9-Chloro-2,3-dihydro-5H-1,4-dioxepino(6,5-b)benzofuran, a novel antilipidemic agent structurally related to clofibrate.
The synthesis and antilipidemic activity of 9-chloro-2,3-dihydro-5H-1,4-dioxepino[6,5-b]benzofuran (3), a novel enol lactone which is considerably more resistant to serum esterase hydrolysis than clofibrate (1), are discussed. Whereas both 3 and 1 reduced hypercholesterolemic and hypertriglyceridemic serum levels in the Triton WR-1339 induced hyperlipidemic Sprague-Dawley rat to normal, the hydrolysis product of 3, namely 5-chloro-3(2'-hydroxyethoxy)-2-benzofurancarboxylic acid (4), was found to be inactive. Further, 3 is comparable to the hydrolysis product of 1 when both were assessed for their ability to block norepinephrine (NE) induced lipolysis in vitro. 4 is inactive at comparable concentrations (5 times 10(-4)-10(-3) M). The antilipidemic action of 3 and 1 may, in part, be due to their ability to block NE-induced lipolysis.
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001572:Benzofurans / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D002994:Clofibrate / Q000097:blood; D003864:Depression, Chemical; D005990:Glycerol / Q000378:metabolism; D006868:Hydrolysis; D000960:Hypolipidemic Agents / Q000097:blood / Q000138:chemical synthesis*; D008297:Male; D013058:Mass Spectrometry; D009638:Norepinephrine / Q000494:pharmacology; D010082:Oxepins / Q000097:blood / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D013055:Spectrophotometry, Infrared; D014280:Triglycerides / Q000097:blood
D001572:Benzofurans; D000960:Hypolipidemic Agents; D010082:Oxepins; D014280:Triglycerides; D002784:Cholesterol; D002994:Clofibrate; D005990:Glycerol; D009638:Norepinephrine