SYNTHESIS AND EVALUATION OF 5-AMINO-5,6,7,8-TETRAHYDROQUINOLINONES ASPOTENTIAL AGENTS FOR THE TREATMENT OF ALZHEIMERS-DISEASE

A series of 5-amino-5,6,7,8-tetrahydroquinolinones was designed and sy nthesized as acetylcholinesterase inhibitors. The compounds are relate d to hyperzine A, a naturally occurring cholinesterase inhibitor. They inhibit acetylcholinesterase in vitro, and many are active in vivo in reversing a scopolamine-induced impairment of 24 h memory in a passiv e avoidance paradigm. Although these compounds were designed as partia l structures of huperzine A, it is unlikely that they bind to the enzy me in a similar fashion, since they lack the unsaturated three-carbon bridge of huperzine A and both the quinolinone nitrogen and the amino group must be substituted in order to obtain good enzyme affinity.