Relative affinity of 17α- and/or 21-esters and 17α,21-diesters of cortisol for a glucocorticoid receptor from rat thymocytes

Abstract

The affinity, relative to cortisol (1), of 17 alpha- and 21-esters and 17 alpha,21-diesters of cortisol for the glucocorticoid receptor of rat thymus cytosol was determined by a competitive binding assay which used [3H]dexamethasone. Esterification of the 21-hydroxy group of cortisol caused a loss of relative affinity to 0.046 for acetate and 0.32 for valerate. Esterification of the 17 alpha-hydroxy group resulted in an increase in relative affinity to 1.14 for acetate, 12.4 for butyrate, and 11.5 for valerate. Diesters had relative affinities which reflected both trends. Thus, the 21-acetate, 21-propionate, 21-butyrate, and 21-valerate of cortisol 17-acetate had relative affinities of 0.036, 0.093, 0.152, and 0.272. The 21-acetate, 21-propionate, and 21-butyrate of cortisol 17-valerate had relative affinities of 0.76, 1.17, and 1.33.

Glucocorticoids: Binding Affinity and Lipophilicity

“…Since the lipophilicity of the steroid and the induction factor qZ4 is increased by the acetate group, the drop in the binding affinity due to the presence of the acetate group at C-17 and/or C-21 is probably related to a steric effect . 26 One might expect from the foregoing that the elongation of the acyl moiety (which leads to an increased substituent size) would cause a further decrease in the steroid binding affinity for the receptor. However, this is not the case.…”

Aspects of pharmacodynamics and biotransformation of the glucocorticoid resocortol butyrate

“…10-14 times higher than the affinity of cortisol and similar to that of triamcinolone acetonide, which belongs to the compounds with the highest affinity for the receptor (Dausse et al, 1977). In addition, esterification of the hydroxyl group in position 17 of glucocorticoids increases the affinity of the glucocorticoids for the glucocorticoid receptor (Solo et al, 1982). The high affinity of RCB is reflected in its high glucocorticoid activity as has been assessed in established models in laboratory animals ( 11 Intervet International bv, unpublished data).…”

“…, 1977). In addition, esterification of the hydroxyl group in position 17 of glucocorticoids increases the affinity of the glucocorticoids for the glucocorticoid receptor (Solo et al. , 1982).…”

New potent topical anti-inflammatory steroids with reduced side effects: Derivatives of steroid-16-carboxy esters

“…The mixture was stirred at 0°C for 30 min, and the solvent was evaporated to give a pale yellow oil. This was chromatographed on a silica gel column, eluting with benzene:ethyl acetate (3:5) to yield 236 mg (73.2%) of 2 as colorless crystals, mp 211-214 "C; 'H NMR: 0.98 (s, 3H, 10-CH,), 1.48 (s, 3H, 13 Anal.-C2,H,,0,: C, H. Methyl 17a,21 -diacetoxy -1 1 P-hydroxy-3,20-dioxo-pregna-l,4 -diene-l6a-carhoxylate IPIGCMl7,ZlAc; 3 t T o a mixture of glacial acetic acid (1.5 mL, dried over a 4 A molecular sieve) and trifluoroacetic anhydride (0.6 mL) was added a solution of 2 (100 mg, 0.2 mmol) and pyridinium p-toluenesulfonate catalyst (50 mg). The mixture was stirred for 3.5 h a t room temperature and then poured into distilled water (100 mL).…”