Chiral Cyclic Aliphatic Linkers as Building Blocks for Selective Dopamine D₂ or D₃ Receptor Agonists.

ABSTRACT: Linkers are emerging as a key component in regulating the pharmacology of bitopic ligands directed toward G-protein coupled receptors (GPCRs). In this study, the role of regio- and stereochemistry in cyclic aliphatic linkers tethering well-characterized primary and secondary pharmacophores targeting dopamine D₂ and D₃ receptor subtypes (D₂R and D₃R, respectively) is described. We introduce several potent and selective D₂R (rel-trans-16b; D₂R K_i = 4.58 nM) and D₃R (rel-cis-14a; D₃R K_i = 5.72 nM) agonists while modulating subtype selectivity in a stereospecific fashion, transferring D₂R selectivity toward D₃

SUBMITTER: Battiti FO 

PROVIDER: S-EPMC11091832 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature