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Potential antitumor agents. 40. Orally active 4,5-disubstituted derivatives of amsacrine.

Abstract：

:The DNA-intercalating agent amsacrine is an effective drug for the treatment of human leukemias and lymphomas but has minimal solid tumor activity. As a first step in identifying analogues with a wider spectrum of activity, a comparison was made of the in vivo antileukemic (P-388) activity of amsacrine analogues given by oral (po) and intraperitoneal (ip) routes. A series of 4-substituted and 4,5-disubstituted derivatives all showed high activity when administered ip against ip-implanted P-388, but activity varied widely when the compounds were given orally. 4-Methoxy and 4-carbamoyl derivatives proved essentially inactive, whereas 4-methyl and 4-methylcarbamoyl derivatives retained activity. Exceptional oral activity was shown by the 4-methyl-5-methylcarbamoyl derivative, making this amsacrine derivative worthy of further testing.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Denny WA,Atwell GJ,Baguley BC

doi

10.1021/jm00369a021

subject

Has Abstract

pub_date

1984-03-01 00:00:00

pages

363-7

issue

3

eissn

0022-2623

issn

1520-4804

journal_volume

27

pub_type

杂志文章

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