5-(quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester | 1141427-91-9

• 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: 5-(quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester
• 英文别名: Ethyl 5-(4-quinolyloxymethyl)isoxazole-3-carboxylate；ethyl 5-(quinolin-4-yloxymethyl)-1,2-oxazole-3-carboxylate
• CAS: 1141427-91-9
• 化学式: C₁₆H₁₄N₂O₄
• 分子量: 298.298
• InChiKey: AQYPGDVWEXMZJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  74.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-羟基喹啉 、 5-溴甲基异噁唑-3-甲酸乙酯 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 0.5h， 以54%的产率得到5-(quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  新型甲氟喹-异恶唑羧酸酯的前药合成与抗结核活性

  摘要：

  据报道，5-（2,8-双（三氟甲基）喹啉-4-基氧基甲基）异恶唑-3-羧酸乙酯（化合物3）对复制型和非复制型结核分枝杆菌均具有优异的抗结核活性，且抑制最小浓度（MIC）分别为0.9μM和12.2μM。在这项研究中，进一步研究了化合物3的抗结核活性。它的活性似乎对结核分枝杆菌复合物的生物非常有特异性，并以4.1μM的EC 90显着降低了感染巨噬细胞中细菌的数量。更重要的是，相应酸的体外抗结核活性增加（化合物4）在pH 6.0时提示它可能在由结核病患者的肺部炎症引起的酸性环境中具有体内活性。化合物3的各种酯生物等排体失去抗TB活性的事实进一步表明，酯化合物3可以起前药的作用。这项研究的详细的结构-活性关系（SAR）应该有助于我们提高该异恶唑酯系列抗TB药效的最终目标。

  DOI：

  10.1016/j.bmcl.2009.11.105

文献信息

• Structure−Activity Relationships for a Series of Quinoline-Based Compounds Active against Replicating and Nonreplicating <i>Mycobacterium tuberculosis</i>
  作者：Annamaria Lilienkampf、Jialin Mao、Baojie Wan、Yuehong Wang、Scott G. Franzblau、Alan P. Kozikowski

  DOI：10.1021/jm900003c

  日期：2009.4.9

  Tuberculosis (TB) remains as a global pandemic that is aggravated by a lack of health care, the spread of HIV, and the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains. New anti-TB drugs are urgently required to shorten the long 6-12 month treatment regimen and to battle drug-resistant Mtb strains. We have identified several potent quinoline-based anti-TB compounds, bearing an isoxazole containing side-chain. The most potent compounds, 7g and 13, exhibited submicromolar activity against the replicating bacteria (R-TB), with minimum inhibitory concentrations (MICs) of 0.77 and 0.95 mu M, respectively. In general, these compounds also had micromolar activity against the nonreplicating persistent bacteria (NRP-TB) and did not show toxicity on Vero cells up to 128 mu M concentration. Compounds 7g and 13 were shown to retain their anti-TB activity against rifampin, isoniazid, and streptomycin resistant Mtb strains. The results suggest that quinoline-isoxazole-based anti-TB compounds are promising leads for new TB drug development.