Propargylamine and 2-butynamine were reported to serve as mechanism-based inactivators of the copper-containing bovine plasma amine oxidase (BPAO). Here, Ar- or Ar-X-extended analogs (X=NH, O, S) of these small molecules were synthesized and evaluated as BPAO inhibitors. 4-Phenoxy-2-butynamine and its aryl ring substituted analogs were found to be both good substrates and time- and concentration-dependent irreversible inactivators. At lower concentrations, loss of activity ceased within minutes, and the plateau data were translated into partition ratio values. For 4-phenoxy-2-butynamine, the turnover product was shown to be the expected corresponding aldehyde, 4-phenoxy-2-butynal, which could inactivate BPAO, but only slowly. The most potent analogs, 4-(4-methylphenoxy-, 4-(4-nitrophenoxy-, 4-(4-methoxyphenoxy-, and 4-(2-naphthyloxy)-2-butynamine, all exhibited 20 min IC(50) values of 20-25 microM at 30 degrees C, and partition ratios of 14-17. Overall, structure-inhibitory data revealed that rigidity and lateral branching reduced inhibitory potency. Although denatured samples of inactivated enzyme retained redox cycling competency of the quinone cofactor, loss of phenylhydrazine reactivity implies covalent blockage of the active site.