Quinazolinone compounds are of interest in medicinal chemistry since they display a wide range of
biological properties. In the present study, a series of C6- and N1-substituted 3-methyl-3,4-dihydroquinazolin-2(1H)-one derivatives were synthesised and evaluated as inhibitors of recombinant human
monoamine oxidase (
MAO). Some of these
quinazolinones are structurally related to a series of
3,4-dihydro-2(1H)-quinolinone derivatives, which have previously been reported to act as specific inhibitors of
MAO-B. The results document that, among 37 compounds synthesised, seven displayed IC50 values < 1 µM for the inhibition of
MAO-B. The most potent
MAO-A inhibitor exhibits an IC50 value of 7.43 µM while the most potent
MAO-B inhibitor possesses an IC50 value of 0.269 µM. Good-potency
MAO inhibition was only observed among C6-substituted 3-methyl-3,4-dihydroquinazolin-2(1H)-one derivatives with N1-substitution yielding comparatively low-potency inhibition.
MAO-B-specific inhibitors such as some of the
quinazolinone compounds investigated here may act as leads for the design of
therapies for
neurodegenerative disorders such as
Parkinson's disease.