2-氟-4-(2-甲基-1H-咪唑-1-基)苯胺 | 218301-88-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-氟-4-(2-甲基-1H-咪唑-1-基)苯胺
• 英文名称: 2-Fluoro-4-(2-methyl-imidazol-1-yl)-phenylamine
• 英文别名: 2-fluoro-4-[2-methylimidazol-1-yl]aniline；1-(4-amino-3-fluoro)phenyl-2-methylimidazole；2-fluoro-4-(2'-methylimidazol-1'-yl)aniline；2-fluoro-4-(2-methylimidazol-1-yl)aniline
• CAS: 218301-88-3
• 化学式: C₁₀H₁₀FN₃
• mdl: MFCD09029879
• 分子量: 191.208
• InChiKey: FYPWCYYDNHFMPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氟-4-(2-甲基-1H-咪唑-1-基)苯胺 在 4-二甲氨基吡啶 、 acetoxyhydroxamic acid 、 potassium tert-butylate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 1-(3'-aminobenzisoxazol-5'-yl)-3-trifluoromethyl-5-[(4-(2'-methylimidazol-1'-yl)-2-fluorophenyl)aminocarbonyl]pyrazoloe
  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
• 作为产物：
  描述：

  在 盐酸 、 sodium hydroxide 作用下， 以 乙酸乙酯 、 水 为溶剂， 反应 1.0h， 生成 2-氟-4-(2-甲基-1H-咪唑-1-基)苯胺
  参考文献：
  名称：

  NOVEL GUANIDINE MIMICS AS FACTOR Xa INHIBITORS

  摘要：

  公开号：

  EP0991638B1

文献信息

• Guanidine mimics as factor Xa inhibitors
  申请人：DuPont Pharmaceuticals Company

  公开号：US06339099B1

  公开（公告）日：2002-01-15

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

  本申请描述了含氮杂环化合物及其衍生物的化学式I：或其药用可接受的盐形式，其中环D—E代表胍嘧啶模拟物，这些化合物可作为凝血因子Xa的抑制剂。
• [EN] INHIBITORS OF FACTOR XA AND OTHER SERINE PROTEASES INVOLVED IN THE COAGULATION CASCADE<br/>[FR] INHIBITEURS DE FACTEUR XA ET AUTRES SERINE PROTEASES INTERVENANT DANS LA CASCADE DE COAGULATION
  申请人：WARNER LAMBERT CO

  公开号：WO2004024679A1

  公开（公告）日：2004-03-25

  This invention discloses amino acid derivatives which display inhibitory effects on the serine protease factor Xa. The invention also discloses pharmaceutically acceptable salts of the compounds, pharmaceutically acceptable compositions comprising the compounds or their salts, methods for the preparation of the compounds, and methods of using them as therapeutic agents for treating or preventing disease states in mammals characterized by abnormal thrombosis.

  该发明揭示了显示对丝氨酸蛋白酶Xa具有抑制作用的氨基酸衍生物。该发明还揭示了该化合物的药用盐、包含该化合物或其盐的药用组合物、制备该化合物的方法，以及将其用作治疗或预防哺乳动物异常血栓形成疾病状态的治疗剂的方法。
• Efficient ligand-mediated ullmann coupling of anilnies and azoles
  申请人：——

  公开号：US20020099225A1

  公开（公告）日：2002-07-25

  The present invention provides of method of preparing phenyl-substituted azoles. This method uses an efficient ligand-accelerated Ullmann coupling reaction of anilines with azoles. The coupling products are useful for preparing factor Xa inhibitors.

  本发明提供了制备苯基取代咪唑的方法。该方法利用了一种高效的配体加速的乌尔曼偶联反应，将苯胺与咪唑偶联。偶联产物可用于制备因子Xa抑制剂。
• Inhibitors of factor Xa and other serine proteases involved in the coagulation cascade
  申请人：——

  公开号：US20030162787A1

  公开（公告）日：2003-08-28

  The present invention provides compounds of Formula (I): 1 wherein A, B, C, G, and W 1 have any of the values defined in the specification, and pharmaceutically acceptable salt thereof, that are useful to treat thrombotic disorders. Also disclosed are pharmaceutical compositions comprising one or more compounds of Formula I, processes for preparing compounds of Formula I, and intermediates useful for preparing compounds of Formula I.

  本发明提供了化合物的结构式（I）：其中A、B、C、G和W1的取值如规范中所定义，以及其药学上可接受的盐，这些化合物对治疗血栓性疾病有用。还公开了包含一个或多个结构式I化合物的药物组合物，用于制备结构式I化合物的方法，以及用于制备结构式I化合物的中间体。
• Inhibitors of fractor Xa and other serine proteases involved in the coagulation cascade
  申请人：Bigge Franklin Christopher

  公开号：US20050250815A1

  公开（公告）日：2005-11-10

  The present invention provides compounds of Formula (I): wherein A, B, C, G, and W 1 have any of the values defined in the specification, and pharmaceutically acceptable salt thereof, that are useful to treat thrombotic disorders. Also disclosed are pharmaceutical compositions comprising one or more compounds of Formula I, processes for preparing compounds of Formula I, and intermediates useful for preparing compounds of Formula I.

  本发明提供了公式（I）的化合物：其中A，B，C，G和W1具有规范中定义的任何值，并且其药学上可接受的盐，用于治疗血栓性疾病。还披露了包含一个或多个公式I化合物的制药组合物，用于制备公式I化合物的过程以及用于制备公式I化合物的中间体。