Studies of Hypolipidemic Agents. I. : Syntheses and Hypolipidemic Activities of 1-Substituted 2-Alkanone Derivatives

• Published in: Chemical & pharmaceutical bulletin Vol. 34; no. 3; pp. 1118 - 1127
• Main Authors: OGAWA, KAZUO, TERADA, TADAFUMI, MURANAKA, YOSHIYUKI, HAMAKAWA, TOSHIHIRO, HASHIMOTO, SADAO, FUJII, SETSURO
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1986; Maruzen
• Subjects: Animals; Chemical Phenomena; Chemistry; Enzyme Inhibitors; Exact sciences and technology; Hypolipidemic Agents - chemical synthesis; Hypolipidemic Agents - pharmacology; Ketones - chemical synthesis; Ketones - pharmacology; Lipids - blood; Male; Noncondensed benzenic compounds; Organic chemistry; Preparations and properties; Rats; Rats, Inbred Strains; structure-activity relationship; Rat; Aliphatic compound; Rodentia; Saturated compound; Enzyme inhibitor; Triacylglycerol lipase; Haloketone; Sulfonic acid; Biological activity; Plasmin; Vertebrata; Mammalia; Aminoketone; Ketoether; Esterase; Structure activity relation; Animal; Antilipemic agent
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.34.1118

Many 1-substituted 2-alkanone derivatives were synthesized and their inhibitory activities toward pancreatic lipase and esterase were examined in order to obtain hypolipidemic agents. 1-Benzenesulfonyloxy-2-pentanone (VI-2a) and 1-(2, 4, 6-trimethylbenzenesulfonyloxy)-2-pentanone (VI-2q) exhibited not only potent and selective esterase inhibitions (IC50 : 9.0×10-7M and 1.0×10-6M, respectively), but also potent hypolipidemic action (90 and 92% reductions of plasma triglyceride, and 53 and 90% reductions of plasma total cholesterol, respectively). A novel working hypothesis is presented to account for the lowering of the plasma lipids level, i.e., that inhibition of esterase and lipase activities in the small intestinal lumen may be responsible for the decrease in the plasma lipids level.