New derivatives of 4,6-dimethylisoxazolo[3,4-b]pyridin-3(1H)-one: synthesis, tautomerism, electronic structure and antibacterial activity

The electronic structure and prototropic tautomerism of 4,6-dimethylisoxazolo[3,4-b]pyridin-3(1H)-one (1) were studied theoretically with use of the B3LYP/6-31G* and omega B97X-D/6-31G* density functional methods and SM8 (H2O, DMF) solvation models. Compound 1, which is a weak acid with a pK(a) of 6.9, undergoes regioselective alkylation and sulfonylation under basic reaction conditions to give a series of N1-substituted products 2a-i. Later compounds were evaluated in vitro for antibacterial activity with the use of 68 strains of aerobic and anaerobic bacteria, including 12 reference strains.