Synthesis, in vitro pharmacology, and molecular modeling of syn-huprines as acetylcholinesterase inhibitors

TitleSynthesis, in vitro pharmacology, and molecular modeling of syn-huprines as acetylcholinesterase inhibitors
Publication TypeJournal Article
Year of Publication2001
AuthorsCamps, P, Gomez E, Munoz-Torrero D, Badia A, Vivas NM, Barril X, Orozco M, Luque FJ
JournalJournal of medicinal chemistry
Volume44
Issue26
Pagination4733 - 4736
Date Published2001/12/20/
KeywordsAcetylcholinesterase/metabolism; Aminoquinolines/chemical synthesis/chemistry; Animals; Cattle; Cholinesterase Inhibitors/chemical synthesis/chemistry; Heterocyclic Compounds with 4 or More Rings/chemical synthesis/chemistry; Humans; Models, Molecular; Stereoisomerism; Structure-Activity Relationship
AbstractTwo 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.