Acetylenic and allenic derivatives of 2-(5-methoxy-1-methylindolyl) alkylamines: Synthesis and evaluation as selective inhibitors of the monoamine oxidases A and B

Abstract

We report the synthesis and in vitro studies as MAO-A and MAO-B inhibitors of a new series of 2-(5-methoxy-1-methylindolyl)alkylamines, including 2-(5-methoxy-1-methylindolyl)amine 9 and its N-methyl derivative 10, 1-[2-(5-methoxy-1-methylindolyl)]ethylamine 1 and its N-methyl derivative 2 and 3-[2-(5-methoxy-1-methylindolyl)propylamine 11 and its N-methyl derivative 12, so as some of the N-(2-propynyl), N-(2,3-butadienyl) and N-(2-butynyl) derivatives of 1, 2, 11 and 12 (compounds 3–8 and 13–18). All compounds were found to inhibit both MAO-A and MAO-B. Comparison with a previous series of 2-(5-methoxy-1-methylindolyl)methylamine derivatives ( A1–A9) shows that in the new series, the inhibitory potency towards MAO-A generally decreases, whereas the inhibitory potency towards MAO-B generally increases, resulting in a loss of the selectivity for MAO-A seen in the reference compounds A1–A9. Structure-activity relationships are discussed.