Potent acetylcholinesterase inhibitors: design, synthesis, and structure-activity relationships of bis-interacting ligands in the galanthamine series.
New galanthamine derivatives, especially bis-interacting ligands 3-5 and 7-9 were prepared in order to interact with the catalytic and the peripheral sites of acetylcholinesterase (AChE). The synthesis, the anticholinesterase activities, and the structure-activity relationships of bis-interacting ligands are reported. Compounds 4d-e were found to be more potent than galanthamine and tacrine in inhibiting AChE.
Mary
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Institut de Chimie des Substances Naturelles, C.N.R.S., Gif-sur-Yvette, France.
Renko
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DZ
Guillou
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Thal
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D000110:Acetylcholinesterase / Q000187:drug effects* / Q000378:metabolism; D001552:Benzazepines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D005702:Galantamine / Q000737:chemistry* / Q000031:analogs & derivatives; D010797:Phthalimides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C116521:9-dehydro-10-N-demethyl--10-N-(10'-phthalimidodecyl)galanthaminium; C116520:9-dehydro-10-N-demethyl-10-N-(8'-phthalimidooctyl)galanthaminium; D001552:Benzazepines; D002800:Cholinesterase Inhibitors; D010797:Phthalimides; D005702:Galantamine; D000110:Acetylcholinesterase