The synthesis of homophthalimide and related derivatives and their hypolipidemic activity in rodents

Homophthalimide and a series of N-alkyl-substituted derivatives were investigated to determine their ability to lower serum cholesterol and triglyceride levels in mice. At 20 mg/kg/day these agents were equally potent or more potent than clofibrate at 150 mg/kg/day. However, the homophthalimide series was not as active as other hypolipidemic cyclic imides investigated by this laboratory. Compounds that caused a greater than 30% reduction of both serum cholesterol and triglyceride levels after 16 days at 20 mg/kg/day ip include the N-propyl, N-phenyl, 3′-methylphenyl, 3′-methoxyphenyl, 3′-chlorophenyl, and the 3′-ethylphenyl derivatives. Substitutions in the 3′ position of the phenyl group afforded the most active compounds for reducing blood lipid levels in rodents.