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Bioorg Med Chem. 2013 Mar 1;21(5):1257-67. doi: 10.1016/j.bmc.2012.12.024. Epub 2012 Dec 27.

Design, synthesis and structure-activity relationship of novel tricyclic benzimidazolone derivatives as potent 18 kDa translocator protein (TSPO) ligands.

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Dainippon Sumitomo Pharma Co. Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan.


The 18 kDa translocator protein (TSPO) was identified as a discrete receptor for diazepam (1). Since TSPO in the central nervous system (CNS) is believed to regulate neurosteroids biosynthesis, selective TSPO ligands are expected to be useful in the treatment of psychiatric disorders. We synthesized three novel tricyclic benzimidazolone derivatives, and selected the dihydroimidazoquinolinone derivative 27 as a lead TSPO ligand. Study of the structure-activity relationship (SAR) of dihydroimidazoquinolinone derivatives revealed compounds with potent affinity for TSPO (subnanomolar K(i) values), but poor metabolic stability. The optimization of these compounds led to compound 48 with potent affinity for TSPO and good in vitro PK profile.

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