Dopaminergic 7-aminotetrahydroindolizines: ex-chiral pool synthesis and preferential D3 receptor binding

Bioorg Med Chem Lett. 2001 Nov 5;11(21):2863-6. doi: 10.1016/s0960-894x(01)00564-9.

Abstract

Starting from both isomers of enantiopure asparagine, heterocyclic bioisosteres of the preferential dopamine D3 receptor agonist (R)-7-OH-DPAT were investigated when SAR studies led to the 3-formyl substituted aminoindolizine (S)-1e (FAUC 54) displaying a K(i) value of 6.0 nM for the high affinity D3 binding site. In contrast, D3 affinity of the enantiomer (R)-1e was 300 fold lower.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Indolizines / chemical synthesis*
  • Indolizines / metabolism*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3

Substances

  • Indolizines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • indolizine