First Nondiscriminating Translocator Protein Ligands Produced from a Carbazole Scaffold.
Hei Wun Alison ChengRenee SokiasEryn L WerryLars M IttnerTristan A ReekieJonathan J DuQuanqing GaoDavid E HibbsMichael KassiouPublished in: Journal of medicinal chemistry (2019)
Development of neuroinflammation agents targeting the translocator protein (TSPO) has been hindered by a common single nucleotide polymorphism (A147T) at which TSPO ligands commonly lose affinity. To this end, carbazole acetamide scaffolds were synthesized and structure activity relationships elaborated to explore the requirements for high-affinity binding to both TSPO wild type (WT) and the polymorphic TSPO A147T. This study reports high binding affinity and nondiscriminating TSPO ligands.