The monoamine oxidase inhibition properties of C6- and N1-substituted 3-methyl-3,4-dihydroquinazolin-2(1H)-one derivatives

Abstract

Abstract: 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. Graphical abstract: [Figure not available: see fulltext.].