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

Histamine H(3) receptor (H(3)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 H(3)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 H(3)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 H(3)R.