Assessment of Structural Requirements for the Monoamine Oxidase-B-Catalyzed Oxidation of 1,4-Disubstituted-1,2,3,6-tetrahydropyridine Derivatives Related to the Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
journal contributionposted on 13.09.1996, 00:00 by Stéphane Mabic, Neal Castagnoli
The monoamine oxidase B (MAO-B) substrate properties and distance measurements along the N1−C4 axis of 38 1,4-disubstituted-1,2,3,6-tetrahydropyridine derivatives, including seven newly synthesized MPTP analogs, were used to define the maximum size that can be accommodated by the MAO-B active site. Only those compounds measuring less than 12 Å displayed significant MAO-B substrate properties. The behavior of various 4-substituted-1-cyclopropyltetrahydropyridine analogs also is discussed in terms of this N1−C4 distance parameter in an effort to understand factors which contribute to their substrate vs inactivator properties. We conclude that this distance parameter will predict the majority of substrates vs nonsubstrates with this class of compound.