2,4-dichloro-6,8-dimethoxyquinoline | 65628-72-0

• 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: 2,4-dichloro-6,8-dimethoxyquinoline
• CAS: 65628-72-0
• 化学式: C₁₁H₉Cl₂NO₂
• 分子量: 258.104
• InChiKey: PJCWWDPIHKIDPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  31.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,4-dichloro-6,8-dimethoxyquinoline 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N-甲基吡咯烷酮 、 异丙醇 为溶剂， 反应 4.33h， 生成 6,8-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinolin-4-amine
  参考文献：
  名称：

  5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors

  摘要：

  一系列喹啉衍生物被合成并生物学评估为增强型Zeste同源物2（EZH2）抑制剂。结构-活性关系（SAR）研究表明，发现了一种化合物5-甲氧基-2-(4-甲基-1,4-二氮杂环庚烷-1-基)-N-(1-甲基哌啶-4-基)喹啉-4-胺（5k），其对EZH2的IC50值为1.2 μM，能降低细胞内全局H3K27me3水平，并显示出对两种肿瘤细胞株的良好抗增殖活性。由于其低分子量且迄今未有喹啉衍生物报道作为EZH2抑制剂，该化合物可能作为进一步优化的先导化合物。

  DOI：

  10.3390/molecules20057620
• 作为产物：
  描述：

  丙二酸 、 2,4-二甲氧基苯胺 在 三氯氧磷 作用下， 反应 16.0h， 生成 2,4-dichloro-6,8-dimethoxyquinoline
  参考文献：
  名称：

  5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors

  摘要：

  一系列喹啉衍生物被合成并生物学评估为增强型Zeste同源物2（EZH2）抑制剂。结构-活性关系（SAR）研究表明，发现了一种化合物5-甲氧基-2-(4-甲基-1,4-二氮杂环庚烷-1-基)-N-(1-甲基哌啶-4-基)喹啉-4-胺（5k），其对EZH2的IC50值为1.2 μM，能降低细胞内全局H3K27me3水平，并显示出对两种肿瘤细胞株的良好抗增殖活性。由于其低分子量且迄今未有喹啉衍生物报道作为EZH2抑制剂，该化合物可能作为进一步优化的先导化合物。

  DOI：

  10.3390/molecules20057620

文献信息

• Preparation of (−)-Nutlin-3 Using Enantioselective Organocatalysis at Decagram Scale
  作者：Tyler A. Davis、Anna E. Vilgelm、Ann Richmond、Jeffrey N. Johnston

  DOI：10.1021/jo401321a

  日期：2013.11.1

  Chiral nonracemic cis-4,5-bis(aryl)imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. The lack of efficient methods for the enantioselective synthesis of cis-imidazolines, however, has limited their more general use. Our disclosure of the first enantioselective synthesis of (-)-Nutlin-3 provided a basis to prepare larger amounts of this tool used widely in cancer biology. Key to the decagram-scale synthesis described here was the discovery of a novel bis(amidine) organocatalyst that provides high enantioselectivity at warmer reaction temperature (-20 degrees C) and low catalyst loadings. Further refinements to the procedure led to the synthesis of (-)-Nutlin-3 in a 17 g batch and elimination of all but three chromatographic purifications.
• 5-Methoxyquinoline Derivatives as a New Class of EZH2 Inhibitors
  作者：Pu Xiang、Hui Jie、Yang Zhou、Bo Yang、Hui-Juan Wang、Jing Hu、Jian Hu、Sheng-Yong Yang、Ying-Lan Zhao

  DOI：10.3390/molecules20057620

  日期：——

  A series of quinoline derivatives was synthesized and biologically evaluated as Enhancer of Zeste Homologue 2 (EZH2) inhibitors. Structure-activity relationship (SAR) studies led to the discovery of 5-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinolin-4-amine (5k), which displayed an IC50 value of 1.2 μM against EZH2, decreased global H3K27me3 level in cells and also showed good anti-viability activities against two tumor cell lines. Due to the low molecular weight and the fact that no quinoline derivative has been reported as an EZH2 inhibitor, this compound could serve as a lead compound for further optimization.

  一系列喹啉衍生物被合成并生物学评估为增强型Zeste同源物2（EZH2）抑制剂。结构-活性关系（SAR）研究表明，发现了一种化合物5-甲氧基-2-(4-甲基-1,4-二氮杂环庚烷-1-基)-N-(1-甲基哌啶-4-基)喹啉-4-胺（5k），其对EZH2的IC50值为1.2 μM，能降低细胞内全局H3K27me3水平，并显示出对两种肿瘤细胞株的良好抗增殖活性。由于其低分子量且迄今未有喹啉衍生物报道作为EZH2抑制剂，该化合物可能作为进一步优化的先导化合物。
• Synthesis of 6-methoxy-N 2,N 2,N 4,N 4,N 5,N 5-hexamethylquinoline-2,4,5-triamine – a new representative of quinoline proton sponges
  作者：Olga V. Dyablo、Alexander F. Pozharskii、Elena A. Shmoilova、Aleksey O. Savchenko

  DOI：10.1007/s10593-015-1693-6

  日期：2015.3

  [GRAPHICS]We report the synthesis of 4-chloro-2-methyl-5-nitro-and 2,4-dichloro-5-nitroquinolines, containing methoxy groups at positions 6 and 8. The reaction of these compounds with dimethylamine solution in alcohol was shown to produce not only aminodehalogenation products, but also resulted in nucleophilic substitution of the methoxy groups. The reduction of 6-methoxy-N-2,N-2,N-4,N-4-tetramethyl-5- nitroquinoline-2,4-diamine with subsequent methylation gave 6-methoxy-N-2,N-2,N-4,N-4,N-5,N-5-hexamethylquinoline-2,4,5-triamine, a new representative of quinoline proton sponges.