Isomeric Activity Cliffs-A Case Study for Fluorine Substitution of Aminergic G Protein-Coupled Receptor Ligands.

ABSTRACT: Currently, G protein-coupled receptors (GPCRs) constitute a significant group of membrane-bound receptors representing more than 30% of therapeutic targets. Fluorine is commonly used in designing highly active biological compounds, as evidenced by the steadily increasing number of drugs by the Food and Drug Administration (FDA). Herein, we identified and analyzed 898 target-based F-containing isomeric analog sets for SAR analysis in the ChEMBL database-F_iSAR sets active against 33 different aminergic GPCRs comprising a total of 2163 fluorinated (1201 unique) compounds. We found 30 F_iSAR sets contain activity cliffs (ACs), defined as pairs of structurally similar compounds showing significant differences in affinity (≥50-fold change), where the change of fluorine posit

SUBMITTER: Pietrus W 

PROVIDER: S-EPMC9863698 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature