Medicinal Chemistry, SAR, and Molecular Insights Into 2,4‐Thiazolidinediones as Antidiabetic Agents (2020–2025)

The thiazolidinedione (TZD) scaffold is recognized for its pharmacological versatility in treating metabolic and inflammatory disorders.

• 2,4-thiazolidinediones (2,4-TZDs) have been identified as significant antidiabetic agents with multiple molecular targets.
• In addition to functioning as PPAR-γ agonists, 2,4-TZDs may inhibit protein tyrosine phosphatase 1B (PTP-1B), α-amylase, α-glucosidase, and aldose reductase.
• These additional mechanisms contribute to improved glucose regulation and diabetes management.
• The development of dual and multitarget inhibitors suggests an expanding therapeutic potential for 2,4-TZDs beyond traditional pathways.
• A comprehensive analysis of recent advancements (2020-2025) in medicinal chemistry and antidiabetic mechanisms of 2,4-TZDs is presented.

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