rivaroxaban

• 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: rivaroxaban
• 英文别名: 5-Methyl-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide；5-methyl-N-[[(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl]methyl]thiophene-2-carboxamide
• 化学式: C₂₀H₂₁N₃O₅S
• 分子量: 415.47
• InChiKey: YWRVKEHHSZEJNV-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-[[(5S)-2-氧代-3-[4-(3-氧代-4-吗啉基)苯基]-5-噁唑烷基]甲基]-1H-异吲哚-1,3(2H)-二酮 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 、 甲胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 rivaroxaban
  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

• 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。
• Pharmaceutical diversification via palladium oxidative addition complexes
  作者：Mycah R. Uehling、Ryan P. King、Shane W. Krska、Tim Cernak、Stephen L. Buchwald

  DOI：10.1126/science.aac6153

  日期：2019.1.25

  product of palladium's reaction with a complex aryl halide ahead of time. Subjecting these compounds to downstream coupling reactions substantially improved yields. Science, this issue p. 405 Isolating products of palladium’s reaction with complex aryl halides facilitates subsequent reactions with coupling partners. Palladium-catalyzed cross-coupling reactions have transformed the exploration of chemical

  提前嵌入钯 钯催化的交叉偶联是药物研究中应用最广泛的反应类别之一。该金属擅长将芳香环相互连接或连接到氮中心。然而，功能复杂性会阻碍反应，需要费力的配体优化。乌林等人。通过提前分离钯与复杂的芳基卤化物反应的稳定产物来缓解这个问题。将这些化合物进行下游偶联反应可显着提高产率。科学，这个问题 p。405 分离钯与复杂芳基卤化物反应的产物有利于与偶联伙伴的后续反应。钯催化的交叉偶联反应改变了化学空间在寻找材料、药物、化学探针和其他功能分子。然而，密集功能化基材的交叉偶联仍然是一个主要挑战。我们设计了一种替代方法，使用化学计量量的钯氧化加成复合物 (OAC)，该复合物源自药物或类药物芳基卤化物作为底物。在大多数情况下，使用 OAC 的交叉偶联反应在更温和的条件下进行，并且比类似的催化反应成功率更高。OAC 表现出非凡的稳定性，在环境条件下在台式储存数月后仍能保持其反应性。我们在各种实验中证明了 OAC