Molecular design, synthesis, and hypoglycemic activity of a series of thiazolidine-2,4-diones

A series of imidazopyridine thiazolidine-2,4-diones were designed and synth esized from their corresponding pyridines. These compounds represent confor mationally restricted analogues of the novel hypoglycemic compound rosiglit azone (5). The series was evaluated for its effect on insulin-induced 3T3-L 1 adipocyte differentiation in vitro and its hypoglycemic activity in the g enetically diabetic KK mouse in vivo. The structure-activity relationships are discussed. On the basis of the in vivo potency, 5-[4-(5-methoxy-3-methy l-3H-imidazo[4,5-b]pyridin-2-ylmethoxy)benzyl]thiazolidine-2,4-dione (19a) was selected as the candidate for further studies in a clinical setting.