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Cardenolide analogues. 14. Synthesis and biological activity of glucosides of C17 beta-modified derivatives of digitoxigenin.

Abstract：

:An improved method for the synthesis of cardiac glycosides was used to prepare 3 beta-glucosides of digitoxigenin derivatives in which the 17 beta side chain was CH=CHX (X = COOH, CONH2, COCH3, CN, or COOR). We compared the inotropic activity of the compounds with that of digitoxigenin glucoside using guinea pig left atria. All compounds were active except for the acid (7) and the amide (8). The inactivity of the amide, in spite of its favorable shape and high capacity for forming intermolecular hydrogen bonds, is incompatible with some previous structure-activity relationship theories. Of the active genins, glucosidation enhanced activity by a factor of about 2. All glucosides, including those with high potency, showed rapid onset and offset of action. The stepwise fall in potency that occurred when the ester group (CH=CHCOOR) was increased in bulk supported previous suggestions that the portion of the digitalis receptor that interacts with the C17 side chain lies within a cleft.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Smith P,Brown L,Boutagy J,Thomas R

doi

10.1021/jm00352a025

subject

Has Abstract

pub_date

1982-10-01 00:00:00

pages

1222-6

issue

10

eissn

0022-2623

issn

1520-4804

journal_volume

25

pub_type

杂志文章

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