(S)-N-((3-(3-fluoro-4-(5-(4-(methylthio)phenyl)-1H-pyrazol-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide | 1416314-61-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-N-((3-(3-fluoro-4-(5-(4-(methylthio)phenyl)-1H-pyrazol-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide
• 英文别名: N-[[(5S)-3-[3-fluoro-4-[5-(4-methylsulfanylphenyl)pyrazol-1-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide
• CAS: 1416314-61-8
• 化学式: C₂₂H₂₁FN₄O₃S
• 分子量: 440.498
• InChiKey: LTBKZLJWPHLZBU-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-(dimethylamino)-1-[4-(methylthio)phenyl]-2-propen-1-one 、 N-{[(5S)-3-(3-fluoro-4-hydrazinophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以34%的产率得到(S)-N-((3-(3-fluoro-4-(5-(4-(methylthio)phenyl)-1H-pyrazol-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide
  参考文献：
  名称：

  Discovery of a Teraryl Oxazolidinone Compound (S)-N-((3-(3-Fluoro-4-(4-(pyridin-2-yl)-1H-pyrazol-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide Phosphate as a Novel Antimicrobial Agent with Enhanced Safety Profile and Efficacies

  摘要：

  A series of novel teraryl oxazolidinone compounds was designed, synthesized, and evaluated for their antimicrobial activity and toxicities. The compounds with aromatic N-heterocyclic substituents at the 4-position of pyrazolyl ring showed better antibacterial activity against the tested bacteria than other compounds with different patterns of substitution. Among all potent compounds, 10f exhibited promising safety profile in MTT assays and in hERG K+ channel inhibition test. Furthermore, its phosphate was found to be highly soluble in water (47.1 mg/mL), which is beneficial for the subsequent in vivo test. In MRSA systemic infection mice models, 10f phosphate exerted significantly improved survival protection compared with linezolid. The compound also demonstrated high oral bioavailability (F = 99.1%). Moreover, from the results of in vivo toxicology experiments, 10f phosphate would be predicted to have less bone marrow suppression.

  DOI：

  10.1021/acs.jmedchem.5b00152

文献信息

• Oxazolidinone Compounds and Their Uses in Preparation of Antibiotics
  申请人：Luo Youfu

  公开号：US20140142144A1

  公开（公告）日：2014-05-22

  The invention belongs to the field of medicaments, and particularly relates to oxazolidinone compounds and their uses in the preparation of antibiotics. A technical problem to be solved by the invention is to provide new oxazolidinone compounds having the structure represented by Formula I. The oxazolidinone compounds of the invention, which are new compounds obtained through numerous screening, have significant antibacterial activity against bacteria such as drug-resistant staphylococcus aureus , fecal coliform bacteria, and streptococcus pneumoniae , while exhibiting low toxicity. The invention provides new options for the development and application of antibiotics.

  这项发明属于药物领域，特别涉及噁唑烷酮化合物及其在抗生素制备中的用途。该发明要解决的技术问题是提供具有由式I表示的结构的新噁唑烷酮化合物。该发明的噁唑烷酮化合物是通过大量筛选获得的新化合物，对耐药性金黄色葡萄球菌、粪大肠杆菌和肺炎链球菌等细菌具有显著的抗菌活性，同时毒性低。该发明为抗生素的开发和应用提供了新选择。
• OXAZOLIDINONE COMPOUNDS AND THEIR USES IN PREPARATION OF ANTIBIOTICS
  申请人：SICHUAN GOODDOCTOR PHARMACEUTICAL GROUP CO., LTD.

  公开号：EP2738169B1

  公开（公告）日：2016-03-23
• US8946436B2
  申请人：——

  公开号：US8946436B2

  公开（公告）日：2015-02-03
• Discovery of a Teraryl Oxazolidinone Compound (<i>S</i>)-<i>N</i>-((3-(3-Fluoro-4-(4-(pyridin-2-yl)-1<i>H</i>-pyrazol-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide Phosphate as a Novel Antimicrobial Agent with Enhanced Safety Profile and Efficacies
  作者：Tao Yang、Gong Chen、Zitai Sang、Yuanyuan Liu、Xiaoyan Yang、Ying Chang、Haiyue Long、Wei Ang、Jianying Tang、Zhenling Wang、Guobo Li、Shengyong Yang、Jingren Zhang、Yuquan Wei、Youfu Luo

  DOI：10.1021/acs.jmedchem.5b00152

  日期：2015.8.27

  A series of novel teraryl oxazolidinone compounds was designed, synthesized, and evaluated for their antimicrobial activity and toxicities. The compounds with aromatic N-heterocyclic substituents at the 4-position of pyrazolyl ring showed better antibacterial activity against the tested bacteria than other compounds with different patterns of substitution. Among all potent compounds, 10f exhibited promising safety profile in MTT assays and in hERG K+ channel inhibition test. Furthermore, its phosphate was found to be highly soluble in water (47.1 mg/mL), which is beneficial for the subsequent in vivo test. In MRSA systemic infection mice models, 10f phosphate exerted significantly improved survival protection compared with linezolid. The compound also demonstrated high oral bioavailability (F = 99.1%). Moreover, from the results of in vivo toxicology experiments, 10f phosphate would be predicted to have less bone marrow suppression.