Dimeric and Hybrid Anti-Alzheimer Drug Candidates

D.      Munoz-Torrero; P.      Camps

doi:10.2174/092986706775527974

Abstract

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 Alzheimers 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 Alzheimers disease. Herein, we review from a structural point of view the main classes of dimeric or hybrid compounds developed for the treatment of Alzheimers disease, along with the pharmacological profile of the most active compounds.

Keywords: N-benzylpiperidines, homodimers, heterodimers, dual-site binding, extended binding, dual action

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