title: Synthesis, in vitro pharmacology, and molecular modeling of syn-huprines as acetylcholinesterase inhibitors.
abstract: Two 12-amino-6,7,8,11-tetrahydro-7,11-methanocycloocta[b]quinoline derivatives [9-Me(Et)] (syn-huprines) have been obtained by condensation of known 7-alkylbicyclo[3.3.1]non-6-en-3-ones with 2-(trifluoromethyl)aniline, followed by basic cyclization of the resulting imine, and chromatographic separation of the regioisomeric mixture of products, thus obtained. The new (+/-)-syn-huprines were shown to be slightly less active bovine or human acetylcholinesterase inhibitors than the corresponding anti-derivatives. Molecular modeling simulations allow us to explain the differences in inhibitory activity of these compounds on the basis of an inverse solvation effect.
authors.affiliation: Laboratori de Química Farmacèutica, Facultat de Farmàcia, Universitat de Barcelona, Av. Diagonal 643, E-08028, Barcelona, Spain. camps@farmacia.far.ub.es
authors.forename: P
authors.initials: P
authors.lastname: Camps
authors.forename: E
authors.initials: E
authors.lastname: Gómez
authors.forename: D
authors.initials: D
authors.lastname: Muñoz-Torrero
authors.forename: A
authors.initials: A
authors.lastname: Badia
authors.forename: N M
authors.initials: NM
authors.lastname: Vivas
authors.forename: X
authors.initials: X
authors.lastname: Barril
authors.forename: M
authors.initials: M
authors.lastname: Orozco
authors.forename: F J
authors.initials: FJ
authors.lastname: Luque
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D002417:Cattle; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D000110:Acetylcholinesterase