title: Synthesis and in vitro evaluation of 7-methoxy-N-(pent-4-enyl)-1,2,3,4-tetrahydroacridin-9-amine-new tacrine derivate with cholinergic properties.
abstract: Cholinesterase inhibitors are, so far, the only successful strategy for the symptomatic treatment of Alzheimer's disease. Tacrine (THA) is a potent acetylcholinesterase inhibitor that was used in the treatment of Alzheimer's disease for a long time. However, the clinical use of THA was hampered by its low therapeutic index, short half-life and liver toxicity. 7-Methoxytacrine (7-MEOTA) is equally pharmacological active compound with lower toxicity compared to THA. In this Letter, the synthesis, biological activity and molecular modelling of elimination by-product isolated during synthesis of 7-MEOTA based bis-alkylene linked compound is described.
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Korabecny
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
authors.forename: Filip
authors.initials: F
authors.lastname: Zemek
authors.forename: Anna
authors.initials: A
authors.lastname: Horova
authors.forename: Ondrej
authors.initials: O
authors.lastname: Holas
authors.forename: Eugenie
authors.initials: E
authors.lastname: Nepovimova
authors.forename: Veronika
authors.initials: V
authors.lastname: Opletalova
authors.forename: Jana
authors.initials: J
authors.lastname: Hroudova
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Fisar
authors.forename: Young-Sik
authors.initials: YS
authors.lastname: Jung
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
mesh_terms: D000166:Acridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018678:Cholinergic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006207:Half-Life; D066298:In Vitro Techniques; D008958:Models, Molecular; D013619:Tacrine / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000166:Acridines; D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D013619:Tacrine