title: Synthesis and pharmacological evaluation of a clofibrate-related tricyclic spirolactone, 5-chloro-4',5-dihydrospiro[benzofuran-2(3H),3'(2'H)-furan]-2'-one.
abstract: The chemistry and pharmacology of the title compound, spirolactone 4, are reported. The synthesis represents a new approach to the preparation of spiro compounds. The pharmacological profiles of 4 are compared to that of clofibrate in Triton-induced hyperlipidemic, sucrose-fed, and normal Sprague-Dawley rat models. Clofibrate was effective in all animal models, but the spirolactone 4 exhibited antitriglyceridemic activity only in the Triton model. The inactivity of 4 in sucrose- and chow-fed rats could not be attributed to a resistance to hydrolysis by serum esterases. Comparative studies revealed that inhibition of hepatic HMG-CoA reductase activity may not be an index of hypocholesterolemic action in sucrose-fed rats. Additionally, only clofibrate exhibited significant changes in components of the hepatic microsomal monooxygenase system.
mesh_terms: D000818:Animals; D002994:Clofibrate / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis / Q000494:pharmacology; D006949:Hyperlipidemias / Q000139:chemically induced / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000138:chemical synthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis / Q000494:pharmacology; D013395:Sucrose / Q000494:pharmacology
chemical_list: D000960:Hypolipidemic Agents; D013148:Spironolactone; D011092:Polyethylene Glycols; D013395:Sucrose; D002994:Clofibrate