Heterocyclic analogues of chlorcyclizine with potent hypolipidemic activity.
A series of [alpha-(heterocyclyl)benzyl]piperazines was synthesized and their effect of reducing serum cholesterol and triglyceride levels in the rat was evaluated. A systematic exploration of the structure-activity relationships led to the synthesis of (R,S)-(3,5-dimethylisoxazol-4-yl)[4-(1-methylethyl)phenyl] (4-methylpiperazin-1-yl)methane dihydrochloride (M&B 31 426), which had potent activity in lowering serum lipid levels at a daily oral dose of 2 mg/kg and was 100 times more potent than clofibrate.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D002791:Cholesterol, Dietary; D004435:Eating / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D008297:Male; D000077489:Piperazine; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D007202:Indicators and Reagents; D000077489:Piperazine