Synthesis and binding studies of 2-O- and 11-O-substituted N-alkylnoraporphines.
July 3rd, 2008 | by admin |Synthesis and binding studies of 2-O- and 11-O-substituted N-alkylnoraporphines.
We synthesized several novel 2-O- or 11-O-substituted N-alkylnoraporphines and assessed their affinities at dopamine D(1) and D(2), and serotonin 5-HT(1A) receptors in rat forebrain tissue. Tested compounds displayed moderate to high affinities to D(2) receptors but low affinities to D(1) and 5HT(1A) receptors. The findings accord with previous evidence of a lipophilic cavity on the surface of the D(2) receptor to accommodate N-alkyl moieties of aporphines. The most D(2)-potent (K(i)=97nM) and selective novel agent (>100-fold vs. D(1) and 5-HT(1A) sites) was R(-)-2-(2-hydroxyethoxy)-11-hydroxy-N-n-propylnoraporphine (compound 11).
Si YG, Gardner MP, Tarazi FI, Baldessarini RJ, Neumeyer JL.
Alcohol Drug Abuse Research Center and Mailman Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.