Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl, 3-acyl, and 3-carboxyhydrazido coumarin derivatives

Several 3-carbonyl (1e26), 3-acyl (27e52), and 3-carboxyhydrazido (53e58) coumarins have been synthesized in high yields (72e99%) and tested in vitro for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory activity. Different substituents on the coumarin nucleus were evaluated for their effect on biological activity and isoform selectivity. Substitution at position C7 of the 3-ethyl ester coumarin ring, or the introduction of a hydrazido substituent at C3, were important to obtain highly potent and selective hMAO-B inhibitors with IC50 values in the nanomolar range. Some derivatives were also submitted to a stability test and showed no chemical cleavage in vitro.