Abstract
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 MT1-selectivity. The most MT1-selective agents 11 and 15 were substituted with a Ph(CH2)(3) or a PhO(CH2)(3) group. Compounds 11 and 15 displayed 11.5-fold and 11-fold higher affinity for the MT1 receptors than for the MT2 subtype. Interestingly, in our binding assay 11 and 15 have shown considerably higher MT1-affinity and selectivity than the reference ligand, the dimeric agomelatine 1a.