Abstract
2-(4-Chloro-2-cyano-2-phenylbutyl)aziridines were employed for the one-step stereoselective construction of both endo- and exo-2-aminomethyl-4-phenyl-1-azabicyclo[2.2.1]heptanes as new azaheterobicyclic scaffolds via a double LiAlH(4)-induced reductive cyclization protocol. Antiplasmodial assessment of these 1-azabicyclo[2.2.1]heptanes revealed moderate to good activities in the micromolar range, with the exo-isomers being the most promising structures. Furthermore, the proposed mode of action was supported by ligand docking studies, pointing to a strong binding interaction with the enzyme plasmepsin II.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aluminum Compounds / chemistry
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Antimalarials / chemical synthesis*
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Antimalarials / chemistry
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Antimalarials / pharmacology*
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Aziridines / chemistry*
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Bridged Bicyclo Compounds / chemical synthesis
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Bridged Bicyclo Compounds / chemistry
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Bridged Bicyclo Compounds / pharmacology
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Cyclization
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Heptanes / chemical synthesis*
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Heptanes / chemistry
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Heptanes / pharmacology*
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Humans
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Ligands
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Lithium Compounds / chemistry
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Molecular Docking Simulation
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Aluminum Compounds
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Antimalarials
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Aziridines
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Bridged Bicyclo Compounds
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Heptanes
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Ligands
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Lithium Compounds
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bicyclo(2.2.1)heptene
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lithium aluminum hydride