methyl 5-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]anthranilate | 179756-40-2

• 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: methyl 5-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]anthranilate
• 英文别名: 4-(N'-(t-butoxycarbonyl)piperidin-4-yl)oxy-2-(methoxycarbonyl)benzenamine；tert-butyl 4-(4-amino-3-methoxycarbonylphenoxy)piperidine-1-carboxylate
• CAS: 179756-40-2
• 化学式: C₁₈H₂₆N₂O₅
• 分子量: 350.415
• InChiKey: OTVCSUPBBHZHNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  91.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 5-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]anthranilate 在 palladium on activated charcoal 吡啶 、 氢气 、 sodium hydride 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 吡啶 、 甲醇 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 62.0h， 生成 methyl 5-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]-N-(tert-butoxycarbonylsulfamoyl)-N-{[(3-cyanophenyl)carbamoyl]methyl}anthranilate
  参考文献：
  名称：

  Design, synthesis and biological activity of YM-60828 derivatives. Part 2: potent and orally-bioavailable factor Xa inhibitors based on benzothiadiazine-4-one template

  摘要：

  Compound YM-60828 was previously characterized in our laboratory as a potent, selective and orally-bioavailable Factor Xa (FXa) inhibitor. The L-shape conformation of this compound in the active site of FXa was recognized as an important factor in displaying its FXa inhibitory activity. This led to the exploration of conformationally restricted cyclic scaffolds bearing a similar active conformation. The current study investigated a novel series of benzothiadiazine-4-one based compounds as FXa inhibitors. Structure-activity relationship (SAR) investigations revealed some potent FXa inhibitors that were selected for further in vitro and ex vivo anticoagulant studies. Among them, compound 6j (YM-169920) was proved to be most effective anticoagulant in this series. The synthesis and SAR in addition to docking studies of this class of inhibitors are described. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00462-5
• 作为产物：
  描述：

  2-氨基-5-羟基苯甲酸甲基 、 N-Boc-4-羟基哌啶 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 methyl 5-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]anthranilate
  参考文献：
  名称：

  Benzenamine derivatives as anti-coagulants

  摘要：

  这项发明涉及式（I）的苯胺衍生物：其中A、W、m、n、R1、R2、R3、R4、R5和R6在此处定义。这些化合物可用作抗凝剂。

  公开号：

  US06350761B1

文献信息

• Benzenamine derivatives as anti-coagulants
  申请人：Berlex Laboratories, Inc.

  公开号：US06350761B1

  公开（公告）日：2002-02-26

  This invention is directed to benzenamine derivatives of formula (I): wherein A, W, m, n, R1, R2, R3, R4, R5 and R6 are defined herein. These compounds are useful as anti-coagulants.

  这项发明涉及式（I）的苯胺衍生物：其中A、W、m、n、R1、R2、R3、R4、R5和R6在此处定义。这些化合物可用作抗凝剂。
• Design, synthesis and biological activity of YM-60828 derivatives. Part 2: potent and orally-bioavailable factor Xa inhibitors based on benzothiadiazine-4-one template
  作者：Fukushi Hirayama、Hiroyuki Koshio、Naoko Katayama、Tsukasa Ishihara、Hiroyuki Kaizawa、Yuta Taniuchi、Kazuo Sato、Yumiko Sakai-Moritani、Seiji Kaku、Hiroyuki Kurihara、Tomihisa Kawasaki、Yuzo Matsumoto、Shuichi Sakamoto、Shin-ichi Tsukamoto

  DOI：10.1016/s0968-0896(02)00462-5

  日期：2003.2

  Compound YM-60828 was previously characterized in our laboratory as a potent, selective and orally-bioavailable Factor Xa (FXa) inhibitor. The L-shape conformation of this compound in the active site of FXa was recognized as an important factor in displaying its FXa inhibitory activity. This led to the exploration of conformationally restricted cyclic scaffolds bearing a similar active conformation. The current study investigated a novel series of benzothiadiazine-4-one based compounds as FXa inhibitors. Structure-activity relationship (SAR) investigations revealed some potent FXa inhibitors that were selected for further in vitro and ex vivo anticoagulant studies. Among them, compound 6j (YM-169920) was proved to be most effective anticoagulant in this series. The synthesis and SAR in addition to docking studies of this class of inhibitors are described. (C) 2002 Elsevier Science Ltd. All rights reserved.