Design, synthesis and hypolipidemic activity of novel 2-(naphthalen-2-yloxy)propionic acid derivatives as desmethyl fibrate analogs.

A series of 2-(naphthalen-2-yloxy)propionic acid derivatives were prepared. The hypolipidemic activity of the new compounds as well as the intermediate acid 2 was evaluated in the high cholesterol diet (HCD) fed hyperlipidemic rat model. Interestingly, the S-alkylated mercaptotriazole 8b and the 1,3,4-oxadiazole 9 produced striking reduction of serum levels of total cholesterol (TC), triglycerides (TGs) and low-density lipoproteins (LDLs) and elevation of serum high-density lipoproteins (HDLs) being more active than the reference gemfibrozil. In addition, the 1,2,4-triazole 7a, the hydroxypyrazoline 10 and the pyrazolone derivative 11 exhibited good hypolipidemic activity on different lipid parameters.