Synthesis of Coumarin-Isoxazole-Pyridine Hybrids with Possible Biological Activity [1]

The 1,3 -dipolar cycloaddition reaction of nitrile oxides, prepared in situ from pyridine aldehyde oximes, with propargyloxy- or propargylaminocoumarins afforded the corresponding new 3,5-disubstituted isoxazoles in moderate to good yields. As oxidants for the formation of nitrile oxides utilized (diacetoxyiodo)benzene (PIDA) at room temperature or under microwave irradiation or tert-butyl nitrite (TBN) under reflux. Preliminary in vitro screening tests for some biological activities of the new compounds have been performed. Compounds 12b and 13a are potent LOX inhibitors with IC50 5 μΜ and 10 μΜ, respectively, while hybrids 12b and 13a exhibit moderate to low anticancer activities on Hela, HT-29, and H1437 cancer cells.