Sulfonyliminoimidazolidines. A new class of oral hypoglycemic agents. 2. Mode of action and X-ray structure of 1-[[p-[2-(crotonylamino)ethyl]phenyl]sulfonyl]-3-cyclohexyl-2-iminoimidazolidine.
Hypoglycemic sulfonyliminoimidazolidines were shown to stimulate insulin release in vitro (rabbit pancreas) and in vivo (normal rats) comparable to tolbutamide and to inhibit glucose oxidation in isolated rat fat cells in vitro similar to phenformin. These results support the hypothesis that the hypoglycemic effect of the compounds in normal and in diabetic animals may be due to a combination of mechanisms operative in sulfonylureas and biguanides. Determination of the three-dimensional structure of the potent analogue 1 by X-ray crystallography enabled us to identify specific regions of the molecule presumed to be involved in the molecular mode of action of sulfonyl-iminoimidazolidines.
D000818:Animals; D001681:Biological Assay; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D048289:Imidazolidines; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008968:Molecular Conformation; D011817:Rabbits; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D007004:Hypoglycemic Agents; D007093:Imidazoles; D048289:Imidazolidines; D007328:Insulin; C038573:1-((4-(2-(crotonylamino)ethyl)phenyl)sulfonyl)-3-cyclohexyl-2-iminoimidazolidine