Institute of Pharmacy and Food Chemistry, Pharmaceutical Chemistry, University of Würzburg, Germany.
Arch Pharm (Weinheim). 2011 Oct;344(10):666-74. doi: 10.1002/ardp.201100125. Epub 2011 Sep 2.
A series of melatonin analogs obtained by the replacement of the ether methyl group with larger arylalkyl and aryloxyalkyl substituents was prepared in order to probe the melatonin receptors for MT(1) -selectivity. The most MT(1) -selective agents 11 and 15 were substituted with a Ph(CH(2) )(3) or a PhO(CH(2) )(3) group. Compounds 11 and 15 displayed 11.5-fold and 11-fold higher affinity for the MT(1) receptors than for the MT(2) subtype. Interestingly, in our binding assay 11 and 15 have shown considerably higher MT(1) -affinity and selectivity than the reference ligand, the dimeric agomelatine 1a.
为了探究褪黑素受体对 MT(1) 的选择性，我们用较大的芳基烷基和芳氧基烷基取代物替换了醚甲基，得到了一系列褪黑素类似物。最具 MT(1) 选择性的化合物 11 和 15 分别用 Ph(CH(2) )(3) 或 PhO(CH(2) )(3) 取代。化合物 11 和 15 对 MT(1) 受体的亲和力比对 MT(2) 亚型的亲和力高 11.5 倍和 11 倍。有趣的是，在我们的结合实验中，11 和 15 对 MT(1) 的亲和力和选择性明显高于参考配体二聚体 agomelatine 1a。
