Enantiomeric resolution of [(2,2-diphenyl-1,3-dioxolan-4-yl)methyl](2-phenoxyethyl)amine, a potent α1 and 5-HT1A receptor ligand: an in vitro and computational study

Abstract

In this paper, the enantiomers of (±)-1, previously studied as α₁ and 5-HT_1A ligands, were prepared both by resolution of the racemate and asymmetric synthesis. The enantiomeric purity and absolute configuration were determined by means of HPLC and polarimetric analysis. Enantiomers were evaluated for in vitro 5-HT_1A and α₁ receptor affinity by binding and functional assays. Results indicate that the two enantiomers are almost equally potent at 5-HT_1A and α₁ receptor systems and, contrary to WB 4101, the stereoselectivity is poor. As further support to these experimental findings, molecular docking studies on the two enantiomers of (±)-1 have been performed and a comparison with those obtained for 5-HT_1A potent agonist (R)-flesinoxan and α_1d antagonist (S)-WB 4101 has been drawn.