Design, synthesis, and evaluation of bitopic arylpiperazine-phthalimides as selective dopamine D₃ receptor agonists.

ABSTRACT: The dopamine D₃ receptor (D₃R) is a proven therapeutic target for the treatment of neurological and neuropsychiatric disorders. In particular, D₃R-selective ligands that can eliminate side effects associated with dopamine D₂ receptor (D₂R) therapeutics have been validated. However, the high homology in signaling pathways and the sequence similarity between D₂R and D₃R have rendered the development of D₃R-selective ligands challenging. Herein, we designed and synthesized a series of piperazine-phthalimide bitopic ligands based on a fragment-based and molecular docking inspired design. Compound 9i was identified as the most selective D₃R ligand among these bitopic ligands. Its selectivit

SUBMITTER: Cao Y 

PROVIDER: S-EPMC6148523 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature