N-Substituted-2-alkyl- and 2-arylnorapomorphines: novel, highly active D2 agonists

Bioorg Med Chem. 2009 Jul 1;17(13):4756-62. doi: 10.1016/j.bmc.2009.04.047. Epub 2009 May 3.

Abstract

Two synthesis routes have been elaborated for the preparation of novel N-substituted-2-alkyl- and 2-arylnorapomorphines. The first one utilizes the traditional methodology of N-substitution of morphinans before acid-catalyzed rearrangements into aporphinoids, while our new approach involves the N-substitution directly on the aporphine backbone. The aimed compounds were obtained in similar overall yields in different synthesis routes and were investigated with respect to their binding affinities and activities to dopamine D(2) and D(1) receptors. These studies revealed remarkable affinity and selectivity of some compounds for D(2) over D(1) receptor subtypes. Partial or full agonist properties were confirmed for all tested compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apomorphine / analogs & derivatives*
  • Apomorphine / chemical synthesis
  • Apomorphine / pharmacology*
  • CHO Cells
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Fibroblasts / metabolism
  • Protein Binding
  • Rats
  • Receptors, Dopamine D1 / agonists*
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, Dopamine D2 / agonists*
  • Receptors, Dopamine D2 / metabolism*
  • Structure-Activity Relationship

Substances

  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Apomorphine