title: Synthesis and evaluation of 5-amino-5,6,7,8-tetrahydroquinolinones as potential agents for the treatment of Alzheimer's disease.
abstract: A series of 5-amino-5,6,7,8-tetrahydroquinolinones was designed and synthesized as acetylcholinesterase inhibitors. The compounds are related to hyperzine A, a naturally occurring cholinesterase inhibitor. They inhibit acetylcholinesterase in vitro, and many are active in vivo in reversing a scopolamine-induced impairment of 24 h memory in a passive avoidance paradigm. Although these compounds were designed as partial structures of huperzine A, it is unlikely that they bind to the enzyme in a similar fashion, since they lack the unsaturated three-carbon bridge of huperzine A and both the quinolinone nitrogen and the amino group must be substituted in order to obtain good enzyme affinity.
authors.affiliation: Department of Medicinal Chemistry, Hoechst-Roussel Pharmaceuticals, Inc, Somerville, New Jersey 08876, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Fink
authors.forename: G M
authors.initials: GM
authors.lastname: Bores
authors.forename: R C
authors.initials: RC
authors.lastname: Effland
authors.forename: F P
authors.initials: FP
authors.lastname: Huger
authors.forename: B E
authors.initials: BE
authors.lastname: Kurys
authors.forename: D K
authors.initials: DK
authors.lastname: Rush
authors.forename: D E
authors.initials: DE
authors.lastname: Selk
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects; D000470:Alkaloids; D000544:Alzheimer Disease / Q000188:drug therapy*; D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D003704:Dementia / Q000139:chemically induced / Q000188:drug therapy; D004341:Drug Evaluation; D008297:Male; D051379:Mice; D051381:Rats; D012601:Scopolamine / Q000494:pharmacology; D012717:Sesquiterpenes / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D012717:Sesquiterpenes; C050426:huperzine A; D012601:Scopolamine; D000110:Acetylcholinesterase