Studies on the oxidation of 1,4-disubstituted-1,2,3,6-tetrahydropyridines.
Interest in the parkinsonian-inducing proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine has prompted extensive studies into the oxidative pathways mediating its bioactivation to the corresponding pyridinium species, a potent inhibitor of the mitochondrial electron transport chain. The initial step in the overall reaction is the two-electron ring alpha-carbon oxidation to give the 1-methyl-4-phenyl-2,3-dihydropyridinium species, a reaction that is catalyzed by monoamine oxidase B. The same a-carbon oxidation is catalyzed by members of the cytochrome P-450 family of oxidases. This paper examines the impact that various structural features of 1,4-disubstituted-1,2,3,6-tetrahydropyridinyl derivatives have on the oxidative fate of this class of compound.
Castagnoli
Neal
N
Department of Chemistry, Virginia Tech, Blacksburg 24061-0212, USA. ncastagnoli@chemserver.chem.vt.edu
Castagnoli
Kay
K
Magnin
Géraldine
G
Kuttab
Simon
S
Shang
Jackie
J
D000588:Amines / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism; D010084:Oxidation-Reduction; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics
D000588:Amines; D011725:Pyridines; D003577:Cytochrome P-450 Enzyme System; D008995:Monoamine Oxidase