Studies on the monoamine oxidase-B-catalyzed biotransformation of 4-azaaryl-1-methyl-1,2,3,6-tetrahydropyridine derivatives

The substrate properties of a series of 1-methyl-4-phenyl-1,2,3,6-tetrahydr opyridinyl (MPTP) analogues in which the C-4 phenyl group has been replaced with various 4-azaaryl moieties have been examined in an effort to evaluat e the contribution of electronic, polar, and steric parameters to the MAO-B -catalyzed oxidation of this type of cyclic tertiary allylamine to the corr esponding dihydropyridinium metabolite. No significant correlation could be found nit-h the calculated energy of the C-H bond undergoing cleavage. A g eneral trend, however, was observed between the magnitude of the log P valu e with the magnitude of k(cat)/K-m. The results indicate that the placement of a polar nitrogen atom in the space occupied by the phenyl group of MPTP leads to a dramatic decrease in substrate properties. Enhanced substrate p roperties, however, were observed when benzoazaarenes replaced the correspo nding five-membered azaarenes. These results are consistent with our previo usly published molecular model of the active site of MAO-B.