2-[(2-chloro-9-isopropyl-9H-purin-6-ylamino)-methyl]-4-fluorophenol | 1427518-63-5

• 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: 2-[(2-chloro-9-isopropyl-9H-purin-6-ylamino)-methyl]-4-fluorophenol
• 英文别名: 2-[[(2-Chloro-9-propan-2-ylpurin-6-yl)amino]methyl]-4-fluorophenol；2-[[(2-chloro-9-propan-2-ylpurin-6-yl)amino]methyl]-4-fluorophenol
• CAS: 1427518-63-5
• 化学式: C₁₅H₁₅ClFN₅O
• 分子量: 335.768
• InChiKey: NKVXHKNKNZBQSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  75.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-氨基丁醇 、 2-[(2-chloro-9-isopropyl-9H-purin-6-ylamino)-methyl]-4-fluorophenol 反应 3.0h， 以82%的产率得到4-fluoro-2-[[[2-[[(2R)-1-hydroxybutan-2-yl]amino]-9-propan-2-ylpurin-6-yl]amino]methyl]phenol
  参考文献：
  名称：

  Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases

  摘要：

  Several inhibitors of cyclin-dependent kinases (CDKs), including the 2,6,9-trisubstituted purine derivative roscovitine, are currently being evaluated in clinical trials as potential anticancer drugs. Here, we describe a new series of roscovitine derivatives that show increased potency in vitro. The series was tested for cytotoxicity against six cancer cell lines and for inhibition of CDKs. For series bearing 2-(hydroxyalkylamino) moiety, cytotoxic potency strongly correlated with anti-CDK2 activity. Importantly, structural changes that increase biochemical and anticancer activities of these compounds also increase elimination half-life. The most potent compounds were investigated further to assess their ability to influence cell cycle progression, p53-regulated transcription and apoptosis. All the observed biological effects were consistent with inhibition of CDKs involved in the regulation of cell cycle and transcription. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.036
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 偶氮二甲酸二异丙酯 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 丙醇 为溶剂， 反应 6.0h， 生成 2-[(2-chloro-9-isopropyl-9H-purin-6-ylamino)-methyl]-4-fluorophenol
  参考文献：
  名称：

  Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases

  摘要：

  Several inhibitors of cyclin-dependent kinases (CDKs), including the 2,6,9-trisubstituted purine derivative roscovitine, are currently being evaluated in clinical trials as potential anticancer drugs. Here, we describe a new series of roscovitine derivatives that show increased potency in vitro. The series was tested for cytotoxicity against six cancer cell lines and for inhibition of CDKs. For series bearing 2-(hydroxyalkylamino) moiety, cytotoxic potency strongly correlated with anti-CDK2 activity. Importantly, structural changes that increase biochemical and anticancer activities of these compounds also increase elimination half-life. The most potent compounds were investigated further to assess their ability to influence cell cycle progression, p53-regulated transcription and apoptosis. All the observed biological effects were consistent with inhibition of CDKs involved in the regulation of cell cycle and transcription. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.036