Hypolipidemic activity of phthalimide derivatives. 2. N-phenylphthalimide and derivatives.
A series of substituted N-phenylphthalimide derivatives was synthesized and examined for their ability to lower serum cholesterol and triglyceride levels in mice at 20 (mg/kg)/day, ip. Of the newly synthesized compounds, the most potent compound, o-(N-phthalimido)acetophenone, lowered serum cholesterol 57% after 16 days and lowered serum triglyceride levels 44% after 14 days. o-(N-Phthalimido)acetophenone was observed to be active in both normogenic (normal blood lipids levels) and hyperlipidemic mice and normogenic rats. In the latter, the reduction of serum lipids was reversible. The mode of this compound appeared to be multiple, including blockage of the de novo synthesis of lipids and acceleration of the excretion of lipids. The lipoprotein fractions of rat blood were reduced significantly in cholesterol, triglyceride, and neutral lipid content after 14 days treatment with o-(N-phthalimido)acetophenone.
D000106:Acetate-CoA Ligase / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000097:blood; D064429:Fatty Acid Synthases / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D006949:Hyperlipidemias / Q000097:blood; D000960:Hypolipidemic Agents / Q000138:chemical synthesis*; D008074:Lipoproteins / Q000097:blood; D051379:Mice; D010711:Phosphatidate Phosphatase / Q000378:metabolism; D010743:Phospholipids / Q000097:blood; D010797:Phthalimides / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood
D000960:Hypolipidemic Agents; D008074:Lipoproteins; D010743:Phospholipids; D010797:Phthalimides; D014280:Triglycerides; C037430:N-phenylphthalimide; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D000217:Acyltransferases; D064429:Fatty Acid Synthases; D010711:Phosphatidate Phosphatase; D000106:Acetate-CoA Ligase; D000103:Acetyl-CoA Carboxylase