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

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Attia MI, Witt-Enderby PA, Julius J

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

Bioorg Med Chem. 2008 Aug 15;16(16):7654-61. doi: 10.1016/j.bmc.2008.07.012. Epub 2008 Jul 10.

PubMed ID

18657980 [ View in PubMed

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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)).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Melatonin	Melatonin receptor type 1A	Ki (nM)	0.525	N/A	N/A	Details
Melatonin	Melatonin receptor type 1B	Ki (nM)	0.741	N/A	N/A	Details