N,N'-di-tert-butoxycarbonyl-7-[1-(2-nitrophenylmethyl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinolin-2-carboxamidine | 854261-83-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N,N'-di-tert-butoxycarbonyl-7-[1-(2-nitrophenylmethyl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinolin-2-carboxamidine
• 英文别名: tert-butyl (NZ)-N-[[(2-methylpropan-2-yl)oxycarbonylamino]-[7-[[1-[(2-nitrophenyl)methyl]piperidin-4-yl]methoxy]-3,4-dihydro-1H-isoquinolin-2-yl]methylidene]carbamate
• CAS: 854261-83-9
• 化学式: C₃₃H₄₅N₅O₇
• 分子量: 623.75
• InChiKey: CIAKSGHDYGGCEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N,N'-di-tert-butoxycarbonyl-7-[1-(2-nitrophenylmethyl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinolin-2-carboxamidine 在 palladium on activated charcoal 氢气 、 三氟乙酸 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、303.98 kPa 条件下， 生成 7-[1-(2-aminobenzyl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinoline-2-carboxamidine
  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
• 作为产物：
  描述：

  7-甲氧基异喹啉 在 platinum(IV) oxide 、 palladium on activated charcoal sodium hydroxide 、 氢溴酸 、 氢气 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、303.98 kPa 条件下， 生成 N,N'-di-tert-butoxycarbonyl-7-[1-(2-nitrophenylmethyl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinolin-2-carboxamidine
  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

• 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。