7-hydroxy-8-(naphth-1-yl)quinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-hydroxy-8-(naphth-1-yl)quinoline
• 英文别名: 8-Naphthalen-1-ylquinolin-7-ol；8-naphthalen-1-ylquinolin-7-ol
• 化学式: C₁₉H₁₃NO
• 分子量: 271.318
• InChiKey: KZVSQEINWPBIEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-hydroxy-8-(naphth-1-yl)quinoline 、 2-溴丙烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 18.0h， 以86%的产率得到7-(isopropyloxy)-8-(naphth-1-yl)quinoline
  参考文献：
  名称：

  作为抗病毒剂的azaBINOL类分子的生物学评估：7-异丙氧基-8-（萘-1-基）喹啉对HIV-1 RNase H活性的抑制作用。

  摘要：

  受植物和海洋环境中含有生物活性的含联芳基天然产物的启发，评估了一系列属于azaBINOL手性配体家族的合成化合物对HIV-1的抗病毒活性。在单轮传染性测定中测试39种独特的azaBINOL和2种BINOL可鉴定出三种有前途的抗病毒化合物，包括7-异丙氧基-8-（萘-1-基）喹啉（azaBINOL B＃24） -微摩尔活性，无相关的细胞毒性。进一步针对三种不同的HIV-1包膜假型病毒以及在全病毒复制系统（EASY-HIT）中测试了活性化合物和几种紧密的结构类似物。体外研究表明azaBINOL B＃24在病毒装配和萌芽之前对病毒复制的早期阶段起作用。接下来，我们探讨了B＃24对HIV-1逆转录酶（RT）的活性，并分别测试了聚合酶和RNase H的活性。azaBINOL B＃24抑制RNase H活性，并直接与HIV-1 RT酶结合。此外，当与临床使用的非核苷逆转录酶抑制剂（NNRTI）依法韦仑

  DOI：

  10.1016/j.bmc.2019.06.044
• 作为产物：
  描述：

  7-(diethylaminocarbonyloxy)-8-iodoquinoline 在 potassium phosphate 、 三苯基膦 、 potassium hydroxide 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 68.0h， 生成 7-hydroxy-8-(naphth-1-yl)quinoline
  参考文献：
  名称：

  Synthesis, Properties, and Enantiomerization Behavior of Axially Chiral Phenolic Derivatives of 8-(Naphth-1-yl)quinoline and Comparison to 7,7′-Dihydroxy-8,8′-biquinolyl and 1,1′-Bi-2-naphthol

  摘要：

  An aza-analogue of 1,1-bi-2-naphthol (BINOL, 3), 7-hydroxy-8-(2-hydroxynaphth-1-yl)quinoline (8-azaBINOL, 2), was prepared in 3 steps and 49% yield from N,N-diethyl O-(7-hydroxy-8-iodoquinolyl)carbamate via Suzuki coupling with 1-naphthylboronic acid followed by Sanford oxidation and saponification. 8-AzaBINOL (2) was resolved into (-)-(aS) and (+)-(aR) atropisomers via enzymatic hydrolysis of its racemic divalerate derivative with bovine pancreas acetone powder. The configurational stability of diol 2 was found to be intermediate to that of 7,7-dihydroxy-8,8-biquinolyl (8,8-diazaBINOL, 1, least stable) and BINOL (3, most stable). Eyring plot analysis of the enantiomerization kinetics of 1, 2, and 3, in DMSO solution revealed activation parameters of H-double dagger = +27.4, +19.9, +23.2 kcal mol(-1), and S-double dagger = +3.8, -27.9, -25.3 cal mol(-1) K-1, respectively. The unique character of H-double dagger and S-double dagger values for biquinolyl 1 suggests that the enantiomerization mechanism for 1 is distinct to that for naphthalenes 2 and 3. Monohydroxy analogues of 2, 7-hydroxy-8-(naphth-1-yl)quinoline (7) and 8-(2-hydroxynaphth-1-yl)quinoline (8), were similarly prepared and their racemization half-lives at room temperature were determined; (1/2(rac)) was strongly dependent on solvent for naphthol 8 [(1/2(rac)) at 24 degrees C: in CHCl3 = 2.7 h, in MeOH = 89 h] but not for the quinol 7 [(1/2(rac)) at 24 degrees C: in CHCl3 = 106 h, in MeOH = 120 h].

  DOI：

  10.1055/s-0035-1560640

文献信息

• Synthesis, Properties, and Enantiomerization Behavior of Axially Chiral Phenolic Derivatives of 8-(Naphth-1-yl)quinoline and Comparison to 7,7′-Dihydroxy-8,8′-biquinolyl and 1,1′-Bi-2-naphthol
  作者：Paul Blakemore、Somdev Banerjee、Brian Riggs、Lev Zakharov

  DOI：10.1055/s-0035-1560640

  日期：——

  An aza-analogue of 1,1-bi-2-naphthol (BINOL, 3), 7-hydroxy-8-(2-hydroxynaphth-1-yl)quinoline (8-azaBINOL, 2), was prepared in 3 steps and 49% yield from N,N-diethyl O-(7-hydroxy-8-iodoquinolyl)carbamate via Suzuki coupling with 1-naphthylboronic acid followed by Sanford oxidation and saponification. 8-AzaBINOL (2) was resolved into (-)-(aS) and (+)-(aR) atropisomers via enzymatic hydrolysis of its racemic divalerate derivative with bovine pancreas acetone powder. The configurational stability of diol 2 was found to be intermediate to that of 7,7-dihydroxy-8,8-biquinolyl (8,8-diazaBINOL, 1, least stable) and BINOL (3, most stable). Eyring plot analysis of the enantiomerization kinetics of 1, 2, and 3, in DMSO solution revealed activation parameters of H-double dagger = +27.4, +19.9, +23.2 kcal mol(-1), and S-double dagger = +3.8, -27.9, -25.3 cal mol(-1) K-1, respectively. The unique character of H-double dagger and S-double dagger values for biquinolyl 1 suggests that the enantiomerization mechanism for 1 is distinct to that for naphthalenes 2 and 3. Monohydroxy analogues of 2, 7-hydroxy-8-(naphth-1-yl)quinoline (7) and 8-(2-hydroxynaphth-1-yl)quinoline (8), were similarly prepared and their racemization half-lives at room temperature were determined; (1/2(rac)) was strongly dependent on solvent for naphthol 8 [(1/2(rac)) at 24 degrees C: in CHCl3 = 2.7 h, in MeOH = 89 h] but not for the quinol 7 [(1/2(rac)) at 24 degrees C: in CHCl3 = 106 h, in MeOH = 120 h].
• Biological evaluation of molecules of the azaBINOL class as antiviral agents: Inhibition of HIV-1 RNase H activity by 7-isopropoxy-8-(naphth-1-yl)quinoline
  作者：Ross D. Overacker、Somdev Banerjee、George F. Neuhaus、Selena Milicevic Sephton、Alexander Herrmann、James A. Strother、Ruth Brack-Werner、Paul R. Blakemore、Sandra Loesgen

  DOI：10.1016/j.bmc.2019.06.044

  日期：2019.8

  activity decreases by 7.6-fold. These results indicate that azaBINOL B#24 is a potentially viable, novel lead for the development of new HIV-1 RNase H inhibitors. Furthermore, this study demonstrates that the survey of libraries of synthetic compounds, designed purely with the goal of facilitating chemical synthesis in mind, may yield unexpected and selective drug leads for the development of new antiviral

  受植物和海洋环境中含有生物活性的含联芳基天然产物的启发，评估了一系列属于azaBINOL手性配体家族的合成化合物对HIV-1的抗病毒活性。在单轮传染性测定中测试39种独特的azaBINOL和2种BINOL可鉴定出三种有前途的抗病毒化合物，包括7-异丙氧基-8-（萘-1-基）喹啉（azaBINOL B＃24） -微摩尔活性，无相关的细胞毒性。进一步针对三种不同的HIV-1包膜假型病毒以及在全病毒复制系统（EASY-HIT）中测试了活性化合物和几种紧密的结构类似物。体外研究表明azaBINOL B＃24在病毒装配和萌芽之前对病毒复制的早期阶段起作用。接下来，我们探讨了B＃24对HIV-1逆转录酶（RT）的活性，并分别测试了聚合酶和RNase H的活性。azaBINOL B＃24抑制RNase H活性，并直接与HIV-1 RT酶结合。此外，当与临床使用的非核苷逆转录酶抑制剂（NNRTI）依法韦仑