Highly Selective Dopamine D₃ Receptor Antagonists with Arylated Diazaspiro Alkane Cores

Abstract

A series of potent and selective D₃ receptor (D₃R) analogues with diazaspiro alkane cores were synthesized. Radioligand binding of compounds 11, 14, 15a, and 15c revealed favorable D₃R affinity (K_i = 12-25.6 nM) and were highly selective for D₃R vs D₃R (ranging from 264- to 905-fold). Variation of these novel ligand architectures can be achieved using our previously reported 10-20 min benchtop C-N cross-coupling methodology, affording a broad range of arylated diazaspiro precursors.