Glucocorticoid activity and structure activity relationships in a series of some novel 17 alpha-ether-substituted steroids: influence of 17 alpha-substituents.
A series of non-fluorinated glucocorticoids, cortienic acid analogs with a 17 beta-chloromethyl ester and various 17 alpha-ether functions, were tested for their affinity to the rat-lung type-II glucocorticoid receptor. The relative binding affinity of a set of 9 compounds was determined in a competitive experiment with [1,2,4-3H]triamcinolone acetonide. The highest binding affinities were observed with the 17 alpha-propoxy and butoxy analogs which were 1.3 times more active than the standard dexamethasone. Quantitative analysis of the results suggested that steric factors and lipophilicity of the side-chain were the major parameters affecting receptor affinity. Representative members of the series were compared to betamethasone 17 alpha-valerate in a vasonstriction test. The results paralleled those of the receptor binding experiment, indicating that the new steroids have good skin-permeation properties and good glucocorticoid activity.
Hochhaus
G
G
College of Pharmacy, University of Florida, Gainesville 32610.
Druzgala
P
P
Hochhaus
R
R
Huang
M J
MJ
Bodor
N
N
D000818:Animals; D001667:Binding, Competitive; D003600:Cytosol / Q000378:metabolism; D004987:Ethers / Q000378:metabolism / Q000494:pharmacology; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013256:Steroids / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004987:Ethers; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D013256:Steroids; D014662:Vasoconstrictor Agents