7-[[4-piperidin-4-yloxy-N-(trifluoromethylsulfonyl)anilino]methyl]naphthalene-2-carboximidamide | 763062-17-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 7-[[4-piperidin-4-yloxy-N-(trifluoromethylsulfonyl)anilino]methyl]naphthalene-2-carboximidamide
• CAS: 763062-17-5
• 化学式: C₂₄H₂₅F₃N₄O₃S
• 分子量: 506.549
• InChiKey: WTKXLPMSAXXBLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  乙基乙酰亚胺盐酸盐 、 7-[[4-piperidin-4-yloxy-N-(trifluoromethylsulfonyl)anilino]methyl]naphthalene-2-carboximidamide 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 96.0h， 生成 N-[4-[(1-Acetoimidoyl-4-piperidyl)oxy]phenyl]-N-[(7-amidino-2-naphthyl)methyl]trifluoromethanesulfonamide dihydrochloride
  参考文献：
  名称：

  The Discovery of YM-60828: A Potent, Selective and Orally-Bioavailable Factor Xa Inhibitor

  摘要：

  Since Factor Xa (FXa) is well known to play a central role in thrombosis and hemostasis, inhibition of FXa is an attractive target for antithrombotic strategies. As a part of our investigation of a non-peptide, orally available FXa inhibitor, we found that a series of N-[(7-amidino-2-naphthyl)methyl]aniline derivatives possessed potent and selective inhibitory activities. Structure-activity relationship (SAR) of the substituent (R-1) on the central aniline moiety suggested that increasing lipophilicity caused a detrimental effect on anticoagulant activity (prothrombin time assay) in plasma. Several compounds bearing a hydrophilic substituent in R-1 showed not only potent FXa inhibitory activities but also high anticoagulant activities. The best compound in this series was sulfamoylacetic acid derivative 8o (YM-60828) which was a potent, selective and orally bioavailable FXa inhibitor and was chosen for clinical development. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00418-7
• 作为产物：
  描述：

  7-({4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]anilino}methyl)naphthalene-2-carbonitrile 在 吡啶 、 盐酸 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 61.0h， 生成 7-[[4-piperidin-4-yloxy-N-(trifluoromethylsulfonyl)anilino]methyl]naphthalene-2-carboximidamide
  参考文献：
  名称：

  The Discovery of YM-60828: A Potent, Selective and Orally-Bioavailable Factor Xa Inhibitor

  摘要：

  Since Factor Xa (FXa) is well known to play a central role in thrombosis and hemostasis, inhibition of FXa is an attractive target for antithrombotic strategies. As a part of our investigation of a non-peptide, orally available FXa inhibitor, we found that a series of N-[(7-amidino-2-naphthyl)methyl]aniline derivatives possessed potent and selective inhibitory activities. Structure-activity relationship (SAR) of the substituent (R-1) on the central aniline moiety suggested that increasing lipophilicity caused a detrimental effect on anticoagulant activity (prothrombin time assay) in plasma. Several compounds bearing a hydrophilic substituent in R-1 showed not only potent FXa inhibitory activities but also high anticoagulant activities. The best compound in this series was sulfamoylacetic acid derivative 8o (YM-60828) which was a potent, selective and orally bioavailable FXa inhibitor and was chosen for clinical development. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00418-7

文献信息

• The Discovery of YM-60828: A Potent, Selective and Orally-Bioavailable Factor Xa Inhibitor
  作者：Fukushi Hirayama、Hiroyuki Koshio、Naoko Katayama、Hiroyuki Kurihara、Yuta Taniuchi、Kazuo Sato、Nami Hisamichi、Yumiko Sakai-Moritani、Tomihisa Kawasaki、Yuzo Matsumoto、Isao Yanagisawa

  DOI：10.1016/s0968-0896(01)00418-7

  日期：2002.5

  Since Factor Xa (FXa) is well known to play a central role in thrombosis and hemostasis, inhibition of FXa is an attractive target for antithrombotic strategies. As a part of our investigation of a non-peptide, orally available FXa inhibitor, we found that a series of N-[(7-amidino-2-naphthyl)methyl]aniline derivatives possessed potent and selective inhibitory activities. Structure-activity relationship (SAR) of the substituent (R-1) on the central aniline moiety suggested that increasing lipophilicity caused a detrimental effect on anticoagulant activity (prothrombin time assay) in plasma. Several compounds bearing a hydrophilic substituent in R-1 showed not only potent FXa inhibitory activities but also high anticoagulant activities. The best compound in this series was sulfamoylacetic acid derivative 8o (YM-60828) which was a potent, selective and orally bioavailable FXa inhibitor and was chosen for clinical development. (C) 2002 Elsevier Science Ltd. All rights reserved.