10.1016/j.ejmech.2007.01.005
The study investigates the synthesis and biological activity of a series of novel 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinolin-6-alkanamides. These compounds were designed to interact with melatonin receptors, specifically the MT1 and MT2 subtypes, which play crucial roles in regulating circadian rhythms and other physiological functions. The researchers synthesized various derivatives with different alkyl and cycloalkyl moieties in the b-position of the alkanamido side chain to explore their effects on melatoninergic activity. The compounds were tested for their ability to activate pigment granule aggregation in Xenopus laevis melanophores and their binding affinity to the recombinant human MT1 and MT2 melatonin receptors. The study found that increasing the length of the spacer in the side chain led to decreased antagonistic activity, while the introduction of two methyl groups in the b-position induced agonist potency. The presence of bulkier b-substituents generally led to antagonism and notable MT2 subtype selectivity. The new N1eC7 annulated derivatives were found to be more potent than their N1eC2 annulated counterparts. These findings provide valuable insights into the structure-activity relationship of melatoninergic ligands and contribute to the development of more effective melatonin receptor modulators.
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