N-1-[2-(N-{2-[N-(2-aminoethyl)]aminoethyl})aminoethyl]-5-methylacridine-4-carboxamide | 206531-19-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-1-[2-(N-{2-[N-(2-aminoethyl)]aminoethyl})aminoethyl]-5-methylacridine-4-carboxamide
• 英文别名: N-[2-[2-(2-aminoethylamino)ethylamino]ethyl]-5-methylacridine-4-carboxamide
• CAS: 206531-19-3
• 化学式: C₂₁H₂₇N₅O
• 分子量: 365.478
• InChiKey: DZWJHRNZVLSFDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  92.1
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  9-methylphenazine-1-carboxylic acid imidazolide 、 N-1-[2-(N-{2-[N-(2-aminoethyl)]aminoethyl})aminoethyl]-5-methylacridine-4-carboxamide 以 四氢呋喃 为溶剂， 反应 20.0h， 以61%的产率得到9-methyl-N-[2-({2-[(2-{[(5-methyl-4-acridinyl)carbonyl]amino}ethyl)amino]ethyl}amino)ethyl]-1-phenazinecarboxamide
  参考文献：
  名称：

  Synthesis and evaluation of unsymmetrical bis(arylcarboxamides) designed as topoisomerase-Targeted anticancer drugs

  摘要：

  Symmetrical dimers of lipophilic intercalating chromophores linked by cation-containing chains have recently been shown to have broad-spectrum in vivo anticancer activity. We report the preparation and evaluation of a series of both symmetric and unsymmetric dimers of a variety of intercalating chromophores of varied DNA binding strength, including naphthalimides, acridines, phenazines, oxanthrenes and 2-phenylquinolines. The unsymmetrical dimers were prepared by sequential coupling of the chromophores to linkers with selectively protected primary terminal amines to ensure high yields and unequivocal product. Protection of the internal (secondary) amines as BOC derivatives was used to ensure complete structural specificity, and was also an aid to the purification of these very polar compounds. The growth inhibitory abilities (as IC50 values) of the compounds in a range of cell lines showed that the nature of the linker chain was important, and independent of the nature of the chromophore, with compounds containing the dicationic linker [-(CH2)(2)NH(CH2)(2)NH(CH2)(2)-] being on average 30-fold more potent than the corresponding compounds containing the monocationic linker [-(CH2)(3)NMe(CH2)(3)-]. However, the chromophores also play a role in determining biological activity, with the cytotoxicities of symmetric and unsymmetric dicationic dimers correlating with the overall DNA binding abilities of the chromophores. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00249-8
• 作为产物：
  描述：

  5-methylacridine-4-carboxylic acid imidazolide 在 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 N-1-[2-(N-{2-[N-(2-aminoethyl)]aminoethyl})aminoethyl]-5-methylacridine-4-carboxamide
  参考文献：
  名称：

  Synthesis and evaluation of unsymmetrical bis(arylcarboxamides) designed as topoisomerase-Targeted anticancer drugs

  摘要：

  Symmetrical dimers of lipophilic intercalating chromophores linked by cation-containing chains have recently been shown to have broad-spectrum in vivo anticancer activity. We report the preparation and evaluation of a series of both symmetric and unsymmetric dimers of a variety of intercalating chromophores of varied DNA binding strength, including naphthalimides, acridines, phenazines, oxanthrenes and 2-phenylquinolines. The unsymmetrical dimers were prepared by sequential coupling of the chromophores to linkers with selectively protected primary terminal amines to ensure high yields and unequivocal product. Protection of the internal (secondary) amines as BOC derivatives was used to ensure complete structural specificity, and was also an aid to the purification of these very polar compounds. The growth inhibitory abilities (as IC50 values) of the compounds in a range of cell lines showed that the nature of the linker chain was important, and independent of the nature of the chromophore, with compounds containing the dicationic linker [-(CH2)(2)NH(CH2)(2)NH(CH2)(2)-] being on average 30-fold more potent than the corresponding compounds containing the monocationic linker [-(CH2)(3)NMe(CH2)(3)-]. However, the chromophores also play a role in determining biological activity, with the cytotoxicities of symmetric and unsymmetric dicationic dimers correlating with the overall DNA binding abilities of the chromophores. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00249-8

文献信息

• [EN] BIS(ACRIDINECARBOXAMIDE) AND BIS(PHENAZINECARBOXAMIDE) AS ANTITUMOUR AGENTS<br/>[FR] (BIS)ACRIDINECARBOXAMIDE ET (BIS)PHENAZINECARBOXAMIDE UTILISES EN TANT QU'AGENTS ANTITUMORAUX
  申请人：XENOVA LIMITED

  公开号：WO1998017650A1

  公开（公告）日：1998-04-30

  (EN) A compound which is a bis(acridinecarboxamide) or bis(phenazinecarboxamide) derivative of formula (I), wherein each X, which may be the same or different in a given molecule, is -CH= or -N= each of R1 to R4 which may be the same or different, H, C1-C4 alkyl, OH, SH, NH2, C1-C4 alkoxy, aryloxy, NHR, N(R)2, SR, SO2R wherein R is C1-C4 alkyl, CF3, NO2 or halogen, or R1 and R2 together form a methylenedioxy group; each of R5 and R6, which may be the same or different, is H or C1-C4 alkyl; Z is (CH2)n, (CH2)nO(CH2)n, (CH2)nN(R7) (CH2)n, (CH2)nN(R7) (CH2)mN(R7) (CH2)n or (CH2)nN(CH2CH2)2N(CH2)n wherein R7 is H or C1-C4 alkyl and n and m, which may be the same or different, are each an integer of 1 to 4; or a pharmaceutically acceptable acid addition salt or N-oxide thereof; has activity as an antitumour and antibacterial agent.(FR) L'invention concerne un composé qui est dérivé de (bis)acridinecarboxamide et de (bis)phénazinecarboxamide de formule (I), dans laquelle chaque X, qui peut être identique ou différent dans une molécule donnée, représente -CH= ou -N=, chacun des R1 à R4, qui peuvent être identiques ou différents, représentant H, un alkyle en C1-C4, OH, SH, NH2, un alkoxy en C1-C4, un aryloxy, NHR; N(R)2, SR, SO2R, R représentant un alkyle en C1-C4, CF3, NO2 ou halogène, ou R1 et R2 formant ensemble un groupe méthylènedioxy; chacun des R5 et R6, qui peuvent être identiques ou différents, représentant H ou un alkyle en C1-C4; Z représente (CH2)n, (CH2)nO(CH2)n, (CH2)nN(R7) (CH2)nN(R7) (CH2)mN(R7) (CH2)n ou (CH2)nN(CH2CH2)2N(CH2)n, R7 représentant H ou un alkyle en C1-C4, et n et m, qui peuvent être identiques ou différents, représentant chacun un nombre entier allant de 1 à 4; ou un sel d'addition d'acide pharmaceutiquement acceptable, ou un N-oxyde dudit sel; présente une activité en tant qu'agent antitumoral et antibactérien.

  一种化合物，其为公式(I)的双(吖啶甲酰胺)或双(菲嗪甲酰胺)衍生物，其中每个X在给定分子中可以相同或不同，为-CH=或-N=，每个R1到R4可以相同或不同，为H、C1-C4烷基、OH、SH、NH2、C1-C4烷氧基、芳氧基、NHR、N(R)2、SR、SO2R，其中R为C1-C4烷基、CF3、NO2或卤素，或者R1和R2组成一个亚甲二氧基基团；每个R5和R6可以相同或不同，为H或C1-C4烷基；Z为(CH2)n、(CH2)nO(CH2)n、(CH2)nN(R7)(CH2)n、(CH2)nN(R7)(CH2)mN(R7)(CH2)n或(CH2)nN(CH2CH2)2N(CH2)n，其中R7为H或C1-C4烷基，n和m可以相同或不同，均为1到4的整数；或其药学上可接受的酸加盐或N-氧化物；具有抗肿瘤和抗菌活性。
• BIS(ACRIDINECARBOXAMIDE) AND BIS(PHENAZINECARBOXAMIDE) AS ANTITUMOUR AGENTS
  申请人：XENOVA LIMITED

  公开号：EP0934278A1

  公开（公告）日：1999-08-11
• Synthesis and evaluation of unsymmetrical bis(arylcarboxamides) designed as topoisomerase-Targeted anticancer drugs
  作者：Julie A Spicer、Swarna A Gamage、Graeme J Finlay、William A Denny

  DOI：10.1016/s0968-0896(01)00249-8

  日期：2002.1

  Symmetrical dimers of lipophilic intercalating chromophores linked by cation-containing chains have recently been shown to have broad-spectrum in vivo anticancer activity. We report the preparation and evaluation of a series of both symmetric and unsymmetric dimers of a variety of intercalating chromophores of varied DNA binding strength, including naphthalimides, acridines, phenazines, oxanthrenes and 2-phenylquinolines. The unsymmetrical dimers were prepared by sequential coupling of the chromophores to linkers with selectively protected primary terminal amines to ensure high yields and unequivocal product. Protection of the internal (secondary) amines as BOC derivatives was used to ensure complete structural specificity, and was also an aid to the purification of these very polar compounds. The growth inhibitory abilities (as IC50 values) of the compounds in a range of cell lines showed that the nature of the linker chain was important, and independent of the nature of the chromophore, with compounds containing the dicationic linker [-(CH2)(2)NH(CH2)(2)NH(CH2)(2)-] being on average 30-fold more potent than the corresponding compounds containing the monocationic linker [-(CH2)(3)NMe(CH2)(3)-]. However, the chromophores also play a role in determining biological activity, with the cytotoxicities of symmetric and unsymmetric dicationic dimers correlating with the overall DNA binding abilities of the chromophores. (C) 2001 Elsevier Science Ltd. All rights reserved.