N-[2-fluoro-4-(1-methyl-4,5-dihydroimidazol-2-yl)phenyl]-2-(3-fluoronaphthalen-2-yl)-5-methylpyrazole-3-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[2-fluoro-4-(1-methyl-4,5-dihydroimidazol-2-yl)phenyl]-2-(3-fluoronaphthalen-2-yl)-5-methylpyrazole-3-carboxamide
• 化学式: C₂₅H₂₁F₂N₅O
• 分子量: 445.471
• InChiKey: XBCIKUZXKQMGHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  62.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氟-4-氨基苯腈 在 硫化氢 、 三甲基铝 、 溶剂黄146 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 正己烷 、 二氯甲烷 、 丙酮 为溶剂， 反应 1.0h， 生成 N-[2-fluoro-4-(1-methyl-4,5-dihydroimidazol-2-yl)phenyl]-2-(3-fluoronaphthalen-2-yl)-5-methylpyrazole-3-carboxamide
  参考文献：
  名称：

  1-(2-Naphthyl)-1 H -pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 3: Design, synthesis and SAR of orally bioavailable benzamidine-P4 inhibitors

  摘要：

  Using N,N-dialkylated benzamidines as the novel P4 motifs, we have designed and synthesized a class of 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides as highly potent and selective fXa inhibitors with significantly improved hydrophilicity and in vitro anticoagulant activity. These benzamidine-P4 fXa inhibitors have displayed excellent oral bioavailability and long half-life. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.12.054

文献信息

• Inhibitors of factor Xa
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20040116399A1

  公开（公告）日：2004-06-17

  Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.

  本发明揭示了一种具有对哺乳动物因子Xa活性的新化合物、其盐和相关组合物。这些化合物在体外或体内用于预防或治疗凝血障碍。
• 1-(2-Naphthyl)-1 H -pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 3: Design, synthesis and SAR of orally bioavailable benzamidine-P4 inhibitors
  作者：Zhaozhong J. Jia、Yanhong Wu、Wenrong Huang、Penglie Zhang、Yonghong Song、John Woolfrey、Uma Sinha、Ann E. Arfsten、Susan T. Edwards、Athiwat Hutchaleelaha、Stanley J. Hollennbach、Joseph L. Lambing、Robert M. Scarborough、Bing-Yan Zhu

  DOI：10.1016/j.bmcl.2003.12.054

  日期：2004.3

  Using N,N-dialkylated benzamidines as the novel P4 motifs, we have designed and synthesized a class of 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides as highly potent and selective fXa inhibitors with significantly improved hydrophilicity and in vitro anticoagulant activity. These benzamidine-P4 fXa inhibitors have displayed excellent oral bioavailability and long half-life. (C) 2003 Elsevier Ltd. All rights reserved.