Synthesis and biological evaluation of XB-1 analogues as novel histamine H₃ receptor antagonists and neuroprotective agents

A novel class of H₃ receptor antagonists, XB-1 analogues based on benzophenone or oxydibenzene scaffolds were synthesized, and their biological activities were evaluated to determine their in vitro neuroprotective effects against Aβ_25–35-induced damage in primary cortical neurons and against glutamate-induced neuronal injury in primary cerebellar granule neurons. The results indicated that all of the tested analogues displayed neuroprotective activity at 0.1 μM or 1 μM. These findings may provide new insights into the development of novel promising H₃ receptor antagonists with potential neuroprotective activity.