benzyl 4-[2-(N,N'-di-tert-butoxycarbonylamidin)-1,2,3,4-tetrahydroisoquinolin-7-yloxymethyl]piperidine-1-carboxylate | 247132-78-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: benzyl 4-[2-(N,N'-di-tert-butoxycarbonylamidin)-1,2,3,4-tetrahydroisoquinolin-7-yloxymethyl]piperidine-1-carboxylate
• 英文别名: benzyl 4-[[2-[(Z)-N,N'-bis[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-3,4-dihydro-1H-isoquinolin-7-yl]oxymethyl]piperidine-1-carboxylate
• CAS: 247132-78-1
• 化学式: C₃₄H₄₆N₄O₇
• 分子量: 622.762
• InChiKey: HZLQIGFDKVNFFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  benzyl 4-[2-(N,N'-di-tert-butoxycarbonylamidin)-1,2,3,4-tetrahydroisoquinolin-7-yloxymethyl]piperidine-1-carboxylate 在 palladium on activated charcoal 吡啶 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 20.0 ℃ 、303.98 kPa 条件下， 反应 5.0h， 生成 N,N'-di-tert-butoxycarbonyl-7-(1-acetylpiperidin-4-ylmethoxy)-1,2,3,4-tetrahydroisoquinolin-2-carboxamidine
  参考文献：
  名称：

  具有四氢异喹啉环的新型选择性因子Xa抑制剂的合成及其构效关系。

  摘要：

  设计并合成了一系列新颖的2,7-二取代的四氢异喹啉衍生物。在这些衍生物中，化合物1和2对Xa因子（FXa）表现出有效的抑制活性，并且对其他丝氨酸蛋白酶（凝血酶，纤溶酶和胰蛋白酶）具有良好的选择性。此外，化合物2在食蟹猴静脉和口服给药后均显示出有效的抗FXa活性，在0.1、0.3和1 mg kg（-1）h（-1）的大鼠模型中显示出剂量依赖性的抗血栓形成作用。静脉血栓形成，并以0.1 mg kg（-1）h（-1）的剂量显着减少了大脑中动脉闭塞模型中脑梗塞的大小。这些结果表明，化合物2（JTV-803）可能同时用作静脉和动脉抗血栓形成剂。

  DOI：

  10.1021/jm058160e
• 作为产物：
  描述：

  7-甲氧基异喹啉 在 platinum(IV) oxide sodium hydroxide 、 氢溴酸 、 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 20.0 ℃ 、303.98 kPa 条件下， 生成 benzyl 4-[2-(N,N'-di-tert-butoxycarbonylamidin)-1,2,3,4-tetrahydroisoquinolin-7-yloxymethyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of novel tetrahydroisoquinoline derivatives as potent and selective factor Xa inhibitors

  摘要：

  A series of novel 2,7-disubstituted tetrahydroisoquinoline derivatives were designed and synthesized. Among these derivatives, compounds I and 2 (JTV-803) exhibited potent inhibitory activity against FXa and good selectivity with respect to other serine proteases (thrombin, plasmin, and trypsin). In addition, compound 2 exhibited potent anti-FXa activity after intravenous and oral administration to cynomolgus monkey, and showed a dose-dependent antithrombotic effect in a rat model of venous thrombosis. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.10.033

文献信息

• Amidine compounds
  申请人：Japan Tobacco Inc.

  公开号：US06562828B1

  公开（公告）日：2003-05-13

  A compound of the formula [I] wherein R1, R2 and R3 are the same or different and each is hydrogen atom, wherein each symbol is as defined in the specification, a salt thereof or a prodrug thereof. The compound of the present invention, a salt thereof and a prodrug thereof are useful as factor Xa inhibitor and blood coagulation inhibitor, and are useful for the prophylaxis and/or treatment of diseases caused by blood coagulation or thrombus.

  其中R1、R2和R3相同或不同，且每个都是氢原子，其中每个符号如规范中定义，其盐或前药。本发明的化合物及其盐和前药可用作因子Xa抑制剂和抗凝血剂，对于预防和/或治疗由血液凝固或血栓引起的疾病有用。
• AMIDINE COMPOUNDS
  申请人：Japan Tobacco Inc.

  公开号：EP1070714A1

  公开（公告）日：2001-01-24

  Compounds represented by general formula [I] or salts thereof or prodrugs of the same [I] wherein R1, R2 end R3 are the same or different and each represents hydrogen, hydroxy, lower alkyl or aryl; and R represents formulas (a), (b) and (c) (wherein each symbol has the meaning as defined in the specification). These compounds, salts thereof or prodrugs of the same are useful as factor Xa inhibitors and anticoagulants and usable in preventing and/or treating diseases caused by blood coagulation or thrombi.

  通式[I]代表的化合物或其盐类或其原药[I]，其中R1、R2和R3是相同或不同的，各自代表氢、羟基、低级烷基或芳基；R代表式(a)、(b)和(c)（其中各符号具有说明书中定义的含义）。这些化合物、其盐类或其原药可作为 Xa 因子抑制剂和抗凝剂，用于预防和/或治疗由血液凝固或血栓引起的疾病。
• US6562828B1
  申请人：——

  公开号：US6562828B1

  公开（公告）日：2003-05-13
• Synthesis and Structure−Activity Relationships of Novel Selective Factor Xa Inhibitors with a Tetrahydroisoquinoline Ring
  作者：Hiroshi Ueno、Katsuyuki Yokota、Jun-ichi Hoshi、Katsutaka Yasue、Mikio Hayashi、Yasunori Hase、Itsuo Uchida、Kazuo Aisaka、Susumu Katoh、Hidetsura Cho

  DOI：10.1021/jm058160e

  日期：2005.5.1

  A series of novel 2,7-disubstituted tetrahydroisoquinoline derivatives were designed and synthesized. Among these derivatives, compounds 1 and 2 exhibited potent inhibitory activity against factor Xa (FXa) and good selectivity with respect to other serine proteases (thrombin, plasmin, and trypsin). In addition, compound 2 exhibited potent anti-FXa activity after intravenous and oral administration

  设计并合成了一系列新颖的2,7-二取代的四氢异喹啉衍生物。在这些衍生物中，化合物1和2对Xa因子（FXa）表现出有效的抑制活性，并且对其他丝氨酸蛋白酶（凝血酶，纤溶酶和胰蛋白酶）具有良好的选择性。此外，化合物2在食蟹猴静脉和口服给药后均显示出有效的抗FXa活性，在0.1、0.3和1 mg kg（-1）h（-1）的大鼠模型中显示出剂量依赖性的抗血栓形成作用。静脉血栓形成，并以0.1 mg kg（-1）h（-1）的剂量显着减少了大脑中动脉闭塞模型中脑梗塞的大小。这些结果表明，化合物2（JTV-803）可能同时用作静脉和动脉抗血栓形成剂。
• Discovery of novel tetrahydroisoquinoline derivatives as potent and selective factor Xa inhibitors
  作者：Hiroshi Ueno、Katsuyuki Yokota、Jun-ichi Hoshi、Katsutaka Yasue、Mikio Hayashi、Itsuo Uchida、Kazuo Aisaka、Yasunori Hase、Susumu Katoh、Hidetsura Cho

  DOI：10.1016/j.bmcl.2004.10.033

  日期：2005.1

  A series of novel 2,7-disubstituted tetrahydroisoquinoline derivatives were designed and synthesized. Among these derivatives, compounds I and 2 (JTV-803) exhibited potent inhibitory activity against FXa and good selectivity with respect to other serine proteases (thrombin, plasmin, and trypsin). In addition, compound 2 exhibited potent anti-FXa activity after intravenous and oral administration to cynomolgus monkey, and showed a dose-dependent antithrombotic effect in a rat model of venous thrombosis. (C) 2004 Elsevier Ltd. All rights reserved.