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Structure-activity relationships in a series of newly synthesized 1-amino-substituted ellipticine derivatives.

Abstract：

:The synthesis of a series of 1-amino-substituted pyrido[4,3-b]carbazole derivatives, based on the substitution of corresponding 1-chloroellipticines, is reported. The cytotoxic properties on tumor cells grown in vitro, the in vivo acute toxicity of the most potent in vitro cytotoxic compounds, and the antitumor properties toward the L1210 leukemia system are described. No correlation between the apparent association constant to DNA and the in vitro cytotoxicity or the in vito antitumor efficiency could be observed in this series. 9-Hydroxylated derivatives were more cytotoxic in vitro than the corresponding 9-methoxylated compounds. However, their antitumor efficiencies on the in vivo experimental systems do not confirm the advantage of demethylation. The presence of a [(dialkylamino)alkyl]amino side chain at the 1 position of ellipticines increases the antitumor potency: 1-[[3-(diethylamino)propyl]amino]-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (5) is a very potent antitumor compound (% ILS of 134 on the L1210 leukemia system).

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Ducrocq C,Wendling F,Tourbez-Perrin M,Rivalle C,Tambourin P,Pochon F,Bisagni E,Chermann JC

doi

10.1021/jm00185a012

subject

Has Abstract

pub_date

1980-11-01 00:00:00

pages

1212-6

issue

11

eissn

0022-2623

issn

1520-4804

journal_volume

23

pub_type

杂志文章

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