5-methylacridine-4-carboxylic acid | 32602-26-9

• 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: 5-methylacridine-4-carboxylic acid
• 英文别名: 5-Methylacridine-4-carboxylic
• CAS: 32602-26-9
• 化学式: C₁₅H₁₁NO₂
• 分子量: 237.258
• InChiKey: MOMKGDFIUWTTFO-UHFFFAOYSA-N

物化性质

• 熔点：
  300-302 °C
• 沸点：
  488.0±18.0 °C(Predicted)
• 密度：
  1.320±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-methylacridine-4-carboxylic acid 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 N-1-(2-[N'-tert-butoxycarbonyl-N'-(2-{N-tert-butoxycarbonyl)-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
• 作为产物：
  描述：

  靛红-7-甲酸甲酯 在 palladium on activated charcoal manganese(IV) oxide 、 sodium hydroxide 、 sodium tetrahydroborate 、 硫酸 、 双氧水 作用下， 以 四氢呋喃 、 氯仿 、 水 、 溶剂黄146 、 邻二氯苯 为溶剂， 反应 9.92h， 生成 5-methylacridine-4-carboxylic acid
  参考文献：
  名称：

  2-氨基-3-甲酰基苯甲酸甲酯的制备及其在弗里德兰德合成中的应用

  摘要：

  摘要 标题化合物由 7-羧酸甲酯经四步制备。与 1-茚满酮和类似物缩合得到 11H-茚并[1,2-b]喹啉-6-羧酸，与环己酮缩合得到吖啶-4-羧酸。

  DOI：

  10.1080/00397919908085895

文献信息

• [EN] DNA-TARGETED BENZOTRIAZINE 1,4-DIOXIDES AND THEIR USE IN CANCER THERAPY<br/>[FR] 1,4-DIOXIDES DE BENZOTRIAZINE CIBLEES SUR ADN ET LEUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2004026846A1

  公开（公告）日：2004-04-01

  The present invention relates to DNA-targeted 1,2,4-benzotriazine- 1,4-dioxides and related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.

  本发明涉及以DNA为靶标的1,2,4-苯并三氮唑-1,4-二氧化物及相关类似物，其制备方法，以及它们作为针对缺氧选择性药物和放射增敏剂在癌症治疗中的应用，无论是单独使用还是与放射线和/或其他抗癌药物结合使用。
• Potential antitumor agents. 50. In vivo solid-tumor activity of derivatives of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide
  作者：Graham J. Atwell、Gordon W. Rewcastle、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm00387a014

  日期：1987.4

  antileukemic activity, with substituents at nearly all acridine positions proving acceptable. The compounds also show remarkable activity against the Lewis lung solid tumor in vivo, with several analogues capable of effecting 100% cures of the advanced disease. The broad SAR and high solid-tumor activity of the 9-acridine-4-carboxamides imply they should be considered as a completely new class of antitumor

  报道了一系列N- [2-（二烷基氨基）烷基] ac啶-4-羧酰胺的合成，理化性质和抗肿瘤活性。这些化合物通过插层与DNA结合，但由于弱碱性a啶发色团（pKa = 3.5-4.5）而在生理条件下以单阳离子形式存在。an啶-4-甲酰胺显示出非常广泛的抗白血病活性的结构-活性关系（SAR），几乎所有all啶位置上的取代基都被证明是可以接受的。所述化合物还具有体内抗路易斯肺实体瘤的显着活性，其几种类似物能够100％治愈晚期疾病。9-ac啶-4-羧酰胺具有宽泛的SAR和较高的固体肿瘤活性，这意味着它们应被视为一类全新的抗肿瘤药物。
• Structure−Activity Relationships for Substituted Bis(acridine-4-carboxamides):  A New Class of Anticancer Agents
  作者：Swarna A. Gamage、Julie A. Spicer、Graham J. Atwell、Graeme J. Finlay、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm980687m

  日期：1999.7.1

  potent bis(5-methylDACA) compound, with second substituents (Me and Cl) in the 1- or 8- position had broadly similar potencies to the 5-Me compound, indicating that, while the 1- and 8-substituents are acceptable, they add little to the enhancing effect of the 5-methyl group. All of the compounds were at least equitoxic (some up to 4-fold more cytotoxic) against the mutant Jurkat lines than in the wild-type

  通过（CH2）3N（Me）（CH2）3链连接的一系列of啶取代的双（ac啶-4-羧酰胺）已通过取代的cr啶-4-羧酸的咪唑化物与N的反应制备。 N-双（3-氨基丙基）甲胺。目前正在临床试验中的这些混合拓扑异构酶I / II抑制剂N- [2-（二甲基氨基）乙基] ac啶-4-羧酰胺（DACA）的二聚体类似物在一组细胞系中显示出比相应的单体DACA类似物更强的效力包括人类Jurkat白血病的野生型（JLC）和突变型（JLA和JLD）。后者的突变体系对拓扑异构酶II靶向试剂有抗性，因为该酶的水平较低。在cr啶5位上带有小的取代基（例如Me，Cl）的类似物明显优于IC50' 对Lewis肺癌的抗药性低至2 nM，而对JLC的抗药性低至11 nM。在任何位置上较大的取代基均会导致效能稳步下降，这可能是由于DNA结合亲和力降低所致。一小部分最有效的双（5-甲基DACA）化合物的类似物，在1-或8位具有
• Synthesis, DNA-Binding and Antiproliferative Properties of Acridine and 5-Methylacridine Derivatives
  作者：Rubén Ferreira、Anna Aviñó、Stefania Mazzini、Ramon Eritja

  DOI：10.3390/molecules17067067

  日期：——

  Several acridine derivatives were synthesized and their anti-proliferative activity was determined. The most active molecules were derivatives of 5-methylacridine-4-carboxylic acid. The DNA binding properties of the synthesized acridines were analyzed by competitive dialysis and compared with the anti-proliferative activities. While inactive acridine derivatives showed high selectivity for G-quadruplex structures, the most active 5-methylacridine-4-carboxamide derivatives had high affinity for DNA but showed poor specificity. An NMR titration study was performed with the most active 5-methylacridine-4-carboxamide, confirming the high affinity of this compound for both duplex and quadruplex DNAs.

  我们合成了几种吖啶衍生物，并测定了它们的抗增殖活性。活性最强的分子是 5-甲基吖啶-4-羧酸的衍生物。通过竞争性透析分析了合成的吖啶类化合物的 DNA 结合特性，并将其与抗增殖活性进行了比较。非活性吖啶衍生物对 G-四链结构具有高选择性，而活性最高的 5-甲基吖啶-4-甲酰胺衍生物对 DNA 具有高亲和力，但特异性较差。对活性最强的 5-甲基吖啶-4-甲酰胺进行了核磁共振滴定研究，证实该化合物对双链和四链 DNA 都有很高的亲和力。
• [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。