(R)-2-methyl-6-nitro-2-{[4-(4-(4-trifluoromethylphenylsulfonyl)piperazin-1-yl)]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole

• 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: (R)-2-methyl-6-nitro-2-{[4-(4-(4-trifluoromethylphenylsulfonyl)piperazin-1-yl)]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole
• 英文别名: [(2R)-2-methyl-2-[[4-[4-[4-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]phenoxy]methyl]-3H-imidazo[2,1-b]oxazol-6-yl]azinic acid；(2R)-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]phenoxy]methyl]-3H-imidazo[2,1-b][1,3]oxazole
• 化学式: C₂₄H₂₄F₃N₅O₆S
• 分子量: 567.546
• InChiKey: QRQUSPAIUYXUFA-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  131
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2-对溴苯氧基四氢吡喃 在 palladium diacetate 、 4-甲基苯磺酸吡啶 、 sodium hydride 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 44.5h， 生成 (R)-2-methyl-6-nitro-2-{[4-(4-(4-trifluoromethylphenylsulfonyl)piperazin-1-yl)]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Polar Functionalities Containing Nitrodihydroimidazooxazoles as Anti-TB Agents

  摘要：

  Novel polar functionalities containing 6-nitro-2,3-dihydroimidazooxazole (NHIO) analogues were synthesized to produce a compound with enhanced solubility. Polar functionalities including sulfonyl, uridyl, and thiouridyl-bearing NHIO analogues were synthesized and evaluated against Mycobacterium tuberculosis (MTB) H(37)Rv. The aqueous solubility of compounds with MIC values <= 0.5 mu g/mL were tested, and six compounds showed enhanced aqueous solubility. The best six compounds were further tested against resistant (Rif(R) and MDR) and dormant strains of MTB and tested for cytotoxicity in HepG2 cell line. Based on its overall in vitro characteristics and solubility profile, compound 6d was further shown to possess high microsomal stability, solubility under all tested biological conditions (PBS, SGF and SIF), and favorable oral in vivo pharmacokinetics and in vivo efficacy.

  DOI：

  10.1021/acsmedchemlett.5b00202

文献信息

• Synthesis and Biological Evaluation of Polar Functionalities Containing Nitrodihydroimidazooxazoles as Anti-TB Agents
  作者：Kushalava Reddy Yempalla、Gurunadham Munagala、Samsher Singh、Gurleen Kour、Shweta Sharma、Reena Chib、Sunil Kumar、Priya Wazir、G. D. Singh、Sushil Raina、Sonali S. Bharate、Inshad Ali Khan、Ram A. Vishwakarma、Parvinder Pal Singh

  DOI：10.1021/acsmedchemlett.5b00202

  日期：2015.10.8

  Novel polar functionalities containing 6-nitro-2,3-dihydroimidazooxazole (NHIO) analogues were synthesized to produce a compound with enhanced solubility. Polar functionalities including sulfonyl, uridyl, and thiouridyl-bearing NHIO analogues were synthesized and evaluated against Mycobacterium tuberculosis (MTB) H(37)Rv. The aqueous solubility of compounds with MIC values <= 0.5 mu g/mL were tested, and six compounds showed enhanced aqueous solubility. The best six compounds were further tested against resistant (Rif(R) and MDR) and dormant strains of MTB and tested for cytotoxicity in HepG2 cell line. Based on its overall in vitro characteristics and solubility profile, compound 6d was further shown to possess high microsomal stability, solubility under all tested biological conditions (PBS, SGF and SIF), and favorable oral in vivo pharmacokinetics and in vivo efficacy.