Synthesis of Tacrine Analogues and Their Structure-Activity Relationships

摘要

Three man synthetic routes to analogues of tacrine are described:nreaction of anthranilonitriles with cyclohexanone and other ketones, reactionnof various anilines with a-cyanoketones, and reactions involving anilines andncyclic b-ketoesters. Although tacrine has a wide range of pharmacological effects, it is bestnknown as an inhibitor of cholinesterase enzymes. Many of the analogues that have been madenhave not been tested against acetylcholinesterase or butyrylcholinesterase activity.nConsequently, there is limited information from which a detailed understanding of structure-nactivity relationships can be derived. However, some halogenated derivatives are not only morenpotent acetylcholinesterase inhibitors than tacrine, they are also more selective fornacetylcholinesterase than for butyrylcholinesterase.