Dimeric and hybrid anti-Alzheimer drug candidates.
In the last decade much attention has been paid to the development of metabolically non-reversible dimeric or hybrid compounds, which combine two structural units of one or two lead compounds of interest for the treatment of Alzheimer's disease. As a consequence of their capability to simultaneously interact with two binding sites of the same biological target (the enzyme acetylcholinesterase in most cases), to expand their interaction in the main binding site of the target molecule, or to interact with two different biological targets of interest in the pathogenesis of the disease, these dimeric or hybrid compounds exhibit an improved pharmacological profile including high affinity interactions, additional non conventional actions or complementary actions, what makes them potential drug candidates for the treatment of Alzheimer's disease. Herein, we review from a structural point of view the main classes of dimeric or hybrid compounds developed for the treatment of Alzheimer's disease, along with the pharmacological profile of the most active compounds.
Laboratori de Química Farmaceutica, Unitat Associada al CSIC, Facultat de Farmacia, Universitat de Barcelona, Av. Diagonal 643, E-08028 Barcelona, Spain. dmunoztorrero@ub.edu
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D000544:Alzheimer Disease / Q000188:drug therapy*; D000634:Aminoquinolines / Q000737:chemistry; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry; D006801:Humans; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000031:analogs & derivatives / Q000737:chemistry
D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; C404518:huprine X; D013619:Tacrine