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

被引：29

作者：

FINK, DM ^{[1
]}

BORES, GM ^{[1
]}

EFFLAND, RC ^{[1
]}

HUGER, FP ^{[1
]}

KURYS, BE ^{[1
]}

RUSH, DK ^{[1
]}

SELK, DE ^{[1
]}

机构：

[1] HOECHST ROUSSEL PHARMACEUT PROPRIETARY LTD, DEPT BIOL RES, SOMERVILLE, NJ 08876 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 18期

关键词：

D O I：

10.1021/jm00018a025

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 5-amino-5,6,7,8-tetrahydroquinolinones was designed and synthesized as acetylcholinesterase inhibitors. The compounds are related 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 passive avoidance paradigm. Although these compounds were designed as partial structures of huperzine A, it is unlikely that they bind to the enzyme 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.

引用

页码：3645 / 3651

页数：7