1-(4-{2-[2-(3-amino-benzo[d]isoxazol-5-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-2-oxo-ethyl}-phenyl)-piperidin-2-one | 1011486-62-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4-{2-[2-(3-amino-benzo[d]isoxazol-5-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-2-oxo-ethyl}-phenyl)-piperidin-2-one
• 英文别名: 1-[4-[2-[2-(3-amino-1,2-benzoxazol-5-yl)-5-(trifluoromethyl)pyrazol-3-yl]-2-oxoethyl]phenyl]piperidin-2-one
• CAS: 1011486-62-6
• 化学式: C₂₄H₂₀F₃N₅O₃
• 分子量: 483.45
• InChiKey: RASIDBNWCVIECX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-fluoro-5-(5-(2-(4-(2-oxopiperidin-1-yl)phenyl)acetyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzonitrile 在 乙酰氧肟酸 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以2%的产率得到1-(4-{2-[2-(3-amino-benzo[d]isoxazol-5-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-2-oxo-ethyl}-phenyl)-piperidin-2-one
  参考文献：
  名称：

  Structure–activity relationship and pharmacokinetic profile of 5-ketopyrazole factor Xa inhibitors

  摘要：

  Efforts to further optimize the clinical candidate razaxaban have led to a new series of pyrazole-based factor Xa (fxa) inhibitors. Designed to prevent the potential formation of primary aniline metabolites in vivo, the nitrogen of the carboxamido linker between the pyrazole and proximal phenyl moiety of the razaxaban scaffold was replaced with a methylene group. The resulting ketones demonstrated excellent potency and selectivity for fXa but initially had poor oral bioavailability. Optimization by conversion from a P1 aminobenzisoxazole to a P1 p-methoxyphenyl residue, replacing the 3-trifluoromethylpyrazole with a 3-amidopyrazole, and employing a pyridone P4 group provided a fXa inhibitor with a potency and pharmacokinetic profile equivalent to that of razaxaban and improved selectivity over thrombin. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.040

文献信息

• Structure–activity relationship and pharmacokinetic profile of 5-ketopyrazole factor Xa inhibitors
  作者：Jeffrey G. Varnes、Dean A. Wacker、Donald J.P. Pinto、Michael J. Orwat、Jay P. Theroff、Brian Wells、Robert A. Galemo、Joseph M. Luettgen、Robert M. Knabb、Steven Bai、Kan He、Patrick Y.S. Lam、Ruth R. Wexler

  DOI：10.1016/j.bmcl.2007.11.040

  日期：2008.1

  Efforts to further optimize the clinical candidate razaxaban have led to a new series of pyrazole-based factor Xa (fxa) inhibitors. Designed to prevent the potential formation of primary aniline metabolites in vivo, the nitrogen of the carboxamido linker between the pyrazole and proximal phenyl moiety of the razaxaban scaffold was replaced with a methylene group. The resulting ketones demonstrated excellent potency and selectivity for fXa but initially had poor oral bioavailability. Optimization by conversion from a P1 aminobenzisoxazole to a P1 p-methoxyphenyl residue, replacing the 3-trifluoromethylpyrazole with a 3-amidopyrazole, and employing a pyridone P4 group provided a fXa inhibitor with a potency and pharmacokinetic profile equivalent to that of razaxaban and improved selectivity over thrombin. (c) 2007 Elsevier Ltd. All rights reserved.