9-((3aR,4R,6R,6aR)-6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-6-chloro-2-fluoro-9H-purine | 1117729-26-6

• 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: 9-((3aR,4R,6R,6aR)-6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-6-chloro-2-fluoro-9H-purine
• CAS: 1117729-26-6
• 化学式: C₁₉H₂₈ClFN₄O₄Si
• 分子量: 458.993
• InChiKey: IVNBZKGPKCJDTQ-XNIJJKJLSA-N

物化性质

• 沸点：
  562.1±60.0 °C(predicted)
• 密度：
  1.38±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.06
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  80.52
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  9-((3aR,4R,6R,6aR)-6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-6-chloro-2-fluoro-9H-purine 在 氨 作用下， 以 异丙醇 为溶剂， 反应 48.0h， 生成 9-((3aR,4R,6R,6aR)-6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyltetrahydrofuran[3,4-d][1,3]dioxazol-4-yl)-2-fluoro-9H-purin-6-amine
  参考文献：
  名称：

  SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes

  摘要：

  The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH- without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N-6-amino moiety favors the inhibition of DNMT3b2 enzyme. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.113
• 作为产物：
  描述：

  9-((3aR,4R,6R,6aR)-6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-6-chloro-9H-purine 在 2,2,6,6-tetramethylpiperidinyl-lithium 、 三丁基氯化锡 、 2,6-二叔丁基-4-甲基吡啶 、 xenon fluoride 、 silver trifluoromethanesulfonate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.75h， 生成 9-((3aR,4R,6R,6aR)-6-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-6-chloro-2-fluoro-9H-purine
  参考文献：
  名称：

  SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes

  摘要：

  The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH- without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N-6-amino moiety favors the inhibition of DNMT3b2 enzyme. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.113

文献信息

• Inhibitors of DNA Methyltransferase
  申请人：Wahhab Amal

  公开号：US20080132525A1

  公开（公告）日：2008-06-05

  The invention relates to the inhibition of DNA methyltransferase isoforms DNMT1 and DNMT3b2. The invention provides compounds and methods for inhibiting DNMT1 and DNMT3b2.

  这项发明涉及抑制DNA甲基转移酶亚型DNMT1和DNMT3b2。该发明提供了用于抑制DNMT1和DNMT3b2的化合物和方法。