Synthesis and Evaluation of 5-Heteroarylidene-2-thioxo-4-thiazolidinones as PIM1 Kinase Inhibitors

The PIM kinases belong to the family of serine/threonine kinases which are involved in a wide range of cellular processes through multiple pathways that can lead to cell proliferation, apoptosis inhibition, migration, survival, and transcription. As such, inhibitors of PIM kinases are of pharmaceutical interest for their potential antitumor activity. A family of five known and seventeen new 5-heteroarylidene-2-thioxo-4-thiazolidinones were prepared through the Knoevenagel condensation of rhodanine with heteroarylaldehydes; the structure of 5i was elucidated by single-crystal X-ray diffraction analysis. The synthesized compounds were evaluated for the inhibition of PIM1 kinase. Two of the previously unknown inhibitors, 5p and 5u (IC50 = 2.60 ± 0.29 nM and 9.01 ± 0.67 nM respectively), were further evaluated for selectivity within the PIM family of kinases as well as against a select group of six other kinases.