Synthesis of new thiopyrano[2,3-d]thiazole-2-thiones as potential pharmacological agents  

Modern medicinal chemistry is actively searching for effective approaches to create heterocyclic molecules with a combination of various pharmacologically significant elements within one structure. Of particular interest is the thiopyrano[2,3-d]thiazole-2-thione framework, which combines the chemical and pharmacological properties of thiazole and thiopyran, opening up new opportunities for the development of medicinal agents. Unlike 2-one analogues, these systems remain almost unstudied, which creates prospects for the discovery of new antimicrobial, antitumor and anti-inflammatory compounds. The implementation of the synthetic part was carried out according to a two-step strategy. At the first stage, the corresponding 5-ylidene derivatives were synthesized using the Knoevenagel reaction between 2-thioxo-thiazolidin-4-one (rhodanine) and various aromatic aldehydes, which were used as starting compounds for subsequent transformations. In the second stage, thionation was performed using phosphorus pentasulfide or Lawesson's reagent, which ensured the formation of a thione functional center. The obtained heterodienes were used in hetero-Diels-Alder reactions with various dienophiles, including maleic anhydride, maleimides, acrolein, and norbornene, which allowed varying the structure of the products. The structures and stereochemistry of the synthesized compounds were confirmed using complex spectroscopic analysis (¹H, ¹³C, 2D NMR) and mass spectrometry (LC-MS). Biological screening was performed for activity against gram-positive and gram-negative bacteria and fungi, which allowed identifying the most promising molecules and drawing preliminary conclusions about the structure-activity relationship. The identified active compounds indicate the potential of this scaffold as a platform for the targeted search for new biologically active substances with high efficiency and selectivity.