Studies on antidiabetic agents. Synthesis and hypoglycemic activity of 5-[4-(pyridylalkoxy)benzyl]-2,4-thiazolidinediones.

The synthesis of a series of 5-[4-(pyridylalkoxy)benzyl]-2, 4-thiazolidinediones is described. These compounds were evaluated for hypoglycemic and hypolipidemic activities in genetically obese and diabetic mice, yellow KK. 2-(2-Pyridyl)alkoxy derivatives were found to have much better hypoglycemic and hypolipidemic activities than 2-(3-pyridyl)- and 2-(4-pyridyl)alkoxy derivatives or even the previously reported compound, ciglitazone. The introduction of a hydroxyl group at the 2-position of the ethoxy chain potentiated the activities. Among the potent compounds, pioglitazone (AD-4833) was selected as a candidate compound.