MedChemComm
Research Article
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in DS,27 with the residues in the binding pocket being
allowed to move. Images of the optimised ligand-receptor
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Conclusions
In this study, a reaction sequence involving catalytic asym-
metric hydrogenation has been shown to be an efficient
method for the synthesis of enantiomerically-pure
aporphines. Both enantiomers of nuciferine and roemerine
were observed to have moderate to good 5-HT2 and α1 antag-
onist activity. (R)-Roemerine was the most potent compound
at 5-HT2A and 5-HT2C receptors with good selectivity com-
pared to (S)-roemerine at these two receptors and compared
to its activity at 5-HT2B and α1 receptor subtypes. These re-
sults will inform ongoing medicinal chemistry efforts to de-
termine the structure–activity relationships of aporphines at
5-HT2 and α1 receptors and evaluate their potential as phar-
macological probes or agents for the treatment of psychotic
disorders and drug addiction.
Conflicts of interest
There are no conflicts of interest to declare.
Acknowledgements
This study was funded by grants from the Ministry of Science,
Technology and Innovation, Malaysia (02-01-03-SF0937) and
the Ministry of Higher Education, Malaysia, High Impact Re-
search Grant (HIR-MoHE: UM.C/625/1/HIR/MOHE/MED/17 &
UM.C/625/1/HIR/MOHE/MED/33).
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