Thiazolidinediones and PPAR orchestra as antidiabetic agents: From past to present

Thiazolidinediones a class of drug, that provided a major breakthrough in the management of type 2 diabetes since 1990. Following the discovery of PPARs, TZDs were the first class to be reported as PPARγ modulators. This review is an attempt to summarize the chemical modifications around TZDs in past two decades to obtain a potent antidiabetic molecule. TZDs literature were initially dominated by their hypoglycemic & hypolipidemic activities, later PPARγ activity was also been incorporated. Moreover, in some cases, both benzyl and benzylidene derivatives were reported in the same manuscript for the sake of comparison. We thought of presenting the review on the basis of the variation in the linker region. Optimal linker at the time of discovery of the Ciglitazone was oxymethyl and it went on to evolve as oxyethyl (Pioglitazone) and oxyethylamino (Rosiglitazone). Few attempts were made to restrict the flexibility of the linker by introducing the cyclic structures and were summarized immediately after the respective linker class.