5-Ene-4-thiazolidinones - An efficient tool in medicinal chemistry

Abstract

The presented review is an attempt to summarize a huge volume of data on 5-ene-4-thiazolidinones being a widely studied class of small molecules used in modern organic and medicinal chemistry. The manuscript covers approaches to the synthesis of 5-ene-4-thiazolidinone derivatives: modification of the C5 position of the basic core; synthesis of the target compounds in the one-pot or multistage reactions or transformation of other related heterocycles. The most prominent pharmacological profiles of 5-ene derivatives of different 4-thiazolidinone subtypes belonging to hit-, lead-compounds, drug-candidates and drugs as well as the most studied targets have been discussed. Currently target compounds (especially 5-en-rhodanines) are assigned as frequent hitters or pan-assay interference compounds (PAINS) within high-throughput screening campaigns. Nevertheless, the crucial impact of the presence/nature of C5 substituent (namely 5-ene) on the pharmacological effects of 5-ene-4-thiazolidinones was confirmed by the numerous listed findings from the original articles. The main directions for active 5-ene-4-thiazolidinones optimization have been shown: i) complication of the fragment in the C5 position; ii) introduction of the substituents in the N3 position (especially fragments with carboxylic group or its derivatives); iii) annealing in complex heterocyclic systems; iv) combination with other pharmacologically attractive fragments within hybrid pharmacophore approach. Moreover, the utilization of 5-ene-4-thiazolidinones in the synthesis of complex compounds with potent pharmacological application is described. The chemical transformations cover mainly the reactions which involve the exocyclic double bond in C5 position of the main core and correspond to the abovementioned direction of the 5-ene-4-thiazolidinone modification.

Keywords: 5-Ene-4-thiazolidinones; Biological activity; Synthesis.