tedizolid mesylate | 856867-59-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: tedizolid mesylate
• 英文别名: (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-(methanesulfonyloxymethyl)oxazolidin-2-one；(R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-methanesulfonyloxymethyl oxazolidin-2-one；[(5R)-3-[3-fluoro-4-[6-(2-methyltetrazol-5-yl)pyridin-3-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl methanesulfonate
• CAS: 856867-59-9
• 化学式: C₁₈H₁₇FN₆O₅S
• 分子量: 448.435
• InChiKey: IINVFBBVWBTXFV-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  138
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tedizolid mesylate 在 sodium azide 、 10% palladium on activated charcoal 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 (S)-N-((3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-2-oxo-oxazolidin-5-yl)methyl)-2-hydroxyacetamide
  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：

  2-(1,2,3,4-tetrazol-5-yl)-5-bromopyridine 在 bis-triphenylphosphine-palladium(II) chloride 、 三乙胺 、 lithium chloride 、 sodium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 tedizolid mesylate
  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。
• OXAZOLIDINONE COMPOUNDS, LIPOSOME COMPOSITIONS COMPRISING OXAZOLIDINONE COMPOUNDS AND METHOD OF USE THEREOF
  申请人：Akagera Medicines, Inc.

  公开号：US20210403463A1

  公开（公告）日：2021-12-30

  Compositions and methods for the treatment of tuberculosis, as well as other mycobacterial and gram positive bacterial infections are disclosed. These compositions contain a highly potent and selective oxazolidinone encapsulated with high efficiency to maximize dosing potential of low toxicity drugs, and are stable in the presence of plasma. The compositions are long circulating and retain their encapsulated drug while in the circulation following intravenous dosing to allow for efficient accumulation at the site of the bacterial or mycobacterial infection. The high doses that can be achieved when combined with the long circulating properties and highly stable retention of the drug allow for a reduced frequency of administration when compared to daily or twice daily administrations of other drugs typically utilized to treat these infections.

  揭示了用于治疗结核病以及其他分枝杆菌和革兰氏阳性细菌感染的组合物和方法。这些组合物含有一种高效、选择性的奥沙林酮，高效地封装以最大限度地发挥低毒性药物的剂量潜力，并在血浆存在的情况下保持稳定。这些组合物在静脉注射后在循环中长时间循环，并保留其封装的药物，以便在细菌或分枝杆菌感染部位有效积累。与通常用于治疗这些感染的其他药物的每日或每日两次给药相比，结合长时间循环特性和高度稳定的药物滞留，可以实现高剂量，从而降低给药频率。
• 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。
• Oxazolidinone derivatives
  申请人：Dong-A Pharm. Co., Ltd.

  公开号：US07816379B2

  公开（公告）日：2010-10-19

  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制药组合物，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，在溶解度方面对水具有优异的效果。此外，本发明的衍生物可以对各种人类和动物病原体产生强效的抗菌活性，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可用作抗生素。
• 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。