Campiani G, Kozikowski A P, Wang S, Ming L, Nacci V, Saxena A, Doctor B P
Dipartimento Farmaco Chimico Tecnologico, Siena University, Italy.
Bioorg Med Chem Lett. 1998 Jun 2;8(11):1413-8. doi: 10.1016/s0960-894x(98)00229-7.
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.
基于使用石杉碱甲与乙酰胆碱酯酶（AChE）复合物的晶体结构获得的建模结果，设计了这种强效AChE抑制剂的两种新型类似物，用苯酚或儿茶酚环取代吡啶酮环。从建模研究来看，儿茶酚类似物似乎能够取代连接石杉碱与AChE的Tyr 130和Glu 199的一个结晶水。详细介绍了使用钯催化双环化策略合成这些材料以及AChE抑制试验的结果。
