title: Hypolipidemic activity of phthalimide derivatives. 7. Structure-activity studies of indazolone analogues.
abstract: The apparent benefit of limiting serum cholesterol and triglyceride levels either by dietary restriction or drug therapy has prompted work in our laboratories toward development of a suitable antihyperlipidemic agent. We have demonstrated the antihyperlipidemic activity of a series of phthalimide derivatives in rodents to be significantly greater than that of clofibrate at a dose of 20 mg/(kg day), intraperitoneally. Here we report the synthesis and biological evaluation of a series of indazolone derivatives, which are heterocycles that are structurally related to the phthalimides . In general, structure-activity relationships within the phthalimide series may be extended to the indazolones . While indazolone itself is only moderately active, N1-carbethoxy substitution produced a more active compound. Substitution of the N2 position with an n-butyl group afforded the most active compound, as also seen in the phthalimide series. Aromatic substitution with electron-releasing and -withdrawing groups lessened the antihyperlipidemic activity.
mesh_terms: D000818:Animals; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000032:analysis / Q000627:therapeutic use; D007191:Indazoles; D008297:Male; D051379:Mice; D010797:Phthalimides / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D000960:Hypolipidemic Agents; D007191:Indazoles; D010797:Phthalimides; C041494:3-indazolinone