Dimerization of an Inactive Fragment of Huperzine A Produces a Drug with Twice the Potency of the Natural Product

Abstract

Simultaneous binding to the catalytic and peripheral sites of acetylcholinesterase (AChE) is invoked to explain why the new drug (S,S)-(−)-3, in which two aminoquinolinone units are linked by a dodecamethylene tether, is more than twice as potent as the natural product huperzine A (−)-1 in the inhibition of AChE. In contrast aminoquinolinone (±)-2, which retains much of the functionality of (−)-1, inhibits AChE only very weakly. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2000/z14260_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.