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Dimerization of an Inactive Fragment of Huperzine A Produces a Drug with Twice the Potency of the Natural Product
Author(s) -
Carlier Paul R.,
Du DaMing,
Han YiFan,
Liu Jing,
Perola Emanuele,
Williams Ian D.,
Pang YuanPing
Publication year - 2000
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/(sici)1521-3773(20000515)39:10<1775::aid-anie1775>3.0.co;2-q
Subject(s) - huperzine a , natural product , potency , acetylcholinesterase , aché , chemistry , stereochemistry , fragment (logic) , product (mathematics) , pharmacology , biochemistry , in vitro , enzyme , computer science , biology , mathematics , algorithm , geometry
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.