title: Novel tricyclic quinazolinimines and related tetracyclic nitrogen bridgehead compounds as cholinesterase inhibitors with selectivity towards butyrylcholinesterase.
abstract: Tetracyclic nitrogen bridgehead compounds, dibenzodiazecines and tricyclic quinazolinimines, in which the size of the alicyclic ring system and the length of the alkyl chain between the quinazolinimine moiety and a phenyl ring connected to the imine nitrogen atom were changed systematically, were synthesized and their ability to inhibit acetyl- and butyrylcholinesterase (AChE/BChE), respectively, was evaluated. Moderate and strong inhibitors of BChE--compared to galanthamine and rivastigmine--were identified, which show mixed affinities or are moderately or highly selective towards BChE, respectively.
authors.affiliation: Lehrstuhl für Pharmazeutische/Medizinische Chemie, Institut für Pharmazie, Friedrich-Schiller-Universität Jena, Philosophenweg 14, D-07743 Jena, Germany. m.decker@uni-jena.de
authors.forename: Michael
authors.initials: M
authors.lastname: Decker
authors.forename: Fabian
authors.initials: F
authors.lastname: Krauth
authors.forename: Jochen
authors.initials: J
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry* / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D007097:Imines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D015394:Molecular Structure; D017672:Nitrogen Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D002800:Cholinesterase Inhibitors; D007097:Imines; D017672:Nitrogen Compounds; D011799:Quinazolines; D002091:Butyrylcholinesterase