Synthesis of Tacrine Analogues and Their Structure-Activity Relationships

Title: Synthesis of Tacrine Analogues and Their Structure-Activity Relationships

Volume: 7 Issue: 3

Author(s): G. R. Proctor and A. L. Harvey,

Affiliation:

Keywords: tacrine analogues, structure activity relationships, anthranilonitriles, cyclohexanone, acetylcholinesterase, butyrycholinesterase, cyanoketones, pharmacological effects, analogues, enzyme, torpedo californica, monohalogen derivatives, aminonitriles

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

Cite this article as:

Proctor R. G. and Harvey, L. A., Synthesis of Tacrine Analogues and Their Structure-Activity Relationships, Current Medicinal Chemistry 2000; 7 (3) . https://dx.doi.org/10.2174/0929867003375218