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Antimitotic agents: structure-activity studies with some pyridine derivatives.

Abstract：

:Antitumor activity in mice was observed for the oxime of the previously reported ethyl [6-amino-4-[(1-methyl-2-phenyl-2-oxoethyl)amino]-5-nitropyridin -2-yl] carbamate (8) and several related compounds. These compounds are precursors of the active ethyl pyrido[3,4-b]pyrazin-7-ylcarbamates (e.g., 4), which are potent antimitotic agents. In the 5-nitropyridine series overall biological activity was reduced by replacement of the oxime moiety with a keto or alcohol group and by replacement of the 1-methyl group of the side chain with hydrogen. Reduction of the nitro group of the 5-nitropyridines containing an alcohol in the side chain to the corresponding 5-aminopyridines increased biological activity. Preliminary studies showed that the 5-nitropyridine oximes were considerably less potent than the pyridopyrazines as antimitotic agents and that the former are apparently not converted to the latter in vivo. The inhibition of the incorporation of pyrimidine nucleosides into DNA and RNA was identified as another possible mode of action of the 5-nitropyridine oximes.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Temple C Jr,Rener GA,Waud WR,Noker PE

doi

10.1021/jm00098a014

keywords:

subject

Has Abstract

pub_date

1992-10-02 00:00:00

pages

3686-90

issue

20

eissn

0022-2623

issn

1520-4804

journal_volume

35

pub_type

杂志文章

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