1-(4-amino-3-fluorophenyl)-2-hydroxymethylimidazole | 540510-47-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-amino-3-fluorophenyl)-2-hydroxymethylimidazole
• 英文别名: [1-(4-Amino-3-fluorophenyl)imidazol-2-yl]methanol
• CAS: 540510-47-2
• 化学式: C₁₀H₁₀FN₃O
• 分子量: 207.207
• InChiKey: WBGNZIOHKVZXKU-UHFFFAOYSA-N

物化性质

• 沸点：
  425.8±55.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  64.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-amino-3-fluorophenyl)-2-hydroxymethylimidazole 在 甲醇 、 4-二甲氨基吡啶 、 sodium azide 、 乙酰氧肟酸 、 四丁基氟化铵 、 三溴化磷 、 potassium carbonate 、 三乙胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 Aminobenzisoxazole 37
  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：

  咪唑-2-甲醇 、 2-氟-4-碘苯胺 在 copper(l) iodide 、 1,10-菲罗啉 、 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 12.0h， 以10%的产率得到1-(4-amino-3-fluorophenyl)-2-hydroxymethylimidazole
  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

• Novel N-[4- (1H-imidazol-1-yl) -2-fluorophenyl ] -3- (trifluoromethyl) -1H-pyrazole-5-carboxamides as factor Xa inhibitors
  申请人：——

  公开号：US20030144287A1

  公开（公告）日：2003-07-31

  The present application describes N-[4-(1H-imidazol-1-yl)-2-fluorophenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamides and derivatives thereof of, which are useful as inhibitors of factor Xa.

  本申请描述了N-[4-(1H-咪唑-1-基)-2-氟苯基]-3-(三氟甲基)-1H-吡唑-5-甲酰胺及其衍生物，这些化合物可作为因子Xa的抑制剂。
• EP1460996A4
  申请人：——

  公开号：EP1460996A4

  公开（公告）日：2005-11-16
• NOVEL-N-4-(1H-IMIDAZOL-1-YL)-2-FLUOROPHENYL]-3-(TRIFLUOROMETHYL)-1-H-PYRAZOLE-5-CARBOXAMIDES AS FACTOR XA
  申请人：Bristol-Myers Squibb Company

  公开号：EP1460996A2

  公开（公告）日：2004-09-29
• US6730689B2
  申请人：——

  公开号：US6730689B2

  公开（公告）日：2004-05-04
• [EN] NOVEL-N-[4-(1H-IMIDAZOL-1-YL)-2-FLUOROPHENYL]-3-(TRIFLUOROMETHYL)-1-H-PYRAZOLE-5-CARBOXAMIDES AS FACTOR XA<br/>[FR] NOUVEAUX N-[4-(1H-IMIDAZOL-1-YL)-2-FLUOROPHENYL]-3-(TRIFLUOROMETHYL)-1H-PYRAZOLE-5-CARBOXAMIDES SERVANT D'INHIBITEURS DU FACTEUR XA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2003047517A2

  公开（公告）日：2003-06-12

  The present application describes N-[4-(1H-imidazol-1-yl)-2-fluoropheny1]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamides and derivatives thereof of, which are useful as inhibitors of factor Xa.