Synthesis, nicotinic acetylcholine receptor binding affinities, and molecular modeling of constrained epibatidine analogues.
Synthesis, nicotinic acetylcholine receptor binding affinities, and molecular modeling of constrained epibatidine analogues.
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受限的皮巴替丁类似物的合成、烟碱乙酰胆碱受体结合亲和力和分子建模。
DOI：
10.1021/jm025613w
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发表时间：
2003
影响因子：
7.3
通讯作者：
Kozikowski,AlanP
中科院分区：
文献类型：
--
作者：
Wei,Zhi-Liang;Petukhov,PavelA;Xiao,Yingxian;Tückmantel,Werner;George,Clifford;Kellar,KennethJ;Kozikowski,AlanP
Conformationally constrained epibatidine analogues20a,band23a,bwere synthesized using a radical cyclization as the key step. Radioligand displacement assays to six defined rat nicotinic acetylcholine receptor (nAChR) subtypes showed that20a,bbind with moderate affinities, while23a,bhave low affinities.20aexhibits higher affinity for the β2 containing subtype than for the β4 containing counterpart, while20bpossesses reversed selectivity. Modeling studies suggest that the spatial distribution of the ligand's atoms around the pharmacophore elements may control their nAChR subtype selectivity.
