1-[1-(4-fluorophenyl)-2,5-dimethylpyrrol-3-yl]-N-phenylmethoxymethanimine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-[1-(4-fluorophenyl)-2,5-dimethylpyrrol-3-yl]-N-phenylmethoxymethanimine
• 化学式: C₂₀H₁₉FN₂O
• mdl: MFCD01872660
• 分子量: 322.382
• InChiKey: WVUSIYMFDCHDGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  26.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[1-(4-fluorophenyl)-2,5-dimethylpyrrol-3-yl]-N-phenylmethoxymethanimine 以 四氢呋喃 为溶剂， 反应 18.0h， 以82%的产率得到O-benzyl-N-((1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrol-3-yl)-methyl)hydroxylamine
  参考文献：
  名称：

  Design and Synthesis of 1-((1,5-Bis(4-chlorophenyl)-2-methyl-1H-pyrrol-3-yl)methyl)-4-methylpiperazine (BM212) and N-Adamantan-2-yl-N′-((E)-3,7-dimethylocta-2,6-dienyl)ethane-1,2-diamine (SQ109) Pyrrole Hybrid Derivatives: Discovery of Potent Antitubercular Agents Effective against Multidrug-Resistant Mycobacteria

  摘要：

  Novel pyrroles have been designed, synthesized, and evaluated against mycobacterial strains. The pyrroles have originally been designed as hybrids of the antitubercular drugs BM212 (1) and SQ109 (2), which showed common chemical features with very similar topological distribution. A perfect superposition of the structures of 1 and 2 revealed by computational studies suggested the introduction of bulky substituents at the terminal portion of the pyrrole C3 side chain and the removal of the CS aryl moiety. Five compounds showed high activity toward Mycobacterium tuberculosis, while 9b and 9c were highly active also against multidrug-resistant clinical isolates. Compound 9c showed low eukaryotic cell toxicity, turning out to be an excellent lead candidate for preclinical trials. In addition, four compounds showed potent inhibition (comparable to that of verapamil) toward the whole-cell drug efflux pump activity of mycobacteria, thus turning out to be promising multidrug-resistance-reversing agents.

  DOI：

  10.1021/acs.jmedchem.6b00031
• 作为产物：
  描述：

  1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole 在 三氯氧磷 作用下， 以 四氢呋喃 、 溶剂黄146 为溶剂， 反应 21.0h， 生成 1-[1-(4-fluorophenyl)-2,5-dimethylpyrrol-3-yl]-N-phenylmethoxymethanimine
  参考文献：
  名称：

  Design and Synthesis of 1-((1,5-Bis(4-chlorophenyl)-2-methyl-1H-pyrrol-3-yl)methyl)-4-methylpiperazine (BM212) and N-Adamantan-2-yl-N′-((E)-3,7-dimethylocta-2,6-dienyl)ethane-1,2-diamine (SQ109) Pyrrole Hybrid Derivatives: Discovery of Potent Antitubercular Agents Effective against Multidrug-Resistant Mycobacteria

  摘要：

  Novel pyrroles have been designed, synthesized, and evaluated against mycobacterial strains. The pyrroles have originally been designed as hybrids of the antitubercular drugs BM212 (1) and SQ109 (2), which showed common chemical features with very similar topological distribution. A perfect superposition of the structures of 1 and 2 revealed by computational studies suggested the introduction of bulky substituents at the terminal portion of the pyrrole C3 side chain and the removal of the CS aryl moiety. Five compounds showed high activity toward Mycobacterium tuberculosis, while 9b and 9c were highly active also against multidrug-resistant clinical isolates. Compound 9c showed low eukaryotic cell toxicity, turning out to be an excellent lead candidate for preclinical trials. In addition, four compounds showed potent inhibition (comparable to that of verapamil) toward the whole-cell drug efflux pump activity of mycobacteria, thus turning out to be promising multidrug-resistance-reversing agents.

  DOI：

  10.1021/acs.jmedchem.6b00031

文献信息

• Design and Synthesis of 1-((1,5-Bis(4-chlorophenyl)-2-methyl-1<i>H</i>-pyrrol-3-yl)methyl)-4-methylpiperazine (BM212) and <i>N</i>-Adamantan-2-yl-<i>N</i>′-((<i>E</i>)-3,7-dimethylocta-2,6-dienyl)ethane-1,2-diamine (SQ109) Pyrrole Hybrid Derivatives: Discovery of Potent Antitubercular Agents Effective against Multidrug-Resistant Mycobacteria
  作者：Sanjib Bhakta、Nicolò Scalacci、Arundhati Maitra、Alistair K. Brown、Saiprasad Dasugari、Dimitrios Evangelopoulos、Timothy D. McHugh、Parisa N. Mortazavi、Alexander Twist、Elena Petricci、Fabrizio Manetti、Daniele Castagnolo

  DOI：10.1021/acs.jmedchem.6b00031

  日期：2016.3.24

  Novel pyrroles have been designed, synthesized, and evaluated against mycobacterial strains. The pyrroles have originally been designed as hybrids of the antitubercular drugs BM212 (1) and SQ109 (2), which showed common chemical features with very similar topological distribution. A perfect superposition of the structures of 1 and 2 revealed by computational studies suggested the introduction of bulky substituents at the terminal portion of the pyrrole C3 side chain and the removal of the CS aryl moiety. Five compounds showed high activity toward Mycobacterium tuberculosis, while 9b and 9c were highly active also against multidrug-resistant clinical isolates. Compound 9c showed low eukaryotic cell toxicity, turning out to be an excellent lead candidate for preclinical trials. In addition, four compounds showed potent inhibition (comparable to that of verapamil) toward the whole-cell drug efflux pump activity of mycobacteria, thus turning out to be promising multidrug-resistance-reversing agents.