Xanthone analogues of clofibrate / Synthesis and biological evaluation as antagonists of lipolysis in vitro.
By appropriate superimposing of fenofibrate and fenofibric acid molecules, two xanthone derivatives (closed models) may be obtained. These compounds as well as their four chlorine-free isomers were prepared and tested on adrenaline- and theophylline-induced lipolysis in rat fat cells in comparison with ethyl 2-(4-chlorophenoxy)-2-methylpropionate (clofibrate). Some of these new derivatives besides being good inhibitors of adrenaline effect, as clofibrate is, were also very active in reducing theophylline-induced lipolysis. Very promising for further studies is the chlorine-free 3-isomer (3e). The possible difference in the action mechanism of these compounds as compared with clofibrate and the structure-activity relationships are briefly discussed.
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002994:Clofibrate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000494:pharmacology
D013806:Theophylline; D002994:Clofibrate; D004837:Epinephrine