2-chloro-3-(bromomethyl)-6-methoxyquinoline | 125917-62-6

• 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-chloro-3-(bromomethyl)-6-methoxyquinoline
• 英文别名: 3-(bromomethyl)-2-chloro-6-methoxyquinoline
• CAS: 125917-62-6
• 化学式: C₁₁H₉BrClNO
• 分子量: 286.556
• InChiKey: YXJGKASYAYPNFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 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：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-3-(bromomethyl)-6-methoxyquinoline 、 5-(3,4,5-triethoxyphenyl)-1,3,4-oxadiazole-2-thiol 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以78%的产率得到
  参考文献：
  名称：

  Synthesis and Antibacterial Evaluation of Some Novel 1,3,4-oxadiazol Derivatives Incorporated with Quinoline Moiety

  摘要：

  5-(3,4,5-三乙氧基苯基)-1,3,4-噁二唑-2-硫醇6与3-(溴甲基)-2-氯喹啉或2-(对甲苯氧基)-3-(溴甲基)喹啉4a-j反应，合成了3-((5-(3,4,5-三乙氧基苯基)-1,3,4-噁二唑-2-硫代)甲基)-2-氯喹啉或3-((5-(3,4,5-三乙氧基苯基)-1,3,4-噁二唑-2-硫代)甲基)-2-(对甲苯氧基)喹啉7a-j。测定了合成的化合物的抗菌活性，化合物7d、7i和7j表现出优秀的活性。在与取代的3-(溴甲基)-2-氯喹啉或2-(对甲苯氧基)-3-(溴甲基)喹啉4a-j反应时，加入K2CO3和DMF，在室温下搅拌，得到了相应的3-((5-(3,4,5-三乙氧基苯基)-1,3,4-噁二唑-2-硫代)甲基)-2-氯喹啉或3-((5-(3,4-三乙氧基苯基)-1,3,4-噁二唑-2-硫代)甲基)-2-(对甲苯氧基)喹啉7a-j。所有合成的化合物都进一步进行了抗菌活性筛选，一些化合物对测试生物和参考标准表现出极佳的抗菌活性。

  DOI：

  10.5012/jkcs.2011.55.4.656
• 作为产物：
  描述：

  2-氯-6-甲氧基喹啉-3-甲醇 在 三溴化磷 作用下， 以 二氯甲烷 为溶剂， 生成 2-chloro-3-(bromomethyl)-6-methoxyquinoline
  参考文献：
  名称：

  Microwave Assisted Synthesis of Quinoline Fused Benzodiazepines as Anxiolytic and Antimicrobial Agents

  摘要：

  在本研究中，通过微波辐射促进的6/7/8-取代的3-溴甲基-2-氯喹啉（3a-j）与1,2-苯二胺反应合成喹啉融合的1,4-苯二氮杂环（4a-j）的高效、简便和环保的合成方案被开发出来。与K+通道的Surflex对接研究是抑制的生理靶标之一，发现在抑郁症的病理生理学中发挥作用，显示出这些化合物的一致得分在2.71-3.68范围内，表明所有相互作用力的总结。此外，化合物4d、4g和4i表现出强大的抗菌活性。

  DOI：

  10.14233/ajchem.2021.23153

文献信息

• Bridged 5,6,7,8-Tetrahydro-1,6-naphthyridines, Analogues of Huperzine A: Synthesis, Modelling Studies and Evaluation as Inhibitors of Acetylcholinesterase
  作者：Sofie Vanlaer、Arnout Voet、Constant Gielens、Marc De Maeyer、Frans Compernolle

  DOI：10.1002/ejoc.200800972

  日期：2009.2

  Derivatives of 6,8-bridged 5,6,7,8-tetrahydro-1,6-naphthyridines, designed as analogues of huperzine A, were synthesised and evaluated as inhibitors of acetylcholinesterase. In a first approach, C3-bridged naphthyridines were constructed by internal nucleophilic aromatic substitution of 2-chloro-3-(1-piperidinylmethyl)pyridine precursors containing a 3-CO2Me group on the 1-piperidinyl ring moiety.

  6,8-桥接 5,6,7,8-四氢-1,6-萘啶的衍生物，设计为石杉碱 A 的类似物，合成并评估为乙酰胆碱酯酶抑制剂。在第一种方法中，C3-桥接萘啶是通过内部亲核芳香取代 2-氯-3-(1-哌啶基甲基)吡啶前体在 1-哌啶基环部分上含有 3-CO2Me 基团来构建的。或者，应用 6,8-二烯丙基取代的四氢-1,6-萘啶的闭环复分解来构建不饱和 C4 桥。一些目标化合物显示出对乙酰胆碱酯酶的抑制，但低于石杉碱甲。抑制活性的相对顺序可以通过基于乙酰胆碱酯酶 - 石杉碱甲复合物的已知晶体结构的比较对接模拟研究来合理化。
• Microwave Assisted Synthesis of Quinoline Fused Benzodiazepines as Anxiolytic and Antimicrobial Agents
  作者：S.B. Marganakop、R.R. Kamble、A.R. Nesaragi、P.K. Bayannavar、S.D. Joshi、P.P. Kattimani、B.S. Sudha

  DOI：10.14233/ajchem.2021.23153

  日期：——

  In the present study, an efficient, facile and green protocol for synthesis of quinoline fused 1,4-benzodiazepine (4a-j) by microwave irradiated condensation of 6/7/8-substituted 3-bromomethyl- 2-chloro-quinoline (3a-j) obtained from 2-chloro 6/7/8-substituted quinoline-3-carbaldehyde (1a-j) with 1, 2-phenylenediamine was developed. Surflex docking studies with K+ channel is one of the physiological targets and inhibition, which plays a role in the pathophysiology of depression revealed that all these compounds show consensus score in the range 2.71-3.68 indicating the summary of all forces of interaction. Further, compounds 4d, 4g and 4i exhibited potent antibacterial activity

  在本研究中，通过微波辐射促进的6/7/8-取代的3-溴甲基-2-氯喹啉（3a-j）与1,2-苯二胺反应合成喹啉融合的1,4-苯二氮杂环（4a-j）的高效、简便和环保的合成方案被开发出来。与K+通道的Surflex对接研究是抑制的生理靶标之一，发现在抑郁症的病理生理学中发挥作用，显示出这些化合物的一致得分在2.71-3.68范围内，表明所有相互作用力的总结。此外，化合物4d、4g和4i表现出强大的抗菌活性。
• Synthesis and topoisomerase poisoning activity of A-ring and E-ring substituted luotonin A derivatives
  作者：Kassoum Nacro、Conxiang (Charles) Zha、Peter R. Guzzo、R. Jason Herr、Denise Peace、Thomas D. Friedrich

  DOI：10.1016/j.bmc.2007.03.067

  日期：2007.6

  A series of A-ring and E-ring analogues of the natural product luotonin A, a known topoisomerase I poison, was evaluated for growth inhibition in human carcinoma and leukemia cell lines. Rational design of structures was based on analogues of the related alkaloid camptothecin, which has been demonstrated to exert cytotoxic effects by the same mechanism of action. When compared to luotonin A, several compounds exhibited an improved topoisomerase I-dependent growth inhibition of a human leukemia cell line. (C) 2007 Elsevier Ltd. All rights reserved.
• Triazolothiadizepinylquinolines as potential MetAP-2 and NMT inhibitors: Microwave-assisted synthesis, pharmacological evaluation and molecular docking studies
  作者：Saba Kauser J. Shaikh、Ravindra R. Kamble、Praveen K. Bayannavar、Shilpa M. Somagond、Shrinivas D. Joshi

  DOI：10.1016/j.molstruc.2019.127445

  日期：2020.3

  The enzymes MetAP-2 and NMT play a crucial role in the process of myristoylation of oncoproteins which is deregulated in many types of cancers. Execution of both these enzymes is considered as strategy for the intervention of various cancers and relative fungal infections, and hence the discovery of novel MetAP-2 and NMT inhibitors necessitate their high relevancy. In this investigation, we have synthesized a series of novel seven-membered triazolothiadiazepinyl quinolines 10(a-m) distinctively under microwave irradiation technique and identified as selective MetAP-2 and NMT inhibitors. Amongst the functionalized derivatives when evaluated for the in vitro antifungal assay, compounds 10b, 10c, 10e and 10f were considered promising due to notable inhibitory effects (MIC = 0.2 mg/mL) on Aspergillus fumigatus. Screening of the anticancer activity against NCI-60 Human tumor cell lines portrayed that conjugates 10b, 10c, 10e and 10f were found to be moderately effective against the Renal Cancer cell line UO-31. The data acquired from biological studies was further validated by molecular docking studies and p harmaco kinetic evaluation. (C) 2019 Elsevier B.V. All rights reserved.
• Tetrazolylmethyl quinolines: Design, docking studies, synthesis, anticancer and antifungal analyses
  作者：Saba Kauser J. Shaikh、Ravindra R. Kamble、Shilpa M. Somagond、H.C. Devarajegowda、Sheshagiri R. Dixit、Shrinivas D. Joshi

  DOI：10.1016/j.ejmech.2017.01.043

  日期：2017.3

  A new series of 2,5 and 1,5-regioisomers of the tetrazolyl group viz., 3-[(5-benzyl/benzylthio-2H-tetrazol-2- yl) methyl]-2-chloro-6-substituted quinoline 6h-q and 3-[(5-benzyl/benzylthio-1H-tetrazol-1-yl) methyl]-2-chloro-6-substituted quinolines 7h-q were synthesized. Docking studies of all these compounds with DNA as target using PDB: 1AU5 and 453D revealed that the compounds 6h and 6i act as covalent cross linker on the DNA helix of the former and intercalate the latter both with higher C score values. Another set of docking studies in the active pocket of dihydrofolate reductase and N-myristoyl transferase as targets to assess antifungal activity revealed that compounds 6k, 6l, 6p and 7q (with bromo and fluro substituents) showcases different binding modes and hydrogen bonding. Further, the compounds were screened for anticancer activity (primary cytotoxicity) against NCI-60 Human tumor cell line at a single high dose (10(-5) M) concentration assay. Among the tested compounds, 6h has shown 99.28% of GI against Melanoma (SK-MEL-5) and compound 6i has shown 97.56% of GI against Breast Cancer (T-47D). Further, in vitro antifungal assay against A. fumigatus and C. albicans for these compounds 6h-q and 7h-q revealed potential to moderate activities as compared to the standard. (C) 2017 Elsevier Masson SAS. All rights reserved.