In this pilot study, a series of new 3,4-dihydroquinolin-2(1H)-one derivatives as potential dopamine receptor D2 (D2R) modulators were synthesized and evaluated in vitro. The preliminary structure-activity relationship disclosed that compound 5e exhibited the highest D2R affinity among the newly synthesized compounds. In addition, 5e showed a very low cytotoxic profile and a high probability to cross the blood-brain barrier, which is important considering the observed affinity. However, molecular modelling simulation revealed completely different binding mode of 5e compared to USC-D301, which might be the culprit of the reduced affinity of 5e toward D2R in comparison with USC-D301.

Biomedical Research Centre University Hospital Hradec Kralove Sokolska 581 500 05 Hradec Kralove Czech Republic

CZ OPENSCREEN National Infrastructure for Chemical Biology Department of Informatics and Chemistry Faculty of Chemical Technology University of Chemistry and Technology Prague Technicka 5 166 28 Prague Czech Republic

Department of Chemistry University of Hradec Kralove Rokitanskeho 62 500 03 Hradec Kralove Czech Republic

Institute of Physiology Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic

National Institute of Mental Health Topolova 748 250 67 Klecany Czech Republic

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