利伐沙班杂质27 | 1369969-44-7

• 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: 利伐沙班杂质27
• 英文名称: 2-((2R)-2-hydroxy-3-{[4-(3-oxomorpholin-4-yl)phenyl]amino}propyl)-1H-isoindole-1,3(2H)-dione
• 英文别名: 2-[(2S)-2-hydroxy-3-[[4-(3-oxo-4-morpholinyl)phenyl]amino]propyl]-1H-isoindole-1,3(2H)-dione；1H-Isoindole-1,3(2H)-dione, 2-[(2S)-2-hydroxy-3-[[4-(3-oxo-4-morpholinyl)phenyl]amino]propyl]-；2-[(2S)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)anilino]propyl]isoindole-1,3-dione
• CAS: 1369969-44-7
• 化学式: C₂₁H₂₁N₃O₅
• 分子量: 395.415
• InChiKey: CKFVSMPWXAASIQ-INIZCTEOSA-N

物化性质

• 沸点：
  734.9±60.0 °C(Predicted)
• 密度：
  1.421±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（轻微）、甲醇（轻微、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  99.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  利伐沙班杂质27 在 4-二甲氨基吡啶 、 甲胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 25.0h， 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：

  (S)-N-缩水甘油邻苯二甲酰亚胺 、 4-(4-氨基苯基)吗啡啉-3-酮 以 水 、 甲苯 为溶剂， 以94.6%的产率得到利伐沙班杂质27
  参考文献：
  名称：

  一种利伐沙班中间体的制备方法

  摘要：

  一种利伐沙班中间体2‑[(2S)‑2‑羟基‑3‑[[4‑(3‑氧代‑4吗啉基)苯基]氨基]丙基]‑1H‑异吲哚‑1,3(2H)‑二酮]的制备方法，所述方法为：室温下，将4‑(4‑氨基苯基)吗啡啉‑3‑酮和S‑缩水甘油邻苯二甲酰亚胺加入到混合溶剂中，搅拌，回流反应1.5～3h后，补加混合溶剂，继续搅拌回流反应3～5h，然后降温至20～40℃，搅拌1～3h，之后经后处理，得到产物；用本发明的混合溶剂作为反应溶剂，能缩短反应时间、溶剂易回收利用，从而降低能耗，同时克服了异构体偏大、成本较高和工艺繁琐等缺陷，是一种工业化生产工艺。

  公开号：

  CN110054623A

文献信息

• COMBINATION THERAPY OF SUBSTITUTED OXAZOLIDINONES
  申请人：Perzborn Elisabeth

  公开号：US20100120718A1

  公开（公告）日：2010-05-13

  The present invention relates to combinations of A) oxazolidinones of the formula (I) with B) acetylsalicylic acid (aspirin) and C) an ADP receptor antagonist, in particular P 2 Y 12 purinoreceptor blocker, to a process for producing these combinations and to the use thereof as medicaments, in particular for the prophylaxis and/or treatment of thromboembolic disorders.

  本发明涉及A) 公式（I）的噁唑烷二酮与B) 乙酰水杨酸（阿司匹林）和C) ADP受体拮抗剂的组合物，特别是P2Y12嘌呤受体阻滞剂，以及制备这些组合物的方法和将其用作药物，特别是用于预防和/或治疗血栓栓塞性疾病。
• MICROANGIOPATHY TREATMENT AND PREVENTION
  申请人：Perzborn Elisabeth

  公开号：US20100160301A1

  公开（公告）日：2010-06-24

  The present invention relates to the use of selective factor Xa inhibitors, in particular of oxazolidinones of the formula (I) for the treatment and/or prophylaxis of microangiopathies and also their use for the production of medicaments for the treatment and/or prophylaxis of microangiopathies.

  本发明涉及选择性因子Xa抑制剂的使用，特别是公式(I)的噁唑烷酮，用于治疗和/或预防微血管病，并且它们用于生产用于治疗和/或预防微血管病的药物。
• Substituted oxazolidinones and their in the field of blood coagulation
  申请人：——

  公开号：US20030153610A1

  公开（公告）日：2003-08-14

  The invention relates to the field of blood coagulation. Novel oxazolidinone derivatives of the general formula (I) 1 processes for their preparation and their use as medicinally active compounds for the prophylaxis and/or treatment of disorders are described.

  这项发明涉及血液凝固领域。描述了一种新颖的一舁氧杂环丙烷衍生物，其一舁通式为（I）的制备方法以及它们作为药用活性化合物用于预防和/或治疗疾病的用途。
• Combination Therapy Comprising Substituted Oxazolidinones for the Prevention and Treatment of Cerebral Circulatory Disorders
  申请人：Perzborn Elisabeth

  公开号：US20080306070A1

  公开（公告）日：2008-12-11

  The present invention relates to combinations of A) oxazolidinones of the formula (I), with B) antiarrhythmics, processes for the production of these combinations, their use for the prophylaxis and/or treatment of diseases, and their use for the manufacture of medicaments for the prophylaxis and/or treatment of diseases, especially of thromboembolic disorders and/or complications.

  本发明涉及A) 具有化学式(I)的噁唑烷二酮与B) 抗心律失常药物的组合物，以及用于制备这些组合物的方法，它们用于预防和/或治疗疾病，并且用于制造用于预防和/或治疗疾病，特别是血栓栓塞性疾病和/或并发症的药物。
• PROCESS FOR PREPARATION OF RIVAROXABAN AND INTERMEDIATES THEREOF
  申请人：MEGAFINE PHARMA (P) LTD

  公开号：US20150011756A1

  公开（公告）日：2015-01-08

  An improved process for the preparation of Rivaroxaban wherein the process substantially eliminates the potential impurities. process for preparation of Rivaroxaban which uses a novel intermediate. A process for preparing the novel intermediate which is used for the preparation of Rivaroxaban.

  一种改进的利伐沙班制备工艺，该工艺基本消除了潜在的杂质。利伐沙班制备工艺使用一种新型中间体。一种用于制备利伐沙班的新型中间体的制备工艺。