@article {473, title = {5-HT2 receptor affinity, docking studies and pharmacological evaluation of a series of 1,3-disubstituted thiourea derivatives}, journal = {European Journal of Medicinal Chemistry}, volume = {116}, year = {2016}, pages = {173{\textendash}186}, abstract = {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 {\textendash} 0.043 nM and 5 {\textendash} 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.}, author = {Anna Bielenica and Ewa Kedzierska and Michal Kolinski and Sebastian Kmiecik and Andrzej Koli{\'n}ski and Ferdinando Fiorino and Beatrice Severino and Elisa Magli and Ilaria Rossi and Paola Massarelli and Anna E Kozio{\l} and Aleksandra Sawczenko and Marta Struga} }