5-[3-[(3,4-difluorophenyl)methoxy]phenyl]-1H-pyrazole-3-carboxylic acid ethyl ester | 1203611-03-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-[3-[(3,4-difluorophenyl)methoxy]phenyl]-1H-pyrazole-3-carboxylic acid ethyl ester
• 英文别名: ethyl 5-[3-[(3,4-difluorophenyl)methoxy]phenyl]-1H-pyrazole-3-carboxylate；ethyl 3-[3-[(3,4-difluorophenyl)methoxy]phenyl]-1H-pyrazole-5-carboxylate
• CAS: 1203611-03-3
• 化学式: C₁₉H₁₆F₂N₂O₃
• 分子量: 358.344
• InChiKey: ZADSAXBXZCOAFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  64.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  重氮乙酸乙酯 、 1-ethynyl-3-[[3,4-difluorophenyl]methoxy]benzene 以 苯 为溶剂， 反应 1.5h， 以80%的产率得到5-[3-[(3,4-difluorophenyl)methoxy]phenyl]-1H-pyrazole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Rational Design of 5-Phenyl-3-isoxazolecarboxylic Acid Ethyl Esters as Growth Inhibitors of Mycobacterium tuberculosis. A Potent and Selective Series for Further Drug Development

  摘要：

  New antituberculosis (anti-TB) drugs are urgently needed to shorten the 6-12 month treatment regimen and especially to battle drug-resistant Mycobacterium tuberculosis (Mtb) strains. In this study, we have continued our efforts to develop isoxazole-based anti-TB compounds by applying rational drug design approach. The biological activity and the structure-activity relationships (SAR) for a designed series of 5-phenyl-3-isoxazolecarboxylic acid ethyl ester derived anti-TB compounds were investigated. Several compounds were found to exhibit nanomolar activity against the replicating bacteria (R-TB) and low micromolar activity against the nonreplicating bacteria (NRP-TB). The series showed excellent selectivity toward Mtb, and in general, no cytotoxicity was observed in Vero cells (IC50 > 128 mu M). Notably, selected compounds also retained their activity against isoniazid (INH), rifampin (RMP), and streptomycin (SM) resistant Mtb strains. Hence, benzyloxy, benzylamino, and phenoxy derivatives of 5-phenyl-3-isoxazolecarboxylic acid ethyl esters represent a highly potent, selective, and versatile series of anti-TB compounds and as Such present attractive lead compounds for further TB drug development.

  DOI：

  10.1021/jm901273n

文献信息

• Rational Design of 5-Phenyl-3-isoxazolecarboxylic Acid Ethyl Esters as Growth Inhibitors of <i>Mycobacterium tuberculosis</i>. A Potent and Selective Series for Further Drug Development
  作者：Annamaria Lilienkampf、Marco Pieroni、Baojie Wan、Yuehong Wang、Scott G. Franzblau、Alan P. Kozikowski

  DOI：10.1021/jm901273n

  日期：2010.1.28

  New antituberculosis (anti-TB) drugs are urgently needed to shorten the 6-12 month treatment regimen and especially to battle drug-resistant Mycobacterium tuberculosis (Mtb) strains. In this study, we have continued our efforts to develop isoxazole-based anti-TB compounds by applying rational drug design approach. The biological activity and the structure-activity relationships (SAR) for a designed series of 5-phenyl-3-isoxazolecarboxylic acid ethyl ester derived anti-TB compounds were investigated. Several compounds were found to exhibit nanomolar activity against the replicating bacteria (R-TB) and low micromolar activity against the nonreplicating bacteria (NRP-TB). The series showed excellent selectivity toward Mtb, and in general, no cytotoxicity was observed in Vero cells (IC50 > 128 mu M). Notably, selected compounds also retained their activity against isoniazid (INH), rifampin (RMP), and streptomycin (SM) resistant Mtb strains. Hence, benzyloxy, benzylamino, and phenoxy derivatives of 5-phenyl-3-isoxazolecarboxylic acid ethyl esters represent a highly potent, selective, and versatile series of anti-TB compounds and as Such present attractive lead compounds for further TB drug development.