Abstract
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.