[EN] 9-AMINOACRIDINE DERIVATIVES, THEIR PREPARATION AND USES<br/>[FR] DÉRIVÉS DE 9-AMINOACRIDINE, LEUR PRÉPARATION ET LEURS UTILISATIONS
申请人:UNIV ARIEL RES & DEV CO LTD
公开号:WO2011051950A1
公开(公告)日:2011-05-05
N-substituted 9-aminoacridine and bis-acridino derivatives containing electron- withdrawing groups (EWG) or electron-donating groups (EDG), including amino acid residues, and one-pot methods for their synthesis are disclosed. The derivatives are potential candidates for cancer treatment.
An efficient N-selective alkylation of primary aromatic amines in molten quaternary ammonium salts, as the solvent, under relatively mild and base-free conditions is presented. On the basis of the Kamlet–Taft parameters and the nucleophilicity of the IL (ionic liquid) anions, the influence of the ionic liquid was evaluated. This protocol was validated on a larger multigram scale and with the syntheses
介绍了在相对温和和无碱的条件下,以熔融季铵盐作为溶剂,伯芳胺的有效 N 选择性烷基化。在 Kamlet-Taft 参数和 IL(离子液体)阴离子的亲核性的基础上,评估了离子液体的影响。该协议在更大的多克规模上进行了验证,并与生物活性杂环(例如,1,4-苯并噻嗪和喹喔啉)和新的高效 MALDI 基质的合成有关。
9-AMINOACRIDINE DERIVATIVES, THEIR PREPARATION AND USES
申请人:Gellerman Gary
公开号:US20120220537A1
公开(公告)日:2012-08-30
N-substituted 9-aminoacridine and bis-acridino derivatives containing electron-withdrawing groups (EWG) or electron-donating groups (EDG), including amino acid residues, and one-pot methods for their synthesis are disclosed. The derivatives are potential candidates for cancer treatment.
Acridine derivatives have been explored as DNA-binding anticancer agents. Some derivatives show undesired pharmacokinetic properties and new derivatives need to be explored. In this work, a series of novel acridine analogues were synthesized by modifying previously unexplored linkers between the acridine and benzene groups and their antiproliferative activity and the DNA-binding ability were evaluated. Among these derivatives, compound 5c demonstrated DNA-binding capability and topoisomerase I inhibitory activity. In K562 cell lines, 5c induced apoptosis through mitochondria-dependent intrinsic pathways. These data suggested that compound 5c and other acridine derivatives with modified linkers between the acridine and benzene groups might be potent DNA-binding agents. (C) 2013 Elsevier Ltd. All rights reserved.