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

0546462 - FGÚ 2022 RIV CH eng J - Journal Article
Jůza, R. - Štefková, K. - Dehaen, W. - Randáková, Alena - Petrásek, T. - Vojtěchová, I. - Kobrlová, T. - Pulkrábková, L. - Mucková, L. - Mecava, M. - Prchal, L. - Mezeiová, E. - Musílek, K. - Soukup, O. - Korábečný, J.
Synthesis and In Vitro Evaluation of Novel Dopamine Receptor D-2 3,4-dihydroquinolin-2(1H)-one Derivatives Related to Aripiprazole.
Biomolecules. Roč. 11, č. 9 (2021), č. článku 1262. E-ISSN 2218-273X
Institutional support: RVO:67985823
Keywords : aripiprazole * dopamine receptor * blood–brain barrier * molecular modeling studies * schizophrenia
OECD category: Pharmacology and pharmacy
Impact factor: 6.064, year: 2021
Method of publishing: Open access
https://www.mdpi.com/2218-273X/11/9/1262

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.
Permanent Link: http://hdl.handle.net/11104/0322976