Structural Basis for D3/D4-Selective Antagonism of Piperazinylalkyl Pyrazole/Isoxazole Analogs.

ABSTRACT: Dopamine D2-like receptors, including D2, D3, and D4, are members of the aminergic G protein-coupled receptor (GPCR) family and are targets for neurological disorders. The development of subtype selective ligands is important for enhanced therapeutics and reduced side effects; however, it is challenging to design and develop selective ligands owing to the high degree of sequence homology among D2-like subtypes. To gain insight into the structural basis of subtype selectivity of piperazinylalkyl pyrazole/isoxazole analogs for D2-like dopamine receptors, we carried out 3D quantitative structure-activity relationship (3D-QSAR) and molecular docking studies. The 3D-QSAR models for the D2, D3, and D4 subtypes showed robust correlation coefficients (r²) of 0.960, 0.912, and 0.946, as

SUBMITTER: Choi KE 

PROVIDER: S-EPMC12526434 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature