Novel and Potent Dopamine D₂ Receptor Go-Protein Biased Agonists.

ABSTRACT: The discovery of functionally biased and physiologically beneficial ligands directed toward G-protein coupled receptors (GPCRs) has provided the impetus to design dopamine D₂ receptor (D₂R) targeted molecules that may be therapeutically advantageous for the treatment of certain neuropsychiatric or basal ganglia related disorders. Here we describe the synthesis of a novel series of D₂R agonists linking the D₂R unbiased agonist sumanirole with privileged secondary molecular fragments. The resulting ligands demonstrate improved D₂R affinity and selectivity over sumanirole. Extensive in vitro functional studies and bias factor analysis led to the identification of a novel class of highly potent Go-protein biased full D₂R

SUBMITTER: Bonifazi A 

PROVIDER: S-EPMC6371206 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature