3-{[tert-butyl(dimethyl)silyl]oxy}-2-[(4-iodophenoxy)methyl]-1-propanol | 1263188-77-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-{[tert-butyl(dimethyl)silyl]oxy}-2-[(4-iodophenoxy)methyl]-1-propanol
• 英文别名: 2-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-(4-iodophenoxy)propan-1-ol
• CAS: 1263188-77-7
• 化学式: C₁₆H₂₇IO₃Si
• 分子量: 422.379
• InChiKey: LISJLDJPZPFZQD-UHFFFAOYSA-N

物化性质

• 沸点：
  429.0±45.0 °C(Predicted)
• 密度：
  1.303±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  tert-butyl((2-(iodomethyl)allyl)oxy)dimethylsilane 在 sodium tetrahydroborate 、 碘 、 potassium carbonate 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 20.0h， 生成 3-{[tert-butyl(dimethyl)silyl]oxy}-2-[(4-iodophenoxy)methyl]-1-propanol
  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

文献信息

• NITROIMIDAZOOXAZINE AND NITROIMIDAZOOXAZOLE ANALOGUES AND THEIR USES
  申请人：Thompson Andrew Mark

  公开号：US20110028466A1

  公开（公告）日：2011-02-03

  The current invention pertains to nitroimidazooxazine and nitroimidazooxazole analogues, their methods of preparation, and uses of the compounds as treatment for Mycobacterium tuberculosis , for use as anti-tubercular drugs, for use as anti-protozoal agents with unexpectedly high potency against Trypanosoma cruzi or Leishmania donovani , and for the treatment of other microbial infections.

  当前的发明涉及硝基咪唑噁啉和硝基咪唑噁唑类似物，它们的制备方法，以及将这些化合物用作治疗结核分枝杆菌、用作抗结核药物、用作对克氏锥虫或唐氏利什曼原虫具有意外高效的抗原虫药剂，以及用于治疗其他微生物感染的用途。
• Nitroimidazooxazine and nitroimidazooxazole analogues and their uses
  申请人：Global Alliance for TB Drug Development

  公开号：US08293734B2

  公开（公告）日：2012-10-23

  The current invention pertains to nitroimidazooxazine and nitroimidazooxazole analogues, their methods of preparation, and uses of the compounds as treatment for Mycobacterium tuberculosis, for use as anti-tubercular drugs, for use as anti-protozoal agents with unexpectedly high potency against Trypanosoma cruzi or Leishmania donovani, and for the treatment of other microbial infections.

  本发明涉及硝基咪唑氧噁啉和硝基咪唑氧唑类似物，其制备方法以及将这些化合物用作治疗结核分枝杆菌的药物、用作抗结核药物、用作抗原虫药物，对Trypanosoma cruzi或Leishmania donovani具有意外的高效性，并用于治疗其他微生物感染。