Selective inhibition of monoamine oxidase B by aminoethyl substituted benzyl ethers

Aminoethyl 3-chlorobenzyl ether was shown previously (Ding, C.Z. and Silver man, R.B. (1993). Bioorg. Meal. Chern. Lett., 3, 2077-2078) to be a potent and selective time-dependent, but reversible inhibitor of monoamine oxidase B (MAO B). Based on this result, a series of novel aminoethyl substituted benzyl ethers was synthesized and the compounds were examined as potential inhibitors of both isozymic forms of MAO. Each compound in the series inhib its both MAO A and MAO B competitively, and IC50 values for each compound w ere determined. In general, the B isozyme is much more sensitive to these i nhibitors than the A isozyme (except for the o- and p-substituted nitro ana logues), in some cases by more than two orders of magnitude. The selectivit y in favor of MAO B inhibition is relatively high for all of the meta-subst ituted analogues and quite low for all of the ortho-substituted analogues. Having the substituent at the ortho-position is most favorable for MAO A in hibition. With MAO B the meta-analogues were, in general, more potent than the corresponding ortho- and para-analogues with respect to their reversibl e binding constants. The meta-iodo analogue is the most potent analogue.