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

Abstract 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 MT 1 receptors ( K i  = 9.8 nM) and for MT 2 subtype ( K i  = 7.8 nM), whereas the rigid pentacyclic ligand 3 showed the highest selectivity towards the MT 2 receptor subtype ( K i  = 319.3 nM for MT 1 and K i  = 65.2 nM for MT 2 ).