Design, Synthesis and Structure–activity Relationship of Novel Tricyclic Benzimidazolone Derivatives As Potent 18kda Translocator Protein (TSPO) Ligands

Selective 18 kDa translocator protein (TSPO) ligands are expected to be therapeutic agents with a wide spectrum of action on psychiatric disorders and fewer side effects. We designed novel benzoxazolone derivatives and examined the structure-activity relationship (SAR) of a series of compounds with various substituents at the amide part and C-5 position. Although a number of the synthesized compounds showed high TSPO binding affinity, these compounds had poor drug-like properties. Further optimization of pharmacokinetic properties of these compounds led to discovery of compound 74, which exhibited anxiolytic effect in the rat Vogel conflict model.