1-methyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-3-[4-(trifluoromethyl)phenyl]-1H-pyrazole | 1202942-17-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-methyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-3-[4-(trifluoromethyl)phenyl]-1H-pyrazole
• 英文别名: 1-Methyl-5-(oxan-2-yloxymethyl)-3-[4-(trifluoromethyl)phenyl]pyrazole
• CAS: 1202942-17-3
• 化学式: C₁₇H₁₉F₃N₂O₂
• 分子量: 340.345
• InChiKey: FSMUEFLTCJUHDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-methyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-3-[4-(trifluoromethyl)phenyl]-1H-pyrazole 在 盐酸 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以75%的产率得到{1-methyl-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-5-yl}methanol
  参考文献：
  名称：

  Synthesis and Structure−activity Relationships of Antitubercular 2-Nitroimidazooxazines Bearing Heterocyclic Side Chains

  摘要：

  Recently described biphenyl analogues Of the antituberculosis drug PA-824 displayed improved potencies against M. tuberculosis but were poorly soluble. Heterobiaryl analogues of these, in which the first phenyl ring was replaced with various 5-membered ring heterocycles, were prepared with the aim of identifying potent new candidates with improved aqueous solubility. The compounds were constructed by coupling the chiral 2-nitroimidazooxazine alcohol with various halomethyl-substituted arylheterocycles, by cycloadditions to a propargyl ether derivative of this alcohol, or by Suzuki couplings on haloheterocyclic methyl ether derivatives. The arylheterocyclic compounds were all more hydrophilic than their corresponding biphenyl analogues, and several showed solubility improvements. 1-Methylpyrazole, 1,3-linked-pyrazole, 2,4-linked-triazole, and tetrazole analogues had 3- to 7-fold higher MIC potencies against replicating M. tb than predicted by their lipophilicities. Two pyrazole analogues were >10-fold more efficacious than the parent drug in a mouse model of acute M. tb infection, and one displayed a 2-fold higher solubility.

  DOI：

  10.1021/jm901378u
• 作为产物：
  描述：

  哌喃 、 一氧化碳 、 4-碘三氟甲苯 、 甲基肼硫酸盐 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 碳酸氢钠 作用下， 以 四氢呋喃 、 水 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 48.0h， 以46%的产率得到1-methyl-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-3-[4-(trifluoromethyl)phenyl]-1H-pyrazole
  参考文献：
  名称：

  Synthesis and Structure−activity Relationships of Antitubercular 2-Nitroimidazooxazines Bearing Heterocyclic Side Chains

  摘要：

  Recently described biphenyl analogues Of the antituberculosis drug PA-824 displayed improved potencies against M. tuberculosis but were poorly soluble. Heterobiaryl analogues of these, in which the first phenyl ring was replaced with various 5-membered ring heterocycles, were prepared with the aim of identifying potent new candidates with improved aqueous solubility. The compounds were constructed by coupling the chiral 2-nitroimidazooxazine alcohol with various halomethyl-substituted arylheterocycles, by cycloadditions to a propargyl ether derivative of this alcohol, or by Suzuki couplings on haloheterocyclic methyl ether derivatives. The arylheterocyclic compounds were all more hydrophilic than their corresponding biphenyl analogues, and several showed solubility improvements. 1-Methylpyrazole, 1,3-linked-pyrazole, 2,4-linked-triazole, and tetrazole analogues had 3- to 7-fold higher MIC potencies against replicating M. tb than predicted by their lipophilicities. Two pyrazole analogues were >10-fold more efficacious than the parent drug in a mouse model of acute M. tb infection, and one displayed a 2-fold higher solubility.

  DOI：

  10.1021/jm901378u