Design and synthesis of photoswitchable desloratadine ligands for histamine H₁ receptor photopharmacology.

ABSTRACT: Despite the pharmacological relevance of the histamine H₁ receptor (H₁R), the second most therapeutically targeted G protein-coupled receptor (GPCR), an effective photoswitchable ligand to optically control this receptor remains elusive. In this work, we aimed to identify a suitable photoswitchable H₁R ligand by performing an 'azoscan' on the H₁R antagonist desloratadine. Taking advantage of the synthetic toolbox available for the desloratadine scaffold, aniline groups were regioselectively installed on the aromatic positions of this scaffold to enable the synthesis of azobenzene analogs targeting the orthosteric binding pocket of H₁R. Additionally, we functionalized the piperidine ring of desloratadine with azobenzene moieties. These

SUBMITTER: Binkhorst LCP 

PROVIDER: S-EPMC12378361 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature