Synthesis and In Vitro Evaluation of Novel Dopamine Receptor D2 3,4-dihydroquinolin-2(1 H)-one Derivatives Related to Aripiprazole

Biomolecules. 2021 Aug 24;11(9):1262. doi: 10.3390/biom11091262.

Abstract

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.

Keywords: aripiprazole; blood–brain barrier; dopamine receptor; molecular modeling studies; schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aripiprazole / chemical synthesis*
  • 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 / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology
  • Receptors, Dopamine D2 / chemistry
  • Receptors, Dopamine D2 / metabolism*

Substances

  • Ligands
  • Quinolones
  • Receptors, Dopamine D2
  • dihydroquinolin-2(1H)-one
  • Aripiprazole