Lipid lowering actions of 7-(2-methylene butyryl)-(2H)-1,4-benzoxazin-3-(4H)-one derivatives in mice, rats and Syrian hamsters.
A series of compounds derived from 7-acyl-(2H)-1,4-benzoxazin-3-(4H)-one was synthesized and evaluated for its lipid lowering actions in animal models. These of three 7-(2-methylene butyryl) 4-methyl and 2,4 dimethyl or 2,2,4 trimethyl benzoxazinone showed very potent activity. Their hypocholesterolemic and hypotriglyceridemic activities were tested in normolipemic and in cholesterol-induced hyperlipidemic mice, rats and Syrian hamsters. Two key enzymatic activities (ACAT, HMG CoA Reductase) of the most active compound were also determined. Additional investigation with these products and other derivatives will be performed using a variety of hepatic enzyme activities to better determine their mechanisms of action.
Moussavi
Z
Z
Institut de Chimie Pharmaceutique, Faculté de Pharmacie, Lille, France.
Plancke
M O
MO
Olivier
P
P
Lesieur
D
D
Fruchart
J C
JC
Sauzieres
J
J
D000818:Animals; D048588:Benzoxazines; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D006224:Cricetinae; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000037:antagonists & inhibitors* / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000032:analysis; D008297:Male; D008647:Mesocricetus; D051379:Mice; D010078:Oxazines / Q000494:pharmacology*; D010743:Phospholipids / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000097:blood
D048588:Benzoxazines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008055:Lipids; D008075:Lipoproteins, HDL; D010078:Oxazines; D010743:Phospholipids; D014280:Triglycerides; C060319:4-methyl-7-(2-methylene-1-oxobutyl)-2H-1,4-benzoxazin-3(4H)-one; C060317:2,4-dimethyl-7-(2-methylene-1-oxobutyl)-2H-1,4-benzoxazin-3(4H)-one; C060316:2,2,4-trimethyl-7-(2-methylene-1-oxobutyl)-2H-1,4-benzoxazin-3(4H)-one; D002784:Cholesterol; D011345:Fenofibrate