title: Huprines for Alzheimer's disease drug development.
abstract: BACKGROUND
  So far, acetylcholinesterase (AChE) inhibitors have dominated the therapeutic arsenal for Alzheimer's disease. Although conceptually developed as symptomatic drugs, mounting evidence suggests that these compounds can positively modify the disease progression, which has spurred the development of novel classes of AChE inhibitors.
  
  
  OBJECTIVE
  This article reviews the development of novel classes of high affinity AChE inhibitors following a design strategy based on molecular hybridization by stepwise incorporation of different fragments of the known AChE inhibitors (-)-huperzine A and tacrine.
  
  
  METHODS
  This review covers the existing literature dealing with the design, synthesis and structural and pharmacological characterization of the title compounds.
  
  
  CONCLUSIONS
  Three novel classes of AChE inhibitors of increasing structural complexity and affinity have been developed, namely huprines, 13-amidohuprines and huprine-tacrine heterodimers. Particularly, huprines and huprine-tacrine heterodimers exhibit a unique profile encompassing both cholinergic and non-cholinergic disease-modifying effects and, thus, constitute promising anti-Alzheimer drug candidates.
authors.affiliation: Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia, and Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Av. Diagonal, 643, E-08028-Barcelona, Spain +34 934024533 ; +34 934035941 ; dmunoztorrero@ub.edu +34 934024536 ; +34 934035941 ; camps@ub.edu.
authors.forename: Diego
authors.initials: D
authors.lastname: Muñoz-Torrero
authors.forename: Pelayo
authors.initials: P
authors.lastname: Camps