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Potential antitumor agents. 61. Structure-activity relationships for in vivo colon 38 activity among disubstituted 9-oxo-9H-xanthene-4-acetic acids.

Abstract：

:Analogues of 9-oxo-9H-xanthene-4-acetic acid (XAA) bearing small, lipophilic 5-substituents are among the most dose-potent compounds yet reported with the capability of causing hemorrhagic necrosis of implanted colon 38 tumors in mice. To further extend structure-activity relationships among this class of compound, a series of XAA derivatives bearing two small lipophilic groups at various positions have been prepared and evaluated. The 5,6-disubstituted compounds in particular show consistently high levels of both dose potency and activity, suggesting this is the optimal configuration among substituted 9-oxo-9H-xanthene-4-acetic acids. The 5,6- dimethyl and 5-methyl-6-methoxy are the most effective analogues, showing in vivo colon 38 activity comparable to that of FAA at 10-15-fold lower doses and superior activity to FAA at the respective optimal doses, and the former has been selected for detailed evaluation.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Rewcastle GW,Atwell GJ,Li ZA,Baguley BC,Denny WA

doi

10.1021/jm00105a034

subject

Has Abstract

pub_date

1991-01-01 00:00:00

pages

217-22

issue

1

eissn

0022-2623

issn

1520-4804

journal_volume

34

pub_type

杂志文章

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