Design, synthesis, and biological evaluation of novel iso-flavones derivatives as H 3 R antagonists.

Histamine H3 receptor (H3 R), a kind of G-protein coupled receptor (GPCR), is expressed mainly in the central nervous system (CNS) and plays a vital role in homoeostatic control. This study describes the design and synthesis of a series of novel H3 R antagonists based on the iso-flavone scaffold. The results of the bioactivity evaluation show that four compounds (1c, 2c, 2h, and 2o) possess significant H3 R inhibitory activities. Molecular docking indicates that a salt bridge, π-π T-shape interactions, and hydrophobic interaction all contribute to the interaction between compound 2h and H3 R.