Synthesis and hypolipidaemic evaluation of a series of alpha-asarone analogues related to clofibrate in mice

A series of alpha-asarone analogues related to clofibrate, containing an ac etic acid group at C-2 of the aromatic ring, has been prepared as the acids or as the ethyl and methyl esters. The corresponding alcohols were also sy nthesized by reduction of the ethyl esters. The compounds were examined in hyperlipidaemic male mice to evaluate their ability to modify serum lipopro tein cholesterol, low-density lipoprotein cholesterol, high-density lipopro tein cholesterol and triglycerides after oral administration of 40 and 80 m g kg(-1) for 6 days. Except for methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate at either dose, these clofibrate-related phenoxyacetic acid derivatives were found to have significant hypocholesterolaemic activity. Levels of low-density lipo protein cholesterol and triglycerides were significantly reduced and those of high-density lipoprotein cholesterol were elevated, 2-Methoxy-5-nitro-4- (2-propenyl)phenoxyacetic acid was active at both doses in all the tests. C lofibrate (150 mg kg(-1)) was more potent at reducing low-density lipoprote in cholesterol. No activity was detected for the alcohol derivatives. These preliminary results suggest that this class of compound might have mo re promise as potential hypolipidaemic agents than other alpha-asarone deri vatives. Further investigation and characterization should be performed to determine the mode of action of these agents on lipid metabolism.