雷扎沙班 | 218298-21-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 雷扎沙班
• 英文名称: razaxaban
• 英文别名: raxazaban；1-(3'-aminobenzisoxazol-5'-yl)-3-trifluoromethyl-5-[[4-[(2'-dimethylaminomethyl)imidazol-1'-yl]-2-fluorophenyl]aminocarbonyl]pyrazole；2-(3-amino-1,2-benzoxazol-5-yl)-N-[4-[2-[(dimethylamino)methyl]imidazol-1-yl]-2-fluorophenyl]-5-(trifluoromethyl)pyrazole-3-carboxamide
• CAS: 218298-21-6
• 化学式: C₂₄H₂₀F₄N₈O₂
• 分子量: 528.469
• InChiKey: OFJRNBWSFXEHSA-UHFFFAOYSA-N

物化性质

• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  11

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	1-(3'-cyano-4'-fluorophenyl)-3-trifluoromethyl-N-[2-fluoro-4-[(2'-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide	405940-74-1	C24H18F5N7O	515.445
  ——	2-(3-cyano-4-fluoro-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carbonyl chloride	754193-45-8	C12H4ClF4N3O	317.63
  ——	1-(3-cyano-4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic Acid	209960-58-7	C12H5F4N3O2	299.184

反应信息

• 作为反应物：
  描述：

  雷扎沙班 以92的产率得到Razaxaban Hydrochloride
  参考文献：
  名称：

  J. Med. Chem. 2005, 48, 1729-1744

  摘要：

  DOI：
• 作为产物：
  描述：

  2-[(二甲氨基)甲基]咪唑 在 4-二甲氨基吡啶 、 copper(l) iodide 、 acetoxyhydroxamic acid 、 potassium tert-butylate 、 potassium carbonate 作用下， 以 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 雷扎沙班
  参考文献：
  名称：

  Discovery of 1-(3‘-Aminobenzisoxazol-5‘-yl)-3-trifluoromethyl-N-[2-fluoro-4- [(2‘-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide Hydrochloride (Razaxaban), a Highly Potent, Selective, and Orally Bioavailable Factor Xa Inhibitor

  摘要：

  Modification of a series of pyrazole factor Xa inhibitors to incorporate an aminobenzisoxazole as the P(1) ligand resulted in compounds with improved selectivity for factor Xa relative to trypsin and plasma kallikrein. Further optimization of the P(4) moiety led to compounds with enhanced permeability and reduced protein binding. The SAR and pharmacokinetic profile of this series of compounds is described herein. These efforts culminated in 1-(3'-aminobenzisoxazol-5'-yl)-3-trifluoromethyl-N-[2-fluoro-4-[(2'-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide (11d), a potent, selective, and orally bioavailable inhibitor of factor Xa. On the basis of its excellent in vitro potency and selectivity profile, high free fraction in human plasma, good oral bioavailability, and in vivo efficacy in antithrombotic models, the HCl salt of this compound was selected for clinical development as razaxaban (DPC 906, BMS-561389).

  DOI：

  10.1021/jm0497949

文献信息

• SUBSTITUTED OXAZOLIDINONES AND THEIR USE
  申请人：Allerheiligen Swen

  公开号：US20100261759A1

  公开（公告）日：2010-10-14

  The invention relates to novel substituted oxazolidinones, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of thromboembolic disorders.

  这项发明涉及新型取代氧唑烷酮，其制备方法，其用于治疗和/或预防疾病以及用于制备用于治疗和/或预防疾病，特别是血栓栓塞性疾病的药物。
• 2-(HETEROARYL) ALKYL INDAZOLE 6-PHENYL AND THIENYL METHYL AMIDE AS THROMBIN INHIBITORS
  申请人：Siegel Stephan

  公开号：US20100105663A1

  公开（公告）日：2010-04-29

  The invention relates to substituted indazoles and methods for production thereof and use thereof for the production of medicinal products for the treatment and/or prophylaxis of diseases, especially of cardiovascular diseases, preferably of thromboembolic diseases.

  该发明涉及取代吲唑并且生产方法以及用于制备治疗和/或预防疾病的药物的用途，特别是心血管疾病，最好是血栓栓塞疾病。
• Novel guanidine mimics as factor Xa inhibitors
  申请人：——

  公开号：US20020025963A1

  公开（公告）日：2002-02-28

  The present application describes nitrogen containing heteroaromatics and derivatives thereof of formula I: 1 or pharmaceutically acceptable salt forms thereof, wherein rings D—E represent guanidine mimics, which are useful as inhibitors of factor Xa.

  本申请描述了公式I的含氮杂环及其衍生物，其中D-E环代表鸟氨酸类似物，其可作为因子Xa的抑制剂，或其药学上可接受的盐形式。
• Novel guanidine mimics factor Xa inhibitors
  申请人：——

  公开号：US20030069258A1

  公开（公告）日：2003-04-10

  The present application describes nitrogen containing heteroaromatics and derivatives thereof of formula I: 1 or pharmaceutically acceptable salt forms thereof, wherein rings D-E represent guanidine mimics, which are useful as inhibitors of factor Xa.

  本申请描述了式I的含氮杂环及其衍生物：1或其药学上可接受的盐形式，其中环D-E代表鸟氨酸类似物，可用作因子Xa的抑制剂。
• Novel intermediates for guanidine mimics as factor Xa inhibitors
  申请人：——

  公开号：US20040063772A1

  公开（公告）日：2004-04-01

  The present application describes intermediates for nitrogen containing heteroaromatics and derivatives thereof of formula I: 1 or pharmaceutically acceptable salt forms thereof, wherein rings D—E represent guanidine mimics, which are useful as inhibitors of factor Xa.

  本申请描述了一些中间体，用于制备公式I：1中的含氮杂环和其衍生物，或其药学上可接受的盐形式，其中环D-E代表鸟氨酸类似物，这些中间体可用作因子Xa的抑制剂。