(8-azidooctyl)benzene | 76264-80-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (8-azidooctyl)benzene
• 英文别名: 8-Azidooctylbenzene
• CAS: 76264-80-7
• 化学式: C₁₄H₂₁N₃
• 分子量: 231.341
• InChiKey: VRLNOUXWHPOGRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  17
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  14.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (8-azidooctyl)benzene 在 五甲基环戊二烯基双(三苯基膦)氯化钌(II) 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.5h， 生成 benzyl (S)-2-(3-(4-((ethoxymethoxy)methyl)benzamido)propanamido)-3-(1-(8-phenyloctyl)-1H-1,2,3-triazol-4-yl)propanoate
  参考文献：
  名称：

  新型和选择性非肽抑制剂针对马球样激酶1的马球盒域的鉴定。

  摘要：

  基于有效和选择性最小的三肽Plk1 PBD抑制剂，设计了一系列针对polo样激酶1（Plk1）的polo-box域（PBD）的非肽抑制剂。设计，合成并评估了7种化合物，用于荧光偏振（FP）分析。最有希望的化合物10与Plk1 PBD结合，IC 50为3.37μM，并且在100μM下不与Plk2 PBD或Plk3 PBD结合。进行了分子对接研究，并提出了可能的结合方式。MM / GBSA结合自由能的计算与观察到的实验结果一致。这些新颖的非肽选择性Plk1 PBD抑制剂为进一步优化提供了新的先导化合物。

  DOI：

  10.1016/j.bioorg.2018.08.030
• 作为产物：
  描述：

  phenyloctyl methanesulfonate 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 以96%的产率得到(8-azidooctyl)benzene
  参考文献：
  名称：

  Non-proteinogenic amino acids in the pThr-2 position of a pentamer peptide that confer high binding affinity for the polo box domain (PBD) of polo-like kinase 1 (Plk1)

  摘要：

  We report herein that incorporating long-chain alkylphenyl-containing non-proteinogenic amino acids in place of His at the pT-2 position of the parent polo-like kinase 1 (Plk1) polo box domain (PBD)-binding pentapeptide, PLHSpT (1a) increases affinity. For certain analogs, approximately two orders-of-magnitude improvement in affinity was observed. Although, none of the new analogs was as potent as our previously described peptide 1b, in which the pT-2 histidine imidazole ring is alkylated at its pi nitrogen (N3), our current finding that the isomeric His(N1)-analog (1c) binds with approximately 50-fold less affinity than 1b, indicates the positional importance of attachment to the His imidazole ring. Our demonstration that a range of modified residues at the pT-2 position can enhance binding affinity, should facilitate the development of minimally-sized Plk1 PBD-binding antagonists. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.10.093

文献信息

• An efficient Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in aqueous medium with a zwitterionic ligand, betaine
  作者：Jung-Ah Shin、Su-Jin Oh、Hee-Yoon Lee、Yeong-Gweon Lim

  DOI：10.1039/c7cy00518k

  日期：——

  Cu-catalyzed azide–alkyne cycloaddition reaction in aqueous medium was dramatically accelerated by a simple zwitterionic additive, betaine, at ambient temperature. In the presence of betaine, 1,4-disubstituted-1,2,3-triazoles were obtained from azides and terminal alkynes in excellent yields under 2.5–200 ppm levels of Cu(I) in water. This method resulted in the remarkable reduction of the Cu(I) concentration

  在环境温度下，简单的两性离子添加剂甜菜碱可显着促进水介质中铜催化的叠氮化物-炔烃环加成反应。在甜菜碱存在的情况下，在2.5–200 ppm的水中铜（I）水平下，叠氮化物和末端炔烃可得到1,4-二取代-1,2,3-三唑。该方法导致Cu （I）浓度显着降低至ppm级。该方案的优点包括使用常规的Cu催化体系和可商购获得的甜菜碱，该甜菜碱对生物应用通常是无毒的。因此，这种有效的催化体系应在生命科学研究和材料科学中具有广泛的应用。
• Development of Highly Selective 1,2,3-Triazole-containing Peptidic Polo-like Kinase 1 Polo-box Domain-binding Inhibitors
  作者：Xue Zhi Zhao、Kohei Tsuji、David Hymel、Terrence R. Burke

  DOI：10.3390/molecules24081488

  日期：——

  Members of the polo-like kinase (Plk) family of serine/threonine protein kinases play crucial roles in cell cycle regulation and proliferation. Of the five Plks (Plk1–5), Plk1 is recognized as an anticancer drug target. Plk1 contains multiple structural components that are important for its proper biological function. These include an N-terminal catalytic domain and a C-terminal non-catalytic polo-box domain (PBD). The PBD binds to phosphothreonine (pT) and phosphoserine-containing sequences. Blocking PBD-dependent interactions offers a potential means of down-regulating Plk1 function that is distinct from targeting its ATP-binding site. Previously, we demonstrated by tethering alkylphenyl chains from the N(π)-position of the His residue in the 5-mer PLHSpT, that we were able to access a hydrophobic “cryptic” binding pocket on the surface of the PBD, and in so doing enhance binding affinities by approximately 1000-fold. More recently, we optimized these PBD-ligand interactions using an oxime ligation-based strategy. Herein, using azide-alkyne cycloaddition reactions, we explore new triazole-containing PBD-binding antagonists. Some of these ligands retain the high PBD-binding affinity of the parent peptide, while showing desirable enhanced selectivity for the PBD of Plk1 relative to the PBDs of Plk2 and Plk3.

  波洛样激酶（Plk）家族的丝氨酸/苏氨酸蛋白激酶在细胞周期调控和增殖中发挥关键作用。在五种Plk（Plk1–5）中，Plk1被认为是一个抗癌药物靶点。Plk1包含多个对其正确生物功能至关重要的结构组分。其中包括一个N-末端催化结构域和一个C-末端非催化波洛盒结构域（PBD）。PBD结合磷酸苏氨酸（pT）和含磷酸丝氨酸的序列。阻断PBD依赖的相互作用提供了一种下调Plk1功能的潜在手段，这与以靶向其ATP结合位点不同。此前，我们通过将烷基苯链从5-mer PLHSpT中的His残基的N（π）位点上锚定，证明我们能够访问PBD表面上的一个疏水“隐蔽”结合口袋，并以此增强约1000倍的结合亲和力。最近，我们使用肟缩合反应基于策略优化了这些PBD-配体相互作用。在这里，通过叠氮-炔基环加成反应，我们探索新的三唑含有PBD结合拮抗剂。其中一些配体保留了母体肽的高PBD结合亲和力，同时显示出对Plk1的PBD相对于Plk2和Plk3的PBD的理想增强选择性。