(R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(4-(4,4-dimethyl-1,4-azasilinan-1-yl)-3,5-difluorophenyl)oxazolidin-2-one | 1430321-59-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(4-(4,4-dimethyl-1,4-azasilinan-1-yl)-3,5-difluorophenyl)oxazolidin-2-one
• 英文别名: (R)-5-((1H-l,2,3-triazol-1-yl)methyl)-3-(4-(4,4-dimethyl-1,4-azasilinan-1-yl)-3,5-difluorophenyl)oxazolidin-2-one；NDS-10058；(5R)-3-[4-(4,4-dimethyl-1,4-azasilinan-1-yl)-3,5-difluorophenyl]-5-(triazol-1-ylmethyl)-1,3-oxazolidin-2-one
• CAS: 1430321-59-7
• 化学式: C₁₈H₂₃F₂N₅O₂Si
• 分子量: 407.495
• InChiKey: HGUSOEBICTYCIM-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.11
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  63.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  bis(2-bromoethyl)dimethylsilane 在 盐酸 、 正丁基锂 、 sodium azide 、 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 正己烷 、 二氯甲烷 、 氯仿 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.5h， 生成 (R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(4-(4,4-dimethyl-1,4-azasilinan-1-yl)-3,5-difluorophenyl)oxazolidin-2-one
  参考文献：
  名称：

  Design, Synthesis, and Identification of Silicon Incorporated Oxazolidinone Antibiotics with Improved Brain Exposure

  摘要：

  Therapeutic options for brain infections caused by pathogens with a reduced sensitivity to drugs are limited. Recent reports on the potential use of linezolid in treating brain infections prompted us to design novel compounds around this scaffold. Herein, we describe the design and synthesis of various oxazolidinone antibiotics with the incorporation of silicon. Our findings in preclinical species suggest that silicon incorporation is highly useful in improving brain exposures. Interestingly, three compounds from this series demonstrated up to a 30-fold higher brain/plasma ratio when compared to linezolid thereby indicating their therapeutic potential in brain associated disorders.

  DOI：

  10.1021/acsmedchemlett.5b00213

文献信息

• SILA ANALOGS OF OXAZOLIDINONE DERIVATIVES AND SYNTHESIS THEREOF
  申请人：Council of Scientific & Industrial Research

  公开号：US20140296133A1

  公开（公告）日：2014-10-02

  The invention discloses silaanalogs of oxazolidinone compounds, to pharmaceutical compositions and to the synthesis of the oxazolidinone derivatives of formula I. The invention further relates to methods of treating a subject suffering with gram positive pathogens including those resistant to methicillin and vancomycin using the compound(s) or modulation of coagulation properties of blood-clotting cascade or compositions of the oxazolidinone derivatives of the invention.

  该发明揭示了氧唑啉酮化合物的硅代体，以及制备公式I的氧唑啉酮衍生物的制药组合物和合成方法。该发明还涉及使用该化合物或调节凝血级联血凝性质或该发明的氧唑啉酮衍生物组合物治疗患有革兰氏阳性病原体的受试者的方法，包括对甲氧西林和万古霉素耐药的病原体。
• [EN] SILA ANALOGS OF OXAZOLIDINONE DERIVATIVES AND SYNTHESIS THEREOF<br/>[FR] SILA-ANALOGUES DE DÉRIVÉS D'OXAZOLIDINONE ET SYNTHÈSE DE CEUX-CI
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2013054275A1

  公开（公告）日：2013-04-18

  The invention discloses silaanalogs of oxazolidinone compounds, to pharmaceutical compositions and to the synthesis of the oxazolidinone derivatives of formula I. The invention further relates to methods of treating a subject suffering with gram positive pathogens including those resistant to methicillin and vancomycin using the compound(s) or modulation of coagulation properties of blood-clotting cascade or compositions of the oxazolidinone derivatives of the invention.

  该发明揭示了氧唑啉酮化合物的硅基类似物，以及药物组合物和合成公式I的氧唑啉酮衍生物。该发明还涉及使用该化合物或调节凝血级联反应的血液凝块性质或该发明的氧唑啉酮衍生物组合物来治疗患有革兰氏阳性病原体的受试者，包括对甲氧西林和万古霉素具有耐药性的病原体。
• Design, Synthesis, and Identification of Silicon Incorporated Oxazolidinone Antibiotics with Improved Brain Exposure
  作者：B. Seetharamsingh、Remya Ramesh、Santoshkumar S. Dange、Pankaj V. Khairnar、Smita Singhal、Dilip Upadhyay、Sridhar Veeraraghavan、Srikant Viswanadha、Swaroop Vakkalanka、D. Srinivasa Reddy

  DOI：10.1021/acsmedchemlett.5b00213

  日期：2015.11.12

  Therapeutic options for brain infections caused by pathogens with a reduced sensitivity to drugs are limited. Recent reports on the potential use of linezolid in treating brain infections prompted us to design novel compounds around this scaffold. Herein, we describe the design and synthesis of various oxazolidinone antibiotics with the incorporation of silicon. Our findings in preclinical species suggest that silicon incorporation is highly useful in improving brain exposures. Interestingly, three compounds from this series demonstrated up to a 30-fold higher brain/plasma ratio when compared to linezolid thereby indicating their therapeutic potential in brain associated disorders.