methyl 5-formyl-2-(trifluoromethoxy)benzoate | 1321963-28-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 5-formyl-2-(trifluoromethoxy)benzoate
• CAS: 1321963-28-3
• 化学式: C₁₀H₇F₃O₄
• 分子量: 248.158
• InChiKey: OYFSENHPNPIBDH-UHFFFAOYSA-N

物化性质

• 沸点：
  293.1±40.0 °C(Predicted)
• 密度：
  1.383±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-2-硝基-6,7-二氢-5H-咪唑并[2,1-B][1,3]噁嗪-6-胺 、 methyl 5-formyl-2-(trifluoromethoxy)benzoate 在 溶剂黄146 、 sodium cyanoborohydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以55%的产率得到(S)-methyl 5-((2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]-oxazin-6-ylamino)methyl)-2-(trifluoromethoxy)benzoate
  参考文献：
  名称：

  Structure–Activity Relationships of Antitubercular Nitroimidazoles. 3. Exploration of the Linker and Lipophilic Tail of ((S)-2-Nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl)-(4-trifluoromethoxybenzyl)amine (6-Amino PA-824).

  摘要：

  The (S)-2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine named PA-824 (1) has demonstrated antitubercular activity in vitro and in animal models and is currently in clinical trials. We synthesized derivatives at three positions of the 4-(trifluoromethoxy)benzylamino tail, and these were tested for whole-cell activity against both replicating and nonreplicating Mycobacterium tuberculosis (Mtb). In addition, we determined their kinetic parameters as substrates of the deazaflavin-dependent nitroreductase (Ddn) from Mtb that reductively activates these pro-drugs. These studies yielded multiple compounds with 40 nM aerobic whole cell activity and 1.6 mu M anaerobic whole cell activity: 10-fold improvements over both characteristics from the parent molecule. Some of these compounds exhibited enhanced solubility with acceptable stability to microsomal and in vivo metabolism. Analysis of the conformational preferences of these analogues using quantum chemistry suggests a preference for a pseudoequatorial orientation of the linker and lipophilic tail.

  DOI：

  10.1021/jm1010644
• 作为产物：
  描述：

  4-(三氟甲氧基)苄醇 在 咪唑 、 四丁基氟化铵 、 仲丁基锂 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 、 环己烷 为溶剂， 反应 22.5h， 生成 methyl 5-formyl-2-(trifluoromethoxy)benzoate
  参考文献：
  名称：

  Structure–Activity Relationships of Antitubercular Nitroimidazoles. 3. Exploration of the Linker and Lipophilic Tail of ((S)-2-Nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl)-(4-trifluoromethoxybenzyl)amine (6-Amino PA-824).

  摘要：

  The (S)-2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine named PA-824 (1) has demonstrated antitubercular activity in vitro and in animal models and is currently in clinical trials. We synthesized derivatives at three positions of the 4-(trifluoromethoxy)benzylamino tail, and these were tested for whole-cell activity against both replicating and nonreplicating Mycobacterium tuberculosis (Mtb). In addition, we determined their kinetic parameters as substrates of the deazaflavin-dependent nitroreductase (Ddn) from Mtb that reductively activates these pro-drugs. These studies yielded multiple compounds with 40 nM aerobic whole cell activity and 1.6 mu M anaerobic whole cell activity: 10-fold improvements over both characteristics from the parent molecule. Some of these compounds exhibited enhanced solubility with acceptable stability to microsomal and in vivo metabolism. Analysis of the conformational preferences of these analogues using quantum chemistry suggests a preference for a pseudoequatorial orientation of the linker and lipophilic tail.

  DOI：

  10.1021/jm1010644

文献信息

• Structure–Activity Relationships of Antitubercular Nitroimidazoles. 3. Exploration of the Linker and Lipophilic Tail of ((<i>S</i>)-2-Nitro-6,7-dihydro-5<i>H</i>-imidazo[2,1-<i>b</i>][1,3]oxazin-6-yl)-(4-trifluoromethoxybenzyl)amine (6-Amino PA-824).
  作者：Joseph Cherian、Inhee Choi、Amit Nayyar、Ujjini H. Manjunatha、Tathagata Mukherjee、Yong Sok Lee、Helena I. Boshoff、Ramandeep Singh、Young Hwan Ha、Michael Goodwin、Suresh B. Lakshminarayana、Pornwaratt Niyomrattanakit、Jan Jiricek、Sindhu Ravindran、Thomas Dick、Thomas H. Keller、Veronique Dartois、Clifton E. Barry

  DOI：10.1021/jm1010644

  日期：2011.8.25

  The (S)-2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine named PA-824 (1) has demonstrated antitubercular activity in vitro and in animal models and is currently in clinical trials. We synthesized derivatives at three positions of the 4-(trifluoromethoxy)benzylamino tail, and these were tested for whole-cell activity against both replicating and nonreplicating Mycobacterium tuberculosis (Mtb). In addition, we determined their kinetic parameters as substrates of the deazaflavin-dependent nitroreductase (Ddn) from Mtb that reductively activates these pro-drugs. These studies yielded multiple compounds with 40 nM aerobic whole cell activity and 1.6 mu M anaerobic whole cell activity: 10-fold improvements over both characteristics from the parent molecule. Some of these compounds exhibited enhanced solubility with acceptable stability to microsomal and in vivo metabolism. Analysis of the conformational preferences of these analogues using quantum chemistry suggests a preference for a pseudoequatorial orientation of the linker and lipophilic tail.