(2R)-2-[[6-benzylamino-9-isopropyl-9H-purin-2-yl]amino]butyl 4-(nitrooxy)-butanoate | 1428319-98-5

• 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: (2R)-2-[[6-benzylamino-9-isopropyl-9H-purin-2-yl]amino]butyl 4-(nitrooxy)-butanoate
• 英文别名: [(2R)-2-[[6-(benzylamino)-9-propan-2-ylpurin-2-yl]amino]butyl] 4-nitrooxybutanoate
• CAS: 1428319-98-5
• 化学式: C₂₃H₃₁N₇O₅
• 分子量: 485.543
• InChiKey: FZZMDHKSGWXEGZ-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  149
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-(nitrooxy)butanoic acid 、 [(1S)-1-氰基-2-甲基丙基]氨基甲酸苄酯 在 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 吡啶 为溶剂， 反应 4.0h， 以48%的产率得到(2R)-2-[[6-benzylamino-9-isopropyl-9H-purin-2-yl]amino]butyl 4-(nitrooxy)-butanoate
  参考文献：
  名称：

  Novel R-roscovitine NO-donor hybrid compounds as potential pro-resolution of inflammation agents

  摘要：

  Neutrophils play a pivotal role in the pathophysiology of multiple human inflammatory diseases. Novel pharmacological strategies which drive neutrophils to undergo programmed cell death (apoptosis) have been shown to facilitate the resolution of inflammation. Both the cyclin-dependent kinase inhibitor (CDKi) R-roscovitine and nitric oxide (NO) have been shown to enhance apoptosis of neutrophils and possess pro-resolution of inflammation properties. In order to search for new multi-target pro-resolution derivatives, here we describe the design, synthesis and investigation of the biological potential of a small series of hybrid compounds obtained by conjugating R-roscovitine with two different NO-donor moieties (compounds 2, 9a, 9c). The synthesized compounds were tested as potential pro-resolution agents, with their ability to promote human neutrophil apoptosis evaluated. Both compound 9a and 9c showed an increased pro-apoptotic activity when compared with either R-roscovitine or structurally related compounds devoid of the ability to release NO (des-NO analogues). Inhibition of either NO-synthase or soluble guanylate cyclase did not affect the induction of apoptosis by the R-roscovitine derivatives, similar to that reported for other classes of NO-donors. In contrast the NO scavenger PTIO prevented the enhanced apoptosis seen with compound 9a over R-roscovitine. These data show that novel compounds such as CDKi-NO-donor hybrids may have additive pro-resolution of inflammation effects. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.009

文献信息

• Novel R-roscovitine NO-donor hybrid compounds as potential pro-resolution of inflammation agents
  作者：Gabriele Montanaro、Massimo Bertinaria、Barbara Rolando、Roberta Fruttero、Christopher D. Lucas、David A. Dorward、Adriano G. Rossi、Ian L. Megson、Alberto Gasco

  DOI：10.1016/j.bmc.2013.01.009

  日期：2013.4

  Neutrophils play a pivotal role in the pathophysiology of multiple human inflammatory diseases. Novel pharmacological strategies which drive neutrophils to undergo programmed cell death (apoptosis) have been shown to facilitate the resolution of inflammation. Both the cyclin-dependent kinase inhibitor (CDKi) R-roscovitine and nitric oxide (NO) have been shown to enhance apoptosis of neutrophils and possess pro-resolution of inflammation properties. In order to search for new multi-target pro-resolution derivatives, here we describe the design, synthesis and investigation of the biological potential of a small series of hybrid compounds obtained by conjugating R-roscovitine with two different NO-donor moieties (compounds 2, 9a, 9c). The synthesized compounds were tested as potential pro-resolution agents, with their ability to promote human neutrophil apoptosis evaluated. Both compound 9a and 9c showed an increased pro-apoptotic activity when compared with either R-roscovitine or structurally related compounds devoid of the ability to release NO (des-NO analogues). Inhibition of either NO-synthase or soluble guanylate cyclase did not affect the induction of apoptosis by the R-roscovitine derivatives, similar to that reported for other classes of NO-donors. In contrast the NO scavenger PTIO prevented the enhanced apoptosis seen with compound 9a over R-roscovitine. These data show that novel compounds such as CDKi-NO-donor hybrids may have additive pro-resolution of inflammation effects. (C) 2013 Elsevier Ltd. All rights reserved.