SYNTHESIS AND ANTICHOLINESTERASE ACTIVITY OF HUPERZINE-A ANALOGS CONTAINING PHENOL AND CATECHOL REPLACEMENTS FOR THE PYRIDONE RING

Authors
CAMPIANI G KOZIKOWSKI AP WANG SM MING L NACCI V SAXENA A DOCTOR BP
Citation
G. Campiani et al., SYNTHESIS AND ANTICHOLINESTERASE ACTIVITY OF HUPERZINE-A ANALOGS CONTAINING PHENOL AND CATECHOL REPLACEMENTS FOR THE PYRIDONE RING, Bioorganic & medicinal chemistry letters, 8(11), 1998, pp. 1413-1418
Citations number
26
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
8
Issue
11
Year of publication
1998
Pages
1413 - 1418
Database
ISI
SICI code
0960-894X(1998)8:11<1413:SAAAOH>2.0.ZU;2-P
Abstract
Based upon modeling results obtained using the crystal structure of hu perzine A in complex with acetylcholinesterase (AChE), two novel analo gues of this potent AChE inhibitor were designed with phenol or catech ol rings replacing the pyridone ring. From the modeling studies, the c atechol analogue appeared capable of replacing one of the crystallogra phic waters bridging huperzine with Tyr 130 and Glu 199 of AChE. The s ynthesis of these materials by use of a palladium catalyzed bicycloann ulation strategy is detailed together with the results of AChE inhibit ion assays. (C) 1998 Elsevier Science Ltd. All rights reserved.