3,4,5-trimethoxy-N-(4-methoxy-3-phenylmethoxyphenyl)aniline | 329008-82-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3,4,5-trimethoxy-N-(4-methoxy-3-phenylmethoxyphenyl)aniline
• CAS: 329008-82-4
• 化学式: C₂₃H₂₅NO₅
• 分子量: 395.455
• InChiKey: OHLJSKDDGXLXPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  58.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,4,5-trimethoxy-N-(4-methoxy-3-phenylmethoxyphenyl)aniline 在 吡啶 、 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 2-methoxy-5-(methyl(3,4,5-trimethoxyphenyl)amino)phenyl acetate
  参考文献：
  名称：

  Discovery of azaisoerianin derivatives as potential antitumors agents

  摘要：

  A series of N-methyl-diarylamines 2 was designed and synthesized as a novel class of CA-4 and isoCA-4 analogues. Compounds 2b and 2m showed excellent antiproliferative activity with mean GI(50) values at a nanomolar level in a diverse set of human cancer cells. These compounds also inhibited tubulin assembly at a micromolar range, arrested the cellular cycle in the G2/M phase and induced apoptosis at very low concentrations. Preliminary in vitro results revealed that 2b and 2m displayed substantial efficacy as potent antivascular agents. Docking studies indicates that these lead compounds showed a binding mode similar to those observed with isoCA-4 at the colchicine binding site of tubulin. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.03.032
• 作为产物：
  描述：

  2-甲氧基-5-硝基苯酚 在 palladium diacetate 、 potassium carbonate 、 双(2-二苯基磷苯基)醚 、 tin(ll) chloride 、 sodium t-butanolate 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 41.0h， 生成 3,4,5-trimethoxy-N-(4-methoxy-3-phenylmethoxyphenyl)aniline
  参考文献：
  名称：

  Antimitotic and cell growth inhibitory properties of combretastatin A-4-like ethers

  摘要：

  A series of diarylamines, diaryl and arylbenzyl ethers based on combretastatin A-4 was prepared and evaluated for anticancer activity. 2-Methoxy-5-(3',4',5'-trimethoxyphenoxymethyl)phenol was the most active (IC50, K562 20nM) and caused significant G2/M cell cycle arrest. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00596-5

文献信息

• DIHYDRO-ISO-CA-4 AND ANALOGUES: POTENT CYTOTOXICS, INHIBITORS OF TUBULIN POLYMERIZATION
  申请人：Alami Mouâd

  公开号：US20110160228A1

  公开（公告）日：2011-06-30

  The present invention relates to compounds of formula (I) below in which: —R 1 and R 3 represent, independently of one another, a methoxy group optionally substituted by one or more fluorine atoms, —R 2 and R 4 represent, independently of one another, a hydrogen atom or a methoxy group optionally substituted by one or more fluorine atoms, —A represents a ring chosen from the group comprising aryl and heteroaryl groups, said ring possibly being substituted by or fused to a heterocycle, —X represents a nitrogen atom or a CH group, and —Z 1 represents a hydrogen atom or a halogen atom, preferably fluorine, and —Z 2 represents a hydrogen atom, a halogen atom, preferably fluorine, a C 1 to C 4 alkyl group, an aryl group or a —CN, —SO 2 NR 12 R 13 , —SO 2 R 9 , —COOR 15 or —COR 15 group, and also to the pharmaceutically acceptable salts thereof, the isomers thereof and the prodrugs thereof.

  本发明涉及以下式（I）的化合物，其中：-R1和R3分别独立地表示一个甲氧基，该甲氧基可以被一个或多个氟原子取代，-R2和R4分别独立地表示一个氢原子或一个甲氧基，该甲氧基可以被一个或多个氟原子取代，-A表示从含有芳基和杂环芳基的群中选择的一个环，该环可能被一个杂环取代或融合，-X表示一个氮原子或一个CH基团，-Z1表示一个氢原子或一个卤原子，优选氟，-Z2表示一个氢原子，一个卤原子，优选氟，一个C1到C4烷基，一个芳基或一个-CN，-SO2NR12R13，-SO2R9，-COOR15或-COR15基团，以及其在药学上可接受的盐，其异构体和其前药。
• [EN] DIHYDRO-ISO-CA-4 AND ANALOGUES: POTENT CYTOTOXICS, INHIBITORS OF TUBULIN POLYMERIZATION<br/>[FR] DIHYDRO ISO CA-4 ET ANALOGUES : PUISSANTS CYTOTOXIQUES, INHIBITEURS DE LA POLYMERISATION DE LA TUBULINE
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2009147217A1

  公开（公告）日：2009-12-10

  La présente invention concerne des composés de formule (I) suivante dans laquelle : - R1 et R3 représentent, indépendamment l'un de l'autre, un groupe méthoxy éventuellement substitué par un ou plusieurs atomes de fluor, - R2 et R4 représentent, indépendamment l'un de l'autre, un atome d'hydrogène ou un groupe méthoxy éventuellement substitué par un ou plusieurs atomes de fluor, - A représente un cycle choisi dans le groupe comprenant les groupes aryles et hétéroaryles, ledit cycle pouvant être substitué ou accolé à un hétérocycle, - X représente un atome d'azote ou un groupe CH, et - Z1 représente un atome d'hydrogène ou un atome d'halogène, de préférence de fluor, et - Z2 représente un atome d'hydrogène, un atome d'halogène, de préférence de fluor, un alkyle en C1 à C4, un aryle ou un groupe -CN, -SO2NR12R13, -SO2R9, -COOR15 ou - COR15, ainsi que leurs sels pharmaceutiquement acceptables, leurs isomères et leurs prodrogues.
• Antimitotic and cell growth inhibitory properties of combretastatin A-4-like ethers
  作者：Nicholas J. Lawrence、David Rennison、Meiki Woo、Alan T. McGown、John A. Hadfield

  DOI：10.1016/s0960-894x(00)00596-5

  日期：2001.1

  A series of diarylamines, diaryl and arylbenzyl ethers based on combretastatin A-4 was prepared and evaluated for anticancer activity. 2-Methoxy-5-(3',4',5'-trimethoxyphenoxymethyl)phenol was the most active (IC50, K562 20nM) and caused significant G2/M cell cycle arrest. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Discovery of azaisoerianin derivatives as potential antitumors agents
  作者：Mohamed Ali Soussi、Olivier Provot、Guillaume Bernadat、Jérome Bignon、Joanna Wdzieczak-Bakala、Déborah Desravines、Joëlle Dubois、Jean-Daniel Brion、Samir Messaoudi、Mouad Alami

  DOI：10.1016/j.ejmech.2014.03.032

  日期：2014.5

  A series of N-methyl-diarylamines 2 was designed and synthesized as a novel class of CA-4 and isoCA-4 analogues. Compounds 2b and 2m showed excellent antiproliferative activity with mean GI(50) values at a nanomolar level in a diverse set of human cancer cells. These compounds also inhibited tubulin assembly at a micromolar range, arrested the cellular cycle in the G2/M phase and induced apoptosis at very low concentrations. Preliminary in vitro results revealed that 2b and 2m displayed substantial efficacy as potent antivascular agents. Docking studies indicates that these lead compounds showed a binding mode similar to those observed with isoCA-4 at the colchicine binding site of tubulin. (C) 2014 Elsevier Masson SAS. All rights reserved.