Synthesis and pharmacological evaluation of pentacyclic 6a,7-dihydrodiindole and 2,3-dihydrodiindole derivatives as novel melatoninergic ligands Original Research Article

The synthesis of novel melatonin analogues 3a and 4a–c designed as melatonin receptor ligands is described. Among the newly synthesized ligands, 2-((S)-2-hydroxymethylindolin-1-ylmethyl)-melatonin 4b displayed the highest affinity for MT1 receptors (Ki = 9.8 nM) and for MT2 subtype (Ki = 7.8 nM), whereas the rigid pentacyclic ligand 3 showed the highest selectivity towards the MT2 receptor subtype (Ki = 319.3 nM for MT1 and Ki = 65.2 nM for MT2).