Synthesis and In Vitro Evaluation of Novel Dopamine Receptor D<sub>2</sub> 3,4-dihydroquinolin-2(1<i>H</i>)-one Derivatives Related to Aripiprazole
Radomir Juza,
Kristyna Stefkova,
Wim Dehaen,
Alena Randakova,
Tomas Petrasek,
Iveta Vojtechova,
Tereza Kobrlova,
Lenka Pulkrabkova,
Lubica Muckova,
Marko Mecava,
Lukas Prchal,
Eva Mezeiova,
Kamil Musilek,
Ondrej Soukup,
Jan Korabecny
Affiliations
Radomir Juza
National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic
Kristyna Stefkova
National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic
Wim Dehaen
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
Alena Randakova
Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic
Tomas Petrasek
National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic
Iveta Vojtechova
National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic
Tereza Kobrlova
Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic
Lenka Pulkrabkova
Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic
Lubica Muckova
Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic
Marko Mecava
Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic
Lukas Prchal
Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic
Eva Mezeiova
National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic
Kamil Musilek
Department of Chemistry, University of Hradec Kralove, Rokitanskeho 62, 500 03 Hradec Kralove, Czech Republic
Ondrej Soukup
Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic
Jan Korabecny
National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic
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.
