Potent, easily synthesized huperzine A-tacrine hybrid acetylcholinesterase inhibitors

Hybrid acetylcholinesterase inhibitors composed of a key fragment of huperzine A and an intact tacrine unit were prepared. The syntheses are quite direct, proceeding in a maximum of 4 linear steps from commercially available starting materials. The optimum hybrid inhibitor (+/-)-9g is 13-fold more potent than (-)-huperzine A, and 25-fold more potent than tacrine. (C) 1999 Elsevier Science Ltd. All rights reserved