N-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]phenyl}methanesulfonamide | 454437-33-3

• 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-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]phenyl}methanesulfonamide
• 英文别名: Tert-butyl 4-[4-(methanesulfonamido)phenoxy]piperidine-1-carboxylate
• CAS: 454437-33-3
• 化学式: C₁₇H₂₆N₂O₅S
• 分子量: 370.47
• InChiKey: RWQXSMPWBTXLLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  93.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]phenyl}methanesulfonamide 在 羟胺 、 乙酸酐 、 caesium carbonate 、 溶剂黄146 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Design, synthesis and structure–Activity relationships of benzoxazinone-Based factor Xa inhibitors

  摘要：

  A series of benzoxazinone derivatives was designed and synthesized as factor Xa inhibitors. We demonstrated that the naphthyl moiety in the aniline-based compounds I and 2 can be replaced with benzene-fused heterobicycles and biaryls to give factor Xa inhibitors with improved trypsin selectivity. The P4 modifications lead to monoamidines which are moderately active. The benzoxazinones 41-45 are potent against factor Xa, retain the improved trypsin selectivity of the corresponding aniline-based compounds, and show strong antithrombotic effect dose responsively. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(02)00927-7
• 作为产物：
  描述：

  对氟硝基苯 在 palladium on activated charcoal 吡啶 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 N-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]phenyl}methanesulfonamide
  参考文献：
  名称：

  Design, synthesis and structure–Activity relationships of benzoxazinone-Based factor Xa inhibitors

  摘要：

  A series of benzoxazinone derivatives was designed and synthesized as factor Xa inhibitors. We demonstrated that the naphthyl moiety in the aniline-based compounds I and 2 can be replaced with benzene-fused heterobicycles and biaryls to give factor Xa inhibitors with improved trypsin selectivity. The P4 modifications lead to monoamidines which are moderately active. The benzoxazinones 41-45 are potent against factor Xa, retain the improved trypsin selectivity of the corresponding aniline-based compounds, and show strong antithrombotic effect dose responsively. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(02)00927-7

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.