%0 Journal Article %J European Journal of Medicinal Chemistry %D 2016 %T 5-HT2 receptor affinity, docking studies and pharmacological evaluation of a series of 1,3-disubstituted thiourea derivatives %A Anna Bielenica %A Ewa Kedzierska %A Michal Kolinski %A Sebastian Kmiecik %A Andrzej Koliński %A Ferdinando Fiorino %A Beatrice Severino %A Elisa Magli %A Ilaria Rossi %A Paola Massarelli %A Anna E Kozioł %A Aleksandra Sawczenko %A Marta Struga %X A series of 10 thiourea derivatives have been synthesized by the reaction of aromatic amine with a substituted aryl (compounds 1-3, 6-8) and alkylphenyl (4, 5, 9, 10) isothiocyanates. Their in vitro and in vivo pharmacological properties were studied. Among the evaluated compounds, two displayed very high affinity for the 5-HT2A receptor (1 – 0.043 nM and 5 – 0.6 nM), being selective over the 5-HT2C receptor. Derivatives 3, 5, 9, 10 by 70- 89 % diminished L-5-HTP-induced head twitch episodes. Compounds 1 and 5 as the 5-HT2A receptor antagonists produced a dose-dependent decrease in the number of DOI-elicited HTR. Compounds 1-5 strongly reduced amphetamine-evoked hyperactivity in rodents. In another test, 1 and 2 caused hyperthermia in mice, whereas 9 and 10 led to hypothermia. Antinociceptive and anticonvulsant properties of selected derivatives were demonstrated. Molecular docking studies using a homology model of 5-HT2A revealed a significant role of hydrogen bonds between both thiourea NH groups and Asp155/Tyr370 residues, as well as Pi-Pi interaction with Phe339. %B European Journal of Medicinal Chemistry %V 116 %P 173–186 %G eng %N 30