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ID: ALA1131362

Journal: Bioorg Med Chem Lett

Title: Synthesis and anticholinesterase activity of huperzine A analogues containing phenol and catechol replacements for the pyridone ring.

Authors: Campiani G, Kozikowski AP, Wang S, Ming L, Nacci V, Saxena A, Doctor BP.

Abstract: Based upon modeling results obtained using the crystal structure of huperzine A in complex with acetylcholinesterase (AChE), two novel analogues of this potent AChE inhibitor were designed with phenol or catechol rings replacing the pyridone ring. From the modeling studies, the catechol analogue appeared capable of replacing one of the crystallographic waters bridging huperzine with Tyr 130 and Glu 199 of AChE. The synthesis of these materials by use of a palladium catalyzed bicycloannulation strategy is detailed together with the results of AChE inhibition assays.

CiteXplore: 9871776

DOI: 10.1016/s0960-894x(98)00229-7