Hypolipidemic activity of a series of N-pyridinyl and N-quinolinyl substituted derivatives of phthalimide and succinimides in rodents.

N-Pyridinyl- and N-quinolinyl-ethyl substituted succinimide and phthalimide derivatives demonstrated significant hypolipidemic activity in rodents lowering both serum cholesterol and triglyceride levels at 20 mg/kg.day i.p. The pyridinyl, quinolinyl and tetrahydro-2-quinolinyl substitution improved the hypolipidemic activity of the succinimide derivatives. Whereas select N-quinolinylethylphthalimide derivatives demonstrated less activity than phthalimide, itself, in lowering serum cholesterol and triglyceride levels, they did cause significant increases in HDL cholesterol and lower LDL cholesterol levels after 14 days of drug administration. Phthalimide actually caused reductions of HDL cholesterol levels in rats. These new agents with heterocyclic substitution of the N atom of phthalimide increased fecal excretion of lipids and suppressed in vitro hepatic rate limiting enzyme activities for de novo synthesis of cholesterol, fatty acids and triglycerides. Acute toxicity studies of the N-quinolinylethylphthalimide derivatives indicated that the agents are safe as potential therapeutic agents at doses necessary for hypolipidemic activity.