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

In this pilot study, a series of new 3,4-dihydroquinolin-2(1H)-one derivatives as potential dopamine receptor D(2) (D(2)R) modulators were synthesized and evaluated in vitro. The preliminary structure–activity relationship disclosed that compound 5e exhibited the highest D(2)R affinity among the new...

Descripción completa

Detalles Bibliográficos
Autores principales: Juza, Radomir, Stefkova, Kristyna, Dehaen, Wim, Randakova, Alena, Petrasek, Tomas, Vojtechova, Iveta, Kobrlova, Tereza, Pulkrabkova, Lenka, Muckova, Lubica, Mecava, Marko, Prchal, Lukas, Mezeiova, Eva, Musilek, Kamil, Soukup, Ondrej, Korabecny, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464836/
https://www.ncbi.nlm.nih.gov/pubmed/34572475
http://dx.doi.org/10.3390/biom11091262
Descripción
Sumario:In this pilot study, a series of new 3,4-dihydroquinolin-2(1H)-one derivatives as potential dopamine receptor D(2) (D(2)R) modulators were synthesized and evaluated in vitro. The preliminary structure–activity relationship disclosed that compound 5e exhibited the highest D(2)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(2)R in comparison with USC-D301.

Ejemplares similares