(R)-3-(3-fluoro-4-morpholinophenyl)-5-((hydroxyamino)methyl)oxazolidin-2-one | 503026-32-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (R)-3-(3-fluoro-4-morpholinophenyl)-5-((hydroxyamino)methyl)oxazolidin-2-one
• 英文别名: (5R)-3-(3-fluoro-4-morpholin-4-ylphenyl)-5-[(hydroxyamino)methyl]-1,3-oxazolidin-2-one
• CAS: 503026-32-2
• 化学式: C₁₄H₁₈FN₃O₄
• 分子量: 311.313
• InChiKey: HTUWLZBHXPUKFI-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  74.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-3-(3-fluoro-4-morpholinophenyl)-5-((hydroxyamino)methyl)oxazolidin-2-one 在 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 1.17h， 生成 (R)-N-((3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl) methyl)-N-hydroxyhexanamide
  参考文献：
  名称：

  新型5-（氧肟酸）甲基恶唑烷酮衍生物作为5-脂氧合酶抑制剂的合成与构效关系。

  摘要：

  摘要 合成了恶唑烷酮异羟肟酸衍生物，并在三个体外基于细胞的测试系统中评估了对白三烯（LT）生物合成的抑制活性，并直接抑制了重组人5-脂氧合酶（5-LO）。合成的19种化合物中有13种被认为具有活性（（在两个或多个测试系统中，50％抑制浓度（IC 50）≤10 µM））。异羟肟酸部分上烷基链长度的增加增强了活性，并且含有吗啉基的衍生物比N-乙酰基-哌嗪基衍生物更具活性。IC 50基于细胞的测定系统中的值与通过直接抑制5-LO活性获得的值相当，这证实了这些化合物是5-LO的直接抑制剂。尤其是，化合物PH-249和PH-251具有出色的效力（IC 50 <1 µM），与原型5-LO抑制剂齐留通的效价相当。发音的体内活性证实在小鼠酵母聚糖诱导的腹膜炎。因此，这些新颖的恶唑烷酮异羟肟酸衍生物是有效的5-LO抑制剂，具有潜在的抗过敏和消炎作用。

  DOI：

  10.1080/14756366.2020.1786082
• 作为产物：
  描述：

  (5R)-3-[3-氟-4-(4-吗啡啉基)苯基]-5-羟甲基-2-恶唑烷酮 在 sodium hydride 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 64.5h， 生成 (R)-3-(3-fluoro-4-morpholinophenyl)-5-((hydroxyamino)methyl)oxazolidin-2-one
  参考文献：
  名称：

  Synthesis and biological evaluation of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives

  摘要：

  Research activities on the oxazolidinone antibacterial class of compounds continue to focus on developing newer derivatives with improved potency, broad-spectrum activity and safety profiles superior to linezolid. Among the safety concerns with the oxazolidinone antibacterial agents is inhibition of monoamine oxidases (MAO) resulting from their structural similarity with toloxatone, a known MAO inhibitor. Diverse substitution patterns at the C-5 position of the oxazolidinone ring have been shown to significantly affect both antibacterial activity and MAO inhibition to varying degrees. Also, the antibacterial activity of compounds containing iron-chelating functionalities, such as the hydroxamic acids, 8-hydroxyquinolines and catechols have been correlated to their ability to alter iron intake and/or metabolism. Hence a series of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives were synthesized and evaluated for their antibacterial and MAO-A and -B inhibitory activities. The compounds were devoid of significant antibacterial activity but most demonstrated moderate MAO-A and -B inhibitory activities. Computer modeling studies revealed that the lack of potent antibacterial activity was due to significant steric interaction between the hydroxamic acid N-OH oxygen atom and one of the G2540 5'-phosphate oxygen atoms at the bacterial ribosomal binding site. Therefore, the replacement of the 5-acetamidomethyl group of linezolid with the 5-(N-hydroxyacetamido)methyl group present in the hydroxamic acid oxazolidinone derivatives was concluded to be detrimental to antibacterial activity. Furthermore, the 5-(hydroxamic acid)methyl oxazolidinone derivatives were also less active as MAO-A and -B inhibitors compared with linezolid and the selective inhibitors clorgyline and pargyline. In general, the 5-(hydroxamic acid)methyl oxazolidinone derivatives demonstrated moderate but selective MAO-B inhibitory activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.025

文献信息

• Synthesis and antibacterial activity of 5-substituted oxazolidinones
  作者：O.A Phillips、E.E Udo、A.A.M Ali、N Al-Hassawi

  DOI：10.1016/s0968-0896(02)00423-6

  日期：2003.1

  A series of 5-substituted oxazolidinones with varying substitution at the 5-position of the oxazolidinone ring were synthesized and their in vitro antibacterial activity was evaluated. The compounds demonstrated potent to weak antibacterial activity. A novel compound (PH-027) demonstrated potent antibacterial activity, which is comparable to or better than those of linezolid and vancomycin against

  合成了一系列在恶唑烷酮环的5-位具有不同取代度的5-取代恶唑烷酮，并评估了它们的体外抗菌活性。该化合物显示出对弱抗菌活性的作用。一种新型化合物（PH-027）表现出强大的抗菌活性，其抗药性标准和临床分离的革兰氏阳性菌耐药性与利奈唑胺和万古霉素相当或更好。尽管已广泛主张在恶唑烷酮的C-5位置存在C-5-乙酰氨基甲基官能团，并已报道其为恶唑烷酮类化合物中最佳抗菌活性的结构要求，
• OXAZOLIDINONE HYDROXAMIC ACID DERIVATIVES
  申请人：KUWAIT UNIVERSITY

  公开号：US20210238151A1

  公开（公告）日：2021-08-05

  Oxazolidione hydroxamic acid derivatives of the general formula (I): where R 1 is hydrogen or hexanoyl and R 2 is amino, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, cyclobutyl, pentyl, cyclopentyl, hexyl or heptyl, and pharmaceutically acceptable salts thereof, act as dual inhibitors of 5-lipoxygenase and mast cell degranulation. The oxazolidinone hydroxamic acid derivatives or pharmaceutically acceptable salts thereof can be used in the prevention and treatment of asthma and allergies, as well as inflammatory conditions.
• US11608320
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and biological evaluation of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives
  作者：Oludotun A. Phillips、Roselyn D'Silva、Teklu O. Bahta、Leyla H. Sharaf、Edet E. Udo、Ludmil Benov、D. Eric Walters

  DOI：10.1016/j.ejmech.2015.10.025

  日期：2015.12

  Research activities on the oxazolidinone antibacterial class of compounds continue to focus on developing newer derivatives with improved potency, broad-spectrum activity and safety profiles superior to linezolid. Among the safety concerns with the oxazolidinone antibacterial agents is inhibition of monoamine oxidases (MAO) resulting from their structural similarity with toloxatone, a known MAO inhibitor. Diverse substitution patterns at the C-5 position of the oxazolidinone ring have been shown to significantly affect both antibacterial activity and MAO inhibition to varying degrees. Also, the antibacterial activity of compounds containing iron-chelating functionalities, such as the hydroxamic acids, 8-hydroxyquinolines and catechols have been correlated to their ability to alter iron intake and/or metabolism. Hence a series of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives were synthesized and evaluated for their antibacterial and MAO-A and -B inhibitory activities. The compounds were devoid of significant antibacterial activity but most demonstrated moderate MAO-A and -B inhibitory activities. Computer modeling studies revealed that the lack of potent antibacterial activity was due to significant steric interaction between the hydroxamic acid N-OH oxygen atom and one of the G2540 5'-phosphate oxygen atoms at the bacterial ribosomal binding site. Therefore, the replacement of the 5-acetamidomethyl group of linezolid with the 5-(N-hydroxyacetamido)methyl group present in the hydroxamic acid oxazolidinone derivatives was concluded to be detrimental to antibacterial activity. Furthermore, the 5-(hydroxamic acid)methyl oxazolidinone derivatives were also less active as MAO-A and -B inhibitors compared with linezolid and the selective inhibitors clorgyline and pargyline. In general, the 5-(hydroxamic acid)methyl oxazolidinone derivatives demonstrated moderate but selective MAO-B inhibitory activity. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Synthesis and structure-activity relationships of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives as 5-lipoxygenase inhibitors
  作者：Oludotun A. Phillips、Mira A. Bosso、Charles I. Ezeamuzie

  DOI：10.1080/14756366.2020.1786082

  日期：2020.1.1

  Increasing alkyl chain length on the hydroxamic acid moiety enhanced activity and morpholinyl-containing derivatives were more active than N-acetyl-piperizinyl derivatives. The IC50 values in cell-based assay systems were comparable to those obtained by direct inhibition of 5-LO activity, confirming that the compounds are direct inhibitors of 5-LO. Particularly, compounds PH-249 and PH-251 had outstanding

  摘要 合成了恶唑烷酮异羟肟酸衍生物，并在三个体外基于细胞的测试系统中评估了对白三烯（LT）生物合成的抑制活性，并直接抑制了重组人5-脂氧合酶（5-LO）。合成的19种化合物中有13种被认为具有活性（（在两个或多个测试系统中，50％抑制浓度（IC 50）≤10 µM））。异羟肟酸部分上烷基链长度的增加增强了活性，并且含有吗啉基的衍生物比N-乙酰基-哌嗪基衍生物更具活性。IC 50基于细胞的测定系统中的值与通过直接抑制5-LO活性获得的值相当，这证实了这些化合物是5-LO的直接抑制剂。尤其是，化合物PH-249和PH-251具有出色的效力（IC 50 <1 µM），与原型5-LO抑制剂齐留通的效价相当。发音的体内活性证实在小鼠酵母聚糖诱导的腹膜炎。因此，这些新颖的恶唑烷酮异羟肟酸衍生物是有效的5-LO抑制剂，具有潜在的抗过敏和消炎作用。