Synthesis and pharmacological evaluation of Tic-hydantoin derivatives as selective σ1 ligands. Part 1

Herein is described a new class of selective σ1 ligands consisting of tetrahydroisoquinoline-hydantoin (Tic-hydantoin) derivatives. Compound 3a has high affinity (IC50 = 16 nM) for the σ1 receptor and is selective in a large panel of therapeutic targets. This first study presents structural changes around the Tic-hydantoin core, leading to a Tic-hydantoin analogue with a higher σ1 affinity (IC50 ≈ 1 nM).