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CHEMICAL STRUCTURE AND PHARMACOLOGICAL ACTIVITY OF SOME DERIVATIVES OF DIGITOXIGENIN AND DIGOXIGENIN
Author(s) -
BROWN B. T.,
STAFFORD ANNE,
WRIGHT S. E.
Publication year - 1962
Publication title -
british journal of pharmacology and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0366-0826
DOI - 10.1111/j.1476-5381.1962.tb01411.x
Subject(s) - digitoxigenin , digoxigenin , inotrope , chemistry , guinea pig , biological activity , cardenolide , aglycone , pharmacology , glycoside , toxicity , potency , papillary muscle , endocrinology , biochemistry , stereochemistry , biology , in vitro , in situ hybridization , gene expression , organic chemistry , gene
A series of derivatives of digitoxigenin and digoxigenin were prepared and tested for toxicity in the cat and the guinea‐pig and on the isolated heart of the 48‐hr chick embryo, and for inotropic activity on the cat isolated papillary muscle and the guinea‐pig Langendorff heart. The order of relative potency of the compounds remained the same whether they were tested for toxicity or for positive inotropic activity. There are three molecular centres in the cardiac aglycone that are linked closely with cardiac activity. These are: ( a ) an OH at carbon‐3 which can be combined as a glycoside, thus enhancing activity, or esterified or oxidized, producing compounds of lower activity; the maximum intensity of the inotropic response was reduced in the less potent compounds; ( b ) a 14‐β‐OH associated with a cis C‐D ring junction, alteration of which abolished activity; ( c ) an unsaturated cyclobutenolide ring which cannot be reduced without a great decrease in activity.