Flexible N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analog: synthesis and monoamine oxidase catalyzed bioactivation
| Autor: | R. J. Boudreau, R. P. Remmel, A. Freshler, R. H. Michelson, Simon M. N. Efange, Aloke K. Dutta |
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| Rok vydání: | 1990 |
| Předmět: |
Monoamine Oxidase Inhibitors
Chemical Phenomena Stereochemistry Monoamine oxidase Molecular Conformation Substituent Substrate Specificity Enzyme catalysis Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Animals Methylene Binding site Monoamine Oxidase Biotransformation Binding Sites Molecular Structure Bicyclic molecule Aryl MPTP Brain Rats Inbred Strains Mitochondria Rats Chemistry Kinetics Pargyline chemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Molecular Medicine |
| Zdroj: | Journal of Medicinal Chemistry. 33:3133-3138 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00174a007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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