1-Methyl-3-pyrrolines and 2-methylisoindolines: new classes of cyclic tertiary amine monoamine oxidase B substrates.

Both 1-methyl-3-pyrrolines and 2-methylisoindolines are substrates for MAO-B with Vmax/Km values ranging from 200 to 2000 min-1 mM-1 at 37 degrees C. These compounds represent new classes of cyclic tertiary amine substrates for this flavoenzyme. The only other known cyclic amines that are MAO-B substrates are 1,4-disubstituted 1,2,3,6-tetrahydropyridinyl derivatives. The presence of an allylic (benzylic) amino functionality in all of these compounds may be linked to their substrate properties since related piperidinyl and pyrrolidinyl analogs are stable in the presence of MAO-B. This paper discusses energetic and geometric features of these compounds in relationship to their substrate properties and in anticipation of their utility to probe the active site of this flavoenzyme.