Ceramidonines, Fused 3,9‐Diazaperylenes, and Related Compounds: From Synthesis to Physicochemical Properties and Evaluation as Inhibitors of PIM Kinases

Substituted ceramidonines were synthesized by cyclization of 1‐(arylamino)anthraquinones under acidic conditions. These key intermediates were prepared either by copper‐promoted N ‐arylation of 1‐aminoanthraquinone with iodoarenes or, more efficiently, by palladium‐catalyzed N ‐arylation of anilines using 1‐chloroanthraquinone. The latter route was then extended to the synthesis of 1‐(arylamino)xanthones and ‐thioxanthones, which were subsequently cyclized to form (thio)chromeno[2,3,4‐ kl ]acridines. Taking the strategy further, stepwise N ‐arylation of 1,5‐dichloroanthraquinone followed by cyclization afforded symmetrical and unsymmetrical benzo‐fused 3,9‐diazaperylenes. Electrochemical studies indicated that substituted ceramidonines are more readily reduced than anthraquinone, based on their first and second reduction potentials. Their photophysical behavior, however, proved remarkably diverse: Although some derivatives exhibited notable fluorescence, others functioned as photosensitizers, depending on the nature of their substituents. Thiochromeno‐ and chromeno[2,3,4‐ kl ]acridines showed only moderate fluorescence, whereas benzo[1,2,3‐ kl :4,5,6‐ k’l’ ]diacridines displayed stronger emission and promising singlet‐oxygen quantum yields. A symmetric indolo‐fused 3,9‐diazaperylene—already known for its high fluorescence—also delivered a significant two‐photon absorption cross section of 118 GM. Finally, biological assays revealed that 2‐hydroxyceramidonine and a helicoidal benzothieno analog of ceramidonine are promising inhibitors of PIM kinase, achieving IC 50 values below the micromolar range.