(R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-[((S)-alanyloxy)methyl]oxazolidin-2-one trifluoroacetate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-[((S)-alanyloxy)methyl]oxazolidin-2-one trifluoroacetate
• 英文别名: (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-(L-alanyloxymethyl)oxazolidin-2-one trifluoroacetic acid salt；[(2S)-1-[[(5R)-3-[3-fluoro-4-[6-(2-methyltetrazol-5-yl)pyridin-3-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methoxy]-1-oxopropan-2-yl]azanium;2,2,2-trifluoroacetate
• 化学式: C₂HF₃O₂*C₂₀H₂₀FN₇O₄
• 分子量: 555.446
• InChiKey: KPCKPZYLONQYDE-YECZQDJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.93
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  176
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-[((S)-alanyloxy)methyl]oxazolidin-2-one trifluoroacetate 在 碳酸氢钠 、 盐酸 作用下， 以 水 、 乙醚 为溶剂， 以62%的产率得到(R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-[((S)-alanyloxy)methyl]oxazolidin-2-one hydrochloride
  参考文献：
  名称：

  Discovery of torezolid as a novel 5-hydroxymethyl-oxazolidinone antibacterial agent

  摘要：

  A series of novel substituted pyridyl phenyl oxazolidinone analogues were synthesized and their structure-activity relationship (SAR) was investigated based on in vitro and in vivo antibacterial activities. The minimum inhibitory concentrations (MICs) of the synthesized compounds against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) ranged from 0.12 to 2.0 mu g/mL, and against Haemophilus influenzae (Hi) from 2.0 to 8.0 mu g/mL. Compared to linezolid, only four compounds (11, 12, 21 and 29) showed higher in vitro antibacterial activities and better in vivo protective effects in mice. To improve the aqueous solubility, various prodrugs of compound 11 (DA-7157), which exerted a potency that was enhanced by 2-8-fold compared to that of linezolid, were synthesized. Among the prodrugs, the phosphate compound 42 exhibited excellent aqueous solubility (>50 mg/mL in DW) and good pharmacokinetic profiles, along with better in vivo efficacy than linezolid. This compound 42 is currently undergoing clinical trials with the brand name Torezolid. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.014
• 作为产物：
  描述：

  特地唑胺 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-[((S)-alanyloxy)methyl]oxazolidin-2-one trifluoroacetate
  参考文献：
  名称：

  Discovery of torezolid as a novel 5-hydroxymethyl-oxazolidinone antibacterial agent

  摘要：

  A series of novel substituted pyridyl phenyl oxazolidinone analogues were synthesized and their structure-activity relationship (SAR) was investigated based on in vitro and in vivo antibacterial activities. The minimum inhibitory concentrations (MICs) of the synthesized compounds against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) ranged from 0.12 to 2.0 mu g/mL, and against Haemophilus influenzae (Hi) from 2.0 to 8.0 mu g/mL. Compared to linezolid, only four compounds (11, 12, 21 and 29) showed higher in vitro antibacterial activities and better in vivo protective effects in mice. To improve the aqueous solubility, various prodrugs of compound 11 (DA-7157), which exerted a potency that was enhanced by 2-8-fold compared to that of linezolid, were synthesized. Among the prodrugs, the phosphate compound 42 exhibited excellent aqueous solubility (>50 mg/mL in DW) and good pharmacokinetic profiles, along with better in vivo efficacy than linezolid. This compound 42 is currently undergoing clinical trials with the brand name Torezolid. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.014

文献信息

• [EN] NOVEL OXAZOLIDINONE DERIVATIVES<br/>[FR] NOUVEAUX DERIVES D'OXAZOLIDINONE
  申请人：DONG A PHARM CO LTD

  公开号：WO2005058886A1

  公开（公告）日：2005-06-30

  The present invention relates to novel derivatives of oxazolidinone, a method thereof and pharmaceutical compositions comprising the derivatives for use in an antibiotic. The oxazolidinone derivatives of the present invention show inhibitory activity against a broad spectrum of bacteria and lower toxicity. The prodrugs, prepared by reacting the compound having hydroxyl group with amino acid or phosphate, have an excellent efficiency on solubility thereof against water. Further, the derivatives of the present invention may exert potent antibacterial activity versus various human and animal pathogens, including Gram-positive bacteria such as Staphylococi, Enterococci and Streptococi, anaerobic microorganisms such as Bacteroides and Clostridia, and acid-resistant microorganisms such as Mycobacterium tuberculosis and Mycobacterium avium. Accordingly, the compositions comprising the oxazolidinone are used in an antibiotic.

  本发明涉及新型氧唑啉酮衍生物，其方法以及包含这些衍生物的制药组合物，用于抗生素。本发明的氧唑啉酮衍生物显示出对广谱细菌的抑制活性和较低的毒性。通过将具有羟基的化合物与氨基酸或磷酸反应制备的前药，在其溶解度对水表现出优异效率。此外，本发明的衍生物可能对各种人类和动物病原体发挥强效的抗菌活性，包括革兰氏阳性细菌如葡萄球菌、肠球菌和链球菌，厌氧微生物如拟杆菌和梭菌，以及耐酸微生物如结核分枝杆菌和分枝杆菌。因此，含有氧唑啉酮的组合物用作抗生素。
• Pyridone Derivatives
  申请人：DAIICHI SANKYO COMPANY, LIMITED

  公开号：US20130281428A1

  公开（公告）日：2013-10-24

  Novel compounds or salts thereof, or crystals thereof, which inhibit Axl and are useful for treating diseases caused by Axl hyperfunction, diseases associated with Axl hyperfunction and/or diseases accompanied by Axl hyperfunction are provided. Pyridone derivatives represented by the formula (1) having various substituents or salts thereof, or crystals thereof (where R 1 , R 2 , R 3 , R 5 , R 6 , A, W, X and n in the formula (1) are as defined in the specification, respectively) are provided.

  提供了抑制Axl并用于治疗由Axl高功能引起的疾病、与Axl高功能相关的疾病和/或伴随Axl高功能的疾病的新型化合物或其盐，或其晶体。提供了由式（1）所代表的吡啶酮衍生物，具有各种取代基或其盐，或其晶体（其中式（1）中的R1、R2、R3、R5、R6、A、W、X和n分别如规范中定义）。
• Novel oxazolidinone derivatives
  申请人：Rhee Keol Jae

  公开号：US20070155798A1

  公开（公告）日：2007-07-05

  The present invention relates to novel derivatives of oxazolidinone, a method thereof and pharmaceutical compositions comprising the derivatives for use in an antibiotic. The oxazolidinone derivatives of the present invention show inhibitory activity against a broad spectrum of bacteria and lower toxicity. The prodrugs, prepared by reacting the compound having hydroxyl group with amino acid or phosphate, have an excellent efficiency on solubility thereof against water. Further, the derivatives of the present invention may exert potent antibacterial activity versus various human and animal pathogens, including Gram-positive bacteria such as Staphylococi, Enterococci and Streptococi, anaerobic microorganisms such as Bacteroides and Clostridia, and acid-resistant microorganisms such as Mycobacterium tuberculosis and Mycobacterium avium . Accordingly, the compositions comprising the oxazolidinone are used in an antibiotic. Data supplied from the esp@cenet database—Worldwide

  本发明涉及一种新型的噁唑烷酮衍生物及其制备方法和含有该衍生物的药物组合物，用于抗生素。本发明的噁唑烷酮衍生物对广谱细菌具有抑制活性，且毒性较低。通过将具有羟基的化合物与氨基酸或磷酸反应制备的前药，在溶解性方面具有优异的效率。此外，本发明的衍生物可能对各种人类和动物病原体具有强效的抗菌活性，包括革兰氏阳性菌，如葡萄球菌、肠球菌和链球菌，厌氧微生物，如拟杆菌和梭状芽孢杆菌，以及耐酸微生物，如结核分枝杆菌和鸟型分枝杆菌。因此，含有噁唑烷酮的组合物用于抗生素。数据来源于esp@cenet数据库-全球。
• NOVEL OXAZOLIDINONE DERIVATIVES
  申请人：DONG-A ST CO., LTD.

  公开号：US20130281492A1

  公开（公告）日：2013-10-24

  The present invention relates to novel derivatives of oxazolidinone, a method thereof and pharmaceutical compositions comprising the derivatives for use in an antibiotic. The oxazolidinone derivatives of the present invention show inhibitory activity against a broad spectrum of bacteria and lower toxicity. The prodrugs, prepared by reacting the compound having hydroxyl group with amino acid or phosphate, have an excellent efficiency on solubility thereof against water. Further, the derivatives of the present invention may exert potent antibacterial activity versus various human and animal pathogens, including Gram-positive bacteria such as Staphylococi, Enterococci and Streptococi , anaerobic microorganisms such as Bacteroides and Clostridia, and acid-resistant microorganisms such as Mycobacterium tuberculosis and Mycobacterium avium . Accordingly, the compositions comprising the oxazolidinone are used in an antibiotic.

  本发明涉及新型的噁唑烷酮衍生物及其制备方法和包含该衍生物的药物组合物，用于抗生素。本发明的噁唑烷酮衍生物显示出对广谱细菌的抑制活性和较低的毒性。通过将具有羟基的化合物与氨基酸或磷酸反应制备的前药，在水中的溶解度具有极高的效率。此外，本发明的衍生物可能对各种人类和动物病原体具有强效的抗菌活性，包括革兰氏阳性菌，如葡萄球菌，肠球菌和链球菌，厌氧微生物，如拟杆菌和梭菌，以及耐酸微生物，如结核分枝杆菌和埃希氏菌。因此，包含噁唑烷酮的组合物用于抗生素。
• Oxazolidinone derivatives
  申请人：Dong-A Pharmaceutical Co., Ltd.

  公开号：EP2305657A2

  公开（公告）日：2011-04-06

  The present invention relates to novel derivatives of oxazolidinone, a method thereof and pharmaceutical compositions comprising the derivatives for use in an antibiotic. The oxazolidinone derivatives of the present invention show inhibitory activity against a broad spectrum of bacteria and lower toxicity. The prodrugs, prepared by reacting the compound having hydroxyl group with amino acid or phosphate, have an excellent efficiency on solubility thereof against water. Further, the derivatives of the present invention may exert potent antibacterial activity versus various human and animal pathogens, including Gram-positive bacteria such as Staphylococi, Enterococci and Streptococi, anaerobic microorganisms such as Bacteroides and Clostridia, and acid-resistant microorganisms such as Mycobacterium tuberculosis and Mycobacterium avium. Accordingly, the compositions comprising the oxazolidinone are used in an antibiotic.

  本发明涉及噁唑烷酮的新型衍生物、其方法以及包含该衍生物的用于抗生素的药物组合物。本发明的噁唑烷酮衍生物对广谱细菌具有抑制活性，毒性较低。通过使具有羟基的化合物与氨基酸或磷酸盐反应制备的原药在水中的溶解度效率极高。此外，本发明的衍生物可对各种人类和动物病原体发挥强效抗菌活性，包括革兰氏阳性细菌（如葡萄球菌、肠球菌和链球菌）、厌氧微生物（如乳酸杆菌和梭状芽孢杆菌）以及耐酸微生物（如结核分枝杆菌和鸟疫分枝杆菌）。因此，包含噁唑烷酮的组合物可用于抗生素。