Novel tricyclic quinazolinimines and related tetracyclic nitrogen bridgehead compounds as cholinesterase inhibitors with selectivity towards butyrylcholinesterase.
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.
Decker
Michael
M
Lehrstuhl für Pharmazeutische/Medizinische Chemie, Institut für Pharmazie, Friedrich-Schiller-Universität Jena, Philosophenweg 14, D-07743 Jena, Germany. m.decker@uni-jena.de
Krauth
Fabian
F
Lehmann
Jochen
J
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
D002800:Cholinesterase Inhibitors; D007097:Imines; D017672:Nitrogen Compounds; D011799:Quinazolines; D002091:Butyrylcholinesterase