title: Synthesis and pharmacological evaluation of huprine-tacrine heterodimers: subnanomolar dual binding site acetylcholinesterase inhibitors.
abstract: A series of huprine-tacrine heterodimers has been developed by connection of huprine Y, a compound with one of the highest affinities for the active site of acetylcholinesterase yet reported, with tacrine, a compound with known affinity for the peripheral site of the enzyme, through a linker of appropriate length to allow simultaneous interaction with both binding sites. These compounds exhibit human acetylcholinesterase and butyrylcholinesterase inhibitory activities with IC(50) values in the subnanomolar and low nanomolar range, respectively.
authors.affiliation: Laboratori de Química Farmacèutica, Facultat de Farmàcia, Universitat de Barcelona, Av. Diagonal 643, E-08028, Barcelona, Spain. camps@ub.edu
authors.forename: Pelayo
authors.initials: P
authors.lastname: Camps
authors.forename: Xavier
authors.initials: X
authors.lastname: Formosa
authors.forename: Diego
authors.initials: D
authors.lastname: Muñoz-Torrero
authors.forename: Julien
authors.initials: J
authors.lastname: Petrignet
authors.forename: Albert
authors.initials: A
authors.lastname: Badia
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Clos
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry; D002417:Cattle; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; C404518:huprine X; C404519:huprine Y; D013619:Tacrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase