5,5-Diaryl-2-thiohydantoins and 5,5-diaryl-N3-substituted-2-thiohydantoins as potential hypolipidemic agents.
A series of 5,5-diaryl-2-thiohydantoins and 5,5-diaryl-N3-substituted-2-thiohydantoins related to 5,5-diphenyl-2-thiohydantoin (DPTH) were investigated as potential hypolipidemic agents with the goal of increased potency over DPTH itself. In the 5,5-diaryl class, the best results were obtained by substituting two pyridyl rings for the phenyl rings found in DPTH. The resulting compound, 5,5-bis(2-pyridyl)-2-thiohydantoin, DPYTH (5), had slightly better activity than DPTH in lowering liver cholesterol values. Further modifications to DPYTH (5) are underway and will be the subject of a future report. In the N3 nitrogen-substituted series one compound, 5,5-diphenyl-N3-n-butyl-2-thiohydantoin, DPBTH (7), showed promise during initial screening, but when analyzed in a dose-response study, its activity was considerably less than that of the parent compound DPTH.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006827:Hydantoins / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D009963:Orotic Acid / Q000378:metabolism; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013867:Thiohydantoins / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D006827:Hydantoins; D000960:Hypolipidemic Agents; D013867:Thiohydantoins; D014280:Triglycerides; C048807:5,5-bis(2-pyridyl)-2-thiohydantoin; D010672:Phenytoin; D009963:Orotic Acid