ACETYLENIC AND ALLENIC DERIVATIVES OF 2-(5-METHOXYINDOLYL)METHYLAMINE - SYNTHESIS AND EVALUATION AS SELECTIVE INHIBITORS OF THE MONOAMINE OXIDASE-A AND OXIDASE-B

A series of acetylenic and allenic derivatives of 2-(5-methoxyindolyl)methylamine has been synthesized. The new compounds were studied as inhibitors of the A and B forms of the mitochondrial monoamine oxidase (MAO) from bovine brain, using 14C-tyramine as the substrate and clorgyline and l-deprenyl as references. All the studied compounds were MAO inhibitors. However, these compounds either did not show selectivity (compounds 3a-3d, 4c, 4e, 4m and 4o) or they were selective for MAO-A (compounds 4a, 4b, 4d, 4f-4l, 4n and 4p). Some of the compounds showed a similar inhibitory potency for MAO-A and lower for MAO-B than clorgyline and the higher selectivity for MAO-A was about 2.5 times that of clorgyline. Selectivity was shown only by acetylenic and allenic potent inhibitors, but no simple relationship between inhibitory potency and selectivity was found. © 1990.