Abstract
Homobivalent dimers of quinazolinimines, which bridge the imine nitrogen atoms via a hepta- and an octamethylene spacer, with different ring sizes of the alicycles were synthesized from the corresponding quinazolinethiones. The resulting compounds show >100-fold increase of inhibitory activities compared to related monomeric compounds yielding low-nanomolar inhibitors. For heptamethylene dimers, mixed inhibition profiles were obtained, whereas for the octamethylene compounds selectivity toward butyrylcholinesterase (>180) can be achieved with an eight-membered alicycle.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholinesterase / chemistry*
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Butyrylcholinesterase / chemistry*
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Cholinesterase Inhibitors / chemical synthesis*
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Cholinesterase Inhibitors / chemistry
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Dimerization
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Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
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Heterocyclic Compounds, 4 or More Rings / chemistry
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Imines / chemical synthesis*
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Imines / chemistry
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Ligands
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Quinazolines / chemical synthesis*
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Quinazolines / chemistry
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Structure-Activity Relationship
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Tacrine / chemistry
Substances
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Cholinesterase Inhibitors
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Heterocyclic Compounds, 4 or More Rings
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Imines
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Ligands
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Quinazolines
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Tacrine
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Acetylcholinesterase
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Butyrylcholinesterase