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

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.