methyl 5-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]-N-[(7-cyano-2-naphthyl)methyl]anthranilate | 179756-41-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 5-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]-N-[(7-cyano-2-naphthyl)methyl]anthranilate
• 英文别名: methyl 5-[(1-t-butoxycarbonyl-4-piperidyl)oxy]-N-[(7-cyano-2-naphthyl)methyl]anthranilate；Tert-butyl 4-[4-[(7-cyanonaphthalen-2-yl)methylamino]-3-methoxycarbonylphenoxy]piperidine-1-carboxylate
• CAS: 179756-41-3
• 化学式: C₃₀H₃₃N₃O₅
• 分子量: 515.609
• InChiKey: VLLMUTICGJRLNC-UHFFFAOYSA-N

物化性质

• 熔点：
  125-126 °C
• 沸点：
  676.5±55.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 5-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]-N-[(7-cyano-2-naphthyl)methyl]anthranilate 在 盐酸 、 三氟乙酸 作用下， 以 吡啶 、 乙醇 、 二氯甲烷 为溶剂， 反应 106.63h， 生成 7-[2,2,4-Trioxo-6-(piperidin-4-yloxy)-3,4-dihydro-2H-2λ⁶-benzo[1,2,6]thiadiazin-1-ylmethyl]-naphthalene-2-carboxamidine
  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 在 三乙酰氧基硼氢化钠 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 113.0h， 生成 methyl 5-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]-N-[(7-cyano-2-naphthyl)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

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）。
• 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.