methyl 8-azidooctanoate | 141446-69-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl 8-azidooctanoate
• 英文别名: 8-azidooctanoate；Methyl 8-azidooctanoate
• CAS: 141446-69-7
• 化学式: C₉H₁₇N₃O₂
• 分子量: 199.253
• InChiKey: FKNJHVLIWFTNKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  14
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  40.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 8-azidooctanoate 在 potassium cyanide 、 羟胺 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 24.0h， 以74%的产率得到8-azidooctahydroxamic acid
  参考文献：
  名称：

  Non-Peptide Macrocyclic Histone Deacetylase Inhibitors

  摘要：

  Inhibition of histone deacetylase inhibitors (HDACi) hold great promise in cancer therapy because of their demonstrated ability to arrest proliferation of nearly all transformed cell types. Of the several structurally distinct small molecule HDACi reported, macrocyclic depsipeptides have the most complex recognition cap-group moieties and present an excellent opportunity for the modulation of the biological activities of HDACi. Unfortunately, the structure-activity relationship (SAR) studies for this class of compounds have been impaired largely because most macrocyclic HDACi known to date comprise complex peptide macrocycles. In addition to retaining the pharmacologically disadvantaged peptidyl backbone, they offer only limited opportunity for side chain modifications. Here, we report the discovery of a new class of macrocyclic HDAG based on the macrolide antibiotics skeletons. SAR studies revealed that these compounds displayed both linker-length and macrolide-type dependent HDAC inhibition activities with IC50 in the low nanomolar range. In addition, these non-peptide macrocyclic HDACi are more selective against HDACs 1 and 2 relative to HDAC 8, another class I HDAC isoform, and hence have subclass HDAC isoform selectivity.

  DOI：

  10.1021/jm801128g

文献信息

• Design and synthesis of novel histone deacetylase inhibitor derived from nuclear localization signal peptide
  作者：Joshua C. Canzoneri、Po C. Chen、Adegboyega K. Oyelere

  DOI：10.1016/j.bmcl.2009.10.028

  日期：2009.12

  We describe herein the synthesis and characterization of a new class of histone deacetylase (HDAC) inhibitors derived from conjugation of a suberoylanilide hydroxamic acid-like aliphatic-hydroxamate pharmacophore to a nuclear localization signal peptide. We found that these conjugates inhibited the histone deacetylase activities of HDACs 1, 2, 6, and 8 in a manner similar to suberoylanilide hydroxamic acid (SAHA). Notably, compound 7b showed a threefold improvement in HDAC 1/2 inhibition, a threefold increase in HDAC 6 selectivity and a twofold increase in HDAC 8 selectivity when compared to SAHA. (C) 2009 Elsevier Ltd. All rights reserved.
• Development of a Chimeric c-Src Kinase and HDAC Inhibitor
  作者：Kristin S. Ko、Michael E. Steffey、Kristoffer R. Brandvold、Matthew B. Soellner

  DOI：10.1021/ml400175d

  日期：2013.8.8

  On the basis of synergism observed between a selective c-Src kinase inhibitor with an HDAC inhibitor, the development of the first chimeric c-Src kinase and HDAC inhibitor is described. The optimized chimeric inhibitor is shown to be a potent c-Src and HDAC inhibitor. Chimeric inhibitor 4 is further shown to be highly efficacious in cancer cell lines and significantly more efficacious than a dual-targeting strategy using discrete c-Src and HDAC inhibitors.
• Non-Peptide Macrocyclic Histone Deacetylase Inhibitors
  作者：Adegboyega K. Oyelere、Po C. Chen、William Guerrant、Sandra C. Mwakwari、Rebecca Hood、Yunzhe Zhang、Yuhong Fan

  DOI：10.1021/jm801128g

  日期：2009.1.22

  Inhibition of histone deacetylase inhibitors (HDACi) hold great promise in cancer therapy because of their demonstrated ability to arrest proliferation of nearly all transformed cell types. Of the several structurally distinct small molecule HDACi reported, macrocyclic depsipeptides have the most complex recognition cap-group moieties and present an excellent opportunity for the modulation of the biological activities of HDACi. Unfortunately, the structure-activity relationship (SAR) studies for this class of compounds have been impaired largely because most macrocyclic HDACi known to date comprise complex peptide macrocycles. In addition to retaining the pharmacologically disadvantaged peptidyl backbone, they offer only limited opportunity for side chain modifications. Here, we report the discovery of a new class of macrocyclic HDAG based on the macrolide antibiotics skeletons. SAR studies revealed that these compounds displayed both linker-length and macrolide-type dependent HDAC inhibition activities with IC50 in the low nanomolar range. In addition, these non-peptide macrocyclic HDACi are more selective against HDACs 1 and 2 relative to HDAC 8, another class I HDAC isoform, and hence have subclass HDAC isoform selectivity.