Synthesis and In Vitro Evaluation of Novel Dopamine Receptor D-2 3,4-dihydroquinolin-2(1H)-one Derivatives Related to Aripiprazole

Jůza, Radomír; Stefkova, Kristyna; Dehaen, Wim; Randakova, Alena; Petrasek, Tomas; Vojtechova, Iveta; Kobrlova, Tereza; Pulkrabkova, Lenka; Muckova, Lubica; Mecava, Marko; Prchal, Lukas; Mezeiova, Eva; Musílek, Kamil; Soukup, Ondrej; Korabecny, Jan

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Synthesis and In Vitro Evaluation of Novel Dopamine Receptor D-2 3,4-dihydroquinolin-2(1H)-one Derivatives Related to Aripiprazole

Jůza, Radomír; Stefkova, Kristyna; Dehaen, Wim; Randakova, Alena; Petrasek, Tomas; Vojtechova, Iveta; Kobrlova, Tereza; Pulkrabkova, Lenka; Muckova, Lubica; Mecava, Marko; Prchal, Lukas; Mezeiova, Eva; Musílek, Kamil; Soukup, Ondrej; Korabecny, Jan

URI: http://hdl.handle.net/20.500.12603/1305

Date: 2021

Résumé:

In this pilot study, a series of new 3,4-dihydroquinolin-2(1H)-one derivatives as potential dopamine receptor D-2 (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.

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