ethyl N-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]phenyl}-N-[(7-cyano-2-naphthyl)methyl]carbamate | 179756-07-1

• 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: ethyl N-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]phenyl}-N-[(7-cyano-2-naphthyl)methyl]carbamate
• 英文别名: ethyl N-[4-[(1-t-butoxycarbonyl-4-piperidyl)oxy]phenyl]-N-[(7-cyano-2-naphthyl)methyl]carbamate；tert-butyl 4-[4-[(7-cyanonaphthalen-2-yl)methyl-ethoxycarbonylamino]phenoxy]piperidine-1-carboxylate
• CAS: 179756-07-1
• 化学式: C₃₁H₃₅N₃O₅
• 分子量: 529.636
• InChiKey: WUWAYVWEDXSGTF-UHFFFAOYSA-N

物化性质

• 沸点：
  689.6±55.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  92.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl N-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]phenyl}-N-[(7-cyano-2-naphthyl)methyl]carbamate 在 盐酸 、 乙酸铵 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 46.0h， 生成
  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：

  对硝基苯酚 在 palladium on activated charcoal 氢气 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 43.25h， 生成 ethyl N-{4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]phenyl}-N-[(7-cyano-2-naphthyl)methyl]carbamate
  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

• Amidinonaphthyl derivative or salt thereof
  申请人：Yamanouchi Pharmaceutical Co. Ltd

  公开号：US05869501A1

  公开（公告）日：1999-02-09

  An amidinonaphthyl derivative represented by the following general formula (I) which has coagulation factor X inhibiting action and is useful as an anti-thrombus agent and the like, a salt thereof, an intermediate thereof and a pharmaceutical composition which comprises the amidinonaphthyl derivative. An amidinonaphthyl derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof. ##STR1## (symbols in the formula have the following meanings; R.sup.1 : a hydrogen atom or a group represented by the formula --A--W--R.sup.4, A: a group represented by the formula ##STR2## a group represented by the formula ##STR3## or a group represented by the formula --SO.sub.2 --, X: an oxygen atom or a sulfur atom, W: a single bond or a group represented by the formula --NR.sup.5 --, R.sup.4 : a hydroxyl group, a lower alkoxy group, etc., R.sup.5 : a hydrogen atom, a carbamoyl group, a lower alkoxycarbonyl group, etc., R.sup.2 : a lower alkyl group, R.sup.3 : a hydrogen atom, a halogen atom, a carboxyl group, B: a lower alkylene group or a carbonyl group, and n: 0 or 1).

  以下是由下列通式（I）表示的酰胺基萘衍生物，具有凝血因子X抑制作用，可用作抗血栓剂等，其盐，中间体以及包括该酰胺基萘衍生物的药物组成物。由下列通式（I）或其药学上可接受的盐表示的酰胺基萘衍生物。 ##STR1## （式中符号的含义如下：R1：氢原子或由公式--A--W--R4表示的基团，A：由公式表示的基团##STR2##由公式表示的基团##STR3##或由公式--SO.sub.2--表示的基团，X：氧原子或硫原子，W：单键或由公式--NR5--表示的基团，R4：羟基，低级烷氧基等，R5：氢原子，氨基甲酰基，低级烷氧羰基基团等，R2：低级烷基，R3：氢原子，卤原子，羧基，B：低级烷基撑或羰基基团，n：0或1）。
• NOVEL AMIDINONAPHTHYL DERIVATIVE OR SALT THEREOF
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP0798295A1

  公开（公告）日：1997-10-01

  An amidinonaphthyl derivative represented by the following general formula (I) which has a platelet aggregation inhibiting action based on the activated blood coagulation factor X inhibiting action and is useful as an anti-thrombus agent and the like, a salt thereof, an intermediate thereof and a pharmaceutical composition which comprises the amidinonaphthyl derivative. An amidinonaphthyl derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof. (symbols in the formula have the following meanings; R1: a hydrogen atom or a group represented by the formula -A-W-R4, A: a group represented by the formula a group represented by the formula or a group represented by the formula -SO2-, X: an oxygen atom or a sulfur atom, W: a single bond or a group represented by the formula -NR5-, R4: a hydroxyl group, a lower alkoxy group, etc., not a hydroxyl group or a lower alkoxy group, R5: a hydrogen atom, a carbamoyl group, a lower alkoxycarbonyl group, etc., R2: a lower alkyl group, R3: a hydrogen atom, a halogen atom, a carboxyl group, B: a lower alkylene group or a carbonyl group, and n: 0 or 1).

  一种由下式通式（I）表示的脒基萘衍生物、其盐、中间体和包含该脒基萘衍生物的药物组合物，该脒基萘衍生物具有基于活化血液凝固因子 X 抑制作用的血小板聚集抑制作用，可用作抗血栓剂等。 由以下通式（I）代表的脒基萘衍生物或其药学上可接受的盐。 (式中符号含义如下； R1：氢原子或由式-A-W-R4 所代表的基团、 A：由式 式所代表的基团 或由式 -SO2- 代表的基团、 X：氧原子或硫原子，W：单键或由式-NR5-代表的基团，R4：羟基、低级烷氧基等，不是羟基或低级烷氧基，R5：氢原子、氨基甲酰基、低级烷氧基羰基等，R2：低级烷基，R3：氢原子、卤素原子、羧基，B：低级亚烷基或羰基，n：0 或 1）。
• 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.