P. Formstecher, P. Lefebvre, T. Burollaud
1991
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0
Influential Citations
3
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Journal
Journal de pharmacie de Belgique
Abstract
Antiglucocorticoids despite very limited clinical application (in contrast with other antisteroids) are extensively studied, since the glucocorticoid receptor, present in numerous target cells, constitute a very convenient experimental model. Structure activity relationships of a series of 17 beta-carboxamide derivatives of dexamethasone are described. The affinity of these compounds for the glucocorticoid receptor depends on the nature of the 17 beta-side chain substituent. An effect is observed at a rather large distance from the steroid nucleus. Maximal affinity is obtained with aromatic substituents. Antiglucocorticoid activity seems to be correlated with a high dissociation rate constant of the steroid receptor complexes and probably exclude the existence of a very active antiglucocorticoid in these series. Dexamethasone 17 beta-carboxamide derivates share with all other antiglucocorticoids tested the same ability to stabilize a high molecular form of the receptor associated to HSP90, a heat shock protein, in intact cells.