Evidence for a Stereoselective Mechanism for Bitopic Activity by Extended-Length Antagonists of the D₃ Dopamine Receptor.

ABSTRACT: The D3 dopamine receptor (D3R) has been suggested as a drug target for the treatment of a number of neuropsychiatric disorders, including substance use disorders (SUD). Many D3R-selective antagonists are bivalent in nature in that they engage two distinct sites on the receptor-a primary pharmacophore binds to the orthosteric site, where dopamine binds, whereas a secondary pharmacophore interacts with a unique secondary binding pocket (SBP). When engagement of the secondary pocket exerts allosteric activity, the compound is said to be bitopic. We recently reported the synthesis and characterization of two bitopic antagonists of the D3R, (±)-VK04-87 and (±)-VK05-95, which incorporated a racemic trans-cyclopropylmethyl linking chain. To gain a better understanding of the role of chiral

SUBMITTER: Moritz AE 

PROVIDER: S-EPMC8262072 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature