利伐沙班4 | 1424944-35-3

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: 利伐沙班4
• 中文别名: 利伐沙班杂质3
• 英文名称: 2-({(5R)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)-1H-isoindole-1,3(2H)-dione
• 英文别名: (R)-2-((2-oxo-3-(4-(3-oxomorpholin-4-yl)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione；(R)-2-((2-oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)isoindoline-1,3-dione；2-[[(5R)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl]methyl]isoindole-1,3-dione
• CAS: 1424944-35-3
• 化学式: C₂₂H₁₉N₃O₆
• 分子量: 421.409
• InChiKey: KUQNYAUTIWQAKY-INIZCTEOSA-N

物化性质

• 沸点：
  702.9±55.0 °C(Predicted)
• 密度：
  1.465±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于乙腈（轻微）、DMSO（轻微）、乙酸乙酯（轻微、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  96.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  利伐沙班4 在 甲胺 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 4-{4-[(5R)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one
  参考文献：
  名称：

  Discovery of the Novel Antithrombotic Agent 5-Chloro-N-({(5S)-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

  摘要：

  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.

  DOI：

  10.1021/jm050101d
• 作为产物：
  描述：

  4-(4-氨基苯基)吗啡啉-3-酮 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 51.0h， 生成 利伐沙班4
  参考文献：
  名称：

  Discovery of the Novel Antithrombotic Agent 5-Chloro-N-({(5S)-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

  摘要：

  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.

  DOI：

  10.1021/jm050101d

文献信息

• [EN] PROCESS FOR THE PREPARATION OF RIVAROXABAN<br/>[FR] PROCÉDÉ DE PRÉPARATION DU RIVAROXABAN
  申请人：CIPLA LTD

  公开号：WO2016030669A1

  公开（公告）日：2016-03-03

  The present invention relates to an environmentally friendly process for preparing rivaroxaban. The present invention provides a process for preparing rivaroxaban of formula I, the process comprising: reacting a compound of formula VI with a base in the presence of a solvent to form a compound of formula VII; and condensing the compound of formula VII with a compound of formula VIII or a compound of formula IX in the presence of a solvent to prepare rivaroxaban of formula I, wherein the solvent used in both steps comprises water.

  本发明涉及一种环保的制备利伐洛班的过程。本发明提供了一种制备利伐洛班的方法，该方法包括：在溶剂存在的条件下，将化合物VI与碱反应以形成化合物VII；并在溶剂存在的条件下，将化合物VII与化合物VIII或化合物IX缩合以制备利伐洛班的方法，其中两个步骤中使用的溶剂均包括水。
• Process for the Preparation of Rivaroxaban
  申请人：Cipla Limited

  公开号：US20170267669A1

  公开（公告）日：2017-09-21

  The present invention relates to an environmentally friendly process for preparing rivaroxaban. The present invention provides a process for preparing rivaroxaban of formula I, the process comprising: reacting a compound of formula VI with a base in the presence of a solvent to form a compound of formula VII; and condensing the compound of formula VII with a compound of formula VIII or a compound of formula IX in the presence of a solvent to prepare rivaroxaban of formula I, wherein the solvent used in both steps comprises water.

  本发明涉及一种环保的制备利伐沙班的方法。本发明提供了一种制备式I利伐沙班的方法，该方法包括：在溶剂存在下，将式VI化合物与碱反应形成式VII化合物；并在溶剂存在下，将式VII化合物与式VIII化合物或式IX化合物缩合，制备出式I利伐沙班，其中在两个步骤中使用的溶剂均为水。
• PROCESSES FOR THE PREPARATION OF 4-MORPHOLIN-3-ONE
  申请人：Mohan Rao Dodda

  公开号：US20130172554A1

  公开（公告）日：2013-07-04

  The present invention provides processes for the preparation of 4-4-[5(S)-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one which are simple, eco-friendly, cost-effective, reproducible, robust and are well amenable on industrial scale.

  本发明提供了制备4-4-[5(S)-(氨甲基)-2-氧代-1,3-噁唑啉-3-基]苯基}吗啡啶-3-酮的工艺，这些工艺简单、环保、经济实惠、可重复、稳健并且非常适合工业规模应用。
• US9663505B2
  申请人：——

  公开号：US9663505B2

  公开（公告）日：2017-05-30