1-(4-methoxyphenyl)-4-[(5-nitrofuran-2-yl)methyl]piperazine | 331854-47-8

• 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-(4-methoxyphenyl)-4-[(5-nitrofuran-2-yl)methyl]piperazine
• 英文别名: SKI-100588；1-(4-Methoxyphenyl)-4-[(5-nitro-2-furyl)methyl]piperazine
• CAS: 331854-47-8
• 化学式: C₁₆H₁₉N₃O₄
• 分子量: 317.345
• InChiKey: YRZASWCXNFLFGT-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：

  4-溴苯甲醚 在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 18.0h， 生成 1-(4-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

• PYRIDAZINONES AND FURAN-CONTAINING COMPOUNDS
  申请人：Djaballah Hakim

  公开号：US20100210649A1

  公开（公告）日：2010-08-19

  The present invention is directed to pyridazinone compounds of formula (I) and furan compounds of formula (II), pharmaceutical compositions of compounds of formula (I) and (II), kits containing these compounds, methods of syntheses, and a method of treatment of a proliferative disease in a subject by administration of a therapeutically effective amount of a compound of formulae (I) or (II). Both classes of compounds were identified through screening of a collection of small molecule libraries.

  本发明涉及式(I)的吡啶二酮化合物和式(II)的呋喃化合物，以及式(I)和(II)化合物的制药组合物、包含这些化合物的试剂盒、合成方法，以及通过给予式(I)或(II)化合物的治疗有效量来治疗受体内增生性疾病的方法。这两类化合物是通过筛选小分子库的集合而确定的。
• US9562019B2
  申请人：——

  公开号：US9562019B2

  公开（公告）日：2017-02-07
• 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.