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

Authors :: Juza R
Stefkova K
Dehaen W
Randakova A
Petrasek T
Vojtechova I
Kobrlova T
Pulkrabkova L
Muckova L
Mecava M
Prchal L
Mezeiova E
Musilek K
Soukup O
Korabecny J
Source :: Biomolecules [Biomolecules] 2021 Aug 24; Vol. 11 (9). Date of Electronic Publication: 2021 Aug 24.
Publication Year :: 2021
Abstract: In this pilot study, a series of new 3,4-dihydroquinolin-2(1 H )-one derivatives as potential dopamine receptor D <subscript>2</subscript> (D <subscript>2</subscript> R) modulators were synthesized and evaluated in vitro. The preliminary structure-activity relationship disclosed that compound 5e exhibited the highest D <subscript>2</subscript> R 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 D <subscript>2</subscript> R in comparison with USC-D301.

Subjects :: Animals
Aripiprazole pharmacology
Binding Sites
Blood-Brain Barrier drug effects
Blood-Brain Barrier pathology
CHO Cells
Cell Death
Central Nervous System drug effects
Cricetulus
Drug Design
Ligands
Models, Molecular
Quinolones chemistry
Quinolones pharmacology
Receptors, Dopamine D2 chemistry
Aripiprazole chemical synthesis
Quinolones chemical synthesis
Receptors, Dopamine D2 metabolism

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