2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine | 1100750-01-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine
• 英文别名: 2-Nitro-6-[[4-(trifluoromethoxy)phenyl]methoxy]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine；2-nitro-6-[[4-(trifluoromethoxy)phenyl]methoxy]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine
• CAS: 1100750-01-3
• 化学式: C₁₄H₁₃F₃N₄O₄
• 分子量: 358.277
• InChiKey: GFVMHDKZPCGREP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  94.1
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  tert-butyl 2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydropyrazolo[1,5-a]pyrimidine-4(5H)-carboxylate 在 lithium methanolate 作用下， 以 甲醇 为溶剂， 反应 15.0h， 以76%的产率得到2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  Synthesis, Reduction Potentials, and Antitubercular Activity of Ring A/B Analogues of the Bioreductive Drug (6S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)

  摘要：

  The nitroimidazooxazine S-1 (PA-824) is a new class of bioreductive drug for tuberculosis. A series of related bicyclic nitroheterocycles was synthesized, designed to have a wide range of one-electron reduction potentials E(1) (from -570 to -338 mV, compared with -534 mV for S-1). The observed E(l) values closely correlated with the sigma(m) values of the heteroatom at the 4/8-position of the adjacent six-membered ring. Although the compounds spanned a range of E(1) values around that of S-1, only the nitroimidazothiazines showed significant antitubercular activity (at a similar level of potency), suggesting that E(1) is not the main driver of efficacy. Furthermore, there was a correlation between activity and the formation of imidazole ring-reduced products at the two-electron level, pointing to the potential importance of this reduction pathway, which is determined by the nature of the substituent at the 2-position of the 4-nitroimidazole ring.

  DOI：

  10.1021/jm801087e

文献信息

• Synthesis, Reduction Potentials, and Antitubercular Activity of Ring A/B Analogues of the Bioreductive Drug (6<i>S</i>)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5<i>H</i>-imidazo[2,1-<i>b</i>][1,3]oxazine (PA-824)
  作者：Andrew M. Thompson、Adrian Blaser、Robert F. Anderson、Sujata S. Shinde、Scott G. Franzblau、Zhenkun Ma、William A. Denny、Brian D. Palmer

  DOI：10.1021/jm801087e

  日期：2009.2.12

  The nitroimidazooxazine S-1 (PA-824) is a new class of bioreductive drug for tuberculosis. A series of related bicyclic nitroheterocycles was synthesized, designed to have a wide range of one-electron reduction potentials E(1) (from -570 to -338 mV, compared with -534 mV for S-1). The observed E(l) values closely correlated with the sigma(m) values of the heteroatom at the 4/8-position of the adjacent six-membered ring. Although the compounds spanned a range of E(1) values around that of S-1, only the nitroimidazothiazines showed significant antitubercular activity (at a similar level of potency), suggesting that E(1) is not the main driver of efficacy. Furthermore, there was a correlation between activity and the formation of imidazole ring-reduced products at the two-electron level, pointing to the potential importance of this reduction pathway, which is determined by the nature of the substituent at the 2-position of the 4-nitroimidazole ring.