Synthesis and optical resolution of (R)- and (S)-trans-7-Hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)amino]tetralin: a new D3 dopamine receptor ligand

J Med Chem. 1993 Dec 24;36(26):4308-12. doi: 10.1021/jm00078a021.

Abstract

An improved method for synthesis and resolution of (R,S)-trans-7-hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)amino]tetralin (trans-7-OH-PlPAT,5), a new D3 dopamine receptor ligand, was reported. Both isomers, (R)-(+)- and (S)-(-)-5, were prepared and characterized. HPLC retention times obtained on a chiral column for these isomers were consistent with those observed for [125I]-(R)-(+)- and (S)-(-)-5. Direct radioiodination of an optically resolved tin precursor, (R)-(+)-7, yielded the desired [125I](R)-(+)-5, which is a simpler method for synthesis of this ligand. Binding studies with membrane preparations containing D3 dopamine receptors expressed in Spodoptera frugiperda (Sf9) cells also suggested that the [125I](R)-(+)-5 is the active isomer (Kd = 0.05 nM). The schemes described may provide an efficient way for synthesizing a large quantity of this new D3 dopamine receptor ligand for in vivo behavior studies.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Chromatography, High Pressure Liquid
  • Iodine Radioisotopes
  • Isotope Labeling
  • Ligands
  • Molecular Structure
  • Moths / metabolism
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D2*
  • Receptors, Dopamine D3
  • Stereoisomerism
  • Tetrahydronaphthalenes / chemical synthesis*
  • Tetrahydronaphthalenes / chemistry
  • Tetrahydronaphthalenes / metabolism
  • Trialkyltin Compounds

Substances

  • Iodine Radioisotopes
  • Ligands
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Tetrahydronaphthalenes
  • Trialkyltin Compounds
  • 7-hydroxy-2-(N-n-propyl-N-(3-iodo-2'-propenyl)-amino)tetralin
  • tributyltin