title: Structure-activity relationship of aldose reductase inhibitors based on X-ray crystal structures of oxazolecarbamate derivatives.
abstract: In order to elucidate the key atoms and/or stereostructures necessary for the inhibitory emergence of aldose reductase, crystal structure determinations were carried out for 11 oxazolecarbamate analogues, which have similar chemical and physicochemical properties but different inhibitory activities. The molecular conformations, revealed by X-ray analyses, were also ascertained to be energetically stable from theoretical conformational energy calculations. A surprising degree of conformational similarity was observed for the potent inhibitors. The analyses of the quantitative structure--activity relationships showed that the molecular conformation and the dipole moment, as well as the hydrophobicity at the oxazole C5-site, were important for high activity.
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D010080:Oxazoles / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*; D014961:X-Ray Diffraction
chemical_list: D010080:Oxazoles; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase