Synthesis of Bitopic Ligands as Potent Dopamine D Receptor Agonists.

In this study, we designed and synthesized twelve bitopic ligands as dopamine D receptor (D R) agonists. The forskolin-induced cAMP accumulation assay revealed that all the finial compounds are able to activate D R. Furthermore, bitopic ligand N-((trans)-4-(((2,3-dihydro-1H-inden-2-yl)(propyl)amino)methyl)cyclo-hexyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide (11 b) showed 21-fold higher potency than lead compound propyl aminoindane (2) and 17-fold higher subtype selectivity for D R over D R, indicating that the optimal length of spacer affects the D R functionality.