(5S)-5-(aminomethyl)-3-(3-fluoro-4-pyrrolidin-1-ylphenyl)-1,3-oxazolidin-2-one | 221201-27-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (5S)-5-(aminomethyl)-3-(3-fluoro-4-pyrrolidin-1-ylphenyl)-1,3-oxazolidin-2-one
• 英文别名: (S)-N-[3-(3-fluoro-4-pyrrolidinylphenyl)-2-oxo-5-oxazolidinyl]methylamine
• CAS: 221201-27-0
• 化学式: C₁₄H₁₈FN₃O₂
• 分子量: 279.314
• InChiKey: DAYRVUFTZUGEKU-NSHDSACASA-N

物化性质

• 沸点：
  449.8±40.0 °C(Predicted)
• 密度：
  1.299±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (5S)-5-(aminomethyl)-3-(3-fluoro-4-pyrrolidin-1-ylphenyl)-1,3-oxazolidin-2-one 在 sodium hydroxide 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 8.0h， 生成 [(5S)-3-(3-fluoro-4-pyrrolidin-1-ylphenyl)-2-oxo-1,3-oxazolidin-5-yl]methylthiourea
  参考文献：
  名称：

  恶唑烷酮抗菌剂的构效关系（SAR）研究。2.在5-硫代羰基恶唑烷酮中亲脂性与抗菌活性之间的关系。

  摘要：

  考虑到分子的疏水性参数，对5-硫代羰基恶唑烷酮抗菌剂的研究继续进行，合成了5-硫脲和5-二硫代氨基甲酸酯恶唑烷酮。结构-活性关系（SAR）研究表明，亲脂性显着影响对5-硫代羰基恶唑烷酮的抗菌活性，尤其是计算出的log P值以及5-亲水（或疏水）取代基与疏水（或亲水）之间的平衡苯环上的取代基。发现一些5-硫代羰基恶唑烷酮对革兰氏阳性细菌具有良好的体外抗菌活性，包括耐甲氧西林的金黄色葡萄球菌（MRSA）和耐万古霉素的肠球菌（VRE）。

  DOI：

  10.1248/cpb.49.353
• 作为产物：
  描述：

  3-氟-4-(四氢吡咯基)苯胺 在 sodium azide 、 水 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 (5S)-5-(aminomethyl)-3-(3-fluoro-4-pyrrolidin-1-ylphenyl)-1,3-oxazolidin-2-one
  参考文献：
  名称：

  恶唑烷酮抗菌剂的构效关系（SAR）研究。2.在5-硫代羰基恶唑烷酮中亲脂性与抗菌活性之间的关系。

  摘要：

  考虑到分子的疏水性参数，对5-硫代羰基恶唑烷酮抗菌剂的研究继续进行，合成了5-硫脲和5-二硫代氨基甲酸酯恶唑烷酮。结构-活性关系（SAR）研究表明，亲脂性显着影响对5-硫代羰基恶唑烷酮的抗菌活性，尤其是计算出的log P值以及5-亲水（或疏水）取代基与疏水（或亲水）之间的平衡苯环上的取代基。发现一些5-硫代羰基恶唑烷酮对革兰氏阳性细菌具有良好的体外抗菌活性，包括耐甲氧西林的金黄色葡萄球菌（MRSA）和耐万古霉素的肠球菌（VRE）。

  DOI：

  10.1248/cpb.49.353

文献信息

• Structure-Activity Relationship (SAR) Studies on Oxazolidinone Antibacterial Agents. 3. Synthesis and Evaluation of 5-Thiocarbamate Oxazolidinones.
  作者：Ryukou TOKUYAMA、Yoshiei TAKAHASHI、Yayoi TOMITA、Masatoshi TSUBOUCHI、Nobuhiko IWASAKI、Noriyuki KADO、Eiichi OKEZAKI、Osamu NAGATA

  DOI：10.1248/cpb.49.361

  日期：——

  A series of 5-thiocarbamate oxazolidinones was prepared and tested for in vitro and in vivo antibacterial activities. The results of in vitro antibacterial activity indicated that the 5-thiocarbamate group was a suitable substituent for the activity by the 5-moderate hydrophilicity. The compounds within a favorable log P value range were found to have potent in vitro antibacterial activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Compounds 3a and 4h were superior to linezolid in both in vitro and in vivo potency and were considered to be hopeful compounds. We also discuss the pharmacokinetic properties of several compounds in mice.

  制备了一系列 5-硫代氨基甲酸酯噁唑烷酮，并对其进行了体外和体内抗菌活性测试。体外抗菌活性结果表明，5-硫代氨基甲酸酯基团具有 5-适度亲水性，是一种合适的活性取代基。在有利的对数值范围内的化合物对革兰氏阳性菌（包括耐甲氧西林金黄色葡萄球菌（MRSA）和耐万古霉素肠球菌（VRE））具有强效的体外抗菌活性。化合物 3a 和 4h 的体外和体内效力均优于利奈唑胺，被认为是有希望的化合物。我们还讨论了几种化合物在小鼠体内的药代动力学特性。
• Novel antimycobacterial compounds
  申请人：Arora Kumar Sudershan

  公开号：US20050192275A1

  公开（公告）日：2005-09-01

  Novel compounds belonging to the class of oxazolidinones possessing potent antimycobacterial properties especially useful in the treatment of acid fast organisms such as Mycobacterium tuberculosis, Mycobacterium avium -intracellular complex, M. fortuitum and M. kansai . The compound and its pharmaceutically acceptable salts thereof act as antibacterial agents. Also disclosed is a method for inhibiting growth of mycobacterial cells as well as a method of treating mycobacterial conditions such as Mycobacterium tuberculosis , drug resistant Mycobacterium tuberculosis, Mycobacterium avium -intracellular complex, M. fortuitum and M. kansai , comprising administering an antimycobacterially effective amount of the said compound and/or pharmaceutically acceptable salts thereof. There is also disclosed a process for the manufacture of the said compound or its pharmaceutically acceptable salts.

  本发明涉及一类属于噁唑烷酮类的新化合物，具有强大的抗结核分枝杆菌的特性，尤其适用于治疗酸性快速生长的微生物，如结核分枝杆菌、肺巨细胞分枝杆菌、幸福分枝杆菌和关西分枝杆菌等。该化合物及其药用盐作为抗菌剂。本发明还公开了一种抑制分枝杆菌细胞生长的方法，以及一种治疗分枝杆菌感染的方法，如结核分枝杆菌、耐药结核分枝杆菌、肺巨细胞分枝杆菌、幸福分枝杆菌和关西分枝杆菌等，包括给予所述化合物和/或其药用盐的抗分枝杆菌有效量。本发明还公开了一种制备所述化合物或其药用盐的方法。
• Discovery of the Novel Antithrombotic Agent 5-Chloro-<i>N</i>-({(5<i>S</i>)-2-oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene- 2-carboxamide (BAY 59-7939):  An Oral, Direct Factor Xa Inhibitor
  作者：Susanne Roehrig、Alexander Straub、Jens Pohlmann、Thomas Lampe、Josef Pernerstorfer、Karl-Heinz Schlemmer、Peter Reinemer、Elisabeth Perzborn

  DOI：10.1021/jm050101d

  日期：2005.9.1

  Despite recent progress in antithrombotic therapy, there is still an unmet medical need for safe and orally available anticoagulants. The coagulation enzyme Factor Xa (FXa) is a particularly promising target, and recent efforts in this field have focused on the identification of small-molecule inhibitors with good oral bioavailability. We identified oxazolidinone derivatives as a new class of potent FXa inhibitors. Lead optimization led to the discovery of BAY 59-7939 (5), a highly potent and selective, direct FXa inhibitor with excellent in vivo antithrombotic activity. The X-ray crystal structure of 5 in complex with human FXa clarified the binding mode and the stringent requirements for high affinity. The interaction of the neutral ligand chlorothiophene in the S1 subsite allows for the combination of good oral bioavailability and high potency for nonbasic 5. Compound 5 is currently under clinical development for the prevention and treatment of thromboembolic diseases.
• US7691889B2
  申请人：——

  公开号：US7691889B2

  公开（公告）日：2010-04-06
• Structure-Activity Relationship (SAR) Studies on Oxazolidinone Antibacterial Agents. 2. Relationship between Lipophilicity and Antibacterial Activity in 5-Thiocarbonyl Oxazolidinones.
  作者：Ryukou TOKUYAMA、Yoshiei TAKAHASHI、Yayoi TOMITA、Masatoshi TSUBOUCHI、Toshihiko YOSHIDA、Nobuhiko IWASAKI、Noriyuki KADO、Eiichi OKEZAKI、Osamu NAGATA

  DOI：10.1248/cpb.49.353

  日期：——

  5-Thiourea and 5-dithiocarbamate oxazolidinones were synthesized as a continuation of research on 5-thiocarbonyl oxazolidinone antibacterial agents considering the hydrophobic parameters of the molecule. The structure-activity relationship (SAR) study revealed that the antibacterial activity on 5-thiocarbonyl oxazolidinones was significantly affected by the lipophilicity, especially the calculated

  考虑到分子的疏水性参数，对5-硫代羰基恶唑烷酮抗菌剂的研究继续进行，合成了5-硫脲和5-二硫代氨基甲酸酯恶唑烷酮。结构-活性关系（SAR）研究表明，亲脂性显着影响对5-硫代羰基恶唑烷酮的抗菌活性，尤其是计算出的log P值以及5-亲水（或疏水）取代基与疏水（或亲水）之间的平衡苯环上的取代基。发现一些5-硫代羰基恶唑烷酮对革兰氏阳性细菌具有良好的体外抗菌活性，包括耐甲氧西林的金黄色葡萄球菌（MRSA）和耐万古霉素的肠球菌（VRE）。