine 在 10percent Pd/C 氢气 、 sodium acetate 作用下， 以 甲醇 、 乙醇 为溶剂， 20.0 ℃ 、137.9 kPa 条件下， 反应 36.75h， 生成 4-phenylamino-N7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Adenosine Kinase Inhibitors. 2. Synthesis, Enzyme Inhibition, and Antiseizure Activity of Diaryltubercidin Analogues

  摘要：

  In the preceding article (Ugarkar et al. J. Med. Chem. 2000, 43) we reported that analogues of tubercidin are potent adenosine kinase (AK) inhibitors with antiseizure activity in the rat maximum electroshock (MES) model. Despite the discovery of several highly potent AK inhibitors (AKIs), e.g., 5'-amino-5'-deoxy-5-iodotubercidin (1c) (IC50 = 0.0006 mu M), no compounds were identified that exhibited a safety, efficacy, and side effect profile suitable for further development. In this article, we demonstrate that substitution of the tubercidin molecule with aromatic rings at the N4- and the C5-positions not only retains AKI potency but also improves in vivo activity. Synthesis of such compounds entailed transformation of 4-arylanlino-5-iodotubercidin analogues to their corresponding 5-aryl derivatives via the Suzuki reaction. Alternatively, 4-N-suylamino-5-arylpyrrolo[2,3-d]pyrimdine bases were constructed and then glycosylated with appropriately protected alpha-ribofuranosyl chlorides using a phase-transfer catalyst. Several compounds exhibited potent activity in the rat MES seizure assay with ED(50)s less than or equal to 2.0 mg/kg, ip, and showed relatively mild side effects.

  DOI：

  10.1021/jm0000259

文献信息

• N-modification of 7-Deazapurine nucleoside analogues as Anti-Trypanosoma cruzi and anti-Leishmania agents: Structure-activity relationship exploration and In vivo evaluation
  作者：Cai Lin、Denise da Gama Jaén Batista、Ana Lia Mazzeti、Roberson Donola Girão、Gabriel Melo de Oliveira、Izet Karalic、Fabian Hulpia、Maria de Nazaré C. Soeiro、Louis Maes、Guy Caljon、Serge Van Calenbergh

  DOI：10.1016/j.ejmech.2022.114165

  日期：2022.3
• Adenosine Kinase Inhibitors. 2. Synthesis, Enzyme Inhibition, and Antiseizure Activity of Diaryltubercidin Analogues
  作者：Bheemarao G. Ugarkar、Angelo J. Castellino、Jay M. DaRe、Joseph J. Kopcho、James B. Wiesner、Juergen M. Schanzer、Mark D. Erion

  DOI：10.1021/jm0000259

  日期：2000.7.1

  In the preceding article (Ugarkar et al. J. Med. Chem. 2000, 43) we reported that analogues of tubercidin are potent adenosine kinase (AK) inhibitors with antiseizure activity in the rat maximum electroshock (MES) model. Despite the discovery of several highly potent AK inhibitors (AKIs), e.g., 5'-amino-5'-deoxy-5-iodotubercidin (1c) (IC50 = 0.0006 mu M), no compounds were identified that exhibited a safety, efficacy, and side effect profile suitable for further development. In this article, we demonstrate that substitution of the tubercidin molecule with aromatic rings at the N4- and the C5-positions not only retains AKI potency but also improves in vivo activity. Synthesis of such compounds entailed transformation of 4-arylanlino-5-iodotubercidin analogues to their corresponding 5-aryl derivatives via the Suzuki reaction. Alternatively, 4-N-suylamino-5-arylpyrrolo[2,3-d]pyrimdine bases were constructed and then glycosylated with appropriately protected alpha-ribofuranosyl chlorides using a phase-transfer catalyst. Several compounds exhibited potent activity in the rat MES seizure assay with ED(50)s less than or equal to 2.0 mg/kg, ip, and showed relatively mild side effects.