2-(1-hydroxypentyl)-1,4,5,8-tetramethoxynaphthalene | 115801-90-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(1-hydroxypentyl)-1,4,5,8-tetramethoxynaphthalene
• 英文别名: 1-(1,4,5,8-tetramethoxynaphthalen-2-yl)pentan-1-ol
• CAS: 115801-90-6
• 化学式: C₁₉H₂₆O₅
• 分子量: 334.412
• InChiKey: AXQLAGCEYKPURN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(1-hydroxypentyl)-1,4,5,8-tetramethoxynaphthalene 在 ammonium cerium (IV) nitrate 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 0.13h， 生成 6-(1-Hydroxy-pentyl)-5,8-dimethoxy-[1,4]naphthoquinone
  参考文献：
  名称：

  6-Substituted 1,4-Naphthoquinone Oxime Derivatives (III): Synthesis and Cytotoxic Evaluation

  摘要：

  As a continuous study, a set of 23 new 6-substituted 1,4-naphthoquinone oxime derivatives are synthesized and screened for their in vitro cytotoxic activity. Four of those oxime derivatives demonstrate more potent cytotoxic activity towards K562, HCT-15, and HCT-116 cell lines than a reference drug 5-Fu. In particular, compound 21g exhibits the strongest inhibitory activity against K562 cell lines with IC50 values of 1.25 mu M. According to flow cytometry data, compound 21g can arrest cell cycle at S phase and induce a strong apoptotic response in K562 cells. The preliminary structure-activity relationship study shows that the nature of substituents in positions 6 and 1' of 1,4-naphthoquinone derivatives significantly affect their cytotoxic activity.

  DOI：

  10.1134/s1070363218050316
• 作为产物：
  描述：

  1,4,5,8-tetramethoxynaphthalene 在 碘 、 magnesium 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 2-(1-hydroxypentyl)-1,4,5,8-tetramethoxynaphthalene
  参考文献：
  名称：

  6-Substituted 1,4-Naphthoquinone Oxime Derivatives (III): Synthesis and Cytotoxic Evaluation

  摘要：

  As a continuous study, a set of 23 new 6-substituted 1,4-naphthoquinone oxime derivatives are synthesized and screened for their in vitro cytotoxic activity. Four of those oxime derivatives demonstrate more potent cytotoxic activity towards K562, HCT-15, and HCT-116 cell lines than a reference drug 5-Fu. In particular, compound 21g exhibits the strongest inhibitory activity against K562 cell lines with IC50 values of 1.25 mu M. According to flow cytometry data, compound 21g can arrest cell cycle at S phase and induce a strong apoptotic response in K562 cells. The preliminary structure-activity relationship study shows that the nature of substituents in positions 6 and 1' of 1,4-naphthoquinone derivatives significantly affect their cytotoxic activity.

  DOI：

  10.1134/s1070363218050316

文献信息

• Naphthazarin derivatives (IV): synthesis, inhibition of DNA topoisomerase I and cytotoxicity of 2- or 6-acyl-5,8-dimethoxy-1,4-naphthoquinones
  作者：Gyu-Yong Song、Yong Kim、Xiang-Guo Zheng、Young-Jae You、Hoon Cho、Jin-Ho Chung、Dai-Eun Sok、Byung-Zun Ahn

  DOI：10.1016/s0223-5234(00)00129-x

  日期：2000.3

  Some 2- or 6-acyl-5,8-dimethoxy-1,4-naphthoquinone (DMNQ) derivatives were synthesized and evaluated for inhibition of DNA topoisomerase I and cytotoxicity against L1210 cells. Compared with 2-acyl-DMNQ derivatives, 6-acyl-DMNQ compounds, bearing a higher electrophilic quinone moiety, showed a higher potency in the inhibition of DNA topoisomerase I and the cytotoxicity, implying the possible participation

  合成了一些2-或6-酰基-5,8-二甲氧基-1,4-萘醌（DMNQ）衍生物，并评估了其对DNA拓扑异构酶I的抑制作用以及对L1210细胞的细胞毒性。与2-酰基-DMNQ衍生物相比，带有较高亲电醌部分的6-酰基-DMNQ化合物在抑制DNA拓扑异构酶I和细胞毒性方面显示出更高的效力，这暗示着亲电子芳基化可能参与了其生物活性。酶抑制的时间和温度依赖性表明芳基化不可逆地发生。在6-酰基-DMNQ衍生物中，具有中等大小（C（5）-C（9））的酰基的衍生物在生物活性方面比其他衍生物更高。此外，为了有效抑制DNA拓扑异构酶I，
• The 2- or 6-(α-Hydroxyalkyl- and α-Oxoalkyl)-5,8-dimethoxy-1,4-naphthoquinones from the Oxidative Demethylation of 2-(α-Hydroxyalkyl- and α-Oxoalkyl)-1,4,5,8-tetramethoxynaphthalenes with Cerium(IV) Ammonium Nitrate, and the Further Demethylations to Naphthazarins
  作者：Yasuhiro Tanoue、Akira Terada

  DOI：10.1246/bcsj.61.2039

  日期：1988.6

  Oxidative demethylation of 2-(α-hydroxyalkyl- and α-oxoalkyl)-1,4,5,8-tetramethoxynaphthalene with (NH4)2Ce(NO3)6 gave two isomeric dimethoxynaphthoquinones: 2-substituted and 6-substituted 5,8-dimethoxy-1,4-naphthoquinones. Further demethylations of the former isomers to the corresponding dihydroxynaphthoquinones required an AgO–40%HNO3 reagent, while the latter isomers needed AlCl3 as the demethylation

  2-(α-羟烷基-和α-氧代烷基)-1,4,5,8-四甲氧基萘与 (NH4)2Ce(NO3)6 的氧化脱甲基得到两种异构二甲氧基萘醌：2-取代和 6-取代的 5,8-二甲氧基-1,4-萘醌。前者异构体进一步去甲基化为相应的二羟基萘醌需要 AgO–40%H 试剂，而后者异构体需要 AlCl3 作为去甲基化试剂。给出了关于这些用 (NH4)2Ce( )6 进行氧化去甲基化的机制的一些评论。
• Discovery and synthesis of sulfur-containing 6-substituted 5,8-dimethoxy-1,4-naphthoquinone oxime derivatives as new and potential anti-MDR cancer agents
  作者：Guang Huang、Jin-Yun Dong、Qi-Jing Zhang、Qing-Qing Meng、Hui-Ran Zhao、Bao-Quan Zhu、Shao-Shun Li

  DOI：10.1016/j.ejmech.2019.01.005

  日期：2019.3

  resistance (MDR) to anticancer drugs is the primary impediment to successful treatment of cancer. Hunting for new compounds with potent anti-MDR activity is an effectual approach to conquer cancer drug resistance. In this work, 33 new sulfur-containing 1,4-naphthoquinone oxime derivatives were prepared and investigated for their cytotoxicity against a panel of tumor cell lines and fibroblast normal

  对抗癌药物的多药耐药性（MDR）是成功治疗癌症的主要障碍。寻找具有有效抗MDR活性的新化合物是征服癌症耐药性的有效方法。在这项工作中，制备了33种新的含硫的1,4-萘醌肟衍生物，并研究了它们对一组肿瘤细胞系和成纤维细胞正常细胞系的细胞毒性。基于细胞的分析表明，大多数靶标化合物均比阳性对照具有更强的细胞毒性。同时，所有化合物均对正常细胞无毒。更重要的是，发现这些肟衍生物对耐药癌细胞系的细胞毒活性要强于对药物敏感细胞系的细胞毒活性（抗药性系数（ADRC）> 1）。这些，化合物12 m被认为是最有效的分子，对MDR子系的IC50值在0.29±0.01至1.33±0.05μM的范围内。进一步的机制研究表明12 m可以抑制菌落形成，引起G1期阻滞并促进通过增加Bel7402 / 5-FU细胞的Bax / Bcl-2比值介导的细胞凋亡。我们的发现为开发含硫的1,4-萘醌肟衍生物作为潜在的抗MDR药物提供了有希望的起点。
• Process for preparing 5,8-dihydroxynaphthoquinone derivatives, novel
  申请人：Kuhnil Pharmaceutical Co., Ltd.

  公开号：US05696276A1

  公开（公告）日：1997-12-09

  5,8-dihydroxynaphthoquinone derivatives represented by the following general formula (IA): ##STR1## in which R.sup.1 represents alkyl or alkenyl, R.sup.2a represents alkyl or a group --C(O)R wherein R represents alkyl, alkenyl, aryl, aralkyl or aralkenyl, which can be substituted or unsubstituted with one or more halogen(s), and R.sup.3 represents hydrogen or alkyl, provided that when R.sup.2a is a group --C(O)R and R.sup.3 is hydrogen, R.sup.1 is other than 3-methyl-2-butenyl; and when R.sup.2a represents methyl and R.sup.3 independently represents hydrogen or methyl, R.sup.1 is other than 3-methylbutyl. Processes for preparing 5,8-dihydroxynaphthoquinone derivatives are also provided.

  以如下一般式（IA）代表的5,8-二羟基萘醌衍生物：##STR1## 其中R.sup.1代表烷基或烯基，R.sup.2a代表烷基或一个基团--C(O)R，其中R代表烷基、烯基、芳基、芳基烷基或芳基烯基，可以被一个或多个卤素取代或未取代，R.sup.3代表氢或烷基，条件是当R.sup.2a是一个基团--C(O)R且R.sup.3是氢时，R.sup.1不是3-甲基-2-丁烯基；当R.sup.2a代表甲基且R.sup.3独立地代表氢或甲基时，R.sup.1不是3-甲基丁基。提供了制备5,8-二羟基萘醌衍生物的方法。
• One-Pot Ortho Hydroxylations of 2-(1-Hydroxyalkyl)naphthalenes and (1-Hydroxyalkyl)benzenes
  作者：Yasuhiro Tanoue、Akira Terada、Iwao Seto、Yasuo Umezu、Otohiko Tsuge

  DOI：10.1246/bcsj.61.1221

  日期：1988.4

  Hydroxylations of 2-(1-hydroxyalkyl)-1,4,5,8(or 1,4,5,6,8)-tetra(or penta)methoxynaphthalenes and 2-(1-hydroxyalkyl)-1,4-dimethoxybenzenes at the 3-position were accomplished by a one-pot procedure. The same procedure has been found to be applicable to 2-(1-hydroxyalkyl)naphthalenes and (1-hydroxyalkyl)benzenes having no methoxyl substituent.

  2-(1- 羟基烷基)-1,4,5,8(或 1,4,5,6,8)-四(或五)甲氧基萘和 2-(1-羟基烷基)-1,4-二甲氧基苯的 3-位羟基化是通过一锅程序完成的。同样的步骤也适用于没有甲氧基取代基的 2-(1-羟基烷基)萘和(1-羟基烷基)苯。