G protein-coupled receptor binding and pharmacological evaluation of indole-derived thiourea compounds

Four 2-(1H-indol-3-yl)ethylthiourea derivatives were prepared by condensation of 2-(1H-indol-3-yl)ethanamine with the corresponding aryl/alkylisothiocyanates in a medium-polarity solvent. Their structures were confirmed by spectral techniques, and the molecular structure of 3 was determined by X-ray crystal analysis. For all derivatives, the binding affinities at the 5-HT_2A and 5-HT_2C receptors, as well as their functional activities at the 5-HT_1A and D₂ receptors, were determined. The arylthioureas 1 and 4 were the most active at the 5-HT_1A receptor, showing, at the same time, significant selectivity over the studied 5-HT₂ and D₂ receptor subtypes. The compounds were tested for their pharmacological activities within the central nervous system in relevant mouse models. The involvement of the serotonergic system in the activity of 1 and 4 was indicated. The antinociceptive action of 4 was linked to its anti-inflammatory activity.