1-[[1-(3-amino-1,2-benzoisooxazol-5-yl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]-5-[2-(aminosulfonyl)phenyl]-2,3-dihydro-1H-indole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-[[1-(3-amino-1,2-benzoisooxazol-5-yl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]-5-[2-(aminosulfonyl)phenyl]-2,3-dihydro-1H-indole
• 英文别名: 1-[[1-(3-amino-1,2-benzisooxazol-5-yl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]-5-[2-(aminosulfonyl)phenyl]-2,3-dihydro-1H-indole；1-[[1-(3-Amino-1,2-benzisoxazol-5-yl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]-5-[2-(aminosulfonyl)phenyl]-2,3-dihydro-1H-indole；1-[[1-(3-Amino-1,2-benzisoxazol-5-yl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]-5-[2-(aminosulfonyl)phenyl]-2,3-dihydro-1H-indol；2-(1-(1-(3-aminobenzo[d]isoxazol-5-yl)-3-(trifluoromethyl)-1H-pyrazole-5-carbonyl)indolin-5-yl)benzenesulfonamide；2-[1-[2-(3-amino-1,2-benzoxazol-5-yl)-5-(trifluoromethyl)pyrazole-3-carbonyl]-2,3-dihydroindol-5-yl]benzenesulfonamide
• 化学式: C₂₆H₁₉F₃N₆O₄S
• 分子量: 568.536
• InChiKey: CCFWKNLIRQRUNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  40
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  159
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 1-[[1-(3-amino-1,2-benzoisooxazol-5-yl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]-5-[2-(aminosulfonyl)phenyl]-2,3-dihydro-1H-indole
  参考文献：
  名称：

  Design, structure–activity relationship, and pharmacokinetic profile of pyrazole-based indoline factor Xa inhibitors

  摘要：

  A new series of pyrazole-based factor Xa inhibitors have been identified as part of our ongoing efforts to optimize previously reported clinical candidate razaxaban. Concern over the possible formation of primary aniline metabolites via amide hydrolysis led to the replacement of the primary amide linker between the pyrazole and phenyl moieties with secondary amides. This was accomplished by replacing the aniline with a variety of heterobicycles, of which indolines were the most potent. The indoline series demonstrated subnanomolar factor Xa binding K(i)s, modest to high selectivity versus other serine proteases, and good in vitro clotting activity. A small number of indoline fXa inhibitors were pro. led in a dog pharmacokinetic model, one of which demonstrated pharmacokinetic parameters similar to that of clinical candidate razaxaban. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.09.091

文献信息

• NITROGEN CONTAINING HETEROBICYCLES AS FACTOR XA INHIBITORS
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP1196412B1

  公开（公告）日：2004-06-09