2-[2-[[(2R)-1-hydroxy-3-methylbutan-2-yl]amino]-9-propan-2-ylpurin-6-yl]guanidine | 1430401-82-3

• 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-[[(2R)-1-hydroxy-3-methylbutan-2-yl]amino]-9-propan-2-ylpurin-6-yl]guanidine
• CAS: 1430401-82-3
• 化学式: C₁₄H₂₄N₈O
• 分子量: 320.398
• InChiKey: ZSUORGHLMRHFOA-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-chloro-2-iodo-9-isopropylpurine 在 三乙烯二胺 、 copper(l) iodide 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 14.0h， 生成 2-[2-[[(2R)-1-hydroxy-3-methylbutan-2-yl]amino]-9-propan-2-ylpurin-6-yl]guanidine
  参考文献：
  名称：

  Synthesis and biological evaluation of guanidino analogues of roscovitine

  摘要：

  A series of 2,9-substituted 6-guanidinopurines, structurally related to the cyclin-dependent kinase (CDK) inhibitors olomoucine and roscovitine, has been synthesized and characterized. A new copper-catalyzed method for the synthesis of 2-substituted 6-guanidino-9-isopropylpurines under mild reaction conditions has been developed. All prepared compounds were screened for their CDK1 and CDK2 inhibitory activities, cytotoxicity and antiproliferative effects in the breast cancer-derived cell line MCF7. The most active derivative 16g possessed an identical side chain in the C2 position to roscovitine; this compound displayed approximately five fold higher inhibitory activity towards CDK2/cyclin E and more than ten fold increase in cytotoxicity in MCF7 cells. Interestingly and in contrast to previously described findings, (S)-6-guanidinopurine derivatives were generally more active than their (R)-counterparts. Kinase selectivity profiling of (R)- and (S)-enantiomers 16e and 16g, respectively, revealed that introduction of a guanidino group at the C6 position of the purine moiety decreased selectivity towards protein kinases compared to roscovitine. Nevertheless, increased inhibitory activity and decreased selectivity offer a good starting point for further development of new protein kinase inhibitors. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.021

文献信息

• Synthesis and biological evaluation of guanidino analogues of roscovitine
  作者：Iva Dolečková、Michal Česnek、Martin Dračinský、Jiří Brynda、Jiří Voller、Zlatko Janeba、Vladimír Kryštof

  DOI：10.1016/j.ejmech.2013.01.021

  日期：2013.4

  A series of 2,9-substituted 6-guanidinopurines, structurally related to the cyclin-dependent kinase (CDK) inhibitors olomoucine and roscovitine, has been synthesized and characterized. A new copper-catalyzed method for the synthesis of 2-substituted 6-guanidino-9-isopropylpurines under mild reaction conditions has been developed. All prepared compounds were screened for their CDK1 and CDK2 inhibitory activities, cytotoxicity and antiproliferative effects in the breast cancer-derived cell line MCF7. The most active derivative 16g possessed an identical side chain in the C2 position to roscovitine; this compound displayed approximately five fold higher inhibitory activity towards CDK2/cyclin E and more than ten fold increase in cytotoxicity in MCF7 cells. Interestingly and in contrast to previously described findings, (S)-6-guanidinopurine derivatives were generally more active than their (R)-counterparts. Kinase selectivity profiling of (R)- and (S)-enantiomers 16e and 16g, respectively, revealed that introduction of a guanidino group at the C6 position of the purine moiety decreased selectivity towards protein kinases compared to roscovitine. Nevertheless, increased inhibitory activity and decreased selectivity offer a good starting point for further development of new protein kinase inhibitors. (C) 2013 Elsevier Masson SAS. All rights reserved.