3-bromo-6-methoxy-2-methylquinolin-4(1H)-one | 690694-88-3

• 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: 3-bromo-6-methoxy-2-methylquinolin-4(1H)-one
• 英文别名: 3-Bromo-4-hydroxy-6-methoxy-2-methylquinoline；3-bromo-6-methoxy-2-methyl-1H-quinolin-4-one
• CAS: 690694-88-3
• 化学式: C₁₁H₁₀BrNO₂
• 分子量: 268.11
• InChiKey: XBVJDXSHXOPCFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-bromo-6-methoxy-2-methylquinolin-4(1H)-one 在 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 五氯化磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.08h， 以82%的产率得到3-bromo-4-chloro-6-methoxy-2-methylquinolin-4(1H)-one
  参考文献：
  名称：

  6H-Chromeno[3,4-b] 喹啉和 6a,12a-Dehydro-7-azarotenoid 的合成

  摘要：

  报道了通过钯介导的偶联反应制备 6H-色烯[3,4-b]喹啉，并首次合成了天然存在的类鱼素的含氮脱氢类似物。

  DOI：

  10.3987/com-09-11868
• 作为产物：
  描述：

  4-羟基-6-甲氧基-2-甲基喹啉 在 N-溴代丁二酰亚胺(NBS) 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 生成 3-bromo-6-methoxy-2-methylquinolin-4(1H)-one
  参考文献：
  名称：

  作为潜在的新型拓扑异构酶 I 抑制剂的氮杂硼烷酮衍生物的设计和合成

  摘要：

  基于天然产物boeravinones的结构骨架，采用氮原子取代策略设计合成了两种6 H-色烯并[3,4- b ]喹啉衍生物。然后，针对六种人类肿瘤细胞系评估它们的细胞毒活性，包括 HepG2（肝细胞癌）、A2780（卵巢癌）、Hela（宫颈癌）、HCT116（结直肠癌）、SW1990（胰腺癌）和 MCF7（乳腺癌） . 结果表明，化合物ZML-8和ZML-14对HepG2细胞具有很强的抑制活性，IC 50值分别为0.58和1.94 μM。此外，ZML-8和ZML-14对 HepG2 和 L-02 细胞的选择性高于 Topotecan。机制上，ZML-8和ZML-14不仅诱导细胞周期停滞在 G2/M 期和细胞凋亡，而且剂量依赖性地抑制 HepG2 细胞的拓扑异构酶 I 活性并诱导 DNA 损伤。分子对接表明ZML-8和ZML-14可以与拓扑异构酶I-DNA复合物相互作用，结合方式与拓扑替康相

  DOI：

  10.1016/j.bioorg.2022.105747

文献信息

• Synthesis of a 6H-Chromeno[3,4-b]quinoline and a 6a,12a-Dehydro-7-azarotenoid
  作者：Yvette A. Jackson、Andrew L. C. Morris

  DOI：10.3987/com-09-11868

  日期：——

  The preparation of a 6H-chromeno[3,4-b]quinoline via a palladium-mediated coupling reaction, and the first synthesis of a nitrogenous dehydroanalogue of the naturally occurring rotenoids are reported.

  报道了通过钯介导的偶联反应制备 6H-色烯[3,4-b]喹啉，并首次合成了天然存在的类鱼素的含氮脱氢类似物。
• Endochin Optimization: Structure−Activity and Structure−Property Relationship Studies of 3-Substituted 2-Methyl-4(1<i>H</i>)-quinolones with Antimalarial Activity
  作者：R. Matthew Cross、Andrii Monastyrskyi、Tina S. Mutka、Jeremy N. Burrows、Dennis E. Kyle、Roman Manetsch

  DOI：10.1021/jm1007903

  日期：2010.10.14

  Since the 1940s endochin and analogues thereof were known to be causal prophylactic and potent erythrocytic stage agents in avian models. Preliminary screening in a current in vitro assay identified several 4(1H)-quinolones with nanomolar EC(50) against erythrocytic stages of mullidrug resistant W2 and TM90-C2B isolates of Plasmodium folciparum. Follow-up structure activity relationship (SAR) studies on 4(1H)-quinolone analogues identified several key features for biological activity. Nevertheless, structure property relationship (SPR) studies conducted in parallel revealed that 4(1H)-quinolone analogues are limited by poor solubilities and rapid microsomal degradations. To improve the overall efficacy, multiple 4(1H)-quinolone series with varying substituents on the benzenoid quinolone ring and/or the 3-position were synthesized and tested for in vitro antimalarial activity. Several structurally diverse 6-chloro-2-methyl-7-methoxy-4(1H)-quinolones with EC(50) in the low nanomolar range against the clinically relevant isolates W2 and TM90-C2B were identified with improved physicochemical properties while maintaining little to no cross-resistance with atovaquone.
• Divergent Route to Access Structurally Diverse 4-Quinolones via Mono or Sequential Cross-Couplings
  作者：R. Matthew Cross、Roman Manetsch

  DOI：10.1021/jo1014504

  日期：2010.12.17

  A divergent route was developed to access 3-iodo- and 6-chloro-3-iodo-4(1H)-quinolones for further elaboration via mono and/or sequential Suzuki-Miyaura cross-coupling to generate novel and medicinally important 4(1H)-quinolones. Copper- and palladium-catalyzed cyanations were used to functionalize the 4-quinolone core further.
• Design and synthesis of Aza-boeravinone derivatives as potential novel topoisomerase I inhibitors
  作者：Yong Zhou、Yin-Peng Bai、Mi Zhang、Jian-Mei Gao、Cheng-Jie Yang、Zhi-Jun Zhang、Nan Deng、Lei Li、Ying-Qian Liu、Chuan-Rui Xu

  DOI：10.1016/j.bioorg.2022.105747

  日期：2022.5

  phase and cell apoptosis, but also dose-dependently inhibited topoisomerase I activity and induced DNA damage in HepG2 cells. Molecular docking showed that ZML-8 and ZML-14 could interact with topoisomerase I-DNA complex with a similar binding mode to Topotecan. Inhibitory activities of these two compounds on topoisomerase I were then confirmed in both cell-free systems and in whole-cell lysates. Taken

  基于天然产物boeravinones的结构骨架，采用氮原子取代策略设计合成了两种6 H-色烯并[3,4- b ]喹啉衍生物。然后，针对六种人类肿瘤细胞系评估它们的细胞毒活性，包括 HepG2（肝细胞癌）、A2780（卵巢癌）、Hela（宫颈癌）、HCT116（结直肠癌）、SW1990（胰腺癌）和 MCF7（乳腺癌） . 结果表明，化合物ZML-8和ZML-14对HepG2细胞具有很强的抑制活性，IC 50值分别为0.58和1.94 μM。此外，ZML-8和ZML-14对 HepG2 和 L-02 细胞的选择性高于 Topotecan。机制上，ZML-8和ZML-14不仅诱导细胞周期停滞在 G2/M 期和细胞凋亡，而且剂量依赖性地抑制 HepG2 细胞的拓扑异构酶 I 活性并诱导 DNA 损伤。分子对接表明ZML-8和ZML-14可以与拓扑异构酶I-DNA复合物相互作用，结合方式与拓扑替康相