Thiazolidinediones: An In–Depth Study of Their Synthesis and Application to Medicinal Chemistry in the Treatment of Diabetes Mellitus

2,4‐Thiazolidinedione (TZD) is a privileged and highly utilised scaffold for the development of pharmaceutically active compounds. This sulfur‐containing heterocycle is a versatile pharmacophore that confers a diverse range of pharmacological activities. TZD has been shown to exhibit biological action towards a vast range of targets interesting to medicinal chemists. In this review, we attempt to provide insight into both the historical conventional and the use of novel methodologies to synthesise the TZD core framework. Further to this, synthetic procedures utilised to substitute the TZD molecule at the activated methylene C5 and N3 position are reviewed. Finally, research into developing clinical agents, which act as modulators of peroxisome proliferator‐activated receptors gamma (PPARγ), protein tyrosine phosphatase 1B (PTP1B) and aldose reductase 2 (ALR2), are discussed. These are the three most targeted receptors for the treatment of diabetes mellitus (DM). A key scaffold: 2,4‐Thiazolidinedione is a widely recognised structural motif present in many therapeutic agents used for the treatment of diabetes mellitus. This review summarises some of the methods used to prepare biologically active members of this class and discusses the pharmacological potency of these compounds.