Synthesis and pharmacological evaluation of novel agomelatine and melatonin analogues with structures combining the features generating MT1 selectivity, namely the bulky hydrophobic ether moiety and the difluoroacetamide group, is reported. The dimeric agomelatine analogue linked by a three methylene spacer displayed the best affinity (Ki = 1.2 nM) and selectivity (7-fold) toward MT1 receptors.