2-(4-fluorophenyl)-7-methyl-3-(morpholine-1-ylmethyl)imidazo[1,2-a]pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 2-(4-fluorophenyl)-7-methyl-3-(morpholine-1-ylmethyl)imidazo[1,2-a]pyridine
• 英文别名: 4-[[2-(4-Fluorophenyl)-7-methylimidazo[1,2-a]pyridin-3-yl]methyl]morpholine；4-[[2-(4-fluorophenyl)-7-methylimidazo[1,2-a]pyridin-3-yl]methyl]morpholine
• 化学式: C₁₉H₂₀FN₃O
• 分子量: 325.386
• InChiKey: ASVKMVREUFQKDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  29.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-4-甲基吡啶 、 2-氯代-4'-氟苯乙酮 在 聚合甲醛 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 生成 2-(4-fluorophenyl)-7-methyl-3-(morpholine-1-ylmethyl)imidazo[1,2-a]pyridine
  参考文献：
  名称：

  Discovery of new leads against Mycobacterium tuberculosis using scaffold hopping and shape based similarity

  摘要：

  BM212 [1,5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)-methyl-pyrrole] is a pyrrole derivative with strong inhibitory activity against drug resistant Mycobacterium tuberculosis and mycobacteria residing in macrophages. However, it was not pursued because of its poor pharmacokinetics and toxicity profile. Our goal was to design and synthesize new antimycobacterial BM212 analogs with lower toxicity and better pharmacokinetic profile. Using the scaffold hopping approach, three structurally diverse heterocycles - 2,3-disubstituted imidazopyridines, 2,3-disubstituted benzimidazoles and 1,2,4-trisubstituted imidazoles emerged as promising antitubercular agents. All compounds were synthesized through easy and convenient methods and their structures confirmed by IR, H-1 NMR, C-11 NMR and MS. In-vitro cytotoxicity studies on normal kidney monkey cell lines and HepG2 cell lines, as well as metabolic stability studies on rat liver microsomes for some of the most active compounds, established that these compounds have negligible cytotoxicity and are metabolically stable. Interestingly the benzimidazole compound (4a) is as potent as the parent molecule BM212 (MIC 2.3 mu g/ml vs 0.7-1.5 mu g/ml), but is devoid of the toxicity against HepG2 cell lines (IC50 203.10 mu M vs 7.8 mu M). (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.07.034

文献信息

• Oxidative Cross-Coupling of sp³- and sp²-Hybridized C–H Bonds: Vanadium-Catalyzed Aminomethylation of Imidazo[1,2-<i>a</i>]pyridines
  作者：Pinku Kaswan、Ashley Porter、Kasiviswanadharaju Pericherla、Marissa Simone、Sean Peters、Anil Kumar、Brenton DeBoef

  DOI：10.1021/acs.orglett.5b02539

  日期：2015.11.6

  The vanadium-catalyzed oxidative coupling of substituted 2-arylimidiazo[1,2-a]pyridines to N-methylmorpholine oxide, which acts as both a coupling partner and an oxidant, has been achieved. This reaction was applied to various substituted imidiazo[1,2-a]pyridine and indole substrates, resulting in yields as high as 90%. Mechanistic investigations indicate that the reaction may proceed via a Mannich-type

  已经实现了取代的2-芳基咪唑并[1,2- a ]吡啶对N-甲基吗啉氧化物的钒催化氧化偶联，N-甲基吗啉既是偶联剂又是氧化剂。该反应用于各种取代的咪唑并[1,2- a ]吡啶和吲哚底物，产率高达90％。机理研究表明该反应可以通过曼尼希型过程进行。这项工作证明了如何将氧化氨基甲基化用作将叔胺引入杂环的有用方法，从而为常规曼尼希型反应提供了另一种方法。
• Discovery of new leads against Mycobacterium tuberculosis using scaffold hopping and shape based similarity
  作者：Ravindra D. Wavhale、Elvis A.F. Martis、Premlata K. Ambre、Baojie Wan、Scott G. Franzblau、Krishna R. Iyer、Kavita Raikuvar、Katarzyna Macegoniuk、Łukasz Berlicki、Santosh R. Nandan、Evans C. Coutinho

  DOI：10.1016/j.bmc.2017.07.034

  日期：2017.9

  BM212 [1,5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)-methyl-pyrrole] is a pyrrole derivative with strong inhibitory activity against drug resistant Mycobacterium tuberculosis and mycobacteria residing in macrophages. However, it was not pursued because of its poor pharmacokinetics and toxicity profile. Our goal was to design and synthesize new antimycobacterial BM212 analogs with lower toxicity and better pharmacokinetic profile. Using the scaffold hopping approach, three structurally diverse heterocycles - 2,3-disubstituted imidazopyridines, 2,3-disubstituted benzimidazoles and 1,2,4-trisubstituted imidazoles emerged as promising antitubercular agents. All compounds were synthesized through easy and convenient methods and their structures confirmed by IR, H-1 NMR, C-11 NMR and MS. In-vitro cytotoxicity studies on normal kidney monkey cell lines and HepG2 cell lines, as well as metabolic stability studies on rat liver microsomes for some of the most active compounds, established that these compounds have negligible cytotoxicity and are metabolically stable. Interestingly the benzimidazole compound (4a) is as potent as the parent molecule BM212 (MIC 2.3 mu g/ml vs 0.7-1.5 mu g/ml), but is devoid of the toxicity against HepG2 cell lines (IC50 203.10 mu M vs 7.8 mu M). (C) 2017 Elsevier Ltd. All rights reserved.