Design, Synthesis and Computational Insight of Isolated and Thiophene fused 2H-Pyran-2-ones as PPAR-γ Agonist

초록

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a well-known member of the PPAR family and a potential target for the treatment of various disorders. Herein, we present the design and synthesis of various 6-aryl-4-sec.amino-2-oxo-2H-pyran-3-carbonitrile derivatives and functionalized thieno[3,2-c]pyran-2-ones, derived from ketene dithioacetal. Then all the synthesized compounds were docked for their activity as PPAR-gamma to predict the binding mechanism and affinities regarding rosiglitazone and muraglitazar. Our studies revealed that three compounds 10 e, 10 f, and 10 h showed significant binding affinities, with energy ranges comparable to standard drugs rosiglitazone and muraglitazar. The docking conformation studies revealed that the selected compounds nicely interact with PPAR-gamma in the ligand binding domain with positive predictive values. We also performed molecular dynamics of the most potent compounds to validate the result. Our results indicate that these novel compounds are potential PPAR-gamma ligands, offering new possibilities for therapeutic applications. This study underscores the potential of these synthesized compounds in the development of novel PPAR-gamma agonists.

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