1-[3-bromo-2-(tetrahydro-2H-pyran-2-yloxy)propyl]-3,5-dinitro-1H-pyrazole | 1100750-36-4

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 1-[3-bromo-2-(tetrahydro-2H-pyran-2-yloxy)propyl]-3,5-dinitro-1H-pyrazole
• 英文别名: 1-[3-Bromo-2-(oxan-2-yloxy)propyl]-3,5-dinitropyrazole
• CAS: 1100750-36-4
• 化学式: C₁₁H₁₅BrN₄O₆
• 分子量: 379.167
• InChiKey: BGOQTXVPJDYDBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  128
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[3-bromo-2-(tetrahydro-2H-pyran-2-yloxy)propyl]-3,5-dinitro-1H-pyrazole 、 三异丙基硅烷硫醇 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 18.08h， 生成
  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
• 作为产物：
  描述：

  2-((1,3-dibromopropan-2-yl)oxy)tetrahydro-2H-pyran 、 3,5-二硝基-1H-吡唑 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 以25%的产率得到1-[3-bromo-2-(tetrahydro-2H-pyran-2-yloxy)propyl]-3,5-dinitro-1H-pyrazole
  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.