(R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-(isoxazol-3-yl)oxymethyloxazolidin-2-one | 717116-80-8

• 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: (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-(isoxazol-3-yl)oxymethyloxazolidin-2-one
• 英文别名: (5R)-3-{3-FLUORO-4-[6-(2-METHYL-2H-TETRAZOL-5-YL)PYRIDIN-3-YL]PHENYL}-5-(ISOXAZOL-3-YLOXYMETHYL)-1,3-OXAZOLIDIN-2-ONE；(5R)-3-[3-fluoro-4-[6-(2-methyltetrazol-5-yl)pyridin-3-yl]phenyl]-5-(1,2-oxazol-3-yloxymethyl)-1,3-oxazolidin-2-one
• CAS: 717116-80-8
• 化学式: C₂₀H₁₆FN₇O₄
• 分子量: 437.39
• InChiKey: INDSFRHHAWVRGR-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  121
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,5-二溴吡啶 在 sodium cyanide 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium azide 、 氯化铵 、 三苯基膦 、 lithium chloride 、 sodium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-(isoxazol-3-yl)oxymethyloxazolidin-2-one
  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] OXAZOLIDINONE DERIVATIVES AS ANTIBACTERIAL<br/>[FR] DERIVES D'OXAZOLIDINONE UTILISES COMME AGENTS ANTIBACTERIENS
  申请人：ASTRAZENECA AB

  公开号：WO2004056818A1

  公开（公告）日：2004-07-08

  A compound of the formula (I), or a pharmaceutically-acceptable salt, or in-vivo hydrolysable ester thereof : formula (I), wherein C is selected from D and E, formula (D), formula (E), R2a, R6a, and R3a are independently selected from for example H, CF3, Me and Et; R2b and R6b are independently selected from for example H, F, CF3, Me and Et; R1b is -X-Z wherein X is O or S and Z is a C-linked 5- or 6-membered heteroaryl ring; R4 is for example an optionally substituted 5- or 6-membered heterocyclic ring system. Methods for making compounds of the formula (I), compositions containing them and their use as antibacterial agents are also described.

  式(I)的化合物，或其药学上可接受的盐，或其中的体内水解酯：式(I)，其中C从D和E中选择，式(D)，式(E)，R2a，R6a和R3a独立选择例如H，CF3，Me和Et; R2b和R6b独立选择例如H，F， ，Me和Et; R1b为-X-Z，其中X为O或S，Z为C-连接的5或6成员杂环芳基环; R4例如为可选取代的5-或6-成员杂环环系。还描述了制备式(I)的化合物的方法，含有它们的组合物以及它们作为抗菌剂的用途。