Synthesis and neuropharmacological evaluation of esters of R(-)-N-alkyl-11-hydroxy-2-methoxynoraporphines

Bioorg Med Chem Lett. 2009 Jan 1;19(1):51-3. doi: 10.1016/j.bmcl.2008.11.025. Epub 2008 Nov 13.

Abstract

We synthesized several esters of R(-)-N-alkyl-11-hydroxy-2-methoxynoraporphines, assessed their affinities at dopamine D(1) and D(2) receptors in rat forebrain tissue and quantified their effects on motor activity in normal adult male rats. Tested compounds displayed moderate to high affinities to D(2) receptors but low affinities to D(1) receptors. The most D(2)-potent (K(i)=18.9nM) and selective novel agent (>529-fold vs D(1) sites) was R(-)-2-methoxy-11-acetyloxy-N-n-propylnoraporphine (compound 4b). At moderate doses, the compound proved to have prolonged behavioral locomotor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aporphines / chemical synthesis*
  • Aporphines / pharmacology*
  • Dose-Response Relationship, Drug
  • Esters / chemical synthesis
  • Male
  • Motor Activity / drug effects
  • Prosencephalon
  • Protein Binding
  • Rats
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, Dopamine D2 / metabolism*
  • Structure-Activity Relationship

Substances

  • Aporphines
  • Esters
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2