methyl 9-azidononanoate | 82610-35-3

• 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 9-azidononanoate
• CAS: 82610-35-3
• 化学式: C₁₀H₁₉N₃O₂
• 分子量: 213.28
• InChiKey: VOWANYLXELXKFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15.0
• 可旋转键数：
  9.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  75.06
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  methyl 9-azidononanoate 在 potassium cyanide 、 羟胺 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 24.0h， 以77%的产率得到9-azidononahydroxamic 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
• 作为产物：
  描述：

  methyl 9-bromononanoate 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以60%的产率得到methyl 9-azidononanoate
  参考文献：
  名称：

  A Novel Potent Nicotinamide Phosphoribosyltransferase Inhibitor Synthesized via Click Chemistry

  摘要：

  The inhibition of NAD synthesis or salvage pathways has been proposed as a novel target for antitumoral drugs. Two molecules with this mechanism of action are at present undergoing clinical trials. In searching for similar novel molecules, we exploited copper-catalyzed [3 + 2] cycloaddition between azides and alkynes (click chemistry) to synthesize 185 novel analogues. The most promising compound displays an IC50 for cytotoxicity in vitro of 3.8 +/- 0.3 nM and an IC50 for NAD depletion of 3.0 +/- 0.4 nM. Herein, we strengthen previous data suggesting that this class of compounds induces autophagic cell death. In addition to characterizing this compound and providing a rationale via molecular docking, we reinforce the excellent potential of click chemistry for rapidly generating structure-activity relationships and for drug screening.

  DOI：

  10.1021/jm9010669