Synthesis of Some Novel Norbornene-Fused Pyridazines as Potent Inhibitors of Carbonic Anhydrase and Acetylcholinesterase

The reaction of benzocyclic norbornene derivatives with tetrazines provided the 1,3-dihydropyridazine derivatives as a single product. The dihydropyridazine derivatives have been dehydrogenated with phenyliodine bis(trifluoroacetate) to yield the corresponding pyridazines in a high yield. Two stable diazines, primary product of corresponding 1,4-dihydropyridazine, were also isolated. Structures were then determined by H-1-NMR, and C-13-NMR beside to elemental analyses. The novel pyridazine derivatives (8-9) efficiently inhibited the cytosolic human carbonic anhydrase isoenzymes I and II (hCA I and II). In addition, these novel pyridazine derivatives (8-9) were evaluated for their in vitro acetylcholinesterase inhibitory activity. Ligand-receptor interactions are tested using molecular docking simulations. Obtained docking scores are in good agreement with in vitro results.