Development of a safe and scalable route towards a tau PET tracer precursor.

A scalable 5-step synthesis of the diazacarbazole derivative 1 used as tau PET tracer precursor is reported. Key features of this synthesis include a Buchwald-Hartwig amination, a Pd catalyzed CH activation and a Suzuki-Miyaura cross-coupling.

Preclinical Evaluation of F-RO6958948, C-RO6931643, and C-RO6924963 as Novel PET Radiotracers for Imaging Tau Aggregates in Alzheimer Disease.

Tau aggregates and amyloid-β (Aβ) plaques are key histopathologic features in Alzheimer disease (AD) and are considered targets for therapeutic intervention as well as biomarkers for diagnostic in vivo imaging agents. This article describes the preclinical in vitro and in vivo characterization of 3 novel compounds-RO6958948, RO6931643, and RO6924963-that bind specifically to tau aggregates and have the potential to become PET tracers for future human use. RO6958948, RO6931643, and RO6924963 were identified as high-affinity competitors at the H-T808 binding site on native tau aggregates in human late-stage AD brain tissue.