915303-09-2Relevant articles and documents
Synthesis and evaluation of indenoisoquinoline topoisomerase I inhibitors substituted with nitrogen heterocycles
Nagarajan, Muthukaman,Morrell, Andrew,Ioanoviciu, Alexandra,Antony, Smitha,Kohlhagen, Glenda,Agama, Keli,Hollingshead, Melinda,Pommier, Yves,Cushman, Mark
, p. 6283 - 6289 (2006)
In connection with an ongoing investigation of indenoisoquinoline topoisomerase I (Top1) inhibitors as potential therapeutic agents, the pharmacophore possessing di(methoxy) and methylenedioxy substituents was held constant, and new derivatives were synthesized with nitrogen heterocycles appended to the lactam side chain. Compounds were evaluated for Top1 inhibition and for cytotoxicity in the National Cancer Institute's human cancer cell screen. Some of the more potent derivatives were also screened for in vivo activity in a hollow fiber assay. The results of these studies indicate that lactam substituents possessing nitrogen heterocycles can provide highly cytotoxic compounds with potent Topi inhibition. Molecular modeling of these compounds in complex with DNA and Top1 suggests that some of the lactam substituents are capable of interacting with the DNA base pairs above and below the site of intercalation and/or with Topi amino acid residues, resulting in increased biological activity.
Synthesis of Biologically Active Indenoisoquinoline Derivatives via a One-Pot Copper(II)-Catalyzed Tandem Reaction
Huang, Chia-Yu,Kavala, Veerababurao,Kuo, Chun-Wei,Konala, Ashok,Yang, Tang-Hao,Yao, Ching-Fa
, p. 1961 - 1968 (2017/02/26)
A concise route for the synthesis of indenoisoquinoline derivatives from 2-iodobenzamide and 1,3-indanedione derivatives in the presence of copper(II) chloride and cesium carbonate in acetonitrile solvent is reported. A wide variety of 2-iodobenzamide derivatives and indandiones could be used to synthesize indenoisoquinoline derivatives and other fused indenoisoquinoline in moderate to good yields. This methodology was adapted for the one-step synthesis of a series of clinically active topoisomerase I inhibitors such as NSC 314622, LMP-400, LMP-776.
N-SUBSTITUTED INDENOISOQUINOLINES AND SYNTHESES THEREOF
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Page/Page column 35-36; 38, (2008/06/13)
N-Substituted indenoisoquinoline compounds, and pharmaceutical formulations of N-substituted indenoisoquinoline compounds are described. Also described are processes for preparing N-substituted indenoisoquinoline compounds. Also described are methods for
