Document Report Card

ID: ALA1125023

Journal: J Med Chem

Title: Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogues: synthesis and monoamine oxidase catalyzed bioactivation.

Authors: Efange SM, Michelson RH, Remmel RP, Boudreau RJ, Dutta AK, Freshler A.

Abstract: Eighteen analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and evaluated as substrates of monoamine oxidase. In general, the flexible analogues, characterized by the presence of a methylene (or ethylene) bridge between the aryl/heteroaryl and tetrahydropyridyl moieties, were better substrates of the enzyme than the conformationally restricted MPTP. It is suggested that the increased oxidative activity of these flexible analogues reflects enhanced binding due to the ability of the C-4-aryl/heteroaryl substituent to gain access to a hydrophobic pocket within the substrate binding site.

CiteXplore: 2258899

DOI: 10.1021/jm00174a007