4-Substituted cubylcarbinylamines: A new class of mechanism-based monoamine oxidase B inactivators

Cubylcarbinylamine (1a), (4-cyclopropylcubyl)carbinylamine (1b), and (4- phenylcubyl)carbinylamine (1c) were synthesized and shown to be time- dependent, irreversible inactivators of monoamine oxidase B (MAO B). Substrate protects the enzyme from inactivation, but β-mercaptoethanol does not, suggesting that these compounds are mechanism-based inactivators. All three compounds were also substrates for MAO B with partition ratios ranging from 152 to 536. The 4-substituted analogues were mere potent inactivators than the unsubstituted analogue, indicating a benefit to 4-substitution in this class of inactivators.