4-SUBSTITUTED CUBYLCARBINYLAMINES - A NEW CLASS OF MECHANISM-BASED MONOAMINE-OXIDASE-B INACTIVATORS

Cubylcarbinylamine (la), (4-cyclopropylcubyl)carbinylamine (Ib), and ( 4-phenylcubyl)carbinylamine (ic) were synthesized and shown: to be tim e-dependent, irreversible inactivators of monoamine oxidase B (MAO B). Substrate protects the enzyme from inactivation, but beta-mercaptoeth anol does not, suggesting that these compounds are mechanism-based ina ctivators. All three compounds were also substrates for MAO B with par tition ratios ranging from 152 to 536. The 4-substituted analogues wer e more potent inactivators than the unsubstituted analogue, indicating a benefit to 4-substitution in this class of inactivators.