A Comprehensive Review on Thiazolidinones and their 5-ene Derivatives: Synthetic Methodologies and Pharmacological Profiles

Abstract:

Thiazolidinones and their 5-ene derivatives have become pivotal in organic and medicinal chemistry due to their diverse pharmacological potential. These compounds have been widely explored for their therapeutic applications, with thiazolidine-based frameworks yielding numerous biologically active molecules. This review consolidates various synthetic approaches to thiazolidinone and 5-ene derivatives, including core modifications, one-pot or multistage syntheses, and transformations of related heterocycles. The manuscript highlights key pharmacological targets of thiazolidinones, ranging from initial hit compounds to fully developed drugs. Specifically, thiazolidinone- rhodanines often appear as frequent hitters or pan-assay interference compounds in highthroughput screens. Studies have shown that modifications at the C5 carbon, particularly through the addition of a 5-ene fraction, enhance the pharmacological profile of these compounds. Additionally, the review addresses substitutions at the C5 and N3 positions, including 5-ene and carboxyl groups, and discusses the biological utility of these modifications. Integrating pharmacologically active groups within a heterocyclic system often results in enhanced bioactivity. The review highlights innovative synthetic strategies for thiazolidinone derivatives, emphasizing the potential of these compounds to explore a broad spectrum of biological activities through structural diversity and targeted modifications.