2-bromo-1-{3-{[tert-butyl(dimethyl)silyl]oxy}-2-[(4-iodophenoxy)methyl]propyl}-4-nitro-1H-imidazole | 1263188-79-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-bromo-1-{3-{[tert-butyl(dimethyl)silyl]oxy}-2-[(4-iodophenoxy)methyl]propyl}-4-nitro-1H-imidazole
• 英文别名: [2-[(2-Bromo-4-nitroimidazol-1-yl)methyl]-3-(4-iodophenoxy)propoxy]-tert-butyl-dimethylsilane
• CAS: 1263188-79-9
• 化学式: C₁₉H₂₇BrIN₃O₄Si
• 分子量: 596.335
• InChiKey: ISROQRAGNONQEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.88
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-bromo-1-{3-{[tert-butyl(dimethyl)silyl]oxy}-2-[(4-iodophenoxy)methyl]propyl}-4-nitro-1H-imidazole 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium hydride 、 sodium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 生成 6-{[(4'-fluoro[1,1'-biphenyl]-4-yl)oxy]methyl}-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
  参考文献：
  名称：

  Biarylmethoxy 2-nitroimidazooxazine antituberculosis agents: Effects of proximal ring substitution and linker reversal on metabolism and efficacy

  摘要：

  Certain biaryl analogues of antitubercular drug PA-824 displayed enhanced in vivo efficacies yet retained some susceptibility towards oxidative metabolism; therefore, two new strategies were explored to address this. Ortho-substitution of the proximal aryl ring with larger electron-withdrawing substituents maintained or improved compound stability but reduced aerobic potency; however, fluoro and cyano were well tolerated. In vivo, only 2'- or 3'-fluoro mono-substitution preserved high efficacy against acute infection, although one example was twofold more effective than delamanid against chronic infection. Reversal of the 6-oxymethylene linkage also permitted high potency and improved stability towards human liver microsomes, albeit, in vivo results were inferior. These novel findings provide further insight into the preferred structural features for lead candidates in this important drug class. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.084
• 作为产物：
  描述：

  3-{[tert-butyl(dimethyl)silyl]oxy}-2-[(4-iodophenoxy)methyl]-1-propanol 在 咪唑 、 碘 、 potassium carbonate 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-bromo-1-{3-{[tert-butyl(dimethyl)silyl]oxy}-2-[(4-iodophenoxy)methyl]propyl}-4-nitro-1H-imidazole
  参考文献：
  名称：

  Biarylmethoxy 2-nitroimidazooxazine antituberculosis agents: Effects of proximal ring substitution and linker reversal on metabolism and efficacy

  摘要：

  Certain biaryl analogues of antitubercular drug PA-824 displayed enhanced in vivo efficacies yet retained some susceptibility towards oxidative metabolism; therefore, two new strategies were explored to address this. Ortho-substitution of the proximal aryl ring with larger electron-withdrawing substituents maintained or improved compound stability but reduced aerobic potency; however, fluoro and cyano were well tolerated. In vivo, only 2'- or 3'-fluoro mono-substitution preserved high efficacy against acute infection, although one example was twofold more effective than delamanid against chronic infection. Reversal of the 6-oxymethylene linkage also permitted high potency and improved stability towards human liver microsomes, albeit, in vivo results were inferior. These novel findings provide further insight into the preferred structural features for lead candidates in this important drug class. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.084