Studies on Antidiabetic Agents. II. Synthesis of 5-[4-(1-Methylcyclohexylmethoxy)-benzyl]thiazolidine-2,4-dione (ADD-3878) and Its Derivatives

Abstract

More than 100 5-substituted thiazolidine-2,4-diones were prepared and their hypoglycemic and hypolipidemic activities were evaluated with genetically obese and diabetic mice, yellow KK. The structure-activity relationship study showed that the 5-(4-oxybenzyl) moiety is essential for substantial activity. Among these compounds, 5-(4-cyclohexyl-methoxy)benzylthiazolidine-2,4-dione (47), 5-[4-(1-methylcyclohexylmethoxy)benzyl]-thiazolidine-2,4-dione (49, ADD-3878) and 5-{4-[2-(3-pyridyl)ethoxy]benzyl}thiazolidine-2,4-dione (59) exhibited the most favorable properties in terms of activity and toxicity. © 1982, The Pharmaceutical Society of Japan. All rights reserved.