1-(3-methoxyphenyl)-4-[(5-nitrofuran-2-yl)methyl]piperazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(3-methoxyphenyl)-4-[(5-nitrofuran-2-yl)methyl]piperazine
• 英文别名: 1-(3-Methoxyphenyl)-4-[(5-nitro-2-furyl)methyl]piperazine
• 化学式: C₁₆H₁₉N₃O₄
• 分子量: 317.345
• InChiKey: BEJVNYJXDQZHGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  74.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-硝基糠醛 、 tert-butyl 4-(3-methoxyphenyl)piperazine-1-carboxylate 在 三氟乙酸 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 以82%的产率得到1-(3-methoxyphenyl)-4-[(5-nitrofuran-2-yl)methyl]piperazine
  参考文献：
  名称：

  Nitrofuranyl Methyl Piperazines as New Anti-TB Agents: Identification, Validation, Medicinal Chemistry, and PK Studies

  摘要：

  Whole-cell screening of 20,000 drug-like small molecules led to the identification of nitrofuranyl methyl-piperazines as potent anti-TB agents. In the present study, validation followed by medicinal chemistry has been used to explore the structure activity relationship. Ten compounds demonstrated potent MIC in the range of 0.17-0.0072 mu M against H(37)Rv Mycobacterium tuberculosis (MTB) and were further investigated against nonreplicating and resistant (Rif(R) and MDR) strains of MTB. These compounds were also tested for cytotoxicity. Among the 10 tested compounds, five showed submicromolar to nanomolar potency against nonreplicating and resistant (Rif(R) and MDR) strains of MTB along with a good safety index. Based on their overall in vitro profiles, the solubility and pharmacokinetic properties of five potent compounds were studied, and two analogues, 14f and 16g, were found to have comparatively better solubility than others tested and acceptable pharmacokinetic properties. This study presents the rediscovery of a nitrofuranyl class of compounds with improved aqueous solubility and acceptable oral PK properties, opening a new direction for further development.

  DOI：

  10.1021/acsmedchemlett.5b00141

文献信息

• Nitrofuranyl Methyl Piperazines as New Anti-TB Agents: Identification, Validation, Medicinal Chemistry, and PK Studies
  作者：Kushalava Reddy Yempalla、Gurunadham Munagala、Samsher Singh、Asmita Magotra、Sunil Kumar、Vikrant Singh Rajput、Sonali S. Bharate、Manoj Tikoo、G. D. Singh、Inshad Ali Khan、Ram A. Vishwakarma、Parvinder Pal Singh

  DOI：10.1021/acsmedchemlett.5b00141

  日期：2015.10.8

  Whole-cell screening of 20,000 drug-like small molecules led to the identification of nitrofuranyl methyl-piperazines as potent anti-TB agents. In the present study, validation followed by medicinal chemistry has been used to explore the structure activity relationship. Ten compounds demonstrated potent MIC in the range of 0.17-0.0072 mu M against H(37)Rv Mycobacterium tuberculosis (MTB) and were further investigated against nonreplicating and resistant (Rif(R) and MDR) strains of MTB. These compounds were also tested for cytotoxicity. Among the 10 tested compounds, five showed submicromolar to nanomolar potency against nonreplicating and resistant (Rif(R) and MDR) strains of MTB along with a good safety index. Based on their overall in vitro profiles, the solubility and pharmacokinetic properties of five potent compounds were studied, and two analogues, 14f and 16g, were found to have comparatively better solubility than others tested and acceptable pharmacokinetic properties. This study presents the rediscovery of a nitrofuranyl class of compounds with improved aqueous solubility and acceptable oral PK properties, opening a new direction for further development.