80353-09-9Relevant articles and documents
Synthesis and monoamine oxidase B catalyzed oxidation of C-4 heteroaromatic substituted 1,2,3,6-tetrahydropyridine derivatives
Nimkar, Sandeep K.,Anderson, Andrea H.,Rimoldi, John M.,Stanton, Matthew,Castagnoli, Kay P.,Mabic, Stephane,Wang,Castagnoli Jr., Neal
, p. 1013 - 1022 (2007/10/03)
The monoamine oxidase B (MAO-B) catalyzed oxidation of amines has been proposed to proceed via a polar pathway, an initial single-electron transfer pathway and an initial hydrogen atom transfer pathway. Results from previous studies on selected N-cyclopropyl-4-substituted-1,2,3,6-tetrahydropyridine derivatives have led us to consider a mechanism for these cyclic tertiary allylamines which may not necessarily involve the aminyl radical cation as required by an initial single-electron transfer step. The studies summarized in this paper were undertaken to explore further the structural features that determine the MAO-B substrate and/or inactivator properties of various 1,4-disubstituted tetrahydropyridine derivatives. We report here the results of our studies on the synthesis and MAO-B catalyzed oxidation of 1-methyl- and 1-cyclopropyl-1,2,3,6-tetrahydropyridine derivatives bearing a variety of heteroaromatic groups at C-4. All of the N-cyclopropyltetrahydropyridine analogs were time and concentration dependent inhibitors of MAO-B while all of the N-methyltetrahydropyridine analogs and the N-cyclopropyl-4-(1- methyl-2-pyrryl)tetrahydropyridine analog were substrates. The substrate properties (k(cat)/K(M)) covered a range of 6 to 1800 min-1 mM-1 while the range for the inactivator properties for which k(inact)/K(I) values could be obtained was 0.1-1.0 min-1 mM-1. The partition ratios for the N-cyclopropyl analogs varied from 4 to 17 except for the 4-(1-methyl-2- pyrryl) analog, which had a partition ratio of 400. These results are discussed in terms of the putative allylic radical intermediate and in the context of the hydrogen atom transfer and single-electron transfer based mechanisms.
