title: Relationships of the molecular structure of aldosterone derivatives with their binding affinity for mineralocorticoid receptor.
abstract: The molecular structures of 19-nor-11-deoxycorticosterone (III) and 21-hydroxypregna-4,11-diene-3,20-dione (IV) were determined by X-ray crystallographic analysis and the factors affecting the binding affinities for the mineralocorticoid receptor were examined with six aldosterone derivatives (I-VI) containing these two compounds. The most important factor was found to be the steric one; affinity increased with increasing flatness of the structure. The electronic factor may be a minor influence although a good relationship was found between the affinity and the 13C-NMR chemical shift of the C(5) atom. The factor playing no role in the binding is the hydrophobic one.
mesh_terms: D000450:Aldosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003600:Cytosol / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008901:Mineralocorticoids / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D000450:Aldosterone