Structure-Activity Studies on Antihyperlipidemic N-Benzoylsulfamates, N-Benzylsulfamates, and Benzylsulfonamides

Abstract

A series of aryl substituted N-benzoyl- and N-benzylsul-famic acid sodium salts and benzylsulfonamide sodium salts have been prepared and examined for antihyperlipidemic activity in male CF1 mice at a dose level of 20 mg/kg/d ip for 16 d. These substances were also subjected to toxicological evaluation and chemical stability studies. In general, both series of sulfamates and sulfonamides significantly lowered serum cholesterol and triglyceride levels in mice. The compounds were nonmutagenic, showed no acute toxicity or impaired liver or kidney function in male mice, and were chemically stable both as the monohydrates and in aqueous solution over a pH range of 3.5–7.4. While both series of sulfamates and sulfonamides lowered serum cholesterol and triglyceride levels, the sulfamates were relatively more potent with regard to decreasing cholesterol levels, while the sulfonamides were more effective in lowering serum triglyceride levels in mice.