Inhibition of monoamine oxidase by indole and benzofuran derivatives

Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. A series of indole and benzofuran derivatives were synthesised and evaluated as inhibitors of the two MAO isoforms, MAO-A and MAO-B. In general, the derivatives were found to be selective MAO-B inhibitors with K(1) values in the nanoMolar (nM) to microMolar (mu M) concentration range. The most potent MAO-B inhibitor, 3,4-dichloro-N-(2-methyl-1H-indol-5-yl)benzamide, exhibited a K, value of 0 03 mu M and was 99 fold more selective for the B isoform. We conclude that these indole and benzofuran derivatives are promising reversible MAO-B inhibitors with a possible role in the treatment of neurodegenerative diseases such as Parkinson's disease (PD). (C) 2010 Elsevier Masson SAS. All rights reserved.