5-Methoxy-1,2-naphthochinon | 61539-67-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-Methoxy-1,2-naphthochinon
• 英文别名: 5-methoxy[1,2]naphthoquinone；5-Methoxynaphthalene-1,2-dione
• CAS: 61539-67-1
• 化学式: C₁₁H₈O₃
• 分子量: 188.183
• InChiKey: VVCISDXAHHGMBS-UHFFFAOYSA-N

物化性质

• 熔点：
  208-210 °C(Solv: acetone (67-64-1))
• 沸点：
  362.0±42.0 °C(Predicted)
• 密度：
  1.284±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-Methoxy-1,2-naphthochinon 在 盐酸 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 19.0h， 生成 4-methoxy-10-methylamino-benzo[a]phenazine-11-carboxylic acid methyl ester
  参考文献：
  名称：

  Novel Angular Benzophenazines:  Dual Topoisomerase I and Topoisomerase II Inhibitors as Potential Anticancer Agents

  摘要：

  A series of substituted angular benzophenazines were prepared using a new synthetic route via a novel regiocontrolled condensation of 1,2-naphthoquinones and 2,3-diaminobenzoic acids. The synthesis and biological activity of this new series of substituted 8,9-benzo[a]phenazine carboxamide systems are described. The analogues were evaluated against the H69 parental human small cell lung carcinoma cell line and H69/LX4 resistant cell line which overexpresses P-glycoprotein. Selected analogues were evaluated against the COR-L23-parental human non small cell lung carcinoma cell line and the COR-L23/R resistant cell line which overexpresses multidrug resistance protein. This series of novel angular benzophenazines were potent cytotoxic agents in these cell lines and may be able to circumvent multidrug resistance mechanisms which result in the lack of efficacy of many drugs in cancer chemotherapy. These compounds show dual inhibition of topoisomerase I and topoisomerase II and thus target two key enzymes responsible for the topology of DNA that are active at different points in the cell cycle. The introduction of chirality into the carboxamide side chain of these novel benzophenazine carboxamides has resulted in the discovery of a potent enantiospecific series of cytotoxic agents, exemplified by 4-methoxy-benzo[a]phenazine-11-carboxylic acid (2-(dimethylamino)-1-(R)methyl-ethyl)-amide, XR11576 ((R)-4j"). In vivo activity has been demonstrated for 4-methoxy-benzo[a]phenazine-11-carboxylic acid (2-(dimethylamino)-1-(R)-methyl-ethyl)-amide, XR11576, after intravenous administration to female mice, and this compound has been selected as a development candidate for further evaluation.

  DOI：

  10.1021/jm010329a
• 作为产物：
  描述：

  5-甲氧基-3,4-二氢-2H-1-萘酮 在 selenium(IV) oxide 作用下， 以 溶剂黄146 为溶剂， 以56%的产率得到5-Methoxy-1,2-naphthochinon
  参考文献：
  名称：

  微波辅助二氧化硒介导的1-四氢萘酮选择性氧化为1,2-萘醌

  摘要：

  我们报告了一种改进的程序，通过微波辅助二氧化硒氧化将选择性的1-四氢萘酮选择性转化为1,2-萘醌。反应时间从数小时缩短至数秒，而收率（40–70％）或选择性没有任何损失。

  DOI：

  10.1016/j.tetlet.2008.10.068

文献信息

• Oxidation with Fremy's salt—VIII
  作者：H. Ishii、T. Hanaoka、T. Asaka、Y. Harada、N. Ikeda

  DOI：10.1016/0040-4020(76)80108-1

  日期：1976.1

  It has been shown by a series of experiments on 5-alkyl, 5-halo-, and other 5-substituted 1-naphthol derivatives that the product ratio of the ortho- and para-naphthoquinones formed on oxidation with Fremy's salt is controlled by the bulkiness of the C5-substituent.

  在5-烷基，5-卤代和其他5-取代的1-萘酚衍生物上进行的一系列实验表明，用Fremy's盐氧化形成的邻萘和对萘萘醌的产物比率受C 5-取代基的体积大。
• Benzo[A] [phenazin-11-carboxamide derivatives and their use as joint inhibitors of topomerase I and II
  申请人：——

  公开号：US20030139409A1

  公开（公告）日：2003-07-24

  A compound which is a benzo[a]phenazine-11-carboxamide derivative of formula (I) wherein each of R 1 to R 4 , which are the same or different, is selected from hydrogen, halogen, hydroxyl, C 1 -C 6 alkoxy which is unsubstituted or substituted, heteroaryloxy, C 1 -C 6 alkyl which is unsubstituted or substituted, nitro, cyano, azido, amidoxime, CO 2 R 10 , CON(R 12 ) 2 , OCON(R 12 ), SR 10 , SOR 11 , SO 2 (R 11 ), SO 2 N(R 12 ) 2 , N(R 12 ) 2 , NR 10 SO 2 R 11 , N(SO 2 R 11 ) 2 NR 10 (CH 2 ) n CN, NR 10 COR 11 , OCOR 11 or COR 10 ; each of R 5 to R 7 , which are the same or different, is selected from hydrogen, halogen, hydroxy, C 1 -C 6 alkoxy, C 1 -C 6 alkyl, SR 10 and N(R 12 ) 2 ; Q is C 1 -C 6 alkylene which is unsubstituted or substituted by (i) C 1 -C 6 alkyl which is unsubstituted or substituted, (ii) hydroxy, provided that the hydroxy group is not, to either of the N atoms adjacent to Q in formula (I), (iii) CO 2 R 10 , or (iv) CON(R 12 ); R 1 and R 9 , which are the same or different, are each hydrogen or C 1 -C 6 alkyl, or R 8 and R 9 together with the nitrogen atom to which they are attached form a saturated 5- or 6-membered N-containing heterocyclic ring which may include one additional heteroatom selected from O, N and S, or one of R 8 and R 9 is an alkylene chain optionally interrupted by O, N or S, which is attached to a carbon atom on the alkylene chain represented by Q to complete a saturated 5- or 6-membered N-containing heterocyclic ring as defined above; or a pharmaceutically acceptable salt thereof; with the proviso that at least one R 1 to R 4 is other than hydrogen. These compounds are inhibitors of topoisomerase I and/or topoisomerase II and can be used to treat tumours, including tumours which express MDR.

  一种化合物，是一种公式（I）的苯并[a]菲啉-11-甲酰胺衍生物，其中R1至R4中的每一个，它们相同或不同，被选择为氢、卤素、羟基、未取代或取代的C1-C6烷氧基、杂环氧基、未取代或取代的C1-C6烷基、硝基、氰基、叠氮基、酰肼基、CO2R10、CON(R12)2、OCON(R12)、SR10、SOR11、SO2(R11)、SO2N(R12)2、N(R12)2、NR10SO2R11、N(SO2R11)2NR10(CH2)nCN、NR10COR11、OCOR11或COR10；R5至R7中的每一个，它们相同或不同，被选择为氢、卤素、羟基、C1-C6烷氧基、C1-C6烷基、SR10和N(R12)2；Q是未取代或取代的C1-C6烷基，其被（i）未取代或取代的C1-C6烷基，（ii）羟基、前提是羟基不是在公式（I）中与Q相邻的任一N原子，（iii）CO2R10，或（iv）CON(R12)所取代；R1和R9，它们相同或不同，分别是氢或C1-C6烷基，或R8和R9连同它们连接到的氮原子形成饱和的5-或6-成员N-含杂环戊或六元环，可能包括一个额外的由O、N和S中选择的杂原子，或R8和R9中的一个是由O、N或S随机中断的烷基链，它连接到由Q表示的烷基链上的碳原子，以完成上述定义的饱和的5-或6-成员N-含杂环戊或六元环；或其药学上可接受的盐；但至少一个R1到R4不是氢。这些化合物是拓扑异构酶I和/或拓扑异构酶II的抑制剂，可用于治疗肿瘤，包括表达MDR的肿瘤。
• Lewis Acid Catalyzed Diels−Alder Reactions of 1,2-Naphthoquinones
  作者：Danny M. Gelman、Craig M. Forsyth、Patrick Perlmutter

  DOI：10.1021/ol9021047

  日期：2009.11.5

  The use of BF3·OEt2 catalysis in Diels−Alder reactions of 3,4-unsubstituted 1,2-naphthoquinones provides direct access to cis-tetrahydrophenanthrene derivatives in good to excellent yields (66−99%) without rapid adduct aromatization commonly associated with corresponding thermal processes.

  在3,4-未取代的1,2-萘醌的Diels-Alder反应中使用BF 3 ·OEt 2催化可直接获得顺式四氢菲衍生物，且收率高至优异（66-99％），而无需通常进行的快速加合物芳构化与相应的热处理过程。
• Understanding and predicting the potency of ROS-based enzyme inhibitors, exemplified by naphthoquinones and ubiquitin specific protease-2
  作者：Pushparathinam Gopinath、Atif Mahammed、Shimrit Ohayon、Zeev Gross、Ashraf Brik

  DOI：10.1039/c6sc02758j

  日期：——

  The same series of compounds was also examined in terms of their inhibitory effect on the enzymatic activity of USP2. One deduction from these investigations was that the ortho-quinone motif in β-lapachone is much better suited for the catalytic reduction of oxygen than the para-quinone motif and some approved quinone based drugs. A broader conclusion, obtained from the series of compounds with ortho-quinone

  最近的研究表明，诱导活性氧（ROS）形成的小分子选择性靶向癌细胞中过表达的酶可能是一种可行的癌症治疗方法。一个这样的例子是泛素特异性蛋白酶2（USP2）（一种对抗前列腺癌的新兴药物靶标）的失活被β-lapachone灭活，已确定其涉及将催化性半胱氨酸的硫醇残基氧化为亚磺酸。合理设计具有改进活性的β-拉帕酮类似物需要对决定此类分子产生ROS的变量有更好的了解。这个关键方面已通过关于其将分子氧还原为ROS的能力，对其1,2-萘醌骨架的调节和建立结构/活性关系。还检查了相同系列的化合物对USP2酶活性的抑制作用。从这些研究中得出的一个推论是，β-lapachone中的邻-醌基序比对-醌基序和某些批准的基于醌的药物更适合于催化还原氧。更广泛的结论，从系列用化合物的获得邻-quinone基序，是只有其氧化还原电位是在窄范围-0.3±0.1的V（剂与pH 7.5的水性缓冲液中的Ag / AgCl诱导R
• [EN] ENZYME INHIBITORS<br/>[FR] INHIBITEURS D'ENZYMES
  申请人：TECHNION RES & DEV FOUNDATION

  公开号：WO2018025259A1

  公开（公告）日：2018-02-08

  Naphthoquinone compounds that induce the formation of reactive oxygen species (ROS) are disclosed. Process of preparing the naphthoquinone compounds are also disclosed. Uses of the compounds for treating a disease or disorder are also disclosed.

  揭示了诱导产生活性氧自由基（ROS）的萘醌类化合物。还揭示了制备萘醌类化合物的方法。还揭示了使用这些化合物治疗疾病或障碍的用途。