N-<(3,4-dimethoxyphenyl)methyl>-N-methyl-2-(4-nitrophenoxy)acetamide | 143666-75-5

• 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: N-<(3,4-dimethoxyphenyl)methyl>-N-methyl-2-(4-nitrophenoxy)acetamide
• 英文别名: N-[(3,4-dimethoxyphenyl)methyl]-N-methyl-2-(4-nitrophenoxy)acetamide
• CAS: 143666-75-5
• 化学式: C₁₈H₂₀N₂O₆
• 分子量: 360.367
• InChiKey: HRPWMKHJUHUCAQ-UHFFFAOYSA-N

物化性质

• 沸点：
  556.8±50.0 °C(predicted)
• 密度：
  1.251±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  93.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-<(3,4-dimethoxyphenyl)methyl>-N-methyl-2-(4-nitrophenoxy)acetamide 在 palladium on activated charcoal lithium aluminium tetrahydride 、 氢气 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 60.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 N-[4-(2-(Methylveratrylamino)ethoxy)phenyl]-1,4-dihydro-4-oxo-2-phenyl-8-quinolinecarboxamide
  参考文献：
  名称：

  Synthesis and Activity against Multidrug Resistance in Chinese Hamster Ovary Cells of New Acridone-4-carboxamides

  摘要：

  A number of tricyclic carboxamides have been synthesized and tested to evaluate their ability to reverse multidrug resistance in the (CHC)-C-R/5 cell line. Among them the acridone derivatives were the most potent, A key feature is the presence of a dimethoxybenzyl or phenethylamine cationic site, separated from the tricyclic lipophilic part by a carbamoylphenyl chain. Optimization led to compounds 2 orders of magnitude more active than the prototype inhibitors verapamil and amiodarone. On the basis of in vitro and in vivo activities, 9,10-dihydro-5-methoxy- 9-oxo-N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinol-2-yl)ethyl]phenyl]-4-acridinecarboxamide (84) has been selected for further development.

  DOI：

  10.1021/jm00013a017
• 作为产物：
  描述：

  4-硝基苯氧乙酸 在 氯化亚砜 、 碳酸氢钠 作用下， 以 丙酮 为溶剂， 反应 7.0h， 生成 N-<(3,4-dimethoxyphenyl)methyl>-N-methyl-2-(4-nitrophenoxy)acetamide
  参考文献：
  名称：

  Synthesis and Activity against Multidrug Resistance in Chinese Hamster Ovary Cells of New Acridone-4-carboxamides

  摘要：

  A number of tricyclic carboxamides have been synthesized and tested to evaluate their ability to reverse multidrug resistance in the (CHC)-C-R/5 cell line. Among them the acridone derivatives were the most potent, A key feature is the presence of a dimethoxybenzyl or phenethylamine cationic site, separated from the tricyclic lipophilic part by a carbamoylphenyl chain. Optimization led to compounds 2 orders of magnitude more active than the prototype inhibitors verapamil and amiodarone. On the basis of in vitro and in vivo activities, 9,10-dihydro-5-methoxy- 9-oxo-N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinol-2-yl)ethyl]phenyl]-4-acridinecarboxamide (84) has been selected for further development.

  DOI：

  10.1021/jm00013a017

文献信息

• EP0494623A1
  申请人：——

  公开号：EP0494623A1

  公开（公告）日：1992-07-15
• ACRIDINE DERIVATIVES
  申请人：LABORATOIRES GLAXO SA

  公开号：EP0569380A1

  公开（公告）日：1993-11-18
• US5604237A
  申请人：——

  公开号：US5604237A

  公开（公告）日：1997-02-18
• [EN] ACRIDINE DERIVATIVES
  申请人：LABORATOIRES GLAXO S.A.

  公开号：WO1992012132A1

  公开（公告）日：1992-07-23

  (EN) Compounds of general formula (I), wherein A represents an oxygen or a sulphur atom, a bond or a group (CH2)lNR9 (where l represents zero or 1 and R9 represents a hydrogen atom or a methyl group); B represents a C1-4alkylene chain optionally substituted by a hydroxyl group, except that the hydroxyl group and moiety A cannot be attached to the same carbon atom when A represents an oxygen or sulphur atom or a group (CH2)lNR9, or when A represents a bond B may also represent a C2-4alkenylene chain; R3 represents a hydrogen atom or a C1-4alkyl group; m represents 1 or 2; R7 represents a hydrogen atom or R3 and R7 together form a group -(CH2)n- where n represents 1 or 2; the novel compounds of formula (I) can sensitize multidrug-resistant cancer cells to chemotherapeutic agents and may be formulated for use in therapy, particularly to improve or increase the efficacy of an antitumour drug.(FR) Composés répondant à la formule générale (I) dans laquelle A représente un atome d'oxygène ou de soufre, une liaison ou un groupe (CH2)lNR9 (où l represente 0 ou 1 et R9 représente un atome d'hydrogène ou un groupe méthyle); B représente une chaîne alkylène C1-4 éventuellement substituée par un groupe hydroxyle, sauf que le groupe hydroxyle et la fraction A ne peuvent être liés au même atome de carbone lorsque A représente un atome d'oxygène ou de soufre ou un groupe (CH2)lNR9, ou lorsque A représente une liaison, B peut également représenter une chaîne alcénylène C2-4; R3 représente un atome d'hydrogène ou un groupe alkyle C1-4; m est 1 ou 2; R7 représente un atome d'hydrogène ou R3 et R7 ensemble forment un groupe -(CH2)n- où n vaut 1 ou 2. Ces nouveaux composés répondant à la formule (I) peuvent sensibiliser aux agents chimiothérapiques les cellules cancéreuses résistantes à divers médicaments, et peuvent s'appliquer à la thérapeutique, notamment afin d'augmenter ou d'améliorer l'efficacité d'un médicament antitumoral.
• Synthesis and Activity against Multidrug Resistance in Chinese Hamster Ovary Cells of New Acridone-4-carboxamides
  作者：Nerina Dodic、Bernard Dumaitre、Alain Daugan、Pascal Pianetti

  DOI：10.1021/jm00013a017

  日期：1995.6

  A number of tricyclic carboxamides have been synthesized and tested to evaluate their ability to reverse multidrug resistance in the (CHC)-C-R/5 cell line. Among them the acridone derivatives were the most potent, A key feature is the presence of a dimethoxybenzyl or phenethylamine cationic site, separated from the tricyclic lipophilic part by a carbamoylphenyl chain. Optimization led to compounds 2 orders of magnitude more active than the prototype inhibitors verapamil and amiodarone. On the basis of in vitro and in vivo activities, 9,10-dihydro-5-methoxy- 9-oxo-N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinol-2-yl)ethyl]phenyl]-4-acridinecarboxamide (84) has been selected for further development.