Hypolipidemic activity of phthalimide derivatives. 3. A comparison of phthalimide and 1,2-benzisothiazolin-3-one 1,1-dioxide derivatives to phthalimidine and 1,2-benzisothiazoline 1,1-dioxide congeners.
Previously it has been observed that N-substituted phthalimide derivatives with chain lengths of four carbon or oxygen atoms showed potent hypolipidemic activity in rodents at 20 (mg/kg)/day ip. The 1,2-benzisothiazolin-3-one 1,1-dioxide (saccharin) nucleus, itself, had also been observed to be active at the same dose. An investigation was undertaken to examine a series of 1,2-benzisothiazolin-3-one 1,1-dioxide analogues for their hypolipidemic activity in mice and to compare them to their respective phthalimide congeners. In addition, a series of 1,2-benzisothiazoline 1,1-dioxide and phthalimidine analogues was prepared, and their hypolipidemic activity was compared to the phthalimide analogues. These studies show that the respective congeners of 1,2-benzisothiazolin-3-one 1,1-dioxide compared favorably to phthalimide congeners in reducing serum triglyceride and cholesterol levels in male CF1 mice at 20 (mg/kg)/day ip. Of the saccharin derivatives, 3-oxo-1,2-benzisothiazoline-2-propionic acid 1,1-dioxide was the most effective in lowering serum cholesterol levels by 53% after 16 days dosing and 3-oxo-1,2-benzisothiazoline-2-valeric acid 1,1-dioxide lowered serum triglycerides 56% after 14 days dosing. The 1,2-benzisothiazoline 1,1-dioxide and phthalimidine compounds were less active as hypolipidemic agents than their 1,2-benzisothiazolin-3-one 1,1-dioxide and phthalimide analogues, respectively.
D000818:Animals; D002784:Cholesterol / Q000097:blood; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007202:Indicators and Reagents; D051379:Mice; D010797:Phthalimides / Q000138:chemical synthesis / Q000494:pharmacology*; D012439:Saccharin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000960:Hypolipidemic Agents; D007202:Indicators and Reagents; D010797:Phthalimides; C037431:phthalimide; C037432:phthalimidine; D002784:Cholesterol; D012439:Saccharin; C037433:1,2-benzoisothiazoline 1,1-dioxide