Hypolipidemic activity of 6-alkoxycarbonyl-3-aryl-1,3,5- triazabicyclo[3.1.0]hexane-2,4-diones and 2-alkoxycarbonyl-5-aryl-1,3,5-triazine-4,6(1H,5H)-diones in rodents.
Significant hypolipidemic activity was demonstrated by 6-ethoxycarbonyl-1-3-phenyl-1,3,5-triazabicyclo[3.1.0]hexane-2,4-dione, 2-ethoxycarbonyl-5-phenyl-1,3,5-triazine-4,6(1H,5H)-dione and 2-ethoxycarbonyl-5-(4-chlorophenyl)-1,3,5-triazine-4,6(1H,5H)-dione in rodents at 20 mg/kg/day. These agents lowered serum cholesterol and triglyceride levels by approximately 40% in mice after 16 d. Tissue lipids in rat liver, small intestinal mucosa, aortic wall and feces were reduced by treatment with the agents. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol levels were reduced in the rat; high density lipoprotein (HDL) cholesterol levels were elevated after 14 d of treatment. The activities of regulatory enzymes, e.g., acetyl-CoA synthetase, acyl-CoA:cholesterol acyltransferase, cholesterol 7 alpha-hydroxylase, sn-glycerol-3-phosphate acyltransferase, phosphatidylate phosphohydrolase and heparin-induced lipoprotein lipase, involved in de novo synthesis of hepatic lipids were affected by the agents. The new compounds may represent another class of potentially useful hypolipidemic agents for the treatment of atherosclerosis since HDL cholesterol levels were increased and VLDL and LDL cholesterol levels were lowered by some of the agents.
Izydore
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Department of Chemistry, North Carolina Central University, Durham 27707.
Wong
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Hall
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D000284:Administration, Oral; D000818:Animals; D001011:Aorta / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000737:chemistry; D007421:Intestine, Small / Q000737:chemistry; D008074:Lipoproteins / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood*
D001643:Bridged Bicyclo Compounds; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014227:Triazines; D014280:Triglycerides; D002784:Cholesterol