Ring-substituted 11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides with similar patterns of cytotoxicity to the dual topo I/II inhibitor DACA

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• 作者：Deady ; Leslie W. ; Desneves ; José ; Kaye ; Anthony J. ; Thompson ; Michelle ; Finlay ; Graeme J. ; et. al.
• 关键词：Antitumour compounds ; chemotherapy ; enzyme inhibitors ; topoisomerase
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：1999
• 出版时间：December, 1999
• 年：1999
• 卷：7
• 期：12
• 页码：2801-2809
• 全文大小：220 K

文摘

A series of ring-substituted analogues of the topoisomerase inhibitor 11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides was prepared and evaluated. The compounds were prepared by Pfitzinger reaction of the appropriate isatin-7-carboxylic acids and 1-indanones, followed by selective thermal decarboxylation of the resulting tetracyclic diacids, subsequent oxidation of the methylene group with alkaline permanganate under carefully controlled conditions, and 1,1'-carbonyldiimidazole-induced amidation. The compounds were evaluated in a panel of cell lines in culture. The largest increases in cytotoxicity (five to tenfold) were shown by 4-substituted analogues, with the 4-Cl derivative having an IC₅₀ of 8 nM against the Lewis lung carcinoma.